Impact of Antibiotics and Chronic Medications on Efficacy of Immune Checkpoint Inhibitors in Patients With Hepatocellular Carcinoma.

Background And Aims: The interaction of immune checkpoint inhibitors (ICI) and concomitant medications such as antibiotics, metformin, statins, beta-blockers, proton pump inhibitors (PPIs), nonsteroidal anti-inflammatory drugs (NSAIDs), and low-dose aspirin has been studied in other malignancies. Our study aims to investigate the relationship between these medications and ICI efficacy in patients with advanced hepatocellular carcinoma (aHCC).

Methods: A retrospective review of patients who received at least one dose of ICIs between May 2015 and November 2019 was performed.

Clinical Efficacy and Safety of Novel Anticoagulants for the Management of Venous Thromboembolism in Patients with Cancer: A Systematic Review and Meta-Analysis.

Purpose: Cancer patients face a four- to sevenfold higher risk of venous thromboembolism (VTE) than the general population. Novel oral anticoagulants (NOACs) provide convenient alternatives to traditional therapies.

Methods: We performed a systematic literature search across PubMed, Embase, and the Cochrane Library, targeting studies that examined the use of NOACs in cancer-associated VTE.

Single-cell RNA sequencing reveals anti-tumor potency of CD56 NK cells and CD8 T cells in humanized mice via PD-1 and TIGIT co-targeting.

In solid tumors, the exhaustion of natural killer (NK) cells and cytotoxic T cells in the immunosuppressive tumor microenvironment poses challenges for effective tumor control. Conventional humanized mouse models of hepatocellular carcinoma patient-derived xenografts (HCC-PDX) encounter limitations in NK cell infiltration, hindering studies on NK cell immunobiology. Here, we introduce an improved humanized mouse model with restored NK cell reconstitution and infiltration in HCC-PDX, coupled with single-cell RNA sequencing (scRNA-seq) to identify potential anti-HCC treatments.

GATA4 downregulation enhances CCL20-mediated immunosuppression in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a deadly cancer with a high global mortality rate, and the downregulation of GATA binding protein 4 (GATA4) has been implicated in HCC progression. In this study, we investigated the role of GATA4 in shaping the immune landscape of HCC.

Methods: HCC tumor samples were classified into "low" or "normal/high" based on GATA4 RNA expression relative to adjacent non-tumor liver tissues.

Sex differences in cancer and immunotherapy outcomes: the role of androgen receptor.

Across the wide range of clinical conditions, there exists a sex imbalance where biological females are more prone to autoimmune diseases and males to some cancers. These discrepancies are the combinatory consequence of lifestyle and environmental factors such as smoking, alcohol consumption, obesity, and oncogenic viruses, as well as other intrinsic biological traits including sex chromosomes and sex hormones. While the emergence of immuno-oncology (I/O) has revolutionised cancer care, the efficacy across multiple cancers may be limited because of a complex, dynamic interplay between the tumour and its microenvironment (TME).

Cost-effectiveness analysis of atezolizumab plus bevacizumab compared with sorafenib as first-line treatment in advanced hepatocellular carcinoma in Singapore.

Objectives: This study aims to explore the cost-effectiveness of atezolizumab plus bevacizumab against sorafenib for first-line treatment of locally advanced or metastatic hepatocellular carcinoma (HCC) in Singapore.

Methods: A partitioned survival model was developed from a healthcare system perspective, with a 10-year lifetime horizon. Clinical inputs and utilities were obtained from the IMbrave150 trial.

Variations in the sleep-related breathing disorder index on polysomnography between men with HIV and controls: a matched case-control study.

Background: Both sleep-related breathing disorders (SRBDs) and HIV infection can interfere with normal sleep architecture, and also cause physical and psychological distress. We aimed to understand the differences in the obstructive patterns, sleep architecture, physical and psychological distress when compared between people living with HIV (PLWH) and matched the severity of SRBDs controls.

Methods: A comparative study using matched case-control design was conducted.

