Glypican-3 is a prognostic factor and an immunotherapeutic target in hepatocellular carcinoma

Glypican-3(GPC3)is a cell surface oncofetal proteoglycan that is anchored by glycosylphosphatidylinositol.Whereas GPC3 is abundant in fetal liver,its expression is hardly detectable in adult liver.Importantly,GPC3is overexpressed in hepatocellular carcinoma(HCC),and several immunohistochemical studies reported that overexpression predicts a poorer prognosis for HCC patients.Therefore,GPC3 would serve as a useful molecular marker for HCC diagnosis and also as a target for therapeutic intervention in HCC.Indeed,some immunotherapy protocols targeting GPC3 are under investigations;those include humanized anti-GPC3cytotoxic antibody,peptide vaccine and immunotoxin therapies.When considering the clinical requirements for GPC3-targeting therapy,companion diagnostics to select the appropriate HCC patients are critical,and both immunohistochemical analysis of tissue sections and measurement of serum GPC3 level have been suggested for this purpose.This review summarizes current knowledge regarding the clinical implication of GPC3detection and targeting in the management of patients with HCC.

Biopsy-driven diagnosis in infants with cholestatic jaundice in Iran

AIM: To determine the frequencies of diagnoses confirmed by liver biopsy in infants with cholestasis in an Iranian pediatric hospital.

Identification of a new target region on the long arm of chromosome 7 in gastric carcinoma by loss of heterozygosity

AIM： To define the common deleted region on the long arm of haman chromosome 7q linked to primary gastric carcinomas in Chinese by loss of heterozygosity （LOH） and its clinical significance. METHODS： Nine microsatellite markers distributed over chromosome 7q with an average marker density of 10cM were used to examine 70 primary gastric carcinomas for LOH by PCR amplification. The PCR products were separated by electrophoresis on polyacrylamide gel. Genescan and Genotyper softwares were used to analyze LOH. RESULTS： LOH with at least one marker on 7q occurred in 34.3% （12/50） of the tumors. Among them, LOH at D7S486 and D7S798 was higher in 24.0% （24/70） and 29.2% （5/26）, respectively. By statistical analysis we also observed an obvious genotype-phenotype correlation on 7q （P〈0.05）. The frequency of LOH at D7S486 in patients with lymph node metastasis was significantly higher than that in those without lymph node metastasis （P=0.015）. CONCLUSION： The high incidence of LOH at D7S486 and its correlation with poorer prognosis suggest that there might be putative tumor suppressor genes in this region involved in the tumorigenesis and progression of gastric carcinoma.

Russell body gastritis with Dutcher bodies evaluated using magnification endoscopy

Russell body gastritis(RBG) is an unusual type of chronic gastritis characterized by marked infiltration of Mott cells,which are plasma cells filled with spherical eosinophilic bodies referred to as Russell bodies.It was initially thought that Helicobacter pylori(H.pylori) infection was a major cause of RBG and that the infiltrating Mott cells were polyphenotypic;however,a number of cases of RBG without H.pylori infection or with monoclonal Mott cells have been reported.Thus,diagnostic difficulty exists in distinguishing RBG with monoclonal Mott cells from malignant lymphoma.Here,we report an unusual case of an 86-year-old-Japanese man with H.pylori-positive RBG.During the examination of melena,endoscopic evaluation confirmed a 13-mm whitish,flat lesion in the gastric antrum.Magnification endoscopy with narrowband imaging suggested that the lesion was most likely a poorly differentiated adenocarcinoma.Biopsy findings were consistent with chronic gastritis with many Mott cells with intranuclear inclusions referred to as Dutcher bodies.Endoscopic submucosal dissection confirmed the diagnosis of RBG with kappa-restricted monoclonal Mott cells.Malignant lymphoma was unlikely given the paucity of cytological atypia and Ki-67 immunoreactivity of monoclonal Mott cells.This is the first reported case of RBG with endoscopic diagnosis of malignant tumor and the presence of Dutcher bodies.

Functional foods effective for hepatitis C: Identification of oligomeric proanthocyanidin and its action mechanism

Hepatitis C virus(HCV)is a major cause of viral hepatitis and currently infects approximately 170 million people worldwide.An infection by HCV causes high rates of chronic hepatitis(】75%)and progresses to liver cirrhosis and hepatocellular carcinoma ultimately.HCV can be eliminated by a combination of pegylatedα-interferon and the broad-spectrum antiviral drug ribavirin;however,this treatment is still associated with poor efficacy and tolerability and is often accompanied by serious side-effects.While some novel direct-actingantivirals against HCV have been developed recently,high medical costs limit the access to the therapy in cost-sensitive countries.To search for new natural anti-HCV agents,we screened local agricultural products for their suppressive activities against HCV replication using the HCV replicon cell system in vitro.We found a potent inhibitor of HCV RNA expression in the extracts of blueberry leaves and then identified oligomeric proanthocyanidin as the active ingredient.Further investigations into the action mechanism of oligomeric proanthocyanidin suggested that it is an inhibitor of heterogeneous nuclear ribonucleoproteins(hn RNPs)such as hn RNP A2/B1.In this review,we presented an overview of functional foods and ingredients efficient for HCV infection,the chemical structural characteristics of oligomeric proanthocyanidin,and its action mechanism.

