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Al‐Lamee H, Soul J, Green D, Drury J, Hill CJ, Vasieva O, Valentijn A, Maclean A, Drakeley A, Tempest N, Hapangama DK. Transcriptional Profiling of SSEA-1 + Endometrial Epithelial Progenitor Cells Highlights Their Role in Endometrial Regeneration, Remodeling, and Homeostasis. FASEB J 2025; 39:e70578. [PMID: 40297954 PMCID: PMC12038780 DOI: 10.1096/fj.202402861r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 03/09/2025] [Accepted: 04/18/2025] [Indexed: 04/30/2025]
Abstract
Stage-specific embryonic antigen-1 (SSEA-1)+ endometrial epithelial cells (EECs) assume the postulated stem/progenitor cell niche within the human endometrium. Previous studies have demonstrated that isolated SSEA-1+ cells have a higher capacity to generate organoids in a three-dimensional matrix, a lower steroid hormone receptor expression, and higher telomerase activity with longer telomere lengths. Here, we present the transcriptomic profile of isolated SSEA-1+ EECs from eight endometrial biopsies compared to SSEA-1- EECs. Transcriptome and pathway analysis indicate that SSEA-1+ EECs play an important role in endometrial regeneration, remodeling and neovascularization as expected from a basal progenitor population. We show that SSEA-1+ EECs play a role in endometrial tissue homeostasis and tumor suppression, and bioinformatically identify potential upstream regulators such as SPDEF and TGFB1, which may be involved in these mechanisms. In vitro EEC organoid models also demonstrate SSEA-1+ EECs to exhibit estrogen responsive proliferation evidenced by stronger immunostaining for progesterone receptor and Ki-67. Our data further suggest a more quiescent, less hormone responsive phenotype for SSEA-1+ EECs that co-localize to SOX9+ EECs within in silico analysis, thus validating previous studies.
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Affiliation(s)
- Hannan Al‐Lamee
- Department of Women's and Children's HealthInstitute of Life Course and Medical Sciences, Centre for Women's Health Research, University of Liverpool, Member of Liverpool Health PartnersLiverpoolUK
- Hewitt Centre for Reproductive MedicineLiverpool Women's NHS Foundation TrustLiverpoolUK
- Liverpool Women's NHS Foundation Trust, Member of Liverpool Health PartnersLiverpoolUK
- Imperial College Healthcare NHS TrustLondonUK
| | - Jamie Soul
- Computational Biology FacilityUniversity of LiverpoolLiverpoolUK
| | - Daniel Green
- Computational Biology FacilityUniversity of LiverpoolLiverpoolUK
| | - Josephine Drury
- Department of Women's and Children's HealthInstitute of Life Course and Medical Sciences, Centre for Women's Health Research, University of Liverpool, Member of Liverpool Health PartnersLiverpoolUK
| | - Christopher J. Hill
- Department of Women's and Children's HealthInstitute of Life Course and Medical Sciences, Centre for Women's Health Research, University of Liverpool, Member of Liverpool Health PartnersLiverpoolUK
| | - Olga Vasieva
- Institute of Systems, Molecular and Integrative BiologyUniversity of LiverpoolLiverpoolUK
| | - Anthony Valentijn
- Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, Centre of Excellence in Long‐Acting Therapeutics (CELT)University of LiverpoolLiverpoolUK
| | - Alison Maclean
- Department of Women's and Children's HealthInstitute of Life Course and Medical Sciences, Centre for Women's Health Research, University of Liverpool, Member of Liverpool Health PartnersLiverpoolUK
| | - Andrew Drakeley
- Hewitt Centre for Reproductive MedicineLiverpool Women's NHS Foundation TrustLiverpoolUK
- Liverpool Women's NHS Foundation Trust, Member of Liverpool Health PartnersLiverpoolUK
| | - Nicola Tempest
- Department of Women's and Children's HealthInstitute of Life Course and Medical Sciences, Centre for Women's Health Research, University of Liverpool, Member of Liverpool Health PartnersLiverpoolUK
- Hewitt Centre for Reproductive MedicineLiverpool Women's NHS Foundation TrustLiverpoolUK
- Liverpool Women's NHS Foundation Trust, Member of Liverpool Health PartnersLiverpoolUK
| | - Dharani K. Hapangama
- Department of Women's and Children's HealthInstitute of Life Course and Medical Sciences, Centre for Women's Health Research, University of Liverpool, Member of Liverpool Health PartnersLiverpoolUK
- Liverpool Women's NHS Foundation Trust, Member of Liverpool Health PartnersLiverpoolUK
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2
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Roig-Martí C, Pérez-Catalán I, Varea-Villanueva M, Folgado-Escudero S, Navarro-Ballester A, Fernández-García MP, Segura-Fábrega A, Herrero-Rodríguez G, Domínguez-Bajo E, Fabra-Juana S, Esteve-Gimeno MJ, Mateu-Campos ML, Usó-Blasco J, Ramos-Rincón JM. Predictors of the presence of radiological abnormalities 6 months after severe COVID-19 pneumonia. BMC Infect Dis 2024; 24:883. [PMID: 39210255 PMCID: PMC11360858 DOI: 10.1186/s12879-024-09767-2] [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] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 08/20/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND SARS-CoV-2 pneumonia can cause significant long-term radiological changes, even resembling pulmonary fibrosis. However, the risk factors for these long-term effects are unknown. This study aims to assess radiological abnormalities and their possible risk factors six months after hospital discharge due to COVID-19 pneumonia. MATERIAL AND METHODS This cross-sectional study in a tertiary hospital included adults admitted for COVID-19 pneumonia from March 2020 to February 2021, who underwent high-resolution computed tomography (HRCT) scans of the chest six months after hospital discharge. The primary outcome was radiological abnormalities on HRCT, while the main explanatory variables were drawn from the patient's medical history along with the disease course, analytical indicators, and the treatment received during admission. RESULTS The 189 included patients had a mean age of 61.5 years; 70.9% were male, and hypertension was the main comorbidity (45%). About two-thirds (67.2%) presented acute respiratory distress syndrome (ARDS). Most (97.9%) received systemic corticosteroid therapy, and 81% presented pathological findings on HRCT, most commonly ground glass (63.5%), followed by bronchial dilatation (36%) and subpleural bands (25.4%). The multivariable analysis showed that age was the main risk factor, associated with most radiological changes. Other factors were the duration of corticosteroid therapy for ground glass (adjusted odds ratio [aOR] 1.020) as well as a longer stay in the intensive care unit (ICU) (aOR 1.290) and high levels of IL-6 for bronchial dilation (aOR 1.002). CONCLUSION Radiological involvement of the lungs six months after COVID-19 pneumonia is frequent, especially ground glass. Elderly patients with prolonged ICU admission and a significant inflammatory response measured by IL-6 are more likely to present worse radiological evolution and are candidates for radiological follow-up after COVID-19 pneumonia.
