High iASPP (PPP1R13L) expression is an independent predictor of adverse clinical outcome in acute myeloid leukemia (AML).

Apoptosis-stimulating proteins of p53 (ASPPs) are a family of proteins that modulate key tumor suppressor pathways via direct interaction with p53. Deregulation of these proteins promotes cancer development and impairs sensitivity to systemic (chemo)therapy and radiation. In this study, we describe that the inhibitor of ASPP (iASPP) is frequently highly expressed in acute myeloid leukemia (AML) and that overexpression correlates with a poor clinical outcome.

Catalytically Active Ti-Based Nanomaterials for Hydroxyl Radical Mediated Clinical X-Ray Enhancement.

Nanoparticle radioenhancement offers a promising strategy for augmenting radiotherapy by locally increasing radiation damage to tumor tissue. While past research has predominantly focused on nanomaterials with high atomic numbers, such as Au and HfO, recent work has revealed that their radioenhancement efficacy decreases considerably when using clinically relevant megavoltage X-rays as opposed to the orthovoltage X-rays typically employed in research settings. Here, radiocatalytically active Ti-based nanomaterials for clinical X-ray therapy settings are designed.

Nanoparticles Dysregulate the Human Placental Secretome with Consequences on Angiogenesis and Vascularization.

Exposure to nanoparticles (NPs) in pregnancy is increasingly linked to adverse effects on embryo-fetal development and health later in life. However, the developmental toxicity mechanisms of NPs are largely unknown, in particular potential effects on the placental secretome, which orchestrates many developmental processes pivotal for pregnancy success. This study demonstrates extensive material- and pregnancy stage-specific deregulation of placental signaling from a single exposure of human placental explants to physiologically relevant concentrations of engineered (silica (SiO) and titanium dioxide (TiO) NPs) and environmental NPs (diesel exhaust particles, DEPs).

Reversible Mechanical Contraception and Endometriosis Treatment Using Stimuli-Responsive Hydrogels.

Female sterilization via fallopian tube ligation is a common procedure; However, after the operation, over 10% of women seek re-fertilization, which is frequently unsuccessful. In addition, there is evidence that fallopian tubes contribute to the spread of endometriotic tissue as they serve as channels for proinflammatory media entering the abdominal cavity via retrograde menstruation. Here, stimuli-degradable hydrogel implants are presented for the functional, biocompatible, and reversible occlusion of fallopian tubes.

The Prevalence of Endometriosis in Patients with Unexplained Infertility.

Endometriosis, a systemic ailment, profoundly affects various aspects of life, often eluding detection for over a decade. This leads to enduring issues such as chronic pain, infertility, emotional strain, and potential organ dysfunction. The prolonged absence of diagnosis can contribute to unexplained obstetric challenges and fertility issues, necessitating costly and emotionally taxing treatments.

Evaluation of apoptosis stimulating protein of TP53-1 (ASPP1/PPP1R13B) to predict therapy resistance and overall survival in acute myeloid leukemia (AML).

ASPP1 (PPP1R13B) belongs to a family of p53-binding proteins and enhances apoptosis by stimulation of p53-transactivation of selected proapoptotic target genes. It is preferentially expressed in hematopoietic stem cells (HSC) and together with p53 preserves the genomic integrity of the HSC pool. Consequently, dysfunction of ASPP1 has been associated with malignant transformation and development of acute lymphoblastic leukemias and lymphomas - whereas methylation of the promoter region is linked to reduced transcription and ultimately attenuated expression of ASPP1.

Modular stimuli-responsive hydrogel sealants for early gastrointestinal leak detection and containment.

Millions of patients every year undergo gastrointestinal surgery. While often lifesaving, sutured and stapled reconnections leak in around 10% of cases. Currently, surgeons rely on the monitoring of surrogate markers and clinical symptoms, which often lack sensitivity and specificity, hence only offering late-stage detection of fully developed leaks.

Alternative splicing of Apoptosis Stimulating Protein of TP53-2 (ASPP2) results in an oncogenic isoform promoting migration and therapy resistance in soft tissue sarcoma (STS).

