Histopathological pattern of ovarian neoplasms in Sub-Himalayan belt of rural India: a four-year study from a tertiary care teaching hospital

Background: Ovarian tumors are one of the ubiquitous and common forms of neoplasms in women. The aim of the study was to understand the pattern of benign and malignant ovarian neoplasms and their distribution in different age groups in rural population of India.Methods: A retrospective study conducted in the Department of Pathology in close collaboration with Department of Obstetrics and Gynecology, Dr. Rajendra Prasad Government Medical College, Kangra at Tanda (HP), India. All the patients irrespective of age group who were operated for ovarian neoplasms (benign or malignant) were included in this retrospective analysis over duration of four years (2013 to 2016). “WHO classification system” was used, for classification of all these ovarian tumors. The incidence of these tumors with respect to age group was also studied.Results: During the study period (2013-2016), there were a total of 242 surgeries for ovarian neoplasms. Of these, majority of the tumours were benign 184 (76%), but an alarming number of women had malignant ovarian tumours 51 (21%), remaining 7 (3%) cases were borderline. Age wise distribution was 7% (16/242) in less than 20 years age, 19% (46/242) in 20-30 years age, 29% (69/242) in 30-40 years age group, 24% (59/242) in 40-50 years and remaining 21% (52/242) in more than 50 years age group. Pre-dominantly benign tumors were surface epithelial tumors (serous/ mucinous cystadenoma), germ cell tumors (mature cystic teratoma) and endometrioma. Major malignant tumors were surface epithelial tumors (serous/mucinous cystadeno-carcinoma), and germ cell tumors (dysgerminoma, immature teratoma).Conclusions: In this sub-Himalayan belt of rural India, the incidence of benign ovarian tumors was 76%. Borderline ovarian tumors were seen in 3% cases and the remaining 21% cases were malignant ones. Even though benign tumors were the commonest for each age group, however as the age of women increased the proportion of malignant tumors in them increased. Surface epithelial tumors are the most common class of tumors in both benign and malignant tumors. Serous cystadenoma is the most common ovarian tumor overall as well as most common benign tumor whereas serous cystadeno-carcinoma is most common malignancy. Stromal ovarian tumor (one case) is a rarity. Only one woman had bilateral ovarian tumor. 

IL-33 expression is altered in hepatitis C virus-related pathologies

Hepatitis C virus (HCV) currently affects approximately 71 million people worldwide and causes extensive liver damage that can transition into hepatocellular carcinoma (HCC), a deadly malignant liver cancer. Unfortunately, patients tend to seek diagnostic testing late, when more severe symptoms exist, indicating advanced disease with severe fibrosis. There is a gap in knowledge about the immunologic process of HCV-induced fibrosis and cirrhosis development. Interleukin-33 (IL-33) is a cytokine implicated in various inflammatory and fibrotic diseases. We hypothesize that IL-33 plays a role in the pathogenesis of HCV, particularly in fibrosis and cirrhosis development leading to malignant transformation and thus may serve as an inflammatory biomarker. We studied livers from normal subjects - no liver-related diagnoses (n=6), subjects with HCV-cirrhosis (n=7), and subjects with HCV/HCC (n=7). We performed immunohistochemistry on paraffin-embedded liver tissue sections using a human IL-33 antibody and DAB staining system. To quantify our results, we performed image analyses quantifying IL-33 chromogen stain using an algorithm to calculate the signal strength of an image to determine the amount of antibody-specific chromogen per pixel, expressed in energy units per pixel (eu/px). We found that IL-33 is normally expressed in human hepatocytes; it is expressed at higher levels in HCV-cirrhosis patients and at lower levels in HCV-HCC patients. We plan to expand this study by including more patients in the future

Alpha-linolenic acid regulates the growth of breast and cervical cancer cell lines through regulation of NO release and induction of lipid peroxidation

