scholarly journals Statin Use Improves Overall Survival of Patients with Gastric Cancer after Surgery and Adjuvant Chemotherapy in Taiwan: A Nationwide Matched Cohort Study

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2055
Author(s):  
Pei-Rung Yang ◽  
Ying-Ying Tsai ◽  
Ko-Jung Chen ◽  
Yao-Hsu Yang ◽  
Wei-Tai Shih

Background: Numerous studies have revealed that statins have antitumor effects in vivo and in vitro. However, few studies have explored the relationship between statin use and the mortality of gastric cancer (GC) patients after treatments. This study examines the relationship between statin use and the overall survival (OS) of GC patients after surgery and adjuvant chemotherapy, using data from the nationwide cohort database of Taiwan. Methods: All patients newly diagnosed with GC from 1999 to 2008 in Taiwan were identified from the Registry of Catastrophic Illness Patients Database. Through propensity score matching, statin users were matched to statin non-users at a 1:4 ratio. The relationship between statin use and the OS of patients with GC was estimated through Cox regression models. Results: The study cohort included 1835 patients with GC who had received therapies during the study period. The death numbers among statin users (defined as those who used more than 28 cumulative defined daily doses (cDDDs)) and statin non-users were 138 and 895, respectively. A dose–response association was noted between statin use and the OS of patients with GC after treatments. The adjusted hazard ratios were 0.62 (95% confidence intervals (CI), 0.50–0.78) and 0.34 (95% CI, 0.26–0.45) for statin users administered 28–167 cDDDs and >168 cDDDs, respectively, compared with no statin use (<28 cDDDs). Conclusions: This study highlights that statin use may dose-dependently improve the OS of patients with GC after surgery and adjuvant chemotherapy in Taiwan. Additional studies are required to confirm the efficacy and safety of statin use.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15594-e15594 ◽  
Author(s):  
Xiaolong Qi ◽  
Yuming Jiang ◽  
Qi Zhang ◽  
Yanfeng Hu ◽  
Tuanjie Li ◽  
...  

e15594 Background: TNM staging system is not adequate to define the prognosis of patients with gastric cancer (GC). This system is also unable to predict whether the GC patients are likely to benefit from adjuvant chemotherapy. We postulated that ImmunoScore of GC (ISGC) could markedly improve the prediction of postsurgical survival and adjuvant chemotherapeutic benefits. Methods: 125 GC patients were enrolled as a training cohort to detect the expression of 27 immune features using immunohistochemistry and then constructed a five-feature-based ISGC using the LASSO Cox regression model. Internal validation cohort (126 specimens) and two external validation cohorts (628 specimens) were utilized to validate the prognostic and predictive value of ISGC. Results: We established the ISGC classifier based on the five features: CD3invasive margin (IM), CD3center of tumor (CT), CD8IM, CD45ROCT, and CD66bIM. The ISGC classifier could distinguish GC patients with high-ISGC from those with low-ISGC with significant differences in 5-year disease-free survival (45.0% v.s. 4.4%, p < 0.001) and 5-year overall survival (48.8% v.s. 6.7%, p < 0.001). According to the multivariate analysis, the ISGC classifier was proved to be an independent prognostic factor. A combination of ISGC and TNM had better prognostic value than TNM stage alone. In a further analysis, stage II and III GC patients with high-ISGC exhibited a favorable response to adjuvant chemotherapy. To provide a quantitative method to predict stage II and III GC patients’ probability of 3- and 5-year overall survival, we constructed two nomograms that integrated the ISGC and clinicopathological risk factors. Calibration plots showed that the nomograms performed well compared with an ideal model. The predictive accuracy and clinical usefulness of the nomograms were also demonstrated. Conclusions: The ISGC classifier could effectively predict recurrence and survival of GC, and complemented the prognostic value to TNM system. Moreover, the classifier might be a useful predictive tool to identify candidates with stage II and III GC who would benefit from adjuvant chemotherapy. Therefore, the ISGC might facilitate the counseling and personalize the postoperative management of GC patients.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1410
Author(s):  
Anna Buchholz ◽  
Aurelia Vattai ◽  
Sophie Fürst ◽  
Theresa Vilsmaier ◽  
Christina Kuhn ◽  
...  

