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1/11. Spontaneous regression of a residual pineal tumor after resection of a cerebellar vermian germinoma.

    A case of multiple intracranial germ cell tumor in which a pineal tumor regressed spontaneously after resection of the cerebellar mass is reported. Immunohistochemical staining of the cerebellar mass showed that most of the infiltrating lymphocytes were positive for CD3 and CD8. The anti-Ki-67 monoclonal antibody MIB-1 staining of the resected tumor revealed a high MIB-1 positivity ratio (36.1%) among the large tumor cells, and TUNEL staining demonstrated that positivity in up to 6% of the tumor cells. Possible mechanisms responsible for this spontaneous regression including immunological responses and apoptosis induced by T lymphocytes are discussed.
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ranking = 1
keywords = apoptosis
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2/11. bowen's disease showing spontaneous complete regression associated with apoptosis.

    Spontaneous regression is sometimes seen in malignant skin tumours. We report a 68-year-old woman whose bowen's disease showed spontaneous complete regression. Prominent infiltration of T cells and increased vascularity were found in the upper dermis of the regressed lesion. Strong expression of Fas (APO-1/CD95) antigen, an apoptosis-related tumour necrosis factor receptor family protein, in the primary lesion and faint expression following regression suggest the involvement of Fas-mediated apoptosis in the spontaneous complete regression of our patient's bowen's disease.
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ranking = 6
keywords = apoptosis
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3/11. Spontaneous remission of cancer--a thyroid hormone dependent phenomenon?

    Spontaneous remission (SR) of neoplasia is a rare biological event. Very few reports provide evidence for an eliciting event or mechanism. The only case in the literature of SR of lung cancer following myxedema coma is suggested to have been an instance of thyroid hormone deprivation-induced total tumor apoptosis. review of the collective data suggests that the thyroid hormones modulate pleiotropic neoplasia--abetting mechanisms and that hypothyroidism may enhance the predisposition of neoplasms to spontaneous and therapy induced regression by lowering thresholds for apoptosis.
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ranking = 2
keywords = apoptosis
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4/11. Alteration of mast cell proliferation/apoptosis and expression of stem cell factor in the regression of mastocytoma--report of a case and a serial immunohistochemical study.

    BACKGROUND: Spontaneous regression of solitary mastocytoma is a well-described phenomenon, but its mechanism is unknown. methods: Serial-section immunohistochemical analyses were performed on biopsies of a mastocytoma from a Japanese child during the proliferation stage (PS, 7 months of age) and the regression stage (RS, 5 years old). RESULTS: Mast cell (MC) density in RS was markedly decreased (406 cells/mm2) compared to that in PS (3554 cells/mm2). MCs in RS were larger than those in PS. With proliferative cell nuclear antigen (PCNA) staining, 1.7% MCs were positive in PS, whereas no positive MCs were seen in RS. TUNEL-labeling index (LI) in RS (2.8%) increased 1.5-fold in PS (1.9%). With stem cell factor (SCF) staining, 57% of lesional MCs in RS revealed strong cytoplasmic immunoreactivity, whereas only 9% of MCs were positive in PS. Epidermal SCF reactivity was found as intracellular and intercellular patterns in both PS and RS. CONCLUSIONS: Loss of MC proliferating activity, an increase in apoptotic MCs, and increased expression of SCF in remaining MCs in RS may play a role in the involution of mastocytomas.
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ranking = 4
keywords = apoptosis
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5/11. Regression of congenital fibrosarcoma to hemangiomatous remnant with histological and genetic findings.

    We report a rare case of congenital fibrosarcoma (CFS) showing regression during the course of disease, in which the histological and genetic alterations were investigated. This CFS, located on the patient's right hand, was a hemangiopericytomatous hypervascular tumor showing frequent mitosis and necrosis. Small lymphocytes, predominantly cytotoxic T cells and natural killer cells, infiltrated the tumor. At the age of 3 months, the patient received a partial resection of the tumor. At the age of 1 year, the hemangiopericytomatous tumor with a dilated vascular lumen remained, although most of the tumor cells exhibited focal necrosis with calcification and no mitotic activity. lymphocytes increased in number and intermingled with the tumor cells. At the age of 4 years, vascular tissue consisting of inner endothelial cells and surrounding pericytomatous actin-positive cells remained at the previous tumor locus. With reverse transcription-polymerase chain reaction analysis, ETV6-NTRK3 fusion transcripts were detected in tumor samples at 3 months and at 1 year, but not from those at 4 years of age. These genetic and histological changes suggest that the CFS either completely disappeared by apoptosis or showed mature transformation to hemangiomatous tissue with aging.
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ranking = 1
keywords = apoptosis
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6/11. Hepatocellular carcinoma with an unusual medullary-like histology and signs of regression ("medullary-like hepatocellular carcinoma").

