Background: Hepatotoxicity is one of the adverse effects that may characterize the clinical use of paclitaxel (PCL). This study examined the protective effects of coenzyme Q10 (CoQ10) and resveratrol (RSV) on PCL-induced hepatotoxicity in albino rats. Methods: Forty-five adult male albino rats randomized into nine groups of n = 5 were used. Group 1 (placebo control) and Group 2 (solvent control) received 0.2 mL of normal saline and corn oil intraperitoneally (ip) daily for 5 days, respectively. Groups 3–5 received CoQ10 (20 mg/kg), RSV (20 mg/kg), and CoQ10 + RSV ip daily for 5 days, respectively. Group 6 received a dose of 20 mg/kg of PCL ip on the 5th day. Groups 7–9 were pretreated daily with CoQ10 (20 mg/kg), RSV (20 mg/kg), and CoQ10 + RSV ip for 5 days and treated with a dose of PCL on the 5th day, respectively. Rats were sacrificed after treatment; liver samples were estimated for histology and biochemical markers. Serum samples were estimated for liver function markers. Results: The liver of PCL-treated rats showed necrosis which correlates with significant (P < 0.001) increases in serum and liver biochemical indexes; gamma glutamyl transferase, lactate dehydrogenase, bilirubin, aminotransferases, alkaline phosphatase, and malondialdehyde levels when compared to control. Liver superoxide dismutase, catalase, glutathione peroxidase, and glutathione levels were significantly (P < 0.001) decreased in PCL-treated rats when compared to control. Importantly, PCL-induced hepatotoxicity was significantly mitigated in CoQ10 (P < 0.05), RSV (P < 0.01), and CoQ10 + RSV (P < 0.001) pretreated rats when compared to PCL. Conclusion: CoQ10 and RSV were effective against PCL-induced hepatotoxicity in albino rats.
{"title":"Coenzyme Q10 and resveratrol abrogate paclitaxel-induced hepatotoxicity in rats","authors":"Elias Adikwu, N. Ebinyo, L. Harris","doi":"10.4103/ctm.ctm_31_19","DOIUrl":"https://doi.org/10.4103/ctm.ctm_31_19","url":null,"abstract":"Background: Hepatotoxicity is one of the adverse effects that may characterize the clinical use of paclitaxel (PCL). This study examined the protective effects of coenzyme Q10 (CoQ10) and resveratrol (RSV) on PCL-induced hepatotoxicity in albino rats. Methods: Forty-five adult male albino rats randomized into nine groups of n = 5 were used. Group 1 (placebo control) and Group 2 (solvent control) received 0.2 mL of normal saline and corn oil intraperitoneally (ip) daily for 5 days, respectively. Groups 3–5 received CoQ10 (20 mg/kg), RSV (20 mg/kg), and CoQ10 + RSV ip daily for 5 days, respectively. Group 6 received a dose of 20 mg/kg of PCL ip on the 5th day. Groups 7–9 were pretreated daily with CoQ10 (20 mg/kg), RSV (20 mg/kg), and CoQ10 + RSV ip for 5 days and treated with a dose of PCL on the 5th day, respectively. Rats were sacrificed after treatment; liver samples were estimated for histology and biochemical markers. Serum samples were estimated for liver function markers. Results: The liver of PCL-treated rats showed necrosis which correlates with significant (P < 0.001) increases in serum and liver biochemical indexes; gamma glutamyl transferase, lactate dehydrogenase, bilirubin, aminotransferases, alkaline phosphatase, and malondialdehyde levels when compared to control. Liver superoxide dismutase, catalase, glutathione peroxidase, and glutathione levels were significantly (P < 0.001) decreased in PCL-treated rats when compared to control. Importantly, PCL-induced hepatotoxicity was significantly mitigated in CoQ10 (P < 0.05), RSV (P < 0.01), and CoQ10 + RSV (P < 0.001) pretreated rats when compared to PCL. Conclusion: CoQ10 and RSV were effective against PCL-induced hepatotoxicity in albino rats.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"34 1","pages":"65 - 71"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83182592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zengzheng Ge, Xiaoyan Xu, Z. Ge, S. Zhou, Xiulin Li, Kai Yao, Lan-qin Deng
The major function of fibrinolytic system is to dissolve the fibrins formed by blood coagulation and maintain the balance between blood coagulation and thrombolysis, which plays an important role in maintaining the liquid state of the blood and unclogging the blood vessels. It is a serious problem that malignant tumor does great harm to human life and health. In recent years, more and more studies signified that the fibrinolytic system in malignant tumors, especially adenocarcinoma, plays a major role in its progression, which indicates that the fibrinolytic system is of great significance in the development of malignant tumors. Besides, the fibrinolytic system has also gradually been known and used to diagnose and treat the adenocarcinoma. This article reviews how the fibrinolytic system works in the occurrence of malignant tumor and summarizes the diagnostic method and treatment of adenocarcinoma according to the latest clinical research progress, laying the foundation for further research.
