Targeting YES1 enhances the efficacy of chemotherapy, targeted therapy and onco-immunotherapy.

YES1 (Yamaguchi sarcoma virus homolog 1), a non-receptor tyrosine kinase of the SRC family (SFK), has been abnormally amplified or mutated in several types of solid tumors. The alteration of YES1 impacted multiple biological processes, including promoting tumor progression and metastasis, especially, producing cancer therapy resistance via bypass pathways. Thus, YES1 can serve as a druggable target to overcome drug resistance and suppress tumor growth.

Beyond cysts: Organization of epithelial networks in the murine thymus.

The thymus originates from the third pharyngeal pouch endoderm, which also gives rise to respiratory tract elements. Here, we examined intrathymic cystic structures, long considered remnants of organogenesis. Through sequential histology and ultrastructural imaging, we uncovered that these "cysts" are in fact continuous and structured epithelial networks embedded within the thymic parenchyma.

Mapping murine thymic epithelial cells: functional ultrastructure and implications for thymopoiesis.

We present a novel classification system for murine thymic epithelial cells (TECs), identifying 11 distinct types, four in the thymic cortex and seven in the medulla, based on their spatial localization and unique ultrastructural features. As key stromal components of the thymic microenvironment, TECs play indispensable roles in T cell development, including thymocyte selection, antigen presentation, and structural support. Our classification spans from the subcapsular cortex to the deep medulla and incorporates microanatomical context, morphology, and functional characteristics, providing a comprehensive and flexible framework to study TEC heterogeneity in relation to thymopoiesis.

Haematopoietic stem cell number is not solely defined by niche availability.

Haematopoietic stem cells (HSCs) reside in specialized microenvironments, referred to as niches, and the classical model suggests that HSC numbers are predominantly determined by the niche size. However, the vast excess of niche cells relative to HSCs challenges this perspective. To rigorously define the role of niche size in regulating HSC numbers, we developed a femur-transplantation system, enabling us to increase available HSC niches.

Clinical strategies for lung cancer management: Recommendations from the Bridging the Gaps Lung Cancer Consensus Conference 2024.

Clinical practice guidelines for nonsmall cell lung cancer (NSCLC) and small cell lung cancer include recommendations based on high-level clinical trial evidence, but complex clinical questions are frequently seen in real-world practice that are not clearly answered by prospective trial data. To address these questions, the Bridging the Gaps Lung Cancer Consensus Conference 2024 (BtG LCCC 2024) convened to develop US-focused expert guidance for clinical situations in which level 1 evidence is lacking. At BtG LCCC 2024, a multidisciplinary expert panel discussed ongoing clinical issues in small cell lung cancer management, targeted therapy in EGFR-mutated NSCLC, management of early stage NSCLC, identification and management of non-EGFR oncogene-driven NSCLC, and use of immunotherapy in advanced/metastatic NSCLC.

Temporal Trends and Socioeconomic Determinants of Cytoreductive Nephrectomy Utilization for Metastatic Renal Cell Carcinoma in the USA.

Background And Objective: The evolving treatment landscape in metastatic renal cell carcinoma (mRCC) since the advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has rendered the role of cytoreductive nephrectomy (CN) unclear. We sought to quantify CN utilization in the USA over the past two decades and assess factors that affect access to CN.

Methods: We analyzed the National Inpatient Sample database from 2006 to 2021, identifying mRCC patients who underwent CN using International Classification of Diseases (ICD)-9 and ICD-10 codes.

A Pilot Study of the Combination of 5-Azacitidine and All-trans Retinoic Acid in Biochemically Recurrent Prostate Cancer.

Purpose: Biochemical recurrence (BCR) after definitive local therapy remains a major clinical challenge in prostate cancer (PCa), with heterogeneous disease trajectories and few established strategies to delay further progression without prolonged androgen deprivation. This pilot study evaluated the combination of 5-azacitidine (AZA) and all-trans retinoic acid (ATRA) to induce tumor dormancy and delay clinical progression in patients with BCR.