In the present work, we have analyzed the effect of the essential fatty acid, alpha linolenic acid (ALA) on nitric oxide release as well as induction of lipid peroxidation in breast (MCF-7 and MDA-MB-231) and cervical (SiHa and HeLa) cancer cell lines. ALA-treated cells showed a dose-dependent decrease in cell viability in both breast and cervical cancer cell lines without affecting the viability of non-cancerous transformed HEK 293 cells. Both types of cancer cells treated with ALA demonstrated a significant reduction in nitric oxide (NO) release with a simultaneous increase in lipid peroxidation (LPO). This was followed by a decrease in the mitochondrial membrane potential as well as activation of caspase 3 leading to apoptosis. Thus, ALA regulated the growth of cancer cell lines through induction of lipid peroxidation and modulation of nitric oxide release resulting in apoptosis

Antimicrobial Resistance with Special Emphasis on Pathogens in Agriculture

Antibiotics have been used globally to manage the bacterial plant diseases irrespective of the expense involved. Although plant pathogenesis by bacteria is far lower than fungal counterparts, disrupted monitoring and surveillance for drug resistance with respect to human health raise serious concerns. The resistance derived by the plant as the host by the antibiotics used for many generations has now posed as a problem in phyto-systems. Although we currently lack the molecular understanding of the pathogens rendering antibiotic resistance to plants, robust resistance management strategies are critical to ensure management of critically important diseases that specifically target crops of high value and/or global agrarian importance. This chapter discusses evolution of plant-pathogenic bacteria, application of antibiotics and its repercussions on the microbiome of plant agricultural systems, and sustainable crop disease management by genetic engineering

Proteomics study reveals a gender-based ribosomal inflammatory biomarker in Hepatitis C virus induced cirrhosis

Hepatitis C Virus (HCV) infection is a major cause of Hepatocellular Carcinoma (HCC). Further, HCC is a leading cause of liver-related death world-wide linked to liver cirrhosis and chronic liver disease. Clinical evidence suggests that pre-menopausal women, with elevated levels of circulating estrogen, clear HCV infection faster than males, and show low incidence of HCC. Our studies have shown gender-based differential estrogen receptor expression in the normal liver, which could contribute to protection in pre-menopausal women against chronic liver diseases including HCC. There is a gap in the current knowledge of biomarkers that could be used for early detection of HCV-related cirrhosis and HCC development. Further, biomarkers that account for gender differences in HCV-related pathogenesis have not yet been identified.The purpose of this study was to identify early cancer biomarkers in HCV-related cirrhosis by analyzing liver proteins-specifically focusing on ribosomal family of proteins (RPs). Ribosomal proteins play an important role in cellular apoptosis, cell proliferation, and cancer development. Ribosomes convert mRNA into proteins using various RPs and have been shown to change in different tissues and tumors. Ribosomal gene FAU (Finkel-Biskis-Reilly murine sarcoma virus) has recently been identified as an apoptosis regulatory gene involved in ovarian, breast, and prostate cancer. To identify gender-based protein differences in male and female liver cirrhosis patients, we investigated RPs via proteomic study. Normal and HCV diseased liver tissue extracts were processed and sent to NIH IDeA National Resource for Quantitative Proteomics core lab for DIA proteomic analysis. We had four experimental groups with 10 samples in each group. The four groups included were normal control male, normal control female, HCV cirrhosis male, and HCV cirrhosis female. A total of 4,443 proteins were identified of which 132 were ribosomal proteins. Within the ribosomal protein cohort, 78 exhibited differential expression in liver cirrhosis compared to normals, with 13 showing gender-based significance.FAU gene encodes for the 40S ribosomal protein S30 in the cytoplasmic ribosome and illustrated gender-based differences in cirrhosis group. FAU was significantly upregulated (logFC 1.04050553) in HCV females compared to HCV male liver tissues (p-value .0012) and was significantly downregulated in HCV male liver tissues compared to normal control males. No differences were observed in remaining experimental groups (HCV F vs. normal control F and normal control M vs. normal control F). This study identified the ribosomal protein FAU and its potential to serve as a novel gender-based biomarker in liver cirrhosis and cancer development.This finding could be essential in understanding why males may be more susceptible to developing HCC. To our knowledge, this is the first report showing FAU ribosomal protein in HCV-related cirrhosis with significant gender-based differences. FAU could serve as a valuable prognostic biomarker to monitor HCC disease progression and response to treatment

