Hydrogen sulfide-mediated persulfidation regulates homocysteine metabolism and enhances ferroptosis in non-small cell lung cancer.

Hydrogen sulfide (H₂S), a metabolite of the transsulfuration pathway, has been implicated in ferroptosis, a unique form of cell death caused by lipid peroxidation. While the exact mechanisms controlling ferroptosis remain unclear, our study reveals that H₂S sensitizes human non-small cell lung cancer (NSCLC) cells to this process, particularly when cysteine levels are low. Combining H₂S with cystine depletion significantly enhances the effectiveness of ferroptosis-based cancer therapy.

ATF3-CBS signaling axis coordinates ferroptosis and tumorigenesis in colorectal cancer.

The induction of ferroptosis is promising for cancer therapy. However, the mechanisms enabling cancer cells to evade ferroptosis, particularly in low-cystine environments, remain elusive. Our study delves into the intricate regulatory mechanisms of Activating transcription factor 3 (ATF3) on Cystathionine β-synthase (CBS) under cystine deprivation stress, conferring resistance to ferroptosis in colorectal cancer (CRC) cells.

BRAF Non-V600 Mutations in Metastatic Colorectal Cancer.

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. Despite advancements in detection and therapeutic options, patients with metastatic CRC continue to face poor survival rates. The heterogeneity of oncogenic alterations, including BRAF mutations, poses a substantial challenge in identifying optimal treatment approaches.

Tumor Response-speed Heterogeneity as a Novel Prognostic Factor in Patients With Metastatic Colorectal Cancer.

Purpose: Differential tumor response to therapy is partially attributed to tumor heterogeneity. Additional efforts are needed to identify tumor heterogeneity parameters in response to therapy that is easily applicable in clinical practice. We aimed to describe tumor response-speed heterogeneity and evaluate its prognostic value in patients with metastatic colorectal cancer.

Nuclear receptor coactivator SRC-1 promotes colorectal cancer progression through enhancing GLI2-mediated Hedgehog signaling.

Overexpression of nuclear coactivator steroid receptor coactivator 1 (SRC-1) and aberrant activation of the Hedgehog (Hh) signaling pathway are associated with various tumorigenesis; however, the significance of SRC-1 in colorectal cancer (CRC) and its contribution to the activation of Hh signaling are unclear. Here, we identified a conserved Hh signaling signature positively correlated with SRC-1 expression in CRC based on TCGA database; SRC-1 deficiency significantly inhibited the proliferation, survival, migration, invasion, and tumorigenesis of both human and mouse CRC cells, and SRC-1 knockout significantly suppressed azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CRC in mice. Mechanistically, SRC-1 promoted the expression of GLI family zinc finger 2 (GLI2), a major downstream transcription factor of Hh pathway, and cooperated with GLI2 to enhance multiple Hh-regulated oncogene expression, including Cyclin D1, Bcl-2, and Slug.

Alkylation of quinoxalin-2(1)-ones using phosphonium ylides as alkylating reagents.

A practical and efficient methodology for the construction of 3-alkylquinoxalinones through base promoted direct alkylation of quinoxalin-2(1)-ones with phosphonium ylides as alkylating reagents under metal- and oxidant-free conditions was developed. Various 3-alkylquinoxalin-2(1)-ones were easily obtained in good to excellent yields. Tentative mechanistic studies suggest that this reaction is likely to involve a nucleophilic addition-elimination process.

The clinical advances of proteolysis targeting chimeras in oncology.

Proteolysis targeting chimeras (PROTACs) are a class of small molecules designed to target proteins for degradation. Their novel and unique modes of action provide PROTACs with the potential for their application in the management of both solid and hematologic malignancies. Since its initial discovery, the technology of targeted protein degradation, especially in the form of PROTACs, has had significant advances.

Role of Surgery and Perioperative Therapy in Older Patients with Resectable Pancreatic Ductal Adenocarcinoma.

Background: It is unclear whether results from recent trials of resectable pancreatic ductal adenocarcinoma (PDAC) are generalizable to older patients, who are underrepresented. We aimed to evaluate outcomes of surgery and of neoadjuvant and adjuvant therapy in older patients with resectable PDAC.

Patients And Methods: We included patients aged ≥65 years with upfront resectable PDAC from a prospectively maintained pancreatic cancer registry from 2007 to 2016.

Survival Benefit of Combination Chemotherapy in Elderly Patients With Metastatic Pancreatic Ductal Adenocarcinoma.

Objectives: Survival benefit of combination over single-agent chemotherapy for metastatic pancreatic ductal adenocarcinoma (PDAC) was demonstrated in younger patients in clinical trials. The authors aimed to evaluate whether this survival benefit of combination chemotherapy is present in elderly patients with metastatic PDAC.

Materials And Methods: The authors identified elderly patients (age 65 y or older) with stage IV PDAC and extracted available clinical information from a prospectively maintained institutional pancreatic cancer registry from 2007 to 2016.

Molecular imprinting on PtPd nanoflowers for selective recognition and determination of hydrogen peroxide and glucose.

PtPd nanoflowers (PtPd NFs) exhibit intrinsic peroxidase-like activity as nanozymes, but the nanozymes lack substrate specificity and have low catalytic activity. Herein, a molecularly imprinted nanogel on PtPd NFs was prepared by using 3,3',5,5'-tetramethylbenzidine (TMB) as the template through the aqueous precipitation polymerization method. After the TMB was washed out, many substrate binding pockets were retained in the PtPd NFs.

The Role of Perioperative Systemic Therapy in Localized Pancreatic Neuroendocrine Neoplasms.

Background: The role of perioperative systemic therapy (PST) in the management of localized pancreatic neuroendocrine neoplasms (PanNEN) is unclear.

Objectives: We aimed to evaluate the benefit of PST compared to surgery alone (SA) in patients with localized PanNEN.

Method: We selected patients with stages I-III PanNEN who underwent curative-intent surgical resection in National Cancer Database from 2006 to 2014.

Diastereoselective syntheses of substituted cis-hydrindanones featuring sequential inter- and intramolecular Michael reactions.

The hydrindane (bicyclo[4.3.0]nonane) structural motif () and related -1-hydrindanone skeleton () are common substructures in many natural products.

Design and Synthesis of Molecular Scaffolds with Anti-infective Activity.

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Expanding the pleuromutilin class of antibiotics by de novo chemical synthesis.

New pleuromutilin-like compounds were synthesized in approximately 11 steps from 3-allylcyclopent-2-enone by a strategy featuring sequential carbonyl addition reactions. Several analogs possessing the C14 tiamulin ester side chain displayed activity in a Mycobacterium tuberculosis mc(2)7000 assay. The results described herein provide a basis for further efforts to expand the structural and stereochemical diversity of the pleuromutilin class of bacterial protein synthesis inhibitors through advances in chemical synthesis.

A concise synthesis of the molecular framework of pleuromutilin.

Two syntheses of the tricyclic carbon skeleton of pleuromutilin are reported. Diastereoselective 1,4-conjugate additions were used to elaborate bicyclic precursors at an early stage of each route, while ring-forming olefin metatheses were executed to complete the pleuromutilin carbon framework. The congeners prepared are appropriately functionalized to enable access to diverse pleuromutilin analogues.