Hepatocellular Carcinoma: Current Drug Therapeutic Status, Advances and Challenges.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for ~90% of liver neoplasms. It is the second leading cause of cancer-related deaths and the seventh most common cancer worldwide. Although there have been rapid developments in the treatment of HCC over the past decade, the incidence and mortality rates of HCC remain a challenge.

Efficacy and Safety of Cell-based Immunotherapy in The Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma - A Systematic Review and Meta-analysis.

Background: Recurrent/Metastatic Nasopharyngeal Carcinoma (RM-NPC) remains difficult to treat and contributes to considerable mortality. The first-line treatment for RM-NPC is Gemcitabine and Cisplatin and second-line treatment options differ. The endemic variant of NPC is associated with Epstein-Barr Virus (EBV).

Assessing the diversity and determinants of health-related quality of life measures in patients with acute heart failure.

Aims: Heart failure with reduced ejection fraction (HFrEF) significantly impacts health-related quality of life (HR-QoL). Existing HR-QoL questionnaires can show inconsistencies, potentially misrepresenting patient self-reports. This study examines the variation in HR-QoL measurement tools for HFrEF patients, identifying related determinants.

The Prognostic Value of CD39 as a Marker of Tumor-Specific T Cells in Triple-Negative Breast Cancer in Asian Women.

Triple-negative breast cancer (TNBC) has a poor prognosis with limited therapeutic options available for affected patients. Efforts are ongoing to identify surrogate markers for tumor-specific CD8 T cells that can predict the response to immune checkpoint inhibitor (ICI) therapies, such as programmed cell death protein 1 or programmed cell death ligand-1 blockade. We have previously identified tumor-specific CD39CD8 T cells in non-small cell lung cancer that might help predict patient responses to programmed cell death protein 1 or programmed cell death ligand-1 blockade.

Pathogenesis and therapeutic implications of EBV-associated epithelial cancers.

Epstein-Barr virus (EBV), one of the most common human viruses, has been associated with both lymphoid and epithelial cancers. Undifferentiated nasopharyngeal carcinoma (NPC), EBV associated gastric cancer (EBVaGC) and lymphoepithelioma-like carcinoma (LELC) are amongst the few common epithelial cancers that EBV has been associated with. The pathogenesis of EBV-associated NPC has been well described, however, the same cannot be said for primary pulmonary LELC (PPLELC) owing to the rarity of the cancer.

Multimodal molecular landscape of response to Y90-resin microsphere radioembolization followed by nivolumab for advanced hepatocellular carcinoma.

Background: Combination therapy with radioembolization (yttrium-90)-resin microspheres) followed by nivolumab has shown a promising response rate of 30.6% in a Phase II trial (CA209-678) for advanced hepatocellular carcinoma (HCC); however, the response mechanisms and relevant biomarkers remain unknown.

Methods: By collecting both pretreatment and on-treatment samples, we performed multimodal profiling of tissue and blood samples and investigated molecular changes associated with favorable responses in 33 patients from the trial.

A review on paying for advanced cancer therapeutics: hard truths and realities in Asia.

Health system expenditure on cancer drugs is rising rapidly in many countries given the high-priced novel treatments as well as the increasing usage due to a growing and ageing global population. The cost of cancer care continues to outstrip other diseases and it presents a global challenge to treatment access and cancer outcomes. Substantial variability exists in drug pricing across Asia, with low- or middle-income countries being heavily impacted.

Operational Challenges of an Asia-Pacific Academic Oncology Clinical Trial.

Purpose: The Asia-Pacific (APAC) region is a major focus for multinational clinical trials, although its cultural, linguistic, economic, and regulatory diversity pose significant challenges for trial conduct, particularly for academic clinical trials.

Methods: We describe our experience running the investigator-initiated phase III randomized, fully accrued, Aspirin for Dukes C and high-risk Dukes B Colorectal cancer trial (ASCOLT, ClinicalTrials.gov identifier: NCT00565708, N = 1,587), studying the benefit of aspirin in resected high-risk colorectal cancer.

Immunohistochemical scoring of LAG-3 in conjunction with CD8 in the tumor microenvironment predicts response to immunotherapy in hepatocellular carcinoma.

