Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a case of testicular B cell lymphoma with deletion of chromosome 5, del(5)(p11), as a sole structural abnormality. Histopathological diagnosis of the tumor was a high-grade lymphoma of the diffuse type containing cells positive for B cell specific antigen (CD20) and negative for the leukocyte common antigen (CD45). Deletion 5p may define the region of a tumor suppressor gene that could be associated with tumor progression and invasiveness and may serve as an indicator of poor prognosis in testicular lymphomas.
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PMID:Deletion 5p11 accompanied by multiple numerical changes in testicular lymphoma. 1173 24

Anthracyclines remain as the best drugs in the treatment of patients with aggressive malignant lymphoma in combination with other cytotoxic drugs. However, dose escalation is poorly tolerated and acute and late cardiac toxicity has limited the use of these compounds. Pegylated liposomal doxorubicin has been proven to be useful in some malignancies, without the presence of acute cardiac toxicity and with a good response rate in patients with relapsed/refractory lymphomas. We report the first study of this drug in combination chemotherapy in patients with previously untreated aggressive malignant lymphoma. Twenty consecutive patients with diagnosis of diffuse large-B-cell lymphoma, age < 18 yr to < 70 yr, without previous treatment, HIV-negative high and high-intermediate clinical risks were treated with the CHOP-Bleo regimen at standard doses, using pegylated-liposomal doxorubicin instead of doxorubicin, at 25 mg/m2 (3 patients), 30 mg/m2 (3 patients), and 35 mg/m2 (14 patients). Complete response was achieved in 17 cases (85%), with failure in 3 patients (15%). At a median follow-up of 18.1 mo, relapse has not been observed. Two patients died secondary to tumor progression. Toxicity was mild, only three episodes of granulocytopenia grade I were observed, and no mucositis, thrombocytopenia, or granulocitopenia grade > 2 was observed. Erythrodisestesias grade II was observed in one case and grade I in two cases. Cardiac function was normal before and 12 mo after chemotherapy. Pegylated liposomal doxorubicin appear as an promising drug in the treatment of patients with aggressive malignant lymphoma.
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PMID:Pegylated liposomal doxorubicin in combination chemotherapy in the treatment of previously untreated aggressive diffuse large-B-cell lymphoma. 1202 91

Splenic marginal zone lymphoma (SMZL) is a specific low-grade small B-cell lymphoma that is incorporated in the World Health Organization classification. Characteristic features are splenomegaly, moderate lymphocytosis with villous morphology, intrasinusoidal pattern of involvement of various organs, especially bone marrow, and relative indolent course. Tumor progression with increase of blastic forms and aggressive behavior are observed in a minority of patients. Molecular and cytogenetic studies have shown heterogeneous results probably because of the lack of standardized diagnostic criteria. To date, no definitive therapy has been established. Therapeutic options include treatment abstention, splenectomy, splenic irradiation, and chemotherapy.
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PMID:Splenic marginal zone lymphoma. 1244 49

Chronic lymphocytic leukemia (CLL) is an indolent B cell non-Hodgkin lymphoma (NHL) that may transform into diffuse large B cell lymphoma (DLBL). This transformation is referred to as Richter's syndrome or transformation. To analyze whether microsatellite instability (MSI) and DNA mismatch repair defects are associated with Richter's transformation, we have performed microsatellite analysis, mutational analysis of hMLH1 and hMSH2 genes and methylation status analysis of CpG island of the hMLH1 promoter on serial biopsy specimens from 19 patients with CLL. Ten cases of CLL showed no histologic alteration in the second biopsy, and nine cases of CLL underwent morphologic transformation to DLBL in the second biopsy. Using eight microsatellite loci, high level of MSI was associated with Richter's transformation in four cases of CLL, but none of the CLLs displayed this level of MSI without transformation. Mutations of the hMLH1 or hMSH2 genes were not detected in any of the lymphoma samples. In five cases of Richter's transformation the hMLH1 promoter was hypermethylated in both CLL and DLBL samples. Hypermethylation of the hMLH1 promoter associated with high-level of MSI in four cases, and low-level of MSI in one case. These results suggest that in certain cases of Richter's transformation the DNA mismatch-repair defect-initiated genetic instability may play a role in tumor progression.
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PMID:Microsatellite instability and hMLH1 promoter hypermethylation in Richter's transformation of chronic lymphocytic leukemia. 1259 41