Experimental Design: In a prospective, open-label, randomized, single-institution pilot trial, patients with BCR of PCa and no recent hormonal or definitive therapy received low-dose AZA and sequential ATRA.

Receiving coupons and discounts for nicotine pouches is associated with current use of nicotine pouches among United States adults: Results from the population assessment of tobacco and health (PATH) study wave 7 (2022-2023).

Background: The rising use of nicotine pouches has emerged as a public health concern. Increasing use might be driven by exposure to marketing (e.g.

Adding the FcRn antagonist efgartigimod for the prevention of IgG-mediated complications in the peri-transplant period.

Background: The management of IgG-mediated diseases in the peri-allogeneic transplant period remains challenging. Specifically, the presence of donor-specific antibodies (DSA) is a major cause of graft failure and poor graft function; despite improvements in desensitization, it remains an unmet need. Similarly, there is no standard approach for the prevention of delayed RBC transfusion independence and pure red blood cell aplasia caused by IgG isoagglutinins after major ABO-mismatched transplant.

The association between sexual identity and cannabis vaping among United States adults: Exploring differences by serious psychological distress.

Introduction: Cannabis vaping has gained popularity, particularly among sexual minority individuals. Sexual minority individuals experience high levels of serious psychological distress, which might worsen cannabis vaping disparities. This study examined cannabis vaping prevalence by sexual identity and serious psychological distress.

SHP2 is a multifunctional target in anaplastic thyroid carcinoma: Cell intrinsic and immune-dependent anti-tumor effects.

Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive malignancy with dismal prognosis. Standard radiotherapy and chemotherapy offer limited efficacy, and emerging treatments, including multi-kinase inhibitors, often result in the development of adaptive drug resistance. Recent studies suggest that targeting SHP2 (PTPN11), a non-receptor tyrosine phosphatase involved in RAS/MAPK signaling, may offer a promising therapeutic strategy for tumors featuring activation of this pathway, including ATC.

Mutations in MLL3 promote breast cancer progression via HIF1α-dependent intratumoral recruitment and differentiation of regulatory T cells.

Loss-of-function mutations in MLL3, encoding the histone methyltransferase MLL3/KMT2C, are frequent in various cancer types. To examine the mechanisms whereby MLL3 suppresses tumorigenesis, we developed a mouse mammary-stem-cell-based tumor model bearing cancer-driver mutations, including loss of MLL3/KMT2C and p53 and constitutive phosphatidylinositol 3-kinase (PI3K) activation, recapitulating a genetic makeup of aggressive human breast cancers. MLL3 loss stabilized the transcription factor HIF1α, which increased secretion of the chemokine CCL2 by tumor cells and promoted recruitment of CCR2 regulatory T (Treg) cells.

Respiratory viral infections awaken metastatic breast cancer cells in lungs.

Breast cancer is the second most common cancer globally, with most deaths caused by metastatic disease, often following long periods of clinical dormancy. Understanding the mechanisms that disrupt the quiescence of dormant disseminated cancer cells (DCCs) is crucial for addressing metastatic progression. Infections caused by respiratory viruses such as influenza and SARS-CoV-2 trigger both local and systemic inflammation.

One-Carbon Metabolism Inhibition Depletes Purines and Results in Profound and Prolonged Ewing Sarcoma Growth Suppression.

Unlabelled: Ewing sarcoma is the second most common primary bone malignancy in adolescents and young adults. Patients who present with localized disease have experienced a steadily improving survival rate over the years, whereas those who present with metastatic disease have the same dismal prognosis as 30 years ago, with long-term survival rates of less than 20%, despite maximal intensification of chemotherapy. Thus, novel treatment approaches are a significant unmet clinical need.

Understanding Associated Factors for IQOS Use Among US Adults: Is the Risk re-Emerging?

Background: IQOS, the leading global brand of heated tobacco products (i.e., nicotine delivery systems that heat tobacco at lower temperatures than combustible tobacco products to produce nicotine-containing aerosols for inhalation), is scheduled to resume sales in the United States in 2025.

