Raghwa Sharma
A5089061061- Ovarian cancer diagnosis and treatment
- PARP inhibition in cancer therapy
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Melanoma and MAPK Pathways
- Virus-based gene therapy research
- Cancer Mechanisms and Therapy
- RNA modifications and cancer
- Cutaneous Melanoma Detection and Management
- Renal cell carcinoma treatment
- Cancer Immunotherapy and Biomarkers
- Reproductive Biology and Fertility
- Cancer-related Molecular Pathways
- Protein Degradation and Inhibitors
- Cancer-related molecular mechanisms research
- Colorectal Cancer Treatments and Studies
- Sarcoma Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Ferroptosis and cancer prognosis
- RNA and protein synthesis mechanisms
- Nonmelanoma Skin Cancer Studies
- PI3K/AKT/mTOR signaling in cancer
- Polyomavirus and related diseases
- CAR-T cell therapy research
- Vascular Malformations and Hemangiomas
Westmead Hospital
2015-2024
The University of Sydney
2013-2024
Western Sydney University
2013-2023
Westmead Institute
2011-2018
St. Vincent's Hospital
2015
St Vincent's Hospital
2015
King Edward Memorial Hospital
2012
The University of Western Australia
2012
Queen Elizabeth II Medical Centre
2012
Royal Prince Alfred Hospital
2004-2012
Abstract Numerous studies have tested the association between TP53 mutations in ovarian cancer and prognosis but these been consistently confounded by limitations study design, methodology, and/or heterogeneity sample cohort. High‐grade serous (HGS) carcinoma is most clinically important histological subtype of cancer. As tumours may arise from ovary, Fallopian tube or peritoneum, they are collectively referred to as high‐grade pelvic (HGPSC). To identify true prevalence HGPSC, we sequenced...
To evaluate the effects of treatment with potent mutant BRAF inhibitors GSK2118436 or vemurafenib (PLX4720) on immune responses to metastatic melanoma in tissues taken before and after treatment.Thirty-seven tumor biopsies were collected from 15 patients unresectable American Joint Committee Cancer stage III IV immediately approximately 7 days commencement inhibitor at time progression. Immunohistochemical staining was carried out using specific antibodies for CD8, CD4, CD20, CD1a, Granzyme...
Cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns TILs by histotype and relation to other clinical factors.
Low grade serous ovarian tumours are a rare and under-characterised histological subtype of epithelial tumours, with little known the molecular drivers facilitators tumorigenesis beyond classic oncogenic RAS/RAF mutations. With move towards targeted therapies due to chemoresistant nature this subtype, it is pertinent more fully characterise genetic events driving tumour type, some which may influence response therapy and/or development drug resistance. We performed genome-wide...
The aim of this study was to investigate the role infiltrating macrophages in renal allograft fibrosis. Forty-six protocol biopsies obtained 1 year after transplantation were stained with Sirius red quantify fibrosis and double CD68 CD206 identify proportion alternatively activated (M2) macrophages. Biopsies analyzed for gene expression by microarray, which correlated macrophage infiltration severity number CD68+ cells strongly percentage interstitial (r = 0.73, p < 0.0001). Macrophage at...
Low-grade serous ovarian carcinomas (LGSC) are Ras pathway-mutated, TP53 wild-type, and frequently associated with borderline tumors. Patients LGSCs respond poorly to platinum-based chemotherapy may benefit from pathway-targeted agents. High-grade (HGSC) TP53-mutated thought be rarely We sought determine whether histology grade 2 or 3 carcinoma was an indicator of mutation, we explored the molecular relationship between coexisting invasive histologies.We reviewed >1,200 patients identified...
Reactivation of BK virus in renal allografts causes a destructive chronic infection. This single-center retrospective cohort study describes the evolution allograft nephropathy (BKVAN) from 63 kidneys (from 61 patients) using sequential histopathology (454 biopsies, averaging 7.8 ± 2.6 per kidney) followed for 60.1 mo. Uninfected protocol biopsies formulated time-matched control Banff scores (n = 975). Interstitial inflammation occurred 73% at diagnosis, correlating with viral (r 0.413, p...
Abstract Approximately, 10% to 15% of serous ovarian tumors fall into the category designated as low malignant potential (LMP). Like their invasive counterparts, LMP may be associated with extraovarian disease, for example, in peritoneal cavity and regional lymph nodes. However, unlike typical carcinomas, patients generally have a favorable prognosis. The mutational profile also differs markedly from that seen most carcinomas. Typically, are KRAS BRAF mutations. Interrogation expression...
Abstract Purpose: Women with epithelial ovarian cancer generally have a poor prognosis; however, subset of patients has an unexpected dramatic and durable response to treatment. We sought identify clinical, pathological, molecular determinants exceptional survival in women high-grade serous (HGSC), disease associated the majority deaths. Experimental Design: evaluated histories 2,283 and, after applying stringent clinical pathological selection criteria, identified 96 HGSC that represented...