New prognostic factors and targeted therapies are urgently needed to improve therapeutic outcomes in vulvar cancer patients and to reduce therapy related morbidity. Previous studies demonstrated the important role of prostaglandin receptors in inflammation and carcinogenesis in a variety of tumor entities. In this study, we aimed to investigate the expression of EP4 in vulvar cancer tissue and its association with clinicopathological data and its prognostic relevance on survival. Immunohistochemistry was performed on tumor specimens of 157 patients with vulvar cancer treated in the Department of Obstetrics and Gynecology, Ludwig-Maximilian-University of Munich, Germany, between 1990 and 2008. The expression of EP4 was analyzed using the well-established semiquantitative immunoreactivity score (IRS) and EP4 expression levels were correlated with clinicopathological data and patients’ survival. To specify the tumor-associated immune cells, immunofluorescence double staining was performed on tissue samples. In vitro experiments including 5-Bromo-2′-Deoxyuridine (BrdU) proliferation assay and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT) viability assay were conducted in order to examine the effect of EP4 antagonist L-161,982 on vulvar carcinoma cells. EP4 expression was a common finding in in the analyzed vulvar cancer tissue. EP4 expression correlated significantly with tumor size and FIGO classification and differed significantly between keratinizing vulvar carcinoma and nonkeratinizing carcinoma. Survival analysis showed a significant correlation of high EP4 expression with poorer overall survival (p = 0.001) and a trending correlation between high EP4 expression and shorter disease-free survival (p = 0.069). Cox regression revealed EP4 as an independent prognostic factor for overall survival when other factors were taken into account. We could show in vitro that EP4 antagonism attenuates both viability and proliferation of vulvar cancer cells. In order to evaluate EP4 as a prognostic marker and possible target for endocrinological therapy, more research is needed on the influence of EP4 in the tumor environment and its impact in vulvar carcinoma.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sheng Zheng ◽  
Zizhen Zhang ◽  
Ning Ding ◽  
Jiawei Sun ◽  
Yifeng Lin ◽  
...  

Abstract Introduction Angiogenesis is a key factor in promoting tumor growth, invasion and metastasis. In this study we aimed to investigate the prognostic value of angiogenesis-related genes (ARGs) in gastric cancer (GC). Methods mRNA sequencing data with clinical information of GC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differentially expressed ARGs between normal and tumor tissues were analyzed by limma package, and then prognosis‑associated genes were screened using Cox regression analysis. Nine angiogenesis genes were identified as crucially related to the overall survival (OS) of patients through least absolute shrinkage and selection operator (LASSO) regression. The prognostic model and corresponding nomograms were establish based on 9 ARGs and verified in in both TCGA and GEO GC cohorts respectively. Results Eighty-five differentially expressed ARGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that ARGs-related signaling pathway genes were highly related to tumor angiogenesis development. Kaplan–Meier analysis revealed that patients in the high-risk group had worse OS rates compared with the low-risk group in training cohort and validation cohort. In addition, RS had a good prognostic effect on GC patients with different clinical features, especially those with advanced GC. Besides, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusions We developed a nine gene signature related to the angiogenesis that can predict overall survival for GC. It’s assumed to be a valuable prognosis model with high efficiency, providing new perspectives in targeted therapy.


2003 ◽  
Vol 21 (12) ◽  
pp. 2282-2287 ◽  
Author(s):  
Atsushi Nashimoto ◽  
Toshifusa Nakajima ◽  
Hiroshi Furukawa ◽  
Masatsugu Kitamura ◽  
Taira Kinoshita ◽  
...  

