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Fu H, Dong S, Li K. Identification of SLC31A1 as a prognostic biomarker and a target for therapeutics in breast cancer. Sci Rep 2024; 14:25120. [PMID: 39448672 PMCID: PMC11502855 DOI: 10.1038/s41598-024-76162-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 10/10/2024] [Indexed: 10/26/2024] Open
Abstract
Copper-induced cell death is regulated through protein lipoylation, which is critical for gene expression and phenotypic regulation. Neverless, the role of Cuproptosis-related genes in breast cancer (BC) remains unknown. This study aimed to construct a prognostic signature based on the expression of Cuproptosis-related genes in order to guide the diagnosis and treatment for BC. Cuproptosis-related genes prognostic signature has ata of 1250 BC tissues and 583 normal breast tissues were obtained from The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), and GEO GSE65212. The prognostic signature was established and evaluated with nineteen Cuproptosis-related genes. A series of in silico analyses based on SLC31A1, included expression analysis, independent prognostic analysis, correlation analysis, immune-related analysis and survival analysis. Finally, a series of cell experiments (including quantitative real-time polymerase chain reaction and western blot), and mice experiments were applied to evaluate the impact of SLC31A1 on BC. Cuproptosis-related genes prognostic signature has good predictive promising for survival in BC patients. We discovered that SLC31A1SLC31A1 was overexpressed in BC and was its independent prognostic factor. High expression of the SLC31A1 was correlated with poor prognosis and immune infiltrating of BC. SLC31A1 expression is associated with immune, chemotherapeutic and targeted therapy outcomes in BC. The proliferation, migration, and invasiveness of Her2 + enriched BC cells were decreased by SLC31A1 knockdown, also resulting in a decrease in tumor volume in mouse model. SLC31A1 is a candidate biomarker or therapeutic target in precision oncology, with diagnostic and prognostic significance in BC.
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Affiliation(s)
- Hongtao Fu
- Department of Breast Surgery, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410006, Hunan, China
- Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210000, China
| | - Shanshan Dong
- Department of Medicine, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410000, China
| | - Kun Li
- Department of Emergency Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, 161 Shaoshan South Road, Changsha, 410000, China.
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2
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Fu H, Li K, Wang S, Li Y. High expression of CCNB1 driven by ncRNAs is associated with a poor prognosis and tumor immune infiltration in breast cancer. Aging (Albany NY) 2022; 14:6780-6795. [PMID: 36040381 PMCID: PMC9467392 DOI: 10.18632/aging.204253] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Accepted: 08/15/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUNDS Breast cancer (BC) is the most frequent cancer diagnosed in women throughout the world. The purpose of this study was to explore new biomarkers for breast cancer diagnosis. CyclinB1 (CCNB1) is found in abundance in a wide range of human malignancies. MATERIAL AND METHODS We evaluated the transcriptional, survival data and expression levels in tissue data of CCNB1 in patients with breast cancer from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), The Human Protein Atlas (THAP) and Genome Tissue Expression (GTEx) database. A series of in silico analyses were used to investigate at noncoding RNAs (ncRNAs), gene ontology (GO) annotation analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), and the Protein-Protein Interaction (PPI) network. A quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate CCNB1 in BC cell lines. RESULTS CCNB1 expression was higher in BC tissues than in normal breast tissues. It was significantly related to survival time, tumor mutation burden (TMB), methylated, immune cell infiltration, and the expressed in estrogen receptor (ER) (-), lymphnode (+), and p53 (+) groups in BC. Moreover, The AC026401.3/CCNB1-miR-139-5p axis was discovered as the most promising upstream ncRNA-related pathway of CCNB1 in BC. CONCLUSION CCNB1 can be used as an independent predictive factor for BC, indicating that this would be a target for highly precise therapy and a biomarker for the disease.
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Affiliation(s)
- Hongtao Fu
- Department of Breast Surgery, Jiangsu Province Hospital, The First Hospital Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China
| | - Kun Li
- Department of emergency, Changsha Central Hospital, The Affiliated Changsha Central Hospital of Hengyang Medical School, University of South China, Changsha 410004, China
| | - Shui Wang
- Department of Breast Surgery, Jiangsu Province Hospital, The First Hospital Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China
| | - Yuming Li
- Department of Traditional Chinese Medicine and Western Medicine, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410006, China
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Frisone D, Sandoval J, Friedlaender A, Olivier T, Addeo A. Trends in incidence and mortality of lung cancer in Switzerland: Possible explanations and open questions. Cancer Epidemiol 2022; 80:102232. [PMID: 35905519 DOI: 10.1016/j.canep.2022.102232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 07/20/2022] [Accepted: 07/22/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND Using US population-level data, it has been suggested that novel treatment advances, particularly targeted therapies, have contributed to a sharp fall in NSCLC mortality. Switzerland is a high-income country, with a universal, highly performant health care system, easy access to novel drugs but with different dynamics concerning the smoking epidemic than the US. METHODS We use population-based data from Swiss cancer registries to analyze the trends in incidence, mortality and survival and relate them to recent drug approvals. RESULTS The incidence of NSCLC and SCLC was stable from 1980 to 2018. We noted an important difference between sexes, with an important decrease in men and increase in women, especially for NSCLC. 1-y and 5-y survival have improved for NSCLC between 2004 and 2008 and 2014-2018. CONCLUSION These findings should be regarded as the results of a multifactorial improvement in care and it is difficult for us to pinpoint a unique cause explaining the reduction in mortality.
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Affiliation(s)
- Daniele Frisone
- Department of Oncology, Geneva University Hospital, SCCL, Switzerland
| | - Jose Sandoval
- Department of Oncology, Geneva University Hospital, SCCL, Switzerland
| | - Alex Friedlaender
- Department of Oncology, Geneva University Hospital, SCCL, Switzerland; Clinique Générale Beaulieu, Geneva, Switzerland
| | - Timothée Olivier
- Department of Oncology, Geneva University Hospital, SCCL, Switzerland; Department of Epidemiology and Biostatistics, University of California San Francisco, 550 16th St, 2nd Fl, San Francisco, CA 94158, USA
| | - Alfredo Addeo
- Department of Oncology, Geneva University Hospital, SCCL, Switzerland; Geneva University, Faculty of Medicine, Switzerland.
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Li L, Zheng J, Stevens M, Oltean S. A repositioning screen using an FGFR2 splicing reporter reveals compounds that regulate epithelial-mesenchymal transitions and inhibit growth of prostate cancer xenografts. Mol Ther Methods Clin Dev 2022; 25:147-157. [PMID: 35402635 PMCID: PMC8971352 DOI: 10.1016/j.omtm.2022.03.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 03/13/2022] [Indexed: 12/13/2022]
Abstract
Research in the area of hallmarks of cancer has opened the possibility of designing new therapies based on modulating these cancer properties. We present here a screen designed to find chemicals that modulate epithelial-mesenchymal transitions (EMTs) in prostate cancer. For screening, we used a repurposing library and, as a readout, an FGFR2-based splicing reporter, which has been shown previously to be a sensor for EMTs. Various properties of cancer cells were assessed, signaling pathways investigated, and in vivo experiments in nude mice xenografts performed. The screen yielded three hit compounds (a T-type Ca channel inhibitor, an L-type Ca channel inhibitor, and an opioid antagonist) that switch FGFR2 splicing and induce an epithelial phenotype in prostate cancer cells. The compounds affected differently various properties of cancer cells, but all of them decreased cell migration, which is in line with modulating EMTs. We further present mechanistic insights into one of the compounds, nemadipine-A. The administration of nemadipine-A intraperitoneally in a nude mouse xenograft model of prostate cancer slowed tumor growth. To conclude, we show that knowledge of the molecular mechanisms that connect alternative splicing and various cancer properties may be used as a platform for drug development.
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Affiliation(s)
- Ling Li
- Institute of Biomedical & Clinical Sciences, Medical School, College of Medicine and Health, University of Exeter, St Luke’s Campus, Exeter EX1 2LU, UK
| | - Jinxia Zheng
- Institute of Biomedical & Clinical Sciences, Medical School, College of Medicine and Health, University of Exeter, St Luke’s Campus, Exeter EX1 2LU, UK
| | - Megan Stevens
- Institute of Biomedical & Clinical Sciences, Medical School, College of Medicine and Health, University of Exeter, St Luke’s Campus, Exeter EX1 2LU, UK
| | - Sebastian Oltean
- Institute of Biomedical & Clinical Sciences, Medical School, College of Medicine and Health, University of Exeter, St Luke’s Campus, Exeter EX1 2LU, UK
- Corresponding author Sebastian Oltean, MD, PhD, Institute of Biomedical & Clinical Sciences, Medical School, College of Medicine and Health, University of Exeter, St Luke’s Campus, Exeter, EX1 2LU, UK.
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T cell therapy against cancer: a predictive diffuse-interface mathematical model informed by pre-clinical studies. J Theor Biol 2022; 547:111172. [DOI: 10.1016/j.jtbi.2022.111172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 05/16/2022] [Accepted: 05/19/2022] [Indexed: 11/18/2022]
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Santucci C, Patel L, Malvezzi M, Wojtyla C, La Vecchia C, Negri E, Bertuccio P. Persisting cancer mortality gap between western and eastern Europe. Eur J Cancer 2022; 165:1-12. [DOI: 10.1016/j.ejca.2022.01.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 12/20/2021] [Accepted: 01/03/2022] [Indexed: 01/16/2023]
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Guo C, Su Y, Wang B, Chen Q, Guo H, Kong M, Chen D. Novel polysaccharide building hybrid nanoparticles: remodelling TAMs to target ERα-positive breast cancer. J Drug Target 2021; 30:450-462. [PMID: 34927506 DOI: 10.1080/1061186x.2021.2020798] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
With the increasing number of oncology patients and the use of chemotherapeutic agents, tumour multidrug resistance is becoming more and more prevalent. The search for new tumour treatment strategies to overcome tumour multidrug resistance is urgent. In this study, we designed GSH and ROS dual-responsive tumour-associated macrophages (TAMs)-targeted nanoparticles (NPs) for the co-delivery of the clinical first-line anti-breast cancer chemotherapy drug paclitaxel (PTX) and baicalin (Bai), which re-educates TAMs to alter their phenotype. We synthesised oligohyaluronic acid-mannose-folic acid (oHA-Man-FA, HMF) and astragalus polysaccharide-dithiodipropionic acid-paeoniflorol (APS-S-Pae, ASP), two hybrid materials that can self-assemble in water to form hybrid nanoparticles (HP-NPs) co-loaded with paclitaxel and baicalin (HP-NPs@PTX/Bai). The experimental results show that our designed hybrid nanoparticles can be specifically released in the tumour microenvironment and deliver the antitumor drug PTX as well as Bai, which reshapes the phenotype of TAMs, to the tumour site. The hybrid nanoparticles not only effectively re-educated TAMs from M2 TAM to M1 TAM, but also ameliorated the cytotoxic side effects caused by free PTX and provided better tumour suppression than free PTX and HP.
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Affiliation(s)
- Chunjing Guo
- College of Marine Life Science, Ocean University of China, Qingdao, PR China
| | - Yanguo Su
- School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs, Yantai University, Yantai, PR China
| | - Bingjie Wang
- School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs, Yantai University, Yantai, PR China.,School of Medicine and Pharmacy, Ocean University of China, Qingdao, PR China
| | - Qiang Chen
- School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs, Yantai University, Yantai, PR China
| | - Huimin Guo
- School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs, Yantai University, Yantai, PR China
| | - Ming Kong
- College of Marine Life Science, Ocean University of China, Qingdao, PR China
| | - Daquan Chen
- School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs, Yantai University, Yantai, PR China
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Mangin D, Lamarche L, Agarwal G, Banh HL, Dore Brown N, Cassels A, Colwill K, Dolovich L, Farrell B, Garrison S, Gillett J, Griffith LE, Holbrook A, Jurcic-Vrataric J, McCormack J, O’Reilly D, Raina P, Richardson J, Risdon C, Savelli M, Sherifali D, Siu H, Tarride JÉ, Trimble J, Ali A, Freeman K, Langevin J, Parascandalo J, Templeton JA, Dragos S, Borhan S, Thabane L. Team approach to polypharmacy evaluation and reduction: study protocol for a randomized controlled trial. Trials 2021; 22:746. [PMID: 34702336 PMCID: PMC8549321 DOI: 10.1186/s13063-021-05685-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 10/05/2021] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Polypharmacy in older adults can be associated with negative outcomes including falls, impaired cognition, reduced quality of life, and general and functional decline. It is not clear to what extent these are reversible if the number of medications is reduced. Primary care does not have a systematic approach for reducing inappropriate polypharmacy, and there are few, if any, approaches that account for the patient's priorities and preferences. The primary objective of this study is to test the effect of TAPER (Team Approach to Polypharmacy Evaluation and Reduction), a structured operationalized clinical pathway focused on reducing inappropriate polypharmacy. TAPER integrates evidence tools for identifying potentially inappropriate medications, tapering, and monitoring guidance and explicit elicitation of patient priorities and preferences. We aim to determine the effect of TAPER on the number of medications (primary outcome) and health-related outcomes associated with polypharmacy in older adults. METHODS We designed a multi-center randomized controlled trial, with the lead implementation site in Hamilton, Ontario. Older adults aged 70 years or older who are on five or more medications will be eligible to participate. A total of 360 participants will be recruited. Participants will be assigned to either the control or intervention arm. The intervention involves a comprehensive multidisciplinary medication review by pharmacists and physicians in partnership with patients. This review will be focused on reducing medication burden, with the assumption that this will reduce the risks and harms of polypharmacy. The control group is a wait list, and control patients will be given appointments for the TAPER intervention at a date after the final outcome assessment. All patients will be followed up and outcomes measured in both groups at baseline and 6 months. DISCUSSION Our trial is unique in its design in that it aims to introduce an operationalized structured clinical pathway aimed to reduce polypharmacy in a primary care setting while at the same time recording patient's goals and priorities for treatment. TRIAL REGISTRATION Clinical Trials.gov NCT02942927. First registered on October 24, 2016.