Abstract We aimed to validate the prognostic association of p16 expression in ovarian high‐grade serous carcinomas (HGSC) and explore it other carcinoma histotypes. protein was assessed by clinical‐grade immunohistochemistry 6525 including 4334 HGSC using tissue microarrays from 24 studies participating Ovarian Tumor Tissue Analysis consortium. patterns were interpreted as abnormal (either overexpression referred block or absence) normal (heterogeneous). CDKN2A (which encodes p16) mRNA also...
Targeted therapies are increasingly being used to treat a variety of cancers. Their efficacy depends upon the accurate detection and targeting specific mutation or aberration in tumor. All cancers, such as melanoma, molecularly heterogeneous, with drug-resistant subclones present before treatment emerging result targeted therapies. Here, we show intralesional molecular heterogeneity progressing V600E BRAF-mutant melanoma metastasis from patient treated for 7 months BRAF inhibitor...
Low-grade serous ovarian carcinomas (LGSC) are associated with a poor response to chemotherapy and molecularly characterized by RAS pathway activation. Using exome whole genome sequencing, we identified recurrent mutations in the protein translational regulator EIF1AX NF1, USP9X, KRAS, BRAF, NRAS were mutually exclusive; however, found significant co-occurrence of Missense clustered at N-terminus region its role ensuring initiation fidelity. Coexpression mutant proteins promoted...
Abstract Purpose: Gene expression–based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation clinical utility has been hindered by nonstandardized methods, which are not applicable in a setting. We sought to generate grade minimal gene set assay classification individual tumor specimens into HGSOC and confirm previously reported subtype-associated...
The aim of the present study was to determine whether micromorphometric features positive sentinel lymph nodes (SLNs) from patients with melanoma are useful for predicting further nodal involvement in completion node dissection (CLND) specimens. Of 986 undergoing SLN biopsy between March 1992 and February 2001, 175 (17.7%) had at least 1 140 subsequent CLND specimens available review. Further 24 (17.1%) patients. 8 SLNs that were assessed, presence metastases correlated significantly a tumor...
Anti-N-methyl D-aspartate receptor (NMDAR) encephalitis is a recently described severe neurological disorder predominantly affecting young women, which presents with psychosis, memory deficits, seizures, and encephalopathy, often requiring prolonged hospitalization. The condition frequently associated an underlying neoplasm, most ovarian teratoma, in such cases appears to be para-neoplastic, immune-mediated encephalopathy. histologic features of the teratomas anti-NMDAR have seldom been...
Australia has implemented a high‐coverage HPV vaccination program but not, to date, established the distribution of types that occur in cervical cancers Australia. This information is important for determining potential cancer prevention with both current and broader spectrum vaccines. We analysed 847 diagnosed 2005 2015 tertiary centres three most populous Australian states resolution specimens containing multiple using laser‐capture microdissection. Archived FFPE tissue was reviewed by...
Inositol pyrophosphates (PP-IPs) comprising inositol, phosphate, and pyrophosphate (PP) are essential for multiple functions in eukaryotes. Their role fungal pathogens has never been addressed. Cryptococcus neoformans is a model pathogenic fungus causing life-threatening meningoencephalitis. We investigate the cryptococcal kinases responsible production of PP-IPs (IP7/IP8) hierarchy PP-IP importance pathogenicity. Using gene deletion inositol polyphosphate profiling, we identified Kcs1 as...
Abstract Background ALM201 is a therapeutic peptide derived from FKBPL that has previously undergone preclinical and clinical development for oncology indications completed Phase 1a trial in ovarian cancer patients other advanced solid tumours. Methods In vitro, stem cell (CSC) assays range of HGSOC lines patient samples, vivo tumour initiation, growth delay limiting dilution assays, were utilised. Mechanisms determined by using immunohistochemistry, ELISA, qRT-PCR, RNAseq western blotting....
Abstract Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes how co-occurrence BRCA1 or BRCA2 (BRCA) alterations loss influences in tubo-ovarian high-grade serous (HGSC). Experimental Design: protein classified by immunohistochemistry carcinomas 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined germline BRCA status a subset 1,134 HGSC, related genotype overall (OS), tumor-infiltrating CD8+ lymphocytes,...
In a previous immunohistochemical study of dendritic cells (DC) in sentinel lymph nodes (SLN) draining regressing melanomas, we found that the accumulation mature DC-LAMP(+) DCs SLNs was associated with local expansion antigen-specific memory effector CTLs and absence metastasis downstream nodes. The aim this to investigate prognostic importance maximal density SLNs.A total 458 consecutive patients micrometastatic melanoma within were eligible for analysis. evaluated by three independent...