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T J Triche

Publications and source records attributed to T J Triche.

At least 19 recordsLinked to original sources
PubMed1992

Dynamic model of differentiation in Ewing's sarcoma cells. Comparative analysis of morphologic, immunocytochemical, and oncogene expression parameters.

We report the establishment of a model of neural differentiation in four well-characterized Ewing's sarcoma cell lines. This process was induced by serum-depleted medium (1% fetal bovine serum) and agents such as dibutyryl cyclic AMP and retinoic acid. The morphologic changes were characterized predominantly by the presence of neurite-like elongated processes showing varicosities and branching along their course with numerous internal filaments and electron-dense granules. Immunocytochemically, differentiation was accompanied by a considerable increase in reactivity for neural markers of several types: neuroblastic, neuroepithelial, neuroendocrine, Schwannian and even glial. In contrast, the tumor promoter, phorbol 12-myristate 13-acetate inhibited differentiation. Several morphologic changes were observed in phorbol 12-myristate 13-acetate-treated cells: the cells became smaller and rounder, were poorly adherent to substrate, by electron microscopy lacked cytoplasmic organelles, electron-dense granules or neural processes, and showed decreased expression of neural markers. Northern blot analysis was performed to establish whether there was any relationship between neural differentiation and degree of N-myc, c-myc and dbl oncogene expression. There was no N-myc oncogene expression in the mRNA of Ewing's sarcoma cells, even after neural induced differentiation. The degree of c-myc and dbl oncogene expression appeared heterogeneous, and varied with the culture condition. Based on these results, it may be inferred that Ewing's sarcoma cells in vitro display a variable neural phenotype, there being a variety of biologic responses to diverse culture media and various differentiation agents, but with no consistent effect on N-myc, c-myc and dbl oncogene expression.

Bucladesine↗
PubMed1992

Peripheral neuroepithelioma: a light microscopic, immunocytochemical, and ultrastructural study.

Forty-two cases of peripheral neuroepithelioma (PN) retrieved from the files of the National Cancer Institute (Bethesda, MD) and the Pathology Department of Padua University, Italy, were reviewed. No sex predilection was observed (25M/17F) and ages ranged from 7 to 54 yr (median 22 yr). Roughly a third of the tumors were thoracopulmonary ("Askin tumor"), a third were axial, and a third were in extremities. A lobular pattern with rosettes or pseudo-rosettes characterized PN. Seventeen cases showed a strong diastase-sensitive PAS positivity. Transitional areas with an Ewing's-like appearance and, in one case, transition to malignant nerve sheath tumor have been documented. The presence of neuron specific enolase (NSE), S-100 protein, HNK-1, neurofilaments, vimentin, keratin (AE1-AE3), beta 2-microglobulin, chromogranin A, and synaptophysin was investigated using the avidin-biotin technique. Immunocytochemically, NSE (95% of cases), beta 2-microglobulin (77.5%), synaptophysin (73.3%), and S-100 protein (67.5%) were the most consistently positive markers. Ultrastructurally, PN is characterized by a primitive appearance, although it was routinely possible to recognize neural features such as primitive neuritic extensions and dense core granules, either in the cytoplasm or in the cellular processes. In our experience, a light microscopic picture of a primitive round cell tumor with a lobular pattern, and particularly with rosettes when present, with NSE and beta 2-microglobulin positivity by immunocytochemistry, ideally with positive synaptophysin, along with supportive electron microscopy, is required for the diagnosis of PN. Conversely, no one feature alone is generally sufficient for diagnosis, but does allow distinction from extraosseous Ewing's, which (like osseous Ewing's) lacks features of neural differentiation.

Adolescent↗
PubMed1991

Prognostic value of histopathology in Ewing's sarcoma. Long-term follow-up of distal extremity primary tumors.

