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Targeting stroma and tumor,silencing galectin 1 treats orthotopic mouse hepatocellular carcinoma

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Acta Pharmaceutica Sinica B 2024年第1期14卷 292-303页

作者： Tahereh Setayesh Ying Hu Farzam Vaziri Xin Chen Jinping Lai Dongguang Wei Yu-Jui Yvonne Wan Department of Medical Pathology and Laboratory Medicine University of CaliforniaDavisSacramentoCA 95817USA Cancer Biology Program the University of Hawaii Cancer CenterHonoluluHI 96813USA Department of Pathology and Laboratory Medicine Kaiser Permanente Sacramento Medical CenterSacramentoCA 95825USA

This study examines inhibiting galectin 1(Gal1)as a treatment option for hepatocellular carcinoma(HCC).Gal1 has immunosuppressive and cancer-promoting roles.Our data showed that Gal1 was highly expressed in human and mouse HCC.The levels of Gal1 positively correlated with the stages of human HCC and negatively with survival.The roles of Gal1 in HCC were studied using overexpression(OE)or silencing using Igals1 siRNA delivered by AAV9.Prior to HCC initiation induced by RAS and AKT mutations,lgals1-OE and silencing had opposite impacts on tumor load.The treatment effect of lgals1 siRNAwas further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9%or even 42%of the body weight.Comparing spatial transcriptomic profiles of Gal1 silenced and OE HCC,inhibiting matrix formation and recognition of foreign antigen in CD45t cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 silencing.Within the tumors,silencing Gal1 inhibited translational initiation,elongation,and termination.Furthermore,Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor,and the anti-HCC effect of lgals1 siRNAwas CD8-dependent.Overall,Gal1 silencing has a promising potential for HCC treatment.

关键词： Liver Hepatocellular carcinoma Carbohydrate-binding lectin Galectin 1 Extracellular matrix Translation Spatial transcriptomics Tumor-margin

New insights of Helicobacter pylori host-pathogen interactions: The triangle of virulence factors, epigenetic modifications and non-coding RNAs

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World Journal of Clinical Cases 2018年第5期6卷 64-73页

作者： Farzam Vaziri Samira Tarashi Abolfazl Fateh Seyed Davar Siadat Microbiology Research Center Pasteur Institute of Iran Department of Mycobacteriology and Pulmonary Research Pasteur Institute of Iran

Helicobacter pylori(H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The progression and exacerbation of H. pylori infection are influenced by some factors of pathogen and host. Several virulence factors involved in the proper adherence and attenuation of immune defense to contribute the risk of emerging gastric cancer, therefore analysis of them is very important. H. pylori also modulates inflammatory and autophagy process to intensify its pathogenicity. From the host regard, different genetic factors particularly affect the development of gastric cancer. Indeed, epigenetic modifications, Micro RNA and long non-coding RNA received more attention. Generally, various factors related to pathogen and host that modulate gastric cancer development in response to H. pylori need more attention due to develop an efficacious therapeutic intervention. Therefore, this paper will present a brief overview of host-pathogen interaction especially emphases on bacterial virulence factors, interruption of host cellular signaling, the role of epigenetic modifications and non-coding RNAs.

关键词： Helicobacter pylori Epigenetic Virulence factor Non-coding RNAs Host pathogen interactions

Hepatocellular carcinoma immunotherapy:The impact of epigenetic drugs and the gut microbiome

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Liver Research 2020年第4期4卷 191-198页

作者： Farzam Vaziri Steven D.Colquhoun Yu-Jui Yvonne Wan Department of Pathology and Laboratory Medicine University of California DavisSacramentoCAUSA Department of Surgery University of California DavisSacramentoCAUSA

