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1.
Braz. J. Pharm. Sci. (Online) ; 58: e20954, 2022. tab, graf
Article in English | LILACS | ID: biblio-1420502

ABSTRACT

Abstract Cisplatin is the primary anti-cancer agent for the treatment of most solid tumors. However, platinum-based anti-cancer chemotherapy produces severe side effects due to its poor specificity. There are a broad interest and literature base for a novel mechanism of action on platinum derivatives. Additionally, combining cisplatin with histone deacetylase inhibitors (HDACi) such as 4-hydroxybenzoic acid derivatives showed promising results in treating solid tumors. Here we aimed to conjugate 4-hydroxybenzoic acid with platinum to obtain a novel platinum derivative that can overcome cisplatin resistance. Cis-4-hydroxyphenylplatinum(II)diamine compound was synthesized under mild conditions and characterized. Cytotoxicity assay was performed on SKOV3-Luc and A549-Luc cells. Hemocompatibility and serum protein binding analysis were performed. Treatment potential was evaluated in xenograft tumor models. Biodistribution was tested on tumor-bearing mice via Pt analysis in organs with ICP-MS, ex vivo. In this study, cis-4-hydroxyphenylplatinum (II) diamine was synthesized with a yield of 62%. The MTT assay on A549-Luc and SKOV3-Luc cell lines resulted in IC50 values of 17.82 and 7.81 µM, respectively. While tumor growth was continued in the control group, the tumor volume decreased in the treatment group. All results point to the conclusion that the new compound has the potential to treat solid tumors


Subject(s)
Platinum/pharmacology , Anticarcinogenic Agents/classification , Histone Deacetylase Inhibitors/adverse effects , Lung Neoplasms/pathology
2.
Chinese Journal of Lung Cancer ; (12): 7-13, 2022.
Article in Chinese | WPRIM | ID: wpr-928773

ABSTRACT

BACKGROUND@#Malignant pleural mesothelioma (MPM) is a highly aggressive disease arising from pleural mesothelial cells. Advanced pleural mesothelioma has a poor prognosis, with a median survival of no more than 15 months. First line standard chemotherapy regimen recommended is Pemetrexed based chemotherapy regimen, with or without bevacizumab. There is no consensus on whether patients who have received first-line standard chemotherapy can benefit from pemetrexed maintenance chemotherapy. The study aimed to investigate the efficacy and safety of pemetrexed maintenance therapy (PMT) after treatment with a pemetrexed and platinum regimen for patients with MPM.@*METHODS@#A total of 40 MPM patients were collected from Cancer Hospital Chinese Academy of Medical Sciences from January 2013 to January 2018, eligible patients were unresectable MPM, without disease progression following 4 to 6 cycles of pemetrexed and platinum, including pemetrexed maintenance therapy group (22 cases) and observation group (18 cases). The last follow-up was conducted in January 2020. The primary endpoint were progression free survival (PFS), and the secondary end points were overall survival (OS), the efficacy, adverse reactions of PMT.@*RESULTS@#The median PFS in the PMT arm was longer than that in the observation arm (8.5 mon vs 3 mon, P=0.008), but there was no significant difference in median OS (26.4 mon vs 15.7 mon, P=0.177). Objective response rate (ORR) of two group were 22.7% and 0%, respectively. The grade 3-4 toxicity in PMT group included grade 4 neutropenia in 1 patient (4.5%), grade 3 neutropenia in 1 patient (4.5%), grade 4 anemia in 1 patient (4.5%) and grade 3 nausea and anorexia in 1 patient (4.5%).@*CONCLUSIONS@#Pemetrexed maintenance therapy following initial pemetrexed and platinum chemotherapy improve PFS in patients with MPM, and is well tolerated.


Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/therapeutic use , Lung Neoplasms/drug therapy , Mesothelioma/drug therapy , Mesothelioma, Malignant , Neutropenia , Pemetrexed/therapeutic use , Platinum/therapeutic use , Pleural Neoplasms/drug therapy
3.
Asian Journal of Andrology ; (6): 180-185, 2022.
Article in English | WPRIM | ID: wpr-928549

ABSTRACT

Neoadjuvant chemotherapy (NAC) has shown promising results in patients with locally advanced penile cancer. However, no consensus exists on its applications for locally advanced penile cancer. Thus, it is unclear which kind of chemotherapy regimen is the best choice. Consequently, a systematic search of PubMed, Web of Science, and EMBASE was performed in March 2021 to assess the efficacy and safety of NAC for the treatment of patients with locally advanced penile cancer. The Newcastle-Ottawa Scale was used to assess the risk of bias in each study. This study synthesized 14 published studies. The study revealed that patients who achieved an objective response to NAC obtained a better survival outcome compared with those who did not achieve an objective response. In addition, the objective response rates (ORRs) and pathological complete response (pCR) rates were 0.57 and 0.11, respectively. The incidence of grade ≥3 toxicity was 0.36. Subgroup analysis found that the ORR and pCR of the taxane-platinum (TP) regimen group performed better than those of the nontaxane-platinum (NTP) regimen group (0.57 vs 0.54 and 0.14 vs 0.07, respectively). Moreover, the TP regimen group had more frequent toxicity than the NTP regimen group (0.41 vs 0.26). However, further studies were warranted to confirm the findings.


Subject(s)
Humans , Male , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoadjuvant Therapy/methods , Penile Neoplasms/drug therapy , Platinum , Treatment Outcome
4.
Chinese Journal of Oncology ; (12): 68-72, 2022.
Article in Chinese | WPRIM | ID: wpr-935183

ABSTRACT

Triple negative breast cancer (TNBC) is prone to recurrence and metastasis, which is the subtype of poorest prognosis. Chemotherapy is the main treatment, although there is lack of effective adjuvant chemotherapy regimens. The unsatisfactory efficacy of chemotherapy has been a bottleneck in improving the outcome of TNBC. Platinum compounds act directly on DNA to kill tumor cells, and they have a stronger killing effect on tumor cells carrying DNA damage repair (DDR) defects, which is an important entry point to improve the efficacy of TNBC. Biomarkers for predicting the efficacy of platinum drugs in TNBC treatment have always been a hot topic. The DDR pathway contains a large number of related genes, and recent studies have shown that deficiencies in the DDR pathway may be associated with the efficacy of platinum drugs, which is expected to be a biomarker for predicting the efficacy of platinum drugs in breast cancer treatment.


Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , DNA Damage , DNA Repair , Pharmaceutical Preparations , Platinum/therapeutic use , Platinum Compounds/therapeutic use , Triple Negative Breast Neoplasms/genetics
5.
Chinese Journal of Oncology ; (12): 167-175, 2021.
Article in Chinese | WPRIM | ID: wpr-877501

ABSTRACT

Breast cancer is the most common and fatal malignant tumor in women, which causes great social burden throughout the world. At present, chemotherapy is still the most important treatment manner of advanced breast cancer, and platinum drugs are one of the commonly used chemotherapeutic drugs. Based on the substantial evidence, the expert committee deeply discusses the clinical application of platinum drugs in advanced breast cancer, gives the reasonable suggestions for its clinical usage, effectiveness and adverse effects. This consensus aims to guide physicians to use drugs reasonably and standardize the diagnosis and treatment.


Subject(s)
Female , Humans , Breast Neoplasms/drug therapy , Consensus , Platinum
6.
Journal of Korean Medical Science ; : 13-2020.
Article in English | WPRIM | ID: wpr-782049

ABSTRACT

No abstract available.