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Affiliation(s)
- Dee Mangin
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Larkin Lamarche
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Gina Agarwal
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Hoan Linh Banh
- University of Alberta, 6-60 University Terrace, Edmonton, Alberta Canada
| | - Naomi Dore Brown
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Alan Cassels
- University of Victoria, 3800 Finnerty Road, Victoria, BC Canada
| | - Kiska Colwill
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Lisa Dolovich
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
- University of Toronto, 144 College Street, Toronto, Ontario Canada
| | - Barbara Farrell
- Bruyère Research Institute, 43 Bruyère Street, Ottawa, Ontario Canada
| | - Scott Garrison
- University of Alberta, 6-60 University Terrace, Edmonton, Alberta Canada
| | - James Gillett
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Lauren E. Griffith
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Anne Holbrook
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Jane Jurcic-Vrataric
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - James McCormack
- University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC Canada
| | - Daria O’Reilly
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Parminder Raina
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Julie Richardson
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Cathy Risdon
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Mat Savelli
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Diana Sherifali
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Henry Siu
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Jean-Éric Tarride
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Johanna Trimble
- University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC Canada
| | - Abbas Ali
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Karla Freeman
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Jessica Langevin
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Jenna Parascandalo
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Jeffrey A. Templeton
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Steven Dragos
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Sayem Borhan
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
| | - Lehana Thabane
- Department of Family Medicine, McMaster University, 100 Main Street West., 5th floor, Hamilton, Ontario L8P 1H6 Canada
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Chen X, Liu F, Xue Q, Weng X, Xu F. Metastatic pancreatic cancer: Mechanisms and detection (Review). Oncol Rep 2021; 46:231. [PMID: 34498718 PMCID: PMC8444192 DOI: 10.3892/or.2021.8182] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 08/19/2021] [Indexed: 12/13/2022] Open
Abstract
Pancreatic cancer (PC) is a lethal malignancy. Its prevalence rate remains low but continues to grow each year. Among all stages of PC, metastatic PC is defined as late-stage (stage IV) PC and has an even higher fatality rate. Patients with PC do not have any specific clinical manifestations. Most cases are inoperable at the time-point of diagnosis. Prognosis is also poor even with curative-intent surgery. Complications during surgery, postoperative pancreatic fistula and recurrence with metastatic foci make the management of metastatic PC difficult. While extensive efforts were made to improve survival outcomes, further elucidation of the molecular mechanisms of metastasis poses a formidable challenge. The present review provided an overview of the mechanisms of metastatic PC, summarizing currently known signaling pathways (e.g. epithelial-mesenchymal transition, NF-κB and KRAS), imaging that may be utilized for early detection and biomarkers (e.g. carbohydrate antigen 19-9, prostate cancer-associated transcript-1, F-box/LRR-repeat protein 7 and tumor stroma), giving insight into promising therapeutic targets.
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Affiliation(s)
- Xiangling Chen
- Department of Public Health, Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China
| | - Fangfang Liu
- Department of Art, Art College, Southwest Minzu University, Chengdu, Sichuan 610041, P.R. China
| | - Qingping Xue
- Department of Public Health, Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China
| | - Xiechuan Weng
- Department of Neuroscience, Beijing Institute of Basic Medical Sciences, Beijing 100850, P.R. China
| | - Fan Xu
- Department of Public Health, Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China
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Arima S, Kawahira M, Shimokawa M, Ido A, Koga F, Ueda Y, Nakazawa J, Komori A, Otsu S, Fukahori M, Makiyama A, Taguchi H, Honda T, Shibuki T, Mitsugi K, Nio K, Ide Y, Ureshino N, Mizuta T, Shirakawa T, Otsuka T. Gemcitabine Plus Nab-Paclitaxel Versus FOLFIRINOX in Locally Advanced, Unresectable Pancreatic Cancer: A Multicenter Observational Study (NAPOLEON Study). Pancreas 2021; 50:957-964. [PMID: 34347735 DOI: 10.1097/mpa.0000000000001859] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVES FOLFIRINOX (FFX, a combination of oxaliplatin, irinotecan, fluorouracil, and leucovorin) and gemcitabine plus nab-paclitaxel (GnP) have been used as standard, first-line treatments for advanced pancreatic cancer. However, no study has compared the efficacy of the 2 regimens. This study retrospectively compared the efficacy and safety of the 2 regimens in patients with locally advanced pancreatic cancer. METHODS We reviewed the records of patients with locally advanced pancreatic cancer who started FFX or GnP as first-line chemotherapy as part of a multicenter retrospective study in patients with unresectable pancreatic cancer treated with FFX or GnP (NAPOLEON study). RESULTS Sixteen of the 63 patients were treated with FFX, and the other 47 patients were treated with GnP between December 2013 and March 2017. There were no significant differences in median overall survival rate between the GnP (15.5 months) and FFX (14.3 months, P = 0.60) groups or median progression-free survival rate between the GnP (8.8 months) and FFX (8.1 months, P = 0.51) groups. Both treatments were generally well tolerated, although anorexia was more severe in the FFX group than in the GnP group. CONCLUSIONS The effects of FFX and GnP were similar but resulted in different toxicities, which could guide agent choice.
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Affiliation(s)
- Shiho Arima
- From the Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima
| | - Machiko Kawahira
- From the Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima
| | | | - Akio Ido
- From the Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima
| | - Futa Koga
- Department of Hepato-biliary-pancreatic Medicine, Saga-ken Medical Center Koseikan, Saga
| | - Yujiro Ueda
- Department of Hematology and Oncology, Japanese Red Cross Kumamoto Hospital, Kumamoto
| | - Junichi Nakazawa
- Department of Gastroenterology and Hepatology, Kagoshima City Hospital, Kagoshima
| | - Azusa Komori
- Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita
| | - Satoshi Otsu
- Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita
| | - Masaru Fukahori
- Department of Medicine, Division of Gastroenterology, Kurume University Hospital
| | | | | | - Takuya Honda
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki
| | | | - Kenji Mitsugi
- Department of Medical Oncology, Hamanomachi Hospital, Fukuoka
| | - Kenta Nio
- Department of Medical Oncology, Sasebo Kyosai Hospital, Nagasaki
| | - Yasushi Ide
- Department of Internal Medicine, Karatsu Red Cross Hospital
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11
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Elbeddini A, Sawhney M, Tayefehchamani Y, Yilmaz Z, Elshahawi A, Josh Villegas J, Dela Cruz J. Deprescribing for all: a narrative review identifying inappropriate polypharmacy for all ages in hospital settings. BMJ Open Qual 2021; 10:e001509. [PMID: 34230053 PMCID: PMC8261885 DOI: 10.1136/bmjoq-2021-001509] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 06/26/2021] [Indexed: 11/09/2022] Open
Affiliation(s)
- Ali Elbeddini
- Family Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Monakshi Sawhney
- School of Nursing & Department of Anesthesiology and Perioperative Medicine, Queen's University, Kingston, Ontario, Canada
| | - Yasamin Tayefehchamani
- Clinical Pharmacy, University of Toronto Leslie Dan Faculty of Pharmacy, Toronto, Ontario, Canada
| | - Zekiye Yilmaz
- Clinical Pharmacy- Head of department, Acibadem University, Istanbul, İstanbul, Turkey
| | - Ahmed Elshahawi
- Assistant professor of Medicine, University of Toronto Faculty of Medicine, Toronto, Ontario, Canada
| | | | - Janelyn Dela Cruz
- MD Candidate, Saint James School of Medicine - Saint Vincent and the Grenadines Campus, Arnos Vale, Saint George, Saint Vincent and the Grenadines
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12
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Zhong P, Shu R, Wu H, Liu Z, Shen X, Hu Y. Low KRT15 expression is associated with poor prognosis in patients with breast invasive carcinoma. Exp Ther Med 2021; 21:305. [PMID: 33717248 PMCID: PMC7885068 DOI: 10.3892/etm.2021.9736] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 12/01/2020] [Indexed: 12/13/2022] Open
Abstract
Although keratin 15 (KRT15) has been indicated to be overexpressed in several types of tumor, its role in breast invasive carcinoma (BRCA) has so far remained elusive. The aim of the present study was to explore KRT15 expression in BRCA based on data obtained from The Cancer Genome Atlas and The Genotype-Tissue Expression. KRT15 expression was compared using a Wilcoxon rank-sum test. Functional enrichment analysis was performed to reveal the biological roles and pathways of KRT15. The association between KRT15 expression and immune-cell infiltration was evaluated via single-sample gene set enrichment analysis (ssGSEA). To investigate the relationship between clinicopathological features and KRT15 expression, the prognostic value of KRT15 and other clinical factors was evaluated using Cox regression analysis and Kaplan-Meier (KM) plots. Subgroup prognostic analysis was also performed using forest plots and KM curves. Finally, a tissue microarray was used to assess KRT15 expression in BRCA tissues. KRT15 expression was significantly lower in BRCA tissues compared with that in normal tissues. Functional enrichment analysis suggested that KRT15-related genes were primarily enriched in the transmembrane transporter complex, cornification and ligand-receptor interactions. Increased KRT15 was associated with several tumor-suppressive pathways. ssGSEA revealed that high KRT15 expression was significantly associated with natural killer-cell, B-cell and mast-cell infiltration. Significant associations were observed between low KRT15 expression and advanced stage clinicopathological factors, as well as unfavorable overall survival (OS) and disease-specific survival. Multivariate Cox regression analysis suggested that KRT15 was an independent prognostic factor for OS (P=0.039; hazard ratio, 0.590; 95% CI, 0.358-0.974). Subgroup prognostic analysis demonstrated that low KRT15 was a reliable predictor of poor OS. Immunohistochemistry of a tissue microarray indicated that positive KRT15 expression rates were significantly higher in normal tissues compared with those in the BRCA tissues. In conclusion, low KRT15 expression was significantly associated with poor prognosis in patients with BRCA. Thus, KRT15 may serve an important role in BRCA progression and may be used as a promising prognostic marker for diagnostic and prognostic analyses in patients with BRCA.
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Affiliation(s)
- Pengcheng Zhong
- Laboratory of Herbal Drug Discovery, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Rong Shu
- Laboratory of Herbal Drug Discovery, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Huiwen Wu
- Laboratory of Herbal Drug Discovery, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Zhiwen Liu
- Laboratory of Herbal Drug Discovery, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Xiaoling Shen
- Laboratory of Herbal Drug Discovery, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Yingjie Hu
- Laboratory of Herbal Drug Discovery, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
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13
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Wang T, Li W, Li H, Li W. Dysregulation of exosomal miR-192 and miR-194 expression in lung adenocarcinoma patients. Saudi J Biol Sci 2021; 28:1561-1568. [PMID: 33732041 PMCID: PMC7938118 DOI: 10.1016/j.sjbs.2021.01.013] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 01/06/2021] [Accepted: 01/07/2021] [Indexed: 12/25/2022] Open
Abstract
Non-small cell lung cancer (NSCLC) is the main reason of cancer linked mortality and around 80% of cases diagnosed in advanced stage. Therefore current study designed to evaluate the deregulation of miRNA-194 and miRNA-192 in different body fluid of Non small cell lung cancer participants. Present study recruited newly diagnosed histopathologically confirmed. It was observed that the 40% NSCLC participants showed elevated miR-194 expression and 60% NSCLC participants showed reduced miR-194 expression in serum sample while in Bronchial wash, only 20% NSCLC participants showed elevated miR-194 expression while 80% showed reduced miR-194 expression (p = 0.003). It was found that the 54% NSCLC participants showed elevated miR-192 expression and 55% NSCLC participants showed reduced miR-192 expression in serum sample while In Bronchial wash sample, only 25% NSCLC participants showed high miR-192 expression while 75% showed low miR-192 expression (P = 0.0004). Expression of miR-194 was significantly associated with TNM stages (p < 0.0001, p < 0.0001), distant organ metastases (p < 0.0001, p < 0.0001), pathological grade (p = 0.0009, p = 0.0005) among serum sample and bronchial wash sample. Same observation was found with expression of miR-192 and it was significantly associated with TNM stages (p < 0.0001, p < 0.0001), distant organ metastases (p < 0.0001, p < 0.0001), pathological grade (p = 0.006, p = 0.001) among serum sample and bronchial wash sample. It was observed that the NSCLC participants who had high serum based miR-194 expression showed 22 months of overall median survival while low expression of serum based miR-194 expression showed 18 months of overall median survival. Present study suggests that decreased expression of miR-194 and miR-192 was significantly associated with different clinical features of NSCLC cases. However, significantly higher number of NSCLC cases showed low expression of miR-194 and miR-192 in bronchial lavage sample. Decreased poor overall survival was found to be associated with bronchial wash sample with respect to low miR-194 and miR-192 expression while NSCLC participants showed better overall survival with high miR-194 and miR-192 expression. This suggested decreased expression of miR-192 and miR-194 expression could be the potential prognostic marker among NSCLC participants.
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Affiliation(s)
- Tongfei Wang
- Department of Oncology, Xi’an No. 3 Hospital, the Affiliated Hospital of Northwest University, Xi’an, Shaanxi 710018, China
| | - Wei Li
- Department of Orthopedics, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi 710038, China
| | - Haitao Li
- Department of Oncology, Xi’an No. 3 Hospital, the Affiliated Hospital of Northwest University, Xi’an, Shaanxi 710018, China
| | - Weina Li
- Biotechnology Center, School of Pharmacy, Fourth Military Medical University, Xi’an, Shaanxi 710032, China
- Corresponding author.
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14
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Torres-Roman JS, Ronceros-Cardenas L, Valcarcel B, Arce-Huamani MA, Bazalar-Palacios J, Ybaseta-Medina J, La Vecchia C, Alvarez CS. Cervical cancer mortality in Peru: regional trend analysis from 2008-2017. BMC Public Health 2021; 21:219. [PMID: 33499858 PMCID: PMC7836503 DOI: 10.1186/s12889-021-10274-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 01/19/2021] [Indexed: 01/23/2023] Open
Abstract
BACKGROUND Cervical cancer is the third leading cause of cancer-related death among Latin American women. Peru has the sixth highest mortality rate for cervical cancer in the region with regional variations. We aimed to determine overall and regional cervical cancer mortality rates and trends in Peru between 2008 and 2017. METHODS We performed an ecological study on the number of deaths by cervical cancer in Peru. Deaths were extracted from the Peruvian Ministry of Health mortality database. Age-standardized mortality rates (ASMR) were estimated per 100,000 women-years using the world standard Segi population. We computed mortality trends using the Joinpoint regression program, estimating the annual percent change (APC). For spatial analysis, GeoDA software was used. RESULTS Peru showed downward trends in the last decade (from 11.62 in 2008 to 9.69 in 2017 (APC = - 2.2, 95% CI: - 4.3, - 0.1, p < 0.05). According to regional-specific analysis, the highest ASMR was in the rainforest region, although this declined from 34.16 in 2008 to 17.98 in 2017 (APC = - 4.3, 95% CI: - 7.2, - 1.3, p < 0.01). Concerning spatial analysis and clustering, the mortality rates from 2008 to 2017 showed a positive spatial autocorrelation and significant clustering (Moran's I: 0.35, p < 0.001) predominantly in the neighboring North-East departments (Loreto, Ucayali, and San Martin). CONCLUSIONS Although mortality trends in the entire population are decreasing, mortality rates remain very high, mainly in the rainforest region. Our results encourage a need for further development and improvement of the current health care delivery system in Peru.
