Sandra Tomek - Academia.edu (original) (raw)
Papers by Sandra Tomek
Anti-Cancer Drugs, Sep 1, 2000
he present phase II trial was performed to assess the efficacy and toxicity of polychemotherapy w... more he present phase II trial was performed to assess the efficacy and toxicity of polychemotherapy with gemcitabine and cisplatin in patients with locally advanced or metastatic carcinoma of the pancreas. Sixteen patients received six courses of an i.v. cytotoxic regimen consisting of gemcitabine (1000 mg/m2, days 1, 8 and 15) and cisplatin (35 mg/m2, days 1, 8 and 15) administered in 28-day intervals. Complete remission (CR) occurred in one patient (6%), partial remission (PR) in four patients (25%) and stable disease in seven patients (44%), whereas four patients (25%) developed progressive disease resulting in an overall response rate of 31%. Mean duration of responses (CR+PR) was 3.6 (range 0.7-8.5) months and mean time to progression was 7.4 (range 3.8-12.6) months. After a mean observation period of 11.5 months the overall survival was 9.6 months with 12 patients (75%) still being alive, which compares favorably with historical data of the administration of gemcitabine alone. The performance status improved in three (19%) and stabilized in eight (50%) out of 16 patients for 4 weeks or longer. Treatment-associated toxicity included alopecia of WHO grade III in all cases, leukopenia of WHO grades I and II in 10 patients (63%), grade III in five patients (31%), and thrombocytopenia grades I and II in four patients (25%), and grades III and IV in 10 patients (63%). We conclude that the administered dosage and schedule of gemcitabine and cisplatin in patients with locally advanced or metastatic cancer of the pancreas constitutes an active cytotoxic regimen associated with moderate toxicity.
Lung Cancer, Aug 1, 2004
This review summarises the results of previously conducted clinical trials, and subsequently pres... more This review summarises the results of previously conducted clinical trials, and subsequently presents data arising from all phase II-III studies on chemotherapy of malignant pleural mesothelioma (MPM) published since the last relevant overview. While response rates exceeding 30% have barely been achieved with established cytotoxic drugs in MPM therapy, novel chemotherapeutic agents and their combinations appear more promising. This applies especially to the antimetabolites, and in particular to pemetrexed that produced response rates of up to 45% in combination with platinum compounds. Raltitrexed combined with oxaliplatin has also been shown to be effective, and gemcitabine-applied as a single agent or in combination with cisplatin-as well as vinorelbine appear to improve the quality of life in patients presenting with MPM. Data can now be more precisely analysed by increasingly implemented randomised studies, applying a standardised staging system, and distinguishing prognostic groups. While chemotherapy for MPM remains a challenging task, important steps have clearly been made in the past years to combat this aggressive disease. The publication of pemetrexed with cisplatin phase III results in a peer-reviewed journal may soon establish a standard of care.
Journal of Clinical Oncology, Jul 15, 2004
7297 Background: Adjuvant chemotherapy treatment for early stage NSCLC patients is not yet standa... more 7297 Background: Adjuvant chemotherapy treatment for early stage NSCLC patients is not yet standard practice. The aim of the present trial is to compare the activity, safety, and quality of life ef...
Journal of Clinical Oncology, 2006
18583 Background: Anemia is a common complication in patients who receive anticancer therapy. We ... more 18583 Background: Anemia is a common complication in patients who receive anticancer therapy. We evaluated the efficacy of darbepoetin alfa in early vs. late treatment in patients with genitourinary tumors undergoing chemotherapy. We wanted to investigate whether an early onset of treatment with darbepoetin alfa reduces frequency of red blood cell transfusion and increases patients’ QoL. Methods: Patients on chemotherapeutic treatment for a urogenital neoplasia and a hemoglobin between 10–12 g/dl were randomized between an immediate start of treatment with darbepoetin alfa 150 μg sc weekly (group A) and a Hb below 10 g/dl or clinical symptoms (group B). Results: 52 patients out of 68 (76.5%) completed the trial, 7/40 patients (17%) in group A and 9/28 patients (32%) in group B withdraw from the study. An intent to treat analysis was performed and showed a significant superiority (p = 0.023, log-rank test) for the early treatment. In group A, only 12.5% of patients (5/40) received at...
Journal of Clinical Oncology, 2004
7297 Background: Adjuvant chemotherapy treatment for early stage NSCLC patients is not yet standa... more 7297 Background: Adjuvant chemotherapy treatment for early stage NSCLC patients is not yet standard practice. The aim of the present trial is to compare the activity, safety, and quality of life ef...
