scholarly journals Hydrogen Sulfide: Emerging Role in Bladder, Kidney, and Prostate Malignancies

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Masoud Akbari ◽  
Emrullah Sogutdelen ◽  
Smriti Juriasingani ◽  
Alp Sener

Hydrogen sulfide (H2S) is the latest member of the gasotransmitter family and known to play essential roles in cancer pathophysiology. H2S is produced endogenously and can be administered exogenously. Recent studies showed that H2S in cancers has both pro- and antitumor roles. Understanding the difference in the expression and localization of tissue-specific H2S-producing enzymes in healthy and cancer tissues allows us to develop tools for cancer diagnosis and treatment. Urological malignancies are some of the most common cancers in both men and women, and their early detection is vital since advanced cancers are recurrent, metastatic, and often resistant to treatment. This review summarizes the roles of H2S in cancer and looks at current studies investigating H2S activity and expression of H2S-producing enzymes in urinary cancers. We specifically focused on urothelial carcinoma, renal cell carcinoma, and prostate cancer, as they form the majority of newly diagnosed urinary cancers. Recent studies show that besides the physiological activity of H2S in cancer cells, there are patterns between the development and prognosis of urinary cancers and the expression of H2S-producing enzymes and indirectly the H2S levels. Though controversial and not completely understood, studying the expression of H2S-producing enzymes in cancer tissue may represent an avenue for novel diagnostic and therapeutic strategies for addressing urological malignancies.

2020 ◽  
Vol 20 ◽  
Author(s):  
Nan Wang ◽  
Rui Kong ◽  
Wei Han ◽  
Jie Lu

Background: Hepatoid adenocarcinoma of the stomach (HAS) has been recognized as a rare primary gastric tumor characterized by hepatocellular carcinoma-like histology. HAS often causes diagnostic confusion with conventional gastric adenocarcinoma (CGA) due to the difficulty to detect hepatoid differentiation solely based on findings from hematoxylin and eosin (H&E) staining. Hence, HAS should be distinguished from solid-type CGA based on their different biological behaviors. β-catenin is highly expressed in hepatocellular carcinoma (HCC), which is involved in the maintenance of tumor initiating cells, drug resistance, tumor progression, and metastasis. Methods and Results: Given the dearth of HAS cases, systematic examination of the expression of β-catenin in HAS remains under-explored. In this study, 14 cases were subjected to immunostaining with with AFP, β-catenin, glypican3, hepar-1 and CerbB-2. In parallel, the clinicopathological characteristics of these patients were collected. We detected statistically significant difference in the expression of β-catenin (P = 0.000), glypican3 (P = 0.019), and hepar-1 (P = 0.007) between HAS cancer tissues and the adjacent non-cancerous tissues. Furthermore, a significant correlation was observed between the expression of β-catenin in HAS cancer tissue and adjacent tissue (Pearson correlation coefficient: 0.686, P = 0.007). Moreover, in cancer tissues, a significant correlation was observed between the expression of β-catenin and survival time (Spearman correlationcoefficient= - 0.482, P = 0.003). However, we found the expression of β-catenin did not correlate with the degree of tumor differentiation and tumor size, age, gender, serum AFP levels, microinvasion, and metastasis (P > 0.05). Conclusion: Our findings establish β-catenin as a useful marker that can distinguish HAS from CGA and may improve the early diagnosis to guide the appropriate and timely treatment of HAS patients.


2021 ◽  
Vol 12 ◽  
pp. 204062072110129
Author(s):  
Songyi Park ◽  
Dong-Yeop Shin ◽  
Junshik Hong ◽  
Inho Kim ◽  
Youngil Koh ◽  
...  

Background: High dose melphalan (HDMEL) is considered the standard conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. Recent studies showed superiority of busulfan plus melphalan (BUMEL) compared to HDMEL as a conditioning regimen. We compared the efficacy of HDMEL and BUMEL in newly diagnosed Asian MM patients, who are often underrepresented. Methods: This is a single-center, retrospective study including MM patients who underwent ASCT after bortezomib-thalidomide-dexamethasone (VTD) triplet induction chemotherapy between January 2015 and August 2019. Result: In the end, 79 patients in the HDMEL group were compared to 31 patients in the BUMEL group. There were no differences between the two groups with regards to sex, age at ASCT, risk group, and stage. The HDMEL group showed better response to pre-transplant VTD compared to BUMEL, but after ASCT the BUMEL group showed better overall response. In terms of progression-free survival (PFS), although BUMEL showed trends towards better PFS regardless of pre-transplant status and age, the difference did not reach statistical significance. The BUMEL group more often experienced mucositis related to chemotherapy, but there was no difference between the two groups with regards to hospitalization days, cell engraftment, and infection rates. Conclusion: BUMEL conditioning deserves attention as the alternative option to HDMEL for newly diagnosed MM patients, even in the era of triplet induction chemotherapy. Specifically, patients achieving very good partial response (VGPR) or better response with triplet induction chemotherapy might benefit the most from BUMEL conditioning. Tailored conditioning regimen, based on patient’s response to induction chemotherapy and co-morbidities, can lead to better treatment outcomes.


