Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From January 1988 to October 1991, one hundred and twelve patients with non metastatic Ewing's sarcoma of bone were treated with a 6 drugs neoadjuvant chemotherapy protocol (IOR/Ew2) in which, to the four drugs usually used in the treatment of this tumor (vincristine, adriamycin, cyclophosphamide and dactinomycin), Ifosfamide and VP-16 were added. The local treatment consisted of radiation therapy in 52 cases, a surgical treatment was performed in 27 cases and in the remaining 33 cases both the previous treatments were used. At a mean follow-up of 4.5 years (3-6.5), 62 patients (55.3%) remained continuously free of disease and 50 relapsed: 41 with metastases, 8 with mestastases and local recurrence and 1 with local recurrence alone. These results do not differ from the ones obtained in our Institution in 98 patients treated between 1983 and 1988 with a neoadjuvant protocol (IOR/Ew1) in which only VCR, ADM, CTX and actD were used (3 year CDFS: IOR/Ew2 = 60.7%-IOR/Ew1 = 55.1%). In IOR/Ew2 a higher DFS rate was observed in the patients with tumor located in the axile bones in comparison with that obtained in the previous study (IOR/Ew2 = 48.6%, IOR Ew1 = 25.6%). Despite the fact that these results came from a not-randomized study, the authors conclude that the addition of Ifosfamide and VP-16 to the four drugs standard regimen do not improve the outcome of patients with Ewing's sarcoma of bone, with the possible exception of the patients with tumor located in the axile bones. This data should be confirmed in further and larger studies.
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PMID:[Neoadjuvant treatment of Ewing's sarcoma: results obtained in 122 patients treated with a 6-drug chemotherapeutic protocol (vincristine, adriamycin, cyclophosphamide, dactinomycin, ifosfamide and etoposide)]. 868 41

Surgical resection remains the only curative therapy for hepatic metastases from colon and rectal carcinoma. Many patients will be unresectable or have close microscopic margins. Cryoablation may improve local control and survival in those cases. From February 1992 to May 1995, patients with metastatic colon and rectal carcinoma who underwent cryoablation of surgical margins following hepatic resection or cryoablation of hepatic metastases were reviewed with attention to patient and tumor characteristics, clinical course, local control, and survival. Twenty-four patients (10 female, 14 male) with a mean age of 63 years (range, 34-84 years) underwent cryosurgical ablation for hepatic metastases. Twelve were for central lesions and 12 for gross or microscopically positive resection margins. Surgery was performed with curative intent for 21 and for palliation in 3 patients. The mean hospital stay was 8.4 days (range, 5-15 days). Complications included three cases of parenchymal cracking and a single bile leak. Two of 14 patients who developed pleural effusions required treatment. Perioperative mortality was 8.3 per cent (2 of 24): one myocardial infarction and one cerebrovascular accident. Four of 21 treated for cure had hepatic recurrence, and six had only extrahepatic recurrence. Median time to recurrence was 9.5 months. With median follow-up of 19 months, mean actuarial disease-free (DFS) and overall survival (OS) rates are as follows. Those with central lesions (n = 12) had a mean OS rate of 31 months and a mean DFS rate of 23 months. Those with close resection margins (n = 12) had a mean OS rate of 31 months and a median DFS rate of 19.5 months. Total patients (n = 24) had a mean OS rate of 32.7 months and a mean DFS rate of 23.5 months. We conclude that cryoablation of unresectable hepatic metastases or close resection margins is safe and may allow for improved survival in selected patients with metastatic colon and rectal carcinoma.
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PMID:Cryosurgical ablation of hepatic metastases from colorectal carcinomas. 898 74

