Tumour-intrinsic PDL1 signals regulate the Chk2 DNA damage response in cancer cells and mediate resistance to Chk1 inhibitors.

Background: Aside from the canonical role of PDL1 as a tumour surface-expressed immune checkpoint molecule, tumour-intrinsic PDL1 signals regulate non-canonical immunopathological pathways mediating treatment resistance whose significance, mechanisms, and therapeutic targeting remain incompletely understood. Recent reports implicate tumour-intrinsic PDL1 signals in the DNA damage response (DDR), including promoting homologous recombination DNA damage repair and mRNA stability of DDR proteins, but many mechanistic details remain undefined.

Methods: We genetically depleted PDL1 from transplantable mouse and human cancer cell lines to understand consequences of tumour-intrinsic PDL1 signals in the DNA damage response.

Oxygen Consumption In Vivo by Ultra-High Dose Rate Electron Irradiation Depends Upon Baseline Tissue Oxygenation.

Purpose: This study aimed to assess the impact of tissue oxygen levels on transient oxygen consumption induced by ultra-high dose rate (UHDR) electron radiation in murine flank and to examine the effect of dose rate variations on this relationship.

Methods And Materials: Real-time oximetry using the phosphorescence quenching method and Oxyphor PdG4 molecular probe was employed. Continuous measurements were taken during radiation delivery on a UHDR-capable Mobetron linear accelerator.

Potential Therapeutic Targets for the Treatment of HPV-Associated Malignancies.

This review article aims to summarize broadly recent developments in the treatment of HPV-associated cancers, including cervical cancer and head and neck squamous cell carcinoma. Relatively new treatments targeting the key HPV E6 and E7 oncoproteins, including gene editing with TALENs and CRISPR/Cas9, are discussed. Given the increased immunogenicity of HPV-related diseases, other therapies such as PRR agonists, adoptive cell transfer, and tumor vaccines are reaching the clinical trial phase.

Medical Tourism for Cancer Treatment: Trends, Trajectories, and Perspectives From African Countries.

Purpose: Cancer continues to be a significant public health concern. Sub-Saharan Africa (SSA) struggles with a lack of proper infrastructure and adequate cancer care workforce. This has led to some countries relying on referrals of cancer care to countries with higher income levels.

A protein phosphatase 1 specific phatase rgeting eptide (PhosTAP) to identify the PP1 phosphatome.

Phosphoprotein phosphatases (PPPs) are the key serine/threonine phosphatases that regulate all essential signaling cascades. In particular, Protein Phosphatase 1 (PP1) dephosphorylates ~80% of all ser/thr phosphorylation sites. Here, we developed a phosphatase targeting peptide (PhosTAP) that binds all PP1 isoforms and does so with a stronger affinity than any other known PP1 regulator.

Alpha-1-B glycoprotein (A1BG) inhibits sterol-binding and export by CRISP2.

Proteins belonging to the CAP superfamily are present in all kingdoms of life and have been implicated in various processes, including sperm maturation and cancer progression. They are mostly secreted glycoproteins and share a unique conserved CAP domain. The precise mode of action of these proteins, however, has remained elusive.

Patient Perceptions on the Follow-Up of Abnormal Cancer Screening Test Results.

Background: Timely follow-up after an abnormal cancer screening test result is needed to maximize the benefits of screening, but is frequently not achieved. Little is known about patient experiences with the process of following up abnormal screening results.

Objective: Assess patient experiences and perceptions regarding the process of a diagnostic workup following abnormal breast, cervical, or colorectal cancer screening results.

Cyclin A/Cdk1 promotes chromosome alignment and timely mitotic progression.

To ensure genomic fidelity, a series of spatially and temporally coordinated events is executed during prometaphase of mitosis, including bipolar spindle formation, chromosome attachment to spindle microtubules at kinetochores, the correction of erroneous kinetochore-microtubule (k-MT) attachments, and chromosome congression to the spindle equator. Cyclin A/Cdk1 kinase plays a key role in destabilizing k-MT attachments during prometaphase to promote correction of erroneous k-MT attachments. However, it is unknown whether Cyclin A/Cdk1 kinase regulates other events during prometaphase.

Off-Protocol Radiation Therapy in Phase 3 Metastatic Solid Tumor Trials.

Purpose: Increasing data suggest that radiation therapy, particularly ablative radiation therapy, alters the natural history of metastatic disease. For patients with metastatic disease enrolled in prospective trials testing systemic therapy, the use of off-protocol radiation therapy to improve clinical symptoms or extend the duration of study systemic therapy may influence study endpoints. We sought to evaluate how often off-protocol radiation therapy was permitted among systemic therapy phase 3 trials, how often off-protocol radiation therapy is used, and whether off-protocol radiation therapy correlated with study outcomes.

