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M Bouvet

Publications and source records attributed to M Bouvet.

At least 19 recordsLinked to original sources
PubMed1999

Recombinant adenovirus expressing wild-type p53 is antiangiogenic: a proposed mechanism for bystander effect.

Angiogenesis is required for the growth and progression of malignancies. Recent studies have demonstrated that genetic alterations may accompany acquisition of the angiogenic phenotype. The tumor suppressor gene p53 is most frequently mutated in human cancers and is also known to be a transcriptional regulator of a variety of genes. Here, we investigated the antiangiogenic effect of the wild-type p53 (wt-p53) gene transfer on a human non-small cell lung cancer cell line. Mutant p53-expressing H226Br non-small cell lung cancer cells were transduced with the wt-p53 gene using a recombinant adenoviral vector (Ad5CMVp53) and applied to semiquantitative reverse transcription-PCRs for the detection of altered mRNA expression of angiogenic and/or antiangiogenic factors. In vivo neovascularization assay of Ad5CMVp53-infected cells was then performed using a membrane-diffusion chamber system s.c. transplanted in nu/nu mice. We also evaluated the effect of Ad5CMVp53-infected H226Br cells on nontransduced tumor cells in vivo by s.c. inoculating mixture of cells into nu/nu mice. Ad5CMVp53 infection markedly inhibited the expression of an angiogenic factor, vascular endothelial growth factor, and increased the expression of a novel antiangiogenic factor, brain-specific angiogenesis inhibitor 1, resulting in reduced neovascularization in vivo. Mixing experiments showed that tumor cells transduced with the wt-p53 gene inhibited the in vivo tumor growth of adjacent nontransduced cells. Our data suggest that a recombinant adenovirus expressing the wt-p53 gene is antiangiogenic, which may explain, in part, the mechanism of the bystander effect induced by the wt-p53 gene transfer on adjacent tumor cells.

Adenoviruses, Human↗
PubMed1998

Gene therapy and pancreatic cancer.

Adenocarcinoma of the pancreas is associated with a short survival due to frequent delays in diagnosis and the lack of effective systemic therapies. Advances in understanding the molecular basis of pancreatic cancer have allowed identification of molecular targets which are amenable to therapeutic intervention. Such targets include p53, K-ras, p16, and DPC-4. Gene therapy involves the transfer of genetic constructs which alter the neoplastic potential of the cancer cell. Vectors used in gene transfer include viral and non-viral methods. Presently, gene therapy of pancreatic cancer is limited to pre-clinical studies using in vitro and in vivo models. However, the initial results from these pre-clinical studies have been encouraging and will form the basis for clinical studies of gene transfer in patients with pancreatic cancer.

Adenocarcinoma↗
PubMed1998

Adenovirus-mediated wild-type p53 gene transfer down-regulates vascular endothelial growth factor expression and inhibits angiogenesis in human colon cancer.

Recent studies have indicated that angiogenesis may be regulated, in part, by p53 tumor suppressor gene function. We hypothesized that wild-type p53 replacement would down-regulate vascular endothelial growth factor (VEGF) expression and inhibit angiogenesis. KM12L4 and SW620, human colon cancer cell lines with p53 mutations, were transduced with a replication-defective adenoviral vector containing the wild-type p53 gene (Ad5/CMV/p53). Reverse transcription-PCR confirmed the presence of p53 in Ad5/CMV/p53-transduced cells. Transduction of colon cancer cells with wild-type p53 decreased VEGF RNA expression compared with that of controls. The decrease in VEGF expression in SW620 cells was dose dependent, with a 49% decrease observed at a multiplicity of infection of 50, and a 71% decrease observed at a multiplicity of infection of 100. Similar effects were seen in KM12L4 cells. VEGF supernatant protein levels were significantly reduced compared with those in nontransduced controls 48 h after the introduction of wild-type p53. Ad5/CMV/p53 inhibited tumor cell-induced angiogenesis in vivo. Restoration of wild-type p53 expression may decrease tumor growth by inhibiting the angiogenic response. These findings may explain, in part, the bystander effect seen with p53 tumor suppressor gene therapy.