2021 ◽  
Author(s):  
Zahra Nouri Ghonbalani ◽  
Shiva Shahmohamadnejad ◽  
Parvin Pasalar ◽  
Ehsan Khalili

Abstract PurposeColorectal cancer (CRC) is the second leading cause of death from cancer in adults. Recent advances have shown that cancer cells can have some epigenetic changes involved in all stages of cancer. It has also been shown that miR-424 acts as gene expression regulators in many biological processes, including angiogenesis with mediators such as VEGF. In the current study, to identify the potential role of miR-424 in colorectal cancer progression, methylation status of miR-424 promoter region and its expression level have been evaluated. Besides, the correlation between VEGF level and miR-424 expression level has been assessed.MethodsMethylation status miR-424 promoter was assessed using methylation-specific polymerase chain reaction (MSP). The expression level of miR-424 in human colorectal cancer tissue was analyzed by quantitative PCR. HCT116 cell line was selected to evaluate the correlation between the miR-424 expression level and the promoter's methylation status. VEGF expression, one out of mir-424 targets involved in angiogenesis and cancer progression, was measured by western blot analysis in the pairs of cancer tissues and their adjacent tissues.ResultsOur results have revealed that the promoter region of miR-424 is methylated in cancer cells compared to normal cells, leading to down-regulation of miR-424 in the colorectal cancer tissues compared to the normal tissues. Also, we found that the expression protein's level of VEGF in the tumor cells increased compared with normal tissues.ConclusionThe present study suggests that hypermethylation downregulates miR-424. VEGF expression is upregulated with decreased miR-424 in colorectal cancer, which results in cancer progression.


2021 ◽  
Author(s):  
Zhishuo Zhang ◽  
Wenxia Zhao ◽  
Yiming Li ◽  
Yang Li ◽  
Yang Liu ◽  
...  

Abstract Background Ubiquitination is a basic post-translational modification of intracellular proteins and can be reversed enzymatically by DUBs (deubiquitinating enzymes). More than 90 DUBs have been identified. Among them, the deubiquitinating enzyme YOD1, a member of the ovarian tumor domain protease (OTUs) subfamily, is involved in the regulation of endoplasmic reticulum (ER)-related degradation pathways. In fact, it is reported that YOD1 is an important proliferation and metastasis-inducing gene, which can stimulate the characteristics of cancer stem cells and maintain circulating tumor cells (CTC). However, the expression level, prognostic effect, biological function and mechanism of YOD1 in pancreatic cancer are still unclear. ResultsIn the GEO and TCGA databases, YOD1 mRNA expression is significantly up-regulated in a variety of human pancreatic cancer tissues. Survival analysis showed that the up-regulation of YOD1 can predict poor prognosis of pancreatic cancer. Cox analysis showed that high YOD1 expression is an independent prognostic factor of pancreatic cancer. ROC analysis shows that YOD1 has significant diagnostic value. The immunohistochemistry (IHC) results showed that the protein expression level of YOD1 in pancreatic cancer tissue was higher than that in neighboring non-pancreatic cancer tissues (P<0.001). In addition, we found that YOD1 expression is negatively correlated with the infiltration level of CD8+ T cells, macrophages, neutrophils and dendritic cells (DC) in pancreatic cancer. The expression of YOD1 has a strong correlation with the different immune marker sets in PAAD. Co-expression network and functional enrichment analysis indicate that YOD1 may participate in the development of pancreatic cancer through cell adhesion molecules, p53, Hippo, TGF-β and other pathways. The experimental results of EDU, Transwell and Western blot indicate that YOD1 is highly expressed in pancreatic cancer cells and pancreatic cancer tissues, and its overexpression can promote the proliferation and metastasis of pancreatic cancer cells.Conclusion Our results indicate that YOD1 may be a useful biomarker for the prognosis of human pancreatic cancer, and it may also be a potential molecular target for the diagnosis and treatment of pancreatic cancer.


