Advances in Immunotherapy in Hepatocellular Carcinoma.

Over the past several years, the therapeutic landscape for patients with advanced, unresectable, or metastatic hepatocellular carcinoma has been transformed by the incorporation of checkpoint inhibitor immunotherapy into the treatment paradigm. Frontline systemic treatment options have expanded beyond anti-angiogenic tyrosine kinase inhibitors, such as sorafenib, to a combination of immunotherapy approaches, including atezolizumab plus bevacizumab and durvalumab plus tremelimumab, both of which have demonstrated superior response and survival to sorafenib. Additionally, combination treatments with checkpoint inhibitors and tyrosine kinase inhibitors have been investigated with variable success.

VDAC2 and Bak scarcity in liver mitochondria enables targeting hepatocarcinoma while sparing hepatocytes.

Differences between normal tissues and invading tumors that allow tumor targeting while saving normal tissue are much sought after. Here we show that scarcity of VDAC2, and the consequent lack of Bak recruitment to mitochondria, renders hepatocyte mitochondria resistant to permeabilization by truncated Bid (tBid), a Bcl-2 Homology 3 (BH3)-only, Bcl-2 family protein. Increased VDAC2 and Bak is found in most human liver cancers and mitochondria from tumors and hepatic cancer cell lines exhibit VDAC2- and Bak-dependent tBid sensitivity.

Predictive validity of the sequential organ failure assessment score for mortality in patients with acute respiratory distress syndrome in Vietnam.

Evaluating the prognosis of ARDS patients using grading systems can enhance treatment decisions. This retrospective observational study evaluated the predictive accuracy of the SOFA score, APACHE II score, SpO/FiO ratio, and PaO/FiO ratio for mortality in ARDS patients in Vietnam. The study included 335 adult ARDS patients admitted to a central hospital from August 2015 to August 2023.

Prognosticating global functional outcome in the recurrent ischemic stroke using baseline clinical and pre-clinical features: A machine learning study.

Background And Purpose: Recurrent ischemic stroke (RIS) induces additional functional limitations in patients. Prognosticating globally functional outcome (GFO) in RIS patients is thereby important to plan a suitable rehabilitation programme. This study sought to investigate the ability of baseline features for classifying the patients with and without improving GFO (task 1) and identifying patients with poor GFO (task 2) at the third month after discharging from RIS.

Meningioma brain tumor detection and classification using hybrid CNN method and RIDGELET transform.

The detection of meningioma tumors is the most crucial task compared with other tumors because of their lower pixel intensity. Modern medical platforms require a fully automated system for meningioma detection. Hence, this study proposes a novel and highly efficient hybrid Convolutional neural network (HCNN) classifier to distinguish meningioma brain images from non-meningioma brain images.

Implementation of deep learning in liver pathology optimizes diagnosis of benign lesions and adenocarcinoma metastasis.

Introduction: Differentiation of histologically similar structures in the liver, including anatomical structures, benign bile duct lesions, or common types of liver metastases, can be challenging with conventional histological tissue sections alone. Accurate histopathological classification is paramount for the diagnosis and adequate treatment of the disease. Deep learning algorithms have been proposed for objective and consistent assessment of digital histopathological images.

Tumor biology and immune infiltration define primary liver cancer subsets linked to overall survival after immunotherapy.

Primary liver cancer is a rising cause of cancer deaths in the US. Although immunotherapy with immune checkpoint inhibitors induces a potent response in a subset of patients, response rates vary among individuals. Predicting which patients will respond to immune checkpoint inhibitors is of great interest in the field.

Stiff matrix induces exosome secretion to promote tumour growth.

Tissue fibrosis and extracellular matrix (ECM) stiffening promote tumour progression. The mechanisms by which ECM regulates its contacting cells have been extensively studied. However, how stiffness influences intercellular communications in the microenvironment for tumour progression remains unknown.

Heterocyclic amines detected in cooked meats and fishes from street markets and restaurants in the city of Hanoi, Vietnam: A Pilot local field investigation findings in 2020.

Background: Street food has been a typical culinary feature of many countries. These foods, mainly, meats and fish, were often fried, and grilled with varied marinade and preparation. However, foods that contain a lot of protein after processing at high temperatures always have many risks, including cancer risks of which heterocyclic aromatic amines (HAAs) have been one of the typical compounds.

Lung_PAYNet: a pyramidal attention based deep learning network for lung nodule segmentation.

Accurate and reliable lung nodule segmentation in computed tomography (CT) images is required for early diagnosis of lung cancer. Some of the difficulties in detecting lung nodules include the various types and shapes of lung nodules, lung nodules near other lung structures, and similar visual aspects. This study proposes a new model named Lung_PAYNet, a pyramidal attention-based architecture, for improved lung nodule segmentation in low-dose CT images.

Reduced Rates of Post-Transplant Recurrent Hepatocellular Carcinoma in Non-Alcoholic Steatohepatitis: A Propensity Score Matched Analysis.

Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) has become the second leading cause of HCC-related liver transplantation in the United States. This study investigated post-transplant recurrence and survival for patients transplanted for NASH-related HCC compared to non-NASH HCC etiologies. Retrospective review of the United Network for Organ Sharing (UNOS) Organ Procurement and Transplantation Network (OPTN) database identified 7,461 patients with HCC-1,405 with underlying NASH and 6,086 with non-NASH underlying diseases.

