A5053367572- Gastrointestinal Tumor Research and Treatment
- Chronic Myeloid Leukemia Treatments
- Microtubule and mitosis dynamics
- Sarcoma Diagnosis and Treatment
- Cancer-related Molecular Pathways
- Chronic Lymphocytic Leukemia Research
- Neurofibromatosis and Schwannoma Cases
- Prostate Cancer Treatment and Research
- Ubiquitin and proteasome pathways
- Renal cell carcinoma treatment
- DNA Repair Mechanisms
- Cancer Immunotherapy and Biomarkers
- Cervical Cancer and HPV Research
- Platelet Disorders and Treatments
- Cancer Genomics and Diagnostics
- Gastrointestinal disorders and treatments
- Gastric Cancer Management and Outcomes
- Multiple Myeloma Research and Treatments
- Cancer Mechanisms and Therapy
- Renal and related cancers
- Phagocytosis and Immune Regulation
- Protein Tyrosine Phosphatases
- Genetic factors in colorectal cancer
- PARP inhibition in cancer therapy
- Prostate Cancer Diagnosis and Treatment
University of Pittsburgh
2014-2024
Heidelberg University
2013-2024
University Hospital Heidelberg
2013-2024
National Center for Tumor Diseases
2020-2024
UPMC Hillman Cancer Center
2015-2024
University of Pittsburgh Medical Center
2021-2024
Cellular Research (United States)
2023
Clinical Orthopaedics and Related Research
2020
Shadyside Hospital
2020
National Cancer Institute
2020
Most gastrointestinal stromal tumors (GISTs) have activating mutations in the KIT receptor tyrosine kinase, and most patients with GISTs respond well to Gleevec, which inhibits kinase activity. Here we show that ∼35% (14 of 40) lacking intragenic activation related platelet-derived growth factor α ( PDGFRA ). Tumors expressing or oncoproteins were indistinguishable respect downstream signaling intermediates cytogenetic changes associated tumor progression. Thus, appear be alternative...
Loss of genomic integrity is a defining feature many human malignancies, including papillomavirus (HPV)-associated preinvasive and invasive genital squamous lesions. Here we show that aberrant mitotic spindle pole formation caused by abnormal centrosome numbers represents an important mechanism in accounting for numeric chromosomal alterations HPV-associated carcinogenesis. Similar to what found histopathological specimens, HPV-16 E6 E7 oncoproteins cooperate induce numbers, formation,...
The diagnosis of gastrointestinal stromal tumor (GIST) is currently based on morphologic features and immunohistochemical demonstration KIT (CD117). However, some tumors (in our estimation approximately 4%) have clinicopathologic GIST but do not express KIT. To determine if these lesions are truly GISTs, we evaluated 25 with clinical histologic typical GIST, negative immunohistochemistry, for PDGFRA mutations using DNA extracted from paraffin-embedded tissue. Most originated in the stomach...
Prior studies of Ki-67, cyclin E, and p16 expression have suggested that these biomarkers may be preferentially expressed in cervical neoplasia. This study examined compared the distribution staining for three antigens 1) normal reactive epithelial changes, 2) diagnostically challenging cases (atypical metaplasia atypical atrophy), 3) squamous intraepithelial lesions (SIL), 4) high-and low-risk human papilloma virus (HPV) type-specific SIL. One hundred four foci from 99 biopsies were...
ERCC1-XPF endonuclease is required for nucleotide excision repair (NER) of helix-distorting DNA lesions. However, mutations in ERCC1 or XPF humans mice cause a more severe phenotype than absence NER, prompting search novel activities the nuclease. In Saccharomyces cerevisiae, orthologs (Rad10-Rad1) participate double-strand breaks (DSBs). Rad10-Rad1 contributes to two error-prone DSB pathways: microhomology-mediated end joining (a Ku86-independent mechanism) and single-strand annealing. To...
Members of a family with hereditary gastrointestinal stromal tumors (GISTs) and germline KIT oncogene mutation were evaluated for other potential syndrome manifestations. A tumor from the proband was analyzed to compare features sporadic GISTs.Members kindred in which six relatives four consecutive generations comprised an autosomal dominant pattern documented GISTs cutaneous lesions underwent physical examination, imaging studies, analysis. recurrent GIST studied using microarray,...
