Biomedical subjects

M Tsokos

Publications and source records attributed to M Tsokos.

At least 19 recordsLinked to original sources

PubMed1995

Nitric oxide potentiates hydrogen peroxide-induced killing of Escherichia coli.

Previously, we reported that nitric oxide (NO) provides significant protection to mammalian cells from the cytotoxic effects of hydrogen peroxide (H2O2). Murine neutrophils and activated macrophages, however, produce NO, H2O2, and other reactive oxygen species to kill microorganisms, which suggests a paradox. In this study, we treated bacteria (Escherichia coli) with NO and H2O2 for 30 min and found that exposure to NO resulted in minimal toxicity, but greatly potentiated (up to 1,000-fold) H2O2-mediated killing, as evaluated by a clonogenic assay. The combination of NO/H2O2 induced DNA double strand breaks in the bacterial genome, as shown by field-inverted gel electrophoresis, and this increased DNA damage may correlate with cell killing. NO was also shown to alter cellular respiration and decrease the concentration of the antioxidant glutathione to a residual level of 15-20% in bacterial cells. The iron chelator desferrioxamine did not stop the action of NO on respiration and glutathione decrease, yet it prevented the NO/H2O2 synergistic cytotoxicity, implicating metal ions as critical participants in the NO/H2O2 cytocidal mechanism. Our results suggest a possible mechanism of modulation of H2O2-mediated toxicity, and we propose a new key role in the antimicrobial macrophagic response for NO.

Catalase↗

PubMed1995

Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B.

BACKGROUND: We describe severe and unexpected multisystem toxicity that occurred during a study of the antiviral nucleoside analogue fialuridine (1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil, or FIAU) as therapy for chronic hepatitis B virus infection. METHODS: Fifteen patients with chronic hepatitis B were randomly assigned to receive fialuridine at a dose of either 0.10 or 0.25 mg per kilogram of body weight per day for 24 weeks and were monitored every 1 to 2 weeks by means of a physical examination, blood tests, and testing for hepatitis B virus markers. RESULTS: During the 13th week lactic acidosis and liver failure suddenly developed in one patient. The study was terminated on an emergency basis, and all treatment with fialuridine was discontinued. Seven patients were found to have severe hepatotoxicity, with progressive lactic acidosis, worsening jaundice, and deteriorating hepatic synthetic function despite the discontinuation of fialuridine. Three other patients had mild hepatotoxicity. Several patients also had pancreatitis, neuropathy, or myopathy. Of the seven patients with severe hepatotoxicity, five died and two survived after liver transplantation. Histologic analysis of liver tissue revealed marked accumulation of microvesicular and macrovesicular fat, with minimal necrosis of hepatocytes or architectural changes. Electron microscopy showed abnormal mitochondria and the accumulation of fat in hepatocytes. CONCLUSIONS: In patients with chronic hepatitis B, treatment with fialuridine induced a severe toxic reaction characterized by hepatic failure, lactic acidosis, pancreatitis, neuropathy, and myopathy. This toxic reaction was probably caused by widespread mitochondrial damage and may occur infrequently with other nucleoside analogues.

Acidosis, Lactic↗

PubMed1995

Relationships between mesangial cell proliferation and types I and IV collagen mRNA levels in vitro.

Changes in the composition of the mesangial extracellular matrix (ECM) and cell turnover are present in glomerular disease. To determine if ECM changes play a role in perpetuating mesangial cell dysfunction, we examined a line of mouse mesangial cells cultured on films or gels of several ECM components and also on methyl cellulose, an inert substrate that prevents attachment. Cells on films of fibronectin or type IV or I collagen had persistently high growth rates and high levels of alpha 1-I and alpha 1-IV collagen mRNAs. In contrast, on gels of type IV or I collagen or matrigel, the growth rate was low. The alpha 1-IV collagen mRNA levels were low on type IV collagen gel or matrigel, whereas the alpha 1-I collagen mRNA levels remained high. In contrast, the alpha 1-I collagen mRNA levels were low on type I collagen gel, and the alpha 1-IV collagen mRNA levels were high. Cells on methyl cellulose formed floating aggregates, did not proliferate, and had a 5- to 10-fold decrease in both alpha 1-I and alpha 1-IV collagen mRNA levels. These phenotypic changes were largely reversible. Finally, when matrigel was layered over cells on fibronectin films, alpha 1-IV collagen mRNA levels decreased, but alpha 1-I collagen mRNA levels and proliferation remained high. Thus proliferation and alpha 1-I and alpha 1-IV collagen mRNA levels in mesangial cells were independently regulated and depended on attachment and the nature of the adjacent matrix.

