hnRNPLL regulates MYOF alternative splicing and correlates with early metastasis in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer known for its high rate of early metastasis, necessitating the discovery of the underlying mechanisms. Herein, we report that heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) expression significantly increases at the invasion forefront in PDAC and is associated with early metastasis and poor prognosis. Our findings revealed that hnRNPLL knockdown resulted in extensive exon skipping (ES) events.

Functional outcomes of single-session holmium laser enucleation of the prostate and high-intensity focused ultrasound in management of patients with prostate cancer and enlarged prostate: results from a pilot study.

Purpose: In patients with prostate cancer (PCa), focal therapy with High-Intensity Focused Ultrasound (HIFU) combined with benign prostatic hyperplasia (BPH) surgery has been used to improve immediate post-operative voiding symptoms. Our study aimed to evaluate the functional outcomes of patients undergoing simultaneous holmium laser enucleation of the prostate (HoLEP) + HIFU and compare them to those who underwent HoLEP for bladder outlet obstruction secondary to BPH.

Methods: We performed retrospective review of patients who underwent HoLEP + HIFU or HoLEP between June 2017 and May 2024.

Impact of insurance on outcomes of patients undergoing endoscopic transsphenoidal surgery for non-functional pituitary adenomas: a single institution study.

Purpose: Uninsured and underinsured patients face notable healthcare disparities in neurosurgery, but limited literature exists on the impact of insurance on non-functioning pituitary adenomas (NFPAs). We investigated how insurance affects outcomes of endoscopic transsphenoidal pituitary surgery (ETPS) for NFPAs.

Methods: We retrospectively reviewed NFPA patients who underwent ETPS at our institution from 2012 to 2023.

The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma.

Isocitrate dehydrogenase (IDH)-mutant gliomas are the most common malignant primary brain tumors in young adults. This condition imposes a substantial burden on patients and their caregivers, marked by neurocognitive deficits and high mortality rates due to tumor progression, coupled with significant morbidity from current treatment modalities. Although surgery, radiation therapy, and chemotherapy improve survival, these treatments can adversely affect cognitive function, quality of life, finances, employment status, and overall independence.

Monoclonal gammopathy of undetermined significance and the risk of thrombotic events: Results from iStopMM, a prospective population-based screening study.

Monoclonal gammopathy of undetermined significance (MGUS) is the asymptomatic precursor of multiple myeloma and related diseases but has also been associated with thrombosis. Prior studies have not been based on screened cohorts leading to bias. We assessed the risk of thrombosis in a cohort of 75 422 individuals over 40 years old who were screened for MGUS in Iceland.

Antigen-presenting cell activation requires intrinsic and extrinsic STING signaling after the phagocytosis of DNA-damaged cells.

Antigen-presenting cells (APCs) are readily activated after phagocytosing infected or DNA-damaged cells but not normal apoptotic cells for reasons that are not well understood. Here, we demonstrate that after DNA damage events, cytosolic dsDNA species trigger intrinsic STING signaling and the production of key immunogenic proteins, including CCL5, which renders such cells capable of APC activation upon phagocytosis. These events involve the generation of immunogenic STING-inducible endosomal vesicles (SIEVEs) additionally comprising critical autophagy-associated proteins associated with cytosolic DNA species.

Olutasidenib demonstrates significant clinical activity in mutated IDH1 acute myeloid leukaemia arising from a prior myeloproliferative neoplasm.

Acute myeloid leukaemia (AML) arising from a myeloproliferative neoplasm (MPN) is more aggressive and less responsive to therapies compared to de novo AML. Olutasidenib, an oral small-molecule inhibitor of mutated IDH1 (mIDH1), showed encouraging and durable responses in a phase 1/2 study of adults with post-MPN mIDH1 AML. Patients received olutasidenib 150 mg BID monotherapy or in combination with azacitidine.

Approaching Hypercalcemia in Monoclonal Gammopathy of Undetermined Significance: Insights from the iStopMM study.

Hypercalcemia in monoclonal gammopathy of undetermined significance (MGUS) presents a clinical challenge since it may indicate progression to multiple myeloma (MM) but could also be due to a multitude of unrelated disorders. To inform the approach to this clinical challenge, we conducted a nested cohort study within the iStopMM screening study. Of the 75,422 Icelanders aged 40 years and above who underwent screening for MGUS, we included 2,546 with MGUS who were in active follow-up, including regular serum calcium measurements.

HRS Improves Active Surveillance for Prostate Cancer by Timely Identification of Progression.

Rationale And Objectives: Active surveillance (AS) is the preferred management strategy for low-risk prostate cancer. This study aimed to evaluate the impact of Habitat Risk Score (HRS), an automated approach for mpMRI analysis, for early detection of progressors in a prospective AS clinical trial (MAST NCT02242773).

Materials And Methods: The MAST protocol includes Confirmatory mpMRI ultrasound fusion (MRI-US) biopsy and yearly surveillance MRI-US biopsies for up to 3 years.

Adaptation of meaning-centered psychotherapy for healthcare providers to buffer work-induced distress and improve wellbeing.

Healthcare providers (HCPs) face high rates of distress, experienced as burnout, moral distress, compassion fatigue, and grief. HCPs are also experiencing a crisis in meaning whereby distress is associated with disconnection from meaning in work and, in turn, a lack of meaning in work can further perpetuate distress for HCPs. Although scalable systems-level solutions are needed to tackle multidimensional HCP distress, it is also necessary to address HCP suffering at individual, team, and institutional levels.

