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Biomedical subjects

G P Stathopoulos

Publications and source records attributed to G P Stathopoulos.

At least 19 recordsLinked to original sources
PubMed2006

Weekly administration of topotecan-paclitaxel as second-line treatment in ovarian cancer.

PURPOSE: To investigate the weekly administration of topotecan combined with paclitaxel in pretreated advanced ovarian cancer patients; our objectives were to determine efficacy, toxicity and survival. METHODS: The chemotherapy agents, topotecan and paclitaxel were administered on a weekly basis for 3 consecutive weeks, every 28 days. The plan was to give three courses (each course included three once-weekly infusions). The dose of topotecan was 1.75 mg/m(2) and of paclitaxel 70 mg/m(2). RESULTS: From January 2004 until January 2006, 45 patients were enrolled in this multicenter trial; 44 patients were evaluable for response and toxicity. The median age was 60 years old (range 39-82 years) and performance status was 0-2. Thirty-nine patients were in stage III and 5 in stage IV. All patients had been pretreated with carboplatin or cisplatin in combination with paclitaxel. Complete and partial responses were seen in 39% of the patients, stable disease in 43% and progressive disease in 18%; median survival time was 9 months, range 2-24+ months, (95% CI: 7.9-10.2). There was a notable absence of grade 3 toxicity except for neutropenia in 11% of the patients. CONCLUSION: The combination of topotecan and paclitaxel administered on a weekly basis is a well-tolerated chemotherapy schedule. The response rate of 39% is quite high for patients with pretreated ovarian cancer.

Adult↗
PubMed2006

A multicenter phase III trial comparing irinotecan-gemcitabine (IG) with gemcitabine (G) monotherapy as first-line treatment in patients with locally advanced or metastatic pancreatic cancer.

Our purpose was to determine the response rate and median and overall survival of gemcitabine as monotherapy versus gemcitabine plus irinotecan in advanced or metastatic pancreatic cancer. Patients with histologically or cytologically confirmed adenocarcinoma who were chemotherapy and radiotherapy naive were enrolled. Patients were centrally randomised at a one-to-one ratio to receive either gemcitabine monotherapy (900 mg m(-2) on days 1, 8 and 15 every 4 weeks (arm G), or gemcitabine (days 1 and 8) plus irinotecan (300 mg m(-2) on day 8) (arm IG), repeated every 3 weeks. The total number of cycles administered was 255 in the IG arm and 245 in the G arm; the median number of cycles was 3. In all, 145 patients (71 in arm IG and 74 in arm G) were enrolled; 60 and 70 patients from arms IG and G, respectively, were evaluable. A complete clinical response was achieved in three (4.3%) arm G patients; nine (15%) patients in arm IG and four (5.7%) in arm G achieved a partial response. The overall response rate was: arm IG 15% and arm G 10% (95% CI 5.96-24.04 and 95% CI 2.97-17.03, respectively; P=0.387). The median time to tumour progression was 2.8 months and 2.9 months and median survival time was 6.4 and 6.5 months for the IG and G arms, respectively. One-year survival was 24.3% for the IG arm and 21.8% for the G arm. No statistically significant difference was observed comparing gemcitabine monotherapy versus gemcitabine plus irinotecan in the treatment of advanced pancreatic cancer, with respect to overall and 1-year survival.

Adenocarcinoma↗
PubMed2006

Front-line paclitaxel and topotecan chemotherapy in advanced or metastatic non-small-cell lung cancer: a phase II trial.

PURPOSE: Based on previous experience, we combined topotecan with paclitaxel (weekly administration) in patients with non-small-cell lung cancer (NSCLC). Our primary objective was to determine the response rate and survival and our secondary objective, the safety of the regimen. METHODS: From October 2003, until March 2005, 45 patients all with histologically or cytologically confirmed NSCLC were enrolled. All patients were chemotherapy and radiotherapy naive. Both agents were infused on day 1 of every week once for three consecutive weeks, every 28 days. Three infusions were considered as one course. The treatment plan was to give three courses (nine infusions) and then to evaluate the response. Topotecan (1.75 mg/m2) was infused for 30 min and paclitaxel (70 mg/m2) for 90 min; these doses had been established as the maximum tolerated dose in a previous phase I-II trial. RESULTS: Eighteen/45 (40%) patients responded, 2 (4.4%) complete responses and 16 (35.6%) partial responses. Twenty-one (46.7%) patients had stable disease, and 6 (13.3%) disease progression. The median duration of response was 8 months and median time to tumor progression 9 months. Grade 3 and 4 neutropenia was observed in two patients (in these two patients, the dose of both drugs was reduced by 25% and G-CSF was given), grade 4 thrombocytopenia in one patient and grade 4 anemia in one patient. CONCLUSION: This novel combination of topotecan-paclitaxel in a weekly administration rendered a 40% response rate, with very low toxicity in stages IIIA, IIIB and IV NSCLC patients.