Animals↗

PubMed1995

Downregulation of mdr-1 expression by 8-Cl-cAMP in multidrug resistant MCF-7 human breast cancer cells.

8-Cl-cAMP, a site-selective analogue of cAMP, decreased mdr-1 expression in multidrug-resistant human breast cancer cells. A sixfold reduction of mdr-1 mRNA expression by 8-Cl-cAMP began within 8 h of treatment and was associated with a decrease in the synthesis of P-glycoprotein and with an increase in vinblastine accumulation. A reduction in mdr-1 expression after 8-Cl-cAMP treatment was also observed in multidrug-resistant human ovarian cancer cell lines. 8-Cl-cAMP is known to change the ratio between the two regulatory subunits, RI and RII, of protein kinase A (PKA). We observed that RI alpha decreased within 24 h of 8-Cl-cAMP treatment, that RII beta increased after as few as 3 h of treatment, and that PKA catalytic activity remained unchanged during 48 h of 8-Cl-cAMP treatment. The results are consistent with the hypothesis that mdr-1 expression is regulated in part by changes in PKA isoenzyme levels. Although 8-Cl-cAMP has been used to differentiate cells in other model systems, the only differentiating effect that could be detected after 8-Cl-cAMP treatment in the MCF-7TH cells was an increase in cytokeratin expression. Evidence that the reduction of mdr-1 mRNA occurred at the level of gene transcription was obtained by measuring chloramphenicol acetyltransferase (CAT) mRNA in MCF-7TH cells transfected with an mdr-1 promoter-CAT construct prior to 8-Cl-cAMP treatment. Thus, 8-Cl-cAMP is able to downregulate mdr-1 expression and suggests a new approach to reversal of drug resistance in human breast cancer.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1995

Cutaneous lymphocytic vasculopathy in lymphoproliferative disorders--a paraneoplastic lymphocytic vasculitis of the skin.

In this report the histopathology and the natural history of cutaneous lymphocytic vasculopathy (lymphocytic vasculitis) in patients with lymphoproliferative diseases, is described. Between January 1986 and June 1992, 116 patients with non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemias (CLL) were followed. Among them 3 patients with NHL, one with angioimmunoblastic lymphadenopathy/lymphoma and 7 with CLL developed cutaneous vasculitic changes during the course of their disease (incidence of 9.5%). All patients had advanced stage disease. Lymphomas were of B-cell origin and either low or intermediate grade. The median time between the diagnosis of NHL or CLL and the appearance of skin manifestations was 18 months. Recurrent vasculitic changes involving exclusively the skin, was characterized by a (maculo)papular rash, most commonly found in the upper and lower extremities. Pruritus of varying intensity was present in 82% of the patients. In the biopsy, all had perivascular and/or vessel wall lymphocytic infiltration of the dermis with occasional red cell extravasation. Immunohistochemical staining revealed that these infiltrates were mainly composed of T-lymphocytes. We conclude, that cutaneous lymphocytic vasculopathy is a relatively common paraneoplastic skin manifestation in patients with lymphoproliferative diseases and histologically is characterized as lymphocytic vasculitis with (peri)vascular infiltration by non-malignant T lymphocytes.

Aged↗

PubMed1994

Agreement among and within groups of pathologists in the classification of rhabdomyosarcoma and related childhood sarcomas. Report of an international study of four pathology classifications.