Purpose: To evaluate the survival benefit of adjuvant chemotherapy after curative resection in serosa-negative gastric cancer patients (excluding patients who were T1N0), we conducted a multicenter phase III clinical trial in which 13 cancer centers in Japan participated. Patients and Methods: From January 1993 to December 1994, 252 patients were enrolled into the study and allocated randomly to adjuvant chemotherapy or surgery alone. The chemotherapy comprised intravenous mitomycin 1.33 mg/m2, fluorouracil (FU) 166.7 mg/m2, and cytarabine 13.3 mg/m2 twice weekly for the first 3 weeks after surgery, and oral FU 134 mg/m2 daily for the next 18 months for a total dose of 67 g/m2. The primary end point was relapse-free survival. Overall survival and the site of recurrence were secondary end points. Results: Ninety-eight percent of patients underwent gastrectomy with D2 or greater lymph node dissection. There were no treatment-related deaths and few serious adverse events. There was no significant difference in relapse-free and overall survival between the arms (5-year relapse-free survival 88.8% chemotherapy v 83.7% surgery alone; P = .14 and 5-year survival 91.2% chemotherapy v 86.1% surgery alone; P = .13, respectively). Nine patients (7.1%) in the chemotherapy arm and 17 patients (13.8%) in the surgery-alone arm had cancer recurrence. Conclusion: There was no statistically significant relapse-free or overall survival benefit with this adjuvant chemotherapy for patients with macroscopically serosa-negative gastric cancer after curative resection, and there was no statistical difference between the two arms relating to the types of cancer recurrence. We do not recommend adjuvant chemotherapy with this regimen for this population in clinical practice.


1994 ◽  
Vol 80 (3) ◽  
pp. 527-534 ◽  
Author(s):  
Yasuhiro Matsuda ◽  
Keiichi Kawamoto ◽  
Katsuzo Kiya ◽  
Kaoru Kurisu ◽  
Kazuhiko Sugiyama ◽  
...  

✓ The presence of the progesterone receptor (PR) in meningioma tissue has been confirmed by previous investigations. Studies have shown that the antiprogesterone drug, mifepristone, is a potent agent that inhibits the growth of cultured meningioma cells and reduces the size of meningiomas in experimental animal models and humans. However, these studies have not fully examined the relationship between the antitumor effects of an antiprogesterone agent and the expression of the PR. The present study examined the antitumor effects of mifepristone and a new potent antiprogesterone agent, onapristone; a correlation between the antitumor effects of these antiprogesterones and the presence of PR's in meningiomas in vitro and in vivo was also investigated. Meningioma tissue surgically removed from 13 patients was used in this study. In the in vitro arm of the study, mifepristone and onapristone exhibited cytostatic and cytocidal effects against cultured meningioma cells, regardless of the presence or absence of PR's; however, three PR-negative meningiomas showed no response to any dose of mifepristone and/or onapristone. In the in vivo arm, meningioma cells, embedded in a collagen gel, were implanted into the renal capsules of nude mice. Antiprogesterone treatment resulted in a marked reduction of the tumor volume regardless of the presence or absence of PR's. No histological changes in the meningioma cells suggestive of necrosis or apoptosis were detected in any of the mice treated with antiprogesterones. These findings suggest that mifepristone and onapristone have an antitumor effect against meningioma cells via the PR's and/or another receptor, such as the glucocorticoid receptor.


2018 ◽  
Vol 160 (4) ◽  
pp. 658-663 ◽  
Author(s):  
Phoebe Kuo ◽  
Sina J. Torabi ◽  
Dennis Kraus ◽  
Benjamin L. Judson

Objective In advanced maxillary sinus cancers treated with surgery and radiotherapy, poor local control rates and the potential for organ preservation have prompted interest in the use of systemic therapy. Our objective was to present outcomes for induction compared to adjuvant chemotherapy in the maxillary sinus. Study Design Secondary database analysis. Setting National Cancer Database (NCDB). Subjects and Methods In total, 218 cases of squamous cell maxillary sinus cancer treated with surgery, radiation, and chemotherapy between 2004 and 2012 were identified from the NCDB and stratified into induction chemotherapy and adjuvant chemotherapy cohorts. Univariate Kaplan-Meier analyses were compared by log-rank test, and multivariate Cox regression was performed to evaluate overall survival when adjusting for other prognostic factors. Propensity score matching was also used for further comparison. Results Twenty-three patients received induction chemotherapy (10.6%) and 195 adjuvant chemotherapy (89.4%). The log-rank test comparing induction to adjuvant chemotherapy was not significant ( P = .076). In multivariate Cox regression when adjusting for age, sex, race, comorbidity, grade, insurance, and T/N stage, there was a significant mortality hazard ratio of 2.305 for adjuvant relative to induction chemotherapy (confidence interval, 1.076-4.937; P = .032). Conclusion Induction chemotherapy was associated with improved overall survival in comparison to adjuvant chemotherapy in a relatively small cohort of patients (in whom treatment choice cannot be characterized), suggesting that this question warrants further investigation in a controlled clinical trial before any recommendations are made.