{"title":"Advances on the components of fibrinolytic system in malignant tumors","authors":"Zengzheng Ge, Xiaoyan Xu, Z. Ge, S. Zhou, Xiulin Li, Kai Yao, Lan-qin Deng","doi":"10.4103/ctm.ctm_14_19","DOIUrl":"https://doi.org/10.4103/ctm.ctm_14_19","url":null,"abstract":"The major function of fibrinolytic system is to dissolve the fibrins formed by blood coagulation and maintain the balance between blood coagulation and thrombolysis, which plays an important role in maintaining the liquid state of the blood and unclogging the blood vessels. It is a serious problem that malignant tumor does great harm to human life and health. In recent years, more and more studies signified that the fibrinolytic system in malignant tumors, especially adenocarcinoma, plays a major role in its progression, which indicates that the fibrinolytic system is of great significance in the development of malignant tumors. Besides, the fibrinolytic system has also gradually been known and used to diagnose and treat the adenocarcinoma. This article reviews how the fibrinolytic system works in the occurrence of malignant tumor and summarizes the diagnostic method and treatment of adenocarcinoma according to the latest clinical research progress, laying the foundation for further research.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"21 1","pages":"56 - 59"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87039862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The nephrotoxic effect of 5-fluorouracil (5-FU) involves alterations in renal function markers and kidney morphology. This study assessed the protective effect of selenium (Se) on 5-FU-induced alterations in renal function markers and kidney morphology in albino rats. Materials and Methods: Forty adult albino rats of (n = 5) used were randomly grouped. Groups B-D received 0.125 mg/kg, 0.25 mg/kg and 0.50 mg/kg of Se intraperitoneally (ip) daily for 5 days, respectively. Group E received 20 mg/kg of 5-FU ip daily for 5 days. Groups F-H received 0.125 mg/kg, 0.25 mg/kg, and 0.5 mg/kg of Se before receiving 20 mg/kg of 5-FU ip daily for 5 days, respectively. Group A (Control) received 0.2 mL of normal saline ip daily for 5 days. Rats were sacrificed on the 6th day, and blood samples were collected and evaluated for markers of serum renal function. Kidneys were assessed for oxidative stress indices and histology. Results: The nephrotoxic effect of 5-FU was characterized by statistically significant (P < 0.001) elevations in creatinine, urea, uric acid, and malondialdehyde levels in comparison to control. Furthermore, significant (P < 0.001) decreases in potassium, sodium, chloride, bicarbonate, glutathione (GSH), catalase, superoxide dismutase, and GSH peroxidase levels were obtained in 5-FU-treated rats in comparison to control. Necroses of kidney tubular epithelial cells and atrophic glomeruli were observed in rats administered with 5-FU. However, 5-FU-induced nephrotoxic changes were significantly downregulated in a dose-dependent fashion in rats supplemented with 0.125 mg/kg (P < 0.05), 0.25 mg/kg (P < 0.01), and 0.50 mg/kg (P < 0.001) of Se when compared to 5-FU treated rats. Conclusion: Supplementation with Se may have clinical benefit in nephrotoxicity caused by 5-FU.