Motility-related protein-1 (MRP-1)/CD9 is a trans-membrane glycoprotein closely associated with suppression of cell motility and reduced metastatic potential of some tumor cells. We currently report that, according to the RT-PCR method for MRP-1/CD9 gene expression, patients with low expression of MRP-1/CD9 in non-small-cell lung cancer, especially the adenocarcinoma type, showed short overall survival. Then, to determine accurately the prognostic value of MRP-1/CD9 product levels in lung-adenocarcinoma cells, we immunohistochemically investigated its expression in 132 lung-adenocarcinoma patients undergoing potentially curative surgery. Of these patients, 44 (33%) showed reduced expression of MRP-1/CD9 in cancer cells, and an inverse association was observed between its expression and factors associated with tumor progression, such as nodal involvement (p = 0.029) or stage (p = 0.028). Patients with reduced expression of MRP-1/CD9 showed a significantly worse prognosis in overall survival (p = 0.005) and disease-free survival (DFS; p < 0.0001) than those with stronger expression; and even among patients with stage-I disease, similar results were obtained (overall survival, p = 0.038; DFS, p = 0.012). In a multivariate analysis, immunohistochemical MRP-1/CD9-expression level was an independent prognostic factor for DFS (p = 0.021), but not for overall survival (p = 0.572). Thus, immunohistochemical MRP-1/CD9-expression level solely in lung-adenocarcinoma cells within the tumor tissue appears to be a prognostic factor for DFS, and may be useful for detecting a high-risk sub-group of recurrence during the post-operative clinical course of the disease.
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PMID:Immunohistochemically detected expression of motility-related protein-1 (MRP-1/CD9) in lung adenocarcinoma and its relation to prognosis. 913 57

One hundred and seventy three women were followed-up for a median of 62 months after surgery for Stage I-III breast cancer. The concentration of cathepsin D (CD) in tumor cytosols was compared to the standard prognostic factors for the disease and related to relapse free and overall survival and type of relapse. Three groups were identified with different prognostic profile. High CD levels significantly shorten DFS in both node-negative and node-positive patients; a correlation between high cathepsin D levels and locoregional relapse should also be noted. This marker should be included in the initial evaluation of breast cancer as an indicator of invasiveness.
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PMID:Cathepsin D concentration in tumor cytosols improves the accuracy of prognostic evaluation of primary breast cancer. 913 6

Between 1977 and 1994, our center administered successively 4 different chemotherapy regimens to 242 evaluable patients with locally advanced breast cancer. Patients with inflammatory signs were excluded. Sixty-eight patients were treated by AVCF (A (adriamycine) + V (vincristine) + C (cytoxan) + F (5FU)), 47 by AECF (A + E (vindesine) + C + F), 81 by CAFP (C + A + F + P (prednisone)) and 46 by AN (A + N (vinorelbine)). The mean number of cycle was 3. One hundred and twenty-five patients (52.5%) responded to chemotherapy and we recorded 35 complete response (14.7%). The response rates at the different combinations were respectively: AVCF: 29.4%, AECF: 53.2%, CAFP: 64.9%, AN: 65.2%, and were independent of tumor size, grade and receptor status. The response rate at the AVCF regimen was significantly worse than the others (p = 0.0005). Breast conserving surgery was performed in 31 patients (14%) and 17 patients (8%) had a complete response. Among the 35 patients with complete response, 21 were treated by radiotherapy alone. Local recurrence occurred in 19 patients (7.9%) and 96 (40%) had advanced disease. The mean follow-up of AVCF regimen was 150 months, 115 months for AECF, 111 for CAFP and 42 months for AN. The disease-free survival and the overall survival were significantly better with AECF, CAFP and AN regimens (DFS p < 0.04, OS p < 0.02). Survival was better in those patients with an objective response (p = 0.002) or with non-affected axillary node at the time of surgery. Our study showed already that AVCF combination was significantly lower than AECF, CAFP, AN in terms of response rate, disease-free survival and overall survival. Waiting the results of randomized studies about the impact of neoadjuvant chemotherapy on survival, we look for chemotherapy regimen improving the rate of conservative surgery.
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PMID:[A comparative study of 4 sequential first-line chemotherapy protocols in locally advanced breast cancer]. 918 Aug 53

