Jonathan Said

University of California, Los Angeles, Los Ángeles, California, United States

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Publications (376)2031.57 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: PARK2 (PARKIN) is an E3 ubiquitin ligase whose dysfunction has been associated with the progression of Parkinsonism and human malignancies, and its role in cancer remains to be explored. In this study, we report that PARK2 is frequently deleted and underexpressed in human glioma, and low PARK2 expression is associated with poor survival. Restoration of PARK2 significantly inhibited glioma cell growth both in vitro and in vivo, whereas depletion of PARK2 promoted cell proliferation. PARK2 attenuated both Wnt- and EGF-stimulated pathways through downregulating the intracellular level of beta-catenin and EGFR. Notably, PARK2 physically interacted with both beta-catenin and EGFR. We further found that PARK2 promoted the ubiquitination of these two proteins in an E3 ligase activity-dependent manner. Finally, inspired by these newly identified tumor-suppressive functions of PARK2, we tested and proved that combination of small-molecule inhibitors targeting both Wnt-beta-catenin and EGFR-AKT pathways synergistically impaired glioma cell viability. Together, our findings uncover novel cancer-associated functions of PARK2 and provide a potential therapeutic approach to treat glioma. Cancer Res; 75(9); 1-13. (c)2015 AACR.
    Cancer Research 04/2015; DOI:10.1158/0008-5472.CAN-14-1433 · 9.28 Impact Factor
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    ABSTRACT: With a limited number of prognostic and predictive biomarkers available, carbonic anhydrase-IX (CAIX) has served as an important prognostic biomarker for patients with clear cell renal cell carcinoma (ccRCC). However, studies have recently called into question the role of CAIX as a biomarker for ccRCC. To investigate this uncertainty, we quantified the association of CAIX with lymphatic involvement and survival using data from ARISER study (WX-2007-03-HR)-a prospective trial involving subjects with high-risk nonmetastatic ccRCC. We reviewed the records of 813 patients enrolled in the ARISER study. Central review of histology, grade, and CAIX staining (frequency and intensity) was performed. CAIX score was derived by multiplying the staining intensity (1-3) by percent positive cells (0%-100%), yielding a range of 0 to 300. We quantified the association of CAIX expression and score with lymphatic spread and survival (disease-free survival [DFS] and overall survival [OS]) using Kaplan-Meier and multivariable propensity score adjusted Cox regression analyses. Median follow-up of the cohort was 54.2 months. Although 56% of subjects with lymphatic involvement had CAIX>85%, only 33% had CAIX score≥200. On multivariable analysis, CAIX>85% was not a statistically significant predictor of DFS and OS (P = 0.06 and P = 0.15, respectively). However, CAIX score≥200, when compared with CAIX score≤100, was associated with improved DFS and OS (P = 0.01 and P = 0.01, respectively) on multivariable analysis. The largest, multicenter, prospective analysis of patients with high-risk nonmetastatic ccRCC demonstrates the utility of CAIX score as a statistically significant prognostic biomarker for survival. We recommend that CAIX score be quantified for all patients with high-risk disease after nephrectomy. Copyright © 2015 Elsevier Inc. All rights reserved.
    Urologic Oncology 03/2015; 33(5). DOI:10.1016/j.urolonc.2015.02.013 · 3.36 Impact Factor
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    ABSTRACT: We investigated the oncogenic role of SETDB1 focusing on non-small cell lung cancer (NSCLC) having high expression of this protein. A total of 387 lung cancer cases were examined by immunohistochemistry, 72% of NSCLC samples were positive for SETDB1 staining, compared to 46% samples of normal bronchial epithelium (106 cases) (p < 0.0001). Percent positive cells and intensity of staining increased significantly with increased grade of disease. Forced expression of SETDB1 in NSCLC cell lines enhanced their clonogenic growth in vitro and markedly increased tumor size in a murine xenograft model; while silencing (shRNA) SETDB1 in NSCLC cells slowed their proliferation. SETDB1 positively stimulated activity of the WNT/beta-catenin pathway and diminished P53 expression resulting in enhanced NSCLC growth in vitro and in vivo. Our finding suggests therapeutic targeting SETDB1 may benefit patients whose tumors express high levels of SETDB1.
