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Ng AP, Chervu N, Branche C, Bakhtiyar SS, Marzban M, Toste PA, Benharash P. National clinical and financial outcomes associated with acute kidney injury following esophagectomy for cancer. PLoS One 2024; 19:e0300876. [PMID: 38547215 PMCID: PMC10977786 DOI: 10.1371/journal.pone.0300876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 03/06/2024] [Indexed: 04/02/2024] Open
Abstract
BACKGROUND Esophagectomy is a complex oncologic operation associated with high rates of postoperative complications. While respiratory and septic complications have been well-defined, the implications of acute kidney injury (AKI) remain unclear. Using a nationally representative database, we aimed to characterize the association of AKI with mortality, resource use, and 30-day readmission. METHODS All adults undergoing elective esophagectomy with a diagnosis of esophageal or gastric cancer were identified in the 2010-2019 Nationwide Readmissions Database. Study cohorts were stratified based on presence of AKI. Multivariable regressions and Royston-Parmar survival analysis were used to evaluate the independent association between AKI and outcomes of interest. RESULTS Of an estimated 40,438 patients, 3,210 (7.9%) developed AKI. Over the 10-year study period, the incidence of AKI increased from 6.4% to 9.7%. Prior radiation/chemotherapy and minimally invasive operations were associated with reduced odds of AKI, whereas public insurance coverage and concurrent infectious and respiratory complications had greater risk of AKI. After risk adjustment, AKI remained independently associated with greater odds of in-hospital mortality (AOR: 4.59, 95% CI: 3.62-5.83) and had significantly increased attributable costs ($112,000 vs $54,000) and length of stay (25.7 vs 13.3 days) compared to patients without AKI. Furthermore, AKI demonstrated significantly increased hazard of 30-day readmission (hazard ratio: 1.16, 95% CI: 1.01-1.32). CONCLUSIONS AKI after esophagectomy is associated with greater risk of mortality, hospitalization costs, and 30-day readmission. Given the significant adverse consequences of AKI, careful perioperative management to mitigate this complication may improve quality of esophageal surgical care at the national level.
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Affiliation(s)
- Ayesha P. Ng
- Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
| | - Nikhil Chervu
- Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
| | - Corynn Branche
- Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
| | - Syed Shahyan Bakhtiyar
- Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
- Department of Surgery, University of Colorado Anschutz Medical Center, Aurora, Colorado, United States of America
| | - Mehrab Marzban
- Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
| | - Paul A. Toste
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
| | - Peyman Benharash
- Cardiovascular Outcomes Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
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Hucke A, Kantauskaite M, Köpp TN, Wehe CA, Karst U, Nedvetsky PI, Ciarimboli G. Modulating the Activity of the Human Organic Cation Transporter 2 Emerges as a Potential Strategy to Mitigate Unwanted Toxicities Associated with Cisplatin Chemotherapy. Int J Mol Sci 2024; 25:2922. [PMID: 38474165 DOI: 10.3390/ijms25052922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 02/27/2024] [Accepted: 02/28/2024] [Indexed: 03/14/2024] Open
Abstract
Cisplatin (CDDP) stands out as an effective chemotherapeutic agent; however, its application is linked to the development of significant adverse effects, notably nephro- and ototoxicity. The human organic cation transporter 2 (hOCT2), found in abundance in the basolateral membrane domain of renal proximal tubules and the Corti organ, plays a crucial role in the initiation of nephro- and ototoxicity associated with CDDP by facilitating its uptake in kidney and ear cells. Given its limited presence in cancer cells, hOCT2 emerges as a potential druggable target for mitigating unwanted toxicities associated with CDDP. Potential strategies for mitigating CDDP toxicities include competing with the uptake of CDDP by hOCT2 or inhibiting hOCT2 activity through rapid regulation mediated by specific signaling pathways. This study investigated the interaction between the already approved cationic drugs disopyramide, imipramine, and orphenadrine with hOCT2 that is stably expressed in human embryonic kidney cells. Regarding disopyramide, its influence on CDDP cellular transport by hOCT2 was further characterized through inductively coupled plasma isotope dilution mass spectrometry. Additionally, its potential protective effects against cellular toxicity induced by CDDP were assessed using a cytotoxicity test. Given that hOCT2 is typically expressed in the basolateral membrane of polarized cells, with specific regulatory mechanisms, this work studied the regulation of hOCT2 that is stably expressed in Madin-Darby Canine Kidney (MDCK) cells. These cells were cultured in a matrix to induce the formation of cysts, exposing hOCT2 in the basolateral plasma membrane domain, which was freely accessible to experimental solutions. The study specifically tested the regulation of ASP+ uptake by hOCT2 in MDCK cysts through the inhibition of casein kinase II (CKII), calmodulin, or p56lck tyrosine kinase. Furthermore, the impact of this manipulation on the cellular toxicity induced by CDDP was examined using a cytotoxicity test. All three drugs-disopyramide, imipramine, and orphenadrine-demonstrated inhibition of ASP+ uptake, with IC50 values in the micromolar (µM) range. Notably, disopyramide produced a significant reduction in the CDDP cellular toxicity and platinum cellular accumulation when co-incubated with CDDP. The activity of hOCT2 in MDCK cysts experienced a significant down-regulation under inhibition of CKII, calmodulin, or p56lck tyrosine kinase. Interestingly, only the inhibition of p56lck tyrosine kinase demonstrated the capability to protect the cells against CDDP toxicity. In conclusion, certain interventions targeting hOCT2 have demonstrated the ability to reduce CDDP cytotoxicity, at least in vitro. Further investigations in in vivo systems are warranted to ascertain their potential applicability as co-treatments for mitigating undesired toxicities associated with CDDP in patients.
