Protocol to study secretome interactions using extracellular proximity labeling.

Biotin ligase-based proximity ligation is a widely used, highly effective technique for the study of in vivo protein-protein interactions. However, there are few reports and little consensus on the most effective methods for studying the proximal interactomes of secreted factors. Here, we present a protocol for studying extracellular proximal interactomes using an adaptation of TurboID/BioID2-based proximity ligation.

Excess shed mesothelin disrupts pancreatic cancer cell clustering to impair peritoneal colonization.

Peritoneum is the second most common site of metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Peritoneal colonization is impaired in PDAC cells with knockout (KO) of the cancer surface antigen mesothelin (MSLN) or by introducing Y318A mutation in MSLN to prevent binding to mucin-16 (MUC-16). MSLN has a membrane-bound form but is also shed to release soluble MSLN (sMSLN).

Sorcin: mechanisms of action in cancer hallmarks, drug resistance and opportunities in therapeutics.

Soluble resistant related calcium binding protein (Sorcin) plays an important role in tumor progression, angiogenesis, metastasis, and multidrug resistance. Differential expression of Sorcin across different cancers significantly correlates with key clinicopathological characteristics and survival outcomes, underscoring its potential as a prognostic marker. Its involvement in drug-resistant cancers further advert Sorcin as a promising therapeutic target.

A Novel Ultrasensitive Second Derivative Synchronous Spectrofluorimetric Approach for the Simultaneous Analysis of the Co-Administered Antihypertensives, Telmisartan and Carvedilol in Biological Fluids and Tablets: Greenness and Blueness Assessment.

Hypertension is the predominant risk factor for cardiovascular diseases and mortality. This study presents the first method for the simultaneous analysis of the co-administered antihypertensive drugs, Carvedilol (CAR) and Telmisartan (TEL) using a fast, highly sensitive, environmentally friendly, and cost-effective second derivative synchronous spectrofluorimetric approach. The fluorescence of CAR and TEL was quantified at 243 nm and 274.

Dose finding, bioavailability, and PK-PD of oral triapine with concurrent chemoradiation for locally advanced cervical cancer and vaginal cancer (ETCTN 9892).

Background: The addition of IV triapine to chemoradiation appeared active in phase I and II studies but drug delivery is cumbersome. We examined PO triapine with cisplatin chemoradiation.

Methods: We implemented a 3 + 3 design for PO triapine dose escalation with expansion, starting at 100 mg, five days a week for five weeks while receiving radiation with weekly IV cisplatin for locally advanced cervical or vaginal cancer.

PTCSC3, XIST, GAS5, UCA1, and HIFAL: Five lncRNAs Emerging as Potential Prognostic Players in Egyptian Adult Acute Myeloid Leukemia (AML) Patients.

Background And Aims: So far, long noncoding RNAs (lncRNAs) signatures in acute myeloid leukemia (AML) are poorly understood. The present study aims to explore the prognostic significance of eleven cancer-related lncRNAs in bone marrow (BM) samples from adult Egyptian AML patients.

Materials And Methods: In this study, we analyzed eleven lncRNAs using the qRT-PCR assay in the bone marrow (BM) of 79 de novo AML adult patients before receiving any therapy.

CRISPR-based dissection of miRNA binding sites using isogenic cell lines is hampered by pervasive noise.

Non-coding regulatory sequences play essential roles in adjusting gene output to cellular needs and are thus critical to animal development and health. Numerous such sequences have been identified in mammalian genomes ranging from transcription factors binding motifs to recognition sites for RNA-binding proteins and non-coding RNAs. The advent of CRISPR has raised the possibility of assigning functionality to individual endogenous regulatory sites by facilitating the generation of isogenic cell lines that differ by a defined set of genetic modifications.

Body size and occupational physical activity during the life course and gastrointestinal cancers.

Evidence on the associations of body size and occupational physical activity (PA) during the life course with gastrointestinal cancers is inconclusive. We analyzed data from the Golestan Cohort Study, a population-based prospective cohort study from Iran, with 50,045 individuals aged 40-75 years enrolled during 2004-2008 and followed through April 2023. Body size during adolescence, early adulthood, and at cohort baseline was assessed using validated pictograms.

How the bone microenvironment shapes the pre-metastatic niche and metastasis.

The bone is a frequent metastatic site, with changes in the mineralized bone and the bone marrow milieu that can also prime other sites for metastasis by educating progenitor cells to support metastatic spread. Stromal and immune populations cooperatively maintain the organizationally complex bone niches and are dysregulated in the presence of a distant primary tumor and metastatic disease. Interrogating the bone niches that facilitate metastatic spread using innovative technologies holds the potential to aid in preventing metastasis in and mediated by the bone.

Interleukin-13 Receptor Subunit Alpha 2 Induces Chemokine Expression and Macrophage Polarization to Promote Inflammation and Fibrosis.

Purpose: Interleukin-13 (IL-13) is a known mediator of radiation-induced lung injury (RILI). IL-13Rα2 has an accepted role in antagonizing IL-13 signaling by acting as a decoy receptor. We sought to understand the role of IL-13Rα2 in the progression of RILI.

Analysis of the progression of cervical cancer in a low-and-middle-income country: From pre-malignancy to invasive disease.

To better understand cervical cancer progression, we analyzed RNA from 262 biopsies from women referred for colposcopy. We determined the HPV type and analyzed the expression of 51 genes. HPV31 was significantly more prevalent in precancer than stage 1 cancer and invasive cancer (p < 0.