Proteomics study reveals a hydroxysteroid dehydrogenase (HSD) as a sex-based biomarker in Hepatitis C virus induced cirrhosis

Hepatitis C virus (HCV) infection-related inflammation, liver fibrosis and cirrhosis often lead to development of hepatocellular carcinoma (HCC). In the United States, 4.6 million people are infected with HCV. Studies show that chronic HCV infections are more prevalent in males and progress more rapidly to cirrhosis and cancer development as compared to females. In contrast, pre-menopausal females and women on hormone replacement therapy have been associated with less-severe disease through all stages of HCV infection. We have previously identified sex-based differences in the expression of estrogen receptors (ERs)in normal livers and dysregulated mRNA and protein expression of ER subtypes in both HCV-related cirrhosis and HCC suggesting a possible role in its pathogenesis. Sex based differential biomarkers could serve as an early prognostic tool for HCV cirrhosis and HCC development. The enzyme families including hydroxysteroid dehydrogenases (HSDs) contribute largely to the synthesis and degradation of steroid hormones such as testosterone and estrogen sex-hormones, as well as cholesterol and fatty acid metabolism. Chronic inflammation due to HCV infection in the liver may alter HSD enzyme regulation and affect hormone metabolism. We hypothesized that chronic HCV infection leads to dysregulated HSDs in male HCV cirrhosis patients leading to development of HCC. Our current study utilized proteomic analysis to determine sex-based differences in HSD protein expression in male and female HCV cirrhosis. We studied a total 40 liver tissues that included both sexes from HCV-related cirrhosis and normal controls. The liver tissues extracts were prepared and sent to NIH IDeA National Resource of Quantitative Proteomics core lab for DIA proteomic analysis. We were able to profile 4,443 genes belonging to different protein families that were differentially expressed in HCV cirrhosis and controls. Within the HSD protein cohort 7 exhibited differential expression in the liver cirrhosis groups compared to healthy controlss. Of these 7 proteins, only HSD17B13 demonstrated a significant sex-based differential expression between male and female HCV cirrhosis groups. More specifically, HCV cirrhosis females demonstrated a positive logFC value of 2.241 (p < 0.01) when compared to HCV cirrhosis males, suggesting HSD17B13 may serve as sex-based pre-cancerous biomarker. Further, HSD17B13 showed downregulation in HCV cirrhosis males compared to normal control males, but not significantly. No differences were observed in the remaining experimental groups (HCV F vs. normal control F and normal control M vs. normal control F). HSD17B13 protein may serve as a sex-based biomarker in liver cirrhosis and cancer development. To the best of our knowledge this is the first report showing sex-based differences in HSD proteins in premalignant HCV-related cirrhosis. Further, detailed studies may lead us to new sex-based tailored clinical therapies in halting cirrhosis and HCC progression in males

Estrogen receptor expression in chronic hepatitis C and hepatocellular carcinoma pathogenesis

AIM: To investigate gender-specific liver estrogen receptor (ER) expression in normal subjects and patients with hepatitis C virus (HCV)-related cirrhosis and hepatocellular carcinoma (HCC).METHODS: Liver tissues from normal donors and patients diagnosed with HCV-related cirrhosis and HCV-related HCC were obtained from the NIH Liver Tissue and Cell Distribution System. The expression of ER subtypes, ERa and ERB, were evaluated by Western blotting and real-time RT-PCR. The subcellular distribution of ERa and ERB was further determined in nuclear and cytoplasmic tissue lysates along with the expression of inflammatory [activated NF-KB and IKB-kinase (IKK)] and oncogenic (cyclin D1) markers by Western blotting and immunohistochemistry. The expression of ERa and ERB was correlated with the expression of activated NF-KB, activated IKK and cyclin D1 by Spearman's correlation.RESULTS: Both ER subtypes were expressed in normal livers but male livers showed significantly higher expression of ERa than females (P < 0.05). We observed significantly higher mRNA expression of ERa in HCV-related HCC liver tissues as compared to normals (P < 0.05) and ERB in livers of HCV-related cirrhosis and HCV-related HCC subjects (P < 0.05). At the protein level, there was a significantly higher expression of nuclear ERa in livers of HCV-related HCC patients and nuclear ERB in HCV-related cirrhosis patients as compared to normals (P < 0.05). Furthermore, we observed a significantly higher expression of phosphorylated NF-KB and cyclin D1 in diseased livers (P < 0.05). There was a positive correlation between the expression of nuclear ER subtypes and nuclear cyclin D1 and a negative correlation between cytoplasmic ER subtypes and cytoplasmic phosphorylated IKK in HCV-related HCC livers. These findings suggest that dysregulated expression of ER subtypes following chronic HCV-infection may contribute to the progression of HCV-related cirrhosis to HCV-related HCC.CONCLUSION: Gender differences were observed in ERa expression in normal livers. Alterations in ER subtype expression observed in diseased livers may influence gender-related disparity in HCV-related pathogenesis.Peer reviewedBiochemistry and MicrobiologyHealth Care AdministrationStatistic

