Alteration of the Tumor Microenvironment With Intratumoral Dendritic Cells Before Chemotherapy in ERBB2 Breast Cancer: A Nonrandomized Clinical Trial.

Importance: Current chemotherapy regimens for patients with ERBB2 (formerly HER2)-positive breast cancer are associated with considerable morbidity. These patients may benefit from more effective and less toxic therapies.

Objective: To evaluate the safety, immunogenicity, and preliminary efficacy of intratumoral (IT) delivery of conventional type 1 dendritic cells (cDC1) in combination with ERBB2-targeted therapies.

Acid ceramidase controls proteasome inhibitor resistance and is a novel therapeutic target for the treatment of relapsed / refractory multiple myeloma.

Multiple myeloma (MM) patients are often refractory to targeted therapies including proteasome inhibitors (PIs). Here, analysis of RNA sequencing data derived from 672 patients with newly diagnosed or relapsed/refractory disease identified the acid ceramidase, ASAH1, as a key regulator of PI resistance. Genetic or pharmacological blockade of ASAH1 remarkably restored PI sensitivity and protected mice from resistant MM progression in vivo.

Vision-language models for medical report generation and visual question answering: a review.

Medical vision-language models (VLMs) combine computer vision (CV) and natural language processing (NLP) to analyze visual and textual medical data. Our paper reviews recent advancements in developing VLMs specialized for healthcare, focusing on publicly available models designed for medical report generation and visual question answering (VQA). We provide background on NLP and CV, explaining how techniques from both fields are integrated into VLMs, with visual and language data often fused using Transformer-based architectures to enable effective learning from multimodal data.

Clinical perspectives on post-induction maintenance therapy in patients with acute myeloid leukaemia in remission who are ineligible for allogeneic haematopoietic stem cell transplantation.

For patients with acute myeloid leukaemia (AML) who achieve complete remission (CR) after induction therapy, subsequent allogeneic haematopoietic stem cell transplantation (allo-HSCT) reduces the risk of relapse. However, not all patients are eligible, warranting effective alternative maintenance strategies. Oral azacitidine is the only non-targeted therapy approved by both the United States (US) Food and Drug Administration and the European Medicines Agency for the maintenance or continued treatment of allo-HSCT-ineligible patients with AML achieving CR or CR with incomplete haematological recovery following induction chemotherapy.

Tales of Cancer-Induced Bone Disease from the Senescent Osteocyte Crypt.

Cancer-induced bone disease greatly diminishes the quality of life for patients with bone metastatic breast cancer, resulting in painful skeletal-related events including bone loss and fracture. Improved understanding of the roles of osteoblasts and osteoclasts, and how tumors alter their biology, has led to blockbuster therapies that significantly reduce skeletal-related events, but the disease remains incurable. However, emerging technologies and tools for studying the role of other stromal and immune components in controlling tumor-host interactions have begun to reveal new insights that may yield tractable therapeutic targets to further mitigate the painful effects of bone metastases.

Data-driven analysis of the effect of screening and treatment on the spread of HIV in developing and developed countries.

Introduction: In this study, we used a mathematical epidemic model to explore the status of the HIV epidemic in the USA and Pakistan. In addition to studying the dynamics of the model, we fitted the model with recent data to estimate the parameters describing the epidemic in both countries.

Results: Our estimation shows that in the USA, the reproduction number is 0.

Associations Between Dietary Patterns and Quality of Life in a Longitudinal Cohort of Colorectal Cancer Survivors.

Purpose: To characterize dietary patterns and examine associations with cross-sectional and longitudinal changes in quality of life (QOL) over approximately one year after colorectal cancer (CRC) diagnosis.

Methods: The ColoCare Study is an international, multi-center, prospective cohort study of newly diagnosed CRC survivors of any stage. A subset of participants with CRC in the United States completed patient-reported outcome measures at 6- and 12-months post-enrollment, including the Food Frequency Questionnaire (FFQ) and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).

An Activity-Based Sensing Approach to Multiplex Mapping of Labile Copper Pools by Stimulated Raman Scattering.

Molecular imaging with analyte-responsive probes offers a powerful chemical approach to studying biological processes. Many reagents for bioimaging employ a fluorescence readout, but the relatively broad emission bands of this modality and the need to alter the chemical structure of the fluorophore for different signal colors can potentially limit multiplex imaging. Here, we report a generalizable approach to multiplex analyte imaging by leveraging the comparably narrow spectral signatures of stimulated Raman scattering (SRS) in activity-based sensing (ABS) mode.

International collaboration of neoadjuvant stereotactic radiosurgery for brain metastases: The INTERNEO individual patient data pooled analysis.

Background And Purpose: Neoadjuvant stereotactic radiosurgery (NaSRS) is an emerging treatment option for brain metastases (BrM) planned for resection. The aim of this study was to report on the efficacy and safety of NaSRS in an individual patient data pooled analysis.

Materials And Methods: Patients undergoing single- and multi-fraction NaSRS for BrM at nine institutions in five countries (Australia, Canada, South Korea, Switzerland and USA) were included.