Wiener klinische Wochenschrift, Jan 30, 2001
Medical information to oncologic patients about their disease as well as regularly updated inform... more Medical information to oncologic patients about their disease as well as regularly updated information about the course of their disease and the therapeutic success are essential components of a comprehensive treatment in cancer patients. The quality of the patient-doctor-interaction as well as the hospital preference of oncologic patients were evaluated by a questionnaire at the Oncologic Out-Patient Clinic of the University Hospital of Vienna. 350 questionnaires containing 12 questions about medical information, anti-cancer therapy, suggestions for improvement and hospital preference were distributed. The questions were correlated with the patients' demographic and medical data. Out of 350 questionnaires, 234 (67%)--160 (68%) by women and 74 (32%) by men--were returned. 75% of the patients were satisfied with the provided medical information. In contrast, 12% of patients felt incompletely informed about their particular cancer and 19% were unsatisfied with their state of infor...
AACR Meeting …, 2005
Introduction. Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a type II transm... more Introduction. Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a type II transmembrane protein of the TNF family. It can be cleaved from the membrane into its soluble form and bind the apoptosis activating receptors DR4 and DR5. In ovarian cancer, elevated TRAIL ...
Oncology reports, 2003
Malignant Triton tumour represents an extremely rare mesenchymal malignancy exhibiting histopatho... more Malignant Triton tumour represents an extremely rare mesenchymal malignancy exhibiting histopathologic patterns of peripheral nerve sheath tumours and rhabdomyoblastic components, the latter usually determining the mostly fatal outcome. We report on a 26-year old patient diagnosed with malignant Triton tumour who developed multiple recurrences despite repeated aggressive surgery, chemo- and radiotherapy during an 8-year period. After Northern blotting analysis of an excised in-transit metastasis had revealed expression of retinoic receptors alpha and gamma, the patient received experimental treatment with isotretinoin and interferon-alpha for one year and remains without any evidence of disease for more than three years. This is the first report on a long-term survivor of multiple recurrences of malignant Triton tumour.
Cancer Immunology, Immunotherapy, 2001
In previous experiments, we demonstrated a decreased expression of intercellular adhesion molecul... more In previous experiments, we demonstrated a decreased expression of intercellular adhesion molecule 1 (ICAM-1) on both tumour cells and antigen-presenting cells derived from patients with breast cancer, resulting in an abrogation of antigen presentation and tumour cell lysis. Recently, increased levels of a soluble isoform of ICAM-1 (sICAM-1) have been detected in the sera of breast cancer patients. The present investigation was performed in order to investigate the biological relevance of serum concentrations and the eects of sICAM-1 in patients with breast cancer. Patients and methods: sICAM-1 was determined using a sandwich enzyme immunoassay on sera from 88 patients with various stages of breast cancer and correlated with clinical parameters. The eect of sICAM-1 present in the sera of patients with breast cancer upon unspeci®c and anti-Her-2/neu antibody-mediated cytotoxicity (ADCC), as well as upon antigen presentation, was determined using a 51 Cr-release assay and [ 3 H]thymidine-uptake of T cells after co-incubation with tetanus-toxoid-pulsed antigen-presenting cells. Results: In patients with early breast cancer, serum levels of sI-CAM-1 were signi®cantly lower compared to patients with metastatic disease, but did not correlate with usual clinical parameters. In patients with metastatic breast cancer, a signi®cant correlation of sICAM-1 with tumour markers CEA and CA 15-3 was observed. No in¯uence of sICAM-1 upon unspeci®c cytotoxicity, ADCC, or the ability to present antigen was observed. Discussion: The origin of sICAM-1 in the sera of patients with breast cancer remains unknown. In contrast to its membrane-bound isoform, sICAM-1 was increased in the sera of patients with various stages of breast cancer, but its presence did not in¯uence unspeci®c cytotoxicity, ADCC, or antigen-induced T cell proliferation. Keywords sICAM-1 á Breast cancer á ADCC á Antigen presentation
Molecular Cancer Research, 2005
Dysregulation of apoptosis may support tumorigenesis by allowing cells to live beyond their norma... more Dysregulation of apoptosis may support tumorigenesis by allowing cells to live beyond their normally intended life span. The various receptors for tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) are located on chromosome 8p21.2, a region frequently deleted in ovarian cancer. Lack of expression of TRAIL receptor 1 (death receptor 4, DR4) correlates with resistance to TRAIL-induced apoptosis in ovarian cancer cells. Reconstitution of DR4 in the TRAIL-resistant A2780 ovarian cancer cell line was investigated with the demethylating agent 5-aza-2′-deoxycytidine and transient gene transfer. Regulation of other genes in the TRAIL pathway by 5-aza-2′-deoxycytidine was assessed in DNA GeneChip experiments. Primary ovarian cancers were analyzed by methylation-specific PCR and immunohistochemical analysis of a tissue microarray. Regulation of DR4 expression by demethylation or transient transfection is of functional relevance for TRAIL resistance in an ovarian cancer cell line....