{"title":"Protective activity of selenium against 5-fluorouracil-induced nephrotoxicity in rats","authors":"Elias Adikwu, N. Ebinyo, Beauty Amgbare","doi":"10.4103/ctm.ctm_26_19","DOIUrl":"https://doi.org/10.4103/ctm.ctm_26_19","url":null,"abstract":"Background: The nephrotoxic effect of 5-fluorouracil (5-FU) involves alterations in renal function markers and kidney morphology. This study assessed the protective effect of selenium (Se) on 5-FU-induced alterations in renal function markers and kidney morphology in albino rats. Materials and Methods: Forty adult albino rats of (n = 5) used were randomly grouped. Groups B-D received 0.125 mg/kg, 0.25 mg/kg and 0.50 mg/kg of Se intraperitoneally (ip) daily for 5 days, respectively. Group E received 20 mg/kg of 5-FU ip daily for 5 days. Groups F-H received 0.125 mg/kg, 0.25 mg/kg, and 0.5 mg/kg of Se before receiving 20 mg/kg of 5-FU ip daily for 5 days, respectively. Group A (Control) received 0.2 mL of normal saline ip daily for 5 days. Rats were sacrificed on the 6th day, and blood samples were collected and evaluated for markers of serum renal function. Kidneys were assessed for oxidative stress indices and histology. Results: The nephrotoxic effect of 5-FU was characterized by statistically significant (P < 0.001) elevations in creatinine, urea, uric acid, and malondialdehyde levels in comparison to control. Furthermore, significant (P < 0.001) decreases in potassium, sodium, chloride, bicarbonate, glutathione (GSH), catalase, superoxide dismutase, and GSH peroxidase levels were obtained in 5-FU-treated rats in comparison to control. Necroses of kidney tubular epithelial cells and atrophic glomeruli were observed in rats administered with 5-FU. However, 5-FU-induced nephrotoxic changes were significantly downregulated in a dose-dependent fashion in rats supplemented with 0.125 mg/kg (P < 0.05), 0.25 mg/kg (P < 0.01), and 0.50 mg/kg (P < 0.001) of Se when compared to 5-FU treated rats. Conclusion: Supplementation with Se may have clinical benefit in nephrotoxicity caused by 5-FU.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"74 1","pages":"50 - 55"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83743228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Crystal Montgomery-Goecker, Andrew A. Martin, C. Timmons, D. Rakheja, V. Rajaram, H. Luu
We describe a case of B-cell lymphoblastic lymphoma with an unusual clinical presentation. A 15-year old male with no significant past medical history presented with persistent foot swelling after an ankle sprain. Imaging revealed a mass in the right foot, which was resected and revealed a diffuse infiltrate of B-lymphoblasts. Peripheral blood and bone marrow examinations revealed no abnormalities. These findings were consistent with B-cell lymphoblastic lymphoma, which is an uncommon disease, accounting for only 2% of lymphomas. This case is a reminder that hematolymphoid malignancies can have presentations that mimic sarcomas with no visible peripheral blood or bone marrow involvement. In addition to describing the clinical and histologic features of this case, we also discuss the challenges that can be encountered when establishing a diagnosis of B lymphoblastic lymphoma
{"title":"A patient with persistent foot swelling after ankle sprain: B-Cell lymphoblastic lymphoma mimicking soft-tissue sarcoma","authors":"Crystal Montgomery-Goecker, Andrew A. Martin, C. Timmons, D. Rakheja, V. Rajaram, H. Luu","doi":"10.4103/ctm.ctm_22_19","DOIUrl":"https://doi.org/10.4103/ctm.ctm_22_19","url":null,"abstract":"We describe a case of B-cell lymphoblastic lymphoma with an unusual clinical presentation. A 15-year old male with no significant past medical history presented with persistent foot swelling after an ankle sprain. Imaging revealed a mass in the right foot, which was resected and revealed a diffuse infiltrate of B-lymphoblasts. Peripheral blood and bone marrow examinations revealed no abnormalities. These findings were consistent with B-cell lymphoblastic lymphoma, which is an uncommon disease, accounting for only 2% of lymphomas. This case is a reminder that hematolymphoid malignancies can have presentations that mimic sarcomas with no visible peripheral blood or bone marrow involvement. In addition to describing the clinical and histologic features of this case, we also discuss the challenges that can be encountered when establishing a diagnosis of B lymphoblastic lymphoma","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"5 1","pages":"60 - 63"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82841205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
U. Saddozai, Qiang Wang, Xiaoxiao Sun, Yifang Dang, Jiajia Lv, Junfang Xin, Wan Zhu, Yongqiang Li, Xinying Ji, Xiangqian Guo
Aims: To develop a free accessible online tool to identify the prognostic markers for Merkel cell carcinoma (MCC) and to estimate the significance of interested gene in a cohort of clinical patients. Settings and Design: R package is used to calculate and plot the Kaplan–Meier survival curve. Subjects and Methods: An online search engine was developed by combining MCC datasets with available anatomoclinical data in Gene Expression Omnibus. In current study, genomic expression profile of thirty patients comprising 42985 probes and 21651 genes was evaluated. Patients were divided into first quartile, second quartile, and third quartile. Information about different cancer patients of varying stages (Stage I–IV) was stored using median survival scale of 14.5 months. Data were stored in SQL Server database and hosted on Windows Server 2008 using Apache Tomcat application server. Statistical Analysis Used: Log-rank test was applied and P < 0.05 was considered statistically significant. Results: An Online Survival analysis tool for MCC abbreviating as OSMCC was developed, which can assess the expression level relevance of various genes on the clinical outcome in MCC patients. By OSMCC, the survival curve could be displayed, and the hazard ratio with 95% confidence intervals and log-rank P value can also be calculated. Conclusions: The study demonstrated the ability of OSMCC to identify and analyze transcriptome and clinical datasets for MCC through prognosis significance analysis. So far, OSMCC is the first advanced and specific tool for the prognostic measurement of MCC. Furthermore, OSMCC can prove to be a highly valuable database for the preliminary assessment and identification of potential MCC prognostic biomarkers. OSMCC is accessible at http://bioinfo.henu.edu.cn/MCC/MCCList.jsp.