    The case of a variant of hepatocellular carcinoma is described, which, based on its unique histology, we propose to term, medullary-like hepatocellular carcinoma. It developed in a 56-year-old male patient with liver cirrhosis, and consisted of large, amphophilic cells with a solid growth pattern. The tumour was densely infiltrated with lymphocytes and plasma cells. lymphocytes formed a mixture of B and T cells, and plasma cells were polytypic. In addition, numerous S-100 protein-reactive stellate cells were observed at the tumour border, where marked apoptosis of hepatocellular carcinoma cells was evident. In areas of dense lymphoplasmacytic infiltration, part of the tumour cells had lost their intercellular connections and their beta-catenin reactivity. Some tumour cells expressed FasL, but not Fas. The tumour exhibited several foci of regression, showing small remnants of damaged tumour cells within dense infiltrations. The patient is alive without evidence of disease 25 months after resection. Medullary-like hepatocellular carcinoma is a lesion which mimics several features known for other medullary carcinomas, including a marked immune response which may be responsible for partial regression of this tumour.
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ranking = 1
keywords = apoptosis
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7/11. Spontaneous regression in Merkel cell (neuroendocrine) carcinoma of the skin.

    In two Japanese women, 68 and 88 years old, Merkel cell (neuroendocrine) carcinoma of the face developed. Their tumors regressed after biopsy was performed, a rare occurrence. Histological and electron microscopic examination showed apoptosis, cellular necrosis, and an infiltration composed mainly of lymphocytes in the tumors. These changes may have been related to the mechanism of regression. It is interesting that our two patients were women, as was another patient described with Merkel cell carcinoma regression, in light of the fact that the prognosis of this tumor is sex dependent.
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ranking = 1
keywords = apoptosis
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8/11. Biological characteristics of neuroblastoma with spontaneous tumor reduction: a case report.

    The authors examined the biological characteristics of a neuroblastoma with spontaneous tumor reduction. A 6-month-old boy with a pelvic neuroblastoma underwent surgical extirpation of the tumor 1 month after diagnosis. The size of the tumor reduced spontaneously while he was awaiting operation. The low proliferative activity of the tumor cells and the presence of apoptosis in the tumor tissue were shown by an immunohistochemical method using anti-PCNA antibody and a dna fragmentation analysis, respectively. These results suggest that the spontaneous tumor reduction seen in this patient may well be caused by the overwhelming apoptosis of tumor cells.
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ranking = 2
keywords = apoptosis
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9/11. Massive apoptosis in infantile myofibromatosis. A putative mechanism of tumor regression.

    Two cases of solitary infantile myofibromatosis (IM) are presented. Solitary IM are tumors prone to spontaneous regression. Histopathologically, several tumor lobules in our IM cases had central areas of massive cell death, with nuclear pyknosis, cytoplasmic hyalinization and nuclear fragmentation but without lymphoid or neutrophilic cell infiltration. These central cell death areas consisted of about 40% in case 2 and 50% in case 1 of the entire tumor tissues, respectively. Electron microscopy revealed that the condensed nuclei and cytoplasm were fragmented into "apoptotic bodies", with or without phagocytosis by histiocytes. dna fragmentation, as evidenced by the terminal deoxy transferase-mediated uptake of biotinylated dUTP, was identified at massive cell death areas on paraffin sections from both cases. A characteristic 180- to 190-bp nucleosomal ladder was detected in DNA obtained from the tumor cells in case 1. The collective evidence suggested that these tumors underwent a central, massive apoptosis. As massive cell death similar to that seen in the present cases has been described in other documented cases of IM, we propose that the spontaneous regression that frequently occurs with this type of tumor may be mediated by massive apoptotic cell death.
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ranking = 5
keywords = apoptosis
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10/11. Chiasmal gliomas with spontaneous regression: proliferation and apoptosis.

    Spontaneous regression of chiasmal gliomas without associated neurofibromatosis has been occasionally described. In this paper we present two patients with chiasmal glioma whose tumors decreased in size during the postoperative course. Neither patient received radiotherapy or chemotherapy. We examined the proliferative activity of the excised tumors by determining the Ki-67 labeling index and searched for apoptotic cells using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method. The Ki-67 labeling index of the tumor of case 1 was 0.63%, and apoptotic cells were detected in some areas. In case 2, the Ki-67 labeling index was 19.5% and a large number of apoptotic cells were evident. As estimated from the respective apoptosis data, our results would indicate that tumor regression may occur when the rate of cell loss is greater than that of tumor growth.
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ranking = 5
keywords = apoptosis
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