PASS-01: Randomized Phase II Trial of Modified FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel and Molecular Correlatives for Previously Untreated Metastatic Pancreatic Cancer.

Purpose: To assess modified folinic acid/leucovorin, fluorouracil, irinotecan, oxaliplatin (FOLFIRINOX; mFFX) versus gemcitabine/nab-paclitaxel (GnP) in de novo metastatic pancreatic ductal adenocarcinoma (PDAC) and explore predictive biomarkers.

Patients And Methods: Patients were randomly assigned 1:1 to mFFX or GnP with exclusion of germline pathogenic variants in or . The primary end point was progression-free survival (PFS) between arms with 0.

Identification of Targetable Mutations in Ovarian Cancer.

Purpose: mutations are classically seen in non-small cell lung cancers (NSCLCs), and EGFR-directed inhibitors have changed the therapeutic landscape in patients with -mutated NSCLC. The real-world prevalence of -mutated ovarian cancers has not been previously described. We aim to determine the prevalence of pathogenic or likely pathogenic mutations in ovarian cancer and describe a case of -mutated metastatic ovarian cancer with a durable response to osimertinib, an EGFR-directed targeted therapy.

Ion channels in NK cells: signaling and functions.

Ion channels are integral membrane proteins which facilitate rapid transport of small ions into and out of the cell and between organelles and cytosol. Cytolytic lymphocytes including natural killer (NK) cells principally kill virus-infected and cancer cells by releasing cytolytic granules within the immunological synapse, formed between target and effector cells. This process strongly depends on Ca2+ signaling, which in human NK cells is controlled by the phospholipase C (PLCγ)/inositol-1,4,5-triphospate receptor (IP3R)/calcium release-activated calcium channel (CRAC) axis.

Challenges in the return of molecular tumor profiling results.

Next-generation sequencing (NGS) has transformed cancer care by providing essential insights for diagnosis, prognosis, and treatment. However, variability in testing timing, reporting practices, and interpretation challenges limits its clinical impact. This manuscript highlights key opportunities to optimize somatic reporting, emphasizing the importance of timely testing throughout the cancer care continuum to maximize the diagnostic and therapeutic relevance of findings.

p53 isoforms have a high aggregation propensity, interact with chaperones and lack binding to p53 interaction partners.

The p53 transcription factor family consists of the three members p53, p63, and p73. Both p63 and p73 exist in different isoforms that are well characterized. Isoforms have also been identified for p53 and it has been proposed that they are responsible for increased cancer metastasis.

Binding of autotransporter adhesin CbpF to human CEACAM1 and CEACAM5: A Velcro model for bacterium adhesion.

In eukaryotic systems, three major types of cell junctions have been well characterized. While bacterial adhesion mechanisms also exhibit remarkable diversity, the molecular processes that regulate the dynamic modulation of binding strength between elongated bacterial cells and host cells remain poorly understood. () utilizes the surface adhesin CbpF to interact with the highly expressed host receptors CEACAM1 and CEACAM5 on cancer cells to facilitate tumor colonization.

Sensitization of cancer cells to DNA-damaging agents by expression of the REV1 C-terminal domain: Implications for chemotherapy.

The mutagenic translesion synthesis (TLS) pathway, which is critically dependent on REV1's ability to recruit inserter TLS polymerases and the POLζ extender polymerase, enables cancer cells to bypass DNA lesions while introducing mutations that likely contribute to the development of chemotherapy resistance and secondary malignancies. Targeting this pathway represents a promising therapeutic strategy. Here, we demonstrate that the expression of the C-terminal domain (CTD) of human REV1, a ca.

Advancing breast cancer and lung cancer screening: Expert perspectives to advance programmes in Singapore.

Introduction: The high prevalence and mortality rates of breast cancer and lung cancer in Singapore necessitate robust screening programmes to enable early detection and intervention for improved patient outcomes, yet 2024 uptake and coverage remain suboptimal. This narrative review synthesises expert perspectives from a recent roundtable discussion and proposes strategies to advance breast cancer and lung cancer screening programmes.

Method: A 2024 roundtable convened clinical practitioners, health policymakers, researchers and patient advocates discussed current challenges and opportunities for improving cancer screening in Singapore.

In silico design, synthesis of a novel chalcone derivative and its in vitro and in vivo anticancer activity against colon cancer-induced mouse model.

This study aimed to synthesize and evaluate the anticancer activity of novel chalcone derivative against colon cancer by in vitro cytotoxicity against HCT-116 (Research Resource Identifiers:CVCL_D4JB) cell line and in vivo using EAC (Research Resource Identifiers: CVCL_1306) and DLA (Research Resource Identifiers: CVCL_VR37) cells inoculated Swiss albino mice. The present study aimed to synthesize the new chalcone derivatives and conduct its anti-colon cancer activity both in vitro and in vivo. The designed compounds were subjected to in silico studies like binding pocket analysis, molecular docking, and ADME studies.

