Non-V600E BRAF mutations and treatment for Hairy Cell Leukemia.

We found 18 patients with immunophenotype consistent with classic hairy cell leukemia (HCL) and BRAF mutations other than just V600E. Twelve had 1 non-V600E BRAF mutation and 6 had V600E with 1 (n=5) or 2 (n=1) non-V600E BRAF co-mutations.

[Updates on hairy cell leukemia (HCL) and HCL-like disorders].

Hairy cell proliferations represent very different entities. They include hairy cell leukemia in its classic form (HCL), a well-defined entity, but also the variant form of HCL (LT-V ou HCL-V), whose presentation is far from HCL and whose prognosis is poorer. Other hairy cell proliferations include splenic red pulp lymphoma (SDRPL) and splenic marginal zone lymphomas (SMZL) with circulating villous cells.

Tackling algorithmic bias and promoting transparency in health datasets: the STANDING Together consensus recommendations.

Without careful dissection of the ways in which biases can be encoded into artificial intelligence (AI) health technologies, there is a risk of perpetuating existing health inequalities at scale. One major source of bias is the data that underpins such technologies. The STANDING Together recommendations aim to encourage transparency regarding limitations of health datasets and proactive evaluation of their effect across population groups.

Resuscitation, yes or no ? the criteria for transferring patients with hematological malignancies to intensive care. A qualitative study.

Background: Having a hematological malignancy increases the risk of a poor-quality end of life and of dying in intensive care. There is no prognostic score to predict survival on admission to intensive care, but many patients die there. To identify the criteria used in deciding to transfer patients with hematological malignancies to intensive care.

Patterns of genomic instability in > 2000 patients with ovarian cancer across six clinical trials evaluating olaparib.

Background: The introduction of poly(ADP-ribose) polymerase (PARP) inhibitors represented a paradigm shift in the treatment of ovarian cancer. Genomic data from patients with high-grade ovarian cancer in six phase II/III trials involving the PARP inhibitor olaparib were analyzed to better understand patterns and potential causes of genomic instability.

Patients And Methods: Homologous recombination deficiency (HRD) was assessed in 2147 tumor samples from SOLO1, PAOLA-1, Study 19, SOLO2, OPINION, and LIGHT using next-generation sequencing technology.

Antitumor activity of selenopsammaplin A analog (SPA-10091-HCl) via histone methyltransferase DOT1L degradation and apoptosis induction in castration-resistant prostate cancer cells.

Castrate-resistant prostate cancer (CRPC) is one of the most difficult cancers in men and is characterized by a poor prognosis and a high risk of metastasis. The overexpression of the disruptor of telomeric silencing 1-like (DOT1L), which is a specific methyltransferase for histone H3 at lysine residue 79 (H3K79), has been related to poor outcomes in patients with CRPC. Therefore, targeting DOT1L is considered a potential therapeutic approach to overcome the significant medical challenges of CRPC.

The role of the JunD-RhoH axis in the pathogenesis of hairy cell leukemia and its ability to identify existing therapeutics that could be repurposed to treat relapsed or refractory disease.

Hairy cell leukemia (HCL) is an indolent malignancy of mature B-lymphocytes. While existing front-line therapies achieve excellent initial results, a significant number of patients relapse and become increasingly treatment resistant. A major molecular driver of HCL is aberrant interlocking expression of the transcription factor JunD and the intracellular signaling molecule RhoH.

Synthesis and Characterization of Thallium-Texaphyrin Nanoparticles and Their Assessment as Potential Delivery Systems for Auger Electron-Emitting Tl to Cancer Cells.

Thallium-201 is an Auger electron-emitting radionuclide with significant potential for targeted molecular radiotherapy of cancer. It stands out among other Auger electron emitters by releasing approximately 37 Auger and Coster-Kronig electrons per decay, which is one of the highest numbers in its category. It has also a convenient half-life of 73 h, a stable daughter product, established production methods, and demonstrated high radiotoxicity.

Differential HBV RNA and HBcrAg patterns in untreated patients with chronic hepatitis delta.

