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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To facilitate investigation of the molecular mechanisms of tumor cell radiosensitivities, we have generated a set of clones with different radiosensitivities from a human glioma cell line U-251 MG-Ho. Forty-four colonies were isolated by subjecting parent cells to the mutagen N-methylnitrosourea and then irradiating these cells with increasing doses of x-rays. About half of the clones displayed different radiosensitivities than the parent cells. We selected one of the most sensitive clones (X3i) and one of the most resistant clones (Y6) for further study. Isoeffective doses for these two clones differed by about a factor of 1.7; the relative radiosensitivities of both clones were stable for at least 30 cell culture passages. These two clones do not differ significantly in either the induction or repair of radiation-induced DNA double-strand breaks as measured by pulsed field gel electrophoresis. Radiation-induced apoptosis measured by terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay and micronucleus formation were similar in both clones. However, potentially lethal damage repair was greater in the radioresistant Y6 clone than in the radiosensitive X3i clone as determined by colony-forming efficiency assay.
Neoplasia 1999 Jun
PMID:Induction and characterization of human glioma clones with different radiosensitivities. 1093 48

The experiments were designed to study correlation between frequency of apoptosis of Reed-Sternberg/Hodgkin (R-S/H) cells, EBV infection of these cells, expression of the key proteins involved in regulation of apoptosis and cell cycle in R-S/H cells, the patients' pretreatment markers and the clinical outcome. One hundred and ten Hodgkin's disease (HD) patients were studies, of which 69 obtained complete remission (CR) after first-line treatment and 41 did not respond. The time of follow-up was from 18 to 242, median 69.7, months. Apoptosis was evaluated by TUNEL technique (TdT-mediated dUTP nick end labeling) and the presence of EBV-latent membrane protein 1 as well as expression of Bcl-2, tumor suppressor p53, p21WAF1, MDM-2, Rb1, PCNA, p27KIP1 and caspase-3, was detected immunocytochemically on paraffin-embedded lymph node specimens obtained at diagnosis. Positive TUNEL reaction was found in 43 patients with apoptotic index (AI) in this group varying between 10% and 60%. In the remaining 57 patients AI of R-S/H cells was below 10%. In 62 patients the cells surrounding R-S/H cells were also TUNEL-positive; their frequency was variable. The expression of LMP1 protein on R-S/H cells was found in 38 patients, without any correlation with the presence or frequency of apoptosis. No significant difference was seen between the AI and both clinical stage and histological type of the disease. However, the mean AI in non-responding patients was significantly higher than in CR group (p=0.015); the high frequency of apoptosis was also negatively correlated with the progression free survival time (p=0.031) and the overall survival (p=0.042). The expression of PCNA, p21WAF1, p53 protein and caspase-3 also showed positive correlation with frequency of apoptosis (p=0.011, p=0.036, and p=0.001, respectively). On the other hand, no statistically confirmed correlation was found between AI and expression of bcl-2, MDM-2, Rb1, and p27KIP1 on R-S/H cells. These data provide evidence that tumor cells in HD undergo spontaneous apoptosis regardless of EBV infection. High pretreatment AI correlates with poor response to the treatment, and may be considered as a potential negative prognostic factor in HD.
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PMID:Spontaneous apoptosis of Reed-Sternberg and Hodgkin cells; clinical and pathological implications in patients with Hodgkin's disease. 1093 5

