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Cell Malignancy (cell + malignancy)
Selected AbstractsRetroperitoneal seminoma with ,burned out' phenomenon in the testisINTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2005PETROS PERIMENIS Abstract The rare ,burned out' phenomenon in germ cell tumors is known as the presence of an extragonadal germ cell tumor without traces of neoplasm in the testis. This condition is different and less common from the primary extragonadal germ cell malignancies. These malignancies are treated surgically with or without adjuvant chemotherapy or radiotherapy and their prognosis is better than that of other types of primary extragonadal tumors. [source] Characteristics of testicular dysgenesis syndrome and decreased expression of SRY and SOX9 in Frasier syndromeMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 9 2008Valérie Schumacher Abstract Frasier syndrome (FS) is characterized by chronic renal failure in early adulthood, varying degrees of gonadal dysgenesis, and a high risk for gonadal germ cell malignancies, particularly gonadoblastoma. Although it is known to arise from heterozygous splice mutations in intron 9 of the Wilms' tumor gene 1 (WT1), the mechanisms by which these mutations result in gonadal dysgenesis in humans remain obscure. Here we show that a decrease in WT1,+,KTS isoforms due to disruption of alternative splicing of the WT1 gene in a FS patient is associated with diminished expression of the transcription factors SRY and SOX9 in Sertoli cells. These findings provide the first confirmation in humans of the results obtained by others in mice. Consequently, Sertoli cells fail to form the specialized environment within the seminiferous tubules that normally houses developing germ cells. Thus, germ cells are unable to fully mature and are blocked at the spermatogonial,spermatocyte stage. Concomitantly, subpopulations of the malignant counterpart of primordial germ cells/gonocytes, the intratubular germ cell neoplasia unclassified type (ITGCN), are identified. Furthermore, dysregulated Leydig cells produce insufficient levels of testosterone, resulting in hypospadias. Collectively, the impaired spermatogenesis, hypospadias and ITGCN comprise part of the developmental disorder known as ,testicular dysgenesis syndrome' (TDS), which arises during early fetal life. The data presented here show that critical levels of WT1,+,KTS, SRY and SOX9 are required for normal Sertoli cell maturation, and subsequent normal spermatogenesis. To further study the function of human Sertoli cells in the future, we have established a human cell line. Mol. Reprod. Dev. 75: 1484,1494, 2008. © 2008 Wiley-Liss, Inc. [source] Toward a comprehensive quantitative proteome database: protein expression map of lymphoid neoplasms by 2-D DIGE and MSPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 17 2006Kazuyasu Fujii Abstract Using 2-D DIGE, we constructed a quantitative 2-D database including 309 proteins corresponding to 389 protein spots across 42 lymphoid neoplasm cell lines. The proteins separated by 2-D PAGE were identified by MS and assigned to the expression data obtained by 2-D DIGE. The cell lines were categorized into four groups: those from Hodgkin's lymphoma (HL) (4 cell lines), B cell malignancies (19 cell lines), T cell malignancies (16 cell lines), and natural killer (NK) cell malignancies (3 cell lines). We characterized the proteins in the database by classifying them according to their expression level. We found 28 proteins with more than a 2-fold difference between the cell line groups. We also noted the proteins that allowed multidimensional separation to be achieved (1) between HL cells and other cells, (2) between the cells derived from B cells, T cells and NK cells, and (3) between HL cells and anaplastic large cell lymphoma cells. Decision tree classification identified five proteins that could be used to classify the 42 cell lines according to differentiation. These results suggest that the quantitative 2-D database using 2-D DIGE will be a useful resource for studying the mechanisms underlying the differentiation phenotypes of lymphoid neoplasms. [source] Detection of WA B cells in hepatitis C virus infection: A potential prognostic marker for cryoglobulinemic vasculitis and B cell malignanciesARTHRITIS & RHEUMATISM, Issue 7 2010Glenn B. Knight Objective An uncommon manifestation of hepatitis C virus (HCV) infection is systemic vasculitis associated with type II cryoglobulinemia (cryoglobulinemic vasculitis), a