目的:开发一个免费的在线工具来识别默克尔细胞癌(MCC)的预后标志物，并估计感兴趣基因在临床患者队列中的意义。设置与设计:使用R软件包计算和绘制Kaplan-Meier生存曲线。对象和方法:将MCC数据集与基因表达Omnibus中可用的解剖临床数据相结合，开发了一个在线搜索引擎。本研究评估了30例患者的基因组表达谱，包括42985个探针和21651个基因。患者被分为第一四分位数、第二四分位数和第三四分位数。采用14.5个月的中位生存期来存储不同分期(I-IV期)的不同癌症患者的信息。数据存储在SQL Server数据库中，使用Apache Tomcat应用服务器托管在Windows Server 2008上。方法:采用Log-rank检验，以P < 0.05为差异有统计学意义。结果:开发了MCC在线生存分析工具(简称OSMCC)，可以评估MCC患者中各种基因的表达水平与临床预后的相关性。通过OSMCC可以显示生存曲线，并可以计算95%置信区间的风险比和log-rank P值。结论:本研究通过预后意义分析证明了OSMCC能够识别和分析MCC的转录组和临床数据集。到目前为止，OSMCC是首个用于MCC预后测量的先进和专用工具。此外，OSMCC可以被证明是一个非常有价值的数据库，用于初步评估和鉴定潜在的MCC预后生物标志物。OSMCC可通过http://bioinfo.henu.edu.cn/MCC/MCCList.jsp访问。
{"title":"OSMCC: An online survival analysis tool for Merkel cell carcinoma","authors":"U. Saddozai, Qiang Wang, Xiaoxiao Sun, Yifang Dang, Jiajia Lv, Junfang Xin, Wan Zhu, Yongqiang Li, Xinying Ji, Xiangqian Guo","doi":"10.4103/ctm.ctm_19_19","DOIUrl":"https://doi.org/10.4103/ctm.ctm_19_19","url":null,"abstract":"Aims: To develop a free accessible online tool to identify the prognostic markers for Merkel cell carcinoma (MCC) and to estimate the significance of interested gene in a cohort of clinical patients. Settings and Design: R package is used to calculate and plot the Kaplan–Meier survival curve. Subjects and Methods: An online search engine was developed by combining MCC datasets with available anatomoclinical data in Gene Expression Omnibus. In current study, genomic expression profile of thirty patients comprising 42985 probes and 21651 genes was evaluated. Patients were divided into first quartile, second quartile, and third quartile. Information about different cancer patients of varying stages (Stage I–IV) was stored using median survival scale of 14.5 months. Data were stored in SQL Server database and hosted on Windows Server 2008 using Apache Tomcat application server. Statistical Analysis Used: Log-rank test was applied and P < 0.05 was considered statistically significant. Results: An Online Survival analysis tool for MCC abbreviating as OSMCC was developed, which can assess the expression level relevance of various genes on the clinical outcome in MCC patients. By OSMCC, the survival curve could be displayed, and the hazard ratio with 95% confidence intervals and log-rank P value can also be calculated. Conclusions: The study demonstrated the ability of OSMCC to identify and analyze transcriptome and clinical datasets for MCC through prognosis significance analysis. So far, OSMCC is the first advanced and specific tool for the prognostic measurement of MCC. Furthermore, OSMCC can prove to be a highly valuable database for the preliminary assessment and identification of potential MCC prognostic biomarkers. OSMCC is accessible at http://bioinfo.henu.edu.cn/MCC/MCCList.jsp.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"26 1","pages":"47 - 49"},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82852721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zengzheng Ge, H. Ling, Ming-Feng Li, Xiaoyan Xu, Y. Kai, Tongzhen Xu, Zengyu Ge, L. Zhou
With the application of many kinds of advanced examination techniques, the detectable rate of mixed adenoneuroendocrine carcinoma (MANEC) of the biliary-pancreatic system has increased substantially. This kind of tumor with high degree of malignancy is rarely seen. Thus, the clinical studies are difficult to carry out, most of which are just case reports. Besides, its treatments do not work effectively, albeit the diagnosis and management have changed tremendously. To deepen the understanding of MANEC of biliary-pancreatic system, this article is an overview making a generalization and summarization of the related literature as well as reviewing the main diagnosis and therapies of these rare tumors. In addition, it lays the foundation for clinical diagnosis and treatment in the future.