The oncoproteins Bcl-2 and Bax, the tumor suppressor gene product p53, TUNEL (TdT [terminal deoxynucleotidyl transferase] dUTP nick end-labeling) and the cell-cycle antigen Ki-67 were studied in 71 cases of mucoepidermoid carcinoma originating in the oral minor salivary glands. Grade I tumors had higher expression of Bcl-2 than Grade II and III tumors (chi2 test, 0.01<P<0.025) and the Bcl-2-positive group had a higher survival rate than the Bcl-2-negative group (generalized Wilcoxon, P = 0.00051). Patients with strong TUNEL positivity had a higher survival rate than those with either weak positivity or negativity (generalized Wilcoxon, P = 0.047). The expression of p53 and TUNEL had a positive correlation (P = 0.0315). Grade II and III tumors had a higher frequency of positive Ki-67 expression than Grade I tumors (chi2 test, 0.01<P<0.025) and patients with Ki-67-negative tumors had better survival than patients with Ki-67-positive tumors (generalized Wilcoxon, P = 0.000099). This study showed that Bcl-2 proteins, p53 protein, TUNEL and Ki-67 are potentially useful prognostic markers for survival in patients with mucoepidermoid carcinoma of the oral minor salivary glands.
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PMID:Apoptosis and apoptotic-related factors in mucoepidermoid carcinoma of the oral minor salivary glands. 1097 57

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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PMID:Analyses of proliferative potential in schwannomas. 1098 8

The study of immunoglobulin genes in multiple myeloma over the last decade has provided important information regarding biology, ontogenetic assignment, disease evolution, pathogenic consequences and tumor-specific therapeutic intervention. Detailed analysis of VH genes has revealed the clonal relationship between switch variants expressed by the bone marrow plasma cell and myeloma progenitors in the marrow and peripheral blood. Regarding VH usage, a bias was found against the V4-34 gene encoding antibodies with cold agglutinin specificity (anti-I/i), thus explaining in part the absence of autoimmune phenomena in myeloma compared to other B cell lymphoproliferative disorders. However, in some studies a substantial number of cases analyzed were carrying the rearranged Humkappav325 Vkapppa gene, known to be over utilized by B cell chronic lymphocytic leukemia clones and possessing autoantibody binding activity. VH genes accumulate somatic hypermutations following a distribution compatible with antigen selection, but with no intraclonal heterogeneity. The analysis of Vkappa genes indicates a bias in usage of Vkappa family members; somatic hypermutation, in line with antigen selection, of the expressed Vkappa genes is higher than any other B cell lymphoid disorder. Similar conclusions were reached for Vlambda genes; in this case, the analysis raises the controversial issue of N nucleotide insertion at Vlambda-Jlambda junctions, apparently as a result of TdT activity. A complementary imprint of antigen selection as evidenced by somatic hypermutation of either the VH or VL clonogenic genes has been observed. The absence of ongoing somatic mutations in either VH or VL genes gives rise to the notion that the cell of origin in myeloma is a post-germinal center memory B cell.
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PMID:Origin and diversification of the clonogenic cell in multiple myeloma: lessons from the immunoglobulin repertoire. 1102 46

Twenty-eight patients with squamous cell carcinoma of the oral cavity were treated with a total dose of 20 Gy. Tissue samples for immunohistochemistry were taken at the time of diagnostic biopsy and at surgery after radiotherapy (RX). For detection of proliferating cells, the immunoperoxidase reaction with Ki67 was performed. Apoptotic cells were detected by the TdT-mediated biotin dUTP nick end labeling (TUNEL) method. RX reduced proliferation in 27 patients, only in one case did the proliferation index (PI) increase. Delta PI (PI before RX PI following RX) amounted to 4.11% (SD=3.2%; P<0.0001). The apoptotic index (AI) increased significantly subsequent to neoadjuvant RX. Delta AI (AI after RX--AI before RX) measured 1.82% (SD=0.9; P<0.001). These data indicate that RX of patients suffering from squamous cell carcinoma of the oral cavity with a dosis of 20 Gy induces apoptosis and inhibits proliferation of tumor cells.
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PMID:Neoadjuvant, hyperfractionated irradiation induces apoptosis and decreases proliferation in squamous cell cancer of the oral cavity. 1103 Apr 1