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Affiliation(s)
- Anna Hucke
- Experimental Nephrology, Department of Internal Medicine D, University Hospital Münster, 48149 Münster, Germany
- Institute of Physiology I, University of Münster, 48149 Münster, Germany
| | - Marta Kantauskaite
- Experimental Nephrology, Department of Internal Medicine D, University Hospital Münster, 48149 Münster, Germany
- Klinik für Nephrologie, Universitätsklinikum Düsseldorf, 40225 Düsseldorf, Germany
| | - Tim N Köpp
- Experimental Nephrology, Department of Internal Medicine D, University Hospital Münster, 48149 Münster, Germany
| | - Christoph A Wehe
- Institute of Inorganic and Analytical Chemistry, University of Münster, 48149 Münster, Germany
| | - Uwe Karst
- Institute of Inorganic and Analytical Chemistry, University of Münster, 48149 Münster, Germany
| | - Pavel I Nedvetsky
- Experimental Nephrology, Department of Internal Medicine D, University Hospital Münster, 48149 Münster, Germany
| | - Giuliano Ciarimboli
- Experimental Nephrology, Department of Internal Medicine D, University Hospital Münster, 48149 Münster, Germany
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Noritake O, Nakamura S, Kinoshita F, Aokage K, Asao T, Matsuura Y, Chen-Yoshikawa TF. Prognostic impact of adjuvant therapy for cisplatin-unfit patients with non-small-cell lung cancer: A multicenter analysis. Lung Cancer 2024; 188:107470. [PMID: 38237212 DOI: 10.1016/j.lungcan.2024.107470] [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: 09/01/2023] [Revised: 01/07/2024] [Accepted: 01/10/2024] [Indexed: 02/03/2024]
Abstract
INTRODUCTION No evidence exists for postoperative adjuvant therapy in elderly or renal dysfunction patients with non-small-cell lung cancer (NSCLC) who are unfit to receive cisplatin (CDDP). Herein, we evaluated the efficacy of postoperative adjuvant therapy for CDDP-unfit patients. MATERIALS AND METHODS We defined CDDP-unfit patients as those aged ≥75 years or with renal dysfunction based on criteria established by expert panels and from prospective studies. CDDP-fit patients comprised all others. Between 2010 and 2020, among 1,423 patients with pathological stage II-III (8th edition of the AJCC-TNM Classification) NSCLC, 454 were identified as unfit for CDDP. Following propensity score matching in CDDP-unfit patients with and without postoperative adjuvant therapy, we analyzed the overall survival (OS) and disease-free survival (DFS) of each group and assessed the impact of adjuvant therapy on survival. RESULTS OS was significantly better in patients who received adjuvant therapy than in those who did not (5-year OS rate: 76.1 % vs. 50.0 %, p < 0.01) among 255 propensity score-matched patients. DFS was also significantly better in patients who received adjuvant therapy than in those who did not (5-year OS: 54.6 % vs. 35.1 %, p < 0.01). CONCLUSIONS Our findings suggest that postoperative adjuvant therapy could be beneficial for CDDP-unfit patients aged ≥75 years or with renal dysfunction. Future studies for CDDP-unfit patients should be designed based on the results of this study to determine the potential benefits of adjuvant therapy.
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Affiliation(s)
- Osamu Noritake
- Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shota Nakamura
- Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
| | - Fumie Kinoshita
- Data Coordinating Center, Department of Advanced Medicine, Nagoya University Hospital, Japan
| | - Keiju Aokage
- Department of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
| | - Tetsuhiko Asao
- Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Yosuke Matsuura
- Department of Thoracic Surgical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
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Muto S, Matsubara T, Inoue T, Kitamura H, Yamamoto K, Ishii T, Yazawa M, Yamamoto R, Okada N, Mori K, Yamada H, Kuwabara T, Yonezawa A, Fujimaru T, Kawano H, Yokoi H, Doi K, Hoshino J, Yanagita M. Chapter 1: Evaluation of kidney function in patients undergoing anticancer drug therapy, from clinical practice guidelines for the management of kidney injury during anticancer drug therapy 2022. Int J Clin Oncol 2023; 28:1259-1297. [PMID: 37382749 DOI: 10.1007/s10147-023-02372-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 06/14/2023] [Indexed: 06/30/2023]
Abstract
The prevalence of CKD may be higher in patients with cancer than in those without due to the addition of cancer-specific risk factors to those already present for CKD. In this review, we describe the evaluation of kidney function in patients undergoing anticancer drug therapy. When anticancer drug therapy is administered, kidney function is evaluated to (1) set the dose of renally excretable drugs, (2) detect kidney disease associated with the cancer and its treatment, and (3) obtain baseline values for long-term monitoring. Owing to some requirements for use in clinical practice, a GFR estimation method such as the Cockcroft-Gault, MDRD, CKD-EPI, and the Japanese Society of Nephrology's GFR estimation formula has been developed that is simple, inexpensive, and provides rapid results. However, an important clinical question is whether they can be used as a method of GFR evaluation in patients with cancer. When designing a drug dosing regimen in consideration of kidney function, it is important to make a comprehensive judgment, recognizing that there are limitations regardless of which estimation formula is used or if GFR is directly measured. Although CTCAEs are commonly used as criteria for evaluating kidney disease-related adverse events that occur during anticancer drug therapy, a specialized approach using KDIGO criteria or other criteria is required when nephrologists intervene in treatment. Each drug is associated with the different disorders related to the kidney. And various risk factors for kidney disease associated with each anticancer drug therapy.