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Affiliation(s)
- Celia Roig-Martí
- Internal Medicine Department, Castellón General University Hospital, Castellón, Spain.
| | - Ignacio Pérez-Catalán
- Internal Medicine Department, Castellón General University Hospital, Castellón, Spain.
| | | | | | | | | | - Ana Segura-Fábrega
- Internal Medicine Department, Castellón General University Hospital, Castellón, Spain
| | | | - Elena Domínguez-Bajo
- Internal Medicine Department, Castellón General University Hospital, Castellón, Spain
| | - Sergio Fabra-Juana
- Internal Medicine Department, Castellón General University Hospital, Castellón, Spain
| | | | | | - Jorge Usó-Blasco
- Internal Medicine Department, Castellón General University Hospital, Castellón, Spain
| | - José-Manuel Ramos-Rincón
- Internal Medicine Department, Alicante General University Hospital, Alicante Institute of Health and Biomedical Research (ISABIAL), Alicante, Spain
- Clinical Medicine Department, Miguel Hernández University of Elche, Elche, Spain
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3
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Zeng Z, Mei Z, Chen M, Cao H, Xiang Q, Cai H, Lu Z, Qiu H. Cadonilimab plus anlotinib effectively relieve rare cardiac angiosarcoma with multiple metastases: a case report and literature review. Clin Res Cardiol 2024; 113:358-365. [PMID: 37405482 PMCID: PMC10850283 DOI: 10.1007/s00392-023-02251-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 06/19/2023] [Indexed: 07/06/2023]
Affiliation(s)
- Ziyue Zeng
- Department of Cardiology, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China
| | - Zijie Mei
- Department of Gynecological Tumor Radiotherapy and Chemotherapy, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China
| | - Min Chen
- Department of Gynecological Tumor Radiotherapy and Chemotherapy, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China
| | - Hong Cao
- Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Qingming Xiang
- Department of Gynecological Tumor Radiotherapy and Chemotherapy, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China
| | - Huanhuan Cai
- Department of Cardiology, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China
| | - Zhibing Lu
- Department of Cardiology, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China.
| | - Hui Qiu
- Department of Gynecological Tumor Radiotherapy and Chemotherapy, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China.
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4
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Wei H, Mao J, Wu Y, Zhou Q. Case Report: Postoperative Recurrence of Adrenal Epithelioid Angiosarcoma Achieved Complete Response by Combination Chemotherapy With Liposomal Doxorubicin and Paclitaxel. Front Oncol 2021; 11:791121. [PMID: 34976833 PMCID: PMC8716616 DOI: 10.3389/fonc.2021.791121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 11/30/2021] [Indexed: 11/13/2022] Open
Abstract
BackgroundPrimary adrenal epithelioid angiosarcoma is an extremely rare cancer with a poor prognosis. Because of the rarity of this disease, treatment options have not been well-studied.Case presentationA 51-year-old man was admitted to Zhejiang Cancer Hospital, diagnosed with a recurrence of adrenal epithelioid angiosarcoma. He had undergone a surgical resection seven months earlier. Combination chemotherapy with liposomal doxorubicin and paclitaxel was administered. After two cycles of chemotherapy, his pain was relieved. Computed tomography (CT) suggested that the soft tissue tumour lesions in the surgical area had disappeared, mediastinal and mediastinal-hilar lymph nodes were significantly reduced or had disappeared, and the patient had achieved a partial response (PR). CT after six cycles of chemotherapy indicated that the patient had achieved a complete response (CR).ConclusionCombination chemotherapy with liposomal doxorubicin and paclitaxel may be a preferred therapy for recurrent or advanced adrenal epithelioid angiosarcoma.