{"title":"Progress in diagnosis and treatment of mixed adenoneuroendocrine carcinoma of biliary-pancreatic system","authors":"Zengzheng Ge, H. Ling, Ming-Feng Li, Xiaoyan Xu, Y. Kai, Tongzhen Xu, Zengyu Ge, L. Zhou","doi":"10.4103/ctm.ctm_5_19","DOIUrl":"https://doi.org/10.4103/ctm.ctm_5_19","url":null,"abstract":"With the application of many kinds of advanced examination techniques, the detectable rate of mixed adenoneuroendocrine carcinoma (MANEC) of the biliary-pancreatic system has increased substantially. This kind of tumor with high degree of malignancy is rarely seen. Thus, the clinical studies are difficult to carry out, most of which are just case reports. Besides, its treatments do not work effectively, albeit the diagnosis and management have changed tremendously. To deepen the understanding of MANEC of biliary-pancreatic system, this article is an overview making a generalization and summarization of the related literature as well as reviewing the main diagnosis and therapies of these rare tumors. In addition, it lays the foundation for clinical diagnosis and treatment in the future.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"79 1","pages":"33 - 36"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79260083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Sharma, Anjali Geethadevi, Jyotsna Mishra, G. Anupa, K. Jadhav, K. Vikramdeo, D. Parashar
The human BRCA1-associated protein 1 (BAP1), a deubiquitinase, is a tumor suppressor protein known to be associated with a multicellular complex containing tumor suppressors, thereby coregulating various cellular processes such as DNA repair, gene transcription, cell cycle progression, and phosphorylation. Mutation and inactivation of BAP1 have long been reported in many malignancies and has been deployed in the prognosis of few malignancies. However, the mechanism of BAP1 regulation and its therapeutic significance have not been thoroughly explored. In addition to deubiquitination, BAP1 also responds to DNA damage and can induce cell death via apoptosis, necrosis, and ferroptosis. The mechanistic insight of BAP1-regulation is a complex subject and its thorough understanding would address the enigma of BAP1 mutation in malignancy. There are various tiers of regulation, though still needs to be explored, of BAP1 activity such as epigenetic regulation and posttranslational modification (PTM). Of various PTMs, posttranslational phosphorylation (PTP) has been poorly understood and meekly addressed in the literature. Here, we aim to provide an updated and integrated understanding of the PTP-mediated BAP1 regulation and its plausible role in cancer prevention. Exploring the functional consequence of BAP1 phosphorylation in its deubiquitinating potential might establish a new paradigm for its regulation in maintaining cellular homeostasis and cancer prevention.