    The Journal of Pathology 03/2015; DOI:10.1002/path.4482 · 7.33 Impact Factor
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    ABSTRACT: Purpose: HIV-related diffuse large B-cell lymphoma (DLBCL) may be biologically different from DLBCL in the general population. We compared, by HIV status, the expression and prognostic significance of selected oncogenic markers in DLBCL diagnosed at Kaiser Permanente California between 1996 and 2007. Design: Eighty HIV-infected DLBCL patients were 1:1 matched to 80 HIV-uninfected DLBCL patients by age, gender and race. Twenty-three markers in the following categories were examined using immunohistochemistry: (1) cell cycle regulators, (2) B-cell activators, (3) anti-apoptotic proteins, and (4) others, such as IgM. Tumor marker expression was compared across HIV infection status by Fisher's exact test. For markers differentially expressed in HIV-related DLBCL, logistic regression was used to evaluate the association between tumor marker expression and 2-year overall mortality, adjusting for international prognostic index, cell-of-origin phenotype and DLBCL morphologic variants. Results: Expression of cMYC (% positive in HIV-related and -unrelated DLBCL: 64% vs. 32%), BCL6 (45% vs. 10%), PKC-beta2 (61% vs. 4%), MUM1 (59% vs. 14%), and CD44 (87% vs. 56%) were significantly elevated in HIV-related DLBCLs, while expression of p27 (39% vs. 75%) was significantly reduced. Of these, cMYC expression was independently associated with increased two-year mortality in HIV-infected patients [relative risk =3.092.80 (0.90-10.550.90-8.70)] in multivariable logistic regression. Conclusion: These results suggest that HIV-related DLBCL pathogenesis more frequently involve cMYC and BCL6 among other factors. In particular, cMYC-mediated pathogenesis may partly explain the more aggressive clinical course of DLBCL in HIV-infected patients. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 01/2015; 21(6). DOI:10.1158/1078-0432.CCR-14-2083 · 8.19 Impact Factor
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    ABSTRACT: Mantle cell lymphoma is a mature B-cell neoplasm composed of small to medium-sized atypical lymphocytes and has a characteristic t(11;14)(q13;q32) translocation, with a variably aggressive and overall incurable course. More aggressive histologic variants have been described, as well as rare cases of transformation to other large cell lymphomas. Here, we describe a novel case of large cell blastic transformation of mantle cell lymphoma/leukemia at presentation with unusual immunophenotypic and cytogenetic features, most consistent with B-lymphoblastic leukemia. Morphologic findings include sheets of large blasts replacing the bone marrow, as well as occasional small to medium-sized atypical lymphocytes in the background. The blasts express CD19, PAX5, CD10, Cyclin D1, and TdT but are negative for CD5, CD20, and BCL2 by immunophenotyping. Cytogenetic studies show a complex karyotype with t(11;14), monosomy 13, gains of 8q, and MYC gene rearrangement and amplification among other changes. This unique case of blastic TdT-positive B-cell leukemia arising from mantle cell lymphoma may represent transformation with complex cytogenetic abnormalities including “double hit” changes. This distinctive presentation may expand our understanding of the biology behind mantle cell lymphoma progression.
    01/2015; 8(1). DOI:10.1007/s12308-014-0229-9
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    ABSTRACT: A 66 year-old woman presented with a breast mass and bilateral axillary adenopathy. Clinicians were initially concerned for the possibility of breast carcinoma, but a breast biopsy demonstrated reactive changes and no malignancy. A subsequent axillary lymph node biopsy revealed a neoplastic proliferation composed of sheets of large atypical cells with ovoid to angulated nuclei, clumped chromatin, distinct nucleoli, and scant eosinophilic cytoplasm (see Fig. 1a).Fig. 1Microscopic photographs. a Sheets of large atypical cells (H&E stain, ×100; inset ×400). b CD20 immunohistochemical stain, ×100. c Pan keratin AE1/AE3 immunohistochemical stain, ×100. d CAM5.2 immunohistochemical stain, ×100Immunohistochemical stains were positive for lymphoid and B cell antigens, including CD45, CD20 (see Fig. 1b), PAX5, CD79a, CD5, CD10, BCL2, BCL6, and MUM1, but negative for cyclin D1 and TdT. No kappa or lambda light chain restriction was seen. The Ki67 proliferation index was approximately 90 %. A cMy ...
