Stochastic modeling of single-cell gene expression adaptation reveals non-genomic contribution to evolution of tumor subclones.

Cancer progression is an evolutionary process driven by the selection of cells adapted to gain growth advantage. We present a formal study on the adaptation of gene expression in subclonal evolution. We model evolutionary changes in gene expression as stochastic Ornstein-Uhlenbeck processes, jointly leveraging the evolutionary history of subclones and single-cell expression data.

Telomere Protection in Stem Cells.

The natural ends of chromosomes resemble double-strand breaks (DSBs), which would activate the DNA damage response (DDR) pathway without the protection provided by a specialized protein complex called shelterin. Over the past decades, extensive research has uncovered the mechanism of action and the high degree of specialization provided by the shelterin complex to prevent aberrant activation of DNA repair machinery at chromosome ends in somatic cells. However, recent findings have revealed striking differences in the mechanisms of end protection in stem cells compared to somatic cells.

Single-cell RNA-seq reveals as a prognostic biomarker in low-grade endometrial stromal sarcoma.

Background: Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine malignancy characterized by its complex tumor microenvironment (TME) and high recurrence rates, posing challenges to accurate prognosis and effective treatment. Identifying prognostic biomarkers is essential for improving patient stratification and guiding therapeutic strategies.

Methods: Using single-cell transcriptome analysis combined with H&E and multiplex immunofluorescence staining, we identified a subpopulation of tumor cells in LG-ESS and further validated the association of this subpopulation and its characteristic genes with LG-ESS prognosis by molecular characterization and bulk transcriptome data.

Charting the transcriptomic landscape of primary and metastatic cancers in relation to their origin and target normal tissues.

Metastasis is a leading cause of cancer-related deaths, yet understanding how metastatic tumors adapt from their origin to their target tissues remains a fundamental challenge. To address this, we assessed whether primary and metastatic tumors more closely resemble their tissues of origin or target tissues in terms of gene expression. We analyzed expression profiles from multiple cancer types and normal tissues, including single-cell and bulk RNA sequencing data from both paired and unpaired patient cohorts.

Tumor and blood B-cell abundance outperforms established immune checkpoint blockade response prediction signatures in head and neck cancer.

Background: Immunotherapy has improved the outcomes for some patients with head and neck squamous-cell carcinoma (HNSCC). However, the low and variable response rates observed highlight the need for robust response biomarkers to select patients for treatment.

Patients And Methods: We assembled and analyzed a large HNSCC dataset, encompassing 11 clinical cohorts including 1232 patient samples, spanning a variety of disease subtypes and immune checkpoint blockade (ICB) treatment types, tissue sources, data modalities, and timing of measurements.

Persistence of activated anti-mesothelin hYP218 chimeric antigen receptor T cells in the tumour is associated with efficacy in gastric and colorectal carcinomas.

Patients with advanced gastric and colorectal cancers have limited treatment options. Since mesothelin is highly expressed in these tumour types, we evaluated the therapeutic benefits of anti-mesothelin hYP218 CAR T cells alone, and in combination with anti-PD1 antibody, pembrolizumab. GEPIA analysis was performed using human gastric (n = 408) and colon cancer tumours (n = 275) in TCGA database, to evaluate mRNA expression of mesothelin, compared to normal tissues.

Decoding β-catenin expression patterns in ovarian serous carcinoma with clinicopathological implications: insights from National Cancer Institute.

Aim: This study aimed to examine the immunohistochemical expression of β-catenin in serous ovarian carcinoma and to investigate its relationship with clinicopathological features and disease outcomes.

Methods: A retrospective analysis was conducted on 67 cases of serous ovarian carcinoma diagnosed at the Pathology Department of the Egyptian National Cancer Institute, Cairo University, between January 1, 2015, and December 31, 2017.

Results: The age of the patients ranged from 26 to 76 years.

Anticancer activity of EMD37 against human head and neck cancer: Impact on apoptotic and inflammatory machineries.

Accumulating evidence emphasizes the tumorigenic role of epidermal growth factor receptor (EGFR) in head and neck cancer (HNC). Although cetuximab is the sole anti-EGFR approved by the Food and Drug Administration for treating HNC patients.its response rates are modest.

Protocol for establishing liver tumors via ultrasound-guided intrahepatic injection prior partial hepatic resection in a mouse model.