The prognostic significance of Bcl-2 protein expression and bcl-2 gene rearrangement in diffuse large cell lymphomas (DLCL) is controversial. Bcl-2 protein expression prevents apoptosis and may have an important role in clinical drug resistance. The presence of a bcl-2 gene rearrangement in de novo DLCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior more akin to low-grade non-Hodgkin's lymphoma (NHL). The purpose of this study was to determine the impact of Bcl-2 protein expression and bcl-2 gene rearrangement (mbr and mcr) on survival of a cohort of patients with DLCL who were uniformly evaluated and treated with effective chemotherapy. Patients included the original MACOP-B cohort (n = 121) and the initial 18 patients treated with the VACOP-B regimen (total = 139). All patients had advanced-stage disease, were 16 to 70 years old, and corresponded to Working Formulation categories F, G, or H. No patients had prior treatment, discordant lymphoma, or human immunodeficiency virus seropositivity. Paraffin sections from diagnostic biopsies were analyzed for bcl-2 gene rearrangement including mbr and mcr breakpoints by polymerase chain reaction and Bcl-2 protein expression by immunohistochemistry. With a median follow-up of 81 months, overall (OS), disease-free (DFS), and relapse-free survival (RFS) were measured to determine the prognostic significance of these parameters. Analyzable DNA was present in 118 of 139 (85%) cases, with 14 demonstrating a bcl-2 rearrangement (11 mbr, 3 mcr). All 14 of these bcl-2 gene rearrangement-positive cases were found in the 102 patients with a B-cell immunophenotype, but the presence of this rearrangement had no significant influence on survival. Bcl-2 protein expression was interpretable in 116 of 139 (83%) cases, with immunopositivity detected in 54 of 116 (47%). Using a cut-off of greater than 10% Bcl-2 immunopositive tumor cells for analysis, positive Bcl-2 protein expression was seen in 28 of 116 (24%) patients and the presence of this expression correlated with decreased 8-year OS (34% v 60%, P < .01), DFS (32% v 66%, P < .001), and RFS (25% v 59%, P < .001). Bcl-2 protein expression remained significant in multivariate analysis that included the clinical international prognostic index factors and immunophenotype (P < .02). In conclusion, although bcl-2 gene rearrangement status could not be shown to have an impact on outcome, Bcl-2 protein expression is a strong significant predictor of OS, DFS, and RFS in DLCLs.
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PMID:Prognostic significance of Bcl-2 protein expression and Bcl-2 gene rearrangement in diffuse aggressive non-Hodgkin's lymphoma. 920 59

The value of cathepsin D determinations done on tumor cytosols in evaluating the prognosis of breast cancer patients has been debated in the literature. Our previous work suggested that cathepsin D determinations were not of prognostic value, but in that study we used immunoblotting and immunohistochemical methods rather than the more widely used double antibody immunoradiometric (IRMA) assay for measuring cathepsin levels. Here we report our results determining cathepsin D using components of a commercially available IRMA system on a large patient sample (n = 1984). Reagents from a commercially available IRMA kit were used to analyze cathepsin D levels in the cytosols of 1984 patients with breast cancer. All patients had invasive breast cancer with known tumor size and with some axillary nodes pathologically examined. Only patients with T1 and T2 tumor sizes were included. Median follow-up was 37 months. The hypothesis that high cathepsin D levels correlated with poorer outcome (poorer DFS or OS) was not confirmed, either in all patients, or in node-positive or node-negative subsets. Only in patients treated with adjuvant therapy were higher cathepsin D levels correlated with negative outcome (worsened OS, but not DFS), although given the large number of subsets analyzed this correlation may be spurious. Multivariate analyses using interaction terms did not support the concept that high cathepsin D levels correlate with resistance to adjuvant therapy. In this study evaluating the value of cathepsin D using components from a kit widely used for measuring cathepsin D levels, we conclude that cathepsin D is of doubtful value in predicting risk of early relapse or death for patients with newly diagnosed invasive breast cancer.
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PMID:Lack of prognostic value of cathepsin D levels for predicting short term outcomes of breast cancer patients. 921 61