    01/2015; DOI:10.1007/s12308-015-0243-6
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    ABSTRACT: Background Preclinical and epidemiologic studies suggest chemopreventive effects of green tea (GT) and black tea (BT) in prostate cancer. In the current study we determined the effect of GT and BT consumption on biomarkers related to prostate cancer development and progression.Methods In this exploratory, open label, phase II trial 113 men diagnosed with prostate cancer were randomized to consume six cups daily of brewed GT, BT or water (control) prior to radical prostatectomy (RP). The primary endpoint was prostate tumor markers of cancer development and progression determined by tissue immunostaining of proliferation (Ki67), apoptosis (Bcl-2, Bax, Tunel), inflammation (nuclear and cytoplasmic nuclear factor kappa B [NFκB]) and oxidation (8-hydroxydeoxy-guanosine [8OHdG]). Secondary endpoints of urinary oxidation, tea polyphenol uptake in prostate tissue, and serum prostate specific antigen (PSA) were evaluated by high performance liquid chromatography and ELISA analysis.ResultsNinety three patients completed the intervention. There was no significant difference in markers of proliferation, apoptosis and oxidation in RP tissue comparing GT and BT to water control. Nuclear staining of NFκB was significantly decreased in RP tissue of men consuming GT (P = 0.013) but not BT (P = 0.931) compared to water control. Tea polyphenols were detected in prostate tissue from 32 of 34 men consuming GT but not in the other groups. Evidence of a systemic antioxidant effect was observed (reduced urinary 8OHdG) only with GT consumption (P = 0.03). GT, but not BT or water, also led to a small but statistically significant decrease in serum prostate-specific antigen (PSA) levels (P = 0.04).Conclusion Given the GT-induced changes in NFκB and systemic oxidation, and uptake of GT polyphenols in prostate tissue, future longer-term studies are warranted to further examine the role of GT for prostate cancer prevention and treatment, and possibly for other prostate conditions such as prostatitis. Prostate © 2014 Wiley Periodicals, Inc.
    The Prostate 12/2014; 75(5). DOI:10.1002/pros.22943 · 3.57 Impact Factor
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    ABSTRACT: Context: Anaplastic thyroid cancer (ATC) has no effective treatment, resulting in a high rate of mortality. We established cell lines from a primary ATC and its lymph node metastasis, and investigated the molecular factors and genomic changes associated with tumor growth. Objective: The aim of the study was to understand the molecular and genomic changes of highly aggressive ATC and its clonal evolution to develop rational therapies. Design: We established unique cell lines from primary (OGK-P) and metastatic (OGK-M) ATC specimen, as well as primagraft from the metastatic ATC, which was serially xeno-transplanted for more than 1 year in NSG mice were established. These cell lines and primagraft were used as tools to examine gene expression, copy number changes, and somatic mutations using RNA array, SNP Chip, and whole exome sequencing. Results: Mice carrying subcutaneous (OGK-P and OGK-M) tumors developed splenomegaly and neutrophilia with high expression of cytokines including CSF1, CSF2, CSF3, IL-1β, and IL-6. Levels of HIF-1α and its targeted genes were also elevated in these tumors. The treatment of tumor carrying mice with Bevacizumab effectively decreased tumor growth, macrophage infiltration, and peripheral WBCs. SNP chip analysis showed homozygous deletion of exons 3-22 of the PARD3 gene in the cells. Forced expression of PARD3 decreased cell proliferation, motility, and invasiveness, restores cell-cell contacts and enhanced cell adhesion. Next generation exome sequencing identified the somatic changes present in the primary, metastatic, and primagraft tumors demonstrating evolution of the mutational signature over the year of passage in vivo. Conclusion: To our knowledge, we established the first paired human primary and metastatic ATC cell lines offering unique possibilities for comparative functional investigations in vitro and in vivo. Our exome sequencing also identified novel mutations, as well as clonal evolution in both the metastasis and primagraft.
