The spatially informed mFISHseq assay resolves biomarker discordance and predicts treatment response in breast cancer.

Current assays fail to address breast cancer's complex biology and accurately predict treatment response. On a retrospective cohort of 1082 female breast tissues, we develop and validate mFISHseq, which integrates multiplexed RNA fluorescent in situ hybridization with RNA-sequencing, guided by laser capture microdissection. This technique ensures tumor purity, unbiased whole transcriptome profiling, and explicitly quantifies intratumoral heterogeneity.

Maximizing the clinical utility and performance of cytology samples for comprehensive genetic profiling.

Comprehensive molecular profiling by next-generation sequencing has revolutionized tumor classification and biomarker evaluation. However, routine implementation is challenged by the scant nature of diagnostic material obtained through minimally invasive procedures. Here, we describe our long-term experience in profiling cytology samples with an in-depth assessment of the performance, quality metrics, biomarker identification capabilities, and potential pitfalls.

Multiparametric MRI and artificial intelligence in predicting and monitoring treatment response in bladder cancer.

Bladder cancer is the 10th most common and 13th most deadly cancer worldwide, with urothelial carcinomas being the most common type. Distinguishing between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) is essential due to significant differences in management and prognosis. MRI may play an important diagnostic role in this setting.

Invasion of glioma cells through confined space requires membrane tension regulation and mechano-electrical coupling via Plexin-B2.

Glioblastoma (GBM) is a malignant brain tumor with diffuse infiltration. Here, we demonstrate how GBM cells usurp guidance receptor Plexin-B2 for confined migration through restricted space. Using live-cell imaging to track GBM cells negotiating microchannels, we reveal endocytic vesicle accumulation at cell front and filamentous actin assembly at cell rear in a polarized manner.

A Bayesian active learning platform for scalable combination drug screens.

Large-scale combination drug screens are generally considered intractable due to the immense number of possible combinations. Existing approaches use ad hoc fixed experimental designs then train machine learning models to impute unobserved combinations. Here we propose BATCHIE, an orthogonal approach that conducts experiments dynamically in batches.

A deep multiple instance learning framework improves microsatellite instability detection from tumor next generation sequencing.

Microsatellite instability (MSI) is a critical phenotype of cancer genomes and an FDA-recognized biomarker that can guide treatment with immune checkpoint inhibitors. Previous work has demonstrated that next-generation sequencing data can be used to identify samples with MSI-high phenotype. However, low tumor purity, as frequently observed in routine clinical samples, poses a challenge to the sensitivity of existing algorithms.

STAT1 regulates immune-mediated intestinal stem cell proliferation and epithelial regeneration.

The role of the immune system in regulating tissue stem cells remains poorly understood, as does the relationship between immune-mediated tissue damage and regeneration. Graft vs. host disease (GVHD) occurring after allogeneic bone marrow transplantation (allo-BMT) involves immune-mediated damage to the intestinal epithelium and its stem cell compartment.

Mms22-Rtt107 axis attenuates the DNA damage checkpoint and the stability of the Rad9 checkpoint mediator.

The DNA damage checkpoint is a highly conserved signaling pathway induced by genotoxin exposure or endogenous genome stress. It alters many cellular processes such as arresting the cell cycle progression and increasing DNA repair capacities. However, cells can downregulate the checkpoint after prolonged stress exposure to allow continued growth and alternative repair.

Adjuvant Dose-Dense Chemotherapy in Hormone Receptor-Positive Breast Cancer.

Purpose: In light of evolving evidence that some patients with node-positive estrogen receptor-positive (ER+) disease may receive less benefit from chemotherapy, this study reports 12-year outcomes of the C9741 trial overall, and by the sensitivity to endocrine therapy (SET2,3) test index, a biomarker measuring endocrine transcriptional activity, to identify patients most likely to benefit from dose-dense chemotherapy.

Methods: In all, 1,973 patients were randomly assigned to dose-dense versus conventional chemotherapy. Hazard ratios (HRs) for prognosis and for predictive interaction with chemotherapy schedule were estimated from Cox models of long-term disease-free survival (DFS) and overall survival (OS).

Voxel-Based Dosimetry Predicts Local Tumor Progression Post 90Y Radiation Segmentectomy of Colorectal Liver Metastases.

Background: Radiation segmentectomy (RS) is an alternative potential local curative treatment for selected colorectal liver metastases (CLMs) not amenable to ablation or limited resection.

Purpose: The aim of this study was to evaluate the dosimetric response of low volume CLMs to RS in heavily pretreated patients who are not candidates for resection or percutaneous ablation.

Patients And Methods: This single-center retrospective study evaluated CLMs patients treated with RS (prescribed tumor dose >190 Gy) from 2015 to 2023.

Rapid on-site evaluation using telecytology: Quality assurance study at a high-volume cancer center.

Background: Telecytology-assisted rapid on-site evaluation (ROSE) offers a cost-effective method to enhance minimally invasive biopsies like fine needle aspiration and core biopsies with touch preparation. By reducing nondiagnostic sampling and the need for repeat procedures, ROSE via telecytology facilitates prompt triage for ancillary tests, improving patient management. This study examines cases initially deemed adequate for diagnosis during telecytology-assisted ROSE but later categorized as nondiagnostic at final evaluation (NDIS).

Evaluation of the Ki-67 labeling index on immediate pre-ablation biopsies as a predictive biomarker of local recurrence of colorectal cancer liver metastases.