Adenoviridae↗
PubMed1998

Evaluation of GAL4/TATA in vivo. Induction of transgene expression by adenovirally mediated gene codelivery.

A synthetic GAL4-responsive promoter consisting of five GAL4-binding sites and a TATA box (GAL4/TATA) was evaluated for its transcriptional activity in an adenoviral backbone using luciferase as the reporter. Basal luciferase activities in vitro were the same for cells infected with either adenovirus-containing luciferase cDNA driven by GAL4/TATA (Ad/GT-Luc) or adenovirus-containing luciferase cDNA not driven by a promoter (Ad/PO-Luc). In vitro induction of GAL4/TATA by coinfection of cells with adenovirus expressing the GAL4/VP16 fusion protein (Ad/3-phosphoglycerate kinase (PGK)-GV16) was dose-dependent and reached as high as 4 x 10(4)- to 9 x 10(4)-fold above basal levels when GAL4/TATA and GAL4/VP16 were delivered at a ratio of 10:1. In vivo studies in Balb/c mice showed no detectable luciferase activities in liver or other tissues examined in mice infused with either Ad/GT-Luc or Ad/PO-Luc. High levels of luciferase activity were, however, elicited when animals were infused with Ad/GT-Luc and Ad/PGK-GV16. Together, these results suggest that combination of the GAL4 gene regulatory system with adenovirally mediated in vivo gene delivery may be applicable to the in vivo evaluation of promoter activities and in vivo targeting of gene expression.

Adenoviridae↗
PubMed1998

Adenovirus-mediated wild-type p53 tumor suppressor gene therapy induces apoptosis and suppresses growth of human pancreatic cancer [seecomments].

BACKGROUND: The p53 tumor suppressor gene is mutated in up to 70% of pancreatic adenocarcinomas. We determined the effect of reintroduction of the wild-type p53 gene on proliferation and apoptosis in human pancreatic cancer cells using an adenoviral vector containing the wild-type p53 tumor suppressor gene. METHODS: Transduction efficiencies of six p53-mutant pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan-1, CFPAC-1, MIA PaCa-2, and PANC-1) were determined using the reporter gene construct Ad5/CMV/beta-gal. Cell proliferation was monitored using a 3H-thymidine incorporation assay, Western blot analysis for p53 expression was performed, and DNA laddering and fluorescence-activated cell sorter analysis were used to assess apoptosis. p53 gene therapy was tested in vivo in a subcutaneous tumor model. RESULTS: The cell lines varied in transduction efficiency. The MIA PaCa-2 cells had the highest transduction efficiency, with 65% of pancreatic tumor cells staining positive for beta-galactosidase (beta-gal) at a multiplicity of infection (MOI) of 50. At the same MOI, only 15% of the CFPAC-1 cells expressed the beta-gal gene. Adenovirus-mediated p53 gene transfer suppressed growth of all human pancreatic cancer cell lines in a dose-dependent manner. Western blot analysis confirmed the presence of the p53 protein product at 48 hours after infection. DNA ladders demonstrated increased chromatin degradation, and fluorescence-activated cell sorter analysis demonstrated a four-fold increase in apoptotic cells at 48 and 72 hours following infection with Ad5/CMV/p53 in the MIA PaCa-2 and PANC-1 cells. Suppression of tumor growth mediated by induction of apoptosis was observed in vivo in an established nude mouse subcutaneous tumor model following intratumoral injections of Ad5/CMV/p53. CONCLUSIONS: Introduction of the wild-type p53 gene using an adenoviral vector in pancreatic cancer with p53 mutations induces apoptosis and inhibits cell growth. These data provide preliminary support for adenoviral mediated p53 tumor suppressor gene therapy of human pancreatic cancer.

Adenocarcinoma↗
PubMed1998

Hemangiopericytoma: a 20-year single-institution experience.

