MRI detects tubulointerstitial changes in mouse models of radiation-induced nephropathy.

Purpose: We hypothesized that radiation-induced tubulointerstitial changes in the kidney can be assessed using MRI-based T relaxation time measurements.

Methods: We performed MRI, histology, and serum biochemistry in two mouse models of radiation nephropathy: one involving external beam radiotherapy and the other using internal irradiation with an α-particle-emitting actinium-225 radiolabeled antibody. We compared the mean T values of different renal compartments between control and external beam radiotherapy or α-particle-emitting actinium-225 radiolabeled antibody-treated groups and between the two radiation-treated groups using a Wilcoxon rank-sum test.

A murine model of induced myocarditis and cardiac dysfunction.

Unlabelled: is a protozoan parasite that causes human and animal African trypanosomiases (HAT and AAT). Cardiac symptoms are commonly reported in HAT patients, and intracardiac parasites with accompanying myocarditis have been observed in both natural hosts and animal models of infection. Despite the importance of as a cause of cardiac dysfunction and the dramatic socioeconomic impact of African trypanosomiases in sub-Saharan Africa, there are currently no reproducible murine models of associated cardiomyopathy.

Characterization of the Rat Osteosarcoma Cell Line UMR-106 by Long-Read Technologies Identifies a Large Block of Amplified Genes Associated with Human Disease.

Background/objectives: The rat osteosarcoma cell line UMR-106 is widely used for the study of bone cancer biology but it has not been well characterized with modern genomic methods.

Methods: To better understand the biology of UMR-106 cells we used a combination of optical genome mapping (OGM), long-read sequencing nanopore sequencing and RNA sequencing.The UMR-106 genome was compared to a strain-matched Sprague-Dawley rat for variants associated with human osteosarcoma while expression data were contrasted with a public osteoblast dataset.

Targeting RNA helicase DDX3X with a small molecule inhibitor for breast cancer bone metastasis treatment.

Patients who present with breast cancer bone metastasis only have limited palliative treatment strategies and efficacious drug treatments are needed. In breast cancer patient data, high levels of the RNA helicase DDX3 are associated with poor overall survival and bone metastasis. Consequently, our objective was to target DDX3 in a mouse breast cancer bone metastasis model using a small molecule inhibitor of DDX3, RK-33.

ErbB2-NOTCH1 axis controls autophagy in cardiac cells.

Although the epidermal growth factor receptor 2 (ErbB2) and Notch1 signaling pathways have both significant roles in regulating cardiac biology, their interplay in the heart remains poorly investigated. Here, we present evidence of a crosstalk between ErbB2 and Notch1 in cardiac cells, with effects on autophagy and proliferation. Overexpression of ErbB2 in H9c2 cardiomyoblasts induced Notch1 activation in a post-transcriptional, p38-dependent manner, while ErbB2 inhibition with the specific inhibitor, lapatinib, reduced Notch1 activation.

Assessing the Efficacy of Tragal Pumping in a Novel Tympanostomy Tube-Rat Model.

Objective: Tragal pumping (TP) is a practice of pushing on the tragus to raise pressure within the external auditory canal and is a commonly recommended adjunctive maneuver believed to facilitate the introduction of ototopical medications into the middle ear cavity via a tympanostomy tube. To investigate the efficacy of TP in the penetration of eardrops into the middle ear cavity via tympanostomy tube, we established the novel tympanostomy tube-rat model. We investigated the histology of the middle ear to determine the efficacy in moving fluid into the middle ear.

TNIK Inhibition Sensitizes TNIK-Overexpressing Lung Squamous Cell Carcinoma to Radiotherapy.

Most patients with lung squamous cell carcinoma (LSCC) undergo chemotherapy, radiotherapy, and adjuvant immunotherapy for locally advanced disease. The efficacy of these treatments is still limited because of dose-limiting toxicity or locoregional recurrence. New combination approaches and targets such as actionable oncogenic drivers are needed to advance treatment options for patients with LSCC.