The aim of this study was to evaluate if the Ki-67 labeling index (LI) on immediate pre-ablation biopsies of colorectal liver metastases (CLM) is associated with the presence of viable tumor cells in subsequent ablation zone biopsies and/or local tumor progression-free survival (LTPFS). Biopsies of CLM were performed before and after microwave ablation (MWA), as part of a prospective clinical trial between October 2013 and May 2019. Pre-ablation biopsy slides were examined for the Ki-67 LI using light microscopy.

First clinical utility of sensing Ultrasound Localization Microscopy (sULM): identifying renal pseudotumors.

Renal pseudotumors, which mimic tumors on imaging, pose diagnostic challenges that can lead to unnecessary interventions. Sensing ultrasound localization microscopy (sULM) is an advanced imaging technique that uses ultrasound imaging and microbubbles as sensors to visualize kidney functional units. This study aims to investigate whether sULM could differentiate between renal pseudotumors and tumors based on the presence of glomeruli.

Tau is a receptor with low affinity for glucocorticoids and is required for glucocorticoid-induced bone loss.

Glucocorticoids (GCs) are the most prescribed anti-inflammatory and immunosuppressive drugs. However, their use is often limited by substantial side effects, such as GC-induced osteoporosis (GIO) with the underlying mechanisms still not fully understood. In this study, we identify Tau as a low-affinity binding receptor for GCs that plays a crucial role in GIO.

Single-cell profiling aligns CD56 and cytomegalovirus-induced adaptive natural killer cells to a naïve-memory relationship.

Development of antigen-specific memory upon pathogen exposure is a hallmark of the adaptive immune system. While natural killer (NK) cells are considered part of the innate immune system, humans exposed to the chronic viral pathogen cytomegalovirus (CMV) often possess a distinct NK cell population lacking in individuals who have not been exposed, termed "adaptive" NK cells. To identify the "naïve" population from which this "memory" population derives, we performed phenotypic, transcriptional, and functional profiling of NK cell subsets.

Professional-patient discrepancies in assessing lung cancer radiotherapy symptoms: An international multicentre study.

Background And Purpose: We investigate discrepancies in the assessment of treatment-related symptoms in lung cancer between healthcare professionals and patients, and factors contributing to these discrepancies.

Materials And Methods: Data from 515 participants in the REQUITE study were analysed. Five symptoms (cough, dyspnoea, bronchopulmonary haemorrhage, chest wall pain, dysphagia) were evaluated both before and after radiotherapy.

Deep Learning Predicts Subtype Heterogeneity and Outcomes in Luminal A Breast Cancer Using Routinely Stained Whole Slide Images.

Intratumor heterogeneity (ITH) presents challenges for precision oncology, but methods for its spatial quantification, scalable at population levels, do not exist. Based on previous work showing that admixture of PAM50 subtype can be measured from bulk tissue using transcriptomic data, we trained a deep neural network (DNN) to quantify subtype ITH in Luminal A (LumA) breast cancer from routinely-stained whole slide images. We tested the hypothesis that subtype admixture detected in images was associated with tumor aggressiveness and adverse outcome.

Clinical outcomes by baseline metastases in patients with renal cell carcinoma treated with lenvatinib plus pembrolizumab versus sunitinib: Post hoc analysis of the CLEAR trial.

Lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib in treatment of advanced renal cell carcinoma (aRCC) in the phase 3 CLEAR study. We report results of an exploratory post hoc analysis of tumor response data based on baseline metastatic characteristics of patients who received lenvatinib plus pembrolizumab versus sunitinib, at the final overall survival analysis time point of CLEAR (cutoff: July 31, 2022). Treatment-naïve adults with aRCC were randomized to: lenvatinib (20 mg PO QD in 21-day cycles) plus pembrolizumab (n = 355; 200 mg IV Q3W); lenvatinib plus everolimus (not reported here); or sunitinib (n = 357; 50 mg PO QD; 4 weeks on/2 weeks off).

Localized molecular chaperone synthesis maintains neuronal dendrite proteostasis.

Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. However, this is challenging in neuronal projections because of their polarized morphology and constant synaptic proteome remodeling. Using high-resolution fluorescence microscopy, we discover that hippocampal and spinal cord motor neurons of mouse and human origin localize a subset of chaperone mRNAs to their dendrites and use microtubule-based transport to increase this asymmetric localization following proteotoxic stress.

PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial.

Here we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.

Combined Autologous Breast Reconstruction and Gynecologic Procedures: Does Timing Affect Clinical and Patient-Reported Outcomes?

Background: Patients with or at risk for breast cancer may opt for risk-reducing gynecologic surgeries, including bilateral salpingo-oophorectomies and/or total abdominal hysterectomy. The timing and safety of combining these procedures with autologous breast reconstruction (ABR) are debated. This study assesses the impact of concurrent ABR and gynecologic surgeries on clinical and patient-reported outcomes.

Moving Towards the Outpatient DIEP Flap: Factors Influencing Early Discharge.

Background: Enhanced Recovery After Surgery (ERAS) protocols can reduce the length of stay (LOS) for surgical patients, including those undergoing unilateral deep inferior epigastric artery perforator (DIEP) flap breast reconstruction, allowing most patients to be discharged by postoperative day 2. However, some patients require a prolonged inpatient stay due to difficulty completing postoperative milestones. This study aims to identify factors associated with increased LOS after DIEP flap breast reconstruction and assess safety of earlier discharge.