The Journal of Urology, 2007
In previous phase I to III studies docetaxel and vinorelbine have shown promising activity in and... more In previous phase I to III studies docetaxel and vinorelbine have shown promising activity in androgen independent prostate cancer. In the present trial we assessed the efficacy and tolerability of single agent low dose docetaxel vs vinorelbine in patients with advanced androgen independent prostate cancer. A total of 40 chemotherapy naive patients with histologically proven androgen independent prostate cancer, adequate androgen ablation, and clinical and/or biochemical progression were randomly assigned to receive either 25 mg/m(2) docetaxel (arm A) or 25 mg/m(2) vinorelbine (arm B) weekly. Treatment was continued until clinical and/or biochemical progression. In cases of progression patients switched to the alternative treatment arm. The primary end point was time to disease progression. Secondary end points included prostate specific antigen response rates in sequential treatment, analgesic response and toxicity. The current analysis showed a doubled risk of progression in treatment arm B. The median time to first disease progression was 14.5 months for arm A vs 4.4 months for arm B. The proportion of patients with a greater than 50% prostate specific antigen decrease on first line therapy was significantly higher in arm A (62.5%) compared to arm B (11.1%) (p = 0.0033). After progression to docetaxel second line vinorelbine yielded a greater than 50% prostate specific antigen response rate of 28.6% vs 62.5% for second line docetaxel. Clinically significant toxicity occurred more often in arm B with neutropenia grade 4 seen in 22% and grade 3 in 28% of patients (p = 0.0005) during the first treatment phase. While weekly application of both cytotoxic agents was well tolerated, this study demonstrates the superiority of docetaxel vs vinorelbine as monotherapy in the treatment of androgen independent prostate cancer.
European Journal of Cancer, 2001
Five human soft tissue sarcoma (STS) cell lines (HTB-82 rhabdomyosarcoma, HTB-91 fibrosarcoma, HT... more Five human soft tissue sarcoma (STS) cell lines (HTB-82 rhabdomyosarcoma, HTB-91 fibrosarcoma, HTB-92 liposarcoma, HTB-93 synovial sarcoma and HTB-94 chondrosarcoma) were analysed for their sensitivity to tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and the function of the TRAIL apoptotic pathway in these cells. TRAIL induced significant apoptosis (> 90%) in HTB-92 and HTB-93 cells, whereas no effect was observed in HTB-82, HTB-91 and HTB-94 cells. TRAIL-Receptor 1 (TRAIL-R1) was expressed in TRAIL-sensitive HTB-92 and HTB-93 cell lines, but not in TRAIL-resistant HTB-91 and HTB-94 cells. HTB-82 cells, which expressed the long (c-FLIP(L)) and short (c-FLIP(S)) splice variants of the FLICE-like inhibitory protein (FLIP), were resistant to TRAIL in spite of the presence of TRAIL-R1. TRAIL-R2,-R3,-R4 and osteoprotegerin (OPG) expression did not correlate with TRAIL sensitivity. Coincubation of TRAIL and doxorubicin led to the overexpression of TRAIL-R2 resulting in a synergistic effect of doxorubicin and TRAIL in TRAIL-sensitive cell lines and in the overcoming of TRAIL-resistance in all of the TRAIL-resistant cell lines, except HTB-91, which lacked caspase 8 expression. These data suggest that TRAIL, either as a single agent or in combination with cytotoxic agents, might represent a new treatment option for advanced STS, which constitutes a largely chemotherapy-resistant disease.
European Journal of Cancer, 2001
European Journal of Cancer, 2001
Current Opinion in Oncology, 2003
Purpose of Review This paper aims to propose an update on therapeutic medical options for maligna... more Purpose of Review This paper aims to propose an update on therapeutic medical options for malignant pleural mesothelioma (MPM). Recent Findings For 13 years, the standard of care in MPM patients has been cisplatin/pemetrexed chemotherapy. Recently, the Cis/Pem/bevacizumab triplet emerged as a new option for MPM patients eligible for bevacizumab, and not as a candidate for multimodality therapy trials, as validated by the last NCCN and French guidelines. Immunotherapy is also emerging as a promising option on its own or in combination with first-line Cis/Pem, or even as a valuable alternative to chemotherapy, radical surgery, and multimodality strategies. Summary Targeted therapies and immunotherapy are new promising treatments in MPM as single agents or in combination with chemotherapy. However, the key challenge remains to find reliable predictive biomarkers for these innovative, exciting, and expensive treatments to select the best patients for each strategy. After years of nihilism and negative trials, numerous therapeutic strategies can now be offered to mesothelioma patients and the future looks brighter.
Clinical Cancer Research, 2004
Purpose: The present pilot study was performed to elucidate whether early changes in serum Her-2/... more Purpose: The present pilot study was performed to elucidate whether early changes in serum Her-2/neu extracellular domain (ECD) levels during trastuzumab-based treatment would predict the clinical course of disease in patients with metastatic breast cancer. Experimental Design: Sera from 55 patients with Her-2/neu-overexpressing metastatic breast cancer obtained immediately before each weekly administration of trastuzumab were analyzed by a serum Her-2/neu ELISA. Results: Whereas response rates were significantly higher in patients with elevated (≥15 ng/ml) ECD levels before initiation of treatment (35% versus 7%, P = 0.045), progression-free and overall survival did not differ significantly between patients with normal and elevated ECD levels. In patients responding to treatment, ECD levels decreased significantly as early as from day 8 of treatment onwards (all P for weekly measurements versus baseline <0.001). In contrast, no significant change in ECD levels was observed in pa...