Perspectives of the medical oncologist regarding adjuvant chemotherapy for pancreatic cancer: An international expert survey and case vignette study.

Introduction: Adjuvant chemotherapy improves survival in patients with resected pancreatic ductal adenocarcinoma (PDAC). The decision to initiate chemotherapy involves both patient and physician factors, decision-specific criteria, and contextual considerations. This study aimed to assess medical oncologists' views on adjuvant chemotherapy following pancreatic resection for PDAC.

High-Throughput Drug Screening in Chondrosarcoma Cells Identifies Effective Antineoplastic Agents Independent of IDH Mutation.

The term chondrosarcoma refers to a rare and heterogeneous group of malignant cartilaginous tumors that are typically resistant to chemotherapy and radiotherapy. Metastatic chondrosarcoma has a poor prognosis, and effective systemic therapies are lacking. Isocitrate dehydrogenase (IDH) mutations represent a potential therapeutic target, but IDH inhibitors alone have shown limited clinical efficacy to date.

Ultra-Processed Food and Prostate Cancer Risk: A Systemic Review and Meta-Analysis.

Prostate cancer is the second leading cause of cancer death among American men, following lung cancer. While diet and exercise have been extensively studied in relation to prostate cancer prevention, the evidence remains inconclusive. : A comprehensive literature search was performed to identify observational studies investigating the association between ultra-processed food (UPF) consumption and prostate cancer risk and mortality, determined by the NOVA classification system.

Vitamin D in patients with low tumor-burden indolent non-Hodgkin lymphoma treated with rituximab therapy (ILyAD): a randomized, phase 3 clinical trial.

Background: There is a significant association between low vitamin D levels at diagnosis of indolent B-cell lymphomas and inferior overall survival (OS). To determine whether supplemental vitamin D improves event-free survival (EFS) in these patients, we conducted a comparative double-blind study of vitamin D vs. placebo.

Dose finding, bioavailability, and PK-PD of oral triapine with concurrent chemoradiation for locally advanced cervical cancer and vaginal cancer (ETCTN 9892).

Background: The addition of IV triapine to chemoradiation appeared active in phase I and II studies but drug delivery is cumbersome. We examined PO triapine with cisplatin chemoradiation.

Methods: We implemented a 3 + 3 design for PO triapine dose escalation with expansion, starting at 100 mg, five days a week for five weeks while receiving radiation with weekly IV cisplatin for locally advanced cervical or vaginal cancer.

Biomarker analyses from the phase 3 randomized CLEAR trial: Lenvatinib plus pembrolizumab versus sunitinib in advanced renal cell carcinoma.

Background: In CLEAR, lenvatinib + pembrolizumab (L+P) significantly improved efficacy versus sunitinib in first-line treatment of patients with advanced renal cell carcinoma (RCC). We report results from CLEAR biomarker analyses.

Methods: PD-L1 immunohistochemistry (IHC) and next-generation sequencing assays (whole exome sequencing/RNA-sequencing) were performed on archival tumor specimens.

Acalabrutinib in combination with rituximab and lenalidomide in patients with relapsed or refractory follicular lymphoma: Results of the phase 1b open-label study (ACE-LY-003).

Patients with relapsed/refractory (R/R) follicular lymphoma (FL) have limited effective treatment options. Bruton tyrosine kinase inhibitors (BTKis) increase the anti-tumoural phenotype of tumour-associated macrophages, providing rationale to combine them with rituximab and lenalidomide (R). Acalabrutinib, a second-generation BTKi, has potential to improve R efficacy without increasing T-cell-mediated toxicity due to its lack of interleukin-2-inducible T-cell kinase inhibition.

Radiation-induced nephrotoxicity: Role of SMPDL3b.

Background: Radiation nephropathy (RN) can be a significant late complication after radiotherapy for abdominal and paraspinal tumors. The mechanisms for the development of RN are thought to involve disruption of podocyte function, leading to podocyte cell death and, finally, impaired renal function. This study investigated the mechanistic role of SMPDL3b in regulating podocyte injury and renal function after irradiation.

Impact of racial, ethnic, and socioeconomic disparities on presentation and survival of HCC: A multicenter study.

Background: Racial and ethnic disparities have been reported for HCC prognosis, although few studies fully account for clinically important factors and social determinants of health, including neighborhood socioeconomic status.

Methods: We conducted a retrospective multicenter cohort study of patients newly diagnosed with HCC from January 2010 through August 2018 at 4 large health systems in the United States. We used multivariable logistic regression and cause-specific Cox proportional hazard models to identify factors associated with early-stage HCC presentation and overall survival.

Second Primary Cancer After Chimeric Antigen Receptor-T-Cell Therapy: A Review.

Importance: The commercialization of chimeric antigen receptor-T-cell (CAR-T) therapy has changed the landscape of treatment of hematological cancers. Numerous studies from the early 2000s paved the way for cell-based targeted therapeutics, which have been established as practice-changing therapies in lymphoma, leukemia, and multiple myeloma. However, there has been some recent concern about the risk for second primary cancers (SPCs).

Assessing the Molecular Heterogeneity of Prostate Cancer Biopsy Sampling: Insights from the MAST Trial.

Background And Objective: Prostate cancer (PC) heterogeneity can result in sampling discrepancies during biopsy, leading to inaccurate molecular classifications that affect treatment decisions. We evaluated transcriptomic profile variability between multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy (TBx) and systematic biopsy (SBx) methods using the Decipher GRID platform.

Methods: The study included 205 men from the MAST trial.