Aged↗
PubMed2005

Front-line paclitaxel and irinotecan combination chemotherapy in advanced non-small-cell lung cancer: a phase I-II trial.

Our purpose was to determine the efficacy of irinotecan plus paclitaxel administered on day 1, repeated every 2 weeks, in untreated patients with advanced or metastatic non-small-cell lung cancer (NSCLC). In total, 56 patients with inoperable or metastatic stage III and IV NSCLC with a histologically or cytologically confirmed diagnosis were enrolled. None of the patients had undergone prior chemotherapy or radiation therapy. Treatment involved irinotecan 125 mg m(-2) and paclitaxel 135 mg m(-2) administered on day 1 and repeated every 2 weeks for a planned number of nine cycles. With a standard dose of paclitaxel at 135 mg m(-2), the dosage of irinotecan was escalated at four levels: 75, 100, 125 and 150 mg m(-2); 125 mg m(-2) was established as the maximum tolerated dose; this dosage was administered to 46 patients. A total of 52 patients (median age 65 years, range 38-77 years) were assessable for toxicity and survival and 46 for response rate. Out of 46 evaluable patients, 19 achieved partial response (41.3%), 17 had stable disease (37%) and 10 (21.7%) experienced disease progression. The median duration of response was 6 months (range 2-9+ months). The main adverse reactions were myelotoxicity (grades 3 and 4) in 10 (19.2%) patients and diarrhoea (grade 3) in four (7.7%) patients. Irinotecan combined with paclitaxel, administered every 2 weeks, appears to be an effective treatment for advanced-stage NSCLC.

Adult↗
PubMed2005

Second-line chemotherapy in small cell lung cancer in a modified administration of topotecan combined with paclitaxel: a phase II study.

PURPOSE: Our main objective was to investigate the response rate in pretreated patients with small cell lung cancer (SCLC) who received a weekly administration of topotecan and paclitaxel; our secondary objectives were to assess toxicity and survival. METHODS: Topotecan 1.75 mg/m2 was combined with paclitaxel 70 mg/m2; these cytotoxic agents were administered once every week (day 1) for 3 consecutive weeks (one cycle), and repeated every 28 days (three infusions per cycle) for a minimum of three cycles. RESULTS: Forty-five patients were enrolled, 41 of whom were evaluable for response and toxicity. The median number of cycles was two (range 1-6). Eleven/forty-one (26.83%) patients responded: one complete response and ten partial responses; the median duration of response was 4 months (range 2-8 months); the median overall survival was 7 months (95% CI: 4.2-9.8). Myelotoxicity was the most common adverse reaction (grade 3 neutropenia in 19.5% of the patients and grade 4 in 7.32%). Non-hematologic toxicities varied from 2.44% to 9.76%. No patient had to stop treatment due to toxicity. CONCLUSION: Topotecan combined with paclitaxel, given on day 1 on a weekly basis, produced a response rate of 26.83% in pretreated patients with SCLC. Myelotoxicity, particularly neutropenia, was the main adverse reaction, but in a minority of patients.

Adult↗
PubMed2005

Paclitaxel plus carboplatin versus paclitaxel plus alternating carboplatin and cisplatin for initial treatment of advanced ovarian cancer: long-term efficacy results: a Hellenic Cooperative Oncology Group (HeCOG) study.