    Journal of Clinical Endocrinology &amp Metabolism 11/2014; 100(2):jc20142359. DOI:10.1210/jc.2014-2359 · 6.31 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):2819-2819. DOI:10.1158/1538-7445.AM2014-2819 · 9.28 Impact Factor
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    ABSTRACT: Bromodomain and extra terminal domain (BET) proteins are important epigenetic regulators facilitating the transcription of genes in chromatin areas linked to acetylated histones. JQ1, a BET protein inhibitor, has antiproliferative activity against many cancers, mainly through inhibition of c-MYC and upregulation of p21. In this research, we investigated the use of JQ1 for human osteosarcoma (OS) treatment. JQ1 significantly inhibited the proliferation and survival of OS cells inducing G1 cell cycle arrest, premature senescence, but little effect on apoptosis. Interestingly, c-MYC protein levels in JQ1-treated cells remained unchanged, whereas the upregulation of p21 protein was still observable. Although effective in vitro, JQ1 alone failed to reduce the size of the MNNG/HOS xenografts in immunocompromised mice. To overcome the resistance of OS cells to JQ1 treatment, we combined JQ1 with rapamycin, an mTOR inhibitor. JQ1 and rapamycin synergistically inhibited the growth and survival of OS cells in vitro and in vivo. We also identified that RUNX2 is a direct target of BRD4 inhibition by JQ1 in OS cells. Chromatin immunoprecipitation (ChIP) showed that enrichment of BRD4 protein around RUNX2 transcription start sites diminished with JQ1 treatment in MNNG/HOS cells. Overexpression of RUNX2 protected JQ1-sensitive OS cells from the effect of JQ1, and siRNA-mediated inhibition of RUNX2 sensitized the same cells to JQ1. In conclusion, our findings suggest that JQ1, in combination with rapamycin, is an effective chemotherapeutic option for OS treatment. We also show that inhibition of RUNX2 expression by JQ1 partly explains the antiproliferative activity of JQ1 in OS cells. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 10/2014; 136(9). DOI:10.1002/ijc.29269 · 5.01 Impact Factor
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    ABSTRACT: Pancreatic ductal adenocarcinoma is a devastating disease with few therapeutic options. Histone deacetylase inhibitors are a novel therapeutic approach to cancer treatment; and two new pan-histone deacetylase inhibitors (HDACi), belinostat and panobinostat, are undergoing clinical trials for advanced hematologic malignancies, non-small cell lung cancers and advanced ovarian epithelial cancers. We found that belinostat and panobinostat potently inhibited, in a dose-dependent manner, the growth of six (AsPc1, BxPc3, Panc0327, Panc0403, Panc1005, MiaPaCa2) of 14 human pancreatic cancer cell lines. Belinostat increased the percentage of apoptotic pancreatic cancer cells and caused prominent G2 /M growth arrest of most pancreatic cancer cells. Belinostat prominently inhibited PI3K-mTOR-4EBP1 signaling with a 50% suppression of phorphorylated 4EBP1 (AsPc1, BxPc3, Panc0327, Panc1005 cells). Surprisingly, belinostat profoundly blocked hypoxia signaling including the suppression of hypoxia response element reporter activity; as well as an approximately 10-fold decreased transcriptional expression of VEGF, adrenomedullin, and HIF1α at 1% compared to 20% O2 . Treatment with this HDACi decreased levels of thioredoxin mRNA associated with increased levels of its endogenous inhibitor thioredoxin binding protein-2. Also, belinostat alone and synergistically with gemcitabine significantly (P = 0.0044) decreased the size of human pancreatic tumors grown in immunodeficiency mice. Taken together, HDACi decreases growth, increases apoptosis, and is associated with blocking the AKT/mTOR pathway. Surprisingly, it blocked hypoxic growth related signals. Our studies of belinostat suggest it may be an effective drug for the treatment of pancreatic cancers when used in combination with other drugs such as gemcitabine. © 2013 Wiley Periodicals, Inc.