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Affiliation(s)
- Hangping Wei
- Department of Medical Oncology, Dongyang Hospital Affiliated to Wenzhou Medical University, Dongyang, China
| | - Jie Mao
- Department of Radiology, Dongyang Hospital Affiliated to Wenzhou Medical University, Dongyang, China
| | - Yandan Wu
- Department of Gynaecology and Obstetrics, Dongyang Hospital Affiliated to Wenzhou Medical University, Dongyang, China
| | - Qinfei Zhou
- Department of Rare and Head and Neck Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China
- Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, China
- *Correspondence: Qinfei Zhou,
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5
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Wang Z, Liu L, Li Y, Song Z, Jing Y, Fan Z, Zhang S. Analysis of CK5/6 and EGFR and Its Effect on Prognosis of Triple Negative Breast Cancer. Front Oncol 2021; 10:575317. [PMID: 33552956 PMCID: PMC7855982 DOI: 10.3389/fonc.2020.575317] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 11/30/2020] [Indexed: 12/17/2022] Open
Abstract
Background Triple-negative breast cancer (TNBC) is considered to be higher grade, more aggressive and have a poorer prognosis than other types of breast cancer. Discover biomarkers in TNBC for risk stratification and treatments that improve prognosis are in dire need. Methods Clinical data of 195 patients with triple negative breast cancer confirmed by pathological examination and received neoadjuvant chemotherapy (NAC) were collected. The expression levels of EGFR and CK5/6 were measured before and after NAC, and the relationship between EGFR and CK5/6 expression and its effect on prognosis of chemotherapy was analyzed. Results The overall response rate (ORR) was 86.2% and the pathological complete remission rate (pCR) was 29.2%. Univariate and multivariate logistic regression analysis showed that cT (clinical Tumor stages) stage was an independent factor affecting chemotherapy outcome. Multivariate Cox regression analysis showed pCR, chemotherapy effect, ypT, ypN, histological grades, and post- NAC expression of CK5/6 significantly affected prognosis. The prognosis of CK5/6-positive patients after NAC was worse than that of CK5/6-negative patients (p=0.036). Changes in CK5/6 and EGFR expression did not significantly affect the effect of chemotherapy, but changes from positive to negative expression of these two markers are associated with a tendency to improve prognosis. Conclusion For late-stage triple negative breast cancer patients receiving NAC, patients who achieved pCR had a better prognosis than those with non- pCR. Patients with the change in expression of EGFR and CK5/6 from positive to negative after neoadjuvant chemotherapy predicted a better prognosis than the change from negative to positive group.
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Affiliation(s)
- Zhen Wang
- The Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Lei Liu
- The Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Ying Li
- The Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Zi'an Song
- The Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Yi Jing
- The Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Ziyu Fan
- The Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Sheng Zhang
- The Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Tianjin's Clinical Research Center for Cancer, Tianjin, China
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6
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Li H, Song G, Zhou Q, Ran R, Jiang H, Zhang R, Liu Y, Zhang J, Meng L, Ma L, Sun Y, Wang M, Zhou Q, Yan H, Zhou Q, Dong X, Tong Y. Activity of preclinical and phase I clinical trial of a novel androgen receptor antagonist GT0918 in metastatic breast cancer. Breast Cancer Res Treat 2021; 189:725-736. [PMID: 34392453 PMCID: PMC8505310 DOI: 10.1007/s10549-021-06345-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 07/29/2021] [Indexed: 11/28/2022]
Abstract
PURPOSE To evaluate GT0918, a 2nd-generation AR antagonist, for its AR down-regulation activity among breast cancer patients. METHODS The effect of GT0918 on AR protein expression was evaluated in AR expression breast cancer cells and in breast cancer xenograft model. A 3 + 3 phase I dose-escalation study was launched in Peking University Cancer Hospital. The endpoints included dose finding, safety, pharmacokinetics, and antitumor activity. RESULTS GT0918 was demonstrated to effectively suppress the expression of AR protein and the growth of AR-positive breast cancer tumors in mouse xenograft tumor models. All patients treated with GT0918 were at a QD dose-escalation of five dose levels from 100 to 500 mg. The most common treatment-related AEs of any grade were asthenia, anemia, decreased appetite, increased blood cholesterol, increased blood triglycerides, decreased white blood cell count, and increased low-density lipoprotein. Grade 3 AEs were fatigue (2 of 18, 11.1%), aspartate aminotransferase increase (1 of 18, 5.6%), alanine aminotransferase increase (1 of 18, 5.6%), and neutrophil count decrease (1 of 18, 5.6%). Clinical benefit rate (CBR) in 16 weeks was 23.1% (3/13). Among 7 AR-positive patients, 6 can evaluate efficacy, and 2 completed 23.5- and 25-cycle treatment, respectively (as of 2020/1/20). PK parameters showed a fast absorption profile of GT0918 in the single-dose study. GT0918 and its major metabolite reached steady-state serum concentration levels at day 21 after multiple dosing. CONCLUSION GT0918 can effectively inhibit AR-positive breast cancer tumor growth. GT0918 was demonstrated well tolerated with a favorable PK profile. The suitable dose of GT0918 was 500 mg QD and may provide clinical benefits for AR-positive mBC.
