A5036532953- Cytokine Signaling Pathways and Interactions
- Peptidase Inhibition and Analysis
- interferon and immune responses
- Immunotherapy and Immune Responses
- Neuroblastoma Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Histone Deacetylase Inhibitors Research
- Genetic factors in colorectal cancer
- Cancer Mechanisms and Therapy
- vaccines and immunoinformatics approaches
- Melanoma and MAPK Pathways
- Cancer Research and Treatments
- Cancer-related Molecular Pathways
- Lung Cancer Research Studies
- Cervical Cancer and HPV Research
- Immune Response and Inflammation
- Cancer-related gene regulation
- Immune cells in cancer
- Digestive system and related health
- Protein Tyrosine Phosphatases
- Natural product bioactivities and synthesis
- CAR-T cell therapy research
- HER2/EGFR in Cancer Research
- Synthesis and biological activity
- Hepatitis B Virus Studies
The University of Texas MD Anderson Cancer Center
2013-2024
Montefiore Medical Center
2002-2023
Albert Einstein College of Medicine
2002-2023
The Ohio State University
2009-2016
Thoracic Surgery Foundation
2001-2012
Ohio University
2012
Ludwig Cancer Research
2010
Ludwig Cancer Research
2010
The gastrointestinal tract is lined by a layer of mucus comprised highly glycosylated proteins called mucins. To evaluate the importance mucin in intestinal carcinogenesis, we constructed mice genetically deficient Muc2, most abundant secreted mucin. Muc2-/- displayed aberrant crypt morphology and altered cell maturation migration. Most notably, frequently developed adenomas small intestine that progressed to invasive adenocarcinoma, as well rectal tumors. Thus, Muc2 involved suppression...
LPS stimulates monocytes/macrophages through the activation of signaling events that modulate production inflammatory cytokines. Apigenin, a flavonoid abundantly found in fruits and vegetables, exhibits anti-proliferative anti-inflammatory activities poorly defined mechanisms. In this study, we demonstrate apigenin inhibits proinflammatory cytokines IL-1beta, IL-8, TNF LPS-stimulated human monocytes mouse macrophages. The inhibitory effect on cytokine persists even when is administered after...
Despite the success of immune checkpoint blockade against melanoma, many "cold" tumors like prostate cancer remain unresponsive. We found that hypoxic zones were prevalent across preclinical and resisted T cell infiltration even in context CTLA-4 PD-1 blockade. demonstrated hypoxia-activated prodrug TH-302 reduces or eliminates hypoxia these tumors. Combination therapy with this hypoxia-prodrug cooperated to cure more than 80% transgenic adenocarcinoma mouse prostate-derived (TRAMP-derived)...
Abstract Relatlimab and nivolumab combination immunotherapy improves progression-free survival over monotherapy in patients with unresectable advanced melanoma 1 . We investigated this regimen resectable clinical stage III or oligometastatic IV (NCT02519322). Patients received two neoadjuvant doses (nivolumab 480 mg relatlimab 160 intravenously every 4 weeks) followed by surgery, then ten of adjuvant therapy. The primary end point was pathologic complete response (pCR) rate 2 resulted 57%...
Hepatocellular carcinoma has high recurrence rates after surgery; however, there are no approved standard-of-care neoadjuvant or adjuvant therapies. Immunotherapy been shown to improve survival in advanced hepatocellular carcinoma; we therefore aimed evaluate the safety and tolerability of perioperative immunotherapy resectable carcinoma.
The platinum compound oxaliplatin has been shown to be an effective chemotherapeutic agent for the treatment of colorectal cancer. In this study, we investigate molecular mechanisms action identify means predicting response agent. Exposure colon cancer cells resulted in G2/M arrest and apoptosis. Immunofluorescent staining demonstrated that apoptotic cascade initiated by is characterised translocation Bax mitochondria cytochrome c release into cytosol. Oxaliplatin caspase 3 activation...
Coordinated manipulation of independent immune regulatory pathways in the tumor microenvironment-including blockade T-cell checkpoint receptors and reversal suppressive myeloid programs-can render aggressive cancers susceptible to rejection. Elevated toxicity associated with combination immunotherapy, however, prevents translation most efficacious regimens. We evaluated checkpoint-modulating antibodies targeting CTLA-4, PD-1, 4-1BB together agonists either STING or Flt3 TRAMP-C2 model...