Anti-Cancer Drugs, 2000
The aim of this phase II study was to investigate the therapeutic value of second-line treatment ... more The aim of this phase II study was to investigate the therapeutic value of second-line treatment with oxaliplatin, irinotecan (CPT-11) and mitomycin C (MMC) in patients with metastatic colorectal cancer pretreated with 5-fluorouracil (5-FU)-based chemotherapy. A total of 10 patients with metastatic colorectal cancer, all of whom had developed progressive disease from advanced or metastatic colorectal cancer while receiving or within 6 months after discontinuing first-line chemotherapy with 5-FU and leucovorin, were entered in this study. At the time of relapse, cytotoxic chemotherapy consisting of oxaliplatin 80 mg/m2 plus CPT-11 80 mg/m2 given i.v. on therapeutic day 1, and MMC 6 mg/ m2 given i.v. on day 15, respectively, was initiated. Treatment courses were repeated every 4 weeks for a total of six courses unless there was prior evidence of progressive disease. The overall response rate was 30% with three partial responses for all 10 assessable patients. Two additional patients (20%) had stable disease and five patients (50%) progressed. The median overall survival duration has not been reached yet and is longer than 7.1 months (range 2-23.5+) from the beginning of second-line therapy. Four patients are currently alive with progressive disease. The tolerance of second-line treatment was generally mild to moderate and easy to treat. Our data suggest that the combination of oxaliplatin, CPT-11 and MMC in patients with metastatic colorectal cancer pretreated with 5-FU-based chemotherapy is feasible and has substantial antitumor activity. Further evaluation of this regimen seems warranted.
The Annals of Thoracic Surgery, 2005
Positron-emission tomography (PET) with 18F-fluorodeoxy-glucose (FDG) frequently gives false-nega... more Positron-emission tomography (PET) with 18F-fluorodeoxy-glucose (FDG) frequently gives false-negative results for well-differentiated adenocarcinomas of the lung, especially, those with ground-glass opacity images. Recently, PET with 11C-acetate (AC) has been reported to detect slow-growing tumors that have failed to be identified by FDG-PET, such as well-differentiated hepatocellular carcinomas and prostate cancers. To determine the usefulness of AC-PET in detecting well-differentiated adenocarcinomas of the lung, we performed both AC-PET and FDG-PET on pulmonary nodules with ground-glass opacity images on computed tomography (CT). Fifty-four pulmonary nodules 1 to 3 cm in size, which showed ground-glass opacity images over their whole or peripheral area on CT, were examined by both AC-PET and FDG-PET. Thirty-seven nodules were adenocarcinoma of the lung, while 17 were inflammatory. Of the 37 adenocarcinomas, 19 (51%) were positively identified by AC-PET and 14 (38%) by FDG-PET. Of the 23 adenocarcinomas which were not identified by FDG-PET, 8 (35%) were positively identified by AC-PET; all were well-differentiated adenocarcinomas. Of the 17 inflammatory nodules, 8 were chronic and 9 were acute ones. While none of the 8 chronic inflammatory nodules were identified by either technique, 9 acute ones showed a variety of the results with AC- and FDG-PET. AC-PET detected approximately one third of well-differentiated adenocarcinomas of the lung which were not identified by FDG-PET. AC-PET could be useful to diagnose pulmonary nodules with ground-glass opacity images which were not identified by FDG-PET.
International Journal of Gynecology & Obstetrics, 2000
Anti-Her-2/neu antibody is known to induce apoptosis in HER-2/neu overexpressing breast cancer ce... more Anti-Her-2/neu antibody is known to induce apoptosis in HER-2/neu overexpressing breast cancer cells. However, exact regulatory mechanisms mediating and controlling this phenomenon are still unknown. In the present study, we have investigated the effect of anti-Her-2/neu antibody on apoptosis of HER-2/neu overexpressing human breast cancer cell lines SK-BR-3, HTB-24, HTB-25, HTB-27, HTB-128, HTB-130 and HTB-131 in relation to p53 genotype and bcl-2 status. SK-BR-3, HTB-24, HTB-128 and HTB-130 cells exhibited mutant p53, whereas wild type p53 was found in HTB-25, HTB-27 and HTB-131 cells. All seven cell lines weakly expressed bcl-2 protein (10-20%). Anti-Her-2/neu antibody, irrespective of p53 and bcl-2 status, induced apoptosis in all 7 cell lines dose-and time-dependently and correlated with Her-2/neu overexpression. In addition, incubation of cell lines with anti-Her-2/neu antibody did not alter p53 or bcl-2 expression. Anti-HER-2/neu antibody did not induce apoptosis in HER-2/neu negative HBL-100 and HTB-132 cell lines. Our results indicate that within the panel of tested breast cancer cell lines, anti-Her-2/neu antibody-induced apoptosis was independent from the presence of intact p53.