Subject(s)
Financial Management , Platinum
7.
Journal of Gynecologic Oncology ; : 15-2020.
Article in English | WPRIM | ID: wpr-811217

ABSTRACT

OBJECTIVE: To evaluate the effectiveness and safety of the combination of pegylated liposomal doxorubicin with carboplatin (CD) compared with those of carboplatin and paclitaxel (CP) for platinum-sensitive recurrent ovarian, fallopian, or primary peritoneal cancer in a real-world setting in Korea.METHODS: We enrolled relevant patients from 9 institutions. All patients received CD or CP as the second- or third-line chemotherapy in routine clinical practice during 2013–2018. The primary endpoints were progression-free survival (PFS) and toxicity. The secondary endpoint included the objective response rate (ORR).RESULTS: Overall, 432 patients (224 and 208 in the CD and CP groups, respectively) were included. With a median follow-up of 18.9 months, the median PFS was not different between the groups (12.7 vs. 13.6 months; hazard ratio, 1.161; 95% confidence interval, 0.923–1.460; p=0.202). The ORR was 74.6% and 80.1% in the CD and CP group, respectively (p=0.556). Age and surgery at relapse were independent prognostic factors. More patients in the CD group significantly experienced a grade 3 to 4 hematologic toxicity and hand-foot syndrome (13.8% vs. 6.3%), whereas grade 2 or more alopecia (6.2% vs. 36.1%), peripheral neuropathy (4.4% vs. 11.4%), and allergic/hypersensitivity reaction (0.4% vs. 8.5%) developed more often in the CP group.CONCLUSIONS: The safety and effectiveness of chemotherapy with CD in a real-world setting were consistent with the results from a randomized controlled study. The different toxicity profiles between the 2 chemotherapy (CD and CP) regimens should be considered in the clinical practice.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03562533


Subject(s)
Humans , Alopecia , Carboplatin , Cohort Studies , Disease-Free Survival , Doxorubicin , Drug Therapy , Follow-Up Studies , Hand-Foot Syndrome , Korea , Ovarian Neoplasms , Paclitaxel , Peripheral Nervous System Diseases , Platinum , Prognosis , Recurrence , Retrospective Studies
8.
Obstetrics & Gynecology Science ; : 55-63, 2020.
Article in English | WPRIM | ID: wpr-782209

ABSTRACT

3.38, PLR >210, CA125 >365, advanced stage, suboptimal disease, serous type, and ascites were significant predictive factors for platinum resistance. However, only NLR >3.38 and advanced stage were independent predictive factors with an adjusted odds ratio of 1.880 and 3.333, respectively. Regarding factors associated with poor survival outcomes, only PLR >210 and advanced stage were independent factors, with a hazard ratio of 1.578 and 3.994, respectively.CONCLUSION: High NLR and advanced stage were potential independent predictive factors for platinum resistance, whereas high PLR and advanced stage were potential independent predictive factors for poor survival outcomes.


Subject(s)
Female , Humans , Ascites , Blood Platelets , Drug Therapy , Fallopian Tubes , Lymphocytes , Medical Records , Multivariate Analysis , Neutrophils , Odds Ratio , Ovarian Neoplasms , Platinum , Prognosis , Retrospective Studies , ROC Curve
9.
Chinese Journal of Lung Cancer ; (12): 137-142, 2019.
Article in Chinese | WPRIM | ID: wpr-775652