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Affiliation(s)
- Satoru Muto
- Department of Urology, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
| | - Takeshi Matsubara
- Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Takamitsu Inoue
- Department of Renal and Urologic Surgery, International University of Health and Welfare Narita Hospital, Chiba, Japan
| | - Hiroshi Kitamura
- Department of Urology, Faculty of Medicine, University of Toyama, Toyama, Japan
| | | | - Taisuke Ishii
- Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
| | - Masahiko Yazawa
- Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Ryohei Yamamoto
- Department of Urology, Akita University Graduate School of Medicine, Akita, Japan
| | - Naoto Okada
- Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan
- Pharmacy Department, Yamaguchi University Hospital, Yamaguchi, Japan
| | - Kiyoshi Mori
- Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan
| | - Hiroyuki Yamada
- Department of Primary Care and Emergency Medicine, Kyoto University Hospital, Kyoto, Japan
| | - Takashige Kuwabara
- Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Atsushi Yonezawa
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan
| | - Takuya Fujimaru
- Department of Nephrology, St Luke's International Hospital, Tokyo, Japan
| | - Haruna Kawano
- Department of Urology, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Hideki Yokoi
- Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Kent Doi
- Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital, Tokyo, Japan
| | - Junichi Hoshino
- Department of Nephrology, Tokyo Women's Medical University, Tokyo, Japan
| | - Motoko Yanagita
- Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan
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The development and progress of nanomedicine for esophageal cancer diagnosis and treatment. Semin Cancer Biol 2022; 86:873-885. [DOI: 10.1016/j.semcancer.2022.01.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 11/22/2021] [Accepted: 01/20/2022] [Indexed: 02/07/2023]
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Isiiko J, Atwiine B, Oloro J. Prevalence and Risk Factors of Nephrotoxicity Among Adult Cancer Patients at Mbarara Regional Referral Hospital. Cancer Manag Res 2021; 13:7677-7684. [PMID: 34675664 PMCID: PMC8504863 DOI: 10.2147/cmar.s326052] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 09/28/2021] [Indexed: 11/23/2022] Open
Abstract
Background Nephrotoxicity is common among cancer patients, yet some anti-cancer drugs, for example, platinum derivatives, are nephrotoxic and have narrow therapeutic indices. If nephrotoxicity is not managed, it can progress to kidney injury, which results in unregulated blood pressure, hormonal imbalance, electrolyte imbalance, body fluid imbalance and death. However, the burden of nephrotoxicity among adult cancer patients in Uganda is not documented in the literature. Objective This study assessed the prevalence and risk factors of nephrotoxicity among cancer patients receiving chemotherapy at Mbarara Regional Referral Hospital Cancer Unit (MRRHCU). Methods The study was a cross-sectional study carried out at the MRRHCU, Uganda. All the 206 adult cancer patients who received at least three cycles of chemotherapy and fulfilled the inclusion criteria were included. A data collection form was used to collect data, which was recorded into Microsoft Excel version 2013. Data were analyzed using Stata version 12.1. Results Of the 206 participants, 74 (35.9%) developed nephrotoxicity with majority in stage 1 (n = 83, 40.3%) and stage 2 (n = 55, 26.7%). In the multivariate logistic regression of risk factors for nephrotoxicity, age >50 years old (aOR: 1.80, 95% CI: 1.06, 1.91; p > 0.001), hypertension (aOR: 1.71, 95% CI: 1.74, 1.94; p = 0.011) and use of platinum agents (aOR: 2.04, 95% CI: 1.82, 3.34; p = 0.002) were significant independent risk factors of nephrotoxicity. Conclusion About one-third (1/3) of the adult cancer patients at MRRHCU develop nephrotoxicity, which indicates a high burden of nephrotoxicity. The prevention of progression of nephrotoxicity from grades 0, 1 or 2 to grade 3 or 4 is therefore necessary, especially among the patients with risk factors, such as hypertension and age >50 years old and use of platinum agents.
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Affiliation(s)
- John Isiiko
- Department of Pharmacy, Mbarara University of Science and Technology, Mbarara, Uganda.,Pharmacy Biotechnology and Traditional Medicine Center, Mbarara University of Science and Technology, Mbarara, Uganda.,Department of Pharmacy, Uganda Cancer Institute, Kampala, Uganda
| | - Barnabas Atwiine
- Department of Pediatrics and Child Health, Mbarara University of Science and Technology, Mbarara, Uganda
| | - Joseph Oloro
- Department of Pharmacology and Therapeutics, Mbarara University of Science and Technology, Mbarara, Uganda
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Li XY, Guan QX, Shang YZ, Wang YH, Lv SW, Yang ZX, Wang R, Feng YF, Li WN, Li YJ. Metal-organic framework IRMOFs coated with a temperature-sensitive gel delivering norcantharidin to treat liver cancer. World J Gastroenterol 2021; 27:4208-4220. [PMID: 34326620 PMCID: PMC8311525 DOI: 10.3748/wjg.v27.i26.4208] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/27/2021] [Accepted: 05/27/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Norcantharidin (NCTD) is suitable for the treatment of primary liver cancer, especially early and middle primary liver cancer. This compound can reduce tumors and improve immune function. However, the side effects of NCTD have limited its application. There is a marked need to reduce the side effects and increase the efficacy of NCTD. AIM To develop a nanomaterial carrier, NCTD-loaded metal-organic framework IRMOF-3 coated with a temperature-sensitive gel (NCTD-IRMOF-3-Gel), aiming to improve the anticancer activity of NCTD and reduce the drug dose. METHODS NCTD-IRMOF-3-Gel was obtained by a coordination reaction. The apparent characteristics and in vitro release of NCTD-IRMOF-3-Gel were investigated. Cell cytotoxicity assays, flow cytometry, and apoptosis experiments in mouse hepatoma (Hepa1-6) cells were used to determine the anti-liver cancer activity of NCTD-IRMOF-3-Gel in in vitro models. RESULTS The particle size of NCTD-IRMOF-3-Gel was 50-100 nm, and the particle size distribution was uniform. The release curve showed that NCTD-IRMOF-3-Gel had an obvious sustained-release effect. The cytotoxicity assays showed that the free drug NCTD and NCTD-IRMOF-3-Gel treatments markedly inhibited Hepa1-6 cell proliferation, and the inhibition rate increased with increasing drug concentration. By flow cytometry, NCTD-IRMOF-3-Gel was observed to block the Hepa1-6 cell cycle in the S and G2/M phases, and the thermosensitive gel nanoparticles may inhibit cell proliferation by inducing cell cycle arrest. Apoptosis experiments showed that NCTD-IRMOF-3-Gel induced the apoptosis of Hepa1-6 cells. CONCLUSION Our results indicated that the NCTD-IRMOF-3-Gel may be beneficial for liver cancer disease treatment.