New Experimental Mouse Models to Evaluate the Role of Transforming Growth Factor-Beta in Liver Tumorigenesis.

Background And Aims: Hepatocellular carcinoma (HCC) has a poor prognosis and limited treatment options. TGF-β is a promising therapeutic target, but its dual role, as both a tumour suppressor and promoter, complicates its clinical application. While its effects on tumour cells are increasingly understood, its impact on the tumour stroma remains unclear.

Replication-competent adenovirus reporters utilizing endogenous viral expression architecture.

Unlabelled: Adenoviruses are double-stranded DNA viruses widely used as platforms for vaccines, oncolytics, and gene delivery. However, tools for studying adenoviral gene expression in real time during infection remain limited. Here, we describe a set of fluorescent and bioluminescent reporter viruses built using the modular AdenoBuilder reverse genetics system and informed by high-resolution maps of Ad5 transcription.

The Specific Genomic Alterations and Molecular Mechanisms of Liver Metastases in Patients with Lung Adenocarcinoma.

Given the limited diagnostic technologies and treatment options available for lung adenocarcinoma (LUAD) patients with liver metastases, it is crucial to identify potential genomic signatures associated with liver metastasis, which could significantly contribute to the development of improved diagnostic tools and treatment strategies for LUAD patients with liver metastases. In this study, we identified specific genetic alterations in tumor samples with liver metastases by targeted capture sequencing. The results showed that the significantly higher mutation frequencies of , and in LUAD patients with liver metastases and and mutations found in both tumor tissues and plasma samples from patients with liver metastases.

Impact of TP53, KRAS, and APC Mutations on Neoadjuvant Chemotherapy Outcomes in Locally Advanced Rectal Cancer.

Despite recent advances in neoadjuvant strategies for locally advanced rectal cancer (LARC), optimal chemotherapy regimens and the role of genetic biomarkers in guiding treatment remain unclear. Moreover, predictive markers are urgently needed for radiation-sparing strategies. Therefore, we aimed to assess the predictive and prognostic value of TP53, KRAS, and APC mutations in patients with LARC undergoing neoadjuvant chemotherapy (NACT) by retrospectively analyzing 43 patients with LARC who underwent NACT without radiation.

Glycerol and glycerol-3-phosphate: multifaceted metabolites in metabolism, cancer and other diseases.

Glycerol and glycerol-3-phosphate are key metabolites at the intersection of carbohydrate, lipid and energy metabolism. Their production and usage are organismal and cell type specific. Glycerol has unique physicochemical properties enabling it to function as an osmolyte, protein structure stabilizer, antimicrobial and antifreeze agent, important to preservation of many biological functions.

Viral warfare: unleashing engineered oncolytic viruses to outsmart cancer's defenses.

Oncolytic virotherapy (OVT) has emerged as a promising and innovative cancer treatment strategy that harnesses engineered viruses to selectively infect, replicate within, and destroys malignant cells while sparing healthy tissues. Beyond direct oncolysis, oncolytic viruses (OVs) exploit tumor-specific metabolic, antiviral, and immunological vulnerabilities to reshape the tumor microenvironment (TME) and initiate systemic antitumor immunity. Despite promising results from preclinical and clinical studies, several barriers, including inefficient intratumoral virus delivery, immune clearance, and tumor heterogeneity, continue to limit the therapeutic advantages of OVT as a standalone modality and hindered its clinical success.

Glycan dysregulation as one of major metabolic subtypes is associated with TERC overexpression and poor outcomes in cervical cancer.

Background: Metabolic reprogramming is an important hallmark of cervical cancer (CC), and extensive studies have provided important information for translational and clinical oncology. Here we sought to determine metabolic association with molecular aberrations, telomere maintenance and outcomes in CC.

Methods: RNA sequencing data from TCGA cohort of CC was analyzed for their metabolic gene expression profile and consensus clustering was then performed to classify tumors into different groups/subtypes.

Collagen proteins, thrombospondin 1 and lumican are differentially expressed across breast cancer subtypes by functional proteomics from core needle biopsy samples of Taiwanese breast cancer.

Purpose: This study aimed to conduct functional proteomics across breast cancer subtypes with bioinformatics analyses.

Methods: Candidate proteins were identified using nanoscale liquid chromatography with tandem mass spectrometry (NanoLC-MS/MS) from core needle biopsy samples of early stage (0-III) breast cancers, followed by external validation with public domain gene-expression datasets (TCGA TARGET GTEx and TCGA BRCA).

Results: Seventeen proteins demonstrated significantly differential expression and protein-protein interaction (PPI) found the strong networks including COL2A1, COL11A1, COL6A1, COL6A2, THBS1 and LUM.