The pathologic material from 56 patients diagnosed initially as Ewing's sarcoma of the distal extremity and treated on National Cancer Institute protocols between 1968 and 1984 was reviewed and correlated with clinical outcome. Histologically, the tumors were categorized, based on recent pathologic criteria, into three diagnostic groups: (1) typical Ewing's sarcoma, (2) atypical Ewing's sarcoma, and (3) other (predominantly peripheral neuroepithelioma [PN]). Thirty-two patients (57%) had typical Ewing's, 13 (23%) were atypical, and 11 (20%) were in the "other" diagnostic category (seven [13%] PN, two primitive rhabdomyosarcoma, one primitive sarcoma of bone, and one synovial cell sarcoma). No cases of metastatic neuroblastoma, osteosarcoma, or lymphoma were found. Forty-five patients had localized disease at diagnosis; 11 had metastases. Patients with typical Ewing's sarcoma were less likely to have metastatic disease at the time of diagnosis. Only two of 32 patients with typical Ewing's sarcoma had metastases compared with nine of 24 patients in the two other groups. The pattern of relapse was also different in these other groups compared with typical Ewing's patients; five patients developed lymph node metastases and two patients developed brain metastases. Although the presence of metastatic disease at diagnosis was a strong negative prognostic factor, our histologic grouping was independently prognostic of clinical outcome in patients with localized disease. Patients with typical osseous Ewing's sarcoma had an improved overall survival (P2 = 0.03) and patients with other tumors (neither typical nor atypical Ewing's sarcoma) had a poorer disease-free survival (P2 = 0.02). Since no generally accepted histopathologic prognostic criteria exist for Ewing's sarcoma, the potential value of our proposed classification should be evaluated in a larger retrospective and a prospective study.

Adolescent↗
PubMed1991

Immunohistochemical analysis of neural cell adhesion molecules. Differential expression in small round cell tumors of childhood and adolescence.

The neural cell adhesion molecule (NCAM) was discovered in a search for cell surface antigens of chicken neurons that contribute to cell adhesion and pattern formation during development. Homologous adhesion molecules have been identified in several species, including humans. In this immunohistochemical study, the authors examine the role of human NCAM in tumor diagnosis. The authors used a monoclonal antibody (MAb), 5.1H11, to examine NCAM immunoreactivity in frozen sections of more than 450 tumors, including more than 80 small round cell tumors (SRCT) of childhood and adolescence (neuroblastomas, Ewing's sarcomas [ES], peripheral neuroepitheliomas [PN], primitive neuroectodermal tumors [PNET], esthesioneuroblastomas, malignant ectomesenchymoma, medulloblastomas, small cell osteosarcomas, mesenchymal chondrosarcomas, embryonal rhabdomyosarcomas, and lymphomas). The authors show that 1) neuroblastomas and primary brain tumors are NCAM+; 2) ES, most PN/PNETs, and melanomas are NCAM-; 3) embryonal rhabdomyosarcomas and various other sarcomas are NCAM+; 4) neuroendocrine tumors are NCAM+; 5) subsets of carcinomas of kidney, ovary, lung and other organs are NCAM+; and 6) lymphoid tumors are NCAM-. Tests with normal fetal and adult tissues indicate that these findings reflect only in part the NCAM phenotypes of corresponding normal tissues. Notably the NCAM- phenotype of ES and PN/PNET is not explained by current histogenetic models for these tumors, which suggest a primitive neuroectodermal origin. Finally the authors show that NCAM expression among SRCT has an inverse relationship with the expression of p30/32MIC2, a cell surface antigen of ES and PN/PNET detected with MAb HBA71. These results suggest that immunohistochemical assays for NCAM and p30/32MIC2 expression may aid in the further characterization of SRCT of childhood and adolescence.

Antibodies, Monoclonal↗
PubMed1991

Immunohistochemical analysis of Ewing's sarcoma cell surface antigen p30/32MIC2.