2020 ◽  
Vol 4 (1) ◽  
pp. 01-03
Author(s):  
Osman Demirhan ◽  
Deniz Taştemir Korkmaz ◽  
Nesrin Çetinel

Breast cancer (BC) is the most prevalent malignant disease in females worldwide. Genomic instability in tumor tissue has been associated with tumor progression. These genetic changes may take a variety of forms, including numerical and structural chromosomal abnormalities (CAs), epigenetic changes, and gene expression alterations. Many tumor tissues are made up of genetically different cell populations, and the study of the causes and consequences of this heterogeneity play a central role in cancer research. In this study, CAs in blood and cancer tissues of patients with sporadic BC were examined. Our findings shows that the increase in numerical sex aneuploidy in BC tissues is significantly higher than in blood tissue. These aneuploidy increases in cancer tissues seem to be compatible with the development and increase of cancer, and can play a role in the pathogenesis of cancers. These changes are consistent with early and long-standing exposure to carcinogens, especially estrogens. These findings should clarify our understanding of breast carcinogenesis in breast tissues and promote development of improved methods for risk assessment and BC prevention in women.


2021 ◽  
Vol 8 (12) ◽  
pp. 1799
Author(s):  
Momammed Mustafizur Rahman ◽  
Shabnam Imam ◽  
Sayedatun Nessa ◽  
A. K. M. Maruf Raza ◽  
Farida Arjuman ◽  
...  

Background: This cross- sectional observational study was carried out with an aim to look for microsatellite instability (MSI) status in colorectal carcinoma and their association with different histomorphological patterns and biological behavior of colorectal carcinoma.Methods: This cross-sectional observational study was done in the Department of Pathology, Bangabandhu Sheikh Mujib Medical University Hospital (BSMMU), Dhaka, Bangladesh during September 2014 to October 2015. A total of 39 surgically resected sample of colorectal carcinoma were included. Consent from each patient was taken. The samples were histopathologically evaluated according to the standard protocol. The statistical analyses were done using Statistical packages for social sciences (SPSS 15) for Windows.Results: A total of 39 cases of colorectal carcinoma were included in this study. Majority of the patients (55.5%) was in 6th decade in MSI and 29.1% were MSI absent group. The mean age was found 47.67±10.97 years in present group and 47.84±14.26 years in absent group. The difference was not statistically significant (p>0.05). TNM stage with MSI was observed. The mean CEA level was 100.74±103.66 and 60.43±91.72. The mean Hb was 9.72±1.99 % and 9.92±2.17, the range was 7.2-12.2 and 4.6-13.4 among the groups. The mean difference was not statistically significant (p>0.05). Ulcerated was 3 (33.3%) and 19 (64.5%). Stage 3 tumor was 4 (44.4%) and 16 (51.6%). Grade 2 tumor was 5 (55.6%) and 17 (58.0%).Conclusions: For the first time in Bangladesh, this study was undertaken to evaluate the microsatellite instability (MSI) status in colorectal cancer tissue and their association with different histomorphological patterns of colorectal carcinoma.   


2021 ◽  
Author(s):  
Juan Wang ◽  
Zihan Zheng ◽  
Qinghua Cao ◽  
Xiufen Liu ◽  
Zhiqing Wang

Abstract Backgroud Obg-like ATPase 1 (OLA1) is a member of the Obg family of P-loop NTPases and has recently been detected in several human cancer cells. However, its expression type and clinical relevance in gastric cancer remains unclear. Methods In the present study, 2 datasets downloaded from the open Gene Expression Omnibus database were used to evaluate the mRNA level of OLA1 in gastric cancer. Quantitative Reverse Transcription PCR further validated the mRNA expression in gastric cancer tissues. Immunohistochemistry was performed on gastric cancer tissue microarray to assess OLA1 protein expression type, prognostic value, biological significance and its association with Snail in 334 patients of gastric cancer. The prognostic value of combination of OLA1 and Snail has been evaluated. Results The results showed that OLA1 mRNA and protein were elevated in gastric cancer tissues. High expression of OLA1 was significantly associated with aggressive features, such as tumor size, lymph node metastasis and TNM stage (P = 0.0146, P = 0.0037, P < 0.001, respectively). Moreover, high levels of OLA1 predicted worse overall survival. Multivariate Cox regression analysis indicated that high expression of OLA1 was an independent prognostic factor for poor overall survival (hazard ratio, 0.573; 95% confidence interval, 0.376–0.872; P = 0.009). Additionally, OLA1 expression was positively correlated with Snail, and combination of them revealed improved prognostic accuracy for gastric cancer patients. Conclusions Our results suggested that OLA1 high expression was considered as an independent factor for the prediction of unfavorable prognosis in gastric cancer patients, and we believe that OLA1 could serve as a biomarker of poor prognosis and a novel target in treating gastric cancers.