proliferative B cell disorder that transforms into B cell malignancy in 5,10% of patients. The monoclonal rheumatoid factors (mRF) that bear the WA cross-idiotype (Xid) are responsible for most cases of cryoglobulinemic vasculitis in patients with HCV infection. The purpose of this study was to determine whether WA B cells can be detected in asymptomatic patients with HCV infection, using sequence analysis of B cell clonal expansions (BCEs) to identify the WA Xid. Methods Asymptomatic patients with HCV infection and those without HCV infection as well as respective control patients with cryoglobulinemic vasculitis, whose serum was either negative or positive for WA mRF, were studied. BCEs were isolated in the patients' blood, and WA BCEs were identified by sequencing analysis. Results BCEs were detected in all control patients with cryoglobulinemic vasculitis, but only control patients with HCV infection had WA BCEs. None of the 33 asymptomatic patients without HCV infection had a BCE. WA BCEs were detected in 4 (7.4%) of 55 asymptomatic patients with HCV infection, in none of 14 patients with HCV infection and type III cryoglobulinemia, and in 5 (13.5%) of 37 patients with HCV infection and serum RF positivity. One patient with a WA BCE had splenic lymphoma markers and villous lymphocytes, and the villous lymphocytes were found to be WA B cells. Conclusion By identification of the WA Xid, WA B cells can be detected in asymptomatic HCV-infected patients. WA B cells in asymptomatic patients with HCV infection may be a marker for the development of cryoglobulinemic vasculitis and associated B cell malignancies. The results of this study provide a basis for the development of the first practical clinical application of cross-idiotype analysis. [source] Losing B cell identityBIOESSAYS, Issue 3 2008Sebastian Carotta The transcription factor Pax5 is essential for the initial commitment of hematopoietic progenitors to the B cell lineage. Recently, our understanding of the lineage commitment process has been extended with the finding that Pax5 is also continuously required throughout B cell development to reinforce commitment, as inactivation of Pax5 in mature B cells results in their de-differentiation to a progenitor stage that is capable of multi-lineage potential.1 The reliance of B cell identity on a single gene is not without its problems as the loss of Pax5 results in B cell malignancies in mouse models and mutation in human PAX5 is the most-common genetic lesion in acute lymphoblastic leukemia. BioEssays 30:203,207, 2008. © 2008 Wiley Periodicals, Inc. [source] SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumorsCANCER, Issue 12 2009Dengfeng Cao MD Abstract BACKGROUND: The correct diagnosis of metastatic germ cell tumors is critical, because these tumors can be effectively treated and are even cured with modern therapy. Their histopathologic diagnosis can be challenging without immunohistochemical markers, which currently have limitations. SALL4 is a novel stem cell marker essential to maintain pluripotency and self-renewal of embryonic stem cells. In the current study, the authors investigated the utility of SALL4 as a potential diagnostic marker for metastatic germ cell tumors. METHODS: Ninety metastatic germ cell tumors from testis, ovary, and extragonadal sites were stained with a monoclonal SALL4 antibody. In addition, 170 metastatic nongerm cell malignancies, including 158 carcinomas (6 head and neck, 8 thyroid, 12 lung, 8 breast, 7 hepatocellular, 3 cholangiocarcinomas, 2 ampullary, 10 pancreatic, 18 gastric, 15 esophageal, 10 renal cell, 10 urothelial, 12 prostatic, 18 ovarian, 6 uterine, and 13 colonic) and 12 melanomas, were also stained to test SALL4 specificity. RESULTS: All 22 seminomas, 7 dysgerminomas, 22 embryonal carcinomas, and 14 of 15 yolk sac tumors displayed strong and diffuse SALL positivity in >90% of tumor cells (80% of tumor cells were strongly positive in the remaining yolk sac tumor). Five of 7 choriocarcinomas and 9 of 18 teratomas were also variably positive for SALL4. In contrast, only 10 (esophageal, gastric, and colonic adenocarcinomas) of 170 metastatic somatic tumors demonstrated focally weak SALL4 reactivity (<25% tumor cells). CONCLUSIONS: SALL4 is a novel sensitive and highly specific marker for metastatic germ cell tumors, and is particularly useful for detecting metastatic yolk sac tumors. Cancer 2009. © 2009 American Cancer Society. [source] Btk and phospholipase,C,2 can function independently during B cell developmentEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2007Kristina Abstract The pre-BCR and the BCR regulate B cell development via a signalosome nucleated by the adaptor protein B cell linker protein (BLNK). Formation of this complex facilitates activation of phospholipase,C (PLC),,2 by Bruton's tyrosine kinase (Btk). To determine whether Btk and PLC,2 also have separate functions, we generated Btk,/,PLC,2,/, mice. They demonstrated a block in development at the pre-B,stage and increased pre-BCR surface expression. This phenotype was more severe than that of Btk,/, or PLC,2,/, mice. Although both Btk and PLC,2 were required for proliferation of splenic B cells in response to BCR cross-linking, they contributed differently to anti-IgM-induced phosphorylation of ERK. Btk,/, and PLC,2,/, mice each had a reduced frequency of Ig,-expressing B cells and impaired migration of pre-B cells towards stromal cell-derived factor,1. However, the increase in pre-B cell malignancy that occurs in BLNK,/, mice in the absence of Btk was not observed in the absence of PLC,2. Thus, Btk and PLC,2 act both in concert and independently throughout B cell development. [source] The imbalance between Bim and Mcl-1 expression controls the survival of human myeloma cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2004Patricia Gomez-Bougie Abstract Multiple myeloma is a fatal B,cell malignancy characterized by the accumulation of plasma cells within the bone marrow. IL-6 is a major survival factor for myeloma cells. Bcl-2 protein family regulates pathways to apoptosis that are activated upon growth factor deprivation. Pro-apoptotic proteins that have only a single Bcl-2 homology domain, BH3-only, are potent inducers of apoptosis. In myeloma cells, Mcl-1 has been shown to be a major anti-apoptotic protein that appears to regulate cell survival through the JAK/STAT pathway. In this study, we examined the regulation of the BH3-only protein Bim and its interaction with Mcl-1. The three major Bim isoforms are expressed in myeloma cells and are negatively regulated by IL-6. Blockade of IL-6 signaling induces an up-regulation of Bim concomitant to Mcl-1 down-regulation. Of major interest, Bim is found strongly associated with Mcl-1 in viable myeloma cells while this interaction is disrupted under apoptosis induction. Of note, while Bim is also found strongly associated to Bcl-2, this interaction is not changed under apoptosis induction. Thus, in myeloma cells, Mcl-1 neutralizes Bim through complex formation and therefore prevents apoptosis. Under apoptosis induction, the disappearance of Mcl-1 allows Bim to exercise its pro-apoptotic function and to activate Bax. [source] Malignant peripheral nerve sheath tumor of the uterine cervix expressing both S-100 protein and HMB-45JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 6 2009Na Rae Kim Abstract A 50-year-old woman presented with a large cervical polypoid mass. Grossly, the mass occupied a substantial proportion of the cervical canal, measuring 6 cm. Histologically, the mass showed a spindle cell malignancy arranged in large fascicles that penetrated deeply into the fibromuscular wall of the cervix. The spindle cells were immunoreactive for both S-100 protein and HMB-45 antigen, but were negative for Melan-A. Electron microscopy showed that cytoplasmic processes of the spindle to oval tumor cells contained microtubules and were lined by basal lamina and abundant intercellular collagen spacing with no melanosomes in any stage. As far as we are aware, this is the ninth reported case of cervical malignant peripheral nerve sheath tumor (MPNST), and the second reported case of MPNST expressing HMB-45 antigen. [source] Blastic natural killer cell lymphoma arising from the mediastinum with terminal deoxynucleotidyl transferase expressionPATHOLOGY INTERNATIONAL, Issue 1 2001Kouichi Isobe Blastic natural killer (NK) cell lymphoma/leukemia is a relatively rare NK cell malignancy. We report the second case of blastic NK cell lymphoma arising from the mediastinum with an aggressive clinical course. The patient was a 63-year-old Japanese man with an anterior mediastinum tumor. The biopsy specimen showed diffuse proliferation of tumor cells with frequent mitotic figures and apoptotic bodies. Both angiocentric features and small foci of coagulative necrosis were found in this section. The tumor cells had medium to large nuclei with a fine chromatin pattern, inconspicuous nucleoli and scanty cytoplasm. The nuclear contour was oval to moderately irregular, showing