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Meletios Dimopoulos

Publications and source records attributed to Meletios Dimopoulos.

10 recordsLinked to original sources

Survivin and glycodelin transcriptional activity in node-positive early breast cancer: mRNA expression of two key regulators of cell survival.

INTRODUCTION: Glycodelin and survivin are key polypeptide regulators of cellular proliferation, apoptosis and angiogenesis. In view of contradictory reports on their functional role in tumors, we studied their transcriptional levels in localized breast cancer. PATIENTS AND METHODS: Glycodelin and survivin messenger ribonucleic acid (mRNA) was isolated and amplified by quantitative reverse-trancription PCR from paraffin-embedded breast carcinomas of 275 women. A normalized score was calculated by the use of GAPDH, RPL37A reference genes and was correlated with clinicopathologic/molecular parameters and patient outcome. RESULTS: A total of 272 patients were eligible, most harbored stage III node-positive breast carcinomas larger than 2 cm. Glycodelin mRNA was expressed in 68 patients (25%), more frequently in premenopausal women (P = 0.01) and those with HER2 mRNA-positive tumors (P = 0.02). Survivin mRNA was present in 263 tumors (97%) and its levels correlated significantly with high nuclear grade, VEGF mRNA and p53 mRNA presence (P < 0.05). At a median follow-up of 64 months, neither glycodelin nor survivin mRNA expression demonstrated prognostic utility for overall or disease-free survival at univariate and multivariate analysis. CONCLUSIONS: Glycodelin and survivin transcriptional activity are associated with adverse clinicopathologic and molecular characteristics of node-positive primary breast cancer but do not predict patient outcome. Further study is needed for illumination of their functional roles in tumorigenesis.

Adult↗

Update on treatment recommendations from the Third International Workshop on Waldenstrom's macroglobulinemia.

Waldenström macroglobulinemia (WM) is a B-cell disorder characterized by the infiltration of lymphoplasmacytic cells into bone marrow and the presence of an IgM monoclonal gammopathy. As part of the Third International Workshop on WM, held October 7 to 10, 2004 in Paris, France, a consensus panel charged with providing treatment recommendations for WM updated its recommendations on both frontline and salvage therapies. The panel considered encouraging results from recent studies that addressed the use of extended-dose rituximab as well as other treatment options: therapy with either nucleoside analogs and alkylator agents, rituximab in combination with nucleoside analogs, nucleoside analogs plus alkylator agents, or combination chemotherapies, such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or cyclophosphamide and dexamethasone. The panel determined that these were reasonable treatment options for WM patients and such therapeutic approaches were likely to yield results that are at least as good as if not better than the currently recommended use of single-agent alkylator, nucleoside analog, or standard-dose rituximab therapy. Such approaches were deemed to be reasonable treatment for WM patients in both the upfront and salvage settings, though randomized studies addressing the efficacy and toxicity of such novel approaches over previously established standard of care options are needed.

Alkylating Agents↗

Primary gastrointestinal non-Hodgkin's lymphoma: a clinicopathologic study of 128 cases in Greece. A Hellenic Cooperative Oncology Group study (HeCOG).

The aim of this retrospective study was to illustrate the clinicopathologic data and the treatment results in patients with primary gastrointestinal tract non-Hodgkin's lymphoma (GI NHL). Among 810 patients with NHL, 128 cases (15.8%) were diagnosed as primary GI tract NHL. There were 79 males and 49 females with median age of 62 years. The most common primary site was the stomach (68%). Overall, 67.2% of the patients were in stages I - II, and 32.8% in stages III - IV. Simultaneous involvement of the GI tract and other extranodal sites was observed in 26 patients (20%). Extranodal marginal zone B-cell lymphoma (MZBL) (i.e., low-grade lymphoma of mucosa-associated lymphoid tissue type) accounted for 48.4% of lymphomas. Aggressive lymphomas (diffuse large B-cell lymphoma [DLBL]) accounted for 44.5%. Eighty-three patients (67.5%) achieved complete response (CR), either by surgery (43/43 patients, 17 with DLBL and 25 with MZBL) or by primary chemotherapy (40/64 patients, 22 with DLBL and 17 with MZBL). Sixty-two patients remain in CR; 33/43 after surgical resection (13/17 with DLBL and 20/25 patients with MZBL), and 29/40 after only chemotherapy (18/22 with DLBL and 10/17 with MZBL). The major prognostic factor for outcome in the present study was the stage of the disease. Patients with localized lymphoma (stage I and II) had significantly longer DFS and OS (DFS and OS at 3-year: 83% and 87%, respectively) than patients with extended disease (stage III and IV) (DFS and OS at 3-year: 46% and 60%, respectively) (P < 0.0001). The International Prognostic Index (IPI) for patients with aggressive lymphomas was prognostic only for DFS (79% for low-risk patients [IPI score 0 - 1] vs 49% for higher risk groups [IPI score >1] at 3-year, P = 0.0131).