Monoclonal antibody (MAb) HBA71, which was raised against Ewing's sarcoma cells, recognizes a cell-surface glycoprotein, p30/32MIC2, that is encoded by the MIC2 gene in the pseudoautosomal region of human chromosomes X and Y. This immunohistochemical study evaluates the specificity and sensitivity of MAb HBA71 for tumor diagnosis. Frozen and paraffin-embedded tissues of more than 300 tumors of diverse histologic type, including more than 100 small round cell tumors of childhood and adolescence, were tested with this MAb by the avidin-biotin immunoperoxidase procedure. The authors found HBA71 immunoreactivity in 61 of 63 Ewing's sarcomas studied and 9 of 11 primitive neuroectodermal tumors and peripheral neuroepitheliomas. HBA71-negative tumors included neuroblastomas (0 of 24), melanomas (0 of 13), an esthesioneuroblastoma, small cell osteosarcomas (0 of 2), a malignant ectomesenchymoma, desmoplastic SRCT (0 of 5), and medulloblastomas (0 of 5). Heterogeneous expression of HBA71 immunostaining was found in some embryonal rhabdomyosarcomas (3 of 14) and astrocytomas (4 of 7), and in a few neuroendocrine tumors (4 of 26), carcinomas (3 of 94), and lymphomas (6 of 30). Because Ewing's sarcomas are consistently HBA71 positive, the authors searched for antigen-positive normal cells that may represent precursors for these tumors; however, no obvious candidate for the elusive cell of origin for Ewing's sarcoma was identified in the normal fetal tissues tested. Their findings indicate that HBA71 is a highly restricted cell-surface antigen of Ewing's sarcomas and primitive neuroectodermal tumors, and immunohistochemistry employing this antibody may be of value in the differential diagnosis of selected small round cell tumors in childhood and adolescence.

12E7 Antigen↗
PubMed1990

Establishment and characterization of a human adrenocortical carcinoma cell line that expresses multiple pathways of steroid biosynthesis.

We established a continuous cell line, NCI-H295, from an invasive primary adrenocortical carcinoma. The cell line was established in a fully defined medium (HITES) and later could be adapted for growth in a simple medium supplemented only with selenium, insulin, and transferrin and devoid of serum, steroids, fibroblast growth factor, and a source of exogenous cholesterol. NCI-H295 cells had a relatively long population doubling time and were tumorigenic when inoculated s.c. into athymic nude mice. The cultured cells had ultrastructural features of steroid-secreting cells and contained complex cytogenetic abnormalities including the presence of multiple marker chromosomes. Steroid analyses (radioimmunoassays and mass spectrometry), performed 7 to 9 years after culture initiation, demonstrated secretion of more than 30 steroids characteristic of adrenocortical cells. Total unconjugated steroid secretion in serum-supplemented medium was 2.83 micrograms/10(6) cells/24 h and about 4-fold less in serum-free medium. The major pathway of pregnenolone metabolism in NCI-H295 cells is androgen synthesis, with formation of dehydroepiandrosterone, androstenedione, testotesterone, and at least three sulfated androgens, as well as estrogens. In addition, formation of cortisol, corticosterone, aldosterone, and 11 beta-hydroxyandrostenidione indicated the presence of 11 beta-hydroxylase. Thus, multiple pathways of steroidogenesis are expressed by NCI-H295 cells, including formation of corticosteroids, mineralocorticoids, androgens, and estrogens. Our findings indicate the presence in NCI-H295 cells of all of the major adrenocortical enzyme systems, including 11 beta-hydroxylase, desmolase, 21 alpha-hydroxylase, 17 alpha-hydroxylase, 18-hydroxylase, lyase, sulfokinase, and aromatase. The NCI-H295 cell line should prove of value in studying the regulation, metabolic pathways, and enzymes involved in steroid formation and secretion. In addition, it may provide insights into the biology and treatment of adrenocortical carcinoma.

Adrenal Cortex Neoplasms↗
PubMed1990

Scanning electron microscopic evidence for neural differentiation in Ewing's sarcoma cell lines.

A number of recent studies have suggested a relationship between Ewing's sarcoma (ES) and other small round cell tumours of childhood such as peripheral neuroepithelioma (PN). We report scanning electron microscopic studies on the character of induced neural differentiation in ES, neuroblastoma, PN, osteosarcoma and colon carcinoma. We found evidence of neural differentiation in both neural lines and in one of two Ewing's lines before treatment. After differentiation, both Ewing's and neural lines developed neuritic processes with varicosities and little arborization, except for the initially undifferentiated Ewing's line (A4573) which displayed extensive lateral sprouting from neuritic processes after differentiation. Neither treated nor untreated osteosarcoma or colon carcinoma displayed any evidence of neural differentiation. Further, neuroblastoma cells are easily distinguished from ES and PN by virtue of their single, unbranched neurites and lack of lateral sprouting or filopodia. These results provide further evidence for the neural character and close relationship between ES and PN.

Adenocarcinoma↗
PubMed1990

Somatic cell genetic analysis of human cell surface antigens 5.1H11 and F35/9 (gp45).