    Molecular Carcinogenesis 09/2014; 53(9). DOI:10.1002/mc.22024 · 4.77 Impact Factor
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    ABSTRACT: Intestinal intraepithelial T lymphocytes express the α E subunit of integrin αEβ7, which is detected by antibodies to CD103. Accordingly, within T-cell neoplasms, CD103 reactivity has most frequently been reported in enteropathy-associated T-cell lymphomas, which are postulated to arise from intestinal intraepithelial T lymphocytes. However, prior studies of CD103 expression in T-cell neoplasms have been limited by the requirement for fresh or frozen tissue, given the historic lack of an antibody to CD103 for use in paraffin-embedded sections. Thus, a thorough assessment of CD103 expression in a broad spectrum of T-cell neoplasms as categorized by the current classification system has not yet been performed. This study uses a newly described antibody to define the profile of CD103 immunoreactivity in paraffin sections of a wide variety of T-cell neoplasms (184 cases). Overall, 22 T-cell neoplasms (12%) were CD103 positive, including 7 of 15 gastrointestinal lymphomas (3.8% of total cases; 46% of gastrointestinal cases). In intestinal cases, CD103 positivity did not correlate with morphology, presence or absence of enteropathy, or immunohistochemical profile. A history of celiac disease was not documented in any case. Frequent but inconsistent reactivity was also noted for adult T-cell leukemia/lymphoma with 4 of 10 cases (40%) positive. In the remaining T-cell neoplasms representing most entities within the current World Health Organization classification, CD103 reactivity was sporadically observed in 11 of 159 cases (6.9%). CD103 positivity is an unusual feature in T-cell neoplasms and tends to occur in gastrointestinal lymphomas and adult T-cell leukemia/lymphoma but is not a consistent characteristic of these neoplasms.
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    ABSTRACT: The gastrointestinal (GI) tract is the most common site of extranodal B-cell lymphomas. However, it is unclear how neoplastic lymphoid cells preferentially home there. We hypothesize that expression of the gastrointestinal-homing chemokine receptor CCR9 may account for the dissemination of B-cell lymphomas to the gastrointestinal tract. To test our hypothesis, we compared the expression of CCR9 using immunohistochemistry on GI versus nodal diffuse large B-cell lymphoma and follicular lymphoma. We found that 27/41 (66%), 12/41 (29%), and 2/41 (5%) of GI lymphoma cases demonstrated 3+, 2+, and 1+ CCR9 staining, respectively. In contrast, 2/39 (5%), 5/39 (13%), 8/39 (20.5%), and 24/39 (61.5%) nodal-restricted lymphoma cases demonstrated 3+, 2+, 1+ and 0+ CCR9 staining (P<0.0001). This was observed for both diffuse large B-cell lymphoma (P<0.001) and follicular lymphoma (P<0.001). We also compared the expression of CCR9 on nodal B-cell lymphomas with involvement of the gastrointestinal tract to those restricted to the lymph node. We found that 10/16 (62%), 3/16 (19%), and 3/16 (19%) nodal lymphomas with gastrointestinal involvement showed 3+, 2+ and 1+ CCR9 staining, respectively. In contrast, 2/39 (5%), 5/39 (13%), 8/39 (20.5%), and 24/39 (61.5%) nodal lymphomas without gastrointestinal involvement demonstrated 3+, 2+, 1+ and 0+ CCR9 staining, respectively (P<0.001). Our finding that CCR9 expression is elevated in the nodal lymphomas of patients with gastrointestinal involvement suggests the potential clinical utility of chemokine receptor status, as assessed by immunohistochemistry, to potentially predict gastrointestinal dissemination and progression to higher stage in patients who initially present with limited nodal-restricted disease.
