Long-Term Risk of Clinically Significant Prostate Cancer in Biopsy-Negative Patients With Baseline Biparametric Prostate MRI.

Background: The long-term prevalence of clinically significant prostate cancer (csPCa) in patients with initial negative prostate biopsy is unknown.

Purpose: To investigate the rate of csPCa of men with initial negative biopsy.

Study Type: Retrospective analysis of prospectively collected data.

Patient Outcomes in Resected Combined Hepatocellular Cholangiocarcinoma (cHCC-ICC) and Intrahepatic Cholangiocarcinoma: A Single Center Study.

Background/objectives: Combined hepatocellular cholangiocarcinoma (cHCC-ICC) is a rare malignancy that involves a combination of features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC) and exhibits a more aggressive clinical course; however, its risk factors and outcomes remain largely undefined.

Methods: This study is a single-center retrospective study of 82 patients diagnosed with ICC or cHCC-ICC who underwent surgical resection from June 2011 to January 2023. Our analysis included 70 patients with resected ICC and 12 with resected cHCC-ICC.

Expansion of an Academic Molecular Tumor Board to Enhance Access to Biomarker-Driven Trials and Therapies in the Rural Southeastern United States.

Targeting tumor-specific molecular alterations has shown significant clinical benefit. Molecular tumor boards (MTBs) connect cancer patients with personalized treatments and clinical trials. However, rural cancer centers often have limited access to MTB expertise.

Imperatorin Suppresses Aberrant Hedgehog Pathway and Overcomes Smoothened Antagonist Resistance via STAT3 Inhibition.

Background: Hyperactive Hedgehog (Hh) signaling initiates and drives the progression of various tumors. Despite the clinical success of Hh inhibitors targeting Smoothened (SMO), drug resistance, often stemming from SMO mutations, remains a formidable obstacle in cancer therapy. Here, we investigated the potential of imperatorin (IMP), a Chinese herbal medicine, to overcome drug resistance and revealed the potential mechanisms.

Screening and surveillance practices for Multiple Endocrine Neoplasia type 1-related Neuroendocrine Tumours in European Neuroendocrine Tumor Society Centers of Excellence (ENETS CoE)-An ENETS MEN1 task force questionnaire study.

Multiple Endocrine Neoplasia type 1 (MEN1) Clinical Practice Guidelines (2012) are predominantly based on expert opinion due to limited available evidence at the time, leaving room for interpretation and variation in practices. Evidence on the natural course of MEN1-related neuroendocrine tumours (NET) and the value of screening programs has increased and new imaging techniques have emerged. The aim of this study is to provide insight in the current practices of screening and surveillance for MEN1-related NETs in ENETS Centers of Excellence (CoEs).

Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer.

Despite the established use of immune checkpoint inhibitors (ICIs) to treat non-small cell lung cancer (NSCLC), only a subset of patients benefit from treatment and ∼50% of patients whose tumors respond eventually develop acquired resistance (AR). To identify novel drivers of AR, we generated murine Msh2 knock-out (KO) lung tumors that initially responded but eventually developed AR to anti-PD-1, alone or in combination with anti-CTLA-4. Resistant tumors harbored decreased infiltrating T cells and reduced cancer cell-intrinsic MHC-I and MHC-II levels, yet remained responsive to IFNγ.

Frailty integration in medical specialties: Current evidence and suggested strategies from the Clin-STAR frailty interest group.

Frailty is a syndrome that can inform clinical treatments and interventions for older adults. Although implementation of frailty across medical subspecialties has the potential to improve care for the aging population, its uptake has been heterogenous. While frailty assessment is highly integrated into certain medical subspecialties, other subspecialties have only recently begun to consider frailty in the context of patient care.

Radiosynthesis and evaluation of a novel F-labeled tracer for PET imaging of glycogen synthase kinase 3.

Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine kinase family that regulates diverse biological processes including glucose metabolism, insulin activity and energy homeostasis. Dysregulation of GSK3 is implicated in the development of several diseases such as type 2 diabetes mellitus, Alzheimer's disease (AD), and various cancer types. In this study, we report the synthesis and evaluation of a novel positron emission tomography (PET) ligand compound 28 (codenamed [F]GSK3-2209).

Radiosynthesis and preclinical evaluation of a carbon-11 labeled PET ligand for imaging metabotropic glutamate receptor 7.

Metabotropic glutamate receptor 7 (mGlu) is a G protein-coupled receptor that is preferentially found in the active zone of neurotransmitter release in the central nervous system (CNS). mGlu plays a vital role in memory, learning, and neuronal development, rendering it a potential target for treating epilepsy, depression, and anxiety. The development of noninvasive imaging ligands targeting mGlu could help elucidate the functional significance of mGlu and accelerate drug discovery for neurological and psychiatric disorders.

Commercial Prices and Care for Medicare Beneficiaries With Prostate Cancer.

