Olaparib and Radiotherapy Induce Type I Interferon- and CD8+ T Cell-Dependent Sensitization to Immunotherapy in Pancreatic Cancer.

PARP inhibitors sensitize pancreatic ductal adenocarcinoma (PDAC) to radiation by inducing DNA damage and replication stress. These mechanisms also have the potential to enhance radiation-induced type I interferon (T1IFN)-mediated antitumoral immune responses. We hypothesized that the PARP inhibitor olaparib would also potentiate radiation-induced T1IFN to promote antitumor immune responses and sensitization of otherwise resistant PDAC to immunotherapy.

Development of a RIPK1 degrader to enhance antitumor immunity.

The scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and emerges as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain of RIPK1, here we harness proteolysis targeting chimera (PROTAC) technology to develop a RIPK1 degrader, LD4172. LD4172 exhibits potent and selective RIPK1 degradation both in vitro and in vivo.

In vitro hydrolysis of areca nut xenobiotics in human liver.

Areca nut (AN) is a substance of abuse consumed by millions worldwide, in spite of established oral and systemic toxicities associated with its use. Previous research demonstrates methyl ester alkaloids in the AN, such as arecoline and guvacoline, exhibit mood-altering and toxicological effects. Nonetheless, their metabolism has not been fully elucidated in humans.

A commissioning protocol for portal imaging-based radiotherapy in vivo dosimetry systems.

Background And Purpose: With the availability of commercial electronic portal imaging detector-based in vivo dosimetry (EPID-based IVD) solutions, many radiotherapy departments are adopting this technology. However, comprehensive commissioning guidance is lacking. This study aims to provide a protocol for testing the accuracy and sensitivity of EPID-based IVD systems.

Unlocking Intracellular Oncology Targets: The Unique Role of Antibody-Based T-Cell Receptor Mimic (TCRm) Therapeutics in T-Cell Engagers (TCEs) and Antibody-Drug Conjugates (ADCs).

Effectively targeting intracellular tumor-associated proteins presents a formidable challenge in oncology, as they are traditionally considered inaccessible to conventional antibody-based therapies and CAR-T cell therapies. However, recent advancements in antibody engineering have revolutionized this field, offering promising new strategies to combat cancer. This review focuses on the innovative use of T-cell receptor mimic (TCRm) antibodies within the therapeutic frameworks of T-cell engagers (TCE) and antibody-drug conjugates (ADCs).

Standard or Extended Lymphadenectomy for Muscle-Invasive Bladder Cancer.

Background: Whether extended lymphadenectomy is associated with improved disease-free and overall survival, as compared with standard lymphadenectomy, among patients with localized muscle-invasive bladder cancer undergoing radical cystectomy is unclear.

Methods: We randomly assigned, in a 1:1 ratio, patients with localized muscle-invasive bladder cancer of clinical stage T2 (confined to muscle) to T4a (invading adjacent organs) with two or fewer positive nodes (N0, N1, or N2) to undergo bilateral standard lymphadenectomy (dissection of lymph nodes on both sides of the pelvis) or extended lymphadenectomy involving removal of common iliac, presciatic, and presacral nodes. Randomization was performed during surgery and stratified according to the receipt and type of neoadjuvant chemotherapy, tumor stage (T2 vs.

Data-Driven Cutoff Selection for the Patient Health Questionnaire-9 Depression Screening Tool.

Importance: Test accuracy studies often use small datasets to simultaneously select an optimal cutoff score that maximizes test accuracy and generate accuracy estimates.

Objective: To evaluate the degree to which using data-driven methods to simultaneously select an optimal Patient Health Questionnaire-9 (PHQ-9) cutoff score and estimate accuracy yields (1) optimal cutoff scores that differ from the population-level optimal cutoff score and (2) biased accuracy estimates.

Design, Setting, And Participants: This study used cross-sectional data from an existing individual participant data meta-analysis (IPDMA) database on PHQ-9 screening accuracy to represent a hypothetical population.

Cyclin D1-negative mantle cell lymphoma.