BACKGROUND: We compared the combination plus Carboplatin plus paclitaxel, which is considered the treatment of choice for initial chemotherapy of advanced ovarian cancer (AOC) with a regimen combining alternating carboplatin and cisplatin plus paclitaxel. The two platinum derivatives have been previously combined as they are not totally cross-resistant and as they share no overlapping toxicities. PATIENTS AND METHODS: Patients with AOC, after the initial cytoreductive surgery were randomized to either 6 courses of paclitaxel at 175 mg/m2 as 3 h infusion plus Carboplatin at 7 AUC (Arm A) or Paclitaxel at the same dose plus Carboplatin again at 7 AUC for cycles 1,3,5, while for cycles 2,4,6 Cisplatin at 75 mg/m2 substituted for Carboplatin (Arm B). RESULTS: 247 patients are analyzed. Significant differences were not found, both in terms of PFS (38 vs 39 months, p=0.95) and overall survival (40.6 vs 38.6 months, p=0.79). There was not also difference in 5-year survival rate (35% vs 39%) or 5-year PFS rate (23% vs 28%). Age >60, PS 2, stage IV disease and presence of residual disease were adversely related to the overall survival. CONCLUSION: Both regimens are well tolerated and effective. Alternating cisplatin with carboplatin does not improve the results compared with the standard combination.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Irinotecan combined with docetaxel in pre-treated metastatic breast cancer patients: a phase II study.

PURPOSE: This is a phase II study where a novel chemotherapy combination was tested in pre-treated breast cancer patients: docetaxel and irinotecan have already been established as agents for breast and colorectal cancer, respectively. METHODS: Forty-eight (median age 54 years, range 26-77 year) patients, all evaluable, were enrolled. All patients had been pre-treated with anthracycline-combined chemotherapy, 30 of whom were also treated with paclitaxel and 2 with docetaxel. World Health Organization (WHO) performance status was 0-2. The dominant metastasis was in the liver (54.17%), in the lungs (27.08%), in soft tissues (12.50%) and in the skeleton (6.25%). Treatment involved irinotecan infusion 200 mg/m(2) for 90 min and docetaxel infusion 80 mg/m(2) for 90 min, repeated once every 3 weeks. RESULTS: Twenty-five (52.08%, 95% confidence interval [CI] 37.95-66.21) patients showed responses: 3 complete (6.25%, 95% CI 0-13.05) and 22 (45.83%, 95% CI 31.74-59.92) partial; the most responsive metastases were observed at the liver site (53.85%). Grade 3 and 4 neutropenia was observed in 18 patients (37.50%); 14 (29.17%) patients developed anaemia and three (6.25%), thrombocytopenia. Concerning non-haematologic toxicity, alopecia and fatigue were common; grade 3 diarrhea was observed in only one (2.08%) patient. CONCLUSION: The irinotecan-docetaxel combination produces quite a high response rate in pre-treated advanced breast cancer patients.

Adult↗
PubMed2004

Front-line treatment of inoperable or metastatic pancreatic cancer with gemcitabine and capecitabine: an intergroup, multicenter, phase II study.

PURPOSE: To evaluate the efficacy and toxicity of gemcitabine (GEM) combined with capecitabine (CAP) in untreated patients with inoperable or metastatic pancreatic cancer. PATIENTS AND METHODS: Fifty-three patients with pancreatic cancer (85% stage IV) were enrolled. Patients were treated with GEM 1000 mg/m2 on days 1 and 8 and CAP 1300 mg/m2 per day PO (per os), divided into two equal doses on days 1-14, in 21-day cycles. RESULTS: In an-intention-to-treat analysis, 10 (18.9%) objective partial responses were achieved (95% confidence interval 8.33% to 29.4%). Twenty-two (42%) patients had stable disease and 15 (28%) had progressive disease. The median response time was 3 months (range 1.5-7.0) and the median time to tumor progression was 6.5 months (range 3.5-15.5). Median overall survival time was 8 months (range 1.0-15.5) and 1-year survival was 34.8%. Pain improvement during treatment was observed in 23 of 43 (53%) patients, and eight of 18 (44%) patients who had been receiving opioids discontinued their use. Weight gain was observed in 12 of 33 (36%) patients. Grade 3 anemia occurred in five (9%) patients and grade 3-4 thrombocytopenia occurred in three (6%). Grade 3-4 neutropenia occurred in 13 (25%) and five (9%) patients, respectively, and two (4%) developed febrile neutropenia. Non-hematological toxicity was mild. CONCLUSION: In patients with pancreatic cancer, the combination of GEM with CAP is an active and well tolerated regimen that merits further evaluation in prospective randomized studies.