slight pleomorphism as compared with typical lymphoblastic lymphoma. The tumor cells were positive for CD2, CD56 and terminal deoxynucleotidyl transferase, but negative for other T-cell antigens, B-cell antigens and myeloid markers. In situ hybridization for Epstein,Barr virus encoded small ribonucleic acid 1 was negative. [source] Occupation and multiple myeloma: An occupation and industry analysisAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 8 2010Laura S. Gold PhD Abstract Background Multiple myeloma (MM) is an incurable plasma cell malignancy with a poorly understood etiology. The purpose of our research was to examine the relationships between lifetime occupations and MM in a relatively large case,control study. Methods MM cases (n,=,180) were identified through cancer registries in the Seattle-Puget Sound area and Detroit. Population-based controls (n,=,481) were identified using random digit dialing and Medicare and Medicaid Services files. In-person interviews were conducted to ascertain occupational histories. Standard occupational classification (SOC) and standard industrial classification (SIC) codes were assigned to each job held by each participant. Unconditional logistic regression was used to generate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between MM and having ever worked in each occupation/industry and according to duration of employment in an occupation/industry. Results The risk of MM was associated with several manufacturing occupations and industries, including machine operators and tenders, not elsewhere classified (SOC 76) (OR,=,1.8, CI,=,1.0,3.3); textile, apparel, and furnishing machine operators and tenders (SOC 765) (OR,=,6.0, CI,=,1.7,21); and machinery manufacturing, except electrical (SIC 35) (OR,=,3.3, CI,=,1.7,6.7). Several service occupations and industries, such as food and beverage preparation (SOC 521) (OR,=,2.0, CI,=,1.1,3.8), were also associated with MM. One occupation that has been associated with MM in several previous studies, painters, paperhangers, and plasterers (SOC 644) was associated with a non-significantly elevated risk (OR,=,3.6, CI,=,0.7,19). Conclusions We found associations between the risk of MM and employment in several manufacturing and service-related occupations and industries. Am. J. Ind. Med. 53:768,779, 2010. © 2010 Wiley-Liss, Inc. [source] Proteomic analysis of membrane rafts of melanoma cells identifies protein patterns characteristic of the tumor progression stagePROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 22 2008Frédérique Baruthio Abstract The molecular mechanisms controlling the progression of melanoma from a localized tumor to an invasive and metastatic disease are poorly understood. In the attempt to start defining a functional protein profile of melanoma progression, we have analyzed by LC-MS/MS the proteins associated with detergent resistant membranes (DRMs), which are enriched in cholesterol/sphingolipids-containing membrane rafts, of melanoma cell lines derived from tumors at different stages of progression. Since membrane rafts are involved in several biological processes, including signal transduction and protein trafficking, we hypothesized that the association of proteins with rafts can be regulated during melanoma development and affect protein function and disease progression. We have identified a total of 177 proteins in the DRMs of the cell lines examined. Among these, we have found groups of proteins preferentially associated with DRMs of either less malignant radial growth phase/vertical growth phase (VGP) cells, or aggressive VGP and metastatic cells suggesting that melanoma cells with different degrees of malignancy have different DRM profiles. Moreover, some proteins were found in DRMs of only some cell lines despite being expressed at similar levels in all the cell lines examined, suggesting the existence of mechanisms controlling their association with DRMs. We expect that understanding the mechanisms regulating DRM targeting and the activity of the proteins differentially associated with DRMs in relation to cell malignancy will help identify new molecular determinants of melanoma progression. [source] Incidence of Unsuspected Metastases in Lateral Cervical Cysts,THE LARYNGOSCOPE, Issue 10 2000Christine G. Gourin MD Abstract Objective Solitary cystic squamous cell carcinoma metastases may be difficult to distinguish clinically from a benign cervical cyst. We sought to identify the incidence of solitary cystic squamous cell carcinoma