Adolescent↗

Update on recommendations for assessing response from the Third International Workshop on Waldenstrom's Macroglobulinemia.

This report by an international consensus panel updates current recommendations for defining clinical response in Waldenstrom's macroglobulinemia (WM). The previously published response criteria incorporated parameters for monoclonal protein reduction and/or improvement of marrow and nodal involvement, and included definitions of complete and partial remissions. The criteria have been updated to include minor response and stable disease categories. In addition, the criteria now recognize that delayed responses after treatment with nucleoside analogues and biologic agents and the time point for assessing response in patients with WM should be considered so as to not miss or miscategorize a response. The new criteria should therefore help in better delineating responses to therapy in patients with WM, particularly with the wide use of nucleoside analogues and biologically based agents for this disease.

Antineoplastic Combined Chemotherapy Protocols↗

Combination chemotherapy with gemcitabine and vinorelbine in the treatment of relapsed or refractory diffuse large B-cell lymphoma: a phase-II trial by the Hellenic Cooperative Oncology Group.

To investigate the efficacy and toxicity of the combination of gemcitabine and vinorelbine in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBL), 22 patients with relapsed or refractory DLBL were treated with gemcitabine 1000 mg/m2 and vinorelbine 30 mg/m2 on days 1 and 8 every 3 wk for a maximum of six cycles. Fourteen patients were considered chemosensitive while eight patients were considered chemoresistant to the last treatment regimen. All 22 patients were assessed for response to treatment. Three patients (14%) achieved complete remission and eight patients (36%) had partial remission of their disease, with an overall response rate of 50%. With a median follow up of 44 months, the median time to progression (TTP) for all patients was 8.1 months while the median overall survival (OS) was 12.9 months. Toxicity was minimal and all patients were treated on an outpatient basis. The combination of gemcitabine and vinorelbine is an effective and well-tolerated regimen for patients with relapsed of refractory DLBL.

Adult↗

Multifocal extranodal non-hodgkin lymphoma: a clinicopathologic study of 37 cases in Greece, a Hellenic Cooperative Oncology Group study.

The purpose of this retrospective study was to illustrate the clinicopathological features of patients presenting with multifocal extranodal non-Hodgkin lymphoma (NHL). Among 810 patients with NHL, 37 cases (4.2%) were found to have multiple extranodal involvement (two or more sites). There were 24 men and 13 women, with a median age of 63 years. The majority of these cases (n = 26) had gastric or intestinal (GI) involvement with or without other extranodal sites. Lung along with another extranodal site was relatively common in the present series. Stratification of the 37 cases according to the International Prognostic Index (IPI) showed that 89% of the patients belonged to the high-risk groups. Diffuse large-B-cell lymphoma (DLBCL) accounted for 62%, and mucosa-associated lymphoma tissue (MALT) lymphoma accounted for 27% of all cases. After induction treatment with anthracycline-based regimens, complete remission was achieved in 21 patients (57%), partial remission was achieved in six patients (16%), and seven patients (19%) had no response, while three patients (8%) were nonevaluable. In conclusion, multifocal extranodal NHL is a heterogeneous group of diseases. The majority of them arise at various sites in the GI tract. DLBCL was the most frequent histological subtype followed by MALT lymphoma. Risk group, as defined by the IPI, was predictive of survival.

Adult↗

The international staging system for multiple myeloma is applicable in symptomatic Waldenstrom's macroglobulinemia.