Collagen hydroxylation couples NAD+/NADH dynamics to tumor dormancy and reactivation.

Metastasis remains the leading cause of cancer-related mortality. Disseminated tumor cells (DTCs) colonize distant organs where they enter a prolonged state of quiescence, named cellular dormancy, within collagen-rich extracellular matrix (ECM) niches. How dormant cells regulate the formation of collagen-rich niches and the mechanisms maintaining collagen proteostasis during dormancy and reactivation are not understood.

Metronomic low-dose regimen of decitabine and venetoclax is safe and reduces monocyte burden in chronic myelomonocytic leukemia.

Not available.

Adjuvant Radiotherapy for Early-Stage Oral Tongue Cancer: Insights From the NCDB Based on Grade.

Background: Oral tongue squamous cell carcinoma (OTSCC) incidence is rising in the United States. While early-stage (pT1-2N0M0) OTSCC is primarily managed with surgery, the role of postoperative radiotherapy (PORT) remains debated, particularly in moderate-to-poor differentiation. Current guidelines do not recommend PORT based on histologic grade alone, yet a retrospective study by Tian et al.

Targeting CSF-1 signaling between tumor cells and macrophages at TMEM doorways inhibits breast cancer dissemination.

Tumor cell intravasation is essential for metastatic dissemination, but its exact mechanism is incompletely understood. We have previously shown that in breast cancer, the direct and stable association of a tumor cell expressing Mena, a Tie2/VEGF macrophage, and a vascular endothelial cell, creates an intravasation portal, called a "tumor microenvironment of metastasis" (TMEM) doorway, for tumor cell intravasation, leading to dissemination to distant sites. The density of TMEM doorways, also called TMEM doorway score, is a clinically validated prognostic marker of distant metastasis in breast cancer patients.

Meeting Report From the 2024 Symposium on IRAK4 in Cancer: Highlights and Clinical Updates.

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a serine/threonine kinase that mediates interleukin-1 and Toll-like receptor (TLR) signaling. IRAK4 drives the activation of nuclear factor kappa B (NF-κB), which promotes cell survival, inflammation, and proliferation. Aberrant activation of IRAK4 and TLR signaling has been implicated in multiple malignancies.

Integrated in vivo functional screens and multiomics analyses identify α-2,3-sialylation as essential for melanoma maintenance.

Aberrant glycosylation is a hallmark of cancer biology, and altered glycosylation influences multiple facets of melanoma progression. To identify glycosyltransferases, glycans, and glycoproteins essential for melanoma maintenance, we conducted an in vivo growth screen with a pooled short hairpin RNA library of glycosyltransferases, lectin microarray profiling of benign nevus and melanoma samples, and mass spectrometry-based glycoproteomics. We found that α-2,3-sialyltransferases ST3GAL1 and ST3GAL2 and corresponding α-2,3-linked sialosides are up-regulated in melanoma compared to nevi and are essential for melanoma growth.

Tobacco and Cannabis Co-use by HIV Status Among United States Adults: Results from the 2021-2023 National Survey on Drug Use and Health.

Tobacco and cannabis use are prevalent among adults with HIV and co-use is associated with drug dependence and negative health outcomes such as lung disease. This study examined the co-use of tobacco and cannabis by HIV status overall and by sociodemographics. Data came from the adult sample from the 2021-2023 National Survey on Drug Use and Health.

Pathologist-Read vs AI-Driven Assessment of Tumor-Infiltrating Lymphocytes in Melanoma.

Importance: Tumor-infiltrating lymphocytes (TILs) are a provocative biomarker in melanoma, influencing diagnosis, prognosis, and immunotherapy outcomes; however, traditional pathologist-read TIL assessment on hematoxylin and eosin-stained slides is prone to interobserver variability, leading to inconsistent clinical decisions. Therefore, development of newer TIL scoring approaches that produce more reliable and consistent readouts is important.

Objective: To evaluate the analytical and clinical validity of a machine learning algorithm for TIL quantification in melanoma compared with traditional pathologist-read methods.