Next generation sequencing-based MSI scoring predict benefit in mismatch repair deficient tumors treated with nivolumab: follow-up on NCI-MATCH arm Z1D.

Purpose: Mismatch repair deficient (dMMR) tumors have demonstrated favorable responses to immune checkpoint inhibition targeting PD-1. However, more in-depth identification of predictors of response could further refine patient selection for immunotherapy treatment.

Experimental Design: We undertook integrated evaluation performed on samples collected from 28 of 42 patients enrolled on the NCI-MATCH arm Z1D trial that evaluated PD-1 inhibition treatment with nivolumab in patients with non-colorectal dMMR tumors.

F-FLT PET and Blood-based Biomarkers for Identifying Gastrointestinal Graft versus Host Disease after Allogeneic Cell Transplantation.

Purpose To determine whether fluorine 18 (F) fluorothymidine (FLT) PET imaging alone or combined with Mount Sinai Acute GVHD International Consortium (MAGIC) biomarkers could help identify subclinical gastrointestinal graft versus host disease (GI-GVHD) by day 100 following hematopoietic stem cell transplantation (HSCT). Materials and Methods F-FLT PET imaging was analyzed in a prospective pilot study (ClinicalTrials.gov identifier no.

Increased frequency of germline pathogenic variants among individuals with dermatofibrosarcoma protuberans.

Purpose: To identify candidate susceptibility genes for dermatofibrosarcoma protuberans (DFSP).

Methods: All individuals with DFSP from the International Sarcoma Kindred Study ( = 3767 individuals with sarcoma diagnoses from Australia, Europe, New Zealand, and United States) and cohorts that were not ascertained based on sarcoma status or other phenotypes (Geisinger MyCode,  = 170,503 individuals, United States; UK Biobank,  = 469,789 individuals, United Kingdom) were evaluated for germline pathogenic or likely pathogenic (P/LP) variants in 156 cancer genes.

Results: There were 92 unrelated individuals with DFSP across the 3 cohorts.

Design, Synthesis and Biological Evaluation of 2-Phenyl Indole Analogues of OXi8006 as Colchicine Site Inhibitors of Tubulin Polymerization and Vascular Disrupting Agents.

Inhibitors of tubulin polymerization represent a promising therapeutic approach for the treatment of solid tumors. Molecules that bind to the colchicine site are of interest as they can function with a dual mechanism of action as both potent antiproliferative agents and tumor-selective vascular disrupting agents (VDAs). One such example is a 2-aryl-3-aroyl-indole molecule (OXi8006) from our laboratory that demonstrates potent inhibition of tubulin polymerization and strong antiproliferative activity (cytotoxicity) against a variety of human cancer cell lines.

Time-Restricted Eating and Cancer: Lessons Learned and Considerations for a Path Forward.

Time-restricted eating (TRE) is a type of intermittent fasting (IF). Food can be consumed as desired during the eating period, but not during the remainder of the day. Studies suggest that many of the health benefits of fasting may not simply be the result of weight loss, but also due to the body's responses to the fasting that lead to improved metabolic functioning.

Phase II Study of Sunitinib in Tumors With Mutations: Results From the NCI MATCH ECOG-ACRIN Trial (EAY131) Subprotocol V.

Purpose: The NCI-MATCH study is a tumor-agnostic platform trial enrolling patients to targeted therapies on the basis of genomic alterations. Subprotocol V investigated sunitinib in patients with tumors harboring - mutations.

Methods: EAY131-V, is an open-label, single-arm, phase II study.

SARS-CoV-2 infection of salivary glands compromises the production of a secreted antifungal peptide with potential implications for development of oral candidiasis.

Saliva contains antimicrobial peptides considered integral components of host innate immunity, and crucial for protection against colonizing microbial species. Most notable is histatin-5 which is exclusively produced in salivary glands with uniquely potent antifungal activity against the opportunistic pathogen Candida albicans. Recently, SARS-CoV-2 was shown to replicate in salivary gland acinar cells eliciting local immune cell activation.

Dual inhibition of oxidative phosphorylation and glycolysis exerts a synergistic antitumor effect on colorectal and gastric cancer by creating energy depletion and preventing metabolic switch.

Pyruvate is situated at the intersection of oxidative phosphorylation (OXPHOS) and glycolysis, which are the primary energy-producing pathways in cells. Cancer therapies targeting these pathways have been previously documented, indicating that inhibiting one pathway may lead to functional compensation by the other, resulting in an insufficient antitumor effect. Thus, effective cancer treatment necessitates concurrent and comprehensive suppression of both.

Evaluating the Use of Environmental and Polygenic Risk Scores to Inform Colorectal Cancer Risk-Based Surveillance Intervals.

Introduction: United States Multi-Society Task Force colonoscopy surveillance intervals are based solely on adenoma characteristics, without accounting for other risk factors. We investigated whether a risk model including demographic, environmental, and genetic risk factors could individualize surveillance intervals under an "equal management of equal risks" framework.

Methods: Using 14,069 individuals from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnostic colonoscopy following an abnormal flexible sigmoidoscopy, we modeled the risk of colorectal cancer, considering the diagnostic colonoscopy finding, baseline risk factors (e.

Organs in plain sight-parotid gland doses in short-course palliative whole-brain radiotherapy.

Purpose: Palliative whole-brain radiotherapy (WBRT) is a useful treatment modality for patients diagnosed with brain metastasis. Our study aimed to document parotid doses using a short course of 20 Gy in five fractions (SC-WBRT) and compare them with the known xerostomia parameters.

Methods And Materials: We retrieved dosimetric parameters for 59 patients who received SC-WBRT.