Project description:BACKGROUND & AIMS: Expression of microRNAs (miRNAs) in metastatic foci of hepatocellular carcinoma (HCC) is unknown. We identified metastasis-related miRNAs in recurrent cases after living donor liver transplantation (LDLT). Methods: We performed a comprehensive analysis of primary HCC (T), noncancerous liver (N), and resected recurrent (metastatic) HCC (M) using microarray analyses to identify metastasis-related miRNAs in in three patients with post-transplant recurrence. The RNA samples from three cases that underwent resection of recurrences after LDLT were made available for miRNA microarray analysis. The three cases included a 57-year-old man (case 1) with peritoneal recurrence and infected by hepatitis B virus (HBV), and a 48-year-old woman (case 2) and a 51-year-old man (case 3) with lung recurrences and hepatitis C virus (HCV) infection. Microarray analysis was performed for each RNA sample from the (T), (N) in the explanted liver, and (M). A sample containing equal amounts of RNAs from histologically normal livers of three living donors (NL: normal liver) was analyzed as a control. The RNA samples from three cases that underwent resection of recurrences after living donor liver transplantation were made available for microRNA microarray analysis. Microarray analysis was performed for each RNA sample from the primary HCC (T), noncancerous liver (N) in the explanted liver, and resected recurrent metastatic HCC (M). A sample containing equal amounts of RNAs from histologically normal livers of three living donors (NL: normal liver) was analyzed as a control.
Project description:We used array-based comparative genomic hybridization (arrayCGH) of 76 hepatocellular carcinomas (HCCs) to search for genetically disrupted genes.
Project description:We used array-based comparative genomic hybridization (arrayCGH) of 76 hepatocellular carcinomas (HCCs) to search for genetically disrupted genes. Seventy-six HCC clinical specimens were analyzed. Genomic DNA of the tumor sample was labeled with Cy5 and reference normal DNA (Promega) was labeled with Cy3.
Project description:Hepatocellular carcinoma (HCC) arises from hepatocytes and accounts for 90% of primary liver cancer. According to Global Cancer Incidence, Mortality and Prevalence (GLOBOCAN) 2020, globally HCC is the sixth most common cancer and the third most common cause of cancer-related deaths. Reasons for HCC prognosis remaining dismal are that HCC is asymptomatic in its early stages, leading to late diagnosis, and it is markedly resistant to conventional chemo- and radiotherapy. Liver transplantation is the treatment of choice in early stages, while surgical resection, radiofrequency ablation (RFA) and trans arterial chemoembolization (TACE) are Food and Drug Administration (FDA)-approved treatments for advanced HCC. Additional first line therapy for advanced HCC includes broad-spectrum tyrosine kinase inhibitors (TKIs), such as sorafenib and lenvatinib, as well as a combination of immunotherapy and anti-angiogenesis therapy, namely atezolizumab and bevacizumab. However, these strategies provide nominal extension in the survival curve, cause broad spectrum toxic side effects, and patients eventually develop therapy resistance. Some common mutations in HCC, such as in telomerase reverse transcriptase (TERT), catenin beta 1 (CTNNB1) and tumor protein p53 (TP53) genes, are still considered to be undruggable. In this context, identification of appropriate gene targets and specific gene delivery approaches create the potential of gene- and immune-based therapies for the safe and effective treatment of HCC. This review elaborates on the current status of HCC treatment by focusing on potential gene targets and advanced techniques, such as oncolytic viral vectors, nanoparticles, chimeric antigen receptor (CAR)-T cells, immunotherapy, and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9), and describes future prospects in HCC treatment.
Project description:BACKGROUND & AIMS: Expression of microRNAs (miRNAs) in metastatic foci of hepatocellular carcinoma (HCC) is unknown. We identified metastasis-related miRNAs in recurrent cases after living donor liver transplantation (LDLT). Methods: We performed a comprehensive analysis of primary HCC (T), noncancerous liver (N), and resected recurrent (metastatic) HCC (M) using microarray analyses to identify metastasis-related miRNAs in in three patients with post-transplant recurrence. The RNA samples from three cases that underwent resection of recurrences after LDLT were made available for miRNA microarray analysis. The three cases included a 57-year-old man (case 1) with peritoneal recurrence and infected by hepatitis B virus (HBV), and a 48-year-old woman (case 2) and a 51-year-old man (case 3) with lung recurrences and hepatitis C virus (HCV) infection. Microarray analysis was performed for each RNA sample from the (T), (N) in the explanted liver, and (M). A sample containing equal amounts of RNAs from histologically normal livers of three living donors (NL: normal liver) was analyzed as a control.
Project description:Background:
There are about 100 trillion microbial cells in a person s gut. This is called the human gut microbiota. When this is disrupted, it can lead to many diseases. Studies show that the gut microbiota in people with cancer is different than that found in healthy people. Researchers want to study links between the gut microbiota and the immune system in people with a liver disease called hepatocellular carcinoma (HCC).
Objective:
To study links between gut microbiota and the immune system in people with HCC.
Eligibility:
People at least 18 years old with HCC. They must be scheduled to have tumors removed by surgery.
Design:
* People having surgery for primary liver tumors at the Mount Sinai Medical Center will be screened for this study.
* At the initial visit, blood, rectal swabs, urine, and stool will be collected. Participants will answer questions about their medical condition.
* Before surgery, blood, rectal swabs, urine, and stool will be collected. This will be done at a routine visit.
* When they have surgery, a piece of liver tissue with the tumor will be collected. This will be sent to the National Cancer Institute for tests.
* After surgery, blood, rectal swabs, urine, and stool will be collected 3 times. This will be done at routine visits.
Project description:We analyzed the proteome of tumor and matched non-tumor biopsies from 51 treatment-naive Hepatocellular carcinoma (HCC) patients by DIA (SWATH). Thereby we aim to find subgroups of patients characterized by specific pathway activation. Furthermore, we aim to find novel factors involved in HCC development and novel biomarkers.
Project description:Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related deaths in the world. More than half of patients with HCC present with advanced stage, and highly active systemic therapies are crucial for improving outcomes. Immune checkpoint inhibitor (ICI)-based therapies have emerged as novel therapy options for advanced HCC. Only one third of patients achieve an objective response with ICI-based therapies due to primary resistance or acquired resistance. The liver tumor microenvironment is naturally immunosuppressive, and specific mutations in cell signaling pathways allow the tumor to evade the immune response. Next, gene sequencing of the tumor tissue or circulating tumor DNA may delineate resistance mechanisms to ICI-based therapy and provide a rationale for novel combination therapies. In this review, we discuss the results of key clinical trials that have led to approval of ICI-based therapy options in advanced HCC and summarize the ongoing clinical trials. We review resistance mechanisms to ICIs and discuss how immunotherapies may be optimized based on the emerging research of tumor biomarkers and genomic alterations.