The formation of liver metastases involves interactions between intravascular cancer cells and the hepatic microvasculature. Here we provide evidence that the arrest of intravascular B16F1 melanoma cells in the liver induces a rapid local release of nitric oxide (NO) that causes apoptosis of the melanoma cells and inhibits their subsequent development into hepatic metastases. B16F1 melanoma cells (5 x 10(5)) labeled with fluorescent microspheres were injected into the portal circulation of C57BL/6 mice. The production of NO in vivo was detected by electron paramagnetic resonance spectroscopy ex vivo using an exogenous NO-trapping agent. A burst of NO was observed in liver samples examined immediately after tumor cell injection. The relative electron paramagnetic resonance signal intensity was 667 +/- 143 units in mice injected with tumor cells versus 28 +/- 5 units after saline injection (P < 0.001). Two-thirds of cells arrested in the sinusoids compared with the terminal portal venules (TPVs). By double labeling of B16F1 cells with fluorescent microspheres and a TdT-mediated UTP end labeling assay, we determined that the melanoma cells underwent apoptosis from 4-24 h after arrest. The mean rate of apoptosis was 2-fold greater in the sinusoids than in the TPVs at 4, 8, and 24 h after injection (P < 0.05-0.01). Apoptotic cells accounted for 15.9 +/- 0.8% of tumor cells located in the sinusoids and 7.1 +/- 0.9% of tumor cells in the TPVs. The NO synthase inhibitor N(G)-nitro-L-arginine methyl ester completely blocked the NO burst (P < 0.001) and inhibited the apoptosis of B16F1 cells in the sinusoids by 77%. However, the rate of tumor cell apoptosis in the TPVs was not changed. There were 5-fold more metastatic nodules in the livers of N(G)-nitro-L-arginine methyl ester-treated mice (P < 0.05). The inactive enantiomer N(G)-nitro-D-arginine methyl ester had no effect on the initial NO burst or on apoptosis of tumor cells in vivo. Both annexin V phosphatidylserine plasma membrane labeling and DNA end labeling of apoptotic cells were demonstrated after a 5-min exposure (a time equivalent to the initial transient NO induction in vivo) of B16F1 cells to a NO donor in vitro. These results identify the existence of a natural defense mechanism against cancer metastasis whereby the arrest of tumor cells in the liver induces endogenous NO release, leading to sinusoidal tumor cell killing and reduced hepatic metastasis formation.
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PMID:B16 melanoma cell arrest in the mouse liver induces nitric oxide release and sinusoidal cytotoxicity: a natural hepatic defense against metastasis. 1105 84

The present study was carried out to elucidate the relationship between cancer cell growth and apoptosis in morphogenesis of colorectal cancer, and the role of p53 expression, one of apoptosis-related genes, in apoptosis. Specimens from 82 cases of colorectal cancer, all surgically resected, were divided into intramucosal polypoid growth (PG) and nonpolypoid growth (NPG) types according to Shimoda's classification. Expressions of proliferating cell nuclear antigen (PCNA) and p53 protein were assessed by immunohistochemical staining, and apoptosis by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. Immunohistological detection of p53 protein was performed by the use of Pab1801. In the assessment of PCNA and apoptosis the numbers of positive cells per 1000 tumor cells were expressed as PCNA labeling index (L.I.) and apoptosis labeling index (Apo L.I.), respectively. In tumor invading muscularis propria (mp), the cancer tumor tissue was equally divided into three by the depth, top, middle, and bottom, and the number of apoptosis-positive cells per 500 tumor cells was calculated per each depth of invasion and compared between PG and NPG types. PCNA L.I. was 658.5 +/- 127.1 (mean +/- SD) in PG type. When determined according to depth of invasion, PCNA L.I. was 533.8 +/- 188.2 for tumor invading submucosa (sm), 741.8 +/- 62.2 for mp, and 679.2 +/- 94.3 for tumor invading subserosa or penetrating the serosa (ss-a). The corresponding values in the NPG type were 651.9 +/- 176.2, 482.2 +/- 227.1, 766.2 +/- 90.7, and 690.9 +/- 84.3, respectively. There was no significant difference in the relationship of PCNA L.I. with the depth of invasion in both growth types. Apo L.I. was 19.9 +/- 9.8 in PG type. When determined according to depth of invasion, Apo L.I. was 29.2 +/- 9.7 for sm, 21.7 +/- 9.0 for mp, and 15.4 +/- 7.0 for ss-a. The corresponding values in the NPG type were 52.8 +/- 25.1, 67.5 +/- 25.6, 37.2 +/- 9.4, and 52.6 +/- 26.3, respectively. Apo L.I. of NPG type was significantly higher than that of PG type in each depth of invasion (p < 0.01). In mp tumor the numbers of apoptosis-positive cells in the top, middle, and bottom of the PG type were 8.0 +/- 4.8, 11.8 +/- 3.9, and 12.9 +/- 5.9, and the corresponding values of the NPG type were 26.6 +/- 7.6, 17.3 +/- 5.3, and 11.8 +/- 4.3, respectively. The number of apoptosis in the top and middle of the lesion of NPG tumors was significantly higher than that of PG tumors. There was no difference in the number of apoptosis in the bottom of the lesion between the NPG and the PG types. There was no significant difference in the Apo L.I. between p53 positive cancers and negative cancers. These results indicate that colorectal cancers show a pattern of PG if apoptosis is low, and a pattern of NPG if apoptosis is high, and that apoptosis of colorectal cancer cell is not regulated by p53.
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PMID:[Significance of cancer cell growth and apoptosis in morphogenesis of colorectal cancer]. 1107 Jul 93