Background And Aim: Serum HBV RNA and HBcrAg levels have been proposed as useful biomarkers in the management of HBV patients, however their role in chronic hepatitis Delta (CHD) is currently unknown.

Methods: Consecutive untreated CHD patients were enrolled in a cross-sectional study in three EU centers. Clinical and virological characteristics were collected.

Non-immunoglobin scaffold binders as efficient affinity ligands for purification of broad-spectrum serum albumins.

Although non-immunoglobin scaffold binders with high affinity and broad spectrum for albumin are attractive for lab-scale albumin purification, affinity chromatography based on these binders has not been developed. Here, the albumin-binding capabilities of representative binders, including protein G-derived albumin binding domain (ABD), albumin binding nanofitins (ABNF), and human serum albumin affimer 31 (HSA31) were predicted by interaction structure analysis and verified by experimental assays. Interaction structure prediction suggested that ABD possessed great potential to bind human (HSA), rhesus monkey (RhSA), mouse (MSA), and rat serum albumin (RSA), whereas ABNF might only bind HSA and bovine serum albumin (BSA), and HSA31 might not bind any of the tested albumins.

Cell therapy for a rare disease- hairy cell leukemia variant.

Hairy cell leukemia variant (HCL-v) is a rare malignancy of clonal mature B-cells that follows a chronic disease course. HCL-v patients are often resistant to purine nucleoside analogs, which are the first-line therapy. To address the shortcomings of current therapy for HCL-v, we investigated the activity of a BAFF ligand-based CAR-T cell which binds to all three BAFF receptors, BAFF-receptor, TACI, and BCMA.

Oxaliplatin-Based Versus Alkylating Agent in Neuroendocrine Tumors According to the O-Methylguanine-DNA Methyltransferase Status: A Randomized Phase II Study (MGMT-NET).

Purpose: Alkylating agents (ALKY) are the main chemotherapies used for advanced neuroendocrine tumors (NETs). O-Methylguanine-DNA methyltransferase (MGMT) status, as proficient (p) or deficient (d), may predict the response to ALKY.

Patients And Methods: MGMT-NET (ClinicalTrials.

Novel -phenyl-2-(aniline) benzamide hydrochloride salt development for colon cancer therapy.

Introduction: -phenyl-2-(aniline) analog is a previously discovered dual inhibitor of Topo I and COX-2, which exhibited significant anti-colon cancer activity , but the poor solubility and moderate anti-cancer activity hindered its further development.

Methods: To rectify the suboptimal drug properties of , a series of salt forms were developed and further evaluated through and experiments.

Results: The hydrochloride () has a well-characterized crystal structure and its solubility reached 540.

Aminodiols, aminotetraols and 1,2,3-triazoles based on -gibberic acid: stereoselective syntheses and antiproliferative activities.

A new series of aminodiols, aminotetraols and 1,2,3-triazoles based on -gibberic acid were synthesized in a stereoselective manner, starting from commercially available gibberellic acid. -Gibberic acid, prepared from gibberellic acid according to a literature method, was applied to SeO/-BuOOH-mediated allylic oxidation, yielding the triol, which is a key intermediate. After protecting the 1,4-diol functionality as acetonide, epoxidation was performed using either -CPBA or -BuOOH/VO(acac) to produce the epoxy alcohol.

Germline BRCA1/2 status and chemotherapy response score in high-grade serous ovarian cancer.

Background: High-grade serous ovarian cancer (HGSOC) can be treated with platinum-based neoadjuvant chemotherapy (NACT) and delayed primary surgery (DPS). Histopathological response to NACT can be assessed using Böhm's chemotherapy response score (CRS). We investigated whether germline BRCA1/2 (gBRCA1/2) genotype associated with omental CRS phenotype.

Whey proteins from camel's milk have higher in vitro wound-healing effect than whey proteins from cow's milk.

Background: The effectiveness of whey obtained by either enzyme (sweet) or acid treatment on wound healing remains unclear. This study investigated the effectiveness of camel and bovine whey prepared enzymatically (CSW and BSW) or by pH reduction (CAW and BAW). After removing the cream from milk, HCl or rennet was used to remove casein, resulting in acid or sweet whey, respectively, followed by lactose removal using dialysis.