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Affiliation(s)
- Xiu-Yan Li
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Qing-Xia Guan
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Yu-Zhou Shang
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Yan-Hong Wang
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Shao-Wa Lv
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Zhi-Xin Yang
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Rui Wang
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Yu-Fei Feng
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Wei-Nan Li
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Yong-Ji Li
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
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8
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Metal-organic framework IRMOFs coated with a temperature-sensitive gel delivering norcantharidin to treat liver cancer. World J Gastroenterol 2021. [DOI: 10.3748/wjg.v27.i26.4203] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/17/2023] Open
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9
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Wang X, Wang Y, Yao F, Chen S, Hou Y, Zheng Z, Luo J, Qiu B, Li Z, Wang Y, Wu Z, Lan J, Chen C. Pharmacokinetics of Linezolid Dose Adjustment for Creatinine Clearance in Critically Ill Patients: A Multicenter, Prospective, Open-Label, Observational Study. DRUG DESIGN DEVELOPMENT AND THERAPY 2021; 15:2129-2141. [PMID: 34040351 PMCID: PMC8142937 DOI: 10.2147/dddt.s303497] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 04/13/2021] [Indexed: 12/11/2022]
Abstract
Purpose The aim of this study is to use a population pharmacokinetic (PK) approach to evaluate the optimal dosing strategy for linezolid (LNZ) in critically ill patients. Methods This multicenter, prospective, open-label, observational study was conducted in 152 patients, and 117 of them were included in the PK model, whereas the rest were in the validation group. The percentage of therapeutic target attainment (PTTA) comprising two pharmacodynamic indices and one toxicity index was used to evaluate dosing regimens based on Monte Carlo simulations stratified by low, normal, and high renal clearance for MICs of 0.25–4 mg/L. Results A single-compartment model with a covariate creatinine clearance (CrCL) was chosen as the final model. The PK parameter estimates were clearance of 5.60 L/h, with CrCL adjustment factor of 0.386, and a distribution volume of 43.4 L. For MIC ≤2 mg/L, the standard dosing regimen (600 mg q12h) for patients with severe renal impairment (CrCL, 40 mL/min) and standard dosing or 900 mg q12h for patients with normal renal functions (CrCL, 80 mL/min) could achieve PTTA ≥74%. The dose of 2400 mg per 24-h continuous infusion was ideal for augmented renal clearance (ARC) with MIC ≤1 mg/L. For MICs >2 mg/L, rare optimal dose regimens were found regardless of renal function. Conclusion In critically ill patients, the standard dose of 600 mg q12h was sufficient for MIC ≤2 mg/L in patients without ARC. Moreover, a 2400 mg/day 24-h continuous infusion was recommended for ARC patients.
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Affiliation(s)
- Xipei Wang
- Department of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Cardiovascular Institute, Guangzhou, 510080, People's Republic of China
| | - Yifan Wang
- Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, People's Republic of China.,School of Biology and Biological Engineering, South China University of Technology, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Fen Yao
- Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, People's Republic of China.,School of Biology and Biological Engineering, South China University of Technology, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Shenglong Chen
- Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Yating Hou
- Department of Oncology, Maoming People's Hospital, Maoming, 525000, Guangdong, People's Republic of China
| | - Zhijie Zheng
- Department of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Cardiovascular Institute, Guangzhou, 510080, People's Republic of China
| | - Jinbiao Luo
- Department of Neurosurgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People's Republic of China
| | - Binghui Qiu
- Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China
| | - Zhanfu Li
- Department of Intensive Care Unit, Guangdong 999 Brain Hospital, Guangzhou, 510510, Guangdong, People's Republic of China
| | - Yirong Wang
- Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Zheng Wu
- Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Jinhua Lan
- Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Chunbo Chen
- Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Laboratory of South China Structural Heart Disease, Guangzhou, 510080, Guangdong, People's Republic of China.,The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510000, Guangdong, People's Republic of China
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Establishment and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Tigecycline in Critically Ill Patients. Int J Anal Chem 2020; 2020:6671392. [PMID: 33456470 PMCID: PMC7785388 DOI: 10.1155/2020/6671392] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Accepted: 12/03/2020] [Indexed: 12/23/2022] Open
Abstract
Utilizing tigecycline-d9 as an internal standard (IS), we establish and validate a simple, effective, and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative measurement of tigecycline (TGC) in patient plasma. Acetonitrile was used as a precipitant to process plasma samples by a protein precipitation method. The analyte and IS were separated on an HSS T3 (2.1 × 100 mm, 3.5 μm) chromatographic column using isocratic program with a mobile phase comprising of 80% solvent A (water containing 0.1% formic acid (v/v) with 5 mM ammonium acetate) and 20% solvent B (acetonitrile) with a flow rate of 0.3 mL/min. The mass spectrometer, scanning in multireaction monitoring (MRM) mode and using an electrospray ion source (ESI), operated in the positive-ion mode. The ion pairs used for quantitative analysis were m/z 586.4 ⟶ 513.3 and m/z 595.5 ⟶ 514.3 for TGC and the IS, respectively. The range of the linear calibration curve obtained with this approach was 50–5000 ng/ml. Intra- and interbatch precision for TGC quantitation were less than 7.2%, and the accuracy ranged from 93.4 to 101.8%. The IS-normalized matrix effect was 87 to 104%. Due to its high precision and accuracy, this novel method allows for fast quantitation of TGC with a total analysis time of 2 min. This approach was effectively applied to study the pharmacokinetics of TGC in critically ill adult patients.
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Huang HB, Gao ZM, Sun AQ, Liang WT, Li K. Subtotal gastrectomy combined with chemotherapy: An effective therapy for patients with circumscribed Borrmann type IV gastric cancer. World J Gastrointest Oncol 2020; 12:1325-1335. [PMID: 33250964 PMCID: PMC7667453 DOI: 10.4251/wjgo.v12.i11.1325] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 08/20/2020] [Accepted: 09/25/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Although Borrmann type IV (B-4) gastric cancer has a higher mortality rate and presents distant metastasis easily, especially peritoneal metastasis, when diagnosed, some B-4 patients were found to have no distant metastasis by preoperative detection and underwent curative surgery, which was defined as circumscribed B-4 in our study. In this study, we focused on the circumscribed B-4 patients without distant metastasis during surgery to identify factors related to prognosis and postoperative peritoneal cavity metastasis (PPCM), which is important for selecting an appropriate therapeutic strategy. AIM To identify factors related to the prognosis and PPCM of B-4 patients. METHODS A total of 117 B-4 patients who underwent gastrectomy between January 2005 and December 2012 were included in this study. Survival analysis was performed using Kaplan-Meier analysis and Cox multivariate models. Pearson correlation analyses were performed to identify the factors related to PPCM. All statistical analyses were performed using SPSS 20.0. RESULTS Lymph node status, gastrectomy type, and postoperative chemotherapy were independent prognostic factors in 117 circumscribed B-4 patients. Subtotal gastrectomy combined with chemotherapy could significantly improve the long-term survival time. Six patients who were diagnosed with pN0 and received the combination therapy had a 3-year survival rate of 100% and a median survival of 77.7 mo. Even for patients with metastatic lymph nodes (n = 13), the combination therapy also increased the 3-year overall survival rate to 57.1%. In addition, positive lymph node status was the only factor (P = 0.005) correlated with PPCM in certain B-4 patients, and chemotherapy was useful for suppressing PPCM in patients with subtotal gastrectomy but not in those with total gastrectomy. CONCLUSION Lymph node status is an independent prognostic factor for circumscribed B-4 patients. In addition, subtotal gastrectomy and postoperative chemotherapy could effectively improve prognosis and even suppress PPCM.