Adenocarcinoma↗
PubMed2004

Front-line paclitaxel-vinorelbine versus paclitaxel-carboplatin in patients with advanced non-small-cell lung cancer: a randomized phase III trial.

PURPOSE: This randomized phase III trial of advanced or metastatic non-small-cell lung cancer (NSCLC) was designed to compare a standard treatment such as carboplatin (CRP)-paclitaxel (PCT) with a new combination, vinorelbine (VRL)-PCT-two agents acting in microtubules. PATIENTS AND METHODS: Three hundred and sixty patients (stage IIIa, IIIb and IV) were included and evaluated for response rate, survival and toxicity. Arm A patients were treated with the control combination of CRP 6 AUC and PCT 175 mg/m(2) repeated every 3 weeks for six cycles, and arm B with the investigational combination of VRL 25 mg/m(2) and PCT 135 mg/m(2) repeated every 2 weeks for nine cycles. The patients were well balanced with respect to gender, disease stage and performance status. Arm A received 849 cycles (mean 4.59 per patient) and arm B 951 cycles (mean 5.39 per patient). RESULTS: Complete and partial response rates were 45.95% and 42.86% for arms A and B, respectively. Median survival was 11 and 10 months, 1-year survival 42.7% and 37.85% and 2-year survival 10.12% and 19% for arms A and B, respectively. Toxicity was similar in all patients, except for neutropenia, which was significantly greater in arm B. CONCLUSIONS: PCT combined with VRL produces similar (non-significant) response rates, survival and toxicity (except for neutropenia, as noted above) to standard CRP-PCT treatment in untreated advanced-stage NSCLC.

Adult↗
PubMed2003

Treatment of pancreatic cancer with a combination of irinotecan (CPT-11) and gemcitabine: a multicenter phase II study by the Greek Cooperative Group for Pancreatic Cancer.

BACKGROUND: The efficacy and toxicity of gemcitabine (GEM) and irinotecan (CPT-11) is evaluated in previously untreated patients with inoperable or metastatic pancreatic cancer. PATIENTS AND METHODS: From January 1999 to July 2001, 60 patients with pancreatic cancer (85% stage IV) were enrolled in a two-step extended phase II trial. Patients were treated with gemcitabine (1,000 mg/m2 on days 1 and 8) and CPT-11 (300 mg/m2 on day 8) in cycles of 3 weeks. No prophylactic use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was initially planned. RESULTS: In an intention-to-treat analysis one (1.7%) complete and 14 (23.3%) partial responses were achieved [objective response rate (ORR) 24.7%; 95% confidence interval 14.04% to 35.96%]. Twenty-two (36.7%) and 23 (38.3%) patients had stable and progressive disease, respectively. The median duration of response was 5 months, the median time to tumor progression (TTP) was 7 months and the median overall survival 7 months. One-year survival was 22.5%. Pain improvement and asthenia during treatment were observed in 45% and 43% of patients, respectively; weight gain occurred in 19.5% of patients. Grade 3 anemia occurred in three (5%) patients who required transfusion of six packed red blood cell (RBC) units. Ten (16.7%) additional patients with grade 2 anemia were treated with recombinant erythropoietin. Grade 3 thrombocytopenia occurred in seven (11.7%) patients and grades 3 and 4 neutropenia in 27 (45%). Ten patients developed febrile neutropenia, two of whom died due to sepsis. Prophylactic use of rhG-CSF was eventually required in 93 (28.3%) of 329 administered cycles. Other toxicities were mild. CONCLUSIONS: The combination of gemcitabine and irinotecan is an active chemotherapy regimen against pancreatic cancer with a 25% ORR. Toxicity was acceptable for the great majority of patients but with a high percentage of hematopoietic growth factor administration.

Aged↗
PubMed2003

Co-expression of trypsin and tumour-associated trypsin inhibitor (TATI) in colorectal adenocarcinomas.

