PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer.

The enhanced permeability and retention (EPR) effect controls passive nanodrug uptake in tumors and may provide a high tumor payload with prolonged retention for cancer treatment. However, EPR-mediated tumor uptake and distribution vary by cancer phenotype. Thus, we hypothesized that a companion PET imaging surrogate may benefit EPR-mediated therapeutic drug delivery.

3D small-scale dosimetry and tumor control of Ac radiopharmaceuticals for prostate cancer.

Radiopharmaceutical therapy using -emitting Ac is an emerging treatment for patients with advanced metastatic cancers. Measurement of the spatial dose distribution in organs and tumors is needed to inform treatment dose prescription and reduce off-target toxicity, at not only organ but also sub-organ scales. Digital autoradiography with -sensitive detection devices can measure radioactivity distributions at 20-40 resolution, but anatomical characterization is typically limited to 2D.

Prostate-Specific Membrane Antigen Targeted StarPEG Nanocarrier for Imaging and Therapy of Prostate Cancer.

The tumor uptake of large non-targeted nanocarriers primarily occurs through passive extravasation, known as the enhanced permeability and retention (EPR) effect. Prior studies demonstrated improved tumor uptake and retention of 4-arm 40 kDa star polyethylene glycol (StarPEG) polymers for cancer imaging by adding prostate-specific membrane antigen (PSMA) targeting small molecule ligands. To test PSMA-targeted delivery and therapeutic efficacy, StarPEG nanodrugs with/without three copies of PSMA-targeting ligands, ACUPA, are designed and synthesized.

Treatment of Prostate Cancer with CD46-targeted 225Ac Alpha Particle Radioimmunotherapy.

Purpose: Radiopharmaceutical therapy is changing the standard of care in prostate cancer and other malignancies. We previously reported high CD46 expression in prostate cancer and developed an antibody-drug conjugate and immunoPET agent based on the YS5 antibody, which targets a tumor-selective CD46 epitope. Here, we present the preparation, preclinical efficacy, and toxicity evaluation of [225Ac]DOTA-YS5, a radioimmunotherapy agent based on the YS5 antibody.

Artificial intelligence in the diagnosis and detection of heart failure: the past, present, and future.

Artificial Intelligence (AI) performs human intelligence-dependant tasks using tools such as Machine Learning, and its subtype Deep Learning. AI has incorporated itself in the field of cardiovascular medicine, and increasingly employed to revolutionize diagnosis, treatment, risk prediction, clinical care, and drug discovery. Heart failure has a high prevalence, and mortality rate following hospitalization being 10.

Effects of Heme Oxygenase-1 on c-Kit-Positive Cardiac Cells.

Heme oxygenase-1 (HO-1) is one of the most powerful cytoprotective proteins known. The goal of this study was to explore the effects of HO-1 in c-kit-positive cardiac cells (CPCs). Lin/c-kit CPCs were isolated and expanded from wild-type (WT), HO-1 transgenic (TG), or HO-1 knockout (KO) mouse hearts.

Cardiac Mesenchymal Cells Cultured at Physiologic Oxygen Tension Have Superior Therapeutic Efficacy in Heart Failure Caused by Myocardial Infarction.

Stem/progenitor cells are usually cultured at atmospheric O tension (21%); however, since physiologic O tension in the heart is ∼5%, using 21% O may cause oxidative stress and toxicity. Cardiac mesenchymal cells (CMCs), a newly discovered and promising type of progenitor cells, are effective in improving left ventricle (LV) function after myocardial infarction (MI). We have previously shown that, compared with 21% O, culture at 5% O increases CMC proliferation, telomerase activity, telomere length, and resistance to severe hypoxia .

Risk of Colorectal Cancer and Cancer Related Mortality After Detection of Low-risk or High-risk Adenomas, Compared With No Adenoma, at Index Colonoscopy: A Systematic Review and Meta-analysis.

Background & Aims: The risk of metachronous colorectal cancer (CRC) among patients with no adenomas, low-risk adenomas (LRAs), or high-risk adenomas (HRAs), detected at index colonoscopy, is unclear. We performed a systematic review and meta-analysis to compare incidence rates of metachronous CRC and CRC-related mortality after a baseline colonoscopy for each group.

Methods: We searched the PubMed, Embase, Google Scholar, and Cochrane databases for studies that reported the incidence of CRC and adenoma characteristics after colonoscopy.

Significant decline in the prevalence of Barrett's esophagus among patients with gastroesophageal reflux disease.

Barrett's esophagus (BE), a premalignant condition for the development of esophageal adenocarcinoma (EAC), is a consequence of chronic gastroesophageal reflux disease (GERD). Although the incidence of EAC is increasing, a similar trend for BE is not clear. We aimed to evaluate the prevalence of newly diagnosed BE over time in a cohort of patients presenting with GERD symptoms.

Efficacy and Safety of Endoscopic Resection of Sessile Serrated Polyps 10 mm or Larger: A Systematic Review and Meta-Analysis.

Background & Aims: The best method for endoscopic resection of sessile serrated polyps (SSP) 10 mm or larger is unclear; studies report variable outcomes in comparison to conventional adenomas. We performed a systematic review and meta-analysis to assess the efficacy and safety of resection of SSPs 10 mm or larger in size.

Methods: We searched the PubMed/MEDLINE, Google Scholar, Embase, and Cochrane databases for studies reporting data on endoscopic resection of SSPs 10 mm or larger, through May 31st, 2019.

Novel Cellularly Active Inhibitor Regresses DDAH1 Induced Prostate Tumor Growth by Restraining Tumor Angiogenesis through Targeting DDAH1/ADMA/NOS Pathway.

Dimethylarginine dimethylaminohydrolase1 (DDAH1) inhibitors are important therapeutics by virtue of their ability to control nitric oxide (NO) production by elevating asymmetric dimethylarginine (ADMA) levels. In a screening campaign, we identified that DD1E5 (3-amino-6- tert-butyl-N-(1,3-thiazol-2-yl)-4-(trifluoromethyl)thieno[2,3- b]pyridine-2- carboxamide) inhibits the DDAH1 activity both in vitro and in cultured cells. Mechanistic studies found that DD1E5 is a competitive inhibitor (dissociation constant ( K) of 2.

Interleukin-6 induced overexpression of valosin-containing protein (VCP)/p97 is associated with androgen-independent prostate cancer (AIPC) progression.

Though Androgen deprivation therapy (ADT) is effective initially, numerous patients become resistant to it and develop castration resistant PCa (CRPC). Cytokines promotes ligand independent activation of AR. Interleukin-6 (IL-6) levels are elevated in CRPC patients and regulate AR activity.

Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is frequently upregulated in prostate cancer, and its overexpression conveys tumor growth and angiogenesis by metabolizing asymmetric dimethylarginine (ADMA).

Tissue microarray analysis confirmed higher dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression in prostate cancer (PCa) compared to benign and normal prostate tissues. DDAH1 regulates nitric oxide (NO) production by degrading endogenous nitric oxide synthase (NOS) inhibitor, asymmetric dimethylarginine (ADMA). This study examined whether DDAH1 has any physiological role in PCa progression.

Tumor protein D52 (isoform 3) contributes to prostate cancer cell growth via targeting nuclear factor-κB transactivation in LNCaP cells.

Our previous study showed that TPD52 overexpression could increase migration and proliferation of LNCaP cells contributing to the development of prostate cancer. However, mechanism of TPD52 in prostate cancer initiation and progression remains elusive. In this study, we investigated the possible underlying mechanism of TPD52 in prostate cancer progression.

All-Trans-Retinoic Acid Stimulates Overexpression of Tumor Protein D52 (TPD52, Isoform 3) and Neuronal Differentiation of IMR-32 Cells.

Tumor protein D52 (TPD52), a proto-oncogene is overexpressed in a variety of epithelial carcinomas and plays an important role in cell proliferation, migration, and cell death. In the present study we found that the treatment of IMR-32 neuroblastoma (NB) cells with retinoic acid (RA) stimulates an increase in expression of TPD52. TPD52 expression is detectable after 72 h, can be maintained till differentiation of NB cells suggesting that TPD52 is involved in differentiation.