{"title":"Phosphorylation of BRCA1-associated protein 1 as an important mechanism in the evasion of tumorigenesis: A perspective","authors":"G. Sharma, Anjali Geethadevi, Jyotsna Mishra, G. Anupa, K. Jadhav, K. Vikramdeo, D. Parashar","doi":"10.4103/ctm.ctm_1_19","DOIUrl":"https://doi.org/10.4103/ctm.ctm_1_19","url":null,"abstract":"The human BRCA1-associated protein 1 (BAP1), a deubiquitinase, is a tumor suppressor protein known to be associated with a multicellular complex containing tumor suppressors, thereby coregulating various cellular processes such as DNA repair, gene transcription, cell cycle progression, and phosphorylation. Mutation and inactivation of BAP1 have long been reported in many malignancies and has been deployed in the prognosis of few malignancies. However, the mechanism of BAP1 regulation and its therapeutic significance have not been thoroughly explored. In addition to deubiquitination, BAP1 also responds to DNA damage and can induce cell death via apoptosis, necrosis, and ferroptosis. The mechanistic insight of BAP1-regulation is a complex subject and its thorough understanding would address the enigma of BAP1 mutation in malignancy. There are various tiers of regulation, though still needs to be explored, of BAP1 activity such as epigenetic regulation and posttranslational modification (PTM). Of various PTMs, posttranslational phosphorylation (PTP) has been poorly understood and meekly addressed in the literature. Here, we aim to provide an updated and integrated understanding of the PTP-mediated BAP1 regulation and its plausible role in cancer prevention. Exploring the functional consequence of BAP1 phosphorylation in its deubiquitinating potential might establish a new paradigm for its regulation in maintaining cellular homeostasis and cancer prevention.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"535 1","pages":"25 - 32"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86372317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-04-01DOI: 10.4103/2395-3977.261826
S. Lehrer, P. Rheinstein
Background: Cognitive problems have been reported in breast cancer patients after chemotherapy. A small group of older breast cancer survivors carrying the APOE4 gene, receiving chemotherapy, was at increased risk of long-term impairment of brain function. We have analyzed the expression of APOE and the next 23-ranked Alzheimer's disease (AD) susceptibility genes in malignant breast tumors. We wished to determine if these 24 genes might be related to breast cancer. Methods: To identify the most important AD susceptibility genes, we consulted the ALZGENE database (http:// www.alzgene.org/) which displays this information and regularly updates it. To analyze the effect of AD susceptibility genes on breast cancer, we used The Cancer Genome Atlas (TCGA). We analyzed TCGA data with cBioPortal for Cancer Genomics. cBioPortal provides visualization, analysis, and download of large-scale cancer genomic data sets. cBioPortal can analyze APOE in breast tumors but cannot distinguish its three alleles: E2, E3, and E4. Results: About 1.6% of the tumors had APOE amplification (copy number alteration). Two percent of the tumors had CD33 alterations. None of the tumors had APOE mutations. Two tumors had CD33 missense mutations of unknown significance. Expression heatmap shows that over- or underexpression of APOE and CD33 was correlated in most of the tumors. APOE alteration significantly co-occurred with CD33 and CD2AP. Conclusion: Alterations of certain cancer genes tend to co-occur, indicating that they may work in tandem to drive tumor formation and development. This may be the case with the co-occurring alterations of APOE, CD33, and CD2AP. It would be important to know which APOE allele(s) were co-occurrent with CD33 and CD2AP and whether co-occurrence in the tumor predicted increased risk of AD. This information could help in identification of specific risk factors for breast cancer-related cognitive decline in older women, which has important implications for oncology care.
背景:已有乳腺癌患者化疗后出现认知问题的报道。一小群携带APOE4基因的老年乳腺癌幸存者接受化疗后，长期脑功能受损的风险增加。我们分析了APOE和接下来的23个阿尔茨海默病(AD)易感基因在乳腺恶性肿瘤中的表达。我们希望确定这24个基因是否可能与乳腺癌有关。方法:通过查阅ALZGENE数据库(http:// www.alzgene.org/)来确定最重要的阿尔茨海默病易感基因信息，并定期更新。为了分析AD易感基因对乳腺癌的影响，我们使用了癌症基因组图谱(TCGA)。我们使用cbiopportal for Cancer Genomics分析TCGA数据。cBioPortal提供大规模癌症基因组数据集的可视化、分析和下载。cBioPortal可以分析乳腺肿瘤中的APOE，但不能区分它的三个等位基因:E2、E3和E4。结果:约1.6%的肿瘤存在APOE扩增(拷贝数改变)。2%的肿瘤有CD33的改变。这些肿瘤都没有APOE突变。两个肿瘤有意义不明的CD33错义突变。表达热图显示，在大多数肿瘤中，APOE和CD33的过表达或过表达是相关的。APOE的改变与CD33和CD2AP同时发生。结论:某些肿瘤基因的改变倾向于同时发生，表明它们可能协同作用，驱动肿瘤的形成和发展。这可能是APOE、CD33和CD2AP共同发生改变的情况。了解哪些APOE等位基因与CD33和CD2AP共发生以及在肿瘤中共发生是否预示着AD的风险增加是很重要的。这一信息有助于确定老年妇女乳腺癌相关认知能力下降的具体危险因素，这对肿瘤治疗具有重要意义。
{"title":"Alzheimer’s Disease Susceptibility Genes in Malignant Breast Tumors","authors":"S. Lehrer, P. Rheinstein","doi":"10.4103/2395-3977.261826","DOIUrl":"https://doi.org/10.4103/2395-3977.261826","url":null,"abstract":"Background: Cognitive problems have been reported in breast cancer patients after chemotherapy. A small group of older breast cancer survivors carrying the APOE4 gene, receiving chemotherapy, was at increased risk of long-term impairment of brain function. We have analyzed the expression of APOE and the next 23-ranked Alzheimer's disease (AD) susceptibility genes in malignant breast tumors. We wished to determine if these 24 genes might be related to breast cancer. Methods: To identify the most important AD susceptibility genes, we consulted the ALZGENE database (http:// www.alzgene.org/) which displays this information and regularly updates it. To analyze the effect of AD susceptibility genes on breast cancer, we used The Cancer Genome Atlas (TCGA). We analyzed TCGA data with