Targeting Tumor-Associated Hypoxia with Bioreductively Activatable Prodrug Conjugates Derived from Dihydronaphthalene, Benzosuberene, and Indole-based Inhibitors of Tubulin Polymerization.

A strategy for targeting tumor-associated hypoxia utilizes reductase enzyme-mediated cleavage to convert biologically inert prodrugs to their corresponding biologically active parent therapeutic agents selectively in areas of pronounced hypoxia. Small-molecule inhibitors of tubulin polymerization represent unique therapeutic agents for this approach, with the most promising functioning as both antiproliferative agents (cytotoxins) and as vascular disrupting agents (VDAs). VDAs selectively and effectively disrupt tumor-associated microvessels, which are typically fragile and chaotic in nature.

Discovery of an exquisitely selective WDR5 chemical probe accelerated by a high-quality DEL-ML Hit.

Herein we present the rapid development of LH168, a potent and highly selective chemical probe for WDR5, streamlined by utilizing a DEL-ML (DNA encoded library-machine learning) hit as the chemical starting point. LH168 was comprehensively characterized in bioassays and demonstrated potent target engagement at the WIN-site pocket of WDR5, with an EC of approximately 10 nM, a long residence time, and exceptional proteome-wide selectivity for WDR5. In addition, we present the X-ray co-crystal structure and provide insights into the structure-activity relationships (SAR).

Exceptional Response to Immunotherapy-based Treatment in Compound -Mutated Oligometastatic Pulmonary Sarcomatoid Carcinoma: A Case Report.

Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC) with limited treatment options and poor prognosis. mutations generally respond to tyrosine kinase inhibitors (TKIs)-based targeted therapy but are typically associated with resistance to immunotherapy. We report a case of oligometastatic PSC harboring compound mutations (p.

Monotherapy With Immune Checkpoint Blockade Improves Survival Outcomes in KRAS-Mutant but Not KRAS Wild-Type Metastatic Lung Adenocarcinoma: Validation From an Extended Swedish Cohort.

Introduction: Immune checkpoint blockade (ICB) is a standard first-line treatment for stage IV NSCLC without actionable oncogenic alterations. mutations, prevalent in 30% to 40% lung adenocarcinomas (LUAD) in Western populations, currently lack targeted first-line therapies. This study aimed to assess the predictive value of mutations for clinical outcomes after distinct ICB regimens, validating our previous findings in a larger cohort with extended follow-up.

Moisturising Gloves as a Solution for Occupational Skin Health: Advances and Challenges.

Extended glove usage is crucial in various occupational settings to safeguard workers and maintain hygiene standards. However, prolonged wear creates an occlusive environment that disrupts normal skin evaporation, leading to temporary overhydration. This reversal of the diffusion gradient facilitates the penetration of residual soaps and alcohol from hand hygiene practices, which can deplete skin moisture and cause irritation.

Ribonuclease-Based Immunotoxins as Anticancer Agents.

Ribonucleases (RNases) represent a distinct category of nucleases that facilitate RNA degradation into smaller components. These enzymes are particularly adept at dismantling RNA strands and other materials. A promising strategy for the targeted treatment of cancer cells involves the administration of antibody-based toxic agents designed to eliminate tumor cells specifically.

Prostate cancer characteristics in fathers and risk of early onset high-risk prostate cancer in sons.

A family history of prostate cancer in first-degree relatives is an established risk factor for prostate cancer, but the specific associations between prostate cancer characteristics in fathers and the risk of high-risk prostate cancer in their sons remain unclear. We identified men in Prostate Cancer data Base Sweden whose fathers had been diagnosed with prostate cancer in 1998-2005. We compared the observed number of prostate cancer diagnoses in these men with the expected number in the Swedish male population, estimating standardized incidence ratios (SIR).

UK recommendations for chimerism testing and monitoring following allogeneic haematopoietic stem cell transplantation (HSCT): Best practice consensus guidelines from the British Society for Blood and Marrow Transplant and Cellular Therapies (BSBMTCT), NHS England Genomic Laboratory Hub (GLH) Haematological Malignancies Working Group, UK Cancer Genetics Group (UKCGG) and the UK National External Quality Assessment Service for Leucocyte Immunophenotyping (UK NEQAS LI).

In allogeneic haematopoietic stem cell transplantation (HSCT), important clinical decisions depend upon assessment of chimerism, including immunosuppressant dosing and donor lymphocyte infusions (DLI), which in turn can have major impacts on disease control, graft-versus-host disease (GVHD), immunity and ultimately patient survival. There is a complex range of clinical and laboratory procedural considerations including methodology of testing, types of cell subset selection, frequency of testing, urgency of turnaround times (TATs), interplay with measurable residual disease (MRD) monitoring and duration of testing post-transplant. These aspects are routinely adapted according to disease indication, patient characteristics, donor source and intensity of transplant technique.