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Affiliation(s)
- Hai-Bo Huang
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Zi-Ming Gao
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - An-Qi Sun
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Wei-Tian Liang
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Kai Li
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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Ma ZH, Wang YP, Zheng WH, Ma J, Bai X, Zhang Y, Wang YH, Chi D, Fu XB, Hua XD. Prognostic factors and therapeutic effects of different treatment modalities for colorectal cancer liver metastases. World J Gastrointest Oncol 2020; 12:1177-1194. [PMID: 33133385 PMCID: PMC7579728 DOI: 10.4251/wjgo.v12.i10.1177] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 08/18/2020] [Accepted: 09/14/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most common malignant tumors in China, and the liver is the most common metastatic site in patients with advanced CRC. Hepatectomy is the gold standard treatment for colorectal liver metastases. For patients who cannot undergo radical resection of liver metastases for various reasons, ablation therapy, interventional therapy, and systemic chemotherapy can be used to improve their quality of life and prolong their survival time.
AIM To explore the prognostic factors and treatments of liver metastases of CRC.
METHODS A retrospective analysis was conducted on 87 patients with liver metastases from CRC treated at the Liaoning Cancer Hospital and Institute between January 2005 and March 2011. According to different treatments, the patients were divided into the following four groups: Surgical resection group (36 patients); ablation group (23 patients); intervention group (15 patients); and drug group (13 patients). The clinicopathological data and postoperative survival of the four groups were analyzed. The Kaplan-Meier method was used for survival analysis, and the Cox proportional hazards regression model was used for multivariate analysis.
RESULTS The median survival time of the 87 patients was 38.747 ± 3.062 mo, and the 1- and 3-year survival rates were 87.5% and 53.1%, respectively. The Cox proportional hazards model showed that the following factors were independent factors affecting prognosis: The degree of tumor differentiation, the number of metastases, the size of metastases, and whether the metastases are close to great vessels. The results of treatment factor analysis showed that the effect of surgical treatment was better than that of drugs, intervention, or ablation alone, and the median survival time was 48.83 ± 4.36 mo. The drug group had the worst prognosis, with a median survival time of only 13.5 ± 0.7 mo (P < 0.05). For patients with liver metastases of CRC near the great vessels, the median survival time (27.3 mo) of patients undergoing surgical resection was better than that of patients using other treatments (20.6 mo) (P < 0.05).
CONCLUSION Patients with a low degree of primary tumor differentiation, multiple liver metastases (number of tumors > 4), and maximum diameter of liver metastases > 5 cm have a poor prognosis. Among drug therapy, intervention, ablation, and surgical treatment options, surgical treatment is the first choice for liver metastases. When liver metastases are close to great vessels, surgical treatment is significantly better than drug therapy, intervention, and ablation alone.
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Affiliation(s)
- Zuo-Hong Ma
- Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Yong-Peng Wang
- Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Wen-Heng Zheng
- Department of Medical Imaging, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Ji Ma
- Department of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Xue Bai
- Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Yong Zhang
- Department of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Yuan-He Wang
- Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Da Chi
- Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Xi-Bo Fu
- Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
| | - Xiang-Dong Hua
- Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, China
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Zhang Y, Zhang B, Wang Y, Zhang J, Wu Y, Xiao T, Liao Y, Bao Y, Qiu H, Sun S, Guo J. Advances in the Prevention and Treatment of Esophageal Stricture after Endoscopic Submucosal Dissection of Early Esophageal Cancer. J Transl Int Med 2020; 8:135-145. [PMID: 33062589 PMCID: PMC7534493 DOI: 10.2478/jtim-2020-0022] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Endoscopic submucosal dissection (ESD) has become the main treatment for early esophageal cancer. While treating the disease, ESD may also cause postoperative esophageal stricture, which is a global issue that needs resolution. Various methods have been applied to resolve the problem, such as mechanical dilatation, glucocorticoids, anti-scarring drugs, and regenerative medicine; however, no standard treatment regimen exists. This article describes and evaluates the strengths and limitations of new and promising potential strategies for the treatment and prevention of esophageal strictures.