BACKGROUND: An International Pathology study was conducted to measure the agreement demonstrated among and within groups of pathologists involved in the categorization of childhood rhabdomyosarcoma according to four pathology classifications. Data concerning agreement and survival experience according to patho-new subtypes were used as a basis for selection of a proposed new pathologic classification. METHODS: A random sample of 800 eligible patients was chosen from the Intergroup Rhabdomyosarcoma Study II (IRS-II) and was reviewed by pathologists representing eight institutions. A 20% sample of the 800 patients was then reviewed by the pathologists to determine the level of agreement with their original classification. In each instance the patients were classified according to four pathology systems: the conventional system, the International Society for Pediatric Oncology system (SIOP), the National Cancer Institute (NCI) system, and the cytohistologic system. RESULTS: Among the groups of pathologists, the highest measure of agreement was a Kappa value of K = 0.451 for the conventional system, followed by K = 0.406 for the SIOP system, K = 0.384 for the NCI system, and K = 0.328 for the cytohistologic system. For reproducibility within the groups of pathologists, the highest measure of agreement was K = 0.605 for the conventional system, followed by K = 0.579 for the NCI system, K = 0.573 for the SIOP system, and K = 0.508 for the cytohistologic system. CONCLUSIONS: There was a general similarity between the agreement reached within the modified conventional, STOP, and NCI systems, with the modified conventional system having the highest Kappa values, and thus the highest measure of agreement, both among and within the groups of pathologists. Also, the subtypes of the conventional system demonstrated a highly significant relationship to survival time. Hence, based on criteria of reproducibilty and prognostic significance, the proposed classification will essentially be a modification of the conventional system with elements of the SIOP and NCI systems.

Adolescent↗

PubMed1994

In vivo treatment with antibody against IGF-1 receptor suppresses growth of human rhabdomyosarcoma and down-regulates p34cdc2.

In a previous study, we have shown that insulin-like growth factor type 2 (IGF-2) functions as an autocrine growth factor in human rhabdomyosarcoma (RMS) cell lines. In addition, we demonstrated that the inhibition of binding of IGF-2 to the IGF-1 receptor, mediated by suramin, blocked the growth of RMS cells in vitro. We now report that, in vivo, a specific IGF-1 receptor blocking antibody (alpha IR-3), but not suramin, suppresses RMS tumor growth. Both progression of tumor growth in tumor-bearing animals and formation of newly established tumors were suppressed by treatment with alpha IR-3. Histological analysis of tumors from treated animals did not reveal necrotic lesions, implying that the treatments had no cytotoxic effect. The decrease in tumor growth was associated with a decrease of p34cdc2, a cellular protein involved in cell cycle regulation, suggesting that treatment resulted in the arrest of cellular proliferation. We speculate, therefore, that agents which block the IGF signaling pathway may find application in treatment of RMS.

Animals↗

PubMed1994

Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP.

Recent clinicopathologic studies have shown that many prostatic adenocarcinomas express focal neuroendocrine differentiation and that neuroendocrine differentiation is most apparent in advanced anaplastic tumors. While studying growth-regulatory signal transduction events in human prostate carcinoma cell lines, we found that in two of four cell lines, the androgen-sensitive line LNCaP and the highly metastatic androgen-independent line PC-3-M, elevation of cAMP through addition of cAMP analogues or phosphodiesterase inhibitors induced a markedly neuronal morphology. Also in LNCaP cells ultrastructural analysis showed that cAMP induced the appearance of neurosecretory cell-like dense-core granules. Phenotypic analysis of untreated LNCaP and PC-3-M cells showed that both cell lines express markers of the neural crest including S-100, chromogranin A, pp60c-src, and neuron-specific enolase as well as the epithelial marker KS1/4 and stage-specific embryonic antigen 4. In PC-3-M cells, cAMP markedly elevated neuron-specific enolase protein and caused an increase in the specific activity of the neuroendocrine marker pp60c-src, and in both cell lines expression of KS1/4 and stage-specific embryonic antigen 4 was down-regulated. In addition to effects on lineage markers, cAMP treatment induced G1 synchronization, growth arrest, and loss of clonogenicity, indicating terminal differentiation. Our data provide direct evidence of plasticity in the lineage commitment of adenocarcinoma of the prostate. We have shown that cell-permeant cAMP analogues can induce terminal differentiation, suggesting that hydrolysis-resistant cyclic nucleotides may present an additional approach to the treatment of advanced prostate cancer.

Adenocarcinoma↗

PubMed1994

Specific expression of insulin-like growth factor-II in rhabdomyosarcoma tumor cells.

