Person: Hecht, Jonathan
Loading...
Email Address
AA Acceptance Date
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
Hecht
First Name
Jonathan
Name
Hecht, Jonathan
3 results
Search Results
Now showing 1 - 3 of 3
Publication Filamin B Regulates Chondrocyte Proliferation and Differentiation through Cdk1 Signaling(Public Library of Science, 2014) Hu, Jianjun; Lu, J; Lian, Gewei; Zhang, Jingping; Hecht, Jonathan; Sheen, VolneyHumans who harbor loss of function mutations in the actin-associated filamin B (FLNB) gene develop spondylocarpotarsal syndrome (SCT), a disorder characterized by dwarfism (delayed bone formation) and premature fusion of the vertebral, carpal and tarsal bones (premature differentiation). To better understand the cellular and molecular mechanisms governing these seemingly divergent processes, we generated and characterized FlnB knockdown ATDC5 cell lines. We found that FlnB knockdown led to reduced proliferation and enhanced differentiation in chondrocytes. Within the shortened growth plate of postnatal FlnB−/− mice long bone, we observed a similarly progressive decline in the number of rapidly proliferating chondrocytes and premature differentiation characterized by an enlarged prehypertrophic zone, a widened Col2a1+/Col10a1+ overlapping region, but relatively reduced hypertrophic zone length. The reduced chondrocyte proliferation and premature differentiation were, in part, attributable to enhanced G2/M phase progression, where fewer FlnB deficient ATDC5 chondrocytes resided in the G2/M phase of the cell cycle. FlnB loss reduced Cdk1 phosphorylation (an inhibitor of G2/M phase progression) and Cdk1 inhibition in chondrocytes mimicked the null FlnB, premature differentiation phenotype, through a β1-integrin receptor- Pi3k/Akt (a key regulator of chondrocyte differentiation) mediated pathway. In this context, the early prehypertrophic differentiation provides an explanation for the premature differentiation seen in this disorder, whereas the progressive decline in proliferating chondrocytes would ultimately lead to reduced chondrocyte production and shortened bone length. These findings begin to define a role for filamin proteins in directing both cell proliferation and differentiation through indirect regulation of cell cycle associated proteins.Publication Ovarian cancer risk factors by tumor dominance, a surrogate for cell of origin(Wiley-Blackwell, 2013) Kotsopoulos, Joanne; Terry, Kathryn; Poole, Elizabeth M.; Rosner, Bernard; Murphy, Megan A.; Hecht, Jonathan; Crum, Christopher; Missmer, Stacey; Cramer, Daniel; Tworoger, ShelleyDifferentiating ovarian tumors based on developmental pathway may further our understanding of the disease. Traditionally, ovarian cancers were thought to arise from the ovarian surface epithelium; however, recent evidence suggests some tumors originate in the fallopian tube. We classified cases in a population-based case-control study (NECC) and two cohort studies (NHS/NHSII) by tumor dominance, a proxy for tissue of origin. Dominant tumors (likely ovarian origin) are restricted to one ovary or are at least twice as large on one ovary compared to the other. Ovarian cancer risk factors were evaluated in relation to dominant and non-dominant tumors (likely tubal origin) using polytomous logistic regression (NECC) or competing risks Cox models (NHS/NHSII). Results were combined using random-effects meta-analyses. Among 1,771 invasive epithelial ovarian cancer cases, we observed 1,089 tumors with a dominant mass and 682 with no dominant mass. Dominant tumors were more likely to be mucinous, endometrioid, or clear cell, whereas non-dominant tumors were more likely to be serous. Tubal ligation, two or more births, endometriosis, and age were more strongly associated with dominant (RRs = 0.60, 0.83, 1.58, 1.37, respectively) than non-dominant tumors (RRs = 1.03, 0.93, 0.84, 1.14 p-difference = 0.0001, 0.01, 0.0003, 0.01, respectively). These data suggest that risk factors for tumors putatively arising from ovarian versus fallopian tube sites may differ; in particular, reproductive factors may be more important for ovarian-derived tumors. As this is the first study to evaluate ovarian cancer risk factors by tumor dominance, these results need to be validated by other studies.Publication Patterns of Misinterpretation of Adnexal Masses on CT and MR in an Academic Radiology Department(Elsevier BV, 2009-08) Asch, Elizabeth; Levine, Deborah; Pedrosa, Ivan; Kruskal, Jonathan; Hecht, JonathanRationale and Objectives. The aim of this study was to assess potential quality assurance (QA) issues in the diagnosis and characterization of adnexal masses on pelvic computed tomographic (CT) and magnetic resonance (MR) imaging studies.Materials and Methods. Images from 128 women who had oophorectomies during a 16-month period with CT and/or MR studies within 5 years of surgery (145 CT scans from 103 women and 49 MR studies from 42 women, with 17 having both MR and CT studies) were reviewed by three radiologists who assigned QA scores of 0 (no QA issue), I (minor issue with minimal impact on clinical care), or 2 (major issue with potential impact on clinical care). The difficulty of diagnosis was assigned a score of 0 (very difficult diagnosis to make), 1 (difficult but possible to make the diagnosis), or 2 (diagnosis should be made). The incidence of adnexal QA issues was calculated using total CT and MR pelvic examinations performed on women during the interval.Results. Twenty-nine QA issues were identified in 28 women in 17 of 145 CT studies (11.7%) and 12 of 49 MR examinations (24.5%) in women having adnexal surgery (17 of 11, 194 [0.15%] of female pelvic CT studies and 12 of 603 [2.0%] of female pelvic MR studies performed in the time interval). Issues included missed lesions, lesions misidentified as leiomyomas, fat described in the lesion but not seen histologically, postmenopausal status of patient not considered, ultrasound correlation not recommended, and confusion of right and left sides.Conclusion. Errors in CT and MR studies regarding the diagnosis and characterization of adnexal masses in a highly enriched population of women undergoing adnexal surgery are common. Knowledge of the types of QA issues found in CT and MR studies of adnexal masses should aid in decreasing future errors.