Person: Young, Robert
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Young
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Young, Robert
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Publication Case 8-2010 — A 22-Year-Old Woman with Hypercalcemia and a Pelvic Mass(Massachusetts Medical Society, 2010-03-18) Young, Robert; Goodman, Annekathryn; Penson, Richard; Russell, Anthony; Uppot, Raul; Tambouret, RosemaryA 22-year-old woman was admitted to this hospital because of hypercalcemia and a pelvic mass. One month before admission, abdominal pain developed, followed by abdominal fullness, anorexia, nausea, vomiting, polydipsia, and nocturia. A computed tomographic scan of the pelvis showed a complex right adnexal mass. The serum calcium level was 17.2 mg per deciliter. A diagnostic procedure was performed.Publication Whole-Slide Imaging Digital Pathology as a Platform for Teleconsultation: A Pilot Study Using Paired Subspecialist Correlations(College of American Pathologists, 2009) Lauwers, Gregory Y.; Wilbur, David; Madi, Kalil; Colvin, Robert; Duncan, Lyn; Faquin, William; Ferry, Judith; Frosch, Matthew; Houser, Stuart L.; Kradin, Richard; Louis, David; Mark, Eugene; Mino-Kenudson, Mari; Misdraji, Joseph; Nielsen, Gunnlauger P.; Pitman, Martha; Rosenberg, Andrew Eric; Smith, R. Neal; Sohani, Aliyah; Stone, James; Tambouret, Rosemary; Wu, Chin-Lee; Young, Robert; Zembowicz, Artur; Wlietmann, WolfgangContext.—Whole-slide imaging technology offers promise for rapid, Internet-based telepathology consultations between institutions. Before implementation, technical issues, pathologist adaptability, and morphologic pitfalls must be well characterized. Objective.—To determine whether interpretation of whole-slide images differed from glass-slide interpretation in difficult surgical pathology cases. Design.—Diagnostically challenging pathology slides from a variety of anatomic sites from an outside laboratory were scanned into whole digital format. Digital and glass slides were independently diagnosed by 2 subspecialty pathologists. Reference, digital, and glass-slide interpretations were compared. Operator comments on technical issues were gathered. Results.—Fifty-three case pairs were analyzed. There was agreement among digital, glass, and reference diagnoses in 45 cases (85%) and between digital and glass diagnoses in 48 (91%) cases. There were 5 digital cases (9%) discordant with both reference and glass diagnoses. Further review of each of these cases indicated an incorrect digital whole-slide interpretation. Neoplastic cases showed better correlation (93%) than did cases of nonneoplastic disease (88%). Comments on discordant cases related to digital whole technology focused on issues such as fine resolution and navigating ability at high magnification. Conclusions.—Overall concordance between digital whole-slide and standard glass-slide interpretations was good at 91%. Adjustments in technology, case selection, and technology familiarization should improve performance, making digital whole-slide review feasible for broader telepathology subspecialty consultation applications.Publication Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin but inhibited by Mullerian inhibiting substance(Proceedings of the National Academy of Sciences, 2012) Meirelles, K.; Benedict, Lance Mitchell; Dombkowski, D.; Pepin, David; Preffer, Frederic; Teixeira, J; Tanwar, Pradeep; Young, Robert; MacLaughlin, D. T.; Donahoe, Patricia; Wei, X.Women with late-stage ovarian cancer usually develop chemotherapeutic-resistant recurrence. It has been theorized that a rare cancer stem cell, which is responsible for the growth and maintenance of the tumor, is also resistant to conventional chemotherapeutics. We have isolated from multiple ovarian cancer cell lines an ovarian cancer stem cell-enriched population marked by CD44, CD24, and Epcam (3+) and by negative selection for Ecadherin (Ecad−) that comprises less than 1% of cancer cells and has increased colony