ABSTRACT

BACKGROUND@#Human epidermal growth factor receptor 2 (HER2) is one of the driver genes of non-small cell lung cancer (NSCLC). Several studies have shown that the efficacy of pemetrexed in HER2-mutant NSCLC is controversial. The aim of this study is to investigate the efficacy of pemetrexed combined with platinum chemotherapy in patients with HER2-mutant and HER2 wild-type lung adenocarcinoma.@*METHODS@#The clinical data of 106 cases of EGFR, ALK, ROS-1, KRAS, BRAF, RET and MET-negative patients with advanced lung adenocarcinoma patients who diagnosed by histopathology in the First Affiliated Hospital of Zhengzhou University were retrospectively reviewed. The relationships between HER2 gene status, clinical characteristics and response and progression-free survival (PFS) were analyzed.@*RESULTS@#All of the 106 patients' HER2 status were determined. HER2 mutations occurred in 32 cases (30.2%), no mutations in 74 cases (69.8%). HER2 mutations were common in young, non-smoking and female patients. All patients received first-line pemetrexed and platinum-based chemotherapy. The objective response rate (ORR) and disease control rate (DCR) of patients with HER2-mutant lung adenocarcinoma were significantly higher than those without HER2 mutations (40.6% vs 14.9%, χ²=8.464, P=0.004; 93.8% vs 68.9%, χ²=6.327, P=0.012), and the difference was statistically significant. According to univariate analysis, the PFS was significantly associated with the brain metastases, maintenance chemotherapy and HER2 gene status (P0.05). Cox multivariate analysis indicated that HER2 mutation was an independent positive prognostic factor of PFS (P=0.038).@*CONCLUSIONS@#HER2-mutant lung adenocarcinoma patients with first-line pemetrexed combined with platinum chemotherapy have greater clinical benefit than HER2 wild-type patients.


Subject(s)
Aged , Female , Humans , Male , Middle Aged , Adenocarcinoma of Lung , Drug Therapy , Genetics , Pathology , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Disease-Free Survival , Genes, erbB-2 , Genetics , Mutation , Pemetrexed , Therapeutic Uses , Platinum , Therapeutic Uses , Retrospective Studies , Treatment Outcome
10.
Journal of Korean Medical Science ; : e180-2019.
Article in English | WPRIM | ID: wpr-765021

ABSTRACT

Open access (OA) publishing is a recent phenomenon in scientific publishing, enabling free access to knowledge worldwide. In the Indian context, OA to science has been facilitated by government-funded repositories of student and doctoral theses, and many Indian society journals are published with platinum OA. The proportion of OA publications from India is significant in a global context, and Indian journals are increasingly available on OA repositories such as Pubmed Central, and Directory of Open Access Journals. However, OA in India faces numerous challenges, including low-quality or predatory OA journals, and the paucity of funds to afford gold OA publication charges. There is a need to increase awareness amongst Indian academics regarding publication practices, including OA, and its potential benefits, and utilize this modality of publication whenever feasible, as in publicly-funded research, or when platinum OA is available, while avoiding falling prey to poor quality OA journals.


Subject(s)
Humans , Accidental Falls , Bibliographies as Topic , Financial Management , India , Open Access Publishing , Platinum , Publications
11.
Journal of Gynecologic Oncology ; : e67-2019.
Article in English | WPRIM | ID: wpr-764552

ABSTRACT

OBJECTIVES: In our institutional experience, involved-field radiation therapy (IFRT) yields favorable outcomes in patients with recurrent epithelial ovarian cancer (EOC). This retrospective study aimed to investigate the clinical benefits of IFRT in this patient population. METHODS: Among patients treated with IFRT for recurrent EOC between 2010 and 2017, 61 patients with 90 treatments were included. IFRT encompassed all treatable lesions identified via imaging studies with 10–15-mm margins. Prescribed doses were ≥45 Gy (equivalent dose in 2 Gy/fraction). RESULTS: Patients were followed up for a median of 19.0 (Interquartile range, 8.6–34.9) months after IFRT. The 2-year in-field control, progression-free survival, and overall survival (OS) rates were 42.7%, 24.2%, and 78.9%, respectively. Fifty-three IFRT sessions (58.9%) were followed by systemic chemotherapy, and the median chemotherapy-free interval (CFI) was 10.5 (95% confidence interval=7.3–13.7) months. A higher carbohydrate antigen-125 (CA-125) level correlated with a worse 2-year OS (69.2% vs. 91.0%; p=0.001) and shorter median CFI (4.7 vs. 11.9 months; p12 months. For patients with a normal CA-125 level and/or platinum-sensitive tumor, IFRT prolonged CFI regardless of pre-existing carcinomatosis, gross tumor volume, and number of treatment sites. CONCLUSION: Our early experience demonstrates the safety and feasibility of IFRT as an effective salvage therapy and enables a “chemotherapy holiday” in selected recurrent EOC settings. The CA-125 value before IFRT (within normal range) and/or platinum sensitivity could be used as selection criteria for IFRT.