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Affiliation(s)
- Yue Zhang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Baozhen Zhang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Yidan Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Jingjing Zhang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Yufan Wu
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Tingyue Xiao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Ye Liao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Yiwen Bao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Hongyu Qiu
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Siyu Sun
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Jintao Guo
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
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Zhang J, Liu L, Li F, Wang Z, Zhao J. Treatment with catalpol protects against cisplatin-induced renal injury through Nrf2 and NF-κB signaling pathways. Exp Ther Med 2020; 20:3025-3032. [PMID: 32855669 PMCID: PMC7444339 DOI: 10.3892/etm.2020.9077] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Accepted: 05/20/2020] [Indexed: 12/21/2022] Open
Abstract
Cisplatin (CP) is one of the most widely used chemotherapy drugs for cancer treatment, but it often leads to nephrotoxicity. It is well known that catalpol exhibits antioxidant and anti-inflammatory functions, thus the present study aimed to investigate the potential protective effects of catalpol on CP-induced kidney injury in rats, in addition to determining the underlying mechanisms. Sprague-Dawley rats were treated with 25, 50 or 100 mg/kg catalpol for two days, injected with 20 mg/kg cisplatin and catalpol on day 3 and sacrificed on day 4. The histological analysis of isolated kidney tissues was performed using hematoxylin and eosin staining, cleaved caspase-3 expression levels were analyzed using western blotting and the expression levels of inflammatory cytokines in the tissues, including tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, IL-10 and inducible nitric oxide synthase (iNOS) were evaluated using ELISAs. Furthermore, the mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), kelch-like ECH-associated protein 1 (Keap1), NF-κB and inhibitory κB (IκB) were determined using reverse transcription-quantitative PCR and western blotting, respectively. The results revealed that the treatment with catalpol prevented the histopathological injury and renal dysfunction caused by CP. In addition, catalpol significantly suppressed the CP-induced apoptosis of tubular cells, inhibited the CP-induced upregulation of TNF-α, IL-1β, IL-6, IL-8 and iNOS and promoted the production of the anti-inflammatory cytokine IL-10. Additionally, the mRNA and protein expression levels of Nrf2, HO-1 and IκB in the kidney tissues were increased, whereas the expression levels of Keap1 and NF-κB were significantly decreased following the treatment with catalpol. In conclusion, these results suggested that catalpol may inhibit CP-induced renal injury and suppress the associated inflammatory response through activating the Nrf2 and inhibiting the NF-κB signaling pathways, respectively.
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Affiliation(s)
- Jun Zhang
- Department of Nephrology, The key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, P.R. China
| | - Li Liu
- Department of Nephrology, The key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, P.R. China
| | - Furong Li
- Department of Nephrology, The key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, P.R. China
| | - Zongqian Wang
- Department of Nephrology, The key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, P.R. China
| | - Jinghong Zhao
- Department of Nephrology, The key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Kidney Center of PLA, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, P.R. China
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Zhan W, Li H, Guo Y, Du G, Wu Y, Zhang D. Construction of Biocompatible Dual-Drug Loaded Complicated Nanoparticles for in vivo Improvement of Synergistic Chemotherapy in Esophageal Cancer. Front Oncol 2020; 10:622. [PMID: 32432038 PMCID: PMC7214620 DOI: 10.3389/fonc.2020.00622] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 04/03/2020] [Indexed: 12/17/2022] Open
Abstract
Combination chemotherapy is a routine treatment for esophageal cancer, but some shortcomings, such as drug toxicity and side effects, greatly limit the clinical application of combination therapy. To overcome these shortcomings, we have developed a mesoporous silica nanoparticle system that was used to load doxorubicin and β-elemene. β-elemene was encapsulated in the pore of mesoporous silica nanoparticle and doxorubicin was electrostatically adsorbed on the surface of mesoporous silica nanoparticle by hyaluronic acid to construct dual drugs synergistic nanoparticles (bMED NPs, ~77.15 nm). In vitro studies demonstrated that bMED NPs had a good treatment effect in esophageal cancer cell lines. In vivo fluorescence imaging results demonstrated that bMED NPs could accumulate in tumor sites and achieve in vivo long-term circulation and continuous drug release. In addition, bMED NPs exhibited significant antitumor effects in the esophageal cancer mouse model, which may provide a great platform for esophageal cancer chemotherapy.
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Affiliation(s)
- Wenhua Zhan
- Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.,Department of Radiation Oncology, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Hanrui Li
- Engineering Research Center of Molecular & Neuro Imaging of the Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, China
| | - Yingying Guo
- Engineering Research Center of Molecular & Neuro Imaging of the Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, China
| | - Getao Du
- Engineering Research Center of Molecular & Neuro Imaging of the Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, China
| | - Yayan Wu
- Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Dexin Zhang
- Department of Respiratory Medicine, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China
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Shen J, Cao D, Sun JL. Ability of human umbilical cord mesenchymal stem cells to repair chemotherapy-induced premature ovarian failure. World J Stem Cells 2020; 12:277-287. [PMID: 32399136 PMCID: PMC7202924 DOI: 10.4252/wjsc.v12.i4.277] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Revised: 03/23/2020] [Accepted: 03/26/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Premature ovarian insufficiency (POI) and premature ovarian failure (POF) have become one of the major problems threatening women of childbearing age. Studies have shown that stem cells transplanted from bone marrow, umbilical cord, peripheral blood and amniotic fluid can migrate and proliferate to the ovary, promote ovarian function repair, increase the number of follicles and granulosa cells at all levels of ovary, improve endocrine function, and can differentiate into oocytes in specific ovarian environment to restore fertility to some extent.
AIM To study the ability of human umbilical cord mesenchymal stem cells (hUCMSCs) to repair ovarian injury after chemotherapy.
METHODS A total of 110 female BALB/c mice (aged 7-8 wk old) with body masses of 16.0-20.0 g were selected. The mice were fed until 12 wk of age, and cyclophosphamide was administered by intraperitoneal injection for 14 consecutive days to induce premature ovarian failure in mice. Seventy-five mice with estrous cycle disorder were screened and randomly divided into 3 groups according to their body weight: model group, positive control group and hUCMSC group, and each group had 25 mice. Another 25 mice were used as negative controls. The mice in the hUCMSC group were injected with hUCMSCs in the tail vein, and the mice in the positive control group were given an oestradiol valerate solution and a medroxyprogesterone acetate solution in the tail vein. On the 1st, 15th, 30th, 45th, and 60th days after intravenous administration, vaginal smears were made to monitor the estrous cycles of the mice. The ovaries were weighed, and pathological sections were made to observe the morphology of the follicles; blood samples were collected to monitor the concentration of sex hormones (oestradiol and follicle-stimulating hormone).
RESULTS The estrous cycles of the model group mice were disrupted throughout the experiment. Mice in the hUCMSC group and the positive control group resumed normal estrous cycles. The ovarian weight of the model group mice continued to decline. The ovarian weight of the hUCMSC group mice and the positive control group mice decreased first and then gradually increased, and the ovarian weight of the hUCMSC group mice was heavier than that of the positive control group mice. The difference was statistically significant (P < 0.05). Compared with the negative control group, the model group experienced a decrease in oestradiol and an increase in follicle-stimulating hormone, and the difference was statistically significant (P < 0.05). Compared with the model group, the hUCMSC and positive control groups experienced a slight increase in oestradiol and a decrease in follicle-stimulating hormone; the difference was statistically significant (P < 0.05). The pathological examination revealed that the mouse ovaries from the model group were atrophied, the volume was reduced, the cortical and medullary structures were disordered, the number of follicles at all stages was significantly reduced, the number of atretic follicles increased, the number of primordial follicles and corpus luteum significantly decreased, and the corpus luteum had an irregular shape. Compared with those of the model group, the lesions of the hUCMSC and positive control groups significantly improved.