Serologic analysis of rodent-human somatic cell hybrids has permitted the assignment of loci coding for cell surface differentiation antigens 5.1H11 (gene symbol MSK39) and F35/9 (MSK40) to human chromosomes 11q13-qter and 22, respectively. Both antigens are expressed in hybrids constructed with antigen-positive human cells and certain hybrids constructed with antigen-negative human cells, indicating that the coding genes are not irreversibly silenced in human nonexpressor cells. Antigens 5.1H11 and F35/9, and at least six additional cell surface antigens encoded by chromosomes 11 and 22, are expressed on human Ewing sarcoma and peripheral neuroepithelioma cells, providing selectable markers for isolating and characterizing the specific t(11;22)(q24;q12) marker chromosomes of these tumors in interspecies hybrids.

Animals↗
PubMed1990

Neuroblastoma and other childhood neural tumors: a review.

Neuroblastoma is the most common nonhematopoietic solid tumor of childhood and has been intensively studied for at least 4 decades. Despite this, few predictive histopathologic clues to its behavior exist. Age, anatomic sites of occurrence, and clinical stage have traditionally been the only reliable prognostic factors in this disease. A number of laboratory studies that focus on biologic features such as neurotransmitter synthesis (adrenergic and noradrenergic catecholamines), neurotransmitter enzyme expression (dopamine beta hydroxylase, choline acetyl transferase), cytogenetics (homogeneously staining regions, double minute chromosomes, chromosome 1p deletions), molecular genetics (N-myc oncogene amplification and expression), and immunophenotype (surface epitopes such as HLA antigens and GD2 ganglioside and intracytoplasmic determinants such as neurofilament protein, synaptophysin, chromogranin, and neuron specific enolase) now enable the pathologist to predict clinical course in many cases and to distinguish bona fide neuroblastomas, regardless of age, site, or histologic appearance, from a host of related but distinctly separate neuroectodermal tumor entities with apparent different histogenesis, treatment sensitivity, and prognosis.

Adolescent↗
PubMed1990

An immunohistochemical study of pi class glutathione S-transferase expression in normal human tissue.

Glutathione S-transferases (GSTs), a family of isoenzymes that play an important role in protecting cells from cytotoxic and carcinogenic agents, can be separated by biochemical and immunologic characteristics into three distinct classes named alpha, mu, and pi. Previous studies have indicated that there is marked heterogeneity in the expression of different GST isoenzymes in different normal and malignant tissues. To better understand the regulation of the human pi class glutathione S-transferase isoenzyme (GST-pi), the tissue distribution of this protein wa studied by an immunohistochemical technique using an anti-GST-pi polyclonal antibody in normal paraffin-embedded human tissues. These studies indicate that there is a broad distribution of GST-pi in normal human tissues and establish a precise localization within the different organs studied. GST-pi was expressed predominantly in normal epithelial cells of the urinary, digestive, and respiratory tracts, suggesting a possible role for GST-pi in detoxication and elimination of toxic substances. Previous studies have indicated that GST-pi and the putative drug efflux pump P-glycoprotein are both overexpressed in multidrug-resistant human breast cancer cells and in xenobiotic resistant preneoplastic rat hyperplastic liver nodules. Results from this study indicate that there are also similarities between the normal tissue distribution GST-pi and that previously reported for mammalian P-glycoprotein, particularly in secretory epithelia. This finding suggests that these two gene products, which have been implicated in the development of resistance to cytotoxic drugs, may be coregulated in normal and malignant cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Stimulation of human neuronectin secretion by brain-derived growth factors.

Neuronectin (NEC1) is a human extracellular matrix protein found throughout the white matter of rostral brain segments but not in most areas of the mesencephalon, in the pons, cerebellum, medulla, spinal cord, and peripheral nerves. This distribution may result from NEC1 expression by a unique subset of neural cells in the rostral brain or from expression by a more widely distributed cell type, conditional on induction of region-specific extrinsic factors. In this study, we show that two brain-derived polypeptides, acidic and basic fibroblast growth factor (FGF), induce NEC1 secretion in cultured neural cells. Induction is detected within five hours after addition of FGF, is reversible, and is blocked by inhibitors of RNA and protein synthesis. Other growth and differentiation factors do not induce NEC1, except for 12-O-tetradecanoyl phorbol-13-acetate, which acts through a different signalling pathway. Acidic and basic FGF may be members of a group of extrinsic factors that determine region-specific NEC1 expression in neural tissues.