2021 ◽  
Author(s):  
Li-Jun Tian ◽  
Hong-Zhi Liu ◽  
Qiang Zhang ◽  
Dian-Zhong Geng ◽  
Jing Yang ◽  
...  

Abstract Background: Apelin is a recently identified endogenous ligand associated with proliferation and angiogenesis of several cancers. However, only few studies have reported on the functions and the role of apelin in gastric cancer (GC). Therefore, in the present study, we investigated the association and the mechanisms underlying Apelin expression and proliferation of GC cells both in vitro and in vivo.Methods: We enrolled 178 postoperative care GC patients to investigate clinicopathological and immunohistochemical factors associated with Apelin expression. The relationship between Survival of patients and apelin expression was evaluated using Kaplan-Meier method and Cox regression analyses. The expression of apelin mRNA and its proteins in GC tissues and cell lines were analyzed using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), western blot and ELISA. The role and mechanisms underlying regulation of Apelin expression in human GC cells were evaluated through several in vitro and in vivo experiments. Results: Apelin was over expressed in human GC cells, relative to adjacent normal tissues. The over expression of apelin was associated with vessel invasion (P <0.01), lymph node metastasis (P <0.01), late-staged tumor (T) (P <0.05), worse pathological type (P <0.05), nerve invasion (P <0.05). In addition, expression of apelin strongly and positively correlated with that of vascular endothelial growth factor (VEGF). Over-expression of apelin promoted proliferation and invasion of MGC-803 cell via the ERK/Cyclin D1/MMP-9 signaling pathway. Apelin over-expression also promoted angiogenesis of GC cells, accelerating growth of subcutaneous xenograft of the cancer cells in vivo.Conclusions: Over-expression of apelin promotes proliferation and metastasis of GC cells via the ERK/Cyclin D1/MMP-9 signaling pathway and is associated with adverse events of the cancer. Consequently, apelin is a potential therapeutic target for human GC.


2021 ◽  
Author(s):  
Pegah Farrokhi ◽  
Alireza Sadeghi ◽  
Mehran sharifi ◽  
Payam Dadvand ◽  
Rachel Riechelmann ◽  
...  

AbstractAimThis study aimed to evaluate and compare the efficacy and toxicity of common regimens used as perioperative chemotherapy including ECF, DCF, FOLFOX, and FLOT to identify the most effective chemotherapy regimen with less toxicity.Material and MethodsThis retrospective cohort study was based on 152 eligible gastric cancer patients recruited in a tertiary oncology hospital in Isfahan, Iran (2014-2019). All resectable gastric cancer patients who had received one of the four chemotherapy regimens including ECF, DCF, FOLFOX, or FLOT, and followed for at least one year (up to five years) were included. The primary endpoint of this study was Overall Survival (OS), Progression-Free Survival (PFS), Overall Response Rate (ORR), and R0 resection. We also considered toxicity according to CTCAE (v.4.0) criteria as a secondary endpoint. Cox -regression models were used applied to estimate OS and PFS time, controlled for relevant covariates.ResultsOf included patients, 32(21%), 51(33.7%), 37(24.3%), and 32(21%) had received ECF, DCF, FOLFOX and FLOT, respectively. After the median 25 months follow-up, overall survival was higher with the FLOT regimen in comparison with other regimens (hazard ratio [HR] = 0. 052). The median OS of the FLOT regimen was not reachable in Kaplan-Meier analysis and the median OS was 28, 26, and 23 months for DCF, FOLOFX, and ECF regimens, respectively. On the other hand, a median PFS of 25, 17, 15, and 14 months was observed for FLOT, DCF, FOLFOX, and ECF regimens, respectively (Log-rank = 0. 021). FLOT regimen showed 84. 4% ORR which was notably higher than other groups (p-value<0. 01).ConclusionsFor resectable gastric cancer patients, the perioperative FLOT regimen seemed to lead to a significant improvement in patients’ OS and PFS in comparison with ECF, DCF, and FOLFOX regimens. As such, the FLOT regimen could be considered as the optimal option for managing resectable gastric cancer patients.