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Affiliation(s)
- J Smith Torres-Roman
- Universidad Científica del Sur, Lima, Peru. .,Latin American Network for Cancer Research (LAN-CANCER), Lima, Peru.
| | | | - Bryan Valcarcel
- Latin American Network for Cancer Research (LAN-CANCER), Lima, Peru
| | - Miguel A Arce-Huamani
- Universidad Científica del Sur, Lima, Peru.,Latin American Network for Cancer Research (LAN-CANCER), Lima, Peru
| | - Janina Bazalar-Palacios
- Latin American Network for Cancer Research (LAN-CANCER), Lima, Peru.,Universidad Católica Los Ángeles de Chimbote, Instituto de Investigación, Chimbote, Peru
| | - Jorge Ybaseta-Medina
- Latin American Network for Cancer Research (LAN-CANCER), Lima, Peru.,Facultad de Medicina Humana, Universidad Nacional San Luis Gonzaga, Ica, Peru
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20133, Milan, Italy
| | - Christian S Alvarez
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
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15
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Berkovic MC, Cigrovski V, Bilic-Curcic I, Mrzljak A. What is the gut feeling telling us about physical activity in colorectal carcinogenesis? World J Clin Cases 2020. [DOI: 10.12998/wjcc.v8.i23.5843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
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16
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Berkovic MC, Cigrovski V, Bilic-Curcic I, Mrzljak A. What is the gut feeling telling us about physical activity in colorectal carcinogenesis? World J Clin Cases 2020; 8:5844-5851. [PMID: 33344583 PMCID: PMC7723696 DOI: 10.12998/wjcc.v8.i23.5844] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 09/28/2020] [Accepted: 10/20/2020] [Indexed: 02/05/2023] Open
Abstract
In the last decades, more efforts are focused on the prevention and treatment of malignant diseases, given the increase in all cancers incidence A lifestyle change, including healthy eating habits and regular physical activity, has significantly impacted colorectal cancer prevention. The effect of dose-dependent physical activity on mortality and recurrence rates of colorectal carcinoma has been unequivocally demonstrated in observational studies. However, clear recommendations are not available on the frequency, duration, and intensity of exercise in patients with colorectal cancer due to the lack of evidence in randomized clinical trials. Regarding pathophysiological mechanisms, the most plausible explanation appears to be the influence of physical activity on reducing chronic inflammation and insulin resistance with a consequent positive effect on insulin growth factor 1 signaling pathways.
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Affiliation(s)
- Maja Cigrovski Berkovic
- Department for Endocrinology, Diabetes and Metabolism, Clinical Hospital Dubrava, Zagreb 10000, Croatia
- Faculty of Kinesiology, University of Zagreb, Zagreb 10000, Croatia
| | | | - Ines Bilic-Curcic
- Department of Pharmacology, Faculty of Medicine, J J Strossmayer University Osijek, Osijek 31000, Croatia
| | - Anna Mrzljak
- Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
- Department of Medicine, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
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17
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Prager GW, Oehler L, Gerger A, Mlineritsch B, Andel J, Petzer A, Wilthoner K, Sliwa T, Pichler P, Winder T, Heibl S, Gruenberger B, Laengle F, Hubmann E, Korger M, Pecherstorfer M, Djanani A, Neumann HJ, Philipp-Abbrederis K, Wöll E, Trondl R, Arnold-Schrauf C, Eisterer W. Comparison of nab-paclitaxel plus gemcitabine in elderly versus younger patients with metastatic pancreatic cancer: Analysis of a multicentre, prospective, non-interventional study. Eur J Cancer 2020; 143:101-112. [PMID: 33296830 DOI: 10.1016/j.ejca.2020.11.003] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 10/20/2020] [Accepted: 11/03/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND Pancreatic cancer (PC) ranks among the deadliest malignancies worldwide. In the MPACT study, first-line nab-paclitaxel plus gemcitabine (nab-P/G) demonstrated activity (median overall survival [OS], 8.7 months) and tolerability in patients with metastatic PC (mPC). However, the clinical evidence of nab-P/G in the elderly (>70 years), who account for the majority of patients with mPC, is limited. This is the first prospective, multicentre, non-interventional study evaluating the tolerability and effectiveness of nab-P/G in younger (≤70 years) versus elderly (>70 years) patients with mPC in the daily clinical routine. METHODS Eligible patients with mPC were treated with nab-P/G and observed until disease progression or unacceptable toxicity. The primary objectives were safety and tolerability of nab-P/G, and the secondary objectives were efficacy and real-life dosing. RESULTS A total of 317 patients with mPC (median age, 70 years) were recruited, of which 299, aged ≤70 (n = 162) and >70 (n = 137) years, were eligible for analysis. Baseline characteristics and the safety profile were comparable between the groups. However, fatigue (22.8% versus 13.0%) and decreased appetite (8.8% versus 1.2%) were more frequent in elderly patients. Younger versus elderly patients equally benefited in terms of objective response rate (36% versus 48%), median progression-free survival (5.6 versus 5.5 months; hazard ratio [HR] = 1.03; p = 0.81) and OS (10.6 versus 10.2 months; HR = 0.89; p = 0.4). In addition, the median treatment duration (5 versus 4 cycles), relative dose intensity (70% versus 74%) or reasons for treatment discontinuation were similar. Most patients (56.2% versus 47.4%) benefited from a second-line therapy. CONCLUSION This prospective real-world analysis confirms the feasibility and tolerability of nab-P/G treatment and reveals OS data similar for younger patients and elderly patients aged >70 years. CLINICALTRIALS. GOV REGISTRATION NCT02555813. AUSTRIAN NIS REGISTRY NIS005071.
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Affiliation(s)
- Gerald W Prager
- Medical University of Vienna, Department of Oncology, Währinger Gürtel 18-20, 1090, Vienna, Austria.
| | - Leopold Oehler
- Sankt Josef Krankenhaus, Internal Medicine 2, Auhofstraße 189, 1130, Vienna, Wien, Austria.
| | - Armin Gerger
- Medical University of Graz, Clinical Institute of Oncology, Auenbruggerplatz 15, 8036, Graz, Austria.
| | - Brigitte Mlineritsch
- Universitätsklinik Salzburg, University Clinic for Internal Medicine III, Müllner Haupstraße 48, 5020, Salzburg, Austria.
| | - Johannes Andel
- Pyhrn-Eisenwurzen Klinikum, Internal Medicine II, Sierningerstraße 170, 4400, Steyr, Austria.
| | - Andreas Petzer
- Ordensklinikum Linz BHS - EKH, Internal Medicine I, Medical Oncology and Hematology, Seilerstätte 4, 4010, Linz Austria.
| | - Klaus Wilthoner
- Landeskrankenhaus Vöcklabruck, Vöcklabruck, Internal Medicine, Hemato-Oncology, Dr. Wilhelm-Bock-Straße 1, 4840 Vöcklabruck, Austria.
| | - Thamer Sliwa
- Hanuschkrankenhaus, Medicine III for Hematology and Oncology, Heinrich-Collin-Straße 30, 1140, Wien, Vienna, Austria.
| | - Petra Pichler
- Universitätsklinikum St. Pölten, Internal Medicine I, Dunant-Platz 1, 3100, Sankt Pölten, Austria.
| | - Thomas Winder
- Landeskrankenhaus Feldkirch, Internal Medicine II, Carinagasse 47, 6807, Feldkirch, Austria.
| | - Sonja Heibl
- Klinikum Wels-Grieskirchen, Internal Medicine IV, Grieskirchner Straße 42, 4600, Wels, Austria.
| | - Birgit Gruenberger
- Landesklinikum Wiener Neustadt, Internal Medicine for Hematology and Internal Oncology, Corvinusring 2-5, 2700, Wiener Neustadt, Austria.
| | - Friedrich Laengle
- Landesklinikum Wiener Neustadt, Department of Surgery, Corvinusring 2-5, 2700, Wiener Neustadt, Austria.
| | - Eva Hubmann
- Krankenhaus der Barmherzigen Brüder, Internal Medicine, Marschallgasse 12, 8020, Graz, Austria.
| | - Markus Korger
- Krankenhaus der Barmherzigen Brüder, Internal Medicine II, Johannes von Gott-Platz 1, 7000, Eisenstadt, Austria.
| | - Martin Pecherstorfer
- Karl Landsteiner University of Health Sciences, Department of Internal Medicine, University Hospital, 3500, Krems an der Donau, Austria.
| | - Angela Djanani
- Medical University of Innsbruck, Institute of Gastroenterology, Internal Medicine I, Institute of Gastroenterology, Anichstraße 35, 6020, Innsbruck, Austria.
| | - Hans-Joerg Neumann
- Krankenhaus der Elisabethinen, Internal Medicine, Völkermarkter Straße 15-19, 9020, Klagenfurt, Austria.
| | - Kathrin Philipp-Abbrederis
- Medical University of Innsbruck, Institute of Hematology and Oncology, Internal Medicine V, Institute of Hematology and Oncology, Anichstraße 35, 6020, Innsbruck, Austria.
| | - Ewald Wöll
- Krankenhaus Zams, Internal Medicine, Sanatoriumstraße 43, 6511, Zams, Austria.
| | - Robert Trondl
- Celgene Austria GmbH, EuroPlaza Building E, Technologiestraße 10, 1120, Vienna, Austria.
| | | | - Wolfgang Eisterer
- Klinikum Klagenfurt Am Wörthersee, Internal Medicine and Oncology, Feschnigstraße 11, 9020, Klagenfurt, Austria.
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18
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Zhao Y, Ye F, Brismar TB, Li X, He R, Heuchel R, El-Sayed R, Feliu N, Zheng W, Oerther S, Dutta J, Parak WJ, Muhammed M, Hassan M. Multimodal Imaging of Pancreatic Ductal Adenocarcinoma Using Multifunctional Nanoparticles as Contrast Agents. ACS APPLIED MATERIALS & INTERFACES 2020; 12:53665-53681. [PMID: 33201660 PMCID: PMC7735668 DOI: 10.1021/acsami.0c15430] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/09/2023]
Abstract
Late diagnosis and refractory behavior toward current treatment protocols make pancreatic ductal adenocarcinoma (PDAC) one of the most difficult cancer forms to treat. The imaging-based approach plays an important role to identify potentially curable PDAC patients in high-risk groups at the early stage. In the present study, we developed a core-shell structured gold nanorod (AuNR) as a contrast agent for multimodal imaging and investigated its application for PDAC diagnosis. The composite nanoparticles composed of a AuNR core inside a layer of mesoporous silica that was then coated with a gadolinium oxide carbonate shell (AuNR-SiO2-Gd) are designed to be used in magnetic resonance imaging (MRI), X-ray computed tomography (CT), and photoacoustic imaging (PAI). A phantom study with the AuNR-SiO2-Gd NPs demonstrated higher MRI contrast compared to Gadovist and higher X-ray attenuation than Visipaque. A strong, stable, and broad wavelength range signal with a peak at 800 nm was observed in PAI. The AuNR-SiO2-Gd NPs showed significant contrast enhancement under PAI/MRI/CT in both the liver and spleen of control mice after intravenous administration. The utility in PDAC was studied in a genetically engineered mouse model carrying Kras and p53 mutations, which develops spontaneous tumors and keeps the desmoplasia and hypovascularity feature of PDAC in patients. The AuNR-SiO2-Gd NPs were highly accumulated in the surrounding soft tissues but were sparsely distributed throughout the tumor due to dense stroma infiltration and poor tumor vascularization. Hence, a negative contrast within the tumor area in CT/PAI and a positive contrast in MRI were observed. In conclusion, AuNR-SiO2-Gd NPs have good potential to be developed as a multimodal contrast agent for PDAC, which might improve early diagnosis and benefit the clinical outcome for PDAC patients.
