Cases reported "Brain Neoplasms"

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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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keywords = apoptosis
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2/11. Treatment of AIDS-related primary central nervous system lymphoma with zidovudine, ganciclovir, and interleukin 2.

    AIDS-related primary central nervous system lymphoma (AIDS PCNSL) is a rapidly fatal disease. Conventional therapeutic modalities offer little and new approaches are needed. Previous work has shown that zidovudine (AZT) in combination with other agents is active in retroviral lymphomas. Epstein-Barr virus (EBV) is detected in tumor tissue and cerebrospinal fluid of AIDS PCNSL patients. In a preliminary in vitro study we found that an Epstein-Barr virus-positive B cell line underwent apoptosis on coculture with AZT. This effect was accentuated by the addition of ganciclovir (GCV). We treated five patients with AIDS PCNSL with a regimen consisting of parenteral zidovudine (1.6 g twice daily), ganciclovir (5 mg/kg twice daily), and interleukin 2 (2 million units twice daily). Four of five had an excellent response. Two patients are alive and free of disease 22 and 13 months later; another responded on two separate occasions, 5 months apart, and the last patient responded with a 70-80% regression of tumor but could not be maintained on therapy owing to myelosuppression. We conclude that parenteral zidovudine, ganciclovir, and interleukin 2 is an active combination for AIDS-related central nervous system lymphoma.
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ranking = 1
keywords = apoptosis
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3/11. Antisense-mediated inhibition of the bcl-2 gene induces apoptosis in human malignant glioma.

    BACKGROUND: The bcl-2 protooncogene represses a number of cellular apoptotic pathways and is known to be expressed in increasing amounts in glial tumors of higher malignancy. We tested whether antisense oligonucleotides to the bcl-2 gene would affect glioma cell viability. methods: Antisense oligonucleotides directed to the first six codons of the human bcl-2 gene, and nonsense oligonucleotides as a control, were transfected into malignant glioma cells. Two human Bcl-2 positive glioblastoma cell lines from our tumor bank (Jon52 and Roc) were both transfected in vitro with bcl-2 antisense (AS) and nonsense (NS) oligonucleotides at 1 microm and 5 microm concentrations for 5 and 24 hr. Cell viability was assessed at 2, 4, 5, and 7 days by using an MTT mitogenic assay and by cell counting via direct visualization using a hemocytometer. RESULTS: There was up to a log-fold decrease in cell growth of the bcl-2 AS treated cells compared to the NS transfected cells for both Roc (p = 0.007 and p = 0.004) and Jon52 (p = 0.02 and p = 0.004) at 5 and 24 hr of transfection. There was as much as 50% cytotoxicity in both glioblastoma cell lines at 1 microm and 5 microm concentrations after 24 hr transfection with AS bcl-2 oligonucleotides (all p < 0.01). Western blot analysis demonstrated a decrease in the expression of the Bcl-2 protein in one cell line, whereas there was a statistically significant increase in the apoptotic index of both cell lines (p < 0.05 by chi square analysis). CONCLUSIONS: Our results suggest that transfection of human glioma cells with antisense bcl-2 results in an increase in apoptotic death. This provides evidence that Bcl-2 plays a role in tumor progression of glioma by acting as an oncogene, and suggests that inhibition of the bcl-2 gene could have a therapeutic effect.
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ranking = 4
keywords = apoptosis
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4/11. Pediatric neuroblastic brain tumors containing abundant neuropil and true rosettes.