Cherenkov imaging combined with scintillation dosimetry provides real-time positional and dose monitoring for radiotherapy patients with cardiac implanted electronic devices.

Background And Purpose: Cardiac implanted electronic devices (CIED) require dose monitoring during each fraction of radiotherapy, which can be time consuming and may have delayed read-out times. This study explores the potential of Cherenkov imaging combined with scintillation dosimetry as an alternative verification system.

Methods And Materials: Time-gated, complementary metal-oxide-semiconductor (iCMOS) cameras were used to collect video images of anthropomorphic phantoms and patients undergoing radiation treatment near chest wall cardiac devices.

An Abscopal Effect on Lung Metastases in Canine Mammary Cancer Patients Induced by Neoadjuvant Intratumoral Immunotherapy with Cowpea Mosaic Virus Nanoparticles and Anti-Canine PD-1.

Neoadjuvant intratumoral (IT) therapy could amplify the weak responses to checkpoint blockade therapy observed in breast cancer (BC). In this study, we administered neoadjuvant IT anti-canine PD-1 therapy (IT acPD-1) alone or combined with IT cowpea mosaic virus therapy (IT CPMV/acPD-1) to companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. CMC patients treated weekly with acPD-1 (n = 3) or CPMV/acPD-1 (n = 3) for four weeks or with CPMV/acPD-1 (n = 3 patients not candidates for surgery) for up to 11 weeks did not experience immune-related adverse events.

Association Between False-Positive Results and Return to Screening Mammography in the Breast Cancer Surveillance Consortium Cohort.

Background: False-positive results on screening mammography may affect women's willingness to return for future screening.

Objective: To evaluate the association between screening mammography results and the probability of subsequent screening.

Design: Cohort study.

Surgeon and Care Team Network Measures and Timely Breast Cancer Treatment.

Importance: Cancer treatment delay is a recognized marker of worse outcomes. Timely treatment may be associated with physician patient-sharing network characteristics, yet this remains understudied.

Objective: To examine the associations of surgeon and care team patient-sharing network measures with breast cancer treatment delay.

Immune checkpoint blockade: timing is everything.

Neoadjuvant immunotherapy effectively uses the in situ tumor as a reservoir of tumor antigens to promote systemic antitumor immunity. Studies indicate that intratumoral responses to immune checkpoint inhibitors (ICIs) are mediated by resident memory T cells cells that are sequestered in tumors and have specificity for a wide range of tumor antigens ICI treatment produces de novo priming of CD8 T cells in tumor and in tumor-draining lymph nodes, and can boost the antitumor immune response by blocking inhibitory checkpoint proteins that can turn off T cells within the tumor. Neoadjuvant ICI treatment can enhance both intratumoral and systemic antitumor immunity, including expansion of intratumoral T-cell clones which is strongly associated with pathological treatment response.

Radiotherapy dosing in intracranial ependymoma using the national cancer database.

Purpose: To determine the dose-dependent effect of adjuvant radiotherapy on survival for pediatric intracranial ependymomas and explore patient and disease characteristics that experience survival benefit from higher doses.

Methods: Data was accessed from the National Cancer Database. Inclusion criteria was comprised of a diagnosis of non-metastatic intracranial ependymoma, World Health Organization (WHO) grade 2 or 3, surgical resection, adjuvant radiotherapy between 4500-6300 cGy, and non-missing survivorship data.

High-Risk HPV Screening Initiative in Kosovo-A Way to Optimize HPV Vaccination for Cervical Cancer.

Nearly all cervical cancers are caused by persistent high-risk human papillomavirus (hrHPV) infection. There are 14 recognized hrHPV genotypes (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), and hrHPV genotypes 16 and 18 comprise approximately 66% of all cases worldwide. An additional 15% of cervical cancers are caused by hrHPV genotypes 31, 33, 45, 52, and 58.

Breast Cancer Screening Using Mammography, Digital Breast Tomosynthesis, and Magnetic Resonance Imaging by Breast Density.

Importance: Information on long-term benefits and harms of screening with digital breast tomosynthesis (DBT) with or without supplemental breast magnetic resonance imaging (MRI) is needed for clinical and policy discussions, particularly for patients with dense breasts.

Objective: To project long-term population-based outcomes for breast cancer mammography screening strategies (DBT or digital mammography) with or without supplemental MRI by breast density.

Design, Setting, And Participants: Collaborative modeling using 3 Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer simulation models informed by US Breast Cancer Surveillance Consortium data.

Quantifying Forms and Functions of Enterohepatic Bile Acid Pools in Mice.

Backgrounds & Aims: Bile acids (BAs) are core gastrointestinal metabolites with dual functions in lipid absorption and cell signaling. BAs circulate between the liver and distal small intestine (i.e.