Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect.

Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal microbiota transplantation (FMT) early after alloHCT reduces the incidence of severe aGVHD. Here, we report the results from the single-arm run-in phase which identified the best of 3 stool donors for the randomized phase.

ZBP1-mediated PANoptosis is a crucial lethal form in diverse keratinocyte death modalities in UVB-induced skin injury.

UVB irradiation induces diverse modalities of regulatory cell death in keratinocytes. Recently, the pattern of coexistence of pyroptosis, apoptosis, and necroptosis has been termed PANoptosis; however, whether PANoptosis occurs in keratinocytes in UVB-induced skin injury remains unclear. We observed that the key molecules of GSDMD-mediated pyroptosis, apoptosis, and necroptosis, which are N-terminal GSDMD, cleaved caspase-3/PARP, and phosphorylated MLKL, respectively, were elevated in keratinocytes of UVB-challenged mice and human skin tissue.

NetSDR: Drug repurposing for cancers based on subtype-specific network modularization and perturbation analysis.

Cancer, a heterogeneous disease, presents significant challenges for drug development due to its complex etiology. Drug repurposing, particularly through network medicine approaches, offers a promising avenue for cancer treatment by analyzing how drugs influence cellular networks on a systemic scale. The advent of large-scale proteomics data provides new opportunities to elucidate regulatory mechanisms specific to cancer subtypes.

Stereotactic body radiotherapy for non-spine bone metastases: A meta-analysis and international stereotactic radiosurgery society (ISRS) clinical practice guidelines.

Background: While SBRT to NSBM has become common, particularly in the oligometastatic population, the approach to treating non-spine bone metastases (NSBM) with stereotactic body radiotherapy (SBRT) varies widely across institutions and clinical trial protocols. We present a comprehensive systematic review of the literatures to inform practice recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS).

Methods: A systematic literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Breast cancer outcomes after skin- and nipple-sparing mastectomy in BRCA pathogenic mutation carriers versus non-BRCA carriers.

Unlabelled: Our previous study on BRCA breast cancer carriers disclosed a high local recurrence (LR) rate in patients who underwent skin sparing (SSM) or nipple sparing mastectomy (NSM) without postoperative radiation therapy (RT), compared to breast conservation surgery or mastectomy with RT. The current study compares the LR rates in BRCA versus non BRCA carriers after SSM/NSM in relation the receipt of RT.

Methods: The study was approved by the institutional ethics committee.

Rewiring cancer: 3D genome determinants of cancer hallmarks.

In modern cancer biology, Hanahan and Weinberg's classic depiction of the Hallmarks of Cancer serves as a heuristic for understanding malignant phenotypes [1]. Genetic determinants of these phenotypes promote cancer induction and progression, and these mutations drive current approaches to understanding and treating cancer. Meanwhile, for over a century, pathologists have noted that profound alterations of nuclear structure accompany transformation, integrating these changes into diagnostic classifications (Figure 1).

Clinical and Genomic Features of Androgen Indifferent Prostate Cancer.

Androgen-indifferent prostate cancer (AIPC) is increasingly common and particularly lethal. Data describing these tumors are sparse, and AIPC remains a poorly understood malignancy. Utilizing the Oncology Research Information Exchange Network (ORIEN) database, we enriched for tumors with features of AIPC using previously described characteristics.

The Impact of Radiotherapy on the Primary Tumor in Patients with Metastatic High-Volume Castration-Sensitive Prostate Cancer: A Propensity Score Matching Analysis.

Retrospective studies suggest that local radiotherapy on the prostate improves overall survival in the metastatic setting, but its benefit in patients with high-burden metastatic disease is still uncertain. We conducted a retrospective study of 100 high-metastatic-burden prostate cancer patients at Hadassah Ein Karem Medical Center from 2004 to 2021. Patients receiving local RT alongside standard treatment were compared to those receiving standard treatment alone.

Lactoferrin Modulates Radiation Response Under Hypoxic Conditions, Possibly Through the Regulation of ROS Production in a Cell Type-Specific Manner.

Lactoferrin (LF) is an iron-binding glycoprotein of the transferrin family and has been suggested to have a variety of biological functions, including anticancer activity. However, the effects of LF and its mechanisms in anticancer therapies, especially in radiotherapy against cancer cells under hypoxic conditions, are not well-determined. In this study, we focused on the molecular mechanisms of LF functions in cells under hypoxic conditions.

Epigenetic Mechanisms in the Transcriptional Regulation of Circadian Rhythm in Mammals.

Almost all organisms, from the simplest bacteria to advanced mammals, havea near 24 h circadian rhythm. Circadian rhythms are highly conserved across different life forms and are regulated by circadian genes as well as by related transcription factors. Transcription factors are fundamental to circadian rhythms, influencing gene expression, behavior in plants and animals, and human diseases.

Paediatric strategy forum for medicinal product development in diffuse midline gliomas in children and adolescents ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

Fewer than 10 % of children with diffuse midline glioma (DMG) survive 2 years from diagnosis. Radiation therapy remains the cornerstone of treatment and there are no medicinal products with regulatory approval. Although the biology of DMG is better characterized, this has not yet translated into effective treatments.

Advancing Radiobiology: Investigating the Effects of Photon, Proton, and Carbon-Ion Irradiation on PANC-1 Cells in 2D and 3D Tumor Models.

Pancreatic cancer (PC) is one of the most aggressive and lethal malignancies, calling for enhanced research. Pancreatic ductal adenocarcinoma (PDAC) represents 70-80% of all cases and is known for its resistance to conventional therapies. Carbon-ion radiotherapy (CIRT) has emerged as a promising approach due to its ability to deliver highly localized doses and unique radiobiological properties compared to X-rays.