The most widely accepted criteria for the evaluation of prognosis malignant melanoma are histopathologic and clinical presentation. No currently available laboratory tests provide additional prognostic information. It has recently been suggested that reverse transcription polymerase chain reaction (RT-PCR)-based detection tyrosinase messenger RNA (mRNA) in peripheral blood might be useful early circulating tumor cells, since is thought to a melanocyte-specific marker.To further evaluate...
KIT expression is a key diagnostic feature of gastrointestinal stromal tumors (GISTs), and virtually all the GISTs express oncogenic forms or PDGFRA receptor tyrosine kinase proteins, which serve as therapeutic targets imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). However, can be low in PDGFRA-mutant GISTs, increasing likelihood misdiagnosis other types sarcoma. We report that signaling intermediate protein C theta (PKCtheta) marker including those lack and/or contain mutations....
The human papillomavirus (HPV) 16 E7 oncoprotein has been reported previously to stimulate DNA damage and activate host cell checkpoints. How HPV-16 maintains proliferation despite activated checkpoints is incompletely understood. Here, we provide evidence that cells expressing the can enter mitosis in presence of damage. We show this activity involves attenuation checkpoint control by accelerating proteolytic turnover claspin. Claspin mediates activation CHK1 ATR response replication...
Gastrointestinal stromal tumors (GIST) can be successfully treated with imatinib mesylate (Gleevec); however, complete remissions are rare and patients frequently achieve disease stabilization in the presence of residual tumor masses. The clinical observation that discontinuation treatment lead to progression suggests cells are, fact, quiescent and, therefore, able re-enter cell-division cycle. In line this notion, we have previously shown induces GIST cell quiescence vitro through...
Intratumoural heterogeneity (ITH) is a major cause of cancer-associated lethality. Extensive genomic ITH has previously been reported in clear cell renal carcinoma (ccRCC). Here we address the question whether increases with malignant progression and can hence be exploited as prognostic marker. Unexpectedly, precision quantitative image analysis reveals that degree functional virtually identical between primary ccRCCs lowest stage advanced, metastatic tumours. Functional was found to show...
ABSTRACT Primary human keratinocytes with ectopic expression of high-risk papillomavirus (HPV) E6 and E7 oncoproteins display abnormal centrosome numbers, multipolar mitoses, aneusomy. However, it has not been explored whether these abnormalities can occur in cells containing HPV episomes where is under viral transcriptional control. Here, we demonstrate that genomic instability organotypic raft cultures episomal HPV-16 even at low copy numbers. We conclude DNA, when maintained as an...
ABSTRACT Fanconi anemia (FA) patients have an increased risk for squamous cell carcinomas (SCCs) at sites of predilection infection with high-risk human papillomavirus (HPV) types, including the oral cavity and anogenital tract. We show here that activation FA pathway is a frequent event in cervical SCCs. found triggered mainly by HPV type 16 (HPV-16) E7 oncoprotein associated enhanced formation large FANCD2 foci recruitment as well FANCD1/BRCA2 to chromatin. Episomal expression HPV-16...
Abstract Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal of gastrointestinal tract and caused by activating mutations KIT or platelet-derived growth factor receptor α (PDGFRA) tyrosine kinases. GISTs can be successfully treated with imatinib mesylate, a selective small-molecule protein kinase inhibitor that was first clinically approved to target oncogenic BCR-ABL fusion in chronic myelogenous leukemia, but which also potently inhibits PDGFR family members. The...
Defects in DNA damage repair caused by mutations BRCA1/2, ATM or other genes have been shown to play an important role the development and progression of prostate cancer. The influence such on anti-tumor immunity cancer, however, is largely unknown. To better understand correlation between BRCA1/2 immune phenotype we characterized infiltrate eight BRCA2-mutated tumors comparison with wild-type patients T-cell receptor sequencing immunohistochemistry for CD45, CD4, CD8, FOXP3, CD163. In...
Background Prospective data registration is the basis of clinical oncological research. Commonly, case documentation restricted to studies investigating a defined hypothesis. Only few institutions prospectively register all patients with reliable, sustainable and continuous follow-up infrastructure. The Department Urology Heidelberg University Hospital started its prospective tumor base in 1992. Since then, course in-patients continuously registered within life-long (success rate: 93%)....