Radiotherapy is an effective treatment for localized prostate cancer. A dose response relationship has been demonstrated for both local tumor control and complications. Reducing the volume of normal tissue treated may allow dose escalation without an increase in RT induced side effects. Androgen blockade before RT could, by reducing tumor volume, increase local control, disease-free (DFS) and overall survival in patients (pts) with prostatic adenocarcinoma. A total of 79 patients with T2-T4 prostate cancer have been treated initially with LHRH agonists and cyproterone acetate followed by radical irradiation between 1988 and 1993. The first cohort of 22 patients were monitored intensively by transrectal ultrasound and computed tomography. For each patient conformal photon beam radiotherapy and conventional treatment plans were produced and dose volume histograms compared for total volume, rectal volume, and bladder volume. Overall mean reduction of prostate volume was about 50%, and radiotherapy target volume was reduced by 37%. 53 further patients without clinical evidence of regional or distant metastases were given 3 months preradiotherapeutic hormonal cytoreduction with a short course of cyproterone acetate and LHRH. PSA level fell rapidly in most patients and after 3 months treatment the median PSA level was 1 ng/ml and 83% had PSA level 10 ng/ml. At 18 months PSA levels continued to be < 2 ng/ml in 70% of the patients. Combined modality treatment with the neoadjuvant or adjuvant androgen deprivation and conformal therapy show considerable promise as novel methods to improve the therapeutic ratio. This treatment approach may be used to explore the possibility of dose escalation in prostate cancer to enhance local control, and therapeutic randomised studies are underway to test these approaches.
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PMID:[Basic principles and initial results of adjuvant hormone therapy and irradiation of prostatic carcinoma]. 948 May 9

From February 1992 to November 1993, forty patients with operable breast cancer tumors larger than three centimeters were enrolled in this study of accelerated neo-adjuvant chemotherapy. Thirty-seven patients are evaluable: one patient was excluded from the protocol and two refused to continue treatment after the first cycle. Chemotherapy consisted of three presurgical cycles of CNF [cyclophosphamide at 600 mg/m2, mitoxantrone (Novantrone) at 10 mg/m2 and 5-fluorouracil at 600 mg/m2] administered every 2 weeks, plus G-CSF (5 microg/kg s.c./day on days 7-12). Twenty-six of 37 patients (70%) achieved objective tumor response and were submitted to quadrantectomy. Toxicity was easily manageable. After a median 55-month follow-up (range 48-70), no locoregional recurrences were observed. Distant metastases occurred in 12/37 (32%) patients. The five-year disease-free (DFS) and overall (OS) survival were 58% and 80%, respectively. Accelerated CNF plus G-CSF proved to be a safe and tolerable regimen yielding a good clinical response thereby increasing the possibility of breast conservation surgery for patients otherwise candidates for mastectomy.
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PMID:Neoadjuvant chemotherapy with accelerated CNF plus G-CSF in patients with breast cancer tumors larger than three centimeters: a pilot study. 953 46

Tumor biological factors uPA, PAI-1, cathepsin D, S-phase fraction (SPF), MIB1 (Ki-67), p53, and HER-2/neu were assessed in 100 node-negative breast cancer patients. Their prognostic impact on disease-free (DFS) as well as overall survival (OS) was compared to that of traditional factors tumor size, grading, and steroid hormone receptor status. Antigen levels of uPA, its inhibitor PAI-1, and cathepsin D were determined in tumor tissue extracts by immunoenzymatic methods. SPF was determined by flow cytofluorometry, MIB1, p53, and HER-2/neu by immunohistochemistry in adjacent routinely formalin-fixed paraffin sections. Median follow-up in all patients still alive at time of analysis was 76 months. Univariate analysis determined PAI-1 (p = 0.0001), uPA (p = 0.0437), MIB1 (p = 0.0214), and SPF (p = 0.0248) as statistically significant prognostic factors for DFS. In contrast, tumor size, steroid hormone receptor status, grading, p53, HER-2/neu, and cathepsin. D failed to be of prognostic value. In multivariate analysis, including the statistically significant prognostic factors PAI-1, uPA, MIB1, and SPF, only PAI-1 (p = 0.0003, relative risk: 4.7) proved to be of independent statistical significance for DFS. Regarding OS, PAI-1 was the only statistically significant prognostic factor in univariate (p = 0.0001) as well as multivariate analysis (p = 0.0000, relative risk: 7.1). Thus, factors describing the invasive and metastatic capacity of tumor cells (uPA, PAI-1) and factors related to their proliferative activity (SPF, MIB1) provide valuable prognostic information in node-negative breast cancer patients.
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PMID:Prognostic impact of tumor biological factors on survival in node-negative breast cancer. 970 82


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