Anti-Cancer Drugs, Sep 1, 2000
he present phase II trial was performed to assess the efficacy and toxicity of polychemotherapy w... more he present phase II trial was performed to assess the efficacy and toxicity of polychemotherapy with gemcitabine and cisplatin in patients with locally advanced or metastatic carcinoma of the pancreas. Sixteen patients received six courses of an i.v. cytotoxic regimen consisting of gemcitabine (1000 mg/m2, days 1, 8 and 15) and cisplatin (35 mg/m2, days 1, 8 and 15) administered in 28-day intervals. Complete remission (CR) occurred in one patient (6%), partial remission (PR) in four patients (25%) and stable disease in seven patients (44%), whereas four patients (25%) developed progressive disease resulting in an overall response rate of 31%. Mean duration of responses (CR+PR) was 3.6 (range 0.7-8.5) months and mean time to progression was 7.4 (range 3.8-12.6) months. After a mean observation period of 11.5 months the overall survival was 9.6 months with 12 patients (75%) still being alive, which compares favorably with historical data of the administration of gemcitabine alone. The performance status improved in three (19%) and stabilized in eight (50%) out of 16 patients for 4 weeks or longer. Treatment-associated toxicity included alopecia of WHO grade III in all cases, leukopenia of WHO grades I and II in 10 patients (63%), grade III in five patients (31%), and thrombocytopenia grades I and II in four patients (25%), and grades III and IV in 10 patients (63%). We conclude that the administered dosage and schedule of gemcitabine and cisplatin in patients with locally advanced or metastatic cancer of the pancreas constitutes an active cytotoxic regimen associated with moderate toxicity.
Lung Cancer, Aug 1, 2004
This review summarises the results of previously conducted clinical trials, and subsequently pres... more This review summarises the results of previously conducted clinical trials, and subsequently presents data arising from all phase II-III studies on chemotherapy of malignant pleural mesothelioma (MPM) published since the last relevant overview. While response rates exceeding 30% have barely been achieved with established cytotoxic drugs in MPM therapy, novel chemotherapeutic agents and their combinations appear more promising. This applies especially to the antimetabolites, and in particular to pemetrexed that produced response rates of up to 45% in combination with platinum compounds. Raltitrexed combined with oxaliplatin has also been shown to be effective, and gemcitabine-applied as a single agent or in combination with cisplatin-as well as vinorelbine appear to improve the quality of life in patients presenting with MPM. Data can now be more precisely analysed by increasingly implemented randomised studies, applying a standardised staging system, and distinguishing prognostic groups. While chemotherapy for MPM remains a challenging task, important steps have clearly been made in the past years to combat this aggressive disease. The publication of pemetrexed with cisplatin phase III results in a peer-reviewed journal may soon establish a standard of care.
Journal of Clinical Oncology, Jul 15, 2004
7297 Background: Adjuvant chemotherapy treatment for early stage NSCLC patients is not yet standa... more 7297 Background: Adjuvant chemotherapy treatment for early stage NSCLC patients is not yet standard practice. The aim of the present trial is to compare the activity, safety, and quality of life ef...
Journal of Clinical Oncology, 2006
18583 Background: Anemia is a common complication in patients who receive anticancer therapy. We ... more 18583 Background: Anemia is a common complication in patients who receive anticancer therapy. We evaluated the efficacy of darbepoetin alfa in early vs. late treatment in patients with genitourinary tumors undergoing chemotherapy. We wanted to investigate whether an early onset of treatment with darbepoetin alfa reduces frequency of red blood cell transfusion and increases patients’ QoL. Methods: Patients on chemotherapeutic treatment for a urogenital neoplasia and a hemoglobin between 10–12 g/dl were randomized between an immediate start of treatment with darbepoetin alfa 150 μg sc weekly (group A) and a Hb below 10 g/dl or clinical symptoms (group B). Results: 52 patients out of 68 (76.5%) completed the trial, 7/40 patients (17%) in group A and 9/28 patients (32%) in group B withdraw from the study. An intent to treat analysis was performed and showed a significant superiority (p = 0.023, log-rank test) for the early treatment. In group A, only 12.5% of patients (5/40) received at...
Journal of Clinical Oncology, 2004
7297 Background: Adjuvant chemotherapy treatment for early stage NSCLC patients is not yet standa... more 7297 Background: Adjuvant chemotherapy treatment for early stage NSCLC patients is not yet standard practice. The aim of the present trial is to compare the activity, safety, and quality of life ef...
Wiener klinische Wochenschrift, Jan 30, 2001
Medical information to oncologic patients about their disease as well as regularly updated inform... more Medical information to oncologic patients about their disease as well as regularly updated information about the course of their disease and the therapeutic success are essential components of a comprehensive treatment in cancer patients. The quality of the patient-doctor-interaction as well as the hospital preference of oncologic patients were evaluated by a questionnaire at the Oncologic Out-Patient Clinic of the University Hospital of Vienna. 350 questionnaires containing 12 questions about medical information, anti-cancer therapy, suggestions for improvement and hospital preference were distributed. The questions were correlated with the patients' demographic and medical data. Out of 350 questionnaires, 234 (67%)--160 (68%) by women and 74 (32%) by men--were returned. 75% of the patients were satisfied with the provided medical information. In contrast, 12% of patients felt incompletely informed about their particular cancer and 19% were unsatisfied with their state of infor...