Subject(s)
Humans , CA-125 Antigen , Carcinoma , Disease-Free Survival , Drug Therapy , Ovarian Neoplasms , Patient Selection , Platinum , Retrospective Studies , Salvage Therapy , Tumor Burden
12.
Journal of Gynecologic Oncology ; : e56-2019.
Article in English | WPRIM | ID: wpr-764527

ABSTRACT

OBJECTIVE: In this study, we evaluated the toxicity and clinical efficacy of nivolumab, a programmed cell death protein 1 (PD-1) inhibitor, on patients with platinum resistant ovarian cancer. METHODS: Every second week, 18 patients with platinum resistance ovarian cancer received nivolumab until disease progression occurred. We assessed toxicity, disease control rate, progression free survival (PFS) and overall survival (OS). Radiological response evaluation according to irRECIST was performed every 12th week, while clinical evaluation was done every second week. RESULTS: The disease control rate was 44% (95% confidence interval [CI]=19–87) as 8 showed stable disease, 6 showed progressive disease and 4 died before the first radiological response evaluation. The median OS was 30 weeks (95% CI=14–42; range, 3–95), and PFS was 15 weeks (95% CI=13–17). The median follow-up time was 30 weeks (range, 3–123). The rate of grade 2–5 adverse events was 28% (5 out of 18). Two patients (11%) developed grade 2 and 3 adverse events, respectively, while no grade 4 events were observed. One patient died from intestinal perforation, believed to be caused by concomitant bevacizumab rather than nivolumab. CONCLUSION: This study shows few adverse events, and promising clinical efficacy when using nivolumab for ovarian cancer.


Subject(s)
Humans , Bevacizumab , Cell Death , Disease Progression , Disease-Free Survival , Follow-Up Studies , Immunotherapy , Intestinal Perforation , Ovarian Neoplasms , Platinum , Treatment Outcome
13.
Journal of Gynecologic Oncology ; : e59-2019.
Article in English | WPRIM | ID: wpr-764524

ABSTRACT

OBJECTIVE: Evidences from animal models seem to suggest that minimally invasive surgery may enhance cisplatin diffusion when the drug is administered in the context of post-operative hyperthermic intraperitoneal chemotherapy (HIPEC). The present study evaluates the cisplatin pharmacokinetic profile in a prospective series of women with platinum sensitive recurrent epithelial ovarian cancer treated with open secondary cytoreductive surgery (O-SCS) or minimally-invasive secondary cytoreductive surgery (MI-SCS). METHODS: Cisplatin levels were assessed at 0, 20, 40, 60, and 120 minutes in: 1) blood samples, 2) peritoneal perfusate, and 3) peritoneal biopsies at the end of HIPEC. Median Cmax has been used to identify women with high and low drug levels. Progression-free survival (PFS) was calculated as the time elapsed between SCS+HIPEC and secondary recurrence or last follow-up visit. RESULTS: Nine (45.0%) women received MI-SCS, and 11 (55.0%) O-SCS. At 60 minutes, median cisplatin Cmax in peritoneal tissue was higher in patients treated with MI-SCS compared to O-SCS (Cmax=8.262 µg/mL vs. Cmax=4.057 µg/mL). Furthermore, median cisplatin plasma Cmax was higher in patients treated with MI-SCS compared to O-SCS (Cmax=0.511 vs. Cmax=0.254 µg/mL; p-value=0.012) at 120 minutes. With a median follow-up time of 24 months, women with higher cisplatin peritoneal Cmax showed a longer PFS compared to women with low cisplatin peritoneal levels (2-years PFS=70% vs. 35%; p-value=0.054). CONCLUSIONS: We demonstrate for the first time that minimally invasive route enhances cisplatin peritoneal tissue uptake during HIPEC, further evaluations are needed to confirm the correlation between peritoneal cisplatin levels after HIPEC and survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01539785