Introduction: Immune checkpoint blockade (ICB) is a systemic therapeutic option for advanced hepatocellular carcinoma (HCC). However, low patient response rates necessitate the development of robust predictive biomarkers that identify individuals who will benefit from ICB. A 4-gene inflammatory signature, comprising , , , and , was recently shown to be associated with a better overall response to ICB in various cancer types.

The East Asian gut microbiome and its role in oncology: a narrative review.

The field of onco-microbiome is rapidly expanding. Multiple studies have shown the crucial role of gut microbiota in the regulation of nutrient metabolism, immunomodulation and protection against pathogens. Tools for manipulating the gut microbiota include dietary modification and faecal microbiota transfer.

Assessment of subclinical cardiac dysfunction by speckle-tracking echocardiography among people living with human immunodeficiency virus.

Background: People living with HIV (PLWH) have an increased risk of developing cardiovascular diseases (CVD). As speckle-tracking echocardiography (STE) has been used to detect subclinical myocardial abnormalities, this study aims to detect early cardiac impairment among Asian PLWH using STE and to investigate the associated risk factors.

Methods: We consecutively recruited asymptomatic PLWH without previous CVD from a medical center of Taiwan, and their cardiac function was evaluated by conventional echocardiogram and STE.

Organoids as an Enabler of Precision Immuno-Oncology.

Since the dawn of the past century, landmark discoveries in cell-mediated immunity have led to a greater understanding of the innate and adaptive immune systems and revolutionised the treatment of countless diseases, including cancer. Today, precision immuno-oncology (I/O) involves not only targeting immune checkpoints that inhibit T-cell immunity but also harnessing immune cell therapies. The limited efficacy in some cancers results mainly from a complex tumour microenvironment (TME) that, in addition to adaptive immune cells, comprises innate myeloid and lymphoid cells, cancer-associated fibroblasts, and the tumour vasculature that contribute towards immune evasion.

The clinical efficacy of melatonin in the treatment of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

Background: The COVID-19 pandemic has resulted in significant morbidity and mortality worldwide, with cytokine storm leading to exaggerating immune response, multi-organ dysfunction and death. Melatonin has been shown to have anti-inflammatory and immunomodulatory effects and its effect on COVID-19 clinical outcomes is controversial. This study aimed to conduct a meta-analysis to evaluate the impact of melatonin on COVID-19 patients.

Unravelling the role of obesity and lipids during tumor progression.

The dysregulation of the biochemical pathways in cancer promotes oncogenic transformations and metastatic potential. Recent studies have shed light on how obesity and altered lipid metabolism could be the driving force for tumor progression. Here, in this review, we focus on liver cancer and discuss how obesity and lipid-driven metabolic reprogramming affect tumor, immune, and stroma cells in the tumor microenvironment and, in turn, how alterations in these cells synergize to influence and contribute to tumor growth and dissemination.

Cost-effectiveness of Intensive vs Standard Blood Pressure Control Among Older Patients With Hypertension.

Importance: Older patients with hypertension receiving intensive systolic blood pressure control (110-130 mm Hg) have lower incidences of cardiovascular events than those receiving standard control (130-150 mm Hg). Nevertheless, the mortality reduction is insignificant, and intensive blood pressure management results in more medical costs from treatments and subsequent adverse events.

Objective: To examine the incremental lifetime outcomes, costs, and cost-effectiveness of intensive vs standard blood pressure control in older patients with hypertension from the health care payer's perspective.

Conditional Knockout of Hypoxia-Inducible Factor 1-Alpha in Tumor-Infiltrating Neutrophils Protects against Pancreatic Ductal Adenocarcinoma.

Large numbers of neutrophils infiltrate tumors and comprise a notable component of the inflammatory tumor microenvironment. While it is established that tumor cells exhibit the Warburg effect for energy production, the contribution of the neutrophil metabolic state to tumorigenesis is unknown. Here, we investigated whether neutrophil infiltration and metabolic status promotes tumor progression in an orthotopic mouse model of pancreatic ductal adenocarcinoma (PDAC).