Trypsin and its specific inhibitor, TATI (tumour-associated trypsin inhibitor), are expressed in normal human pancreas and in a variety of tumours. The aim of the present study was to assess the parallel expression of trypsin and TATI in colorectal cancer, in comparison with their expression in normal epithelial tissue, since proteases and their inhibitors are thought to be co-expressed in malignant neoplasms. We also assessed the possible significance of their expression as a means of differentiation between normal and malignant tissue. We examined qualitatively and semi-quantitatively the immunohistochemical expression of trypsin and TATI on paraffin-embedded serial tissue sections from 91 colorectal adenocarcinomas. The reverse-transcriptase-polymerase-chain reaction (RT-PCR) was also performed on fresh malignant tissue from 55 of the above adenocarcinomas. Normal and non-malignant tissues adjacent to the tumours were also evaluated. Cytoplasmic expression of trypsin (more than 25% of the cancer cells positive) was found in 67 (73.6%) adenocarcinomas, whereas TATI was expressed in the cytoplasm of 59 (64.8%) cases studied. Statistical analysis using Spearman's test has demonstrated a significant correlation between trypsin and TATI immunohistochemical expression (p<0.01). RT-PCR showed co-expression of trypsin and TATI mRNA in all carcinomas studied. Distinct patterns of trypsin and TATI immunohistochemical expression were observed in adjacent, non-malignant tissues, where both trypsin and TATI mRNA were also detected. Normal tissues were negative by immunohistochemistry. Our results indicate co-expression of trypsin and TATI in colorectal tumours both at the mRNA and protein level. We conclude that in colorectal neoplasms, high levels of trypsin and TATI may be important for malignant tumour formation and/or metastatic process.

Adenocarcinoma↗
PubMed2001

A phase II study of 9-nitrocamptothecin in patients with advanced pancreatic adenocarcinoma.

PURPOSE: Preclinical and phase I clinical data suggest that 9-nitrocamptothecin (9NC) is an agent with potential anticancer activity. A phase II study was undertaken in order to evaluate the potential benefit of oral 9NC administration in patients with advanced pancreatic cancer. This was the first clinical study of 9NC in Europe. METHODS: A total of 19 consecutive patients with locally advanced or metastatic adenocarcinoma were enrolled (8 males and 11 females, aged 37-73 years). The patients were given 9NC orally five times a week, once a day. The end-points of this study were toxicity, objective response rate, subjective response rate (i.e. pain control, performance status and body weight), and survival. RESULTS: An objective response was documented in 4 of the 14 evaluable patients (28.6%), while a subjective response was observed in 13 patients (92.9%). Overall median survival was 21 weeks (31 weeks in the group of 14 patients evaluable for response), and the 1-year survival was 16.7% and 23.1%, respectively. Toxicity leading to temporary discontinuation of 9NC was encountered in seven patients (36.8%), all related to a prior dose increase, while milder toxicity was observed in eight patients (42.1%). CONCLUSIONS: 9NC administered orally to patients with advanced pancreatic cancer gave promising results, while the toxicity of the therapy was mild and readily overcome. A larger scale clinical trial should be organized in order to establish the potential benefit of 9NC in patients with pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed2001

Treatment of pancreatic cancer with a combination of docetaxel, gemcitabine and granulocyte colony-stimulating factor: a phase II study of the Greek Cooperative Group for Pancreatic Cancer.

PURPOSE: To evaluate the tolerance and efficacy of front-line docetaxel plus gemcitabine treatment in patients with inoperable pancreatic cancer. PATIENTS AND METHODS: Fifty-four patients with locally advanced or metastatic pancreatic cancer were enrolled. Gemcitabine (1000 mg/m2) was administered on days 1 and 8 and docetaxel (100 mg/m2) on day 8, every three weeks; rh-G-CSF (150 ig/m2 s.c.) was given prophylactically on days 9-15. RESULTS: Seven (13%) patients achieved partial response and 18 (33%) stable disease (intent-to-treat). The median duration of response was 24 weeks, time to tumour progression 32 weeks, and overall survival 26 weeks. Performance status was improved in 33% of patients, pain in 43%, asthenia in 16%, weight gain in 28% and appetite in 27%. Grade 3-4 neutropenia occurred in 17 (31%) patients and grade 3-4 thrombocytopenia in four (4%). Six (11%) patients developed febrile neutropenia and one of them died from sepsis. CONCLUSIONS: This combination is a relatively well-tolerated out-patient regimen for patients with inoperable pancreatic cancer.