Development and therapeutic evaluation of 5D3(CC-MLN8237) antibody-theranostic conjugates for PSMA-positive prostate cancer therapy.

Prostate cancer (PC) is an aggressive cancer that can progress rapidly and eventually become castrate-resistant prostate cancer (CRPC). Stage IV metastatic castrate-resistant prostate cancer (mCRPC) is an incurable late-stage cancer type with a low 5-year overall survival rate. Targeted therapeutics such as antibody-drug conjugates (ADCs) based on high-affinity monoclonal antibodies and potent drugs conjugated via smart linkers are being developed for PC management.

TNIK inhibition sensitizes TNIK-overexpressing lung squamous cell carcinoma to radiotherapy.

Most patients with lung squamous cell carcinoma (LSCC) undergo chemotherapy, radiotherapy, and adjuvant immunotherapy for locally advanced disease. The efficacy of these treatments is still limited due to dose-limiting toxicity or locoregional recurrence. New combination approaches and targets such as actionable oncogenic drivers are needed to advance treatment options for LSCC patients.

Combined, yet separate: cocktails of carriers (not drugs) for actinium-225 α-particle therapy of solid tumors expressing moderate-to-low levels of targetable markers.

Unlabelled: Alpha-particle radionuclide-antibody conjugates are being clinically evaluated against solid tumors even when they moderately express the targeted markers. At this limit of lower tumor-absorbed doses, to maintain efficacy, the few(er) intratumorally delivered alpha-particles need to traverse/hit as many different cancer cells as possible. We complement antibody-radioconjugate therapies with a separate nanocarrier delivering a fraction of the same total injected radioactivity to tumor regions geographically different than those affected by targeting antibodies; these carrier-cocktails collectively distribute the alpha-particle emitters better.

TRBC1-targeting antibody-drug conjugates for the treatment of T cell cancers.

Antibody and chimeric antigen receptor (CAR) T cell-mediated targeted therapies have improved survival in patients with solid and haematologic malignancies. Adults with T cell leukaemias and lymphomas, collectively called T cell cancers, have short survival and lack such targeted therapies. Thus, T cell cancers particularly warrant the development of CAR T cells and antibodies to improve patient outcomes.

Tissue-location-specific transcription programs drive tumor dependencies in colon cancer.

Cancers of the same tissue-type but in anatomically distinct locations exhibit different molecular dependencies for tumorigenesis. Proximal and distal colon cancers exemplify such characteristics, with BRAF predominantly occurring in proximal colon cancers along with increased DNA methylation phenotype. Using mouse colon organoids, here we show that proximal and distal colon stem cells have distinct transcriptional programs that regulate stemness and differentiation.

The Role of γδ T-Lymphocytes in Glioblastoma: Current Trends and Future Directions.

Cell-based immunotherapy for glioblastoma (GBM) encounters major challenges due to the infiltration-resistant and immunosuppressive tumor microenvironment (TME). γδ T cells, unconventional T cells expressing the characteristic γδ T cell receptor, have demonstrated promise in overcoming these challenges, suggesting great immunotherapeutic potential. This review presents the role of γδ T cells in GBM and proposes several research avenues for future studies.

Therapeutic efficacy of an alpha-particle emitter labeled anti-GD2 humanized antibody against osteosarcoma-a proof of concept study.

Purpose: Current treatments for osteosarcoma (OS) have a poor prognosis, particularly for patients with metastasis and recurrence, underscoring an urgent need for new targeted therapies to improve survival. Targeted alpha-particle therapy selectively delivers cytotoxic payloads to tumors with radiolabeled molecules that recognize tumor-associated antigens. We have recently demonstrated the potential of an FDA approved, humanized anti-GD2 antibody, hu3F8, as a targeted delivery vector for radiopharmaceutical imaging of OS.