cBioPortal for Cancer Genomics. cBioPortal provides visualization, analysis, and download of large-scale cancer genomic data sets. cBioPortal can analyze APOE in breast tumors but cannot distinguish its three alleles: E2, E3, and E4. Results: About 1.6% of the tumors had APOE amplification (copy number alteration). Two percent of the tumors had CD33 alterations. None of the tumors had APOE mutations. Two tumors had CD33 missense mutations of unknown significance. Expression heatmap shows that over- or underexpression of APOE and CD33 was correlated in most of the tumors. APOE alteration significantly co-occurred with CD33 and CD2AP. Conclusion: Alterations of certain cancer genes tend to co-occur, indicating that they may work in tandem to drive tumor formation and development. This may be the case with the co-occurring alterations of APOE, CD33, and CD2AP. It would be important to know which APOE allele(s) were co-occurrent with CD33 and CD2AP and whether co-occurrence in the tumor predicted increased risk of AD. This information could help in identification of specific risk factors for breast cancer-related cognitive decline in older women, which has important implications for oncology care.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"175 1","pages":"42 - 46"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88466188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guoyu Qiu, Xiaohui Xu, L. Ji, Ruiping Ma, Zi-long Dang, Huan Yang
Surface-Enhanced Raman Spectroscopy (SERS) is a sensitive and selective spectroscopic technique for the detection and characterization of analytes, which are adsorbed on suitable metal surfaces. SERS as a strategy has been widely used in detecting target molecules, and the screening of drug activity is mainly to study the biological effects of drug combined with target, so a study on biological activity of anticancer drug based on SERS is a concern to some researchers. SERS combines the advantages of positive identification of molecules in situ, stand-alone detection, well-established instrumentation with high sensitivity, and its noninvasive detection. In this paper, we review on the application of SERS in studying anticancer agent from three aspects, such as studying the effects of anticancer agent on cancer cells, detection of anticancer agent in human plasma, and testing the interaction between anticancer agent and DNA or protein.
{"title":"Surface-Enhanced Raman Spectroscopy to study the biological activity of anticancer agent","authors":"Guoyu Qiu, Xiaohui Xu, L. Ji, Ruiping Ma, Zi-long Dang, Huan Yang","doi":"10.4103/ctm.ctm_18_19","DOIUrl":"https://doi.org/10.4103/ctm.ctm_18_19","url":null,"abstract":"Surface-Enhanced Raman Spectroscopy (SERS) is a sensitive and selective spectroscopic technique for the detection and characterization of analytes, which are adsorbed on suitable metal surfaces. SERS as a strategy has been widely used in detecting target molecules, and the screening of drug activity is mainly to study the biological effects of drug combined with target, so a study on biological activity of anticancer drug based on SERS is a concern to some researchers. SERS combines the advantages of positive identification of molecules in situ, stand-alone detection, well-established instrumentation with high sensitivity, and its noninvasive detection. In this paper, we review on the application of SERS in studying anticancer agent from three aspects, such as studying the effects of anticancer agent on cancer cells, detection of anticancer agent in human plasma, and testing the interaction between anticancer agent and DNA or protein.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"103 1","pages":"37 - 41"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86702588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim: The aim of the study is to conduct a systematic review and meta-analysis of data showing the association of lactate levels with mortality and neurologic outcome in patients who achieved return of spontaneous circulation (ROSC) after cardiac arrest. Methods: An electronic search of PubMed, Embase, Web of Science, and Cochrane Library databases was conducted. Lactate levels at 0, 6, 12, 24, and 48 h after ROSC in survivors versus nonsurvivors and in good versus poor neurologic outcome patients were extracted. Continuous variable and odds ratio were applied for data analysis. Inverse-variance fixed effects model with 95% confidence interval (CI) was used depending on interstudy heterogeneity. Results: A total of 18 articles meeting the study criteria were included for systematic review and 15 for meta-analysis. The results showed that initial serum lactate levels in nonsurvivors were significantly higher than survivors (standardized mean difference [SMD] = −0.43; 95% CI = [−0.52, −0.33]; P < 0.00001), and a higher lactate level at admission was associated with increased hospital mortality. In addition, initial serum lactate levels were significantly higher in poor neurologic outcome patients than good neurologic outcome patients (SMD = −0.44; 95% CI = [−0.54, −0.34]; P < 0.00001), and initial higher lactate level was associated with poor neurologic outcome. There was a statistically significant difference in lactate levels at 6, 12, 24, and 48 h after ROSC, among survivors versus nonsurvivors and among patients presenting good neurologic outcome versus poor neurologic outcome. However, the included studies had small sample size and highly inconsistent data. Conclusions: Higher lactate levels were associated with increased mortality and poor neurologic outcome. Lower lactate levels or faster lactate clearance was associated with higher survival and good neurologic outcome.