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Affiliation(s)
- Huiping Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Rd, Haidian district, Beijing, 100142, People's Republic of China.
| | - Guohong Song
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Rd, Haidian district, Beijing, 100142 People’s Republic of China
| | - Qiaoxia Zhou
- Kintor Pharmaceutical Limited, No. 20 Songbei Road, Suzhou Industrial Park, Jiangsu, 215123 People’s Republic of China
| | - Ran Ran
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Rd, Haidian district, Beijing, 100142 People’s Republic of China
| | - Hanfang Jiang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Rd, Haidian district, Beijing, 100142 People’s Republic of China
| | - Ruyan Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Rd, Haidian district, Beijing, 100142 People’s Republic of China
| | - Yaxin Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Rd, Haidian district, Beijing, 100142 People’s Republic of China
| | - Jiayang Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Rd, Haidian district, Beijing, 100142 People’s Republic of China
| | - Luping Meng
- Kintor Pharmaceutical Limited, No. 20 Songbei Road, Suzhou Industrial Park, Jiangsu, 215123 People’s Republic of China
| | - Liandong Ma
- Kintor Pharmaceutical Limited, No. 20 Songbei Road, Suzhou Industrial Park, Jiangsu, 215123 People’s Republic of China
| | - Ye Sun
- Kintor Pharmaceutical Limited, No. 20 Songbei Road, Suzhou Industrial Park, Jiangsu, 215123 People’s Republic of China
| | - Meiyu Wang
- Kintor Pharmaceutical Limited, No. 20 Songbei Road, Suzhou Industrial Park, Jiangsu, 215123 People’s Republic of China
| | - Qingqing Zhou
- Kintor Pharmaceutical Limited, No. 20 Songbei Road, Suzhou Industrial Park, Jiangsu, 215123 People’s Republic of China
| | - Honghua Yan
- Kintor Pharmaceutical Limited, No. 20 Songbei Road, Suzhou Industrial Park, Jiangsu, 215123 People’s Republic of China
| | - Qianxiang Zhou
- Kintor Pharmaceutical Limited, No. 20 Songbei Road, Suzhou Industrial Park, Jiangsu, 215123 People’s Republic of China
| | - Xunwei Dong
- Kintor Pharmaceutical Limited, No. 20 Songbei Road, Suzhou Industrial Park, Jiangsu, 215123 People’s Republic of China
| | - Youzhi Tong
- Kintor Pharmaceutical Limited, No. 20 Songbei Road, Suzhou Industrial Park, Jiangsu, 215123 People’s Republic of China
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7
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Wang Q, Xie L, Dang Y, Sun X, Xie T, Guo J, Han Y, Yan Z, Zhu W, Wang Y, Li W, Guo X. OSlms: A Web Server to Evaluate the Prognostic Value of Genes in Leiomyosarcoma. Front Oncol 2019; 9:190. [PMID: 30984618 PMCID: PMC6449415 DOI: 10.3389/fonc.2019.00190] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Accepted: 03/05/2019] [Indexed: 12/30/2022] Open
Abstract
The availability of transcriptome data and clinical annotation offers the opportunity to identify prognosis biomarkers in cancer. However, efficient online prognosis analysis tools are still lacking. Herein, we developed a user-friendly web server, namely Online consensus Survival analysis of leiomyosarcoma (OSlms), to centralize published gene expression data and clinical datasets of leiomyosarcoma (LMS) patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). OSlms comprises of a total of 268 samples from three independent datasets, and employs the Kaplan Meier survival plot with hazard ratio (HR) and log rank test to estimate the prognostic potency of genes of interests for LMS patients. Using OSlms, clinicians and basic researchers could determine the prognostic significance of genes of interests and get opportunities to identify novel potential important molecules for LMS. OSlms is free and publicly accessible at http://bioinfo.henu.edu.cn/LMS/LMSList.jsp.
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Affiliation(s)
- Qiang Wang
- Department of Preventive Medicine, Institute of Biomedical Informatics, Joint National Laboratory for Antibody Drug Engineering, Cell Signal Transduction Laboratory, Bioinformatics Center, School of Software, School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Longxiang Xie
- Department of Preventive Medicine, Institute of Biomedical Informatics, Joint National Laboratory for Antibody Drug Engineering, Cell Signal Transduction Laboratory, Bioinformatics Center, School of Software, School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Yifang Dang
- Department of Preventive Medicine, Institute of Biomedical Informatics, Joint National Laboratory for Antibody Drug Engineering, Cell Signal Transduction Laboratory, Bioinformatics Center, School of Software, School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Xiaoxiao Sun
- Department of Preventive Medicine, Institute of Biomedical Informatics, Joint National Laboratory for Antibody Drug Engineering, Cell Signal Transduction Laboratory, Bioinformatics Center, School of Software, School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Tiantian Xie
- Department of Preventive Medicine, Institute of Biomedical Informatics, Joint National Laboratory for Antibody Drug Engineering, Cell Signal Transduction Laboratory, Bioinformatics Center, School of Software, School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Jinshuai Guo
- Department of Preventive Medicine, Institute of Biomedical Informatics, Joint National Laboratory for Antibody Drug Engineering, Cell Signal Transduction Laboratory, Bioinformatics Center, School of Software, School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Yali Han
- Department of Preventive Medicine, Institute of Biomedical Informatics, Joint National Laboratory for Antibody Drug Engineering, Cell Signal Transduction Laboratory, Bioinformatics Center, School of Software, School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Zhongyi Yan