Subject(s)
Female , Humans , Biopsy , Cisplatin , Cytoreduction Surgical Procedures , Diffusion , Disease-Free Survival , Drug Therapy , Endoscopy , Follow-Up Studies , Injections, Intraperitoneal , Minimally Invasive Surgical Procedures , Models, Animal , Ovarian Neoplasms , Pharmacokinetics , Plasma , Platinum , Prospective Studies , Recurrence
14.
Gut and Liver ; : 498-505, 2019.
Article in English | WPRIM | ID: wpr-763877

ABSTRACT

Family history of pancreatic cancer (PC) is a risk factor for PC development, and the risk level correlates with the number of affected families. A case of PC with ≥1 PC cases in the first-degree relative is broadly defined as familial pancreatic cancer (FPC) and accounts for 5% to 10% of total PC cases. FPC possesses several epidemiological, genetic and clinicopathological aspects that are distinct from those of conventional PCs. In Western countries, FPC registries have been established since the 1990s, and high-risk individuals are screened to detect early PCs. For the pharmacotherapy of FPC, especially in cases with germline pathogenic BRCA mutations, regimens using platinum and poly (ADP-ribose) polymerase inhibitor have recently been studied for their effectiveness. To date, the concept of FPC has prevailed in Western countries, and it has begun to infiltrate into Eastern countries. As the genetic background and environmental conditions vary in association with ethnicity and living area, we need to establish our own FPC registries and accumulate data in Asian countries.


Subject(s)
Humans , Asian People , Drug Therapy , Genetic Background , Pancreatic Neoplasms , Platinum , Registries , Risk Factors
15.
Gut and Liver ; : 366-372, 2019.
Article in English | WPRIM | ID: wpr-763841

ABSTRACT

BACKGROUND/AIMS: Radiopaque metal markers are required to improve X-ray absorption by self-expandable metal stents (SEMSs) to enable precise stent placement. A new tantalum radiopaque marker was recently developed using an ultrasonic spray technique. The aim of the present study was to evaluate the safety and visibility of tantalum markers. METHODS: A total of three beagle dogs were used for a gastrointestinal tract absorption test. Five tantalum markers were placed in the stomach of each dog endoscopically. Excreted tantalum markers were collected, and their weights were compared to the original weights. In radiopacity tests, marker radiopacities on X-ray images were quantified using ImageJ software and compared with those of commercially available metal markers. Finally, the radiographic images of six patients who underwent biliary SEMS placement using tantalum marker Nitinol SEMSs (n=3) or gold marker Nitinol SEMSs (n=3) were compared with respect to marker brightness on fluoroscopic images. RESULTS: Absorption testing showed that the marker structures and weights were unaffected. Radiopacity tests showed that the mean brightness and total brightness scores were greater for tantalum markers (226.22 and 757, respectively) than for gold (A, 209 and 355, respectively; B, 204.96 and 394, respectively; C, 194.34 and 281, respectively) or platinum markers (D, 203.6 and 98, respectively). On fluoroscopic images, tantalum markers had higher brightness and total brightness scores (41.47 and 497.67, respectively) in human bile ducts than gold markers (28.37 and 227, respectively). CONCLUSIONS: Tantalum markers were found to be more visible than other commercially available markers in X-ray images and to be resistant to gastrointestinal absorption.