Adult↗
PubMed2001

Angiogenesis and apoptosis-related protein (p53, bcl-2, and bax) expression versus response of gastric adenocarcinomas to paclitaxel and carboplatin chemotherapy.

The role of angiogenesis and apoptosis-related proteins in defining response to chemotherapy is poorly understood. We examined the microvessel density (MVD) and the expression of p53, bcl-2, and bax proteins in a series of 28 locally advanced gastric adenocarcinomas, treated with paclitaxel and carboplatin. A strong cytoplasmic reactivity in more than 10% of cancer cells was recorded in 25% of cases for p53 protein, and in 14% and 64% of cases for bcl-2 and bax proteins, respectively. Microvessel density was assigned in three categories: low (<35), medium (35-60), and high (>60). Tumors of medium MVD showed a significantly higher response rate compared with those of high or low MVD (p = 0.01 and 0.001, respectively), and prognosis was significantly better in this group of patients with medium MVD tumors (p < 0.02). Loss of bax protein expression was somewhat more frequent in tumors resistant to chemotherapy, but this difference was not of statistical significance. Nuclear p53 reactivity was associated with higher MVD (p = 0.02). The expression of p53 and bcl-2 did not influence the outcome of treatment. The present study suggests that although apoptosis-related proteins may have a role in defining response to taxanes, parameters related to tumors' vasculature, such as drug availability or angiogenic tissue regeneration, may be equally important.

Adenocarcinoma↗
PubMed2000

Synergy between interleukin-2 and prothymosin alpha for the increased generation of cytotoxic T lymphocytes against autologous human carcinomas.

Peripheral blood mononuclear cells (PBMC) from cancer patients were cultured in vitro with irradiated autologous tumor cells isolated from malignant effusions (mixed lymphocyte tumor cultures, MLTC) and low-dose (50 IU/ml) recombinant interleukin-2 (IL-2). The combination of IL-2 and prothymosin alpha (ProTalpha) resulted in a greater PBMC-induced response to the autologous tumor than that brought about by IL-2 alone. In particular, ProTalpha specifically enhanced the CD4+ T-cell-mediated proliferation against the autologous tumor. CD4+ T cells seemed to recognize tumor antigens presented by HLA-DR molecules expressed on the autologous monocytes, since preincubation of the latter with an anti-HLA-DR monoclonal antibody (mAb) abrogated the response. In addition, MLTC set up with IL-2 and ProTalpha also generated more MHC-class-I-restricted cytotoxic T lymphocytes (CTL) against the autologous tumor than did MLTC set up with IL-2 alone. The MLTC-induced CTL contained high levels of cytoplasmic perforin and their development was strictly dependent on the presence of both autologous CD4+ T cells and monocytes. In the absence of either population there was a strong impairment of both proliferative and cytotoxic responses which was not restored by the presence of ProTalpha. In contrast, when both cell populations were present, ProTalpha exerted optimal enhancement of CD4+ T cell proliferation, which was associated with potentiated CTL responses. Our data emphasize the role of ProTalpha for the enhancement of IL-2-induced CTL responses against autologous tumor cells. Such responses require collaborative interactions between CD4+, CD8+ T cells and monocytes as antigen-presenting cells. Our data are relevant for adoptive immunotherapeutic settings utilizing IL-2 and ProTalpha-induced autologous-tumor-specific CTL.

Aged↗
PubMed2000

Angiogenic interactions of vascular endothelial growth factor, of thymidine phosphorylase, and of p53 protein expression in locally advanced gastric cancer.