The role of RNA binding proteins in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of overall cancer deaths worldwide with limited therapeutic options. Due to the heterogeneity of HCC pathogenesis, the molecular mechanisms underlying HCC development are not fully understood. Emerging evidence indicates that RNA-binding proteins (RBPs) play a vital role throughout hepatocarcinogenesis.

Single-cell biology uncovers apoptotic cell death and its spatial organization as a potential modifier of tumor diversity in HCC.

Background And Aims: HCC is a highly aggressive and heterogeneous cancer type with limited treatment options. Identifying drivers of tumor heterogeneity may lead to better therapeutic options and favorable patient outcomes. We investigated whether apoptotic cell death and its spatial architecture is linked to tumor molecular heterogeneity using single-cell in situ hybridization analysis.

Noninvasive risk stratification of intraductal papillary mucinous neoplasia with malignant potential by serum apolipoprotein-A2-isoforms.

Intraductal papillary mucinous neoplasms (IPMNs) are premalignant lesions of pancreatic cancer. An accurate serum biomarker, which allows earlier identification of asymptomatic individuals with high-risk for developing cancer, is of urgent need. Apolipoprotein A2-isoforms (apoA2-i) have previously been identified as biomarkers in pancreatic cancer.

Evaluating Outcomes Related to Donor and Recipient Metabolic Environment: Macrosteatotic Allografts and Nonalcoholic Steatohepatitis.

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) affects both recipient and donor populations in liver transplantation. Presently, it is unclear whether transplantation of macrosteatotic allografts is affected by the metabolic milieu of liver transplant recipients. This study investigates fatty liver disease at the intersection of donor and recipient.

Tumor metabolism and associated serum metabolites define prognostic subtypes of Asian hepatocellular carcinoma.

Treatment effectiveness in hepatocellular carcinoma (HCC) depends on early detection and precision-medicine-based patient stratification for targeted therapies. However, the lack of robust biomarkers, particularly a non-invasive diagnostic tool, precludes significant improvement of clinical outcomes for HCC patients. Serum metabolites are one of the best non-invasive means for determining patient prognosis, as they are stable end-products of biochemical processes in human body.

Attachment of human adenovirus onto household paints.

Attachment of human adenovirus 40 (HAdV40) onto surfaces coated with three compositionally different household paints was evaluated experimentally and interpreted based on measured physicochemical properties of the paints. Polar, dispersive and electrostatic interactions between HAdV40 and the paints were predicted using the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) model. Quartz crystal microbalance (QCM-D) was used to quantify virus attachment to paints from 1 mM and 150 mM NaCl solutions, with the latter having the ionic strength of a typical respiratory fluid.

Simultaneous liver kidney allocation policy and the Safety Net: an early examination of utilization and outcomes in the United States.

Rates of simultaneous liver kidney (SLK) transplantation in the United States have progressively risen. On 8/10/17, the Organ Procurement and Transplantation Network implemented a policy defining criteria for SLK, with a "Safety Net" to prioritize kidney allocation to liver recipients with ongoing renal failure. We performed a retrospective review of the United Network for Organ Sharing (UNOS) database to evaluate policy impact on SLK, kidney after liver (KAL) and kidney transplant alone (KTA).

Population genetic structure and demographic history of the dipterocarp species Anisoptera costata Korth revealed by microsatellite analysis.

Moderate levels of genetic diversity and differentiation of Anisoptera costata were determined. A population divergence occurred during Younger Dryas. The anthropogenic disturbance had significantly affected the genetic diversity of the species in low tropical forests.

Hepatocellular Carcinoma-The Influence of Immunoanatomy and the Role of Immunotherapy.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality worldwide. Most patients are diagnosed with advanced disease, limiting their options for treatment. While current treatments are adequate for lower staged disease, available systemic treatments are limited, with marginal benefit at best.

Serum IL6 as a Prognostic Biomarker and IL6R as a Therapeutic Target in Biliary Tract Cancers.

Purpose: Biliary tract cancer (BTC) is a heterogeneous group of rare gastrointestinal malignancies with dismal prognosis often associated with inflammation. We assessed the prognostic value of IL6 and YKL-40 compared with CA19-9 before and during palliative chemotherapy. We also investigated in mice whether IL6R inhibition in combination with gemcitabine could prolong chemosensitivity.

Hepatic Stellate Cells and Hepatocarcinogenesis.

Hepatic stellate cells (HSCs) are a significant component of the hepatocellular carcinoma (HCC) tumor microenvironment (TME). Activated HSCs transform into myofibroblast-like cells to promote fibrosis in response to liver injury or chronic inflammation, leading to cirrhosis and HCC. The hepatic TME is comprised of cellular components, including activated HSCs, tumor-associated macrophages, endothelial cells, immune cells, and non-cellular components, such as growth factors, proteolytic enzymes and their inhibitors, and other extracellular matrix (ECM) proteins.

Intratumoral γδ T-Cell Infiltrates, Chemokine (C-C Motif) Ligand 4/Chemokine (C-C Motif) Ligand 5 Protein Expression and Survival in Patients With Hepatocellular Carcinoma.

Background And Aims: Hepatocellular carcinoma (HCC) is an aggressive malignancy which is often associated with a complex tumor microenvironment attributable to etiology-induced cellular inflammation. γδ T cells are known to detect and react to chronic inflammation, which is linked to cancer development, progression, and metastasis. Our recent genomic study revealed an increased infiltration of several immune cell types, including γδ T cells, in tumor microenvironments of a Thai HCC subtype associated with a good prognosis.