10 results on '"Uma N.M. Rao"'
Search Results
2. Extensive three-dimensional intratumor proteomic heterogeneity revealed by multiregion sampling in high-grade serous ovarian tumor specimens
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Allison L. Hunt, Nicholas W. Bateman, Waleed Barakat, Sasha Makohon-Moore, Brian L. Hood, Kelly A. Conrads, Ming Zhou, Valerie Calvert, Mariaelena Pierobon, Jeremy Loffredo, Tracy J. Litzi, Julie Oliver, Dave Mitchell, Glenn Gist, Christine Rojas, Brian Blanton, Emma L. Robinson, Kunle Odunsi, Anil K. Sood, Yovanni Casablanca, Kathleen M. Darcy, Craig D. Shriver, Emanuel F. Petricoin, Uma N.M. Rao, G. Larry Maxwell, and Thomas P. Conrads
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Oncology ,Cancer systems biology ,Proteomics ,Transcriptomics ,Science - Abstract
Summary: Enriched tumor epithelium, tumor-associated stroma, and whole tissue were collected by laser microdissection from thin sections across spatially separated levels of ten high-grade serous ovarian carcinomas (HGSOCs) and analyzed by mass spectrometry, reverse phase protein arrays, and RNA sequencing. Unsupervised analyses of protein abundance data revealed independent clustering of an enriched stroma and enriched tumor epithelium, with whole tumor tissue clustering driven by overall tumor “purity.” Comparing these data to previously defined prognostic HGSOC molecular subtypes revealed protein and transcript expression from tumor epithelium correlated with the differentiated subtype, whereas stromal proteins (and transcripts) correlated with the mesenchymal subtype. Protein and transcript abundance in the tumor epithelium and stroma exhibited decreased correlation in samples collected just hundreds of microns apart. These data reveal substantial tumor microenvironment protein heterogeneity that directly bears on prognostic signatures, biomarker discovery, and cancer pathophysiology and underscore the need to enrich cellular subpopulations for expression profiling.
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- 2021
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3. Table S1, Table S2 from E3611—A Randomized Phase II Study of Ipilimumab at 3 or 10 mg/kg Alone or in Combination with High-Dose Interferon-α2b in Advanced Melanoma
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John M. Kirkwood, Robert M. Conry, Phu V. Truong, Noel Laudi, Mark A. Taylor, Stuart J. Wong, Jerry W. Mitchell, Mark R. Albertini, Arun Nagarajan, Uma N.M. Rao, Xiaoxue Li, Sandra J. Lee, and Ahmad A. Tarhini
- Abstract
Table S1- Tumor response by RECIST criteria. Table S2- Treatment details and reasons for discontinuation.
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- 2023
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4. Data from E3611—A Randomized Phase II Study of Ipilimumab at 3 or 10 mg/kg Alone or in Combination with High-Dose Interferon-α2b in Advanced Melanoma
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John M. Kirkwood, Robert M. Conry, Phu V. Truong, Noel Laudi, Mark A. Taylor, Stuart J. Wong, Jerry W. Mitchell, Mark R. Albertini, Arun Nagarajan, Uma N.M. Rao, Xiaoxue Li, Sandra J. Lee, and Ahmad A. Tarhini
- Abstract
Purpose:Interferon-α favors a Th1 shift in immunity, and combining with ipilimumab (ipi) at 3 or 10 mg/kg may downregulate CTLA4-mediated suppressive effects, leading to more durable antitumor immune responses. A study of tremelimumab and high-dose interferon-α (HDI) showed promising efficacy, supporting this hypothesis.Patients and Methods:E3611 followed a 2-by-2 factorial design (A: ipi10+HDI; B: ipi10; C: ipi3+HDI; D: ipi3) to evaluate (i) no HDI versus HDI (across ipilimumab doses) and (ii) ipi3 versus ipi10 (across HDI status). We hypothesized that median progression-free survival (PFS) would improve from 3 to 6 months with HDI versus no HDI and with ipi10 versus ipi3.Results:For eligible and treated patients (N = 81) at a median follow-up time of 29.8 months, median PFS was 4.4 months [95% confidence interval (CI), 2.7–8.2] when ipilimumab was used alone and 7.5 months (95% CI, 5.1–11.0) when HDI was added. Median PFS was 3.8 months (95% CI, 2.6–7.5) with 3 mg/kg ipilimumab and 6.5 months (95% CI, 5.1–13.5) with 10 mg/kg. By study arm, median PFS was 8.0 months (95% CI, 2.8–20.2) in arm A, 6.2 months (95% CI, 2.7–25.7) in B, 5.7 months (95% CI, 1.5–11.1) in C, and 2.8 months (95% CI, 2.6–5.7) in D. The differences in PFS and overall survival (OS) did not reach statistical significance. Adverse events were consistent with the known profiles of ipilimumab and HDI and significantly higher with HDI and ipi10.Conclusions:Although PFS was increased, the differences resulting from adding interferon-α or a higher dose of ipilimumab did not reach statistical significance and do not outweigh the added toxicity risks.