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Affiliation(s)
- Ying Zhao
- Division of Experimental
Cancer Medicine, Department of Laboratory Medicine (LABMED), Karolinska Institutet, SE-141 86 Stockholm, Sweden
- Clinical Research Center, and Center for Allogeneic Stem
Cell Transplantation (CAST), Karolinska
University Hospital—Huddinge, SE-141 86 Stockholm, Sweden
| | - Fei Ye
- Division of Experimental
Cancer Medicine, Department of Laboratory Medicine (LABMED), Karolinska Institutet, SE-141 86 Stockholm, Sweden
- KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden
| | - Torkel B. Brismar
- Division of Medical Imaging and Technology, Department of Clinical
Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86 Stockholm, Sweden
| | - Xuan Li
- Pancreatic
Cancer Research Laboratory, Department of Clinical Science, Intervention
and Technology (CLINTEC), Karolinska Institutet, SE-141 86 Stockholm, Sweden
| | - Rui He
- Division of Experimental
Cancer Medicine, Department of Laboratory Medicine (LABMED), Karolinska Institutet, SE-141 86 Stockholm, Sweden
- Clinical Research Center, and Center for Allogeneic Stem
Cell Transplantation (CAST), Karolinska
University Hospital—Huddinge, SE-141 86 Stockholm, Sweden
| | - Rainer Heuchel
- Pancreatic
Cancer Research Laboratory, Department of Clinical Science, Intervention
and Technology (CLINTEC), Karolinska Institutet, SE-141 86 Stockholm, Sweden
| | - Ramy El-Sayed
- Division of Experimental
Cancer Medicine, Department of Laboratory Medicine (LABMED), Karolinska Institutet, SE-141 86 Stockholm, Sweden
| | - Neus Feliu
- Division of Experimental
Cancer Medicine, Department of Laboratory Medicine (LABMED), Karolinska Institutet, SE-141 86 Stockholm, Sweden
- Center for Hybrid Nanostructures (CHyN), University of Hamburg, 22607 Hamburg, Germany
| | - Wenyi Zheng
- Division of Experimental
Cancer Medicine, Department of Laboratory Medicine (LABMED), Karolinska Institutet, SE-141 86 Stockholm, Sweden
- Clinical Research Center, and Center for Allogeneic Stem
Cell Transplantation (CAST), Karolinska
University Hospital—Huddinge, SE-141 86 Stockholm, Sweden
| | - Sandra Oerther
- Division of Experimental
Cancer Medicine, Department of Laboratory Medicine (LABMED), Karolinska Institutet, SE-141 86 Stockholm, Sweden
- Clinical Research Center, and Center for Allogeneic Stem
Cell Transplantation (CAST), Karolinska
University Hospital—Huddinge, SE-141 86 Stockholm, Sweden
| | - Joydeep Dutta
- KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden
| | - Wolfgang J. Parak
- Center for Hybrid Nanostructures (CHyN), University of Hamburg, 22607 Hamburg, Germany
| | - Mamoun Muhammed
- KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden
- Institute of Graduate Studies and Research (IGSR), Alexandria University, Alexandria 21526, Egypt
| | - Moustapha Hassan
- Division of Experimental
Cancer Medicine, Department of Laboratory Medicine (LABMED), Karolinska Institutet, SE-141 86 Stockholm, Sweden
- Clinical Research Center, and Center for Allogeneic Stem
Cell Transplantation (CAST), Karolinska
University Hospital—Huddinge, SE-141 86 Stockholm, Sweden
- Institute of Graduate Studies and Research (IGSR), Alexandria University, Alexandria 21526, Egypt
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19
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Illés D, Ivány E, Holzinger G, Kosár K, Adam MG, Kamlage B, Zsóri G, Tajti M, Svébis MM, Horváth V, Oláh I, Márta K, Váncsa S, Zádori N, Szentesi A, Czakó B, Hegyi P, Czakó L. New Onset of DiabetEs in aSsociation with pancreatic ductal adenocarcinoma (NODES Trial): protocol of a prospective, multicentre observational trial. BMJ Open 2020; 10:e037267. [PMID: 33444177 PMCID: PMC7678370 DOI: 10.1136/bmjopen-2020-037267] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 09/05/2020] [Accepted: 09/22/2020] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with an overall 5-year survival of approximately 8%. The success in reducing the mortality rate of PDAC is related to the discovery of new therapeutic agents, and to a significant extent to the development of early detection and prevention programmes. Patients with new-onset diabetes mellitus (DM) represent a high-risk group for PDAC as they have an eightfold higher risk of PDAC than the general population. The proposed screening programme may allow the detection of PDAC in the early, operable stage. Diagnosing more patients in the curable stage might decrease the morbidity and mortality rates of PDAC and additionally reduce the burden of the healthcare. METHODS AND ANALYSIS This is a prospective, multicentre observational cohort study. Patients ≥60 years old diagnosed with new-onset (≤6 months) diabetes will be included. Exclusion criteria are (1) Continuous alcohol abuse; (2) Chronic pancreatitis; (3) Previous pancreas operation/pancreatectomy; (4) Pregnancy; (5) Present malignant disease and (6) Type 1 DM. Follow-up visits are scheduled every 6 months for up to 36 months. Data collection is based on questionnaires. Clinical symptoms, body weight and fasting blood will be collected at each, carbohydrate antigen 19-9 and blood to biobank at every second visit. The blood samples will be processed to plasma and analysed with mass spectrometry (MS)-based metabolomics. The metabolomic data will be used for biomarker validation for early detection of PDAC in the high-risk group patients with new-onset diabetes. Patients with worrisome features will undergo MRI or endoscopic ultrasound investigation, and surgical referral depending on the radiological findings. One of the secondary end points is the incidence of PDAC in patients with newly diagnosed DM. ETHICS AND DISSEMINATION The study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (41085-6/2019). We plan to disseminate the results to several members of the healthcare system includining medical doctors, dietitians, nurses, patients and so on. We plan to publish the results in a peer-reviewed high-quality journal for professionals. In addition, we also plan to publish it for lay readers in order to maximalise the dissemination and benefits of this trial. TRIAL REGISTRATION NUMBER ClinicalTrials.gov NCT04164602.
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Affiliation(s)
- Dóra Illés
- First Department of Medicine, University of Szeged Faculty of Medicine, Szeged, Hungary
| | - Emese Ivány
- First Department of Medicine, University of Szeged Faculty of Medicine, Szeged, Hungary
| | - Gábor Holzinger
- First Department of Medicine, University of Szeged Faculty of Medicine, Szeged, Hungary
| | - Klára Kosár
- First Department of Medicine, University of Szeged Faculty of Medicine, Szeged, Hungary
| | - M Gordian Adam
- Tegeler Weg 33, 10589, Metanomics Health GmbH, Berlin, Germany
| | - Beate Kamlage
- Tegeler Weg 33, 10589, Metanomics Health GmbH, Berlin, Germany
| | - Gábor Zsóri
- First Department of Medicine, University of Szeged Faculty of Medicine, Szeged, Hungary
| | - Máté Tajti
- First Department of Medicine, University of Szeged Faculty of Medicine, Szeged, Hungary
| | - Márk M Svébis
- Department of Internal Medicine, Semmelweis University of Medicine, Budapest, Hungary
| | - Viktor Horváth
- Department of Internal Medicine, Semmelweis University of Medicine, Budapest, Hungary
| | - Ilona Oláh
- Ilona Tóth Outpatient Clinic, Budapest, Hungary
| | - Katalin Márta
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
- János Szentágothai Research Center, University of Pécs, Pécs, Hungary
| | - Szilárd Váncsa
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
- János Szentágothai Research Center, University of Pécs, Pécs, Hungary
| | - Noémi Zádori
- Institute for Translational Medicine, Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar, Pecs, Hungary
| | - Andrea Szentesi
- Institute for Translational Medicine, Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar, Pecs, Hungary
- MTA-SZTE Translational Gastroenterology Research Group, Szegedi Tudomanyegyetem, Szeged, Hungary
| | - Bálint Czakó
- Medical School, University of Szeged Faculty of Medicine, Szeged, Hungary
| | - Péter Hegyi
- Institute for Translational Medicine, Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar, Pecs, Hungary
| | - László Czakó
- First Department of Medicine, University of Szeged, Szeged, Hungary
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Li Z, Zou W, Zhang J, Zhang Y, Xu Q, Li S, Chen C. Mechanisms of CDK4/6 Inhibitor Resistance in Luminal Breast Cancer. Front Pharmacol 2020; 11:580251. [PMID: 33364954 PMCID: PMC7751736 DOI: 10.3389/fphar.2020.580251] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Accepted: 09/30/2020] [Indexed: 12/22/2022] Open
Abstract
As a new-generation CDK inhibitor, a CDK4/6 inhibitor combined with endocrine therapy has been successful in the treatment of advanced estrogen receptor-positive (ER+) breast cancer. Although there has been overall progress in the treatment of cancer, drug resistance is an emerging cause for breast cancer-related death. Overcoming CDK4/6 resistance is an urgent problem. Overactivation of the cyclin-CDK-Rb axis related to uncontrolled cell proliferation is the main cause of CDK4/6 inhibitor resistance; however, the underlying mechanisms need to be clarified further. We review various resistance mechanisms of CDK4/6 inhibitors in luminal breast cancer. The cell signaling pathways involved in therapy resistance are divided into two groups: upstream response mechanisms and downstream bypass mechanisms. Finally, we discuss possible strategies to overcome CDK4/6 inhibitor resistance and identify novel resistance targets for future clinical application.
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Affiliation(s)
- Zhen Li
- Department of the Third Breast Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Wei Zou
- Queen Mary Institute, Nanchang University, Nanchang, China
| | - Ji Zhang
- Department of the Third Breast Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yunjiao Zhang
- Kunming Medical University Haiyuan College, Kunming, China
| | - Qi Xu
- Department of Molecular Biosciences, Institute of Cellular and Molecular Biology, The University of Texas, Austin, TX, United States
| | - Siyuan Li
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China
| | - Ceshi Chen
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China
- KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China
- Institute of Translation Medicine, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
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21
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Fiorelli A, Vitiello F, Morgillo F, Di Crescenzo RM, Bianco A, Santini M, Di Domenico M. Adjuvant treatment with EGFR TKI in resected non-small cell lung cancer with EGFR mutation: all that glitters is not gold! ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1199. [PMID: 33241048 PMCID: PMC7576010 DOI: 10.21037/atm.2020.04.57] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- Alfonso Fiorelli
- Thoracic Surgery Unit, University of Campania "Luigi Vanvitelli", Naples, Italy
| | | | - Floriana Morgillo
- Oncology Unit, University of Campania "Luigi Vanvitelli", Naples, Italy
| | | | - Andrea Bianco
- Pneumology Unit, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Mario Santini
- Thoracic Surgery Unit, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Marina Di Domenico
- Pathology Unit, University of Campania "Luigi Vanvitelli", Naples, Italy
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Xi Y, Dong W, Qiao L, Han K, Chen W, Wang W. Trends in incidence and mortality of esophageal cancer in Inner Mongolia, 2010-2015. Thorac Cancer 2020; 11:2440-2448. [PMID: 32716130 PMCID: PMC7471038 DOI: 10.1111/1759-7714.13552] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 06/02/2020] [Accepted: 06/05/2020] [Indexed: 12/24/2022] Open
Abstract
Background Esophageal cancer is among the leading cancer types in Inner Mongolia. This study aimed to investigate the incidence and mortality rates of esophageal cancer in 2015 and the trends in these rates in the 2010–2015 period in this region. Methods National Colorectal Cancer Roundtable (NCCR) screening methods and criteria were used to extract data from 10 cancer registries stratified by area (urban/rural), sex, and age group. The Chinese standard population in 2000 and Segi's world population were used to calculate age‐standardized rates. The annual percentage change (APC) in these rates was calculated using the Joinpoint Regression Program. Results In 2015, Inner Mongolia had 4324 new cases (4027 male vs. 297 female patients) and 3559 deaths (3300 male vs. 259 female patients) from esophageal cancer. The crude incidence, age‐standardized incidence by Chinese population, age‐standardized incidence by world population, and cumulative incidence were 13.45/100 000, 9.92/100 000, 10.18/100 000, and 1.30%, respectively. The corresponding figures for mortality were 11.32/100 000, 8.35/100 000, 8.53/100 000, and 1.04%. The incidence and mortality increased with age between 40 and 80 years. The rates in rural dwellers, especially men, showed negative APC (−13.25% vs. −11.08%; P < 0.05). Conclusions The incidence and mortality rates of esophageal cancer in Inner Mongolia increased between 2010 and 2015. The rates were higher in men in rural areas, middle‐aged and elderly individuals. Prevention and control programs focused on these groups, in addition to early diagnosis and treatment of esophageal cancer, are needed to reduce these rates. Key points Significant findings of the study: In Inner Mongolia, incidence and mortality rates of esophageal cancer were higher in urban areas than in rural areas and in men than in women between 2010 and 2015, and in middle‐aged and elderly than in younger people. What this study adds: Prevention and control programs, in addition to early diagnosis and treatment of esophageal cancer, should be tailored to specifically target men in rural areas and middle‐aged and elderly individuals in order to reduce the incidence and mortality rates of this pathology.
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Affiliation(s)
- Yunfeng Xi
- The Inner Mongolia Autonomous Region Comprehensive Center for Disease Control and Prevention, Hohhot, China
| | | | - Liying Qiao
- The Inner Mongolia Autonomous Region Comprehensive Center for Disease Control and Prevention, Hohhot, China
| | - Ke Han
- The Inner Mongolia Autonomous Region Comprehensive Center for Disease Control and Prevention, Hohhot, China
| | - Wenjie Chen
- The Inner Mongolia Autonomous Region Comprehensive Center for Disease Control and Prevention, Hohhot, China
| | - Wenrui Wang
- The Inner Mongolia Autonomous Region Comprehensive Center for Disease Control and Prevention, Hohhot, China
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Antiangiogenesis Roles of Exosomes with Fei-Liu-Ping Ointment Treatment are Involved in the Lung Carcinoma with the Lewis Xenograft Mouse Model. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:9418593. [PMID: 32308722 PMCID: PMC7142396 DOI: 10.1155/2020/9418593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 10/16/2019] [Accepted: 10/22/2019] [Indexed: 11/24/2022]
Abstract
Exosomes display efficient biocompatibility and represent valuable vehicles for drug or effective material delivery in a tumour-therapeutic approach. Following treatment with Fei-Liu-Ping (FLP) ointment, a traditional Chinese herbal formula, which is used for treating lung cancer patients, could inhibit lung carcinoma growth in clinical and animal studies. In the present study, the values of VEGF and PDGF, which were closely related to angiogenesis, were estimated in serum and carcinoma tissue exosomes to unveil the FLP effects on angiogenesis. The common inflammatory factors of IL-6, IL-1β, TNF-α, and TGF-β in serum exosomes were also detected with the Lewis xenograft model. Methods. Male C57BL/6 mice were randomly divided into four groups, namely, normal, model, cyclophosphamide (CTX), and FLP treatment groups. Histological structures were observed and imaged by H&E. CD31 expressions in tumour tissues were detected by immunofluorescence (IF) and western blot (WB). VEGF, PDGF, and PDGFR levels in exosomes, serum, tumour, and lung tissues were detected by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and WB, respectively. IL-6, IL-1β, TNF-α, and TGF-β levels in exosomes were measured by multiplex immunoassay panels. Results. The results showed that FLP had tumour growth inhibition rate (39.31%). CD31 protein expression was obviously decreased in tumour tissues of CTX- and FLP-treated MO mice, compared to that of MO mice (P < 0.05 or P < 0.001). VEGF, PDGF, and PDGFR expression levels with FLP treatment were downregulated in exosomes, serum, tumour, and lung tissues compared to model group (P < 0.05 or P < 0.01). The expressions of IL-6, IL-1β, and TNF-α were downregulated in exosomes compared to the model group (P < 0.05 or P < 0.01). Conclusions. This study suggested that FLP had the ability of inhibiting tumourigenesis in a Lewis lung xenograft mouse model, whose therapeutic mechanisms might relate with the downregulation of angiogenesis factor and tumour inflammatory cytokines levels.
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Zawadzka I, Jeleń A, Pietrzak J, Żebrowska-Nawrocka M, Michalska K, Szmajda-Krygier D, Mirowski M, Łochowski M, Kozak J, Balcerczak E. The impact of ABCB1 gene polymorphism and its expression on non-small-cell lung cancer development, progression and therapy - preliminary report. Sci Rep 2020; 10:6188. [PMID: 32277145 PMCID: PMC7148348 DOI: 10.1038/s41598-020-63265-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Accepted: 03/27/2020] [Indexed: 01/12/2023] Open
Abstract
The ABCB1 gene belongs to ATP binding cassette (ABC) transporter genes that has been previously implicated in cancer progression and drug response. This study aimed to evaluate the association between the SNP 3435 and the expression of the ABCB1 gene in lung cancer patients in the Polish population in comparison to clinicopathological parameters and treatment. 150 RNA and 47 DNA samples were isolated from 49 lung cancer cases including both tissue samples and blood taken from the same patients at three time points: diagnosis, 100 days and one year after the surgical intervention. Qualitative and real-time PCR analysis of expression were done, also genotyping by PCR-RFLP. Mutant homozygous TT and allele T are present statistically significantly more frequently in the group of patients with lung cancer. There is no difference with expression level in lung cancer tissue and blood sample taken from the same patients before surgical treatment. On the basis of blood samples analysis it was observed that the expression level of ABCB1 mRNA was growing in time. Higher levels were marked after 100 days and one year after the surgical intervention. The complementary pharmacological treatment induced higher expression levels of ABCB1. The presented data suggest an important role of ABCB1 in lung cancer, the increasing level of ABCB1 mRNA which can be connected with induction of multidrug resistance mechanism is also significant, that observation must be confirmed in further analysis.