AACR Meeting …, 2005
Introduction. Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a type II transm... more Introduction. Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a type II transmembrane protein of the TNF family. It can be cleaved from the membrane into its soluble form and bind the apoptosis activating receptors DR4 and DR5. In ovarian cancer, elevated TRAIL ...
Oncology reports, 2003
Malignant Triton tumour represents an extremely rare mesenchymal malignancy exhibiting histopatho... more Malignant Triton tumour represents an extremely rare mesenchymal malignancy exhibiting histopathologic patterns of peripheral nerve sheath tumours and rhabdomyoblastic components, the latter usually determining the mostly fatal outcome. We report on a 26-year old patient diagnosed with malignant Triton tumour who developed multiple recurrences despite repeated aggressive surgery, chemo- and radiotherapy during an 8-year period. After Northern blotting analysis of an excised in-transit metastasis had revealed expression of retinoic receptors alpha and gamma, the patient received experimental treatment with isotretinoin and interferon-alpha for one year and remains without any evidence of disease for more than three years. This is the first report on a long-term survivor of multiple recurrences of malignant Triton tumour.
Cancer Immunology, Immunotherapy, 2001
In previous experiments, we demonstrated a decreased expression of intercellular adhesion molecul... more In previous experiments, we demonstrated a decreased expression of intercellular adhesion molecule 1 (ICAM-1) on both tumour cells and antigen-presenting cells derived from patients with breast cancer, resulting in an abrogation of antigen presentation and tumour cell lysis. Recently, increased levels of a soluble isoform of ICAM-1 (sICAM-1) have been detected in the sera of breast cancer patients. The present investigation was performed in order to investigate the biological relevance of serum concentrations and the eects of sICAM-1 in patients with breast cancer. Patients and methods: sICAM-1 was determined using a sandwich enzyme immunoassay on sera from 88 patients with various stages of breast cancer and correlated with clinical parameters. The eect of sICAM-1 present in the sera of patients with breast cancer upon unspeci®c and anti-Her-2/neu antibody-mediated cytotoxicity (ADCC), as well as upon antigen presentation, was determined using a 51 Cr-release assay and [ 3 H]thymidine-uptake of T cells after co-incubation with tetanus-toxoid-pulsed antigen-presenting cells. Results: In patients with early breast cancer, serum levels of sI-CAM-1 were signi®cantly lower compared to patients with metastatic disease, but did not correlate with usual clinical parameters. In patients with metastatic breast cancer, a signi®cant correlation of sICAM-1 with tumour markers CEA and CA 15-3 was observed. No in¯uence of sICAM-1 upon unspeci®c cytotoxicity, ADCC, or the ability to present antigen was observed. Discussion: The origin of sICAM-1 in the sera of patients with breast cancer remains unknown. In contrast to its membrane-bound isoform, sICAM-1 was increased in the sera of patients with various stages of breast cancer, but its presence did not in¯uence unspeci®c cytotoxicity, ADCC, or antigen-induced T cell proliferation. Keywords sICAM-1 á Breast cancer á ADCC á Antigen presentation
Molecular Cancer Research, 2005
Dysregulation of apoptosis may support tumorigenesis by allowing cells to live beyond their norma... more Dysregulation of apoptosis may support tumorigenesis by allowing cells to live beyond their normally intended life span. The various receptors for tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) are located on chromosome 8p21.2, a region frequently deleted in ovarian cancer. Lack of expression of TRAIL receptor 1 (death receptor 4, DR4) correlates with resistance to TRAIL-induced apoptosis in ovarian cancer cells. Reconstitution of DR4 in the TRAIL-resistant A2780 ovarian cancer cell line was investigated with the demethylating agent 5-aza-2′-deoxycytidine and transient gene transfer. Regulation of other genes in the TRAIL pathway by 5-aza-2′-deoxycytidine was assessed in DNA GeneChip experiments. Primary ovarian cancers were analyzed by methylation-specific PCR and immunohistochemical analysis of a tissue microarray. Regulation of DR4 expression by demethylation or transient transfection is of functional relevance for TRAIL resistance in an ovarian cancer cell line....