The incidence of hepatocellular carcinoma(HCC)has been increasing for decades.This disease has now risen to become the sixth most common malignancy overall,while ranking as the third most frequent cause of cancer mortality.While several surgical interventions and loco-regional treatment options are available,up to 80%of patients present with advanced disease not amenable to standard therapies.Indeed,traditional cytotoxic chemotherapeutic agents are notoriously ineffective and essentially play no role in the management of affected patients.This has led to an enormous need for more effective sys-temic therapeutic options.In recent years,immunotherapy has emerged as a potentially viable and exciting new alternative for the treatment of HCC.Although the current immunotherapeutic options remain imperfect,various strategies can be employed to further improve their efficacy.New findings have revealed epigenetic modulation can be effective as a new approach for improving HCC immuno-therapy.Studying the gut microbiome(gut-liver axis)can also be an interesting subject in this regard.Here,we explore the latest insights into the role of immunotherapy treating HCC,both mono and in combination with other agents.We also focus on the impact of epigenetic drugs and the microbiome in the overall effectiveness of HCC immunotherapy.

关键词： Hepatocellular carcinoma(HCC) Immunotherapy Gut microbiota Epigenetic drugs Combination therapy

Diversity of Helicobacter pylori genotypes in Iranian patients with different gastroduodenal disorders

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World Journal of Gastroenterology 2013年第34期19卷 5685-5692页

作者： Farzam Vaziri Shahin Najar Peerayeh Masoud Alebouyeh Tabassom Mirzaei Yoshio Yamaoka Mahsa Molaei Nader Maghsoudi Mohammad Reza Zali Department of Bacteriology Faculty of Medical SciencesTarbiat Modares University Gastroenterology and Liver Diseases Research Center Shahid Beheshti University of Medical Sciences Department of Environmental and Preventive-Medicine Oita University Faculty of Medicine Department of Medicine-Gastroenterology Baylor College of Medicine Basic and Molecular Epidemiology of Gastroin-testinal Disorders Research Center Shahid Beheshti University of Medical Sciences Neuroscience Research Center (NRC) Shahid Beheshti University of Medical Sciences

AIM:To investigate the diversity of Helicobacter pylori(H.pylori)genotypes and correlations with disease outcomes in an Iranian population with different gastroduodenal disorders.METHODS:Isolates of H.pylori from patients with different gastroduodenal disorders were analyzed after culture and identification by phenotypic and genotypic methods.Genomic DNA was extracted with the QIAamp DNA mini kit(Qiagen,Germany).After DNA extraction,genotyping was done for cagA,vacA(s and m regions),iceA(iceA1,iceA2)and babA with specific primers for each allele using polymerase chain reaction(PCR).All patients’pathologic and clinical data and their relation with known genotypes were analyzed by using SPSS version 19.0 software.2test and Fisher’s exact test were used to assess relationships between categorical variables.The level of statistical significance was set at P<0.05.RESULTS:A total of 71 isolates from 177 patients with different gastroduodenal disorders were obtained.Based on analysis of the cagA gene(positive or negative),vacA s-region(s1or s2),vacA m-region(m1or m2),iceA allelic type(iceA1and iceA2)and babA gene(positive or negative),twenty different genotypic combinations were recognized.The prevalence of cagA,vacA s1,vacA s2,vacA m1,vacA m2,iceA1,iceA2,iceA1+iceA2and babA were 62%,78.9%,19.7%,21.1%,78.9%,15.5%,22.5%,40.8%and 95.8%,respectively.Interestingly,evaluation of PCR results for cagA in 6 patients showed simultaneous existence of cagA variants according to their size diversities that proposed mixed infection in these patients.The most prevalent genotype in cagA-positive isolates was cagA+/vacAs1m2/iceA1+A2/babA+and in cagA-negative isolates was cagA-/vacAs1m2/iceA-/babA+.There were no relationships between the studied genes and histo-pathological findings(H.pylori density,neutrophil activity,lymphoid aggregation in lamina propria and glandular atrophy).The strains which carry cagA,vacAs1/m1,iceA2and babA genes showed significant associations with severe active chronic gastritis(P=0.011,0.025,0.020 and 0.031,r

关键词： Helicobacter pylori cagA vacA iceA babA