- Department of Preventive Medicine, Institute of Biomedical Informatics, Joint National Laboratory for Antibody Drug Engineering, Cell Signal Transduction Laboratory, Bioinformatics Center, School of Software, School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Wan Zhu
- Department of Anesthesia, Stanford University, Stanford, CA, United States
| | - Yunlong Wang
- Henan Bioengineering Research Center, Zhengzhou, China
| | - Wei Li
- Division of Biostatistics, Dan L. Duncan Cancer Center Department of Molecular and Cellular Biology Baylor College of Medicine, Houston, TX, United States
| | - Xiangqian Guo
- Department of Preventive Medicine, Institute of Biomedical Informatics, Joint National Laboratory for Antibody Drug Engineering, Cell Signal Transduction Laboratory, Bioinformatics Center, School of Software, School of Basic Medical Sciences, Henan University, Kaifeng, China
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8
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Koratala A, Alquadan KF. Prolonged renal allograft survival without immunosuppressive therapy. CEN Case Rep 2018; 7:178-179. [DOI: 10.1007/s13730-017-0294-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2017] [Accepted: 12/13/2017] [Indexed: 10/18/2022] Open
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9
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Barraco D, Cerquozzi S, Gangat N, Patnaik MM, Lasho T, Finke C, Hanson CA, Ketterling RP, Pardanani A, Tefferi A. Monocytosis in polycythemia vera: Clinical and molecular correlates. Am J Hematol 2017; 92:640-645. [PMID: 28370365 DOI: 10.1002/ajh.24740] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Revised: 03/20/2017] [Accepted: 03/22/2017] [Indexed: 01/06/2023]
Abstract
Monocytosis (absolute monocyte count, AMC ≥ 1 × 109 /L) might accompany a spectrum of myeloid neoplasms, other than chronic myelomonocytic leukemia (CMML). In the current study, we examined the prevalence, laboratory and molecular correlates, and prognostic relevance of monocytosis in polycythemia vera (PV). Among 267 consecutive patients with World Health Organization (WHO)-defined PV, 55 (21%) patients displayed an AMC of ≥1 × 109 /L and 18 (7%) an AMC of ≥1.5 × 109 /L. In general, PV patients with monocytosis were significantly older and displayed higher frequencies of leukocytosis (81% vs. 50% at AMC ≥1 × 109 /L) and TET2/SRSF2 mutations (57%/29% vs. 19%/1% at AMC ≥ 1.5 × 109 /L). In univariate analysis, AMC ≥1.5 × 109 /L adversely affected overall (OS; P = .004; HR 2.6, 95% CI 1.4-4.8) and myelofibrosis-free (MFFS; P = .02; HR 4.4, 95% CI 1.3-15.1) survival; during multivariable analysis, significance was borderline sustained for OS (P = .05) and MFFS (P = .06). Other independent risk factors for OS included unfavorable karyotype (P = .02, HR 3.39, 95% CI 1.17-9.79), older age (P < .0001, HR 3.34 95% CI 1.97-5.65), and leukocytosis ≥15 × 109 /L (P = .004, HR 2.04, 95% CI 1.26-3.29). In conclusion, in the current study, we encountered a higher than expected prevalence of monocytosis in patients with PV and the mutation profile and age distribution of PV patients with monocytosis is akin to those of patients with CMML and might partly contribute to their worse prognosis.
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Affiliation(s)
- Daniela Barraco
- Division of Hematology; Department of Internal Medicine, Mayo Clinic; Rochester Minnesota USA
| | - Sonia Cerquozzi
- Division of Hematology; Department of Internal Medicine, University of Calgary; Calgary Alberta USA
| | - Naseema Gangat
- Division of Hematology; Department of Internal Medicine, Mayo Clinic; Rochester Minnesota USA
| | - Mrinal M. Patnaik
- Division of Hematology; Department of Internal Medicine, Mayo Clinic; Rochester Minnesota USA
| | - Terra Lasho
- Division of Hematology; Department of Internal Medicine, Mayo Clinic; Rochester Minnesota USA
| | - Christy Finke
- Division of Hematology; Department of Internal Medicine, Mayo Clinic; Rochester Minnesota USA
| | - Curtis A. Hanson
- Division of Hematopathology; Mayo Clinic; Rochester Minnesota USA
| | - Rhett P. Ketterling
- Department of Laboratory Medicine and Pathology; Mayo Clinic; Rochester Minnesota USA
| | - Animesh Pardanani
- Division of Hematology; Department of Internal Medicine, Mayo Clinic; Rochester Minnesota USA
| | - Ayalew Tefferi
- Division of Hematology; Department of Internal Medicine, Mayo Clinic; Rochester Minnesota USA
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10
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Preda O, Nogales FF. Diagnostic Immunopathology of Germ Cell Tumors. PATHOLOGY AND BIOLOGY OF HUMAN GERM CELL TUMORS 2017:131-179. [DOI: 10.1007/978-3-662-53775-6_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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11
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Yu SR, Huang XJ, Zhang YP. Gastric cancer related genes. Shijie Huaren Xiaohua Zazhi 2016; 24:4381-4388. [DOI: 10.11569/wcjd.v24.i32.4381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer is one of the most common malignant tumors. In addition to environmental, socioeconomic, and dietary factors, hereditary factors also play an important role in the development of gastric cancer. Although some driver genes have been identified in gastric cancer, the molecular compositions of gastric cancer have not been fully understood. Genome-wide association studies, copy number variations and next-generation sequencing provide systematic methods to identify all genetic alterations in the cancer genome, especially in the field of mutation detection. Here we make a brief review of the current status of research on gastric cancer genetics.