2020 ◽  
Vol 19 ◽  
pp. 153303381990112
Author(s):  
Kan-kan Yang ◽  
Hui-mian Xu ◽  
Jin-yu Huang ◽  
Yu-xuan Guo ◽  
Zhen-ning Wang

Background: SRY-related HMG box-12, which is associated with the prognosis of cancer, has been frequently described. However, both SRY-related HMG box-12 expression and its relationship with clinicopathological variables and patient survival have not been defined in gastric cancer. The aim of our study was to examine the prognostic value of SRY-related HMG box-12 expression in patients with gastric cancer. Methods: In this study, we determined SRY-related HMG box-12 expression in 79 primary gastric cancer tissues and 79 matched adjacent nontumor tissues by immunohistochemistry and then calculated the survival rate using the Kaplan-Meier method. Cox proportional hazard regression model was used to analyze predictors of gastric cancer. Western blot and quantitative real-time polymerase chain reaction were used to investigate the difference in SRY-related HMG box-12 expression between normal gastric epithelial cells and gastric cancer cells at the protein level and RNA level, respectively. Results: SRY-related HMG box-12 was downregulated in gastric cancer tissues. Low SRY-related HMG box-12 expression was significantly associated not only with lymph node metastasis ( P = .027) and TNM stage ( P = .021) but also with disease-specific survival in patients with gastric cancer. Multivariate analysis demonstrated TNM stage was an independent factor predicting poor survival ( P = .034). Conclusions: Low SRY-related HMG box-12 expression is associated with poor clinical outcomes in gastric cancer.


2019 ◽  
Vol 316 (6) ◽  
pp. H1237-H1252 ◽  
Author(s):  
Sumit Kar ◽  
Tyler N. Kambis ◽  
Paras K. Mishra

The death of cardiomyocytes is a precursor for the cascade of hypertrophic and fibrotic remodeling that leads to cardiomyopathy. In diabetes mellitus (DM), the metabolic environment of hyperglycemia, hyperlipidemia, and oxidative stress causes cardiomyocyte cell death, leading to diabetic cardiomyopathy (DMCM), an independent cause of heart failure. Understanding the roles of the cell death signaling pathways involved in the development of cardiomyopathies is crucial to the discovery of novel targeted therapeutics and biomarkers for DMCM. Recent evidence suggests that hydrogen sulfide (H2S), an endogenous gaseous molecule, has cardioprotective effects against cell death. However, very little is known about signaling by which H2S and its downstream targets regulate myocardial cell death in the DM heart. This review focuses on H2S in the signaling of apoptotic, autophagic, necroptotic, and pyroptotic cell death in DMCM and other cardiomyopathies, abnormalities in H2S synthesis in DM, and potential H2S-based therapeutic strategies to mitigate myocardial cell death to ameliorate DMCM.


Materials ◽  
2019 ◽  
Vol 13 (1) ◽  
pp. 85 ◽  
Author(s):  
Roman Grigorev ◽  
Anna Kuzikova ◽  
Petr Demchenko ◽  
Artem Senyuk ◽  
Anna Svechkova ◽  
...  

In recent times, terahertz (THz) technologies have been actively applied in many biomedical research work, including gastric cancer diagnosis. In order to provide an effective removal of tumor during surgery, it is necessary to clearly distinguish it from different membranes of the stomach. In this work, we reported an investigation of various normal and cancer fresh gastric tissues using terahertz time-domain spectroscopy in the reflection mode. Refractive index and absorption coefficient of moderately differentiated and poorly differentiated gastric adenocarcinomas, as well as both serosa and mucosa were obtained in the frequency range from 0.2 to 1 THz. All cancer tissues were distinguishable from normal ones. The influence of the morphology of the investigated tissues on the obtained optical properties is discussed. The obtained results demonstrated a potential of THz time-domain spectroscopy to discriminate a tumor from normal serous and mucous gastric membranes. Thus, this method might be applied to gastric cancer diagnosis.


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