    Human pathology 07/2014; 45(7). DOI:10.1016/j.humpath.2014.02.021 · 2.81 Impact Factor
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    ABSTRACT: ALK-negative anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell non-Hodgkin lymphoma that morphologically resembles ALK-positive ALCL but lacks chromosomal rearrangements of the ALK gene. The genetic and clinical heterogeneity of ALK-negative ALCL has not been delineated. We performed immunohistochemistry and fluorescence in situ hybridization on 73 ALK-negative ALCLs and 32 ALK-positive ALCLs and evaluated the associations among pathology, genetics, and clinical outcome. Chromosomal rearrangements of DUSP22 and TP63 were identified in 30% and 8% of ALK-negative ALCLs, respectively. These rearrangements were mutually exclusive and were absent in ALK-positive ALCLs. Five-year overall survival rates were 85% for ALK-positive ALCLs, 90% for DUSP22-rearranged ALCLs, 17% for TP63-rearranged ALCLs, and 42% for cases lacking all three genetic markers (p<0.0001). Hazard ratios for death in these 4 groups after adjusting for International Prognostic Index and age were 1.0 (reference group), 0.58, 8.63, and 4.16, respectively (p=7.10 x 10(-5)). These results were similar when restricted to patients receiving anthracycline-based chemotherapy as well as to patients not receiving stem-cell transplantation. Thus, ALK-negative ALCL is a genetically heterogeneous disease with widely disparate outcomes following standard therapy. DUSP22 and TP63 rearrangements may serve as predictive biomarkers to help guide patient management.
    Blood 06/2014; 124(9). DOI:10.1182/blood-2014-04-571091 · 10.43 Impact Factor
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    ABSTRACT: Intravascular large B-cell lymphomas and EBV NK/T-cell lymphomas commonly follow an aggressive clinical course. We recently reported an entirely intravascular anaplastic large cell lymphoma (ALCL) in the skin with a surprisingly indolent clinical course; interestingly, this lymphoma involved the lymphatic rather than the blood vasculature. We hypothesized that intravascular skin-limited ALCL is distinct from aggressive systemic intravascular lymphomas in its intralymphatic localization and clinical course. We now describe 18 cases of cutaneous intravascular large cell lymphoproliferations from 4 institutions. All 12 intravascular large T-cell lesions were intralymphatic; the majority (9) were CD30 T-cell lymphoproliferative disorders (TLPDs), 5 further classified as intravascular ALK ALCL. One ALK ALCL and 2 benign microscopic intravascular T-cell proliferations were also intralymphatic. A single case of otherwise typical cutaneous follicle center lymphoma contained intralymphatic centroblasts. The clinical and pathologic characteristics of the CD30 TLPDs were similar to those of their extravascular counterparts, including extralymphatic dermal involvement in a subset, DUSP22-IRF4 translocations in half of tested ALK ALCLs, and associated mycosis fungoides in 1; most were skin-limited at baseline and remained so at relapse. All 5 cases of intravascular large B-cell lymphoma involved the blood vasculature and behaved in a clinically aggressive manner; the ALK ALCL, although intralymphatic, was systemic and clinically aggressive. We propose that cutaneous ALK ALCL and related CD30 ALK TLPDs involving the lymphatics are part of an expanding spectrum of CD30 TLPDs. The identification of intralymphatic as distinct from blood vascular localization may provide critical prognostic and therapeutic information.
    The American journal of surgical pathology 05/2014; DOI:10.1097/PAS.0000000000000217 · 4.59 Impact Factor
  • Jonathan Said, Mark Lones, Steven Yea
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    ABSTRACT: Burkitt lymphoma (BL) is the most common non-Hodgkin lymphoma in children and adolescents, but at least 30% of cases occur in patients older than 60 years, and the absolute number of BL cases in adults exceeds those in childhood. BL is described as a monomorphic proliferation of medium-sized transformed B cells with round nuclei, clumped chromatin, basophilic cytoplasm, and squared-off cell borders, cytoplasmic vacuoles, medium-sized paracentral nucleoli, and a starry sky pattern. Translocation involving MYC is characteristic but not specific for BL. No single parameter is the gold standard for diagnosis; morphology, cytogenetics, immunophenotype, and gene expression profiles all may contribute to the diagnosis. Although neither EBV nor MYC are sufficient to cause BL there is increasing information from techniques such as complete RNA sequencing that identify essential pathways that are activated in the pathogenesis of BL. These findings suggest novel opportunities for improved therapeutic intervention.