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Affiliation(s)
- Izabela Zawadzka
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, ul. Muszynskiego 1, 90-151, Lodz, Poland
| | - Agnieszka Jeleń
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, ul. Muszynskiego 1, 90-151, Lodz, Poland
| | - Jacek Pietrzak
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, ul. Muszynskiego 1, 90-151, Lodz, Poland
| | - Marta Żebrowska-Nawrocka
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, ul. Muszynskiego 1, 90-151, Lodz, Poland
| | - Katarzyna Michalska
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, ul. Muszynskiego 1, 90-151, Lodz, Poland
| | - Dagmara Szmajda-Krygier
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, ul. Muszynskiego 1, 90-151, Lodz, Poland
| | - Marek Mirowski
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, ul. Muszynskiego 1, 90-151, Lodz, Poland
| | - Mariusz Łochowski
- Department of Thoracic Surgery, Memorial Copernicus Hospital, Medical University of Lodz, Lodz, Poland
| | - Józef Kozak
- Department of Thoracic Surgery, Memorial Copernicus Hospital, Medical University of Lodz, Lodz, Poland
| | - Ewa Balcerczak
- Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, ul. Muszynskiego 1, 90-151, Lodz, Poland.
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Bhattacharjee A, Rajendra J, Dikshit R, Dutt S. HER2 borderline is a negative prognostic factor for primary malignant breast cancer. Breast Cancer Res Treat 2020; 181:225-231. [PMID: 32236825 DOI: 10.1007/s10549-020-05608-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Accepted: 03/21/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND HER-(human epidermal growth factor receptor 2) gene amplification and protein overexpression are important predictive, prognosis markers, and therapeutic target for breast cancer, emphasizing the importance of categorizing patients into HER2 positive and negative. However, from immunohistochemistry scores, 2% patients are neither HER2 + nor -ve, but borderline called HER2B. To make informed treatment decisions of these patients, it is important to know how different this group is compared to HER-2 positive/negative. METHODS We analyzed n = 104,668 breast cancer patient samples from Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis was performed using open source R (Cran project R version 3.5.0) "survival" package. Hazard ratio with confidence intervals was computed using coxph function. RESULTS Of n = 104,668, 2239 (2.13%) patients were HER2 borderline, 87,157 (83.26%) HER2-negative, and 15,272 (14.6%) HER2-positive. The breast cancer as primary malignancy was observed in 84,944 (81.16%) patients. In primary malignant breast cancer (PMBC) patients, the hazard ratio among HER2-negative patients was significantly higher than HER2-positive patient samples (HR = 0.772, 95% CI 0.715-0.833, p = < .001), whereas HER2 negative status was not significantly favorable in PMBC negative patients in HER2-positive (HR = .919, 95% 0.797-1.06, p = .248). Most importantly in PMBC patients, the HR for HER2-borderline was poor in comparison to HER2 negative (HR = 1.354, 95% CI 1.126-1.627, p = < .001). CONCLUSION This is the first report with large cohort of patient samples and significant statistical power to demonstrate that HER2 borderline represents a negative prognostic factor for PMBC. Thus providing rationale for controlled clinical trial for HER2-targeted therapies in HER2-borderline patients.
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Affiliation(s)
- Atanu Bhattacharjee
- Section of Biostatistics, Centre for Cancer Epidemiology, Tata Memorial Centre, Kharghar Navi, Mumbai, 410210, India.,Homi Bhabha National Institute, Anushakti Nagar, Mumbai, 400085, India
| | - Jacinth Rajendra
- Shilpee Dutt Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi, Mumbai, Maharashtra, 410210, India.,Training School Complex, Homi Bhabha National Institute, Anushakti Nagar, Mumbai, 400085, India
| | - Rajesh Dikshit
- Centre for Cancer Epidemiology, Tata Memorial Centre, Mumbai, India
| | - Shilpee Dutt
- Shilpee Dutt Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi, Mumbai, Maharashtra, 410210, India. .,Training School Complex, Homi Bhabha National Institute, Anushakti Nagar, Mumbai, 400085, India.
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Damanakis AI, Ostertag L, Waldschmidt D, Kütting F, Quaas A, Plum P, Bruns CJ, Gebauer F, Popp F. Proposal for a definition of "Oligometastatic disease in pancreatic cancer". BMC Cancer 2019; 19:1261. [PMID: 31888547 PMCID: PMC6937989 DOI: 10.1186/s12885-019-6448-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 12/11/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND To date, patients with metastasized pancreatic ductal adenocarcinoma (PDAC M1) are regarded as a uniform collective. We hypothesize the existence of oligometastatic disease (OMD): a state of PDAC M1 disease with better tumor biology, limited metastasis, and increased survival. METHODS Data of 128 PDAC M1 patients treated at the University of Cologne between 2008 and 2018 was reviewed. Interdependence between clinical parameter was calculated using the Mann-Whitney U-Test. Survival curves were generated using the Kaplan-Meier method and analyzed using the log-rank test. RESULTS Eighty-one (63%) patients had metastases confined to one organ (single organ metastasis, SOG) whereas the remaining 47 (37%) showed multiple metastatic sites (multi-organ metastasis, MOG). Survival analysis revealed a median overall survival (OS) of 12.2 months for SOG vs 4.5 months for MOG (95% CI 5.7-9.8; p < 0.001). We defined limited disease by the presence of ≤4 metastases in liver or lung. Limited disease together with CA 19-9 baseline < 1000 U/ml and response or stable disease after first-line chemotherapy defined OMD. We identified 8 patients with hepatic metastases and 2 with pulmonary metastases matching all OMD criteria. This group of 10 (7.8%) had a median overall survival of 19.4 vs 7.2 months compared to the remaining patients (95% CI 5.7-9.8; p = 0.009). CONCLUSION We propose a definition of oligometastatic disease in PDAC including anatomical criteria and biological criteria reflecting better tumor biology. The 10 OMD patients (7.8%) survived significantly longer and might even benefit from surgical resection in the future.
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Affiliation(s)
- Alexander I Damanakis
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany.
| | - Luisa Ostertag
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany
| | - Dirk Waldschmidt
- Department of Gastroenterology, University Hospital of Cologne, Cologne, Germany
| | - Fabian Kütting
- Department of Gastroenterology, University Hospital of Cologne, Cologne, Germany
| | - Alexander Quaas
- Institute of Pathology, University Hospital of Cologne, Cologne, Germany
| | - Patrick Plum
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany
| | - Christiane J Bruns
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany
| | - Florian Gebauer
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany
| | - Felix Popp
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany
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Malvezzi M, Carioli G, Bertuccio P, Boffetta P, Levi F, La Vecchia C, Negri E. European cancer mortality predictions for the year 2018 with focus on colorectal cancer. Ann Oncol 2019; 29:1016-1022. [PMID: 29562308 DOI: 10.1093/annonc/mdy033] [Citation(s) in RCA: 147] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Background We projected cancer mortality statistics for 2018 for the European Union (EU) and its six more populous countries, using the most recent available data. We focused on colorectal cancer. Materials and methods We obtained cancer death certification data from stomach, colorectum, pancreas, lung, breast, uterus, ovary, prostate, bladder, leukaemia, and total cancers from the World Health Organisation database and projected population data from Eurostat. We derived figures for France, Germany, Italy, Poland, Spain, the UK, and the EU in 1970-2012. We predicted death numbers by age group and age-standardized (world population) rates for 2018 through joinpoint regression models. Results EU total cancer mortality rates are predicted to decline by 10.3% in men between 2012 and 2018, reaching a predicted rate of 128.9/100 000, and by 5.0% in women with a rate of 83.6. The predicted total number of cancer deaths is 1 382 000 when compared with 1 333 362 in 2012 (+3.6%). We confirmed a further fall in male lung cancer, but an unfavourable trend in females, with a rate of 14.7/100 000 for 2018 (13.9 in 2012, +5.8%) and 94 500 expected deaths, higher than the rate of 13.7 and 92 700 deaths from breast cancer. Colorectal cancer predicted rates are 15.8/100 000 men (-6.7%) and 9.2 in women (-7.5%); declines are expected in all age groups. Pancreatic cancer is stable in men, but in women it rose +2.8% since 2012. Ovarian, uterine and bladder cancer rates are predicted to decline further. In 2018 alone, about 392 300 cancer deaths were avoided compared with peak rates in the late 1980s. Conclusion We predicted continuing falls in mortality rates from major cancer sites in the EU and its major countries to 2018. Exceptions are pancreatic cancer and lung cancer in women. Improved treatment and-above age 50 years-organized screening may account for recent favourable colorectal cancer trends.
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Affiliation(s)
- M Malvezzi
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - G Carioli
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - P Bertuccio
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - P Boffetta
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, USA
| | - F Levi
- Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland
| | - C La Vecchia
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
| | - E Negri
- Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, Milan, Italy
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Jung G, Kim SH, Kim TG, Kim YZ. Demographic and Socioeconomic Factors for Renouncing Further Active Therapy for Patients with Brain Metastasis of Non-Small Cell Lung Cancer. Brain Tumor Res Treat 2019; 7:112-121. [PMID: 31686442 PMCID: PMC6829092 DOI: 10.14791/btrt.2019.7.e35] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 07/12/2019] [Accepted: 09/03/2019] [Indexed: 12/22/2022] Open
Abstract
Background As patients with brain metastasis (BM) of non-small cell lung cancer (NSCLC) have dismal prognosis, some of them decide to discontinue further treatment for BM. The objective of this study was to determine factors for renouncing further active therapy in patients with BM of NSCLC, focusing on their demographic and socioeconomic status. Methods Medical records of 105 patients with radiological diagnosis of BM of NSCLC for the recent 11 years at authors' institution were retrospectively reviewed. Clinical features as well as demographic and socioeconomic characteristics such as marriage status, cohabiting family members, religious affiliations, educational background, and economic responsibility were reviewed. Results Median overall survival (OS) was 13.84 (95% CI: 10.26–17.42) years in 67 patients (group A) who underwent active treatment (radiotherapy and/or chemotherapy) and 4.76 (95% CI: 3.12–6.41) years in 38 patients (group B) who renounced active treatment. Less patients were unmarried (p=0.046), more cohabitating family members (p=0.008), and economically independent (p=0.014) in group A than those in group B. Similarly, the unmarried, and none cohabitating family members had short OS (5.17 and 7.38 years, respectively). In multivariate analysis for predisposing factors of OS in these patients, the following demographic and socioeconomic factors had independent significance: marriage status and cohabitating family members. Conclusion This study suggests that demographic and socioeconomic status as well as clinical factors could influence the decision of further active treatment and prognosis of patients with BM of NSCLC.
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Affiliation(s)
- Gyuseo Jung
- Division of Neuro-Oncology and Department of Neurosurgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Seok Hyun Kim
- Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Tae Gyu Kim
- Department of Radiation Oncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Young Zoon Kim
- Division of Neuro-Oncology and Department of Neurosurgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
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Mangin D, Garfinkel D. Foreword to the first special collection: Addressing the invisible iatrogenic epidemic: the role of deprescribing in polypharmacy and inappropriate medication use. Ther Adv Drug Saf 2019; 10:2042098619883156. [PMID: 31673327 PMCID: PMC6804352 DOI: 10.1177/2042098619883156] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Affiliation(s)
- Dee Mangin
- Department of Family Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Doron Garfinkel
- Geriatric-Palliative consultant, Sheba Medical Center and Homecare Hospice, Israel Cancer Association, Israel
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30
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Hwang SH, Kim HY, Lee EJ, Hwang HK, Park MS, Kim MJ, Lee WJ, Chung YE, Kang CM. Preoperative Clinical and Computed Tomography (CT)-Based Nomogram to Predict Oncologic Outcomes in Patients with Pancreatic Head Cancer Resected with Curative Intent: A Retrospective Study. J Clin Med 2019; 8:1749. [PMID: 31640240 PMCID: PMC6833079 DOI: 10.3390/jcm8101749] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 09/25/2019] [Accepted: 10/17/2019] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Currently, proposed nomograms are mainly based on post-operative histopathology. The purpose of this study was to identify preoperative computed tomography (CT) and clinical information that allow prediction of disease-free (DFS) and overall survival (OS) of patients surgically treated for pancreatic head cancer. METHODS A total of 136 patients who underwent curative-intent surgery were retrospectively reviewed. Based on results from multivariate Cox regression analysis, a prediction model was constructed with preoperative CT features and clinical information. Overall performance of the nomogram was calculated by Harrell's C-index. RESULTS Symptoms at diagnosis, preoperative serum CA 19-9 ≥ 34 U/mL, and four imaging features (necrosis (DFS, P = 0.066; OS, P = 0.002), possible venous invasion (DFS, P = 0.150, OS, P = 0.055), suspected metastatic regional lymph node (DFS, P = 0.001; OS, P = 0.099), and associated pancreatitis or pseudocyst (DFS, P = 0.013; OS, P = 0.041)) were included to build the nomogram. The c-statistics for the discrimination power of the proposed nomogram was 0.6496 for DFS and 0.6746 for OS. CONCLUSION A nomogram derived from preoperative CT and clinical information could estimate the risk of recurrence and all-cause death after curative-intent surgery for radiologically resectable pancreatic head cancer.
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Affiliation(s)
- Shin Hye Hwang
- Department of Radiology, National Health Insurance Service Ilsan Hospital, Goyang 410-719, Korea.
| | - Ha Yan Kim
- Department of Biomedical Systems Informatics, Biostatistics Collaboration Unit and Yonsei University College of Medicine, Seoul 03722, Korea.
| | - Eun Ju Lee
- Department of Biomedical Systems Informatics, Biostatistics Collaboration Unit and Yonsei University College of Medicine, Seoul 03722, Korea.
| | - Ho Kyoung Hwang
- Division of HBP Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Korea.
| | - Mi-Suk Park
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.
| | - Myeong-Jin Kim
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.
| | - Woo Jung Lee
- Division of HBP Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Korea.
| | - Yong Eun Chung
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea.
| | - Chang Moo Kang
- Division of HBP Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Korea.