Insulin-like growth factor II (IGF-II) acts as autocrine growth and motility factor in human rhabdomyosarcoma cell lines, and Northern blot analysis of tumor biopsy specimens from both alveolar and embryonal rhabdomyosarcoma demonstrates high levels of IGF-II mRNA expression. To determine the frequency and site of expression of IGF-II in these tumors, the authors performed in situ hybridization. All tumor specimens examined expressed the gene for IGF-II, and this expression was localized to the tumor cells themselves and not to the surrounding stroma. These data suggest that the IGF-II autocrine loop may be operating not only in vitro but also in vivo.

Adolescent↗

PubMed1994

Immunohistochemical detection of P-glycoprotein in Ewing's sarcoma and peripheral primitive neuroectodermal tumors before and after chemotherapy.

The authors evaluated P-glycoprotein expression in a total of 35 cases of Ewing's sarcoma and peripheral primitive neuroectodermal tumors (PNET). Fifteen cases had matched tumors before and after treatment. The 20 unmatched tumors included 14 pretreatment PNETs and Ewing's sarcomas and 6 posttreatment Ewing's sarcomas. Two antibodies, C219 and JSB-1, were used. Immunoreactivity was almost exclusively membranous. Variability in the number of positive cells and in staining intensity was noted within individual tumors. Among the 15 matched tumors, 7 were positive for P-glycoprotein before treatment; 6 of these remained positive after treatment. Four of the 8 that were negative for P-glycoprotein before treatment became positive after treatment. Of the unmatched tumors, 9 of 14 pretreatment and 3 of 6 posttreatment tumors were positive. When relapse-free survival time, based on the presence or absence of P-glycoprotein positivity in pretreatment tumor samples, was evaluated in this group, no significant difference was found (P2 = .92); however, the numbers are too small to draw definitive conclusions. The high incidence of positive primary tumors suggests that P-glycoprotein expression is probably intrinsic in Ewing's sarcoma and PNET and not necessarily induced by therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1994

Pleomorphic rhabdomyosarcoma arising in association with the right pulmonary artery.

Pulmonary artery rhabdomyosarcomas are rare lesions, with a small number of cases reported in the literature. We report a case of pulmonary artery rhabdomyosarcoma that arose in the right pulmonary artery. The patient presented with cough, chest pain, and hemoptysis and was found to have a sarcoma arising in the right pulmonary artery and extending distally within the pulmonary vasculature into the right lung. The gross pathologic features, microscopic appearance, immunohistochemical profile, and computed tomographic and electron microscopic findings are presented. The site of origin and differential diagnosis of these lesions are discussed.

Adult↗

PubMed1994

The diagnosis and classification of childhood rhabdomyosarcoma.

Although the typical subtypes of embryonal, botryoid, alveolar, and pleomorphic rhabdomyosarcoma are easily recognized by simple light microscopic examination, poorly differentiated forms are difficult to diagnose and classify. The availability of markers connoting simple myogenous or skeletal muscle differentiation has contributed tremendously to the diagnosis of even poorly differentiated rhabdomyosarcoma. Definition of typical and minimal ultrastructural criteria has also been instrumental. Proper classification of rhabdomyosarcoma into subtypes with prognostic significance has been a difficult task. Although most pathologists have accepted the original classification scheme of embryonal, botryoid, alveolar, and pleomorphic rhabdomyosarcoma, they have used variable histologic criteria to define the various subtypes. Most of the major discrepancies occurred in the definition of embryonal versus alveolar rhabdomyosarcoma, especially in those cases that required establishment of minimal criteria. For example, poorly differentiated round-cell rhabdomyosarcoma has frequently been erroneously classified as embryonal, because of the absence of an alveolar pattern. This variety has been recognized as a form of alveolar (solid alveolar) rhabdomyosarcoma by the National Cancer Institute (NCI) scheme. Comparative analysis of several proposed classification schemes has led to the establishment of well-defined criteria for the major subtypes of rhabdomyosarcoma and to the recognition of subtypes with prognostic significance.

Child↗

PubMed1993

Regulation of T cell receptor expression in immature CD4+CD8+ thymocytes by p56lck tyrosine kinase: basis for differential signaling by CD4 and CD8 in immature thymocytes expressing both coreceptor molecules.

