The CD123 antibody-drug conjugate pivekimab sunirine exerts profound activity in preclinical models of pediatric acute lymphoblastic leukemia.

Antibody-drug conjugates (ADCs) combining monoclonal antibodies with cytotoxic payloads are a rapidly emerging class of immune-based therapeutics with the potential to improve the treatment of cancer, including children with relapse/refractory acute lymphoblastic leukemia (ALL). CD123, the α subunit of the interleukin-3 receptor, is overexpressed in ALL and is a potential therapeutic target. Here, we show that pivekimab sunirine (PVEK), a recently developed ADC comprising the CD123-targeting antibody, G4723A, and the cytotoxic payload, DGN549, was highly effective in vivo against a large panel of pediatric ALL patient-derived xenograft (PDX) models ( = 39).

Discovery of a nasal spray steroid, tixocortol, as an inhibitor of SARS-CoV-2 main protease and viral replication.

Coronaviruses rely on the viral-encoded chymotrypsin-like main protease (M or 3CL) for replication and assembly. Our previous research on M of SARS-CoV-2 identified cysteine 300 (Cys300) as a potential allosteric site of M inhibition. Here, we identified tixocortol (TX) as a covalent modifier of Cys300 which inhibits M activity as well as in a cell-based M expression assay.

Impact of HLA class I functional divergence on HIV control.

Heterozygosity of () class I genes is linked to beneficial outcomes after HIV infection, presumably through greater breadth of HIV epitope presentation and cytotoxic T cell response. Distinct allotype pairs, however, differ in the extent to which they bind shared sets of peptides. We developed a functional divergence metric that measures pairwise complementarity of allotype-associated peptide binding profiles.

Presurgical Oral Tamoxifen vs Transdermal 4-Hydroxytamoxifen in Women With Ductal Carcinoma In Situ: A Randomized Clinical Trial.

Importance: Oral tamoxifen citrate benefits women with ductal carcinoma in situ (DCIS), but concern about toxic effects has limited acceptance. Previous pilot studies have suggested transdermal 4-hydroxytamoxifen gel has equivalent antiproliferative efficacy to oral tamoxifen, with low systemic exposure.

Objective: To demonstrate that 4-hydroxytamoxifen gel applied to the breast skin is noninferior to oral tamoxifen in its antiproliferative effect in DCIS lesions.

Elimination of cervical cancer in Latin America (Project ECHO-ELA): lessons from phase one of implementation.

We describe the outcomes of The Extension for Community Healthcare Outcomes-Elimination of Cervical Cancer in The Americas (ECHO-ELA) program, which was developed as a tri-lateral cooperation between Pan American Health Organization (PAHO), the U.S. National Cancer Institute (NCI) and The University of Texas MD Anderson Cancer Center (MD Anderson).

Impact of the built, social, and food environment on long-term weight loss within a behavioral weight loss intervention.

Background: Behavioral weight loss interventions can lead to an average weight loss of 5%-10% of initial body weight, however there is wide individual variability in treatment response. Although built, social, and community food environments can have potential direct and indirect influences on body weight (through their influence on physical activity and energy intake), these environmental factors are rarely considered as predictors of variation in weight loss.

Objective: Evaluate the association between built, social, and community food environments and changes in weight, moderate-to-vigorous physical activity (MVPA), and dietary intake among adults who completed an 18-month behavioral weight loss intervention.

Patient-reported outcomes following autologous stem cell transplant for patients with multiple myeloma.

We evaluated changes in patient-reported outcomes and cognitive function from pre- to 3-6 months post-treatment among 42 newly diagnosed patients with multiple myeloma undergoing transplant with complete data using PROMIS-29. There were statistically significant improvements in physical ( < .001) and mental health ( < .

Inequity in Cardio-Oncology: Identifying Disparities in Cardiotoxicity and Links to Cardiac and Cancer Outcomes.

Minority and underresourced communities experience disproportionately high rates of fatal cancer and cardiovascular disease. The intersection of these disparities within the multidisciplinary field of cardio-oncology is in critical need of examination, given the risk of perpetuating health inequities in the growing vulnerable population of patients with cancer and cardiovascular disease. This review identifies 13 cohort studies and 2 meta-analyses investigating disparate outcomes in treatment-associated cardiotoxicity and situates these data within the context of oncologic disparities, preexisting cardiovascular disparities, and potential system-level inequities.