Cyclin D1-negative mantle cell lymphoma (MCL) is regarded as a B-cell neoplasm that has morphologic and immunophenotypic findings indistinguishable from typical MCL. These neoplasms lack cyclin D1 overexpression by immunohistochemistry and t(11;14)(q13;q32)/IGH::CCND1. Since cyclin D1-negative MCL was first recognized by gene expression profiling in 2003, there has been diagnostic confusion regarding this entity, mostly attributable to a lack of diagnostic tools to recognize these neoplasms in most clinical laboratories.

Hematopoietic Cell Transplant compared with Standard Care in Adolescents and Young Adults with Sickle Cell Disease.

Disease-modifying therapies are standard of care (SOC) for sickle cell disease (SCD), but hematopoietic cell transplantation (HCT) has curative potential. We compared outcomes prospectively through 2-years after biologic assignment to a Donor or No Donor (SOC) Arm based on the availability of an HLA-matched sibling or unrelated donor (BMTCTN 1503; NCT02766465). A donor search was commenced after eligibility confirmation.

Impact of Six Months of Three Different Modalities of Exercise on Stress in Post-Treatment Breast Cancer Survivors.

Background/objectives: Extensive evidence suggests that exercise is physically and mentally beneficial for cancer survivors. This study reports on changes in self-reported stress, physiological biomarkers for stress (salivary cortisol), and HR-QOL constructs for fifty breast cancer survivors participating in one of three different exercise programs over 6 months.

Methods: Fifty post-treatment breast cancer survivors were randomized to either therapeutic yoga-based exercise (YE), comprehensive exercise (CE) (aerobic, resistance, flexibility), or choosing (C) their own exercise activities.

Pediatric Ewing Sarcoma Presentation, Treatment, and Outcomes Across Sociodemographic Groups.

Introduction: In this study, we evaluate the association between sociodemographics and disease presentation, treatment, and survival for children, adolescents, and young adults with Ewing sarcoma.

Methods: Case-level data were downloaded from The Surveillance, Epidemiology, and End Results database. Cases included patients ages 0-24 who were diagnosed with Ewing sarcoma between 2004 and 2020.

The impact of negative COVID-19 experiences on cancer survivors' health-related quality of life and psychological distress: a moderated mediation model.

Introduction: Cancer survivors experienced poorer health-related quality of life (HRQoL) and greater psychological distress during the COVID-19 pandemic than those without cancer. However, the underlying mechanisms that may explain how negative experiences during the pandemic are associated with distress and HRQoL remain unknown. We examined whether psychosocial risk factors (i.

Optical imaging for screening and early cancer diagnosis in low-resource settings.

Low-cost optical imaging technologies have the potential to reduce inequalities in healthcare by improving the detection of pre-cancer or early cancer and enabling more effective and less invasive treatment. In this Review, we summarise technologies for in vivo widefield, multi-spectral, endoscopic, and high-resolution optical imaging that could offer affordable approaches to improve cancer screening and early detection at the point-of-care. Additionally, we discuss approaches to slide-free microscopy, including confocal imaging, lightsheet microscopy, and phase modulation techniques that can reduce the infrastructure and expertise needed for definitive cancer diagnosis.

Blast phase of chronic myeloid leukemia presenting as early T-cell precursor acute lymphoblastic leukemia.

Objectives: The blasts in most cases of chronic myeloid leukemia blast phase (CML-BP) have a myeloid or precursor-B immunophenotype, with only a small subset having T-cell or natural killer-cell lineage. Patients with CML-BP having early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) are extremely rare.

Methods: We report the clinicopathologic, immunophenotypic, and molecular genetic features and outcome of 3 patients with CML-BP who had ETP-ALL, with a review of the literature.

Computer-Aided Design and Manufacturing to Facilitate Microvascular Free Tissue Transfer in Extremity, Pelvic, and Spinal Reconstructions.

Background:  Numerous surgical fields have embraced computer-aided design and computer-aided manufacturing (CAD/CAM), including plastic and reconstructive surgery. However, most of the literature and clinical use pertains to reconstruction of the head and neck. Herein, we provide a case series and systematic review of the literature, documenting the use of CAD/CAM in facilitating complex microvascular free tissue transfer for reconstructions involving the extremities, pelvis, and spine (EPS).