A murine model of -induced myocarditis and cardiac dysfunction.

is a protozoan parasite that causes human and animal African trypanosomiases (HAT and AAT). Cardiac symptoms are commonly reported in HAT patients, and intracardiac parasites with accompanying myocarditis have been observed in both natural hosts and animal models of infection. Despite the importance of as a cause of cardiac dysfunction and the dramatic socioeconomic impact of African trypanosomiases in sub-Saharan Africa, there are currently no reproducible murine models of -associated cardiomyopathy.

Erratum: Comparison of Cardiovascular Pathology in Animal Models of SARS-CoV-2 Infection: Recommendations Regarding Standardization of Research Methods.

This corrects the article DOI: 10.30802/AALAS-CM-22-000095. In the original article entitled "Comparison of Cardiovascular Pathology in Animal Models of SARS-CoV-2 Infection: Recommendations Regarding Standardization of Research Methods," published in Vol 73, Issue 1 (February 2023), the grant information appearing in the Acknowledgments section should read: We acknowledge training support from the National Institutes of Health (T32 OD011089) for IAJ and SM.

ME3BP-7 is a targeted cytotoxic agent that rapidly kills pancreatic cancer cells expressing high levels of monocarboxylate transporter MCT1.

Unlabelled: Nearly 30% of Pancreatic ductal adenocarcinoma (PDAC)s exhibit a marked overexpression of Monocarboxylate Transporter 1 (MCT1) offering a unique opportunity for therapy. However, biochemical inhibitors of MCT1 have proven unsuccessful in clinical trials. In this study we present an alternative approach using 3-Bromopyruvate (3BP) to target MCT1 overexpressing PDACs.

Gut colonization with an obesity-associated enteropathogenic microbe modulates the premetastatic niches to promote breast cancer lung and liver metastasis.

Introduction: Obesity, an independent risk factor for breast cancer growth and metastatic progression, is also closely intertwined with gut dysbiosis; and both obese state and dysbiosis promote each other. Enteric abundance of is strongly linked with obesity, and we recently discovered the presence of in malignant breast cancer. Given that enterotoxigenic or ETBF, which secretes toxin (BFT), has been identified as a procarcinogenic microbe in breast cancer, it is necessary to examine its impact on distant metastasis and underlying systemic and localized alterations promoting metastatic progression of breast cancer.

FLASH Effects Induced by Orthovoltage X-Rays.

Purpose: This work describes the first implementation and in vivo study of ultrahigh-dose-rate radiation (>37 Gy/s; FLASH) effects induced by kilovoltage (kV) x-ray from a rotating-anode x-ray source.

Methods And Materials: A high-capacity rotating-anode x-ray tube with an 80-kW generator was implemented for preclinical FLASH radiation research. A custom 3-dimensionally printed immobilization and positioning tool was developed for reproducible irradiation of a mouse hind limb.

Non-Viral Gene Delivery to Hepatocellular Carcinoma via Intra-Arterial Injection.

Purpose: Hepatocellular carcinoma (HCC) has limited treatment options, and modest survival after systemic chemotherapy or procedures such as transarterial chemoembolization (TACE). There is therefore a need to develop targeted therapies to address HCC. Gene therapies hold immense promise in treating a variety of diseases, including HCC, though delivery remains a critical hurdle.

Bacterial Cholecystitis and Cholangiohepatitis in Common Marmosets ().

The common marmoset (), a New World NHP, has emerged as important animal model in multiple areas of translational biomedical research. The quality of translational research in marmosets depends on early diagnosis, treatment, and prevention of their spontaneous diseases. Here, we characterize an outbreak of infectious cholangiohepatitis that affected 7 adult common marmosets in a single building over a 10-mo period.

HMGA1 induces FGF19 to drive pancreatic carcinogenesis and stroma formation.

High mobility group A1 (HMGA1) chromatin regulators are upregulated in diverse tumors where they portend adverse outcomes, although how they function in cancer remains unclear. Pancreatic ductal adenocarcinomas (PDACs) are highly lethal tumors characterized by dense desmoplastic stroma composed predominantly of cancer-associated fibroblasts and fibrotic tissue. Here, we uncover an epigenetic program whereby HMGA1 upregulates FGF19 during tumor progression and stroma formation.