formation and shorter tumor-free intervals in vivo after limiting dilution. Surprisingly, these cells are not only resistant to chemotherapeutics such as doxorubicin, but also are stimulated by it, as evidenced by the significantly increased number of colonies in treated 3+Ecad− cells. Similarly, proliferation of the 3+Ecad− cells in monolayer increased with treatment, by either doxorubicin or cisplatin, compared with the unseparated or cancer stem cell-depleted 3−Ecad+ cells. However, these cells are sensitive to Mullerian inhibiting substance (MIS), which decreased colony formation. MIS inhibits ovarian cancer cells by inducing G1 arrest of the 3+Ecad− subpopulation through the induction of cyclin-dependent kinase inhibitors. 3+Ecad− cells selectively expressed LIN28, which colocalized by immunofluorescence with the 3+ cancer stem cell markers in the human ovarian carcinoma cell line, OVCAR-5, and is also highly expressed in transgenic murine models of ovarian cancer and in other human ovarian cancer cell lines. These results suggest that chemotherapeutics may be stimulative to cancer stem cells and that selective inhibition of these cells by treating with MIS or targeting LIN28 should be considered in the development of therapeutics.Publication Leiomyoma With Bizarre Nuclei: A Morphological, Immunohistochemical and Molecular Analysis of 31 Cases(2017) Bennett, Jennifer A.; Weigelt, Britta; Chiang, Sarah; Selenica, Pier; Chen, Ying-Bei; Bialik, Ann; Bi, Rui; Schultheis, Anne M.; Lim, Raymond S.; Ng, Charlotte KY; Morales-Oyarvide, Vicente; Young, Robert; Reuter, Victor E.; Soslow, Robert A.; Oliva, EstherLeiomyomas associated with hereditary leiomyomatosis and renal cell carcinoma syndrome and leiomyomas with bizarre nuclei often show overlapping morphological features, in particular cells with prominent eosinophilic nucleoli, perinucleolar halos and eosinophilic cytoplasmic inclusions. While hereditary leiomyomatosis and renal cell carcinoma syndrome is defined by fumarate hydratase (FH) germline mutations, resulting in S-(2-succino)-cysteine (2SC) formation, it is unknown if leiomyomas with bizarre nuclei show similar alterations. In this study, we evaluated the morphology and FH/2SC immunoprofile of 31 leiomyomas with bizarre nuclei. DNA from tumor and normal tissues from 24 cases was subjected to massively parallel sequencing targeting 410 key cancer genes. Somatic genetic alterations were detected using state-of-the-art bioinformatics algorithms. No patient reported a personal history of renal neoplasia or cutaneous leiomyomas, but one had a family history of renal cell carcinoma while another had a family history of uterine leiomyomas. Aberrant FH/2SC expression was noted in 17 tumors (16 FH-negative/2SC-positive, 1 FH-positive/2SC-positive). On univariate analysis, staghorn vessels, eosinophilic cytoplasmic inclusions, diffuse distribution of prominent eosinophilic nucleoli with perinucleolar halos and an “alveolar pattern of edema” were associated with an abnormal immunoprofile, but only staghorn vessels remained significant on multivariate analysis. Massively parallel sequencing analysis (n=24) revealed that 13/14 tumors with aberrant FH/2SC immunoprofile harbored somatic FH somatic genetic alterations, including homozygous deletions (n=9), missense mutations coupled with loss of heterozygosity (n=3), and a splice site mutation (n=1), whereas no somatic FH mutations/deletions were found in tumors with normal immunoprofile (n=10; p<0.0001). Leiomyomas with bizarre nuclei with normal FH/2SC staining pattern more frequently harbored TP53 and/or RB1 alterations than those with aberrant FH/2SC immunoprofile (60% vs 14%; p=0.032). These data demonstrate that leiomyomas with bizarre nuclei are morphologically and genetically heterogeneous, and that hereditary leiomyomatosis and renal cell carcinoma syndrome-related morphologic features, abnormal FH/2SC staining, and somatic FH mutations/deletions can be seen in a subset of sporadic tumors.