    We have encountered a series of seven unusual neuroblastic pediatric central nervous system (CNS) neoplasms with a unique constellation of histologic, immunohistochemical, and ultrastructural features. The tumors presented in five girls and two boys, ages 1 to 3 years. In six cases the lesions involved the frontoparietal region, in one case the tectal plate. The tumors consisted of small to medium-sized, round to oval, hyperchromatic cells with poorly defined cytoplasmic borders. cells were found in clusters and cords set in a paucicellular fibrillar neuropil matrix. Distinctive, virtually anuclear regions of neuropil were scattered throughout the lesions. True rosettes with well-formed central lumens often filled with granular debris were present, along with perivascular pseudorosettes and occasional Homer-Wright rosettes. Mitoses and apoptosis were frequent, but large regions of confluent necrosis were absent. Immunohistochemically, the neuropil-like areas as well as the perinuclear cytoplasm of many embryonal tumor cells were positive for synaptophysin and neurofilament protein. Ultrastructurally, the tumor cells showed microtubule-containing neuronal processes, some with neurosecretory granules. While the lesions were largely glial fibrillary acidic protein (GFAP) negative, there was focal GFAP positivity consistent with divergent differentiation in one case. The clinical outcome was poor, with five patients dead from their disease 5 to 14 months after initial presentation and one patient with recurrent disease 7 months after resection and chemotherapy. The final patient is alive without recurrent disease 30 months after initial presentation. These lesions present distinctive histological features within the group of primitive neuroectodermal tumors.
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ranking = 1
keywords = apoptosis
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5/11. Analyses of proliferative potential in schwannomas.

    We report studies of schwannomas with a high percentage of MIB-1 positive cells. Thirty-eight specimens from 36 cases of schwannoma in the intracranial and spinal regions comprise the substance of this study. The MIB-1 positive cells were measured using immunohistochemical staining. In nine cases with a positivity index (PI) of 5% or more, immunohistochemical staining using DNA topoisomerase IIalpha (topo-II) and CD68 was performed. In some cases, we also searched for apoptosis with the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) method. Three of nine cases with 5% or more positive MIB-1 cells had a very high cellularity with mitotic figures and were considered cellular Schwannomas. Their MIB-1 PI values were 8.21%, 10.00%, and 21.37%. However, the remaining six cases showed little evidence of malignancy. Their PIs were comparatively low, ranging from 5.19% to 8.41%, and the positive findings were localized in many cases. In these cases, we examined the sites where MIB-1 was measured and found that they corresponded to the borderline site between Antoni type A and B patterns and tended to be associated with an infiltration of CD68-positive macrophage. Furthermore, apoptotic cells appeared in the sites. With topo-II staining, the PIs in the same sites of these six cases were low, ranging from 0.78% to 1.93%. This implies that the high MIB-1 PI that was seen in these six cases was caused by reaction of MIB-1 to tumor cells that brought about an abnormality in the cell cycle by degeneration, such as apoptosis. In the site of formation of Antoni type B, MIB-1 may be a false positive in tumors with degenerative findings such as schwannomas. Topo-II was useful in these cases.
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ranking = 2
keywords = apoptosis
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6/11. Identifying differentially expressed genes associated with metastasis of follicular thyroid cancer by cDNA expression array.

    patients with follicular thyroid carcinoma have a higher incidence of metastasis than papillary thyroid carcinoma when thyroid cancer is diagnosed. The cDNA expression array technology is utilized herein to profile differentially expressed genes from metastatic human follicular thyroid carcinoma and reveal new tumor markers as well as target genes for therapeutic intervention. Tissue samples were obtained during surgical resection of the thyroid follicular carcinoma and metastatic tissue in the brain of the same patient. Two identical Atlas human cDNA expression arrays were hybridized with 32P-labeled cDNA probes derived from rna of either primary thyroid cancer or metastatic tissue. Parallel analysis of the hybridized signals allowed us to identify the alteration of gene expression in the metastasis process. Eighteen genes significantly overexpressed and 40 genes significantly underexpressed were identified in the metastatic thyroid cancer. genes that displayed an altered expression were associated with the processes of cell cycle regulation, apoptosis, dna damage response, angiogenesis, cell adhesion and mobility, invasion, and immune response. An expression profile of genes that are associated with metastasis process of follicular thyroid cancer was also discussed. Further investigation is required to understand the precise relationship between the altered expression of these genes and the metastasis process of follicular thyroid cancer.
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ranking = 1
keywords = apoptosis
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7/11. A novel germline mutation of PTEN associated with brain tumours of multiple lineages.