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12
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Lu C, Redd PS, Lee JR, Savage N, Liu K. The expression profiles and regulation of PD-L1 in tumor-induced myeloid-derived suppressor cells. Oncoimmunology 2016; 5:e1247135. [PMID: 28123883 DOI: 10.1080/2162402x.2016.1247135] [Citation(s) in RCA: 177] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Revised: 09/27/2016] [Accepted: 10/05/2016] [Indexed: 12/22/2022] Open
Abstract
Programmed death-ligand 1 (PD-L1) is an inhibitory ligand that binds to PD-1 to suppress T cell activation. PD-L1 is constitutively expressed and inducible in tumor cells, but the expression profiles and regulatory mechanism of PD-L1 in myeloid-derived suppressor cells (MDSCs) are largely unknown. We report that PD-L1 is abundantly expressed in tumor-infiltrating leukocytes in human patients with both microsatellite instable and microsatellite stable colon cancer. About 60% CD11b+CD33+HLA-DR- MDSCs from peripheral blood of human colon cancer patients are PD-L1+. PD-L1+ MDSCs are also significantly higher in tumor-bearing mice than in tumor-free mice. Interestingly, the highest PD-L1+ MDSCs were observed in the tumor microenvironment in which 56-71% tumor-infiltrating MDSCs are PD-L1+in vivo. In contrast, PD-L1+ MDSCs are significantly less in secondary lymphoid organs and peripheral blood as compared to the tumor tissues, whereas bone marrow MDSCs are essentially PD-L1- in tumor-bearing mice. IFNγ is highly expressed in cells of the tumor tissues and IFNγ neutralization significantly decreased PD-L1+ MDSCs in the tumor microenvironment in vivo. However, IFNγ-activated pSTAT1 does not bind to the cd274 promoter in MDSCs. Instead, pSTAT1 activates expression of IRF1, IRF5, IRF7 and IRF8 in MDSCs, and only pSTAT1-activated IRF1 binds to a unique IRF-binding sequence element in vitro and chromatin in vivo in the cd274 promoter to activate PD-L1 transcription. Our data determine that PD-L1 is highly expressed in tumor-infiltrating MDSCs and in a lesser degree in lymphoid organs, and the pSTAT1-IRF1 axis regulates PD-L1 expression in MDSCs.
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Affiliation(s)
- Chunwan Lu
- Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA, USA; Charlie Norwood VA Medical Center, Augusta, GA, USA
| | - Priscilla S Redd
- Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA, USA; Charlie Norwood VA Medical Center, Augusta, GA, USA; Georgia Cancer Center, Augusta University, Augusta, GA, USA
| | - Jeffrey R Lee
- Charlie Norwood VA Medical Center, Augusta, GA, USA; Pathology, Medical College of Georgia, Augusta, GA, USA
| | - Natasha Savage
- Pathology, Medical College of Georgia , Augusta, GA, USA
| | - Kebin Liu
- Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA, USA; Charlie Norwood VA Medical Center, Augusta, GA, USA; Georgia Cancer Center, Augusta University, Augusta, GA, USA
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13
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Gargiulo P, Pensabene M, Milano M, Arpino G, Giuliano M, Forestieri V, Condello C, Lauria R, De Placido S. Long-term survival and BRCA status in male breast cancer: a retrospective single-center analysis. BMC Cancer 2016; 16:375. [PMID: 27377827 PMCID: PMC4932666 DOI: 10.1186/s12885-016-2414-y] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2015] [Accepted: 06/28/2016] [Indexed: 11/17/2022] Open
Abstract
Background Male breast cancer (MBC) is rare. Given the paucity of randomized trials, treatment is generally extrapolated from female breast cancer guidelines. Methods This is a retrospective analysis of all male patients presenting with MBC at the Department of Oncology at University Federico II of Naples between January 1989 and January 2014. We recorded the following data: baseline characteristics (age, height, weight, body mass index, risk factors, family history), tumor characteristics (side affected, stage, histotype, hormonal and HER2 status, and Ki-67 expression), treatment (type of surgery, chemotherapy, endocrine therapy, and/or radiotherapy), BRCA1/2 mutation status (if available), other tumors, and long-term survival. Results Forty-seven patients were analyzed. Median age was 62.0 [55.0–72.0]. Among risk factors, obesity and family history of breast cancer were associated with 21 % and 30 % of MBC cases, respectively. The majority of tumors were diagnosed at an early stage: stage I (34.0 %) and stage II (44.7 %). Infiltrating ductal carcinoma was the most frequent histologic subtype (95.8 %). Hormone receptors were generally positive (88.4 % of cases were Estrogen receptor [ER] positive and 81.4 % Progesteron receptor [PgR] positive). Human epidermal growth factor receptor 2 (HER2) was positive in 26.8 % of cases; 7.0 % of MBCs were triple negative. The tumor had high proliferation index (Ki67 ≥ 20 %) in 64.7 %. Surgery was predominantly mastectomy (85.1 %), whereas quadrantectomy was performed in 14.9 % of patients. Adjuvant chemotherapy was administered to 70.7 % of patients, endocrine therapy to 90.2 %, trastuzumab to 16.7 % and radiotherapy to 32.6 %. BRCA status was available for 17 patients: 10 wild-type, 1 BRCA1 carrier, 5 BRCA2 carriers, 1 unknown variant sequence. The overall estimated long-term survival was about 90 % at 5 years, 80 % at 10 years and 70 % at 20 years. Patients carrying a BRCA mutation had a significantly lower survival than patients with wild-type BRCA (p = 0.04). Conclusions Long-term survival was high in MBC patients referred to our clinical unit. Survival was poorer in BRCA-mutated patients than in patients with wild-type BRCA.