In this report, we present a six-year-old male patient with partial intestinal obstruction due to refractory Non-Hodgkin's lymphoma (NHL) whose partial obstruction was successfully treated with Taxol(R) without any surgical intervention. Following an unsuccessful treatment attempt to treat his high-grade (stage 3) B-cell lymphoma with standard and second-line chemotherapy regimens he was started on radiotherapy and third line chemotherapy during which he was admitted with partial obstructive ileus as a result of tumor progression. Treatment was continued with Taxol(R) and resulted in total cure of the ileus with reduction of palpable tumor mass over 24 h without necessitating any surgery. Taxol(R) (200 mg/m (2)/week) was administered without any major side effects/toxicities for six courses. A control CT of the abdomen revealed a significant reduction in tumor size. After the next course, the patient developed severe thrombocytopenia that unfortunately did not resolve before the patient died as a result of further tumor growth and dissemination. Although there are studies that report response to Taxol(R) treatment in adult patients with refractory NHL, our review of the literature failed to demonstrate any report about the effectiveness of Taxol(R) in childhood NHL. In conclusion, our case may indicate that Taxol(R) can be effective and be administered safely in an outpatient setting in children with refractory NHL with the aim of prolonging the survival without sacrificing good quality of life. Studies on larger number of patients are needed to make a definitive conclusion about the value of Taxol(R) in refractory childhood NHL.
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PMID:Partial intestinal obstruction due to childhood refractory hon-Hodgkin's lymphoma, successfully treated with taxol. 1368 May

The anti-CD20 monoclonal antibody rituximab induces remission in 40% to 60% of patients with indolent B-cell lymphoma, but virtually all patients have relapses. We evaluated the efficacy of concurrent administration of another biologic agent, N-(4-hydroxyphenyl) retinamide (4HPR, fenretinide) with rituximab against a variety of human B-cell lymphoma cell lines (Ramos, DHL-4, and FL-18) in vivo. Concurrent 4HPR and rituximab administration prevented tumor progression of lymphoma-bearing mice in a minimal disease model (rituximab + 4HPR, 100% progression free; rituximab alone, 37.5% progression free, P =.01; 4HPR alone, 12.5% progression free, P <.01; controls, 0% progression free, P <.01). Combinations of 4HPR + rituximab exceeded the predicted 50% additive rate of disease control from each agent alone (P =.038). Administering 4HPR and rituximab to mice with established tumors induced complete responses (CRs) in 80% of animals compared with 20% to 40% CRs using either agent alone (P =.07), resulting in significantly improved survival. Tumors harvested from 4HPR + rituximab-treated mice displayed elevated caspase activation compared with untreated controls (P =.02). Adding a broad-spectrum caspase inhibitor in vivo fully abrogated the antitumor effects of 4HPR + rituximab (P =.05). These results establish the efficacy of 4HPR/rituximab combinations, confirm their caspase-mediated mechanism of action, and offer the potential for disease control with minimal toxicity for patients with B-cell malignancies.
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PMID:Fenretinide enhances rituximab-induced cytotoxicity against B-cell lymphoma xenografts through a caspase-dependent mechanism. 1469 37

We describe three lymphoid tumors with the same immunophenotype characteristic for chronic lymphoid leukemia (CD19+/CD5+, clonality of the light immunoglobulin chains, CD23+ and CD10-). However, clinical picture and morphology of neoplastic cells dictate different clinical forms of these cases: chronic lymphoid leukemia, large cell transformation of chronic lymphoid leukemia and diffuse large B-cell lymphoma. Taking into account that immunophenotype reflects the origin of tumor, while clinical outcome and morphological features of cells reflect the stage of tumor progression and/or pathway of tumor formation, we discuss the approach to natural classification of lymphoid tumors based on the process of their evolution.
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PMID:[Comparative characteristics of immunological, clinical and morphological features of human lymphoid tumors in respect with tumor genesis and progression]. 1533 26