Several studies have indicated that age, hemoglobin and serum albumin are among the most important prognostic factors for survival of patients with Waldenstrom's macroglobulinemia (WM). Furthermore, recent data indicate that serum b2-microglobulin may be also significant. The recently proposed International Staging System (ISS) for multiple myeloma is based on serum albumin and b2-microglobulin. We designed a study to assess this model in patients with WM. Our analysis included 83 previously untreated patients with WM who required systemic treatment and in whom pretreatment values for both serum albumin and b2-microglobulin were available. Based on these variables the patients were stratified into three ISS stages. Stage I: albumin > or = 3.5 g/dl and b2-microglobulin < 3.5 mg/dl, stage II: albumin < 3.5 g/dl and b2-microglobulin < 3.5 mg/gl or b2-microglobulin 3.5-5.5 mg/dl and stage III: b2-microglobulin > 5.5 mg/dl. Low albumin (< 3.5 g/dl) and high b2-microglobulin (> or = 3.5 mg/dl) were recorded in 45% and 52% of patients respectively. The distribution of patients in the three ISS stages was: stage I: 30%, stage II: 43% and stage III: 27%. The median overall survival from the date of treatment initiation was 115 months. The median survival according to ISS was not reached for stage I, 116 months for stage II and 54 months for stage III (P = 0.02). Our analysis indicated that the recently proposed ISS for multiple myeloma could stratify the patients with WM into three distinct subgroups with significantly different survival times. If this model is validated in independent series, it could provide a new staging system for WM based on readily available and reproducible variables.

Adult↗

Rituximab in combination with CNOP chemotherapy in patients with previously untreated indolent non-Hodgkin's lymphoma.

Rituximab, a chimeric monoclonal antibody, produces response rates of up to 73% in patients with previously untreated indolent non-Hodgkin's lymphoma (NHL), and has high activity when combined with chemotherapy. The purpose of this phase II study was to determine the efficacy and safety of rituximab plus cyclophosphamide, mitoxantrone, vincristine and prednisone (CNOP) chemotherapy in patients with indolent NHL. In all, 42 patients (median age 67 years) with previously untreated follicular, marginal zone or small lymphocytic/lymphoplasmacytic NHL received six infusions of rituximab (375 mg/m(2)) in combination with six cycles of CNOP. The overall response rate was 90% comprising 30 complete (71%) and eight partial (19%) responses. Although patients with marginal zone lymphoma or International Prognostic Index (IPI) score 3 had lower complete response rates, no significant difference in overall response rate was observed between the histological groups (P=0.24) or between patients stratified according to IPI score (P>0.05). Median overall survival, time-to-progression and response duration had not been reached after a median 19.5-month follow-up. In all, 31 patients (74%) are currently free from progression and 38 (90%) remain alive. Treatment was well tolerated. One patient (2%) experienced grade 3/4 infusion-related toxicity; 13 (31%) grade 3/4 leukopenia and 18 (43%) grade 3/4 neutropenia. Infection was observed in nine patients: eight (19%) grade 1/2 and one (2.4%) grade 3. This study demonstrates that combining rituximab with CNOP achieves high remission rates without significant additional toxicity in patients with previously untreated indolent NHL. Further follow-up will determine response duration and survival.

Adult↗

Paclitaxel plus carboplatin versus gemcitabine plus paclitaxel in advanced non-small-cell lung cancer: a phase III randomized trial.

PURPOSE: We conducted this randomized study comparing the activity and toxicity of paclitaxel and gemcitabine (PG) and paclitaxel and carboplatin (PC) combinations for the treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients were randomized to paclitaxel 200 mg/m(2) on day 1 plus either carboplatin at an area under the concentration-time curve of 6 on day 1 (group A) or gemcitabine 1,000 mg/m(2) on days 1 and 8 (group B) every 3 weeks. A retrospective cost analysis was conducted using Student's t test to compare independent samples between groups. RESULTS: A total of 509 patients (group A, 252 patients; group B, 257 patients) were enrolled; all characteristics were well balanced. The median survival time was 10.4 months (95% confidence interval [CI], 8.8 to 12 months) for group A and 9.8 months (95% CI, 8.0 to 11.7 months) for group B (P =.32). Respective 1-year survival rates were 41.7% and 41.4%. The response rate for group A was 28.0% (2% complete response [CR], 26% partial response [PR] [95% CI, 22% to 34%]), and the response rate for group B was 35.0% (5% CR, 30% PR) [95% CI, 29% to 41%]) (P =.12). Toxicity was mild. Grades 3/4 neutropenia, thrombocytopenia, and anemia for groups A and B were seen in 15% and 15%, 2% and 1%, and 5% and 2%, respectively. The mean total cost (outpatient clinic visits plus chemotherapy drug fee) for group A (euro; 7,612.64) versus group B (euro; 7,484.77) was not statistically significant (P <.66). CONCLUSION: The PG combination is as equally active and well tolerated as the PC combination in patients with advanced NSCLC.

Adult↗