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Affiliation(s)
- Piera Gargiulo
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - Matilde Pensabene
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - Monica Milano
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - Grazia Arpino
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - Mario Giuliano
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy.,Lester and Sue Smith Breast Center at Baylor College of Medicine, Houston, Tx, USA
| | - Valeria Forestieri
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - Caterina Condello
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - Rossella Lauria
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy.
| | - Sabino De Placido
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
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Liu Y, Yu XF, Zou J, Luo ZH. Prognostic value of c-Met in colorectal cancer: A meta-analysis. World J Gastroenterol 2015; 21:3706-3710. [PMID: 25834339 PMCID: PMC4375596 DOI: 10.3748/wjg.v21.i12.3706] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Revised: 10/31/2014] [Accepted: 12/01/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the prognostic value of c-Met status in colorectal cancer.
METHODS: We conducted a search in PubMed, Web of Science, and the Cochrane Library covering all published papers up to July 2014. Only studies assessing survival in colorectal cancer by c-Met status were included. This meta-analysis was performed by using STATA11.0.
RESULTS: Ultimately, 11 studies were included in this analysis. Meta-analysis of the hazard ratios (HR) indicated that patients with high c-Met expression have a significantly poorer overall survival (OR) (HR = 1.33, 95%CI: 1.06-1.59) and progression-free survival (PFS) (HR = 1.47, 95%CI: 1.03-1.91). Subgroup analysis showed a significant association between high c-Met expression and poorer overall survival in the hazard ratio reported (HR = 1.41, 95%CI: 1.08-1.74).
CONCLUSION: The present meta-analysis indicated that high c-Met expression was associated with poor prognosis in patients with colorectal cancer.
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Verma S, Kesh K, Ganguly N, Jana S, Swarnakar S. Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants. World J Biol Chem 2014; 5:355-376. [PMID: 25225603 PMCID: PMC4160529 DOI: 10.4331/wjbc.v5.i3.355] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2014] [Revised: 05/07/2014] [Accepted: 06/11/2014] [Indexed: 02/05/2023] Open
Abstract
The process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases (MMPs). Degradation of extracellular matrix (ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metalloproteinase (TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK (reversion including cysteine-rich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2, -9 and -14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species (ROS) through mitochondrial dysfunction leading to altered protease/anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is associated with a lower cancer incidence. Evidence indicates that some antioxidants inhibit the growth of malignant cells by inducing apoptosis and inhibiting the activity of MMPs. This review is discussed in six subchapters, as follows.
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Cai TT, Yan LP, Li H. Effect of cisplatin implantation on human gastric carcinoma xenograft growth in nude mice and tumor expression of SYK and HER2. Shijie Huaren Xiaohua Zazhi 2014; 22:2734-2739. [DOI: 10.11569/wcjd.v22.i19.2734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the effect of cisplatin implantation on human gastric carcinoma xenograft growth and tumor expression of SYK and HER2 in nude mice, and to discuss the mechanism of action of sustained-release cisplatin.
METHODS: A xenograft model of human gastric carcinoma was established by subcutaneous injection of SGC7901 cells in Balb/c nude mice. The mice were then randomly divided into four groups to receive intravenous injection of PBS (group A), intravenous injection of cisplatin (group B), intratumor injection of cisplatin (group C), and implantation of cisplatin (group D). After drug intervention, tumor weight and tumor inhibition rate were measured. Tumor tissues were observed after HE staining. Expression of SYK/HER2 was detected by immunohistochemsitry. Besides, the cell suspensions prepared from the tumor tissues from the four groups were tested by FCM.
RESULTS: Sustained-release cisplatin could promote apoptosis and suppress tumor growth significantly, and it also could enhance the expression of SYK (group D: 73.42 ± 4.92 vs group C: 30.42 ± 3.92, P < 0.05; group B: 14.14 ± 2.84 vs group A: 5.06 ± 2.96, P < 0.05) and reduce the expression of HER2 (group D: 16.32 ± 4.82 vs group C: 34.82 ± 7.32, P < 0.05; group B: 45.8 ± 6.60 vs group A: 77.34 ± 9.04, P < 0.05).
CONCLUSION: Cisplatin implantation induces tumor cell apoptosis and exerts anticancer function possibly by enhancing the expression of SYK and reducing the expression of HER2.
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Zhou HB, Hu JY, Hu HP. Hepatitis B virus infection and intrahepatic cholangiocarcinoma. World J Gastroenterol 2014; 20:5721-5729. [PMID: 24914333 PMCID: PMC4024782 DOI: 10.3748/wjg.v20.i19.5721] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Accepted: 12/13/2013] [Indexed: 02/06/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a devastating malignant tumor arising from the peripheral intrahepatic bile duct epithelium. The incidence and mortality of ICC is markedly increasing over the past two decades worldwide, though the cause for this rise in incidence is unclear, thus intensifying the search for alternative etiological agents and pathogenetic mechanisms. Hepatolithiasis, primary sclerosing cholangitis, parasitic infection (Opisthorchis viverrini or Clonorchis sinensis), fibropolycystic liver disease, and chemical carcinogen exposure are thought to be the risk factors for ICC. Nevertheless, the majority of ICC patients do not have any of these risk factors, and none of the established risk factors can explain the recent increasing trend of ICC. Therefore, identifying other risk factors may lead to the prevention and early detection of ICC. Chronic hepatitis B virus (HBV) infection is the predominant cause of hepatocellular carcinoma in HBV-endemic areas. This review discusses the evidence implicating chronic HBV infection as a likely etiology of ICC and the pathogenetic mechanisms that might be involved.