CONCLUSION hUCMSCs can repair ovarian tissue damaged by chemotherapy to a certain extent, can improve the degree of apoptosis in ovarian tissue, and can improve the endocrine function of mouse ovaries.
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Affiliation(s)
- Jian Shen
- Department of Obstetrics and Gynecology, General Hospital of Northern Theater Command (Heping Campus), Shenyang 110000, Liaoning Province, China
| | - Dai Cao
- Department of Obstetrics and Gynecology, General Hospital of Northern Theater Command (Heping Campus), Shenyang 110000, Liaoning Province, China
| | - Jing-Li Sun
- Department of Obstetrics and Gynecology, General Hospital of Northern Theater Command (Heping Campus), Shenyang 110000, Liaoning Province, China
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17
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Zheng C, Gao ZM, Sun AQ, Huang HB, Wang ZN, Li K, Gao S. Prognostic significance of 14v-lymph node dissection to D2 dissection for lower-third gastric cancer. World J Clin Cases 2019; 7:2712-2721. [PMID: 31616687 PMCID: PMC6789393 DOI: 10.12998/wjcc.v7.i18.2712] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 08/06/2019] [Accepted: 08/20/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Radical gastrectomy with D2 lymph node (LN) dissection is the standard surgical procedure for patients with resectable gastric cancer (GC). In the fifteenth edition of the Japanese Classification of Gastric Carcinoma, the 14v LN (LNs along the root of the superior mesenteric vein) was defined as the regional gastric LN. The efficacy of 14v LN dissection during radical distal gastrectomy for lower-third GC remains controversial.
AIM To analyze whether the addition of 14v LN dissection improved the survival of patients with lower-third GC.
METHODS The data from 65 patients who underwent 14v LN dissection and 65 patients treated without 14v LN dissection were selected using the propensity score-matched method from our institute database constructed between 2000 and 2012. Overall survival was compared between the groups.
RESULTS Overall survival was similar between patients with 14v LN metastasis and those with distant metastasis (P = 0.521). Among patients with pathological stage IIIA disease, those who were treated with 14v LN dissection had a significantly higher overall survival than those treated without it (P = 0.020). Multivariate analysis showed that age < 65 years and pT2-3 stage were independent favorable prognostic factors for prolonged overall survival in patients with pathological stage IIIA disease. Patients with No. 1, No. 6, No. 8a, or No. 11p LN metastasis were at higher risk of having 14v LN metastasis.
CONCLUSION Adding 14v LN dissection to D2 dissection during radical distal gastrectomy may improve the overall survival of patients with pathological stage IIIA lower-third GC.
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Affiliation(s)
- Chen Zheng
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Zi-Ming Gao
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - An-Qi Sun
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Hai-Bo Huang
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Zhen-Ning Wang
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Kai Li
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Shan Gao
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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Pan HM, Lang WY, Yao LJ, Wang Y, Li XL. shRNA-interfering LSD1 inhibits proliferation and invasion of gastric cancer cells via VEGF-C/PI3K/AKT signaling pathway. World J Gastrointest Oncol 2019; 11:622-633. [PMID: 31435463 PMCID: PMC6700030 DOI: 10.4251/wjgo.v11.i8.622] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 07/31/2019] [Accepted: 08/03/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Histone Lysine Specific Demethylase 1 (LSD1) is the first histone demethylase to be discovered, which regulates various biological functions by making lysine of histone H3K4, H3K9 and non-histone substrates demethylated. Abnormal regulation of LSD1 is closely related to the occurrence and development of gastric cancer. The change of LSD1 expression level plays an important role in the proliferation and metastasis of gastric cancer cells. The study of its function and mechanism may provide a theoretical basis for early diagnosis and targeted therapy of gastric cancer.
AIM To investigate the effect of downregulation of lysine-specific demethylase 1 (LSD1) expression on proliferation and invasion of gastric cancer cells and the possible regulatory mechanisms of the VEGF-C/PI3K/AKT signaling pathway.
METHODS The LSD1-specific short hairpin RNA (shRNA) interference plasmid was transiently transfected, and expression of LSD1 was downregulated. The cell proliferation ability of LSD1 was observed by CCK-8 assay after downregulating expression of LSD1. Transwell invasion assay was used to observe the change of cell invasion ability after downregulating expression of LSD1. Expression of phosphorylated phosphoinositide 3-kinase (p-PI3K), PI3K, p-AKT, AKT, vascular endothelial growth factor receptor (VEGFR)-3, matrix metalloproteinase (MMP)-2 and MMP-9 in each group was detected by Western blotting.
RESULTS The cell proliferation ability of transiently transfected LSD1-shRNA interference plasmid group was significantly lower than that of the control group (P < 0.05). Transwell invasion assay showed that the number of cells across the membrane of the LSD1-shRNA transfection group (238.451 ± 5.216) was significantly lower than that of the control group (49.268 ± 6.984) (P < 0.01). Western blotting showed that expression level of VEGF-C, p-PI3K, PI3K, p-AKT, AKT, VEGFR-3, MMP-2 and MMP-9 in the LSD1-shRNA group was significantly lower than that in the control group (P < 0.05).
CONCLUSION Downregulation of LSD1 expression inhibits metastatic potential of gastric cancer cells, and VEGF-C-mediated activation of PI3K/AKT signaling pathway, which may be an important mechanism for inhibiting lymph node metastasis in gastric cancer cells.