Resistance to Radiotherapy in Cancer.

Radiation therapy or radiotherapy is a medical treatment that uses high doses of ionizing radiation to eliminate cancer cells and shrink tumors. It works by targeting the DNA within the tumor cells restricting their proliferation. Radiotherapy has been used for treating cancer for more than 100 years.

CPSF1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cells.

Localized prostate cancer can be cured by radiation or surgery, but advanced prostate cancer continues to be a clinical challenge. Altered alternative polyadenylation occurs in numerous cancers and can downregulate tumor-suppressor genes and upregulate oncogenes. We found that the cleavage and polyadenylation specificity factor (CPSF) complex factor CPSF1 is upregulated in patients with advanced prostate cancer, with high CPSF1 expression correlating with worse progression-free survival.

Senolytic Targeting of Anti-Apoptotic Bcl Family Increases Cell Death in UV-Irradiated Senescent Melanocytes: Search for Senolytics.

Senescent melanocytes have been suggested to play a role in the development of ageing-associated pigmentary changes and skin ageing. Here, we assessed the senolytic capacity of recognised senolytic chemicals and natural compounds in UV-irradiated senescent melanocytes. Among the tested agents, only ABT-737 and ABT-263 showed a significant reduction in the number of SA-β-Gal-positive senescent melanocytes and in the expressions of p16 and p21.

Receptor discordance after nipple-sparing mastectomy.

Background: Recent studies have shown that receptor status of breast cancer change between primary tumor and recurrence, which may influence treatment strategy and prognosis, but there are few reports on receptor discordance between primary tumors and local recurrence (LR) after nipple-sparing mastectomy (NSM).

Patients And Methods: We collected 74 patients who had LR after NSM for newly diagnosed stages 0 to 3 breast cancer between 2008 and 2016 at 14 institutions. We classified into 4 subtypes based on hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2).

Immune Checkpoint Inhibitors +/- Chemotherapy for Patients With NSCLC and Brain Metastases: A Systematic Review and Network Meta-Analysis.

Background: Multiple studies have demonstrated the intracranial efficacy of immune checkpoint inhibitors (ICI) +/- chemotherapy. The efficacy of chemoimmunotherapy compared to ICI alone in patients with metastatic NSCLC and brain metastases (BM) remains unknown.

Methods: A systematic review and network meta-analysis were performed to evaluate ICI efficacy and the influence of additional chemotherapy on survival outcomes in treatment-naïve metastatic NSCLC with BM.

Targeted internalization and activation of glycosidic switch liposomes by a biological macromolecule mPEG×EphA2 increases therapeutic efficacy against lung cancer.

Glycosidic switch liposome (GSL) technology efficiently encapsulates and stabilizes potent anticancer drugs in liposomes using a reversible glucuronide ester. Enzymatic hydrolysis of the glucuronide switch in target cell lysosomes produces parental drug. Our study examined the potential of a bispecific macromolecule, a polyethylene glycol (PEG) engager (mPEG×EphA2), generated by fusing a humanized anti-methoxy PEG (mPEG) Fab with an anti-EphA2 single-chain antibody, to increase GSL uptake into cancer cells and boost the anticancer activity by targeting PEG on GSL and an internalizing tumor antigen.

Depressive Symptoms and Amyloid Pathology.

Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.

Long-term effects of combined exposures to simulated microgravity and galactic cosmic radiation on the mouse lung: sex-specific epigenetic reprogramming.

Most studies on the effects of galactic cosmic rays (GCR) have relied on terrestrial irradiation using spatially homogeneous dose distributions of mono-energetic beams comprised of one ion species. Here, we exposed mice to novel beams that more closely mimic GCR, namely, comprising poly-energetic ions of multiple species. Six-month-old male and female C57BL/6J mice were exposed to 0 Gy, 0.

Targeting EPHB2/ABL1 restores antitumor immunity in preclinical models of ependymoma.

Ependymoma (EPN) is a common form of brain tumor in children, often resistant to available cytotoxic therapies. Molecular profiling studies have led to a better understanding of EPN subtypes and revealed a critical role of oncogenes ZFTA-RELA fusion and EPHB2 in supratentorial ependymoma (ST-EPN). However, the immune system's role in tumor progression and response to therapy remains poorly understood.

Recommendations for reporting and evaluating proton therapy beyond dose and constant relative biological effectiveness.

Background And Purpose: In proton therapy, a relative biological effectiveness (RBE) of 1.1 is used to convert proton dose into an equivalent photon dose. However, RBE varies with tissue type, fraction dose, and beam quality parameters beyond dose such as linear energy transfer (LET) raising concerns about increased local effectiveness and potential toxicity.

Radiomics model based on computed tomography images for prediction of radiation-induced optic neuropathy following radiotherapy of brain and head and neck tumors.

Purpose: We aimed to build a machine learning-based model to predict radiation-induced optic neuropathy in patients who had treated head and neck cancers with radiotherapy.

Materials And Methods: To measure radiation-induced optic neuropathy, the visual evoked potential values were obtained in both case and control groups and compared. Radiomics features were extracted from the area segmented which included the right and left optic nerves and chiasm.

Brain-derived textiloma post glioblastoma resection and application of oxidized regenerated cellulose: A pilot, bedside-to-bench, translational study.

Oxidized regenerated cellulose (ORC; marketed as Surgicel® and Tabotamp®) is routinely used as an intraoperative hemostatic agent. Rarely, residual ORC has been associated with a foreign body reaction generating cystic or granulomatous lesions (i.e.