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- 2023
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5. Pathology of Melanoma
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Uma N.M. Rao, Asmita Chopra, and Rohit Sharma
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Pathology ,medicine.medical_specialty ,Skin Neoplasms ,Lymphovascular invasion ,Biopsy ,Lymph node metastasis ,Melanocyte ,Malignancy ,medicine ,Humans ,neoplasms ,Melanoma ,Nevus ,Neoplasm Staging ,business.industry ,Sentinel Lymph Node Biopsy ,Sentinel node ,medicine.disease ,medicine.anatomical_structure ,Depth of invasion ,Lymphatic Metastasis ,Immunohistochemistry ,Surgery ,business ,Carcinoma in Situ - Abstract
Melanoma is an aggressive malignancy arising from melanocytes in the skin and rarely in extracutaneous sites. The understanding of pathology of melanoma has evolved over the years, with the initial classifications based on the clinical and microscopic features to the current use of immunohistochemistry and genetic sequencing. The depth of invasion and lymph node metastasis are still the most important prognostic features of melanoma. Other important prognostic features include ulceration, lymphovascular invasion, mitosis, and tumor-infiltrating lymphocytes. This article reviews the pathology of melanoma and its precursor lesions, along with the recent advances in pathologic diagnosis of melanoma.
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- 2019
6. Increased gene copy number of The transcription factor E2F1 In malignant melanoma
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Anthony Beas, Uma N.M. Rao, Yongmei Feng, Mark A. Nelson, Jamie R. Senft, Linda M. Sargent, Steven H. Reynolds, Barbara Honchak, Amy M. Jefferson, Robert C. Johnson, Anne Christine Goulet, Jim Averill, and David T. Lowry
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endocrine system ,Cancer Research ,Blotting, Western ,Biology ,Translocation, Genetic ,RNA interference ,Cell Line, Tumor ,Gene duplication ,medicine ,Humans ,E2F1 ,Genetic Predisposition to Disease ,Copy-number variation ,Melanoma ,neoplasms ,Gene ,In Situ Hybridization, Fluorescence ,Pharmacology ,Chromosomes, Human, Pair 12 ,Cell growth ,medicine.disease ,Molecular biology ,Oncology ,Cell culture ,Lymphatic Metastasis ,Cancer research ,Melanocytes ,Molecular Medicine ,RNA Interference ,biological phenomena, cell phenomena, and immunity ,E2F1 Transcription Factor - Abstract
Translocations and unique chromosome break points in melanoma will aid in the identification of the genes that are important in the neoplastic process. We have previously shown a unique translocation in malignant melanoma cells der(12)t(12;20). The transcription factor E2F1 maps to 20q11. Increased expression of E2F has been associated with the autonomous growth of melanoma cells, however, the molecular basis has not yet been elucidated. To this end, we investigated E2F1 gene copy number and structure in human melanoma cell lines and metastatic melanoma cases. Fluorescent in situ hybridization (FISH) analysis using a specific E2F1 probe indicated increased E2F1 gene copies in melanoma cell lines compared to normal melanocytes. We also observed increased copies of the E2F1 gene in lymph node metastases of melanoma. In addition, Western blot analysis demonstrated increased E2F1 protein levels in 8 out of 9 melanoma cell lines relative to normal melanocytes. Inhibition of E2F1 expression with RNAi also reduced melanoma cell growth. Our results suggest that the release of E2F activity by elevated E2F1 gene copy numbers may play a functional role in melanoma growth.
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- 2006
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7. Complex karyotypic aberrations, including i(12p), in malignant mixed mullerian tumor of uterus
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Avery A. Sandberg, Uma N.M. Rao, and Chandrika Sreekantaiah
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Genetic Markers ,endocrine system ,Cancer Research ,medicine.medical_specialty ,Mediastinal germ cell tumor ,Isochromosome ,Uterus ,Ovary ,Biology ,Internal medicine ,Genetics ,medicine ,Humans ,Mixed Müllerian tumor ,Molecular Biology ,Chromosome Aberrations ,Cytogenetics ,Karyotype ,Middle Aged ,Neoplasms, Germ Cell and Embryonal ,medicine.disease ,Endocrinology ,medicine.anatomical_structure ,Karyotyping ,Uterine Neoplasms ,Cancer research ,Female ,Germ cell tumors - Abstract
We report the cytogenetic findings in a malignant mixed mullerian tumor of the uterus in a 59-year-old woman. Karyotypic analysis of short-term cultures revealed two abnormal clones of cells characterized by extensive structural and numerical rearrangements. An i(12p) maker chromosome was present in addition to other changes in both clones. This marker, characteristically associated with testicular germ cell tumors in males, has recently been reported in ovarian germ cell tumors, a mediastinal germ cell tumor and in a mixed mullerian tumor of the ovary.