目的:该研究的目的是对心脏骤停后实现自然循环恢复(ROSC)的患者的乳酸水平与死亡率和神经系统预后的关系进行系统回顾和荟萃分析。方法:电子检索PubMed、Embase、Web of Science、Cochrane Library数据库。提取ROSC后0、6、12、24和48小时幸存者与非幸存者以及神经系统预后良好与较差患者的乳酸水平。采用连续变量和优势比进行数据分析。根据研究间异质性，采用95%置信区间(CI)的反方差固定效应模型。结果:共有18篇符合研究标准的文章被纳入系统评价，15篇被纳入元分析。结果显示，非幸存者的初始血清乳酸水平显著高于幸存者(标准化平均差[SMD] = - 0.43;95% ci =[−0.52，−0.33];P < 0.00001)，入院时较高的乳酸水平与住院死亡率增加相关。此外，神经转归差患者的初始血清乳酸水平显著高于神经转归好患者(SMD = - 0.44;95% ci =[−0.54，−0.34];P < 0.00001)，初始较高的乳酸水平与较差的神经预后相关。在ROSC后6、12、24和48小时，幸存者与非幸存者以及神经系统预后良好与神经系统预后较差的患者中，乳酸水平存在统计学上的显著差异。然而，纳入的研究样本量小，数据高度不一致。结论:较高的乳酸水平与死亡率增加和神经系统预后不良相关。较低的乳酸水平或较快的乳酸清除与较高的生存率和良好的神经系统预后相关。
{"title":"The prognostic role of lactate in patients who achieved return of spontaneous circulation after cardiac arrest: A systematic review and meta-analysis","authors":"Dongni Ren, Xin Wang, Y. Tu","doi":"10.4103/ctm.ctm_6_19","DOIUrl":"https://doi.org/10.4103/ctm.ctm_6_19","url":null,"abstract":"Aim: The aim of the study is to conduct a systematic review and meta-analysis of data showing the association of lactate levels with mortality and neurologic outcome in patients who achieved return of spontaneous circulation (ROSC) after cardiac arrest. Methods: An electronic search of PubMed, Embase, Web of Science, and Cochrane Library databases was conducted. Lactate levels at 0, 6, 12, 24, and 48 h after ROSC in survivors versus nonsurvivors and in good versus poor neurologic outcome patients were extracted. Continuous variable and odds ratio were applied for data analysis. Inverse-variance fixed effects model with 95% confidence interval (CI) was used depending on interstudy heterogeneity. Results: A total of 18 articles meeting the study criteria were included for systematic review and 15 for meta-analysis. The results showed that initial serum lactate levels in nonsurvivors were significantly higher than survivors (standardized mean difference [SMD] = −0.43; 95% CI = [−0.52, −0.33]; P < 0.00001), and a higher lactate level at admission was associated with increased hospital mortality. In addition, initial serum lactate levels were significantly higher in poor neurologic outcome patients than good neurologic outcome patients (SMD = −0.44; 95% CI = [−0.54, −0.34]; P < 0.00001), and initial higher lactate level was associated with poor neurologic outcome. There was a statistically significant difference in lactate levels at 6, 12, 24, and 48 h after ROSC, among survivors versus nonsurvivors and among patients presenting good neurologic outcome versus poor neurologic outcome. However, the included studies had small sample size and highly inconsistent data. Conclusions: Higher lactate levels were associated with increased mortality and poor neurologic outcome. Lower lactate levels or faster lactate clearance was associated with higher survival and good neurologic outcome.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"92 1","pages":"1 - 9"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91051656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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