Interleukin-1α release during necrotic-like cell death generates myeloid-driven immunosuppression that restricts anti-tumor immunity.

Necroptosis can promote antigen-specific immune responses, suggesting induced necroptosis as a therapeutic approach for cancer. Here we sought to determine the mechanism of immune activation but found the necroptosis mediators RIPK3 and MLKL dispensable for tumor growth in genetic and implantable models of breast or lung cancer. Surprisingly, inducing necroptosis within established breast tumors generates a myeloid suppressive microenvironment that inhibits T cell function, promotes tumor growth, and reduces survival.

Multi-institutional report of trastuzumab deruxtecan and stereotactic radiosurgery for HER2 positive and HER2-low breast cancer brain metastases.

Trastuzumab-deruxtecan (T-DXd) has demonstrated intracranial efficacy; however, safety and efficacy data remains limited with stereotactic radiosurgery (SRS). A multi-institutional review was performed with HER2+ or HER2-low metastatic breast cancer treated with T-DXd and SRS for active brain metastases. We identified 215 lesions treated over 48 SRS courses in 34 patients.

Hypofractionated accelerated radiation dose-painting (HARD) improves outcomes in unresected soft-tissue sarcoma.

Soft tissue sarcomas (STS) are radioresistant with a low α/β, which may have a biologic benefit with hypofractionation. For unresectable STS, the dose escalation required to achieve durable control is often limited by long-term toxicity risk. We sought to compare an isotoxic approach utilizing hypofractionated accelerated radiation dose-painting (HARD) versus standard fractionated radiation therapy (SFT) in patients with unresected STS.

SART1 modulates poly-(ADP-ribose) chain accumulation and PARP1 chromatin localization.

PARP1 inhibitors (PARPis) are used for treatment of cancers with mutations in or that are deficient in homologous recombination. The identification of modulators of PARP1 activity is critical to understand and overcome resistance to PARPis. We integrated data from three omics-scale screens to discover new regulators of PARP1 activity.

Metastasis development in non-muscle-invasive bladder cancer.

Non-muscle-invasive bladder cancer (NMIBC) is the most common type of bladder cancer presentation and is characterized by a varying probability of recurrence and progression. Sporadically, patients with NMIBC might also develop tumour metastases without any pathological evidence of muscle-invasive disease within the bladder, a condition known as metastatic NMIBC. In the published literature, this phenomenon is limited to several case reports and small reviews, with few data regarding the possible aetiologies.

mxfda: a comprehensive toolkit for functional data analysis of single-cell spatial data.

Summary: Technologies that produce spatial single-cell (SC) data have revolutionized the study of tissue microstructures and promise to advance personalized treatment of cancer by revealing new insights about the tumor microenvironment. Functional data analysis (FDA) is an ideal analytic framework for connecting cell spatial relationships to patient outcomes, but can be challenging to implement. To address this need, we present mxfda, an R package for end-to-end analysis of SC spatial data using FDA.

Impact of Myc-Altered Pathology on Radiation Therapy Efficacy Among Patients With Relapsed/Refractory Large-B Cell Lymphoma: A Collaborative Study by ILROG.

Purpose: The presence of MYC and BCL2 translocations (ie, double-hit lymphoma, DHL) in large B-cell lymphoma (LBCL) is associated with reduced chemosensitivity, but less is known on its impact on radiotherapy (RT) efficacy.

Methods And Materials: Patients with LBCL who received their first course of RT for relapsed/refractory disease between 2008 and 2020 were eligible if there was adequate pathologic evaluation to be categorized as DHL versus non-DHL as per the World Health Organization (fifth edition). Separate analyses were conducted by treatment intent.

Towards melanoma in situ vaccination with multiple ultra-narrow X-ray beams.

Despite the recent progress, current treatment modalities are not able to eradicate cancer. We show that Microbeam Radiotherapy (MRT), an innovative type of Spatially Fractionated Radiotherapy, can control murine melanoma by activating the host's own immune system. The beneficial effects are very pronounced in comparison to uniform radiotherapy traditionally employed in the clinic.

Survival Distinctions for Cases Representing Immunologically Cold Tumors via Intrinsic Disorder Assessments for Blood-Sourced TRB Variable Regions.

T cell receptor beta (TRB) sequences were recovered from the Cancer Genome Atlas Uveal Melanoma blood exome files. Intrinsic disorder scores for amino acid (AA) sequences of the entire TRB variable region were obtained and evaluated as potentially representative of overall survival (OS) distinctions, i.e.

Evolution of Molecular Biomarkers and Precision Molecular Therapeutic Strategies in Glioblastoma.

Glioblastoma is the most commonly occurring malignant brain tumor, with a high mortality rate despite current treatments. Its classification has evolved over the years to include not only histopathological features but also molecular findings. Given the heterogeneity of glioblastoma, molecular biomarkers for diagnosis have become essential for initiating treatment with current therapies, while new technologies for detecting specific variations using computational tools are being rapidly developed.