A Study of Prevalence of Diabetes and Prediabetes in Patients of Non-Alcoholic Fatty Liver Disease and the Impact of Diabetes on Liver Histology in Coastal Eastern India

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is more common in diabetic patients. There are limited studies on clinical, biochemical and histological features of NAFLD patients who are diabetic. The aim of the study was to determine the prevalence of diabetes and prediabetes in a cohort of NAFLD patients and to compare anthropometry, biochemical and metabolic parameters and hepatic histology of diabetic NAFLD patients with non-diabetic NAFLD patients. Methods: 515 consecutive NAFLD patients diagnosed by abdominal ultrasound and 100 healthy controls were subjected to detailed anthropometric measurements and biochemical assays including blood sugars, LFT, lipid profile and HOMA. Diabetes and prediabetes were defined according to WHO criteria. Patients were categorized and compared according to the presence or absence of diabetes. Liver biopsy was performed in 240 NAFLD patients and the liver histology was also compared between the two groups. Statistical analysis was performed on SPSS 16. Results: 124 out of the 515 (24.08%) NAFLD patients were diabetics, 118 out of 515 (22.9%) were pre-diabetics, while only 3 out of 100 controls had impaired glucose tolerance. Diabetic patients were older. NAFLD patients with diabetes had significantly higher waist circumference [98.02 ± 12.01 vs 93.89 ± 8.8, p = 0.000] as compared to the NAFLD patients without diabetes. Fasting blood sugar [124 ± 46.3 vs 90.8 ± 10.2, p = 0.000], triglyceride level [218.4 ± 17.6 vs 192 ± 9, p = 0.03] and HOMA-IR [2.6 ± 0.36 vs 1.84 ± 0.2, p < 0.001] were significantly higher in NAFLD-diabetes group. Hypertension [35% vs 11.7%, p = 0.000] was commoner in diabetic NAFLD patients. Histopathology in the diabetic patients revealed steatosis alone in 34.2% cases, borderline NASH in 31.4% and definite NASH in 34.2%. Fatty change alone was noted in 16.5% cases, borderline NASH in 34.1%, while 49% had definite NASH on liver biopsy of NAFLD patients without diabetes. Fibrosis was noted in 31.4% in diabetic and 27% in non-diabetic patients. IR alone had a linear correlation with necroinflammatory activity. Conclusion: The prevalence of diabetes and prediabetes is six times more in NAFLD patients than in healthy controls. NAFLD patients with diabetes have higher metabolic risk factors such as large waistline, hypertension, high triglyceride levels and increased insulin resistance. Diabetes or pre diabetes patients per se do not have histologically severe disease, rather insulin resistance play an important role in increasing the severity of the disease.

Undergraduate Pathology Education: Meeting the Challenge Ahead

Background: In India, undergraduate medical education has remained more or less static and for last so many decades no effective development has been done. Therefore this study is done for restructuring it and to meet the challenges faced thereby. Material and methods: Depending on the problems faced during undergraduate pathology teaching, questions were prepared and sent to pathology teachers of Odisha. In few aspects, suggestions were also asked for modification of the present system of medical curriculum including the problem of factual or information overload on students. Results: 18 questions were prepared and asked to 96 pathology teachers. The opinions mostly were to introduce small group teaching or problem based learning (PBL) and multidisciplinary integrated teaching. The opinion of students of 3rd and 4th MBBS were also taken into consideration for taking the decisions of modification. Conclusion: Efforts should be taken to bring the desired changes in undergraduate pathology education to produce need based human resources for health care in society.

Assessing fertility preservation strategies: A scoping review

Objective:To describe the various options available for preserving female and/or male fertility,taking into account both social and medical aspects,and to identify the effects of different natural products on male infertility extracted from plants.Methods:We reviewed the literature and included full-text publications in English provided by international biomedical databases,including Sciences Direct,Google Scholar,OVID,PubMed,and MEDLINE between 2016 and 2023.Search terms,such as fertility preservation,in vitro maturation,cryopreservation,plants for the treatment of male infertility,were taken from Medical Subject Headings(MeSH)and Boolean operators were used to improve sensitivity.Results:112 papers were identified in the initial search,of which 18 were excluded due to duplication.After reviewing titles and abstracts,70 papers were finally included.The main findings of this study are presented under three key themes:gametogenesis,fertility preservation techniques,and plant-based alternatives.Regarding gametogenesis,significant progress has been made in understanding oocyte and sperm maturation,with optimized conditions improving maturation rates and motility.For fertility preservation,techniques such as rescue in vitro maturation and cryopreservation have shown the enhanced outcomes,particularly in maintaining gamete quality.Lastly,plant-based alternatives,including extracts and essential oils,have demonstrated potential in reducing oxidative stress,improving sperm motility,and supporting oocyte development,thus providing a promising complementary approach to conventional methods.Conclusions:Fertility preservation is achieved in a variety of ways,including oocyte and embryo vitrification and sperm cryopreservation,and the use of plant-based treatment of male infertility.