Subject(s)
Animals , Dogs , Humans , Absorption , Bile Ducts , Gastrointestinal Absorption , Gastrointestinal Tract , Platinum , Self Expandable Metallic Stents , Stents , Stomach , Tantalum , Ultrasonics , Weights and Measures
16.
Korean Journal of Urological Oncology ; : 75-80, 2019.
Article in Korean | WPRIM | ID: wpr-760335

ABSTRACT

To systematically review relevant literature on efficacy and safety of immune checkpoint inhibitors (ICIs) in patients with advanced and metastatic urothelial cell cancer (UCC), renal cell cancer (RCC), and prostate cancer. In platinum pretreated UCC, efficacy of pembrolizumab was superior to chemotherapy, with longer median overall survival (OS; 10.3 months vs. 7.4 months), a higher objective response rate (ORR; 21.1% vs. 11.4%, p=0.001), and a lower adverse event rate (60.9% vs. 90.2%). Three randomized controlled trials (RCTs) assessed the safety and efficacy of nivolumab in advanced RCC. The median OS (25.0 months vs. 19.6 months) and the ORR (25% vs. 5%) were higher in patients treated with nivolumab compared with second-line everolimus. In patients with metastatic castration-resistant prostate cancer, 2 RCTs were identified, which did not show significant benefits for ipilimumab over placebo. In UCC and RCC, there was no conclusive association between programmed cell death receptor ligand 1 (PD-L1) expression in tumor tissue and clinical outcome during pembrolizumab and nivolumab treatment, respectively. Therefore, in metastatic UCC and RCC, pembrolizumab and nivolumab have superior efficacy and safety to second-line chemotherapy and everolimus, respectively. No beneficial effect of ipilimumab was observed in prostate cancer patients. PD-L1 expression status is currently not suitable as a predictive marker for treatment outcome.


Subject(s)
Humans , Carcinoma, Renal Cell , Cell Death , Drug Therapy , Everolimus , Immunotherapy , Platinum , Prostatic Neoplasms , Treatment Outcome , Urologic Neoplasms
17.
Safety and Health at Work ; : 188-195, 2019.
Article in English | WPRIM | ID: wpr-761353

ABSTRACT

BACKGROUND: Mine workers in South Africa face challenges relating to poor health and safety, including fatigue risks, and poor socioeconomic and living conditions. Fatigue results in impaired mental and physical performance. The aim of this study was to assess contributors to fatigue of mine workers in South Africa. METHODS: Data collection took place at four gold mines and one platinum mine in South Africa. A total of 21 focus groups were held with individuals in management, union representatives, and mine workers, and 564 questionnaires were completed by mine workers to gather information about fatigue and potential contributors to fatigue at these mines. RESULTS: Qualitatively (through focus groups), fatigue was attributed to extended working hours, harsh working conditions, high workloads, production pressure, and resource constraints, along with aspects relating to demographic and socioeconomic factors, living conditions, lifestyle, health, and wellness. Greater fatigue was significantly associated with younger age, indebtedness, a lack of exercise, poor nutrition, less sleep, increased alcohol use, poor self-reported health, more sick leave, higher stress, and lower job satisfaction. CONCLUSION: The aim of the study was achieved; numerous work-, sociodemographic-, lifestyle-, and wellness-related factors were linked to fatigue in the participating mine workers. Contributors to fatigue should be addressed to improve health, safety, and sustainability in the industry.


Subject(s)
Data Collection , Environment and Public Health , Fatigue , Focus Groups , Job Satisfaction , Life Style , Miners , Mining , Platinum , Sick Leave , Social Conditions , Socioeconomic Factors , South Africa
18.
Cancer Research and Treatment ; : 1086-1097, 2019.
Article in English | WPRIM | ID: wpr-763171