The Journal of Urology, 2007
In previous phase I to III studies docetaxel and vinorelbine have shown promising activity in and... more In previous phase I to III studies docetaxel and vinorelbine have shown promising activity in androgen independent prostate cancer. In the present trial we assessed the efficacy and tolerability of single agent low dose docetaxel vs vinorelbine in patients with advanced androgen independent prostate cancer. A total of 40 chemotherapy naive patients with histologically proven androgen independent prostate cancer, adequate androgen ablation, and clinical and/or biochemical progression were randomly assigned to receive either 25 mg/m(2) docetaxel (arm A) or 25 mg/m(2) vinorelbine (arm B) weekly. Treatment was continued until clinical and/or biochemical progression. In cases of progression patients switched to the alternative treatment arm. The primary end point was time to disease progression. Secondary end points included prostate specific antigen response rates in sequential treatment, analgesic response and toxicity. The current analysis showed a doubled risk of progression in treatment arm B. The median time to first disease progression was 14.5 months for arm A vs 4.4 months for arm B. The proportion of patients with a greater than 50% prostate specific antigen decrease on first line therapy was significantly higher in arm A (62.5%) compared to arm B (11.1%) (p = 0.0033). After progression to docetaxel second line vinorelbine yielded a greater than 50% prostate specific antigen response rate of 28.6% vs 62.5% for second line docetaxel. Clinically significant toxicity occurred more often in arm B with neutropenia grade 4 seen in 22% and grade 3 in 28% of patients (p = 0.0005) during the first treatment phase. While weekly application of both cytotoxic agents was well tolerated, this study demonstrates the superiority of docetaxel vs vinorelbine as monotherapy in the treatment of androgen independent prostate cancer.
European Journal of Cancer, 2001
Five human soft tissue sarcoma (STS) cell lines (HTB-82 rhabdomyosarcoma, HTB-91 fibrosarcoma, HT... more Five human soft tissue sarcoma (STS) cell lines (HTB-82 rhabdomyosarcoma, HTB-91 fibrosarcoma, HTB-92 liposarcoma, HTB-93 synovial sarcoma and HTB-94 chondrosarcoma) were analysed for their sensitivity to tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and the function of the TRAIL apoptotic pathway in these cells. TRAIL induced significant apoptosis (> 90%) in HTB-92 and HTB-93 cells, whereas no effect was observed in HTB-82, HTB-91 and HTB-94 cells. TRAIL-Receptor 1 (TRAIL-R1) was expressed in TRAIL-sensitive HTB-92 and HTB-93 cell lines, but not in TRAIL-resistant HTB-91 and HTB-94 cells. HTB-82 cells, which expressed the long (c-FLIP(L)) and short (c-FLIP(S)) splice variants of the FLICE-like inhibitory protein (FLIP), were resistant to TRAIL in spite of the presence of TRAIL-R1. TRAIL-R2,-R3,-R4 and osteoprotegerin (OPG) expression did not correlate with TRAIL sensitivity. Coincubation of TRAIL and doxorubicin led to the overexpression of TRAIL-R2 resulting in a synergistic effect of doxorubicin and TRAIL in TRAIL-sensitive cell lines and in the overcoming of TRAIL-resistance in all of the TRAIL-resistant cell lines, except HTB-91, which lacked caspase 8 expression. These data suggest that TRAIL, either as a single agent or in combination with cytotoxic agents, might represent a new treatment option for advanced STS, which constitutes a largely chemotherapy-resistant disease.
European Journal of Cancer, 2001
European Journal of Cancer, 2001
Current Opinion in Oncology, 2003
Purpose of Review This paper aims to propose an update on therapeutic medical options for maligna... more Purpose of Review This paper aims to propose an update on therapeutic medical options for malignant pleural mesothelioma (MPM). Recent Findings For 13 years, the standard of care in MPM patients has been cisplatin/pemetrexed chemotherapy. Recently, the Cis/Pem/bevacizumab triplet emerged as a new option for MPM patients eligible for bevacizumab, and not as a candidate for multimodality therapy trials, as validated by the last NCCN and French guidelines. Immunotherapy is also emerging as a promising option on its own or in combination with first-line Cis/Pem, or even as a valuable alternative to chemotherapy, radical surgery, and multimodality strategies. Summary Targeted therapies and immunotherapy are new promising treatments in MPM as single agents or in combination with chemotherapy. However, the key challenge remains to find reliable predictive biomarkers for these innovative, exciting, and expensive treatments to select the best patients for each strategy. After years of nihilism and negative trials, numerous therapeutic strategies can now be offered to mesothelioma patients and the future looks brighter.
Clinical Cancer Research, 2004
Purpose: The present pilot study was performed to elucidate whether early changes in serum Her-2/... more Purpose: The present pilot study was performed to elucidate whether early changes in serum Her-2/neu extracellular domain (ECD) levels during trastuzumab-based treatment would predict the clinical course of disease in patients with metastatic breast cancer. Experimental Design: Sera from 55 patients with Her-2/neu-overexpressing metastatic breast cancer obtained immediately before each weekly administration of trastuzumab were analyzed by a serum Her-2/neu ELISA. Results: Whereas response rates were significantly higher in patients with elevated (≥15 ng/ml) ECD levels before initiation of treatment (35% versus 7%, P = 0.045), progression-free and overall survival did not differ significantly between patients with normal and elevated ECD levels. In patients responding to treatment, ECD levels decreased significantly as early as from day 8 of treatment onwards (all P for weekly measurements versus baseline <0.001). In contrast, no significant change in ECD levels was observed in pa...