Reappraisal of Oncocytic Adenocarcinoma: Unveiling Its Connection to Oncocytic Variants of Salivary Duct Carcinoma and Mucoepidermoid Carcinoma Through ImmunoHisto-Molecular Perspectives.

Oncocytic adenocarcinoma (OC) of the salivary glands is a rare and controversial entity. It was recently reclassified as "salivary carcinoma NOS and emerging entities" in the 2022 WHO classification of head and neck tumors. The lack of specific molecular alterations and its potential affiliation with other salivary gland carcinomas, such as the oncocytic mucoepidermoid carcinomas (OMEC) or the oncocytic subtype of salivary duct carcinomas (OSDC) justified this reclassification.

Validation of Radiosynthesis and First in-Human Dosimetry of Ga-NOTA-UBI-29-41: A Proof of Concept Study.

Antimicrobial peptides (AMPs) such as UBI-29-41 offer a distinctive approach for precise detection due to their unique interactions with bacteria and makes them promising candidates for specific and selective imaging. The study was aimed to corroborate the in-house manual synthesis of Ga-NOTA-UBI-29-41, evaluate its uptake in patients with suspected infection, and estimate of patient-specific dosimetry to ensure optimal clinical application. Ga-NOTA-UBI-29-41 was synthesized by using a variable amount of UBI-29-41 (60-90 μg) to 555 MBq of Ga-68 in 0.

BCL-2 and γ-H2AX immunostaining profile in urothelial bladder cancer prognosis.

Urothelial bladder carcinoma (UBC) is a malignant neoplasm of the urinary tract that is highly prevalent worldwide and has a high rate of tumor recurrence. It is known that the BCL2 apoptosis regulator (BCL-2) gene encodes a mitochondrial protein that regulates programmed death cells by apoptosis. In contrast, the H2A.

Applications of CRISPR/Cas as a Toolbox for Hepatitis B Virus Detection and Therapeutics.

Hepatitis B virus (HBV) infection remains a significant global health challenge, leading to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Covalently closed circular DNA (cccDNA) and integrated HBV DNA are pivotal in maintaining viral persistence. Recent advances in CRISPR/Cas technology offer innovative strategies to inhibit HBV by directly targeting both cccDNA and integrated HBV DNA or indirectly by degrading HBV RNAs or targeting host proteins.

Synergistic effect between denosumab and immune checkpoint inhibitors (ICI)? A retrospective study of 268 patients with ICI and bone metastases.

Background: Bone metastasis is a significant concern in advanced solid tumors, contributing to diminished patient survival and quality of life due to skeletal-related events (SREs). Denosumab (DMAB), a monoclonal antibody targeting the receptor activator of nuclear factor kappa-B ligand (RANKL), is used to prevent SREs in such cases. The RANK/RANKL axis, crucial in immunological processes, has garnered attention, especially with the expanding use of immune checkpoint inhibitors (ICI) in modern oncology.

Coordinately unsaturated single Fe-atoms with N vacancies and enhanced sp carbon defects in Fe-N(sp)-C structural units for suppression of cancer cell metabolism and electrochemical oxygen evolution.

Installing coordinately unsaturated Fe-N-C structural units on polymer-composite-derived N-doped carbon offers highly active Fe-N sites for the electrochemical oxygen evolution reaction (OER) and reactive oxygen species (ROS) generation in tumor cells. An NHCl-driven high-temperature etching method was employed for the formation of FeSA950NC with coordinately unsaturated single Fe-atoms in an Fe-N(sp)-C structural unit together with N vacancies () and sp defects. The carbonization of Fe-phen@ZIF-8 at 800 °C for 30 min under argon, followed by grinding Fe-ZIF-8@RF-urea with NHCl at 950 °C for 2 hours, resulted in sp carbon defects and sites with coordination unsaturation in Fe-N due to NHCl decomposition to NH and HCl, which produced substantial internal stress for etching the carbon matrix.