Abstract Cutaneous squamous cell carcinoma (cuSCC) comprises 15–20% of all skin cancers, accounting for over 700,000 cases in USA annually. Most cuSCC arise association with a distinct precancerous lesion, the actinic keratosis (AK). To identify potential targets molecularly targeted chemoprevention, here we perform integrated cross-species genomic analysis development through preneoplastic AK stage using matched human samples and solar ultraviolet radiation-driven Hairless mouse model. We...
<h3>Background</h3> The US is experiencing an epidemic of HPV<sup>+</sup> oropharyngeal cancers (OPC), the rates and burden which now exceed that for cervical cancer. Immunotherapy targeting programmed death 1 (PD-1) on tumor-infiltrating lymphocytes and/or its ligand PD-L1 tumor cells, was effective in several has however, showed efficacy only less than 15% patients. <h3>Methods</h3> We used a preclinical oral model, mEER, consisting mouse tonsil derived epithelial cells expressing HPV-16...
Stable mutants with reduced capacity to produce capsules were isolated from suspensions of Cryptococcus neoformans after treatment the wild type a mutagen. The could be assigned one two phenotypes, hypocapsular or acapsular. Hypocapsular immunochemically and physicochemically indistinguishable type, whereas acapsular lacked major capsular antigen negatively charged exterior. In genetic analysis, mutant trait segregated as Mendelian gene (1:1) when random basidiospores an outcross studied,...
Abstract Histone deacetylase inhibitors (HDACi) induce growth arrest and apoptosis in colon cancer cells are being considered for therapy. The underlying mechanism of action these effects is poorly defined with both transcription-dependent -independent mechanisms implicated. We screened a panel 30 cell lines sensitivity to HDACi-induced correlated the differences gene expression patterns induced by HDACi five most sensitive resistant lines. A robust reproducible transcriptional response...
The Janus kinase-2 (Jak2)-signal transducer and activator of transcription-3 (STAT3) pathway is critical for promoting an oncogenic metastatic phenotype in several types cancer including renal cell carcinoma (RCC) melanoma. This study describes two small molecule inhibitors the Jak2-STAT3 pathway, FLLL32 its more soluble analog, FLLL62. These compounds are structurally distinct curcumin analogs that bind selectively to SH2 domain STAT3 inhibit phosphorylation dimerization. We hypothesized...
Protein arginine methyltransferase-5 (PRMT5) is a Type II methyltransferase that regulates various cellular functions. We hypothesized PRMT5 plays role in regulating the growth of human melanoma cells. Immunohistochemical analysis indicated significant upregulation melanocytic nevi, malignant melanomas and metastatic as compared to normal epidermis. Furthermore, nuclear was significantly decreased primary cutaneous melanomas. In cell lines, predominantly cytoplasmic, associated with its...
The increasing prevalence of inflammatory diseases and the adverse effects associated with long-term use current anti-inflammatory therapies prompt identification alternative approaches to reestablish immune balance. Apigenin, an abundant dietary flavonoid, is emerging as a potential regulator inflammation. Here, we show that apigenin has immune-regulatory activity in vivo. Apigenin conferred survival mice treated lethal dose Lipopolysaccharide (LPS) restoring normal cardiac function heart...
The proto-oncogene c-Myc is overexpressed in 70% of colorectal tumours and can modulate proliferation apoptosis after cytotoxic insult. Using an isogenic cell system, we demonstrate that overexpression colon carcinoma LoVo cells resulted sensitisation to camptothecin-induced apoptosis, thus identifying as a potential marker predicting response tumour camptothecin. Both camptothecin exposure elevation p53 protein levels, suggesting role the c-Myc-imposed apoptotic effects This was confirmed...
Abstract High-risk human papillomavirus (HPV)–associated squamous cell carcinomas of the oropharynx (SCCOP) are among fastest growing cancers. After standard-of-care treatment, however, patients with HPV+ SCCOP have better overall and disease-specific survival than HPV− SCCOP, suggesting importance HPV-specific immunity. We reasoned that therapeutic vaccination targeting HPV-16 E6 E7 oncogenes could elicit high-affinity, high-frequency tumor antigen–specific T-cell responses, which then be...