ABSTRACT

PURPOSE: Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) axis blockades have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). We assessed the effect of platinum-based chemotherapy on tumor PD-L1 expression and its clinical implications. MATERIALS AND METHODS: We used immunohistochemistry to retrospectively evaluate the percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) in paired tumor specimens obtained before and after platinum-based neoadjuvant chemotherapy (NACT) in 86 patients with NSCLC. We analyzed the correlation between the change in PD-L1 tumor proportion score and clinicopathologic characteristics, response to NACT, and survival. RESULTS: The PD-L1 tumor proportion score increased in a significant proportion of patients with NSCLC after platinum-based NACT (Wilcoxon signed-rank test, p=0.002). That pattern was consistent across clinically defined subgroups except for patients with partial response to NACT. Tumors from 26 patients (30.2%) were PD-L1‒negative before NACT but PD-L1-positive after NACT, whereas the reverse pattern occurred in six patients (7%) (McNemar’s test, p < 0.001). Increase in PD-L1 tumor proportion score was significantly associated with lack of response to NACT (Fisher exact test, p=0.015). There was a tendency, albeit not statistically significant, for patients with an increase in PD-L1 tumor proportion score to have shorter survival. CONCLUSION: Tumor PD-L1 expression increased after platinum-based NACT in a significant proportion of patients with NSCLC. Increase in tumor PD-L1 expression may predict poor clinical outcome.


Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung , Drug Therapy , Immunohistochemistry , Neoadjuvant Therapy , Platinum , Prognosis , Retrospective Studies
19.
Cancer Research and Treatment ; : 1144-1155, 2019.
Article in English | WPRIM | ID: wpr-763165

ABSTRACT

PURPOSE: Discovery of models predicting the exact prognosis of epithelial ovarian cancer (EOC) is necessary as the first step of implementation of individualized treatment. This study aimed to develop nomograms predicting treatment response and prognosis in EOC. MATERIALS AND METHODS: We comprehensively reviewed medical records of 866 patients diagnosed with and treated for EOC at two tertiary institutional hospitals between 2007 and 2016. Patients’ clinico-pathologic characteristics, details of primary treatment, intra-operative surgical findings, and survival outcomes were collected. To construct predictive nomograms for platinum sensitivity, 3-year progression-free survival (PFS), and 5-year overall survival (OS), we performed stepwise variable selection by measuring the area under the receiver operating characteristic curve (AUC) with leave-one-out cross-validation. For model validation, 10-fold cross-validation was applied. RESULTS: The median length of observation was 42.4 months (interquartile range, 25.7 to 69.9 months), during which 441 patients (50.9%) experienced disease recurrence. The median value of PFS was 32.6 months and 3-year PFS rate was 47.8% while 5-year OS rate was 68.4%. The AUCs of the newly developed nomograms predicting platinum sensitivity, 3-year PFS, and 5-year OS were 0.758, 0.841, and 0.805, respectively. We also developed predictive nomograms confined to the patients who underwent primary debulking surgery. The AUCs for platinum sensitivity, 3-year PFS, and 5-year OS were 0.713, 0.839, and 0.803, respectively. CONCLUSION: We successfully developed nomograms predicting treatment response and prognosis of patients with EOC. These nomograms are expected to be useful in clinical practice and designing clinical trials.


Subject(s)
Humans , Area Under Curve , Disease-Free Survival , Medical Records , Nomograms , Ovarian Neoplasms , Platinum , Prognosis , Recurrence , ROC Curve
20.
Journal of Central South University(Medical Sciences) ; (12): 1376-1379, 2018.
Article in Chinese | WPRIM | ID: wpr-813123

ABSTRACT

Platinum drugs are widely used in the treatment of various solid tumors, but their resistance to platinum is the most significant obstacle to successful treatment. Copper transporter 1 (CTR1) is the specific transporter for copper, and it mainly locates at the plasma membrane and plays a role in pumping copper into the cell. CTR1 is also the major platinum influx transporter and plays a key role in platinum resistance. The expression, polymorphism, and degradation of CTR1 affect platinum resistance in tumors. Therefore, CTR1 may be a potential predictive biomarker of platinum resistance and a therapeutic target for overcoming platinum resistance.


Subject(s)
Antineoplastic Agents , Therapeutic Uses , Cation Transport Proteins , Genetics , Metabolism , Cisplatin , Therapeutic Uses , Copper , Copper Transporter 1 , Drug Resistance, Neoplasm , Genetics , Platinum , Therapeutic Uses , Research
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