Author(s):  
Zhuohui Chen ◽  
Tong Wu ◽  
Zhouyi Yan ◽  
Mengqi Zhang

BackgroundGlioma is the most common primary malignant brain tumor with significant mortality and morbidity. Ferroptosis, a novel form of programmed cell death (PCD), is critically involved in tumorigenesis, progression and metastatic processes.MethodsWe revealed the relationship between ferroptosis-related genes and glioma by analyzing the mRNA expression profiles from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), GSE16011, and the Repository of Molecular Brain Neoplasia Data (REMBRANDT) datasets. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to construct a ferroptosis-associated gene signature in the TCGA cohort. Glioma patients from the CGGA, GSE16011, and REMBRANDT cohorts were used to validate the efficacy of the signature. Receiver operating characteristic (ROC) curve analysis was applied to measure the predictive performance of the risk score for overall survival (OS). Univariate and multivariate Cox regression analyses of the 11-gene signature were performed to determine whether the ability of the prognostic signature in predicting OS was independent. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to identify the potential biological functions and pathways of the signature. Subsequently, we performed single sample gene set enrichment analysis (ssGSEA) to explore the correlation between risk scores and immune status. Finally, seven putative small molecule drugs were predicted by Connectivity Map.ResultsThe 11-gene signature was identified to divide patients into two risk groups. ROC curve analysis indicated the 11-gene signature as a potential diagnostic factor in glioma patients. Multivariate Cox regression analyses showed that the risk score was an independent predictive factor for overall survival. Functional analysis revealed that genes were enriched in iron-related molecular functions and immune-related biological processes. The results of ssGSEA indicated that the 11-gene signature was correlated with the initiation and progression of glioma. The small molecule drugs we selected showed significant potential to be used as putative drugs.Conclusionwe identified a novel ferroptosis-related gene signature for prognostic prediction in glioma patients and revealed the relationship between ferroptosis-related genes and immune checkpoint molecules.


2021 ◽  
Author(s):  
An Shang ◽  
Zeyun Zhao ◽  
Zhaoyong Wang ◽  
Donglin Li ◽  
Yu Guo ◽  
...  

Abstract Background MSI CRCs were associated with better prognosis and limited predictive value for adjuvant chemotherapy. However, whether the same is true in Northeastern China is still unclear. The aim of the present study was to evaluate the association of clinicopathologic features and MMR/MSI status determined with immunohistochemistry analysis in Northeast China patients with stage Ⅱ/Ⅲ CRCs. Particularly, we sought to detect the relationship between MMR/MSI status and efficacy of oxaliplatin and fluoropyrimidine based adjuvant chemotherapy.MethodsIn total, 476 pathological specimens from eligible stage Ⅱ/Ⅲ CRCs were analyzed with IHC between 2016 and 2018, of which 63 CRCs were diagnosed with MMR protein deficiency. Clinicopathological features and overall survival (OS) were compared between these above two groups. Result The incidence of dMMR CRCs in our cohort was 13.2 % (63/476). Immunohistochemistry (IHC) revealed two common dMMR IHC patterns in 63 dMMR CRCs. And dMMR type1 showed a higher proportion of women (P=0.001) and earlier pathological N stage (P=0.075). In the multivariate Cox regression model, POC and dMMR were associated with a favor prognosis in CRC patients with stage II/III (HR 0.47, 95%CI 0.30-0.74, P=.001; HR 0.34, 95%CI 0.14-0.79, P=.013). However, adjuvant chemotherapy based on oxaliplatin and fluorouracil cannot prolong the OS of dMMR CRCs (P=0.182). Conclusions MMR protein appeared distinct associations with tumor staging, serum CEA level and tumor size. And MMR protein was an independent prognostic marker in patients with stage Ⅱ CRC, whereas dMMR CRC patients did not seem to benefit from oxaliplatin combined with fluorouracil-based adjuvant chemotherapy.


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