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Goodwin R, Jonker D, Chen E, Kennecke H, Cabanero M, Tsao MS, Vickers M, Bohemier C, Lim H, Ritter H, Tu D, Seymour L. A phase Ib study of a PI3Kinase inhibitor BKM120 in combination with panitumumab in patients with KRAS wild-type advanced colorectal cancer. Invest New Drugs 2019; 38:1077-1084. [PMID: 31506897 DOI: 10.1007/s10637-019-00814-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Accepted: 06/07/2019] [Indexed: 11/29/2022]
Abstract
Background Resistance to Epidermal Growth Factor inhibition (EGFRi) in patients with KRAS wild-type (wt) Colorectal Cancer (CRC) may occur as a result of PI3K/AKT/mTOR signaling. We conducted a study to establish the recommended phase II dose (RP2D) and response rate of panitumumab, an EGFRi, plus BKM120, a PI3K inhibitor, in advanced CRC. Methods Patients with chemotherapy refractory KRAS wt CRC, who were EGFRi naive were enrolled. A 3 + 3 dose escalation design was utilized. The starting dose of panitumumab was 6 mg/kg iv every 2 weeks with BKM120 at 60 mg oral daily. Results Nineteen patients were treated and 17 were evaluable for response. The starting dose was not tolerable (mucositis, fatigue). At dose level (DL) 1, three of six patients discontinued treatment due to toxicity, DL - 1 had no significant toxicity. Panitumumab 6 mg/kg iv q 2 weeks with BKM120 60 mg given 5 out of 7 days per week was declared the RP2D. One patient (5.9%) who was PTEN and PIK3CA negative by IHC had a partial response, seven had stable disease, and nine had disease progression. Conclusion Panitumumab (6 mg/kg iv q 2 weeks) with BKM120 60 mg given 5 out of 7 days per week was declared the RP2D. Toxicities including fatigue, rash and mucositis. There was little evidence of activity in this biomarker unselected cohort.
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Affiliation(s)
- Rachel Goodwin
- Ottawa Hospital Research Institute, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, K1H 8L6, Canada.
| | - Derek Jonker
- Ottawa Hospital Research Institute, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, K1H 8L6, Canada
| | - Eric Chen
- Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | | | - Michael Cabanero
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Ming-Sound Tsao
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Michael Vickers
- Ottawa Hospital Research Institute, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, K1H 8L6, Canada
| | - Caryn Bohemier
- Ottawa Hospital Research Institute, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, K1H 8L6, Canada
| | - Howard Lim
- BCCA-Vancouver Centre, Vancouver, BC, Canada
| | - Heather Ritter
- Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada
| | - Dongsheng Tu
- Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada
| | - Lesley Seymour
- Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada
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Residential radon, genetic polymorphisms in DNA damage and repair-related. Lung Cancer 2019; 135:10-15. [DOI: 10.1016/j.lungcan.2019.07.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Revised: 06/10/2019] [Accepted: 07/03/2019] [Indexed: 02/05/2023]
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Castellan P, Castellucci R, Marchioni M, De Nunzio C, Tema G, Primiceri G, Schips L, Cindolo L. A drug safety evaluation of abiraterone acetate in the treatment of prostate cancer. Expert Opin Drug Saf 2019; 18:759-767. [DOI: 10.1080/14740338.2019.1648428] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Affiliation(s)
| | | | | | - Cosimo De Nunzio
- Department of Urology, Sant’Andrea Hospital, University “La Sapienza”, Rome, Italy
| | - Giorgia Tema
- Department of Urology, Sant’Andrea Hospital, University “La Sapienza”, Rome, Italy
| | - Giulia Primiceri
- Department of Urology, University “G. d’Annunzio”, Chieti, Italy
| | - Luigi Schips
- Department of Urology, SS. Annunziata Hospital, Chieti, Italy
- Department of Urology, University “G. d’Annunzio”, Chieti, Italy
| | - Luca Cindolo
- Department of Urology, SS. Annunziata Hospital, Chieti, Italy
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Roviello G, Corona SP, Conca R, Petrioli R, Rosellini P, Bonetta A, Aieta M. Is there still a place for vinorelbine in advanced metastatic castration resistant prostate cancer? Medicine (Baltimore) 2019; 98:e16249. [PMID: 31261590 PMCID: PMC6616091 DOI: 10.1097/md.0000000000016249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Revised: 05/14/2019] [Accepted: 06/06/2019] [Indexed: 11/26/2022] Open
Abstract
The aim of this paper was to evaluate the activity and tolerability of oral vinorelbine in patients with advanced castration resistant prostate cancer (CRPC) who progressed after a minimum of three lines including: abiraterone acetate, docetaxel, cabazitaxel, and enzalutamide.Treatment consisted of weekly oral vinorelbine 60 mg/m. Chemotherapy was administered until disease progression or unacceptable toxicity.Twenty-six patients received vinorelbine: their median age was 74 years (range 58-84 years). Twenty-four (92.3%) patients had bone metastases. A decrease in PSA levels ≥50% was observed in 2 patients (7.7%). Among the subjects who were symptomatic at baseline, pain was reduced in 3 patients (13.6%) with a significant decrease in analgesic use. Median progression-free survival was 9 weeks (95% CI: 7 to 11) and median overall survival was 17 weeks (95% CI: 12 to 22). Treatment was well tolerated, and no grade 4 toxicities were observed.Our findings do not suggest the use of oral vinorelbine on a weekly schedule, in CRPC heavily pre-treated.
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Affiliation(s)
- Giandomenico Roviello
- Division of Medical Oncology, Department of Onco-Hematology, IRCCS-CROB, Referral Cancer Center of Basilicata, via Padre Pio 1, Rionero, Vulture (PZ), Italy
| | - Silvia Paola Corona
- Peter MacCallum Cancer Centre, Radiation Oncology Department, Moorabbin Campus, East Bentleigh Victoria, Australia
| | - Raffaele Conca
- Division of Medical Oncology, Department of Onco-Hematology, IRCCS-CROB, Referral Cancer Center of Basilicata, via Padre Pio 1, Rionero, Vulture (PZ), Italy
| | - Roberto Petrioli
- Department of Medicine, Surgery and Neurosciences, Medical Oncology Unit, University of Siena, Viale Bracci - Policlinico “Le Scotte”, Siena
| | - Pietro Rosellini
- Department of Medicine, Surgery and Neurosciences, Medical Oncology Unit, University of Siena, Viale Bracci - Policlinico “Le Scotte”, Siena
| | - Alberto Bonetta
- Radiotherapy department, ASST Cremona, Viale Concordia 1, Cremona, Italy
| | - Michele Aieta
- Division of Medical Oncology, Department of Onco-Hematology, IRCCS-CROB, Referral Cancer Center of Basilicata, via Padre Pio 1, Rionero, Vulture (PZ), Italy
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Abstract
Although a large number of studies have shown the associations of high plasma lipid profile levels with cancer, few studies demonstrate the association between low serum cholesterol (<160 mg/dl) and risk for cancer mortality. The aim of this study was to determine the association of low serum cholesterol level as a risk factor for mortality in cancer. The prospective cohort studies were conducted on 19 of 52 cohort studies including 30 179 male and 26 005 female participants who were followed up for 9 years. Cox proportion hazard model was applied to analyze these data. The associations are presented as hazard ratios (HRs) with 95% confidence intervals (CI). The statistical package for the social sciences software was used for analysis. The multivariate analysis results showed risk associations with low serum cholesterol for the first decile among male participants (cancer: HR=1.52, 95% CI: 1.06-2.18; noncancer liver dysfunction: HR=10.73, 95% CI: 3.74-30.18) and female participants (cancer: HR=1.03, 95% CI: 0.52-2.05; noncancer liver dysfunction: HR=25.8, 95% CI: 3.09-217.70). Furthermore, in the second decile, this association among male patients (noncancer liver dysfunction: HR=3.73, 95% CI: 1.16-11.95) had a statistically significant result. For the remaining deciles in both sexes, cancer and noncancer liver dysfunction has some risk or protective association, although not significant. Findings of this study indicated an inverse association between low serum cholesterol and cancer and noncancer liver dysfunction mortality.
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Vickers AD, Winfree KB, Cuyun Carter G, Kiiskinen U, Jen MH, Stull D, Kaye JA, Carbone DP. Relative efficacy of interventions in the treatment of second-line non-small cell lung cancer: a systematic review and network meta-analysis. BMC Cancer 2019; 19:353. [PMID: 30987609 PMCID: PMC6466705 DOI: 10.1186/s12885-019-5569-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Accepted: 04/02/2019] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Locally advanced or metastatic non-small cell lung cancer (NSCLC) that has progressed after first-line treatment has a poor prognosis. Recent randomized clinical trials (RCTs) have demonstrated survival benefits of alternative treatments to docetaxel. However, information is lacking on which patients benefit the most and what drug or regimen is optimal. We report a systematic review and network meta-analysis (NMA) of second-line treatments in all subgroup combinations determined by histology, programmed death ligand 1 (PD-L1) expression, and epidermal growth factor receptor (EGFR) mutation. METHODS MEDLINE, PubMed, EMBASE, Biosciences Information Service (using the Dialog Platform), Cochrane Library, and abstracts from scientific meetings were searched for RCTs published up to September 2015. Key outcomes were overall survival (OS) and progression-free survival (PFS). Bayesian hierarchical exchangeable NMAs were conducted to calculate mean survival times and relative differences for eight subgroups, using docetaxel as the reference comparator. For OS, the NMA was based on hazard ratios applied to a first-order fractional polynomial model fitted to the reference treatment. For PFS, a second-order fractional polynomial model was fitted to reconstructed patient-level data for the entire network of evidence. RESULTS The search identified 30 studies containing 17 different treatment regimens. Docetaxel plus ramucirumab was associated with a significant improvement in OS and PFS, relative to docetaxel, regardless of patient type. Docetaxel plus nintedanib showed similar efficacy to docetaxel plus ramucirumab in the nonsquamous populations. EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib showed superior levels of efficacy in EGFR mutation-positive populations and the one PD-1 immunotherapy (nivolumab) studied showed superior efficacy in the populations exhibiting high PD-L1 expression. CONCLUSIONS In the absence of head-to-head comparisons, we performed a mixed-treatment analysis to synthesize evidence of the efficacy of each treatment. Benefits are optimized by targeting specific treatments to individual patients guided by histology, PD-L1 expression, and EGFR mutation status. SYSTEMATIC REVIEW REGISTRATION This review is registered in PROSPERO (registration number: CRD42014013780 available at www.crd.york.ac.uk/PROSPERO ).
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Affiliation(s)
- Adrian D Vickers
- RTI Health Solutions, The Pavilion, Towers Business Park, Wilmslow Road, Didsbury, Manchester, M20 2LS, UK.
| | | | | | | | - Min-Hua Jen
- Eli Lilly and Company Limited, Windlesham, Surrey, UK
| | - Donald Stull
- RTI Health Solutions, Research Triangle Park, NC, USA
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Cancer Mortality Trend in Central Italy: Focus on A "Low Rate of Land Use" Area from 1982 to 2011. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16040628. [PMID: 30795508 PMCID: PMC6406941 DOI: 10.3390/ijerph16040628] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 02/13/2019] [Accepted: 02/15/2019] [Indexed: 02/07/2023]
Abstract
The aim of the present study was to estimate total cancer mortality trends from 1982 to 2011 in a “low rate of land use” province of the Latium region (Rieti, central Italy) characterized by a low degree of urbanization, a high prevalence of elderly, and a low number of births. Mortality data of the studied period, provided by the Italian National Institute of Statistics, were used for calculating standardized cancer mortality rates. Trends in mortality were analyzed using Joinpoint regression analysis. Results showed that total standardized cancer mortality rates decreased in the monitored area over the study period. A comparison with other provinces of the same region evidenced that the studied province presented the lowest cancer mortality. The three systems/apparatuses affected by cancer that mainly influenced cancer mortality in the monitored province were the trachea-bronchus-lung, colorectal-anus, and stomach. These findings could be attributed to the implement of preventive initiatives performed in the early 2000s, to healthier environmental scenario, and to lower levels of carcinogenic pollutants in air, water, and soil matrices. Thus, our results indicate that the studied area could be considered a “healthy” benchmark for studies in oncological diseases.
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Lu X, Chen F, Liu X, Yuan D, Zi Y, He X, Zhu D. Detection and clinical significance of DNA repair gene ERCC8 tag SNPs in gastric cancer. TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 29:392-396. [PMID: 30249552 DOI: 10.5152/tjg.2018.17662] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND/AIMS Excision repair cross-complementing group 8 (ERCC8) is one of the members of the nucleotide excision repair pathway. This study aimed to explore the association between ERCC8 tag single nucleotide polymorphisms (SNPs) and gastric cancer. MATERIALS AND METHODS Totally, 120 patients with gastric cancer treated from March 2010 to March 2011 were selected as the observation group and 120 healthy individuals were selected as the control group during the same period. The Sequenom MassARRAY system was used to identify genotypes in these samples. The genetic locus of ERCC8 tag SNPs and the relevance of gastric cancer risk to the different ERCC8 genotypes alone or in combination with Helicobacter pylori infection were observed and analyzed. The AA, GA, and GG genotypes on rs158572 and rs158916 in the observation and control groups were compared. RESULTS The results showed that the odds ratio of the different ERCC8 rs158572 and rs158916 genotypes was not significantly increased in the observation group compared with that in the control group. By contrast, in patients with H. pylori infection, the ERCC8 rs158572 GA/GG and rs158916 TT genotypes showed a 7.921-fold and 8.021-fold [95% confidence interval (CI)=4.022-15.921, p=0.029 and 95% CI=3.021-15.092, p=0.021, respectively] increased risk of gastric cancer than the AA and CT/CC genotypes, respectively. CONCLUSION Helicobacter pylori infection combined with ERCC8 rs158572 and rs158916 can be used as a predictive index of gastric cancer occurrence.