    Advances in anatomic pathology 05/2014; 21(3):160-5. DOI:10.1097/PAP.0b013e3182a92cde · 3.10 Impact Factor
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    ABSTRACT: LNK (SH2B3) is an adaptor protein studied extensively in normal and malignant hematopoietic cells. In these cells, it downregulates activated tyrosine kinases at the cell surface resulting in an antiproliferative effect. To date, no studies have examined activities of LNK in solid tumors. In this study, we found by in silico analysis and staining tissue arrays that the levels of LNK expression were elevated in high-grade ovarian cancer. To test the functional importance of this observation, LNK was either overexpressed or silenced in several ovarian cancer cell lines. Remarkably, overexpression of LNK rendered the cells resistant to death induced by either serum starvation or nutrient deprivation, and generated larger tumors using a murine xenograft model. In contrast, silencing of LNK decreased ovarian cancer cell growth in vitro and in vivo. Western blot studies indicated that overexpression of LNK upregulated and extended the transduction of the mitogenic signal, whereas silencing of LNK produced the opposite effects. Furthermore, forced expression of LNK reduced cell size, inhibited cell migration and markedly enhanced cell adhesion. Liquid chromatography-mass spectroscopy identified 14-3-3 as one of the LNK-binding partners. Our results suggest that in contrast to the findings in hematologic malignancies, the adaptor protein LNK acts as a positive signal transduction modulator in ovarian cancers.Oncogene advance online publication, 7 April 2014; doi:10.1038/onc.2014.34.
    Oncogene 04/2014; 34(11). DOI:10.1038/onc.2014.34 · 8.56 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e372. DOI:10.1016/j.juro.2014.02.1049 · 3.75 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e386. DOI:10.1016/j.juro.2014.02.1083 · 3.75 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e383. DOI:10.1016/j.juro.2014.02.1076 · 3.75 Impact Factor

Publication Stats

15k Citations
2,031.57 Total Impact Points

Institutions

  • 1985–2015
    • University of California, Los Angeles
      • • Department of Pathology and Laboratory Medicine
      • • Department of Urology
      • • Division of Hematology and Medical Oncology
      • • Department of Medicine
      Los Ángeles, California, United States
  • 1997–2014
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      • Department of Medicine
      Torrance, California, United States
    • U.S. Department of Veterans Affairs
      Washington, Washington, D.C., United States
    • Truman Medical Center
      Kansas City, Kansas, United States
  • 2012
    • Universitätsklinikum Münster
      Muenster, North Rhine-Westphalia, Germany
  • 2010
    • Harbor-UCLA Medical Center
      Torrance, California, United States
  • 2004–2010
    • CSU Mentor
      • Department of Medicine
      Long Beach, California, United States
    • Kochi University
      Kôti, Kōchi, Japan
    • University of California, Davis
      • Department of Dermatology
      Davis, California, United States
  • 2009
    • California State University, Northridge
      Northridge, Ohio, United States
  • 2006–2009
    • Multiple Myeloma - Institute for Myeloma & Bone Cancer Research
      California City, California, United States
    • Boston University
      Boston, Massachusetts, United States
  • 1984–2008
    • Cedars-Sinai Medical Center
      • • Division of Hematology and Oncology
      • • Cedars Sinai Medical Center
      • • Department of Pathology and Laboratory Medicine
      • • Department of Medicine
      Los Ángeles, California, United States
  • 2005
    • Oita University
      Ōita, Ōita, Japan
    • University of Washington Seattle
      Seattle, Washington, United States
    • Comprehensive Cancer Centers of Nevada
      Las Vegas, Nevada, United States
  • 1988–2005
    • Harvard Medical School
      • Department of Pathology
      Boston, MA, United States
  • 2003
    • Cornell University
      Итак, New York, United States
  • 2001
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States
  • 1982–2001
    • Brigham and Women's Hospital
      • Department of Pathology
      Boston, Massachusetts, United States
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States
  • 2000
    • University of Michigan
      Ann Arbor, Michigan, United States
    • Hiroshima University
      • Research Institute for Radiation Biology and Medicine (RIRBM)
      Hirosima, Hiroshima, Japan
  • 1998
    • Children's Hospital of Orange County
      Orange Cove, California, United States
  • 1988–1990
    • Beth Israel Deaconess Medical Center
      • Department of Pathology
      Boston, MA, United States
  • 1983
    • National Cancer Institute (USA)
      베서스다, Maryland, United States