Frequency of gall bladder metaplasia and its distribution in different regions of gall bladder in routine cholecystectomy specimens

Background: In India, gall stone disease is more common in women in the north, north east and east as compared to other zones in the country. Gall bladder metaplasia has been documented as the precursor lesion of dysplasia and therefore carcinoma. Present study was conducted to ascertain the frequency and type of metaplasia along with distribution in different regions of gall bladder.Methods: All the post cholecystectomy gallbladder samples submitted for histopathology comprised the study material. Three sections were from body, fundus, and neck each. The five microns thick paraffin sections were cut with microtome and stained with Hemotoxylin and Eosin (H and E).Results: The present study was conducted on 119 cholecystectomy specimens submitted for histopathological examination. Amongst premalignant lesions, cholecystitis with metaplasia was seen in 55 (46.2%) cases. Pyloric metaplasia without intestinal metaplasia was most common metaplasia (30.2%) followed by combined metaplasia (12.60%) and only intestinal metaplasia (3.36%). Out of 55 cases, fundus showed metaplasia in 47 followed by body (44) and neck (36).Conclusions: Very high frequency of metaplasias was observed (46.2%) in routine cholecystectomy specimen with pyloric metaplasia as the predominant type and intestinal metaplasia was accompanied with pyloric metaplasia in most of the cases. Metaplasia was found to be more or less equally distributed in different regions of gall bladder

17β-HSD13 has sex-based differential expression in Hepatitis C virus-induced cirrhosis and hepatocellular carcinoma

Background: Sex-based differences are observed in chronic hepatitis C virus (HCV) infections leading to cirrhosis and hepatocellular carcinoma (HCC). We previously showed that liver estrogen receptor (ER-) mediated sex-based differences exist in cirrhosis and HCC. Liver ER-binding may lead to protective effects in pre-menopausal women. This study aimed to determine sex-based differential role of 17βHSD13 in development of cirrhosis and HCC. We hypothesized that chronic HCV infection leads to dysregulated 17β-HSD13 in male cirrhosis and progression to HCC.Methods: 65 (normal, cirrhosis, HCC) liver tissues were obtained from NIH Liver Tissue Bank. DIA proteomics mapped 4445 proteins, including 17β-HSD13. Clinical correlation with bilirubin, AST, ALP, and creatinine was determined (spearman’s). Immunohistochemistry validated 17β-HSD13 protein expression in tissues.Results: 17β-HSD13 had significantly lower expression in male cirrhosis group than females (P<0.05). In contrast, 17β-HSD13 expression in normal males was significantly greater than normal females (P<0.05). In HCC group, the expression in males was down-regulated compared to HCC females (P<0.05). Bilirubin values showed negative correlation with 17β-HSD13 expression (P<0.05) between cirrhosis and HCC (males alone and combined sex data).Conclusions: Low 17β-HSD13 levels may predict worse disease in males with cirrhosis or HCC serving as disease biomarker. This novel report shows sex-based differences in 17β-HSD13 during HCV-induced cirrhosis development