    We have identified a novel germline mutation in the PTEN tumour suppressor gene. The mutation was identified in a patient with a glioma, and turned out to be a heterozygous germline mutation of PTEN (Arg234Gln), without loss of heterozygosity in tumour DNA. The biological consequences of this germline mutation were investigated by means of transfection studies of the mutant PTEN molecule compared to wild-type PTEN. In contrast to the wild-type molecule, the mutant PTEN protein is not capable of inducing apoptosis, induces increased cell proliferation and leads to high constitutive PKB/Akt activation, which cannot be increased anymore by stimulation with insulin. The reported patient, in addition to glioma, had suffered from benign meningioma in the past but did not show any clinical signs of Cowden disease or other hereditary diseases typically associated with PTEN germline mutations. The functional consequences of the mutation in transfection studies are consistent with high proliferative activity. Together, these findings suggest that the Arg234Gln missense mutation in PTEN has oncogenic properties and predisposes to brain tumours of multiple lineages.
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ranking = 1
keywords = apoptosis
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8/11. Postoperative regression of desmoplastic infantile gangliogliomas: report of two cases.

    OBJECTIVE AND IMPORTANCE: Desmoplastic infantile gangliogliomas (DIGs) are extremely rare tumors that respond well to treatment. However, their biological behavior remains to be clarified. We describe two patients whose DIGs spontaneously regressed after surgery, without adjuvant therapy. CLINICAL PRESENTATION: A 9-month-old girl presented with left hemiparesis, and a 6-month-old boy presented with increasing head circumference. For both patients, neuroimaging demonstrated a huge cystic tumor that included a solid portion and was widely attached to the dura. gadolinium-diethylenetriamine penta-acetic acid produced strong enhancement. INTERVENTION: One patient underwent partial and the other subtotal tumor removal. Histologically, both tumors were diagnosed as DIGs. Postoperatively, the residual tumors were monitored without adjuvant therapy, and both regressed in several months. CONCLUSION: Our experience suggests that DIGs may include a subgroup of tumors with a tendency for spontaneous regression, possibly attributable to the induction of apoptosis.
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ranking = 1
keywords = apoptosis
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9/11. High levels of sFas and PBMC apoptosis before and after excision of malignant melanoma--case report.

    In our study we investigated the level of apoptosis in PBMCs and the serological level of sFas (CD95/APO-1) in 22 patients with malignant melanoma (12 patients with unique cutaneous primary tumour and 10 patients with unique brain metastasis). The first determination was performed before tumour excision and the second at 6-7 months after excision. Results in patients with primary tumour in the first determination: 6 patients with over normal values in PBMCs apoptosis and 5 patients with increased values of sFas. In the second determination: apoptosis was increased in 5 patients and sFas level was increased in 4 cases. In patients with metastases in the first determination apoptosis of PBMC was increased in 7 cases and sFas in 5 cases. In the second determination apoptosis was increased in 4 cases and sFas was increased in 4 cases. Our results show that half of the investigated patients presented elevated values of PBMCs apoptosis and Fas receptor both before and 6-7 months after tumour excision. apoptosis values for PBMCs and sFas values were with 1/4 higher than normals. There was no difference in clinical evolution of the patients with normal or increased values for studied parameters. Clinical evolution was performed for 1 year. The presence of increased values for PBMCs and sFas after tumour excision, primary or metastasis is surprising and hard to explain. It is possible that tumoral evolution induces a disregulation at PBMCs level or other cells level that persists unexpectedly, after tumour excision or apoptotic processes, in a certain level to be independent and anterior to tumour development.
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ranking = 10
keywords = apoptosis
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10/11. Irinotecan-induced colitis.

    Irinotecan (CPT-11) is a chemotherapeutic drug used to treat tumors by acting on malignant cells through inhibition of DNA topoisomerase I and inducing premature apoptosis. Major toxic effects of Irinotecan are myelosuppression and gastrointestinal (GI) toxicity, which limits the dose of administration, particularly severe diarrhea with a delay of onset. However, according to the literature, serious GI side effects are uncommon, comprising 3% of the reported cases. The mechanism of Irinotecan-induced delayed diarrhea is unknown and unpredictable. To our knowledge, this is the first case of colitis associated with Irinotecan administration for temporal glioblastoma documented by biopsies. The histopathologic findings are described and the potential mechanisms inducing such lesions are discussed.
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ranking = 1
keywords = apoptosis
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