Background: Metastatic soft tissue sarcoma (STS) are a heterogeneous group of malignancies which are not curable with chemotherapy alone. Therefore, understanding the molecular mechanisms of sarcomagenesis and therapy resistance remains a critical clinical need. ASPP2 is a tumor suppressor, that functions through both p53-dependent and p53-independent mechanisms.

Catalytic activity imperative for nanoparticle dose enhancement in photon and proton therapy.

Nanoparticle-based radioenhancement is a promising strategy for extending the therapeutic ratio of radiotherapy. While (pre)clinical results are encouraging, sound mechanistic understanding of nanoparticle radioenhancement, especially the effects of nanomaterial selection and irradiation conditions, has yet to be achieved. Here, we investigate the radioenhancement mechanisms of selected metal oxide nanomaterials (including SiO, TiO, WO and HfO), TiN and Au nanoparticles for radiotherapy utilizing photons (150 kVp and 6 MV) and 100 MeV protons.

Stereotactic Radiotherapy after Radical Prostatectomy in Patients with Prostate Cancer in the Adjuvant or Salvage Setting: A Systematic Review.

(1) Background: Prostate cancer is the most common cancer in men and can be treated with radical prostatectomy (RPE) or radiotherapy in the primary setting. Stereotactic radiotherapy (SBRT) has proven to be effective and well tolerated in this setting. However, if SBRT is an equally promising treatment option if applied in the adjuvant or salvage setting after RPE remains unknown.

ASPP2κ Is Expressed In Human Colorectal Carcinoma And Promotes Chemotherapy Resistance And Tumorigenesis.

Alternative splicing is a common physiologic mechanism to generate numerous distinct gene products from one gene locus, which can result in unique gene products with differing important functional outcomes depending on cell context. Aberrant alternative splicing is a hallmark of cancer that can contribute to oncogenesis and aggressiveness of the disease as well as resistance to therapy. However, aberrant splicing might also result in novel targets for cancer therapy.

Stereotactic Body Radiotherapy for High-Risk Prostate Cancer: A Systematic Review.

Background: Radiotherapy (RT) is an established, potentially curative treatment option for all risk constellations of localized prostate cancer (PCA). Androgen deprivation therapy (ADT) and dose-escalated RT can further improve outcome in high-risk (HR) PCA. In recent years, shorter RT schedules based on hypofractionated RT have shown equal outcome.

Impact of Low-Dose Irradiation of the Lung and Heart on Toxicity and Pulmonary Function Parameters after Thoracic Radiotherapy.

Objective: To assess the impact of (low) dose irradiation to the lungs and heart on the incidence of pneumonitis and pulmonary function changes after thoracic radiotherapy (RT). Methods/Material: Data of 62 patients treated with curative thoracic radiotherapy were analyzed. Toxicity data and pulmonary function tests (PFTs) were obtained before RT and at 6 weeks, at 12 weeks, and at 6 months after RT.

Epigenetic activation of O-linked β-N-acetylglucosamine transferase overrides the differentiation blockage in acute leukemia.

Background: Overriding the differentiation blockage in acute myeloid leukemia (AML) is the most successful mode-of-action in leukemia therapy - now curing the vast majority of patients with acute promyelocytic leukemia (APL) using all-trans retinoic acid (ATRA)-based regimens. Similar approaches in other leukemia subtypes, such as IDH1/2-mutated AML, are under active investigation. We herein present successful release of the differentiation blockage upon treatment with the natural (-)-Δ-Tetrahydrocannabinol isomer dronabinol in vitro and in vivo.

Generation of a recombinant Gag virus-like-particle panel for the evaluation of p24 antigen detection by diagnostic HIV tests.

Background: Detection of HIV-1 p24 antigen permits early identification of primary HIV infection and timely intervention to limit further spread of the infection. Principally, HIV screening should equally detect all viral variants, but reagents for a standardised test evaluation are limited. Therefore, we aimed to create an inexhaustible panel of diverse HIV-1 p24 antigens.