Small molecule microarray identifies inhibitors of tyrosyl-DNA phosphodiesterase 1 that simultaneously access the catalytic pocket and two substrate binding sites.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a member of the phospholipase D family of enzymes, which catalyzes the removal of both 3'- and 5'-DNA phosphodiester adducts. Importantly, it is capable of reducing the anticancer effects of type I topoisomerase (TOP1) inhibitors by repairing the stalled covalent complexes of TOP1 with DNA. It achieves this by promoting the hydrolysis of the phosphodiester bond between the Y723 residue of human TOP1 and the 3'-phosphate of its DNA substrate.

Testosterone Metabolite 6β-Hydroxytestosterone Contributes to Angiotensin II-Induced Abdominal Aortic Aneurysms in Male Mice.

Background Sex is a prominent risk factor for abdominal aortic aneurysms (AAAs), and angiotensin II (Ang II) induces AAA formation to a greater degree in male than in female mice. We previously reported that cytochrome P450 1B1 contributes to the development of hypertension, as well as AAAs, in male mice. We also found that a cytochrome P450 1B1-generated metabolite of testosterone, 6β-hydroxytestosterone (6β-OHT), contributes to Ang II-induced hypertension and associated cardiovascular and renal pathogenesis in male mice.

Health economic evaluation of primary human papillomavirus screening in urban populations in China.

Background: On Nov 17, 2020, WHO launched a global initiative to accelerate the elimination of cervical cancer through the implementation of HPV vaccination, cervical cancer screening and treatment for precancer and cancer. China has the largest burden of cervical cancer in the world, but only has a national cervical cancer screening program in rural areas since 2009. Here, we aimed to evaluate the effectiveness and cost-effectiveness of cervical cancer screening in urban China, using Shenzhen City as an example.

Follow-Up Care for Breast and Colorectal Cancer Across the Globe: Survey Findings From 27 Countries.

Purpose: The purpose of this study was to describe follow-up care for breast and colorectal cancer survivors in countries with varying levels of resources and highlight challenges regarding posttreatment survivorship care.

Methods: We surveyed one key stakeholder from each of 27 countries with expertise in survivorship care on questions including the components/structure of follow-up care, delivery of treatment summaries and survivorship care plans, and involvement of primary care in survivorship. Descriptive analyses were performed to characterize results across countries and variations between the WHO income categories (low, middle, high).

Analysis of aflatoxin signature mutation in hepatocellular carcinomas from Guatemala: A cross-sectional study (2016-2017).

Background And Aims: Guatemala has the highest incidence of hepatocellular carcinoma (HCC) in the Western hemisphere. The major risk factors in Guatemala are not well characterized, but the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) appears to be low, while the prevalence of aflatoxin (AFB) exposure appears to be high. To examine whether AFB may contribute to the elevated incidence of HCC in Guatemala, this study examined the frequency of the AFB-signature mutation in the gene (R249S) as well as other somatic mutations.

Validity evaluation of the genetics and genomics in nursing practice survey.

Aim: To psychometrically test the Genetics and Genomics Nursing Practice Survey (GGNPS) for evidence of content, face and construct validity.

Design: This study was a secondary data analysis.

Method: Data collected from the Method for Introducing a New Competency into Nursing Practice (MINC) study were used to evaluate the GGNPS for evidence of construct validity via structural equation modelling and confirmatory factor analysis.

Turmeric, Pepper, Cinnamon, and Saffron Consumption and Mortality.

Background Previous studies have reported the beneficial effects of spice consumption on lipid profiles, fasting glucose, and blood pressure, which suggests that spice consumption could affect the risk of cardiovascular disease, diabetes mellitus, and consequently mortality. The objective of this study was to evaluate the relationship between consumption of turmeric, black or chili pepper, cinnamon, and saffron with overall and cause-specific mortality in an adult population in Iran. Methods and Results We used data from the Golestan Cohort Study, which has followed 50 045 participants aged 40 to 75 years from baseline (2004-2008).