metastasis in patients presenting with apparently benign cervical cysts. Study Design Retrospective review. Methods The records of all patients who presented with isolated lateral cervical cysts between 1983 and 1999 were reviewed. Patients with a clinically apparent primary malignancy, a history of head and neck cancer, a history of irradiation, or age less than 18 years were excluded from analysis, as were patients with a histological diagnosis of nonsquamous cell malignancy or those without a final histological diagnosis. Results One hundred twenty-one adult patients presented with an initial diagnosis of lateral cervical cyst. Metastatic squamous cell carcinoma was demonstrated histologically after surgical excision in 12 patients (9.9%). The incidence of malignancy was significantly greater in patients greater than 40 years of age (23.5%, P < .0001). Results of preoperative fine-needle aspiration (FNA) were negative for malignancy in five cases of metastatic squamous cell carcinoma. Panendoscopy with directed biopsies revealed an occult primary in the base of tongue in three patients, tonsil in one patient, and nasopharynx in one. No primary was found in six patients, despite repeated examinations and close follow-up. Conclusions Solitary cervical cysts in patients older than 40 years of age should be presumed to be carcinoma until proven otherwise. A negative FNA result may be misleading, because of hypocellularity of the cyst fluid. Excisional biopsy should be undertaken with provisions made for frozen-section analysis of the specimen and contingency panendoscopy with directed biopsies of Waldeyer's ring if frozen-section histological examination reveals malignancy. [source] Detection of WA B cells in hepatitis C virus infection: A potential prognostic marker for cryoglobulinemic vasculitis and B cell malignanciesARTHRITIS & RHEUMATISM, Issue 7 2010Glenn B. Knight Objective An uncommon manifestation of hepatitis C virus (HCV) infection is systemic vasculitis associated with type II cryoglobulinemia (cryoglobulinemic vasculitis), a proliferative B cell disorder that transforms into B cell malignancy in 5,10% of patients. The monoclonal rheumatoid factors (mRF) that bear the WA cross-idiotype (Xid) are responsible for most cases of cryoglobulinemic vasculitis in patients with HCV infection. The purpose of this study was to determine whether WA B cells can be detected in asymptomatic patients with HCV infection, using sequence analysis of B cell clonal expansions (BCEs) to identify the WA Xid. Methods Asymptomatic patients with HCV infection and those without HCV infection as well as respective control patients with cryoglobulinemic vasculitis, whose serum was either negative or positive for WA mRF, were studied. BCEs were isolated in the patients' blood, and WA BCEs were identified by sequencing analysis. Results BCEs were detected in all control patients with cryoglobulinemic vasculitis, but only control patients with HCV infection had WA BCEs. None of the 33 asymptomatic patients without HCV infection had a BCE. WA BCEs were detected in 4 (7.4%) of 55 asymptomatic patients with HCV infection, in none of 14 patients with HCV infection and type III cryoglobulinemia, and in 5 (13.5%) of 37 patients with HCV infection and serum RF positivity. One patient with a WA BCE had splenic lymphoma markers and villous lymphocytes, and the villous lymphocytes were found to be WA B cells. Conclusion By identification of the WA Xid, WA B cells can be detected in asymptomatic HCV-infected patients. WA B cells in asymptomatic patients with HCV infection may be a marker for the development of cryoglobulinemic vasculitis and associated B cell malignancies. The results of this study provide a basis for the development of the first practical clinical application of cross-idiotype analysis. [source] Subacute cutaneous lupus erythematosus: a paraneoplastic dermatosis?CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 6 2005S. I. Chaudhry Summary Subacute cutaneous lupus erythematosus (SCLE) is characterized by clinical, laboratory and immunological features different from those of systemic lupus erythematosus (SLE). We describe the case of a patient with a 2-year history of SCLE that demonstrated a close temporal relationship with a squamous cell malignancy of the head and neck. This association has not been previously reported. We also review the evidence for SCLE as a ,paraneoplastic dermatosis' and discuss the criteria for diagnosis and possible pathogenesis. [source] | |||||||||||||