Objective: To examine the relationship between market dynamics, in the form of commercial prices paid to urologists, and utilization of services, as measured by Medicare spending, in men with newly diagnosed prostate cancer.

Methods: We performed a retrospective national cohort study of Medicare beneficiaries with newly diagnosed prostate cancer between 2014 and 2019, with follow-up through 2020. The primary exposure was the commercial price index (ie, the ratio of commercial prices to Medicare prices for a common set of services performed by urologists).

The toxicological role of Myricetin in the progression of human anaplastic thyroid cancer SW1736 cell line.

Aims And Background: Anaplastic thyroid cancer cells lack the capacity to effectively accumulate iodine and are therefore unresponsive to treatment with radioactive iodine. The main objective of this study was to examine the possible therapeutic effects of Myricetin on the SW1736 ATC cell line. In this study, we assessed the influence of Myricetin on iodide absorption, sodium iodide symporter gene expression, and apoptosis induction.

Setting the Standard for the Future of Cancer Surgery: Utilizing the Operative Standards for Trainees.

The purpose of this editorial is to illustrate how the Operative Standards for Cancer Surgery can be used as a tool to support education of surgical trainees. The three-volume text is a valuable resource not only for learning the scientific principles related to surgical oncology, but also as a technical guide for critical aspects of performing operations and a primer for quality assurance going forward in a surgical career.

Associations of blood lipids and LDL cholesterol lowering drug-targets with colorectal cancer risk: a Mendelian randomisation study.

Background: Whether blood lipids are causally associated with colorectal cancer (CRC) risk remains unclear.

Methods: Using two-sample Mendelian randomisation (MR), our study examined the associations of genetically-predicted blood concentrations of lipids and lipoproteins (primary: LDL-C, HDL-C, triglycerides, and total cholesterol), and genetically-proxied inhibition of HMGCR, NPC1L1, and PCSK9 (which mimic therapeutic effects of LDL-lowering drugs), with risks of CRC and its subsites. Genetic associations with lipids were obtained from the Global Lipids Genetics Consortium (n = 1,320,016), while genetic associations with CRC were obtained from the largest existing CRC consortium (n = 58,221 cases and 67,694 controls).

Differentiating Separate Primary Lung Adenocarcinomas From Intrapulmonary Metastases With Emphasis on Pathological and Molecular Considerations: Recommendations From the International Association for the Study of Lung Cancer Pathology Committee.

Introduction: With the implementation of low-dose computed tomography screening, multiple pulmonary tumor nodules are diagnosed with increasing frequency and the selection of surgical treatments versus systemic therapies has become challenging on a daily basis in clinical practice. In the presence of multiple carcinomas, especially adenocarcinomas, pathologically determined to be of pulmonary origin, the distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is important for staging, management, and prognostication.

Methods: We systemically reviewed various means that aid in the differentiation between SPLCs and IPMs explored by histopathologic evaluation and molecular profiling, the latter includes DNA microsatellite analysis, array comparative genomic hybridization, TP53 and oncogenic driver mutation testing and, more recently, with promising effectiveness, next-generation sequencing comprising small- or large-scale multi-gene panels.

Ga labeled Olmutinib: Design, synthesis, and evaluation of a novel PET EGFR probe.

Radiolabeled tyrosine kinase inhibitors (TKIs) offer a promising approach for molecular imaging of EGFR-positive cancers. Despite the development of various EGFR small-molecule probes, none of the Ga-labeled small-molecule probes based on the chelator DOTA have shown tumor-specific uptake. To address this challenge, we selected Olmutinib, a third-generation EGFR covalent inhibitor, as a PET imaging tracer for EGFR-positive tumors.

Integrating machine learning-predicted circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in metastatic breast cancer: A proof of principle study on endocrine resistance profiling.

The study explored endocrine resistance by leveraging machine learning to establish the prognostic stratification of predicted Circulating tumor cells (CTCs), assessing its integration with circulating tumor DNA (ctDNA) features and contextually evaluate the potential of CTCs-based transcriptomics. 1118 patients with a diagnosis of luminal-like Metastatic Breast Cancer (MBC) were characterized for ctDNA through NGS before treatment start, predicted CTCs were computed through a K nearest neighbor algorithm. Differences across subgroups were analyzed through chi square or Fisher's exact test according to sample size and corrected for False Discovery Rate.

Cancer cells restrict immunogenicity of retrotransposon expression via distinct mechanisms.

To thrive, cancer cells must navigate acute inflammatory signaling accompanying oncogenic transformation, such as via overexpression of repeat elements. We examined the relationship between immunostimulatory repeat expression, tumor evolution, and the tumor-immune microenvironment. Integration of multimodal data from a cohort of pancreatic ductal adenocarcinoma (PDAC) patients revealed expression of specific Alu repeats predicted to form double-stranded RNAs (dsRNAs) and trigger retinoic-acid-inducible gene I (RIG-I)-like-receptor (RLR)-associated type-I interferon (IFN) signaling.