Anti-Cancer Drugs, 2000
The aim of this phase II study was to investigate the therapeutic value of second-line treatment ... more The aim of this phase II study was to investigate the therapeutic value of second-line treatment with oxaliplatin, irinotecan (CPT-11) and mitomycin C (MMC) in patients with metastatic colorectal cancer pretreated with 5-fluorouracil (5-FU)-based chemotherapy. A total of 10 patients with metastatic colorectal cancer, all of whom had developed progressive disease from advanced or metastatic colorectal cancer while receiving or within 6 months after discontinuing first-line chemotherapy with 5-FU and leucovorin, were entered in this study. At the time of relapse, cytotoxic chemotherapy consisting of oxaliplatin 80 mg/m2 plus CPT-11 80 mg/m2 given i.v. on therapeutic day 1, and MMC 6 mg/ m2 given i.v. on day 15, respectively, was initiated. Treatment courses were repeated every 4 weeks for a total of six courses unless there was prior evidence of progressive disease. The overall response rate was 30% with three partial responses for all 10 assessable patients. Two additional patients (20%) had stable disease and five patients (50%) progressed. The median overall survival duration has not been reached yet and is longer than 7.1 months (range 2-23.5+) from the beginning of second-line therapy. Four patients are currently alive with progressive disease. The tolerance of second-line treatment was generally mild to moderate and easy to treat. Our data suggest that the combination of oxaliplatin, CPT-11 and MMC in patients with metastatic colorectal cancer pretreated with 5-FU-based chemotherapy is feasible and has substantial antitumor activity. Further evaluation of this regimen seems warranted.
The Annals of Thoracic Surgery, 2005
Positron-emission tomography (PET) with 18F-fluorodeoxy-glucose (FDG) frequently gives false-nega... more Positron-emission tomography (PET) with 18F-fluorodeoxy-glucose (FDG) frequently gives false-negative results for well-differentiated adenocarcinomas of the lung, especially, those with ground-glass opacity images. Recently, PET with 11C-acetate (AC) has been reported to detect slow-growing tumors that have failed to be identified by FDG-PET, such as well-differentiated hepatocellular carcinomas and prostate cancers. To determine the usefulness of AC-PET in detecting well-differentiated adenocarcinomas of the lung, we performed both AC-PET and FDG-PET on pulmonary nodules with ground-glass opacity images on computed tomography (CT). Fifty-four pulmonary nodules 1 to 3 cm in size, which showed ground-glass opacity images over their whole or peripheral area on CT, were examined by both AC-PET and FDG-PET. Thirty-seven nodules were adenocarcinoma of the lung, while 17 were inflammatory. Of the 37 adenocarcinomas, 19 (51%) were positively identified by AC-PET and 14 (38%) by FDG-PET. Of the 23 adenocarcinomas which were not identified by FDG-PET, 8 (35%) were positively identified by AC-PET; all were well-differentiated adenocarcinomas. Of the 17 inflammatory nodules, 8 were chronic and 9 were acute ones. While none of the 8 chronic inflammatory nodules were identified by either technique, 9 acute ones showed a variety of the results with AC- and FDG-PET. AC-PET detected approximately one third of well-differentiated adenocarcinomas of the lung which were not identified by FDG-PET. AC-PET could be useful to diagnose pulmonary nodules with ground-glass opacity images which were not identified by FDG-PET.
International Journal of Gynecology & Obstetrics, 2000
Anti-Her-2/neu antibody is known to induce apoptosis in HER-2/neu overexpressing breast cancer ce... more Anti-Her-2/neu antibody is known to induce apoptosis in HER-2/neu overexpressing breast cancer cells. However, exact regulatory mechanisms mediating and controlling this phenomenon are still unknown. In the present study, we have investigated the effect of anti-Her-2/neu antibody on apoptosis of HER-2/neu overexpressing human breast cancer cell lines SK-BR-3, HTB-24, HTB-25, HTB-27, HTB-128, HTB-130 and HTB-131 in relation to p53 genotype and bcl-2 status. SK-BR-3, HTB-24, HTB-128 and HTB-130 cells exhibited mutant p53, whereas wild type p53 was found in HTB-25, HTB-27 and HTB-131 cells. All seven cell lines weakly expressed bcl-2 protein (10-20%). Anti-Her-2/neu antibody, irrespective of p53 and bcl-2 status, induced apoptosis in all 7 cell lines dose-and time-dependently and correlated with Her-2/neu overexpression. In addition, incubation of cell lines with anti-Her-2/neu antibody did not alter p53 or bcl-2 expression. Anti-HER-2/neu antibody did not induce apoptosis in HER-2/neu negative HBL-100 and HTB-132 cell lines. Our results indicate that within the panel of tested breast cancer cell lines, anti-Her-2/neu antibody-induced apoptosis was independent from the presence of intact p53.