The aim of the present study was to evaluate an intensive chemotherapy regimen in patients with diffuse large B-cell lymphoma and poor prognosis, as presence of high- or high-intermediate clinical risk, bulky disease, high levels of beta 2 microgloblin, and more than two extranodal sites of involvement at diagnosis. One hundred previously untreated patients were treated with an intensive CEOP-Bleo regimen with increased doses of cyclophosphamide (1000 mg/m(2)) and epirubicin (120 mg/m(2)) in each cycle. Granulocyte colony-stimulating factors was employed to ameliorate severe granulocytopenia. Complete response was achieved in 79 cases (79%). With a median follow-up of 32.3 mo (range 10-45 mo) only seven patients have relapsed. Thus, actuarial curves at 3 yr, showed that event-free survival was 72%. Five died secondary to tumor progression, actuarial curves at 3-yr for overall survival were 75%. Toxicity was mild, granulocytopenia grade III or IV were observed in the 46% of the cycles; infection-related granulocytopenia was observed in 17%, but no fatality due to therapy was observed. Cardiac toxicity was mild, only seven patients showed a drop in left ejection ventricular function, but no symptomatic heart failure has been observed. The intensive CEOP-Bleo regimen with increasing doses of cyclophosphamide and epirubicin is a useful and well-tolerated regimen in the treatment of poor prognosis diffuse large B-cell lymphoma.
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PMID:Intensive chemotherapy in the treatment of aggressive diffuse large B-cell lymphoma: malignant lymphoma. 1545 55

p16/INK4a gene alterations have been associated with tumor progression in lymphoid malignancies. However, their significance in mucosa-associated lymphoid tissue (MALT) lymphoma is unclear. We investigated p16 gene methylation and mutation in a large series of untreated cases of pulmonary MALT lymphoma and diffuse large B-cell lymphoma (DLBL), and correlated p16 gene alterations with a MALT lymphoma-specific API2-MALT1 fusion and the clinicopathologic features of MALT lymphoma. The API2-MALT1 fusion was detected by multiplex reverse transcription polymerase chain reaction in 25/60 (42%) cases of MALT lymphoma, but none of 11 DLBLs. Methylation-sensitive single-strand conformation analysis showed that p16 gene methylation was frequently detected in 36/60 (60%) cases of MALT lymphoma. The gene was similarly methylated in DLBL cases (6/11, 55%). A p16 gene mutation was found in one (p16 gene-methylation) of 44 MALT lymphomas and in none of six diffuse large B-cell lymphomas. Statistical analysis showed that the p16 gene methylation status did not correlate with API2-MALT1 fusion or any of the clinicopathologic factors including serum LDH, clinical stage, and increased large cells. These findings suggest that p16 methylation is not associated with tumor progression, but may be an early event in MALT lymphomagenesis that might be maintained through the progression of the tumor.
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PMID:p16/INK4a gene methylation is a frequent finding in pulmonary MALT lymphomas at diagnosis. 1583 93

Telomeres are essential for maintaining chromosomal integrity and stability. We studied here telomere length (TL) in bone marrow and/or lymph node from 36 patients: 29 with follicular lymphoma (FL) at diagnosis and 7 with diffuse large B cell lymphoma secondary to FL (S-DLBCL). TL was evaluated using terminal restriction fragments (TRF) assay. BCL-2 gene rearrangement was analyzed by nested and long distance PCR. Mean TRF values showed significant telomere shortening in FL (4.18 +/- 0.18 Kb) and S-DLBCL (3.31 +/- 0.25 Kb) respect to controls (8.50 +/- 0.50 Kb) (p<0.001). Differences between both histological subtypes (p=0.036) were also detected. Moreover, the samples positive for BCL-2 rearrangements showed longer TL (4.25 +/- 0.19 Kb) than the negative ones (3.39 +/- 0.30 Kb) (p=0.023). A trend to telomere shortening was observed when Major Breakpoint Region (MBR-JH), minor cluster region (mcr-JH) and BCL-2 negative patients were compared (4.35 +/- 0.21 Kb; 3.84 +/- 0.45 Kb and 3.39 +/- 0.30 Kb, respectively). Our results show a TL reduction in FL and S-DLBCL, with significant short TRFs in the last group, suggesting the participation of telomere shortening in tumor progression. Furthermore, the differences detected between BCL-2 positive and negative FL support the involvement of diverse pathogenic mechanisms.
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PMID:[Molecular analysis of telomere length in follicular lymphomas. Its participation in tumor progression]. 1607 9


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