Astrocytoma↗
PubMed1989

Intensive combined modality therapy of small round cell and undifferentiated sarcomas in children and young adults: local control and patterns of failure.

Seventy-five patients (ages 4-35 years) with the following small round cell tumors and undifferentiated sarcoma were treated at the National Cancer Institute: Ewing's sarcoma (n = 32), peripheral neuroepithelioma (n = 14), rhabdomyosarcoma (n = 24), undifferentiated sarcoma (n = 5). Most patients had poor prognostic features including 36 (48%) with metastatic disease, and 42 (56%) with central (truncal) tumors (22 in the pelvis). Treatment included 5 cycles of intensive induction chemotherapy with vincristine, cyclophosphamide and adriamycin, plus aggressive local radiation therapy using simulation and computerized treatment planning for all patients. Thereafter, complete clinical responses were consolidated with intensive chemotherapy, total body irradiation and autologous bone marrow transplantation. There were three local only failures, 10 local plus distant failures, 36 distant only failures, 3 treatment-related deaths, and one intercurrent death. Overall actuarial survival and event-free survival at 4 years are 49 and 29%, respectively. Actuarial freedom from local progression was seen in 74% of patients at 4 years, quite remarkable considering the bulk and location of most of these tumors. Without aggressive surgery, many of these high risk patients had satisfactory outcomes, but better systemic treatments are still needed.

Adolescent↗
PubMed1989

Treatment of sarcomas of the chest wall using intensive combined modality therapy.

As part of two sequential protocols using intensive combined modality treatment in pediatric and adolescent sarcomas, 31 consecutive patients with primary chest wall tumors were treated between November 1977 and March 1986. This group included 13 patients with peripheral neuroepithelioma (Askin's tumor), 11 patients with Ewing's sarcoma, 3 patients with rhabdomyosarcoma, and 4 patients with undifferentiated sarcomas. Following complete work-up, 17 patients presented with localized disease and 14 patients presented with metastases. Patients received intensive combined modality treatment with combination chemotherapy (vincristine, cyclophosphamide, Adriamycin, +/- actinomycin-D and DTIC) and high-dose conventionally fractionated radiation therapy to the primary (55-60 Gy) and non-pulmonary metastases (45-50 Gy). Radiation techniques used for the primary chest wall tumor varied with the clinical presentation. Patients achieving a complete response received either low-dose fractionated TBI (1.5 Gy/0.15 Gy fx/5 weeks) or high-dose TBI (8 Gy/4 Gy fx/2 days) and an intensive cycle of chemotherapy followed by autologous bone marrow transplantation. Twenty-five of 31 patients were judged to have a complete response (including 1 patient with complete resection). With minimum follow-up of 6 months and median follow-up of 36 months from completion of treatment, 14 patients remain disease-free with 2 additional patients alive in second remission after relapse. Patients with localized disease at presentation have improved disease-free survival and overall survival compared to patients with metastases at presentation. All 17 localized patients achieved a CR and 11 are NED compared to 8 of 14 metastatic patients achieving a CR and only 3 are NED. There have been 5 loco-regional recurrences with 3 "in-field" failures and 2 failures in the regional pleura. There were no treatment-related deaths and no clinically significant cases of pneumonitis. To date, 2 patients have significant treatment related morbidity, including 1 patient with scoliosis requiring surgery and 1 patient with acute leukemia developing 42 months after the start of therapy (presently in remission). We conclude that this intensive combined modality therapy results in a high CR rate and good local control with acceptable morbidity. Patients with metastatic disease at presentation remain a therapeutic challenge.

Adolescent↗
PubMed1989

In vitro chemosensitivity of two Ewing's sarcoma cell lines: implication for autologous bone marrow transplantation.