We present a protocol to generate a liver tumor murine model utilizing orthotopic ultrasound-guided intrahepatic injections of tumor cells and a partial hepatectomy. We describe cell and animal preparation and ultrasound-guided intrahepatic injections. We then depict how to conduct a partial hepatectomy addressing solutions to potential problems.

A machine learning model reveals expansive downregulation of ligand-receptor interactions that enhance lymphocyte infiltration in melanoma with developed resistance to immune checkpoint blockade.

Immune checkpoint blockade (ICB) is a promising cancer therapy; however, resistance frequently develops. To explore ICB resistance mechanisms, we develop Immunotherapy Resistance cell-cell Interaction Scanner (IRIS), a machine learning model aimed at identifying cell-type-specific tumor microenvironment ligand-receptor interactions relevant to ICB resistance. Applying IRIS to deconvolved transcriptomics data of the five largest melanoma ICB cohorts, we identify specific downregulated interactions, termed resistance downregulated interactions (RDI), as tumors develop resistance.

Use of optimized single-cell RNA flow cytometry protocol identifies monocytes as main producers of type I interferon in mouse syngeneic tumors.

The tumor microenvironment (TME) consists of complex interactions between cellular and extracellular components, among which the immune system is known to play an integral role in disease progression and response to therapy. Cytokines and chemokines are cell signaling proteins used by immune cells to communicate with each other as well as with other cell types in the body. These proteins control systemic and local immune responses and levels of cytokines/chemokines in the TME have been associated with tumor outcomes.

Muti-target rationale design of novel substituted N-phenyl-2-((6-phenylpyridazin-3-yl)thio)acetamide candidates as telomerase/JAK1/STAT3/TLR4 inhibitors: In vitro and in vivo investigations.

In this work, additional effort was applied to design new BIBR1532-based analogues with potential inhibitory activity against telomerase and acting as multitarget antitumor candidates to overcome the resistance problem. Therefore, novel substituted N-phenyl-2-((6-phenylpyridazin-3-yl)thio)acetamide candidates (4a-n) were synthesized. Applying the lead optimization strategy of the previously designed compound 8e; compound 4l showed an improved telomerase inhibition of 64.

Unveiling Disparities: Analyzing Hispanic Inclusion in Liver Cancer Research Databases in the United States.

Primary liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma was the sixth leading cause of cancer death in the United States in 2023. Hispanic people constitute approximately 19% of the nation's total population according to the US Census. Hispanic patients have the highest relative incidence rates of liver cancer compared to non-Hispanic Whites and non-Hispanic Blacks, a disparity frequently overlooked in cancer research.

Smyd3-mediated immuno-modulation in HPV-negative head and neck squamous cell carcinoma mouse models.

SET and MYND-domain containing protein 3 (SMYD3) mediates epigenetic repression of type I IFN response genes in human papillomavirus (HPV)-negative HNSCC cells, and Smyd3 depletion using anti-sense oligonucleotides (ASOs) increases the sensitivity of syngeneic mouse oral carcinoma (MOC1) models to anti-PD-1 therapy. In this study, we utilized single-cell RNA-seq of MOC1 tumors treated with Smyd3 ASOs and found enrichment of type I IFN response pathways in cancer cells, a shift of CD8 T-cells toward an activated/memory phenotype, and a shift of neutrophils toward an anti-tumorigenic phenotype. Mechanisms of resistance to the Smyd3 ASO and anti-PD-1 combination were derived from cancer cells, macrophages, and CD8 T-cells, including neutrophil enrichment through the upregulation of , repression of and defective antigen presentation.

Applicability and performance of F-FDG PET-based modalities for whole-body cancer screening: a systematic review and meta-analysis.

Purpose: Screening tests are the cornerstone for early detection and optimal management of cancers. Most of the present cancer-screening tests are intrusive, time-consuming, and specifically target a particular anatomical site or cancer type. Only a few studies have reported the objective measures of F-FDG PET-based cancer screening in asymptomatic individuals.

Design and synthesis of novel multi-target tetrabromophthalimides as CBS and Topo-II inhibitors and DNA intercalators.

Microtubules are highly dynamic structures and constitute a crucial component of the cellular cytoskeleton. Besides, topoisomerases (Topo) play a fundamental role in maintaining the appropriate structure and organization of DNA. On the other hand, dual mechanism drug candidates for cancer treatment primarily aim to enhance the efficacy of cancer treatment and potentially overcome drug resistance.