Signals transduced through the T cell antigen receptor (TCR) are modulated by the src family tyrosine kinase p56lck (lck), which associates in mature T cells with the coreceptor molecules CD4 and CD8. Here we describe a novel function of lck in immature CD4+CD8+ thymocytes, that of regulating TCR expression. Activation of lck in immature CD4+CD8+ thymocytes by intrathymic engagement of CD4 maintains low TCR expression by causing most TCR components to be retained and degraded within the endoplasmic reticulum. Importantly, activation of lck in immature CD4+CD8+ thymocytes results from engagement of surface CD4 molecules, but not surface CD8 molecules, despite the nearly fourfold greater surface expression of CD8 than CD4. The competence of CD4 to activate lck in CD4+CD8+ thymocytes relates to the fact that a relatively large fraction of surface CD4 molecules (25-50%) are associated with intracellular lck molecules, whereas only 2% of surface CD8 molecules are associated with lck. The amount of lck associated with CD4 in CD4+CD8+ thymocytes is diminished by chronic CD4 engagement in the thymus, as activated lck molecules subsequently dissociate from CD4. Indeed, the amount of lck associated with CD4 in CD4+CD8+ thymocytes is markedly increased in major histocompatibility complex (MHC) class II- mice that lack the intrathymic ligand for CD4 and in which surface CD4 molecules are consequently not engaged. Thus, the present study demonstrates that (a) activation of lck in CD4+CD8+ thymocytes regulates distribution and expression of TCR components; (b) unlike CD4 molecules, CD8 molecules on CD4+CD8+ thymocytes cannot efficiently activate lck despite their significantly greater surface expression; and (c) the amount of lck associated with CD4 in the CD4+CD8+ thymocytes is inversely related to the extent of CD4 engagement by MHC class II molecules in the thymus.

Animals↗

PubMed1993

Increased mdr-1/P-glycoprotein expression after treatment of human colon carcinoma cells with P-glycoprotein antagonists.

We observed increased levels of mdr-1 mRNA and its protein product P-glycoprotein (Pgp) in the human colon carcinoma cell line, LS 180, and its drug-resistant sublines, LS 180-Ad50 and LS 180-Vb2, after treatment with the Pgp antagonists, verapamil, nifedipine, and cyclosporin A. Increases in mdr-1 RNA were observed within 8 h of the addition of the Pgp antagonists and continued to rise over time. Peak levels were attained after several weeks and were sustained for the duration of treatment up to several months, with a rapid decline in mdr-1 mRNA levels after removal of the Pgp antagonist. Corresponding changes in Pgp were demonstrated with addition and removal of the Pgp antagonists. Increased mdr-1 mRNA was also seen with two other calcium channel blockers, nicardipine and diltiazem, but not with the Pgp antagonists, quinidine and chlorpromazine. Treatment with verapamil or nifedipine was associated with electron microscopic changes consistent with increased differentiation and resulted in increased carcinoembryonic antigen expression, suggesting that the increase in mdr-1 expression was associated with the process of differentiation. Nuclear runoff experiments and inhibition of new RNA synthesis with actinomycin D treatment failed to detect an increase in mdr-1 transcription or stabilization of the mdr-1 mRNA suggesting that the effect of these agents is mediated posttranscriptionally within the nucleus.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1993

Malignant schwannoma with melanocytic and neuroepithelial differentiation in an infant with congenital giant melanocytic nevus: a complex neurocristopathy.

We describe an infant girl, born with a pigmented giant nevus, who developed a malignant schwannoma in the retroperitoneum at 16 months of age. At birth the nevus covered over 50% of her body and histologically was a compound nevus with extension into the deep dermis surrounding dermal appendages. The malignant schwannoma was biphasic with areas composed of spindle and round cells. Ultrastructurally, the majority of the tumor cells exhibited a Schwann cell phenotype, but neuroepithelial and melanocytic cells were identified as well. We believe that this constellation of findings represents a form of neurocristopathy. Neurocristopathy, as defined by Bolande (Hum Pathol 5:409-429, 1974), is a disease that results from aberrations in the migration, growth, or cytodifferentiation of neural crest tissues. These diseases may be simple (a singular pathologic process, usually localized) or complex (multiple neuroectodermal lesions). We report this case because the occurrence of retroperitoneal malignant schwannoma arising in a 16-month-old infant born with a pigmented giant nevus is unique, and may represent a previously undescribed form of a complex neurocristopathy.

Female↗

PubMed1993

Characterization of a new IL-6-dependent human B-lymphoma cell line in long term culture.