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Affiliation(s)
- Xingre Lu
- Department of Clinical Laboratory, The People's Hospital of Wenshan Prefecture, Yunnan, China
| | - Fengyu Chen
- Department of Clinical Laboratory, The People's Hospital of Wenshan Prefecture, Yunnan, China
| | - Xiaowen Liu
- Department of Clinical Laboratory, The People's Hospital of Wenshan Prefecture, Yunnan, China
| | - Diao Yuan
- Department of Clinical Laboratory, The People's Hospital of Wenshan Prefecture, Yunnan, China
| | - Yunju Zi
- Department of Clinical Laboratory, The People's Hospital of Wenshan Prefecture, Yunnan, China
| | - Xiang He
- Department of Clinical Laboratory, The People's Hospital of Wenshan Prefecture, Yunnan, China
| | - Deyong Zhu
- Department of Clinical Laboratory, The People's Hospital of Wenshan Prefecture, Yunnan, China
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Activation of TAp73 and inhibition of TrxR by Verteporfin for improved cancer therapy in TP53 mutant pancreatic tumors. Future Sci OA 2019; 5:FSO366. [PMID: 30820346 PMCID: PMC6391631 DOI: 10.4155/fsoa-2018-0082] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Accepted: 12/03/2018] [Indexed: 12/12/2022] Open
Abstract
Aim: TAp73 is a tumor suppressor, which compensates for p53 loss and induces apoptosis in tumors in response to genotoxic stress or small-molecule treatments. Pancreatic ductal adenocarcinoma has a late onset of the disease, responds poorly to the existing therapies and has a very low survival rates. Result: Here, using drug-repurposing approach, we found that protoporphyrin IX (PpIX) and benzoporphyrin derivative (BPD) monoacid ring A activate TAp73 and induce apoptosis in pancreatic cancer cells. PpIX and BPD induce reactive oxygen species and inhibit thioredoxin reductase 1. Conclusion: Thus, PpIX and BPD target cancer cells’ vulnerabilities namely activate TAp73 tumor suppressor and inhibit oncogenic Trx1. Our findings may contribute to faster repurposing of PpIX and BPD to treat pancreatic tumors. Despite all efforts, pancreatic cancer remains one of the most aggressive tumors. Late diagnoses, often linked with the asymptomatic disease progression, make pancreatic cancer extremely difficult to treat. We have assessed drugs that are already clinically used in the photodynamic therapy of actinic keratosis and age-related macular degeneration and showed that the compounds induce apoptotic death of cancer cells. The mechanism is via activation of the p73 tumor suppressor and inhibition of the oncogenic thioredoxin reductase. Molecules with a complementary mechanism of action inducing cell death might be very promising candidates for improved cancer therapy in pancreatic cancer patients.
Two pathways leading to the induction of potent apoptosis by protoporphyrin IX and Verteporfin in mutant TP53 pancreatic cancer cells. One pathway is through inhibition of TAp73/MDM2 interactions and induction of TAp73-related apoptosis and the second pathway converges on inhibition of oncogenic TrxR and accumulation of reactive oxygen species.
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Wong HCY, Lam KY, Chong CCN, Chan AWH, Chan SL. Impact of Weight Loss During Chemotherapy in Chinese Patients with Unresectable Pancreatic Cancer. Nutr Cancer 2019; 71:954-970. [PMID: 31058551 DOI: 10.1080/01635581.2019.1595047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Background: Weight loss is frequently observed in pancreatic cancer patients. We aimed to study the prognostic impacts of weight loss early during chemotherapy. Methods: A total of 72 patients of Chinese ethnicity with unresectable pancreatic cancer who underwent chemotherapy were reviewed. Critical weight loss (CWL) was defined as weight loss ≥ 5% within one month after treatment. The prognostic impact of weight loss and CWL were analyzed. Results: 47 patients (65.3%) had weight loss after one month of treatment, with 14 (19.4%) suffering from CWL. Baseline characteristics were similar between patients with and without CWL. The median OS and Time-to-treatment-failure (TTF) of patients with CWL were shorter than those without CWL (OS: 4.8 months [CWL] versus [vs.] OS 7.1 months [No CWL]; TTF 1.6 months [CWL] vs. 3.2 months [No CWL]; both P < 0.01). CWL was an independent adverse prognosticator for OS (Hazard Ratio [HR] = 2.50; P = 0.01) and TTF (HR = 2.71; P < 0.01). Other independent prognosticators for OS were serum albumin <35 mg/dl and CA19-9 ≥ 1000 IU/ml, while CWL was the only independent prognosticator for TTF (HR 2.71 [95% CI 1.33-5.52]; P < 0.01). Conclusions: Development of CWL in early course of chemotherapy was associated with worse prognosis in Chinese patients with unresectable pancreatic cancers.
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Affiliation(s)
- Henry C Y Wong
- a Department of Oncology , Princess Margaret Hospital , Hong Kong
| | - Kwan Y Lam
- b Department of Clinical Oncology , Sir YK Pao Center for Cancer, Prince of Wales Hospital , Hong Kong
| | - Charing C N Chong
- c Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery , The Chinese University of Hong Kong , Hong Kong
| | - Anthony W H Chan
- d Department of Anatomical and Cellular Pathology , Prince of Wales Hospital, The Chinese University of Hong Kong , Hong Kong
- e State Key Laboratory in Oncology in South China , The Chinese University of Hong Kong , Hong Kong
| | - Stephen L Chan
- b Department of Clinical Oncology , Sir YK Pao Center for Cancer, Prince of Wales Hospital , Hong Kong
- e State Key Laboratory in Oncology in South China , The Chinese University of Hong Kong , Hong Kong
- f Institute of Digestive Disease , The Chinese University of Hong Kong , Hong Kong
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Cózar JM, Miñana B, Gómez-Veiga F, Rodríguez-Antolín A. Three-year interim results of overall and progression-free survival in a cohort of patients with prostate cancer (GESCAP group). Actas Urol Esp 2019; 43:4-11. [PMID: 29891440 DOI: 10.1016/j.acuro.2018.03.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 03/13/2018] [Accepted: 03/13/2018] [Indexed: 12/24/2022]
Abstract
AIMS To describe the 3-year progression-free survival (PFS), overall survival (OS) and disease-specific mortality in the prospective prostate cancer GESCAP cohort, as well as the progression to castration resistance in patients on hormone therapy. MATERIAL AND METHODS Prospective, observational, epidemiological, multicentre study. Of the 4087 patients recruited, 3843 were evaluable. The variables analysed were the risk group (localized, locally advanced, lymph involvement, metastatic), age, prostate-specific antigen (PSA) levels, Gleason score and initial treatment. Kaplan Meier survival analysis, the log-rank test and the Cox model were used to evaluate the survival data. RESULTS Three-year PFS was 81.4% and OS was 92.4%. During the 3 years of follow-up, 303 patients died (7.9%), 110 of them (36.3%) due to disease-related causes. The probability of castration resistance for all patients on hormone therapy (n=715) was 14.2%: 5%, 9.9%, 26.1% and 44.4% in localized, locally advanced, lymph involvement and metastatic cancer, respectively (log-rank P<.0001). Patients with metastases had poorer outcomes with respect to PFS, OS, disease-specific mortality and castration resistance. In the multivariate analysis, the Gleason score, PSA and presence of metastases were associated with shorter OS and PFS. CONCLUSIONS Our study showed stratification of risk, with a more unfavourable prognosis for patients with metastases. Patients with locally advanced disease differed with respect to those with localized disease due to their higher risk as regards disease-specific mortality. (Controlled-trials.com ISRCTN19893319).
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Affiliation(s)
- J M Cózar
- Servicio de Urología, Hospital Virgen de las Nieves, Granada, España.
| | - B Miñana
- Servicio de Urología, Hospital Morales Meseguer, Murcia, España
| | - F Gómez-Veiga
- Servicio de Urología, Hospital Universitario de Salamanca-IBSAL-GITUR, Salamanca, España
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Okui N, Kamata Y, Sagawa Y, Kuhara A, Hayashi K, Uwagawa T, Homma S, Yanaga K. Claudin 7 as a possible novel molecular target for the treatment of pancreatic cancer. Pancreatology 2019; 19:88-96. [PMID: 30416041 DOI: 10.1016/j.pan.2018.10.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Revised: 08/22/2018] [Accepted: 10/22/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Pancreatic cancer consists of various subpopulations of cells, some of which have aggressive proliferative properties. The molecules responsible for the aggressive proliferation of pancreatic cancer may become molecular targets for the therapies against pancreatic cancer. METHODS From a human pancreatic cancer cell line, MIA PaCa-2, MIA PaCa-2-A cells with an epithelial morphology and MIA PaCa-2-R cells with a non-epithelial morphology were clonogenically isolated by the limiting dilution method. Gene expression of these subpopulations was analyzed by DNA microarray. Gene knockdown was performed using siRNA. RESULTS Although the MIA PaCa-2-A and MIA PaCa-2-R cells displayed the same DNA short tandem repeat (STR) pattern identical to that of the parental MIA PaCa-2 cells, the MIA PaCa-2-A cells were more proliferative than the MIA PaCa-2-R cells both in culture and in tumor xenografts generated in immunodeficient mice. Furthermore, the MIA PaCa-2-A cells were more resistant to gemcitabine than the MIA PaCa-2-R cells. DNA microarray analysis revealed a high expression of claudin (CLDN) 7 in the MIA PaCa-2-A cells, as opposed to a low expression in the MIA PaCa-2-R cells. The knockdown of CLDN7 in the MIA PaCa-2-A cells induced a marked inhibition of proliferation. The MIA PaCa-2-A cells in which CLDN7 was knocked down exhibited a decreased expression of phosphorylated extracellular signal-regulated kinase (p-Erk)1/2 and G1 cell cycle arrest. CONCLUSIONS CLDN7 may be expressed in the rapidly proliferating and dominant cell population in human pancreatic cancer tissues and may be a novel molecular target for the treatment of pancreatic cancer.
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Affiliation(s)
- Norimitsu Okui
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Yuko Kamata
- Division of Oncology, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan
| | - Yukiko Sagawa
- Division of Oncology, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan
| | - Akiko Kuhara
- Division of Oncology, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan
| | - Kazumi Hayashi
- Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Tadashi Uwagawa
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Sadamu Homma
- Division of Oncology, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan.
| | - Katsuhiko Yanaga
- Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
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Ko W, Miccinesi G, Beccaro M, Moreels S, Donker GA, Onwuteaka-Philipsen B, Alonso TV, Deliens L, Van den Block L. Factors Associated with Fulfilling the Preference for Dying at Home among Cancer Patients: The role of General Practitioners. J Palliat Care 2018. [DOI: 10.1177/082585971403000303] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Aim: This study aimed to explore clinical and care-related factors associated with fulfilling cancer patients’ preference for home death across four countries: Belgium (BE), the Netherlands (NL), Italy (IT), and Spain (ES). Methods: A mortality follow-back study was undertaken from 2009 to 2011 via representative networks of general practitioners (GPs). The study included all patients aged 18 and over who had died of cancer and whose home death preference and place of death were known by the GP. Factors associated with meeting home death preference were tested using multivariable logistic regressions. Results: Among 2,048 deceased patients, preferred and actual place of death was known in 42.6 percent of cases. Home death preference met ranged from 65.5 to 90.9 percent. Country-specific factors included older age in BE, and decisionmaking capacity and being female in the NL GPs’ provision of palliative care was positively associated with meeting home death preference. Odds ratios (ORs) were: BE: 9.9 (95 percent confidence interval [CI] 3.7–26.6); NL: 9.7 (2.4–39.9); and IT: 2.6 (1.2–5.5). ORs for Spain are not shown because a multivariate model was not performed. Conclusion: Those who develop policy to facilitate home death need to examine available resources for primary end-of-life care. But: Cette étude avait pour objectif d'examiner les facteurs cliniques associés aux demandes des patients désirant mourir à la maison. Cette re-cherche s'étendait sur quatre pays soit la Belgique, les Pays-Bas, l'Italie, et l'Espagne. Méthode: Par l'inter-médaire des réseaux représentatifs d'omnipraticiens, nous avons pu faire un suivi rétrospectif des mortalités survenues durant les années 2009, 2010, et 2011. Cette étude comprenait les patients agés de 18 ans et plus morts du cancer et dont les médecins connaissaient tout autant les volontés de pouvoir mourir à la maison que l'endroit où les patients étaient morts. Les facteurs correspondants aux préférences des patients ont été validés à l'aide de la méthode statistique de regression logistique à variables multiples. Résultats: Parmi les 2 048 personnes décédées on connaissait, chez 42,6 pourcent d'entre elles, la préférence et l'endroit de la mort. Le choix de mourir à domicile variait de 65,5 pourcent à 90,9 pourcent. Les facteurs spécifiques à certains pays étaient l'âge avancé pour la Belgique et, pour les Pays-Bas, la capacité décisionnelle et le fait d'être de sexe feminin. La prestation des soins palliatifs par les omnipraticiens est associée de façon positive au choix de mourir à la maison. Les rapports de probabilités étaient les suivants: Belgique: 9,9 [95 pourcent d'intervalle de fiabilité (3,7–26,6)], Pays-Bas: 9,7 (2,4–39,9) et l'Italie: 2,6 (1,2–5,5). Les facteurs de probabilité pour l'Espagne ne sont pas indiqués car on n'a pas fait d'analyse selon le modèle multivariable. Conclusion: Les professionnels de la santé ayant pour tâche d'établir les politiques pour faciliter la mort à la maison doivent connnaître toutes les resources dont ils disposent dans leur communauté afin de pouvoir offrir les soins de première ligne à domicile.