BACKGROUND: Hemangiopericytoma is an uncommon soft tissue sarcoma. We sought to evaluate the long-term outcome of a consecutively treated patient cohort with hemangiopericytoma. METHODS: The study involved 36 adult patients (older than 16 years) with hemangiopericytoma treated at The University of Texas M. D. Anderson Cancer Center between July 1975 and July 1995. Data on clinicopathologic parameters, surgical treatment, adjuvant therapy, disease recurrence, and survival were obtained from a review of medical records. RESULTS: The median follow-up was 57 months. Twenty-eight patients (78%) underwent complete and potentially curative resection of their primary disease. Of the nine patients (32%) who had local recurrences, four (57%) had epidural tumors and three (43%) had retroperitoneal tumors, but none had extremity tumors. Extremity tumors were associated with a significantly prolonged local recurrence-free survival compared to tumors at nonextremity anatomic sites (P <.05). Ten patients had recurrences at distant sites. Of the 13 patients who experienced any form of disease recurrence, four had recurrences after a disease-free interval of more than 5 years. The 5-year actuarial survival rate for the entire group of 36 patients was 71%. Noncurative surgical treatment (P=.007) and development of distant metastatic disease (P=.013) were associated with shortened survival. CONCLUSION: Extended survival is common in hemangiopericytoma patients treated with curative intent. However, local and distant recurrences may occur after a prolonged disease-free interval, emphasizing the need for long-term follow-up. Retroperitoneal and meningeal tumors were associated with higher local recurrence rates; therefore, adjuvant therapies should be considered and evaluated for tumors at these sites.

Adult↗
PubMed1998

Clinical, pathologic, and economic parameters of laparoscopic colon resection for cancer.

BACKGROUND: The appropriateness of laparoscopic colon resection (LCR) as treatment for malignancy has been questioned. METHODS: From 1992 to 1997, 91 patients were entered into a prospective study of LCR for cancer. Clinical, pathologic, and economic parameters of LCR were compared in a cohort of patients matched for age, tumor stage, and type of colectomy who underwent open colon resection (OCR) during the same time period. RESULTS: With a median follow-up of 26 months, there were no significant differences in survival rate for patients in the LCR, converted colon resection, and OCR groups. There were no port-site recurrences and the number of lymph nodes harvested was similar among the procedures. Hospital stay was significantly shorter if laparoscopic resection was successful. Total hospital costs were similar for LCR and OCR; however, the costs were significantly higher for converted colon resection. CONCLUSIONS: LCR is a sound oncologic procedure that can be performed with costs similar to OCR.

Adult↗
PubMed1998

Suppression of the immune response to an adenovirus vector and enhancement of intratumoral transgene expression by low-dose etoposide.

Adenoviral vectors are commonly used in gene therapy trials because of their efficiency in gene transfer. However, their use is limited by cellular and humoral immune responses that result in temporary transgene expression and reduced efficacy of repeated vector administration. We hypothesized that certain oncolytic agents commonly used to treat cancer patients could suppress the immune response to adenoviral vectors, and enable repeated adenovirus-mediated cancer gene therapy. Etoposide and cyclophosphamide were tested for their ability to suppress the humoral and cellular immune responses to an adenoviral vector in immunocompetent C3H mice. Intratumoral transgene expression was monitored in adenovirus-immunized animals treated with etoposide or cyclophosphamide. Neutralizing antibodies to adenovirus and cytotoxic T lymphocyte (CTL) lysis of virally transduced cells were significantly suppressed in mice treated with etoposide at 2 or 10 mg/kg/day or cyclophosphamide at 10 mg/kg/day compared with untreated mice (P < 0.05). Significantly larger areas of gene transduction were observed in treated animals compared with untreated mice or the mice treated with cyclophosphamide at 2 mg/kg/day (P < 0.05). Our results suggest that repeated adenovirally mediated gene therapy is achievable in cancer patients who are concurrently undergoing treatment with chemotherapy.

Adenoviridae↗
PubMed1998

Primary pancreatic lymphoma.

BACKGROUND: Primary pancreatic lymphoma is a rare neoplasm that may be confused with pancreatic adenocarcinoma. We reviewed retrospectively our contemporary experience with this disease to define more clearly the clinical presentation of this disease and the proper role for percutaneous fine-needle aspiration biopsy and surgery. METHODS: From 1980 to 1995, 11 patients with primary pancreatic lymphoma were treated at The University of Texas M. D. