A5062384041- Cancer Immunotherapy and Biomarkers
- Adenosine and Purinergic Signaling
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Genetic factors in colorectal cancer
- Immunotherapy and Immune Responses
- Cancer Research and Treatments
- Inflammatory mediators and NSAID effects
- Cancer Genomics and Diagnostics
- Cancer, Lipids, and Metabolism
- Pancreatic and Hepatic Oncology Research
- Bladder and Urothelial Cancer Treatments
- Adolescent and Pediatric Healthcare
- Cytomegalovirus and herpesvirus research
- Viral-associated cancers and disorders
- PI3K/AKT/mTOR signaling in cancer
- Colorectal Cancer Treatments and Studies
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- HIV/AIDS Research and Interventions
- Monoclonal and Polyclonal Antibodies Research
- Gastric Cancer Management and Outcomes
- Peptidase Inhibition and Analysis
- Pancreatitis Pathology and Treatment
- Lung Cancer Research Studies
National Cancer Institute
2016-2025
National Institutes of Health
1991-2024
Center for Cancer Research
2016-2024
Office of Disease Prevention
2023
Prevention Group
2021-2023
The University of Texas MD Anderson Cancer Center
2019-2022
Government of the United States of America
2021
Sensor Research and Development Corporation (United States)
2019
Science Applications International Corporation (United States)
1999-2017
Interface (United States)
1999-2005
Replication-selective oncolytic viruses (virotherapeutics) are being developed as novel cancer therapies with unique mechanisms of action, but limitations in i.v. delivery to tumors and systemic efficacy have highlighted the need for improved agents this therapeutic class realize its potential. Here we describe rational, stepwise design evaluation a systemically effective virotherapeutic (JX-963). We first identified highly potent poxvirus strain that also trafficked efficiently human after...
DNA mismatch repair deficiency drives microsatellite instability (MSI). Cells with MSI accumulate numerous frameshift mutations. Frameshift mutations affecting cancer-related genes may promote tumorigenesis and, therefore, are shared among independently arising tumors. Consequently, such recurrent can give rise to immunogenic peptides (FSPs) that represent ideal candidates for a vaccine against cancer. Pathogenic germline variants of cause Lynch syndrome (LS), hereditary cancer approximately...
Lung cancer is the leading cause of death worldwide. Vaccination against EGFR can be one venues to prevent lung cancer. Blocking glutamine metabolism has been shown improve anticancer immunity. Here, authors report that JHU083, an orally active antagonist prodrug designed preferentially activated in tumor microenvironment, potent effects on EGFR-driven mouse tumorigenesis. development significantly suppressed when treatment with JHU083 combined peptide vaccine (EVax) than either single...
Discovery of diketoacid-containing compounds as HIV-1 integrase (IN) inhibitors played a major role in validating this enzyme an important target for the development therapeutics against HIV infection. In fact, S-1360, first clinically used IN inhibitor containing triazole ring bioisostere carboxylic acid moiety belongs to class compounds. To understand divalent metal-chelating inhibition (J. Med. Chem. 2002, 45, 5661−5670), we designed and synthesized series novel dimeric diketo-containing...
Diketo acids such as S-1360 (1A) and L-731,988 (2) are potent selective inhibitors of HIV-1 integrase (IN). A plethora diketo acid-containing compounds have been claimed in patent literature without disclosing much biological activities synthetic details (reviewed Neamati, N. Exp. Opin. Ther. Pat. 2002, 12, 709−724). To establish a coherent structure−activity relationship among the substituted indole nucleus bearing β-diketo acid moiety, series indole-β-diketo (4a−f 5a−e) were synthesized....
Reovirus type 3 Dearing strain (ReoT3D) has an inherent propensity to preferentially infect and destroy cancer cells. The oncolytic activity of ReoT3D as a single agent been demonstrated in vitro vivo against various cancers, including colon, pancreatic, ovarian breast cancers. Its human safety potential efficacy are currently being investigated early clinical trials. In this study, we the combination effects chemotherapeutic agents non-small cell lung (NSCLC). alone exerted significant...
Patients with Lynch syndrome (LS) are at markedly increased risk for colorectal cancer. It is being increasingly recognised that the immune system plays an essential role in LS tumour development, thus making ideal target cancer prevention. Our objective was to evaluate safety, assess activity and discover novel molecular pathways involved of naproxen as primary secondary chemoprevention patients LS.
Abstract The microenvironment that surrounds pancreatic ductal adenocarcinoma (PDAC) is profoundly desmoplastic and immunosuppressive. Understanding triggers of immunosuppression during the process tumorigenesis would aid in establishing targets for effective prevention therapy. Here, we interrogated differential molecular mechanisms dependent on cell origin subtype promote PDAC initiation established tumors. Transcriptomic analysis cell-of-origin–dependent epithelial gene signatures...
BackgroundNo effective approaches to target mutant Kras have yet been developed. Immunoprevention using KRAS-specific antigenic peptides trigger T cells capable of targeting tumor relies heavily on lipid metabolism. To facilitate better TCR/peptide/MHC interactions that result in cancer preventive efficacy, we combined KVax with avasimibe, a specific ACAT1 inhibitor, tested their anti-cancer efficacy mouse lung models, where mutation was induced before vaccination.MethodsControl growth...
Abstract A previously reported clinical trial in familial adenomatous polyposis (FAP) patients treated with erlotinib plus sulindac (ERL + SUL) highlighted immune response/interferon‐γ signaling as a key pathway. In this study, we combine intermittent low‐dose ERL ± SUL treatment the rat colon (Pirc) model mechanistic studies on tumor‐associated modulation. At clinically relevant doses, short‐term (16 weeks) and long‐term (46 administration results near‐complete tumor suppression Pirc...
Background. Ritonavir, a potent antiretroviral protease inhibitor, has been approved for the treatment of adults and children with human immunodeficiency virus (HIV) infection. In phase I/II study, we assessed safety, tolerability, pharmacokinetic profile oral solution ritonavir in HIV-infected studied preliminary antiviral clinical effects. Methods. between 6 months 18 years age were eligible. Four dose levels (250, 300, 350, 400 mg/m2 given every 12 hours) evaluated two groups (≤2 years,...
HIV-1 Integrase (IN) is an essential enzyme for viral replication. The discovery of β-diketo acids was crucial in the validation IN as a legitimate target drug against HIV infection. In this study, we discovered novel class inhibitors using 3D pharmacophore guided database search. We used S-1360 (1), first inhibitor to undergo clinical trials, and three other analogues develop common feature hypothesis. Testing four-featured multiconformational 150 000 structurally diverse small molecules...
Background. Indinavir, an inhibitor of the human immunodeficiency virus type 1 (HIV-1) protease, is approved for treatment HIV infection in adults when antiretroviral therapy indicated. We evaluated safety and pharmacokinetic profile indinavir free-base liquid suspension sulfate salt dry-filled capsules HIV-infected children, studied its preliminary antiviral clinical activity this patient population. In addition, we a jet-milled after single dose. Methods. Previously untreated children or...
We established a method to estimate the amounts of HIV-1 particles in plasma from patients with infection by using polymerase chain reaction (PCR) following reverse transcription (RT) viral RNA (RNA-PCR) and assessed potential usefulness this approach monitor changes load AIDS or AIDS-related complex (ARC) receiving 2′,3′-dideoxyinosine (ddI). Plasma samples were obtained 77 (49 AIDS/ARC 28 asymptomatic seropositives). Following ultracentrifugation plasma, was extracted pelleted virus...
Abstract MicroRNAs are potential candidates for lung cancer prevention and therapy. A major limitation is the lack of an efficient delivery system to directly deliver miRNA cells while limiting systemic exposure. The via inhalation a strategy in high‐risk individuals. In this study, authors investigate efficacy aerosolized let‐7b treatment prevention. Let‐7b shows significant inhibition B[a]P‐induced adenoma with no detectable side effects. Single‐cell RNA sequencing tumor‐infiltrating T...
Most recent evidence suggests that human herpesvirus 8 (HHV-8) infection is restricted to persons with Kaposi's sarcoma (KS) or who may subsequently develop KS. To accurately determine the prevalence of in United States, children and adults AIDS were examined for HHV-8 see whether (like other herpesviruses) would be readily detected immunosuppressed persons. By use nested polymerase chain reaction, DNA specific HHV-8, Epstein-Barr virus, cytomegalovirus was blood leukocytes from 0, 26 (51%),...
The amount of human immunodeficiency virus (HIV) type 1 RNA and the presence a codon 215 mutation indicative zidovudine resistance were evaluated in cerebrospinal fluid (CSF) plasma obtained from HIV-1-infected children. level HIV-1 CSF was highest children with severe encephalopathy (n = 25; median, 430 copies/mL; range, 0-2.2 × 105 copies/ mL) followed by moderately encephalopathic 7; 330; 0-1130) nonencephalopathic groups 9; 0; 0-566) (P .007).There no correlation between levels. Five 7...
// Jing Pan 1, * , Qi Zhang Shizuko Sei 2 Robert H. Shoemaker Ronald A. Lubet Yian Wang 1 and Ming You Cancer Center Department of Pharmacology & Toxicology, Medical College Wisconsin, Milwaukee, WI, USA Chemopreventive Agent Development Research Group, Division Prevention, National Institute, Bethesda, MD, These authors have contributed equally to this work Correspondence to: You, email: myou@mcw.edu Keywords: immunoprevention, KRAS, lung adenocarcinoma, peptide vaccine, MHC class II...
Abstract Expressed on cells of the myeloid and lymphoid lineages, V-domain Ig Suppressor T cell Activation (VISTA) is an emerging target for cancer immunotherapy. Blocking VISTA activates both innate adaptive immunity to eradicate tumors in mice. Using a tripeptide small molecule antagonist CA170, we found that it exhibited potent anticancer efficacy carcinogen-induced mouse lung tumorigenesis. Remarkably, tumor development was almost completely suppressed when CA170 combined with...