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Affiliation(s)
- Hong-Ming Pan
- Department of Biochemistry, Qiqihar Medical University, Qiqihar 161000, Heilongjiang Province, China
| | - Wei-Ya Lang
- Department of Histology and Embryology, Qiqihar Medical University, Qiqihar 161000, Heilongjiang Province, China
| | - Li-Jie Yao
- Department of Anatomy, Qiqihar Medical University, Qiqihar 161000, Heilongjiang Province, China
| | - Yan Wang
- Department of Anatomy, Qiqihar Medical University, Qiqihar 161000, Heilongjiang Province, China
| | - Xiao-Ling Li
- Department of Anatomy, Qiqihar Medical University, Qiqihar 161000, Heilongjiang Province, China
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Ataizi ZS, Ertilav K, Nazıroğlu M. Mitochondrial oxidative stress-induced brain and hippocampus apoptosis decrease through modulation of caspase activity, Ca 2+ influx and inflammatory cytokine molecular pathways in the docetaxel-treated mice by melatonin and selenium treatments. Metab Brain Dis 2019; 34:1077-1089. [PMID: 31197678 DOI: 10.1007/s11011-019-00428-x] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Accepted: 05/01/2019] [Indexed: 01/03/2023]
Abstract
Docetaxel (DOCE) is widely used to treat several types of glioblastoma. Adverse effects DOCE seriously limit its clinical use in several tissues. Its side effects on brain cortex and hippocampus have not been clarified yet. Limited data indicated a protective effect of melatonin (MLT) and selenium (SELEN) on DOCE-induced apoptosis, Ca2+ influx and mitochondrial reactive oxygen species (ROS) in several tissues except brain and hippocampus. The purpose of this study is to discover the protective effect of MLT and SELEN on DOCE-induced brain and hippocampus oxidative toxicity in mice. MLT and SELEN pretreatments significantly ameliorated acute DOCE-induced mitochondrial ROS production in the hippocampus and brain tissues by reducing levels of lipid peroxidation, intracellular ROS production and mitochondrial membrane depolarization, while increasing levels of total antioxidant status, glutathione, glutathione peroxidase, MLT, α-tocopherol, γ-tocopherol, vitamin A, vitamin C and β-carotene in the tissues. Furthermore, MLT and SELEN pretreatments increased cell viability and TRPM2 channel activation in the hippocampus and brain followed by decreased activations of TNF-α, IL-1β, IL-6, and caspase -3 and - 9, suggesting a suppression of calcium ion influx, apoptosis and inflammation responses. However, modulator role of SELEN on the values in the tissues is more significant than in the MLT treatment. MLT and SELEN prevent DOCE-induced hippocampus and brain injury by inhibiting mitochondrial ROS and cellular apoptosis through regulating caspase -3 and - 9 activation signaling pathways. MLT and SELEN may serve as potential therapeutic targets against DOCE-induced toxicity in the hippocampus and brain.
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Affiliation(s)
- Zeki Serdar Ataizi
- Departmant of Neurosurgery, Yunus Emre General State Hospital, Eskişehir, Turkey
| | - Kemal Ertilav
- Departmant of Neurosurgery, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
| | - Mustafa Nazıroğlu
- Neuroscience Research Center, Suleyman Demirel University, Isparta, Turkey.
- Drug Discovery Unit, BSN Health, Analysis and Innovation Ltd. Inc. Teknokent, Isparta, Turkey.
- Süleyman Demirel Üniversitesi, Tıp Fakültesi, Biyofizik Anabilim Dalı, TR-32260, Isparta, Turkey.
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Adeel M, Asif M, Faisal MN, Chaudary MH, Malik MS, Khalid M. Comparative study of adjuvant chemotherapeutic efficacy of docetaxel plus cyclophosphamide and doxorubicin plus cyclophosphamide in female breast cancer. Cancer Manag Res 2019; 11:727-739. [PMID: 30697066 PMCID: PMC6339652 DOI: 10.2147/cmar.s180802] [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] [Indexed: 01/09/2023] Open
Abstract
Purpose This retrospective study presents a comparative analysis of the overall survival and toxicities, as side effects, of docetaxel plus cyclophosphamide (TC) and doxorubicin plus cyclophosphamide (AC). The study measured their efficacies during adjuvant chemotherapy, treating Pakistani breast cancer patients by validating the results obtained, with the published analysis of the same treatment given to US patients. Patients and methods Between June 2015 and September 2017, for four chemotherapy cycles, 189 patients out of 358 received TC (75 mg/m2 of docetaxel, 600 mg/m2 of cyclophosphamide) and 169 were treated with AC (60 mg/m2 of doxorubicin, 600 mg/m2 of cyclophosphamide). On the basis of using pathological markers to assess patients, toxicities, as side effects, (due to docetaxel, doxorubicin, and cyclophosphamide) were listed in the database of this study. Common factors with respect to common terminology criteria for adverse events version 5.0 and side effects listed in MedlinePlus, NIH US database, and from the database of this study were then separated to be included in comparison for this study. Statistically, chi-squared test was used at α=0.05. Results There was no statistically significant difference between the proportions of patients with vomiting, extreme tiredness, diarrhea, mild anemia, stability, and overall survival because P-value >0.05. However, AC remained less toxic (P-value <0.05) by 22.6%, 25.7%, 25.3%, 12.4%, 20.8%, and 16.4% compared to TC for changes in taste, muscle pain, burning hands, change in hemoglobin level, moderate anemia, and needing blood transfusion respectively, whereas TC remained less toxic by 52.9%, 32.5%, and 26.3% for dizziness, weight loss, and sores in throat and mouth, respectively. Conclusion At 27 months, TC was more toxic than AC, whereas both combinations had the same overall survival rate.
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Affiliation(s)
- Muhammad Adeel
- Department of Computer Science, Faculty of Science, National Textile University, Faisalabad, Punjab, Pakistan,
| | - Muhammad Asif
- Department of Computer Science, Faculty of Science, National Textile University, Faisalabad, Punjab, Pakistan,
| | - Muhammad Naeem Faisal
- Faculty of Veterinary Science, Institute of Pharmacy, Physiology, and Pharmacology, University of Agriculture, Faisalabad, Punjab, Pakistan
| | | | - Muhammad Sheraz Malik
- Department of Information Technology, Government College University, Faisalabad, Punjab, Pakistan
| | - Muhammad Khalid
- Oncology Department, Faisalabad Medical University, Allied Hospital, Faisalabad, Punjab, Pakistan
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