We have established a cell line (DS-1) of B-cell lineage in long-term culture. It was derived from an immunodeficient patient with intestinal lymphangiectasia and lymphoma by culturing malignant pleural effusion cells with IL-6 in vitro. The cell surface phenotype was; PCA-1, HLA Class II(+); CD25, CD19, CD20, CD30, CD38(-). Cell proliferation was poor in medium and exhibited an eight-fold, dose-dependent increase of proliferation in response to rIL-6 of human but not murine origin. The secretion of IgG into culture supernatants by DS-1 was not enhanced by rIL-6. While constitutive production of IL-6 was not detected by bioassay using murine B9 hybridoma cells or by ELISA, the presence of IL-6 message was detected in polyA+ selected mRNA by Northern analysis. Spontaneous proliferation of DS-1 cells was inhibited by neutralizing polyclonal antibodies to IL-6 (37%) and mAb to IL-6 (54%) and IL-6R (53%). DS-1 expressed both high and low affinity IL-6 receptors (Kd 1.2 x 10(-11) and 6.7 x 10(-10), respectively) by radiolabelled binding and Scatchard analysis. Thus, DS-1 represents an autocrine IL-6-producing cell line of B-cell lineage which resembles lymphoid malignancies arising in patients with AIDS and other immunodeficiency diseases. Despite constitutive IL-6 production, the in vitro growth of DS-1 is dependent upon exogenous IL-6. DS-1 may thus be useful as a model of IL-6 dependency. This cell line may also facilitate development of strategies for diagnosis and treatment of B-cell lymphomas in immunocompromised patients.

Adult↗

PubMed1993

dbl oncogene expression in childhood tumors and tumor cell lines.

We studied the expression of the dbl oncogene in the total RNA obtained from a wide spectrum of childhood tumors, including Ewing's sarcomas, peripheral neuroectodermal tumors (PNET), esthesioneuroblastomas, neuroblastomas, retinoblastomas, rhabdomyosarcomas, osteosarcomas, and synovial sarcomas. Material was obtained from primary tumors, nude mice xenografts, and tumor cell lines. Following the Northern blot technique, a single band of 2.8 kb was found in each analyzed case. Induction of neural differentiation in Ewing's sarcoma, peripheral PNET, and neuroblastoma cell lines with dibutyryl cyclic AMP did not change the expression of the dbl oncogene. We conclude that the wide expression of the dbl oncogene in these childhood tumors reduces its value as a molecular marker for their differential diagnosis; on the other hand, the dbl oncogene does not appear to be an essential molecular factor in the process of neuroectodermal differentiation of small round cell tumors of childhood.

Animals↗

PubMed1993

Expression of transforming growth factor-beta isoforms in small round cell tumors of childhood. An immunohistochemical study.

The transforming growth factor (TGF)-betas are a highly conserved group of potent multifunctional cell regulatory proteins with variable effects on cell growth and differentiation. Most of the small round cell group of childhood tumors are thought to arise from either primitive mesenchyme or neuroectoderm and show evidence of skeletal muscle or neural differentiation, and rarely both. To investigate the possibility that the TGF-betas have a role in the growth or differentiation of these neoplasms, we used antibodies specific for peptide sequences of the three known mammalian TGF-beta isoforms (TGF-betas 1, 2, and 3) to probe for TGF-beta protein expression in a total of 49 cases. TGF-beta 1 immunoreactivity was present in 16/17 (94%) of rhabdomyosarcomas, and the staining intensity was usually strong. TGF-beta 1 was also present in three of three ectomesenchymomas. In contrast, TGF-beta 1 was absent in all but one out of nine poorly differentiated neuroblastomas. Differentiating neuronal cells of ganglioneuroblastomas, however, were strongly positive for TGF-beta 1. Ewing's sarcomas and peripheral primitive neuroectodermal tumors had a less consistent, but usually positive, staining pattern. TGF-beta 3 staining patterns were very similar to those of TGF-beta 1. TGF-beta 2 immunoreactivity was only rarely detected in this group of tumors. The results suggest different roles for TGF-betas 1 and 3 in neuroblastoma and rhabdomyosarcoma. Expression of TGF-betas 1 and 3 is associated with neuronal differentiation of neuroblastoma. In contrast, these proteins may promote the growth of rhabdomyosarcoma by suppressing differentiation.

Adolescent↗