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- 1992
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8. Long-term viability of articular cartilage after microsurgical whole-joint transplantation and immunosuppression with rapamycin, mycophenolate mofetil, and tacrolimus
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Uma N.M. Rao, Neil F. Jones, and Esther Vögelin
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musculoskeletal diseases ,Cartilage, Articular ,Graft Rejection ,medicine.medical_specialty ,Microsurgery ,Time Factors ,Knee Joint ,medicine.medical_treatment ,Tacrolimus ,medicine ,Animals ,Transplantation, Homologous ,Orthopedics and Sports Medicine ,Immunosuppression Therapy ,Sirolimus ,Chemotherapy ,business.industry ,Cartilage ,Graft Survival ,Immunosuppression ,Mycophenolic Acid ,Surgery ,Rats ,Rats, Inbred ACI ,Transplantation ,surgical procedures, operative ,medicine.anatomical_structure ,Logistic Models ,Bone marrow suppression ,Rats, Inbred Lew ,Drug Therapy, Combination ,Female ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
The survival or rejection of articular cartilage in heterotopic vascularized joint transplants in rats immunosuppressed with rapamycin (SDZ RAD), mycophenolate mofetil (MMF), and tacrolimus was evaluated histologically up to 1 year after surgery. The vascularized knee joint of an ACI donor rat was transplanted to the groin of a Lewis recipient rat. Nonimmunosuppressed allografts were evaluated after 6 weeks and 3 months, and immunosuppressed allografts and control isografts were evaluated after 6 weeks, 3 months, 6 months, and 1 year. No rejection was seen in the control isografts. All allografts without immunosuppression were rejected at 6 weeks and 3 months. Eighteen of 21 knee joint transplants immunosuppressed with SDZ RAD and 17 of 22 knee joint transplants immunosuppressed with MMF were rejected between 6 weeks and 1 year. SDZ RAD and MMF caused significant side effects including compromised wound healing and bone marrow suppression culminating in weight loss and death. Eighteen of 19 knee joints immunosuppressed with tacrolimus showed no signs of rejection up to 1 year after surgery. Long-term intermittent immunosuppression with tacrolimus was significantly superior to SDZ RAD and MMF in preventing rejection of the transplanted articular cartilage of a vascularized knee joint allograft up to 1 year after surgery.
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- 2002
9. Cytokeratin immunophenotyping of an unusual cervical vertebral chordoma with extensive chondroid foci and perilaryngeal recurrence: a case report with review of the literature
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E. Leon Barnes, Ricardo L. Carrau, Jason C. Fowler, Uma N.M. Rao, and Kevin D. Horn
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Larynx ,Male ,Photomicrography ,Pathology ,medicine.medical_specialty ,Laryngectomy ,Metastasis ,Immunophenotyping ,Cytokeratin ,Fatal Outcome ,Notochord ,medicine ,Chordoma ,Humans ,Thyroid Neoplasms ,Laryngeal Neoplasms ,Aged ,Spinal Neoplasms ,business.industry ,Biopsy, Needle ,Mediastinum ,medicine.disease ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Treatment Outcome ,Otorhinolaryngology ,Cervical Vertebrae ,Immunohistochemistry ,Keratins ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies - Abstract
Chordomas are midline, slowly growing, and locally destructive tumors derived from vestigial remnants of the notochord. We present an unusual case of a cervical vertebral chordoma with extensive chondroid change that aggressively recurred in the anterior larynx and surrounding neck structures, and subsequently in the mediastinum, resulting in the death of the patient. Recent literature has investigated and debated the significance of chondroid elements in chordomas as a differential diagnostic and a prognostic indicator. In particular, the use of immunohistochemical stains for cytokeratin and mesenchymal markers in these areas as a means of distinguishing true from pseudocartilage has received much attention. In this study, we used a spectrum of cytokeratin subtypes (CK 7, 20, 5/6, AE1/3) to further characterize these chondroid areas, and observed that they were positive for the majority of the cytokeratin subtypes, suggesting pseudo, rather than true, cartilaginous change. Clinicopathologic features of this lesion and the recent literature are reviewed.
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- 2001
10. Clonal chromosomal abnormalities in hemangiopericytoma
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Julia A. Bridge, Uma N.M. Rao, Avery A. Sandberg, Chandrika Sreekantaiah, and James R. Neff
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Hemangiopericytoma ,Genetics ,Chromosome Aberrations ,Cancer Research ,Pathology ,medicine.medical_specialty ,Cytogenetics ,Chromosome ,Chromosomal translocation ,Karyotype ,Chromosome Disorders ,Biology ,medicine.disease ,Translocation, Genetic ,Chromosome Banding ,Clone Cells ,medicine ,Tumor Cells, Cultured ,Humans ,Abnormality ,Molecular Biology - Abstract
We report the cytogenetic findings in nine hemangiopericytomas studied after short-term culture. Clonal chromosome abnormalities were present in four cases. One case had a simple translocation (12;19)(q13;q13.3) as the sole abnormality whereas complex and multiple chromosomal abnormalities involving almost all chromosomes in the complement characterized tumors from the three other cases.
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- 1991
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