The assessment of the angiogenic profile of tumors may become an important tool as a guide for the inclusion of novel drugs and molecular therapies into the standard chemoradiotherapy policy. Several studies have shown the prognostic importance of microvessel density (MVD) and of angiogenic factor expression in operable gastric cancer. In the present study we investigated, with immunohistochemistry the MVD, the expression of vascular endothelial growth factor (VEGF) and of thymidine phosphorylase (TP) expression, as well as the nuclear expression of p53 protein, in a series of patients with locally advanced inoperable gastric cancer. A strong association of VEGF with TP expression was noted (P = 0.005), and tumors coexpressing these factors had a statistically higher MVD (P = 0.0001). Nuclear p53 accumulation was also related to a high MVD (P = 0.004), and this was independent of VEGF or TP expression. Microvessel density showed a bell-shaped association with prognosis; cases with an intermediate MVD exhibit a favorable outcome (P < 0.05). A trend of nuclear TP expression to define a group of patients with poorer prognosis was noted (P = 0.06), while none of the remaining variables showed any significant association. The immunostaining results allowed the grouping of the angiogenic profile in four major categories: 1) highly vascularized tumors with VEGF and/or TP expression (about 36% of cases); 2) highly angiogenic tumors with p53 nuclear accumulation and low VEGF/TP expression (7% of cases); 3) poorly vascularized tumor with low VEGF/TP and negative nuclear p53 staining (32% of cases); 4) poorly vascularized tumors with TP expression (7% of cases). Specific therapies targeting hypoxia, VEGF, or TP expression as well as p53 gene therapy have entered clinical experimentation or are already available for clinical use. Using the suggested markers more than 80% of locally advanced gastric carcinomas can be grouped in different categories according to their angiogenic profile. Such a categorization may be useful for phase III trials on novel therapies targeting the major angiogenesis-related features studied here.

Adenocarcinoma↗
PubMed1999

Combined role of tumor angiogenesis, bcl-2, and p53 expression in the prognosis of patients with colorectal carcinoma.

BACKGROUND: The objective of this study was to evaluate intratumoral neoangiogenesis in Dukes Stage B and Stage C (AJCC/UICC Stage I and III) colorectal adenocarcinoma and its correlation with nuclear p53 oncoprotein accumulation and cytoplasmic bcl-2 expression as well as to assess the prognostic significance of these features in patient outcome. METHODS: Paraffin embedded specimens from 55 patients with Dukes Stage B (AJCC/UICC Stage I) and 51 patients with Dukes Stage C (AJCC/UICC Stage III) colorectal adenocarcinoma who were treated with surgery were assessed. Patients with lymph node involvement (Dukes Stage C [AJCC/UICC Stage III]) also were treated with postoperative pelvic radiotherapy and adjuvant chemotherapy with 5-fluorouracil and leucovorin with or without interferon-alpha. Immunohistochemistry was performed using the anti-CD31 monoclonal antibody (MoAb) for vessel staining, the DO7 MoAb for nuclear p53 expression, and the clone 124 for cytoplasmic/perinuclear bcl-2 expression. Patient follow-up ranged from 4-70 months (median, 28 months). RESULTS: High vascular grade (microvessel score [MS] >/= 40) was observed in 39 of 106 specimens (37%), a medium MS (16-39) was observed in 29 of 106 cases (27%), and a low MS (7-15) was observed in 38 of 106 cases (36%). Positive expression of the bcl-2 protein in > 10% of cells was observed in 33 of 106 cases (31%), whereas p53 nuclear oncoprotein accumulation in > 10% of cells occurred more frequently (44 of 106 cases [42%]). No correlation among p53 expression, bcl-2 expression, and vascular grade was observed. Stroma infiltration by CD31 positive lymphocytes was associated strongly with increased vessel density (P = 0.0001). In univariate analysis Dukes stage was the only significant prognostic parameter (P = 0.02), whereas p53 and vascular grade showed marginal prognostic significance (P = 0.07 and P = 0.09, respectively). In Dukes Stage C (AJCC/UICC Stage III) patients, high vascular grade was the only parameter that predicted a worse overall survival (P = 0.04). Double stratification showed that patients with high vascular grade and positive p53 expression had a poorer survival (P = 0.03). CONCLUSIONS: The results of the current study suggest that p53 mutations, loss of bcl-2 expression, and tumor angiogenesis are events linked to the processes of metastases and local invasion in patients with colorectal carcinoma. Increased vascularization appears to be the most important prognostic factor in patients with Dukes Stage C (AJCC/UICC Stage III) colorectal adenocarcinoma.

Adenocarcinoma↗