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Abstract
Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are rare neoplasms of unknown etiology. Only 67 cases have been reported in the literature, to our knowledge, so far. The neoplasm usually occurs in middle-aged women. Most patients present with abnormal uterine bleeding and/or abdominal pain, along with an enlarged uterus or a palpable uterine mass. There is no specific imaging finding, and the diagnosis is made exclusively on histopathologic examination. A multitude of architectural patterns are described, which include plexiform cords, anastomosing trabeculae, watered-silk, microfollicle, macrofollicle, tubules, retiform, solid cellular islands, and diffuse pattern of growth. The neoplastic cells are usually small with round to ovoid nuclei, nuclear monotony, mild nuclear hyperchromasia, and inconspicuous nucleoli with scant eosinophilic cytoplasm. Nuclear grooves are rare. Mitotic figures are infrequent, and necrosis is mostly absent. This tumor depicts a diverse immunohistochemical profile with expression of sex cord, epithelial, and smooth muscle lineages markers. Sex cord markers, such as inhibin, calretinin, CD99, WT1, and MART-1; epithelial markers, such as pancytokeratin and epithelial membrane antigen; smooth muscle markers, such as smooth muscle actin, desmin, and histone deacetylase 8; and miscellaneous markers, such as CD10, estrogen receptor, progesterone receptor, S100, and CD117, are often coexpressed. Immunoexpression for calretinin and at least for one of the other sex cord markers is required to establish a diagnosis of UTROSCT. Hysterectomy with or without bilateral salpingo-oophorectomy is usually the treatment for UTROSCT. Although most UTROSCTs behave benignly, some do recur, and thus, this entity should be considered as a tumor of low malignant potential. In this review, we discuss the current knowledge on UTROSCT and its clinical relevance.
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Affiliation(s)
- Dinesh Pradhan
- From the Department of Pathology and Laboratory Medicine, Pushpanjali Crosslay Hospital, Ghaziabad, Delhi NCR, India
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Fan XS, Chen JY, Li CF, Zhang YF, Meng FQ, Wu HY, Feng AN, Huang Q. Differences in HER2 over-expression between proximal and distal gastric cancers in the Chinese population. World J Gastroenterol 2013; 19:3316-3323. [PMID: 23745034 PMCID: PMC3671084 DOI: 10.3748/wjg.v19.i21.3316] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2013] [Revised: 02/22/2013] [Accepted: 04/10/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate HER2 expression and its correlation with clinicopathological variables between proximal and distal gastric cancers (GC) in the Chinese population.
METHODS: Immunostaining of HER2 was performed and scored on a scale of 0-3 in 957 consecutive GC cases, according to the revised scoring criteria of HercepTestTM as used in the ToGA trial. Correlations between HER2 expression and clinicopathologic variables of proximal (n = 513) and distal (n = 444) GC were investigated.
RESULTS: Our results showed that HER2 expression was significantly higher in the proximal than in distal GC (P < 0.05). Overall, HER2 expression was significantly higher in male patients (P < 0.01), the Lauren intestinal type (P < 0.001), low-grade (P < 0.001) and pM1 (P < 0.01) diseases, respectively. There was a significant difference in HER2 expression among some pTNM stages (P < 0.05). In contrast, HER2 expression in the distal GC was significantly higher in male patients (P < 0.001), low-grade histology (P < 0.001), the Lauren intestinal type(P < 0.001), and pM1 (P < 0.001). In the proximal GC, however, higher HER2 expression scores were observed only in tumors with low-grade histology (P < 0.001) and the Lauren intestinal type (P < 0.001).
CONCLUSION: HER2 over-expression in GC of Chinese patients was significantly more common in proximal than in distal GC, and significantly correlated with the Lauren intestinal type and low-grade histology in both proximal and distal GC, and with pM1 disease and male gender in distal GC.
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Wang G, Yang ZQ, Zhang K. Endoplasmic reticulum stress response in cancer: molecular mechanism and therapeutic potential. Am J Transl Res 2010; 2:65-74. [PMID: 20182583 PMCID: PMC2826823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2009] [Accepted: 12/12/2009] [Indexed: 05/28/2023]
Abstract
In eukaryotic cells, the endoplasmic reticulum (ER) is an organelle that is responsible for protein folding and assembly, lipid and sterol biosynthesis, and free calcium storage. In the past decade, intensive research effort has been focused on intracellular stress signaling pathways from the ER that lead to transcriptional and translational reprogramming of stressed cells. These signaling pathways, which are collectively termed Unfolded Protein Response (UPR), are critical for the cell to make survival or death decision under ER stress conditions. In recent years, research in the cancer field has revealed that ER stress and the UPR are highly induced in various tumors and are closely associated with cancer cell survival and resistance to anti-cancer treatments. Identifying the UPR components that are activated or suppressed in malignancy and exploring cancer therapeutic potentials by targeting the UPR are hot research spots. In this review, we summarize the recent progress in understating UPR signaling in cancer and its related therapeutic potential.
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