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Affiliation(s)
- Winne Ko
- End-of-Life Care Research Group, Room 126, Building K, Department of Family Medicine, Vrije Universiteit Brussel Laarbeeklaan 103, 1090 Brussels, Belgium; and Ghent University, Ghent, Belgium
| | - Guido Miccinesi
- Clinical and Descriptive Epidemiology Unit, Cancer Prevention and Research Institute, ISPO, Florence, Italy
| | - Monica Beccaro
- Regional Palliative Care Network, IRCCS AOU San Martino-IST, Genoa, Italy
| | - Sarah Moreels
- Public Health and Surveillance, Scientific Institute of Public Health, Brussels, Belgium
| | - Gé A. Donker
- NIVEL (Netherlands Institute for Health Services Research), Utrecht, Netherlands
| | - Bregje Onwuteaka-Philipsen
- EMGO Institute for Health and Care Research, Department of Public and Occupational Health; and Palliative Care Expertise Centre, VU University Medical Centre, Amsterdam, Netherlands
| | - Tomás V. Alonso
- Public Health Directorate General, Health Department, Valencia, Spain; L Deliens: End-of-Life Care Research Group, Vrije Universiteit Brussel, Brussels, Belgium; Ghent University, Ghent, Belgium; EMGO Institute for Health and Care Research, Department of Public and Occupational Health; and Palliative Care Expertise Centre, VU University Medical Centre, Amsterdam, Netherlands
| | - Luc Deliens
- End-of-Life Care Research Group and Department of Family Medicine, Vrije Universiteit Brussel, Brussels, Belgium; and Ghent University, Ghent, Belgium
| | - Lieve Van den Block
- Lieve Van den Block, Zeger De Groote, Sarah Brearley, Augusto Caraceni, Joachim Cohen, Massimo Costantini, Anneke Francke, Richard Harding, Irene Higginson, Stein Kaasa, Karen Linden, Guido Miccinesi, Bregje Onwuteaka-Philipsen, Koen Pardon, Roeline Pasman, Sophie Pautex, Sheila Payne, and Luc Deliens
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44
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Hao EIIU, Hwang HK, Yoon DS, Lee WJ, Kang CM. Aggressiveness of solid pseudopapillary neoplasm of the pancreas: A literature review and meta-analysis. Medicine (Baltimore) 2018; 97:e13147. [PMID: 30544374 PMCID: PMC6310540 DOI: 10.1097/md.0000000000013147] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Accepted: 10/13/2018] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare tumors considered to be benign although 10% to 15% of SPNs have been reported to be aggressive. Due to its rarity, there have only been a few cases reported regarding the clinical course of patients with aggressive SPNs. The goal of this study is to describe the clinical course of patients diagnosed with aggressive SPNs. METHODS A PubMed search was done looking for articles describing the clinical course of patients diagnosed with SPN that locally invaded, recurred, or metastasized. Institutional experience was also added to the pooled data. Patient information was extracted from the articles. Survival and recurrence curves were plotted and factors associated with survival and recurrences were analyzed. RESULTS A total of 59 patients were identified to have aggressive SPN. Seven patients were males and 52 were females and the mean age was 37.44 ± 2.21 years. Systemic metastasis constituted 81.4% while recurrence and deep tissue invasion were found in 11.9% and 6.8% of the patients, respectively. Disease-free survival was 45 ± 6.28 months and disease-specific survival was 152.67 ± 12.8 months. In survival analysis, age, gender, tumor size, tumor location, combined resection, type of recurrence, and stage IV on diagnosis were not significant factors in predicting survival. However, an unresectable tumor (hazards ratio [HR] = 4.871, 95% confidence interval [CI] 1.480-16.03, P = .009), and metastasis within 36 months (HR = 6.399, 95% CI: 1.390-29.452, P = .017) were identified as independent variables in predicting survival. CONCLUSION SPNs of the pancreas carry a favorable course. Despite having aggressive properties, patients can still survive for more than 10 years as long as the tumor can be resected completely.
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Affiliation(s)
- Emmanuel II Uy Hao
- Department of Surgery, Philippine General Hospital, University of the Philippines, Diliman Quezon City, Philippines
| | - Ho Kyung Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine
| | - Dong-Sub Yoon
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine
- Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
| | - Woo Jung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine
- Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
| | - Chang Moo Kang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine
- Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
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45
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Rodríguez-Blanco G, Zeneyedpour L, Duijvesz D, Hoogland AM, Verhoef EI, Kweldam CF, Burgers PC, Smitt PS, Bangma CH, Jenster G, van Leenders GJLH, Dekker LJM, Luider TM. Tissue proteomics outlines AGR2 AND LOX5 as markers for biochemical recurrence of prostate cancer. Oncotarget 2018; 9:36444-36456. [PMID: 30559929 PMCID: PMC6284859 DOI: 10.18632/oncotarget.26342] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 10/21/2018] [Indexed: 12/22/2022] Open
Abstract
Although many patients are cured from prostate cancer (PCa) by surgery only, there are still patients who will experience rising prostate-specific antigen (PSA) levels after surgery, a condition known as biochemical recurrence (BCR). Novel protein prognostic markers in PCa tissue might enable finding better treatment for those patients experiencing BCR with a high chance of metastasis. In this study, we aimed to identify altered proteins in prostate cancer tissue, and to evaluate their potential role as prognostic markers. We used two proteomics strategies to analyse 34 prostate tumours (PCa) and 33 normal adjacent prostate (NAP) tissues. An independent cohort of 481 samples was used to evaluate the expression of three proteins: AGR2, FASN and LOX5 as prognostic markers of the disease. Tissue microarray immunohistochemical staining indicated that a low percentage of positive tumour cells for AGR2 (HR (95% CI) = 0.61 (0.43-0.93)), and a low percentage of positive tumour cells for LOX5 expression (HR (95% CI) = 2.53 (1.23-5.22)) are predictors of BCR after RP. In contrast, FASN expression had no prognostic value for PCa.
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Affiliation(s)
| | - Lona Zeneyedpour
- Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Diederick Duijvesz
- Department of Urology, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - A Marije Hoogland
- Department of Pathology, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Esther I Verhoef
- Department of Pathology, Erasmus Medical Centre, Rotterdam, The Netherlands
| | | | - Peter C Burgers
- Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands
| | | | - Chris H Bangma
- Department of Urology, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Guido Jenster
- Department of Urology, Erasmus Medical Centre, Rotterdam, The Netherlands
| | | | - Lennard J M Dekker
- Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Theo M Luider
- Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands
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Giuliani J, Bonetti A. First-line therapies in metastatic colorectal cancer: integrating clinical benefit with the costs of drugs. Int J Colorectal Dis 2018; 33:1505-1516. [PMID: 30196427 DOI: 10.1007/s00384-018-3158-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/29/2018] [Indexed: 02/04/2023]
Abstract
PURPOSE In light of the relevant expenses of pharmacological interventions, it might be interesting to make a balance between the cost of the new drugs administered and the added value represented by the improvement in progression free survival (PFS) in first-line for metastatic colorectal cancer CRC (mCRC). METHODS Phase III randomized controlled trials (RCTs) that compared at least two first-line chemotherapy regimens for mCRC patients were evaluated. Differences in PFS between the different arms were compared with the pharmacological costs (at the pharmacy of our hospital). The European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) was applied to the above RCTs. RESULTS Overall 28 phase III RCTs, including 19,958 patients, were analyzed. The FOLFOX resulted the least expensive (56 € per month of PFS gained) while the addition of irinotecan to FOLFOX (FOLFOXIRI) increased only marginally the costs (90 € per month of PFS gained). Treatments including the monoclonal antibodies showed a cost per month of PFS gained of 2823 € (FOLFIRI with cetuximab in KRAS wild-type patients and liver-only metastases), of € 15,822 (FOLFOX with panitumumab in KRAS wild type), and of 13,383 € (FOLFOX with bevacizumab). According to the ESMO-MCBS, the treatments including an EGFR-inhibitor (cetuximab or panitumumab) were associated with a score of 4, while the inclusion of bevacizumab reached a score of 3. CONCLUSIONS Our data demonstrate a huge difference in cost per month of PFS gained in modern first-line treatments in mCRC.
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Affiliation(s)
- Jacopo Giuliani
- Department of Oncology, Mater Salutis Hospital-Az. ULSS 9 Scaligera, Via Gianella 1-37045, Legnago, VR, Italy.
| | - Andrea Bonetti
- Department of Oncology, Mater Salutis Hospital-Az. ULSS 9 Scaligera, Via Gianella 1-37045, Legnago, VR, Italy
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Radke DI, Ling Q, Häsler R, Alp G, Ungefroren H, Trauzold A. Downregulation of TRAIL-Receptor 1 Increases TGFβ Type II Receptor Expression and TGFβ Signalling Via MicroRNA-370-3p in Pancreatic Cancer Cells. Cancers (Basel) 2018; 10:399. [PMID: 30366420 PMCID: PMC6267290 DOI: 10.3390/cancers10110399] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Accepted: 10/09/2018] [Indexed: 12/28/2022] Open
Abstract
The accumulation of perturbations in signalling pathways resulting in an apoptosis-insensitive phenotype is largely responsible for the desperate prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). Accumulating evidence suggests that the death receptors TRAIL-R1 and TRAIL-R2 play important roles in PDAC biology by acting as either tumour suppressors through induction of cell death or tumour promoters through induction of pro-inflammatory signalling, invasion and metastasis. TRAIL-R2 can also associate with nuclear proteins and alter the maturation of micro RNAs (miRs). By genome-wide miR profiling and quantitative PCR analyses we now demonstrate that knockdown of TRAIL-R1 in PDAC cells decreased the level of mature miR-370 and led to an increased abundance of the type II receptor for transforming growth factor β (TGFβ). Transfection of cells with an artificial miR-370-3p decreased the levels of TGFβ-RII. We further show that transient expression of the miR-370 mimic decreased TGFβ1-induced expression of SERPINE1 encoding plasminogen activator-inhibitor 1 and partially relieved TGFβ1-induced growth inhibition. Moreover, stable TRAIL-R1 knockdown in Colo357 cells increased TGFβ1-induced SERPINE1 expression and this effect was partially reversed by transient expression of the miR-370 mimic. Finally, after transient knockdown of TRAIL-R1 in Panc1 cells there was a tendency towards enhanced activation of Smad2 and JNK1/2 signalling by exogenous TGFβ1. Taken together, our study reveals that TRAIL-R1 through regulation of miR-370 can decrease the sensitivity of PDAC cells to TGFβ and therefore represents a potential tumour suppressor in late-stage PDAC.
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Affiliation(s)
- David I Radke
- Institute for Experimental Cancer Research, University of Kiel, D-24105 Kiel, Germany.
| | - Qi Ling
- Institute for Experimental Cancer Research, University of Kiel, D-24105 Kiel, Germany.
- Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 31000, China.
| | - Robert Häsler
- Institute of Clinical Molecular Biology, University of Kiel, D-24105 Kiel, Germany.
| | - Gökhan Alp
- Institute for Experimental Cancer Research, University of Kiel, D-24105 Kiel, Germany.
| | - Hendrik Ungefroren
- Clinic for General Surgery, Visceral, Thoracic, Transplantation and Pediatric Surgery, University Hospital Schleswig-Holstein, Campus Kiel, D-24105 Kiel, Germany.
- First Department of Medicine, University Hospital Schleswig-Holstein, Campus Lübeck, D-23538 Lübeck, Germany.
| | - Anna Trauzold
- Institute for Experimental Cancer Research, University of Kiel, D-24105 Kiel, Germany.
- Clinic for General Surgery, Visceral, Thoracic, Transplantation and Pediatric Surgery, University Hospital Schleswig-Holstein, Campus Kiel, D-24105 Kiel, Germany.
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Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C, Mok TS, Reck M, Van Schil PE, Hellmann MD, Peters S. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2018; 29:iv192-iv237. [PMID: 30285222 DOI: 10.1093/annonc/mdy275] [Citation(s) in RCA: 1588] [Impact Index Per Article: 226.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Affiliation(s)
- D Planchard
- Department of Medical Oncology, Thoracic Group, Gustave-Roussy Villejuif, France
| | - S Popat
- Royal Marsden Hospital, London
| | - K Kerr
- Aberdeen Royal Infirmary, Aberdeen University Medical School, Aberdeen, UK
| | - S Novello
- Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Italy
| | - E F Smit
- Thoracic Oncology Service, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - C Faivre-Finn
- Division of Cancer Sciences, University of Manchester, Manchester, UK
| | - T S Mok
- Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - M Reck
- LungenClinic Airway Research Center North (ARCN), German Center for Lung Research, Grosshansdorf, Germany
| | - P E Van Schil
- Department of Thoracic and Vascular Surgery, Antwerp University Hospital and Antwerp University, Antwerp, Belgium
| | | | - S Peters
- Medical Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
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Anti-angiogenic agents in second-line treatment for metastatic colorectal cancer: the optimization of pharmacological costs. Int J Colorectal Dis 2018; 33:1487-1491. [PMID: 29804191 DOI: 10.1007/s00384-018-3077-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/02/2018] [Indexed: 02/04/2023]
Abstract
PURPOSE In western Countries, colorectal cancer (CRC) is the second most common cause of death from cancer. In particular, the introduction of active new anti-angiogenic agents for the second-line treatment of metastatic CRC (mCRC) is associated with a relevant increase of costs, and it is therefore important to make a balance between the costs of treatment and the added value represented by the improvement of the clinical parameters of interest such as progression-free survival (PFS). METHODS The analysis was conducted to assess the effect of second-line therapy with anti-angiogenic agents on the PFS and was restricted to pivotal phase III randomized controlled trials (RCTs). RESULTS The present analysis evaluated four phase III RCTs, including 3938 patients. Dividing the costs of therapy by the measure of efficacy represented by PFS, we found out that the lowest cost per month of PFS gained (4581 €) was associated with the use of FOLFIRI plus aflibercept. CONCLUSIONS Combining pharmacological costs of drugs with the measure of efficacy represented by the PFS, aflibercept in combination with FOLFIRI is a cost-effective second-line treatment for patients with mCRC.
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50
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Ostwal V, Sahu A, Zanwar S, Nayak L, Shrikhande SV, Shetty N, Gupta S, Ramaswamy A. Experience with non-cremophor-based paclitaxel-gemcitabine regimen in advanced pancreatic cancer: Results from a single tertiary cancer centre. Indian J Med Res 2018; 148:284-290. [PMID: 30425218 PMCID: PMC6251278 DOI: 10.4103/ijmr.ijmr_249_17] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND & OBJECTIVES Gemcitabine combined with non-cremophor-based paclitaxel is one of the standards of care in advanced inoperable pancreatic cancer. This study was undertaken to retrospectively evaluate real world non-trial outcomes with this combination. METHODS Patients with histologically proven advanced inoperable pancreatic adenocarcinoma (PDAC), treated with non-cremophor-based paclitaxel-gemcitabine combination (PG) (gemcitabine-nanoxel or gemcitabine-abraxane) between January 2012 and June 2015, were retrospectively analyzed. Response assessment was done every 8-12 wk with computed tomography scan and responses were measured as per the Response Evaluation Criteria in Solid Tumours 1.1 criteria where feasible. Toxicity was recorded as per the Common Terminology Criteria for Adverse Events (CTCAE) v4 criteria. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS A total of 78 patients with PDAC were treated with the combination. Of these, 83.3 per cent of patients had metastatic disease. The median number of chemotherapy cycles administered was three. The objective response rate for the whole group was 30.8 per cent. Grade III/IV toxicities were seen in 35.9 per cent of patients. Median PFS was 5.6 months and median OS was 11.6 months. INTERPRETATION & CONCLUSIONS Non-cremophor-based paclitaxel in combination with gemcitabine appeared efficacious for advanced pancreatic cancers in routine clinical practice. Within the confines of a single-centre retrospective analysis, gemcitabine-nanoxel and gemcitabine-abraxane appeared to have similar efficacy and toxicity in advanced pancreatic cancers.
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Affiliation(s)
- Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India
| | - Arvind Sahu
- Department of Medicine, H. M. Patel Center for Medical Care & Education, Anand, India
| | - Saurabh Zanwar
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India
| | - Lingaraj Nayak
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India
| | | | - Nitin Shetty
- Department of Interventional Radiology, Tata Memorial Hospital, Mumbai, India
| | - Sudeep Gupta
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India
| | - Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India
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