Intensive chemotherapy requiring rescue with autologous bone marrow may be an encouraging mode of treatment for poor prognosis Ewing's sarcoma (ES). In vitro chemosensitivity test may be useful for establishing an effective purging condition. We studied the in vitro effects of a variety of chemotherapeutic agents on two established ES cell lines (ES-5838 and ES-A4573) and marrow colony-forming unit-granulocyte macrophage (CFU-GM). 4-Hydroperoxycyclophosphamide (4-HC), at 100 microM produced complete inhibition (greater than 5 log) of clonogenic growth of both ES cell lines and spared 6.9% of normal CFU-GM growth. Etoposide (VP-16), at 100 microM produced 3-3.5 log inhibition of ES cell lines and complete inhibition of CFU-GM growth. Adriamycin (ADR) and vincristine (VCR) were more cytotoxic to ES-5838 cells than ES-A4573 cells. ADR at 1 microM produced 99.7% inhibition of ES-5838 cells, 92.2% of ES-A4573 cells, and 86% inhibition of CFU-GM. VCR at 1 microM produced 98.6% inhibition of ES-5838 cells, only 43.7% of ES-A4573 cells, and 75% inhibition of CFU-GM growth. Addition of verapamil did not enhance VCR cytotoxicity of ES cell lines. These studies indicate that 4-HC may be a useful agent for purging metastatic ES cells from the bone marrow for autologous marrow transplantation.

Antineoplastic Agents↗
PubMed1989

Expression of the dbl proto-oncogene in Ewing's sarcomas.

We have investigated the expression of the dbl proto-oncogene in childhood tumors of known or suspected neuroectodermal origin. We found that while the dbl gene is consistently found expressed in Ewing's sarcoma as a single mRNA species, of approximately 5.0 kb, it is generally absent in two seemingly related categories of tumors, neuroblastoma and neuroepithelioma. The specificity of expression of the dbl proto-oncogene in Ewing's sarcoma supports the concept that Ewing's sarcoma may be differentiated from two closely related tumors, neuroblastoma and neuroepithelioma, on the basis of the presence of specific molecular markers.

Guanine Nucleotide Exchange Factors↗
PubMed1989

Malignant rhabdoid tumor of the kidney and soft tissues. Evidence for a diverse morphological and immunocytochemical phenotype.

Three malignant rhabdoid tumors of the kidney and two extrarenal rhabdoid tumors of soft tissues were studied by light and electron microscopy and by immunocytochemistry for the expression of keratin, vimentin, desmin, neurofilament triplet proteins, epithelial membrane antigen, myoglobin, and HNK-1 (Leu-7). Electron microscopy revealed the characteristic cytoplasmic whorled filamentous inclusions in all tumors. An epithelial phenotype (presence of cytoplasmic tonofilaments) was observed in two tumors (one renal and one extrarenal); and a focal primitive neural phenotype (cytoplasmic processes with neurosecretory granules), in a renal rhabdoid tumor. Strands of basal lamina were seen in two renal and one extrarenal rhabdoid tumors. Evaluation of basal lamina was more difficult in the third renal rhabdoid tumor, in which tissue preservation was not optimal. Primitive attachments were present in all rhabdoid tumors. Immunocytochemical staining supported a diverse phenotype, ranging from epithelial and/or mesenchymal to myogenous and/or neuroectodermal. Simultaneous expression of several of the studied antigenic determinants by the same tumor was noted. The findings suggest that both renal and extrarenal rhabdoid tumors express a diverse morphological and immunocytochemical phenotype.

Child, Preschool↗
PubMed1988

Indistinguishable patterns of protooncogene expression in two distinct but closely related tumors: Ewing's sarcoma and neuroepithelioma.

Genetic characterization of human tumors promises new insights of biological importance and clinical relevance. We have found that two solid tumors, peripheral neuroepithelioma and Ewing's sarcoma of bone, which share a common cytogenetic rearrangement, are characterized by an indistinguishable and highly reproducible pattern of protooncogene expression. c-myc, N-myc, c-myb, and c-mil/raf-1 are all expressed at similar levels in these tumors. c-fes and c-sis expression was not detected in any specimens of either tumor. In contrast, the protooncogene c-ets-1, located near the breakpoint of the chromosomal translocation in these tumors, is variable in its expression. We also detected high levels of choline acetyltransferase in these tumors, which suggests a common neural origin. Since it is likely that the clinical behavior and therapeutic responsiveness of tumors relate closely to their biological and genetic features, the pattern of protooncogene expression of individual tumors may provide a novel basis for their characterization.

Bone Neoplasms↗