A 20 year-old male patient was admitted to our department for the treatment of recurrence of fever and pancytopenia developed despite of temporal remission of hemophagocytosis syndrome that had been treated with large doses of methylprednisolone in our hospital. Superficial lymph nodes were not palpable. CT scan and echography revealed neither findings of splenohepatomegalia or enlargement of intraabdominal lymph nodes. Bone marrow aspiration showed an increase of histiocytes, the cells phagocytizing erythrocytes and platelets, and a negative test for peroxidase stain. Analysis of surface antigens showed that 11.3% of cells were blast cells positive for CD10, CD19, CD20, CD34 and TdT. Bone marrow biopsy revealed a localized increase in tumor cells positive for L26, CD10 and negative for UCHL-1. Because of the absence of detectable tumor masses and the difficulty in differentiating between malignant lymphoma and lymphatic leukemia, we diagnosed the condition as B precursor lymphoblastic leukemia/lymphoma. If diagnosed with malignant lymphoma preceded by hemophagocytic syndrome(LAHS), he might have a rare type of LAHS-associated malignant lymphoma since histological examination did not reveal diffuse large cell lymphoma, a condition found in most patients with LAHS-associated malignant lymphoma. Whereas if diagnosed as ALL, he was the first adult patient with ALL with HPS at onset as far as we know. In any of these possibilities, the case was considered rare.
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PMID:[B precursor lymphoblastic leukemia/lymphoma manifested at onset as hemophagocytic syndrome]. 1121 14

Lymphoma/leukemia derived from immature natural killer (NK) cells occur most commonly in adults and are characterized by blastic cytologic features and an aggressive outcome. Predilection for extranodal sites and absence of the Epstein-Barr virus associated with mature NK cell malignancies further distinguish this entity. We present a NK precursor acute lymphoma presenting with multiple masses in an infant without circulating blasts or marrow replacement by disease. The diagnostic difficulty arose from several factors, including young age, presentation with multiple masses, blastic cytologic features mistaken for a small, round, blue cell tumor, and the absence of lineage-specific markers. The CD56+, CD34+, CD33+, MPO-, cytoplasmic CD3+, CD45-, CD7-, HLA-DR-, and TdT- immunophenotype of this neoplasm overlaps with previously reported cases of myeloid/NK precursor acute leukemia and blastic NK cell lymphoma/leukemia. This case emphasizes the need for a strong index of suspicion to recognize this rare entity and to distinguish it from solid tumors and other hematolymphoid neoplasms that occur in infancy.
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PMID:Natural killer cell precursor acute lymphoma/leukemia presenting in an infant. 1123 95


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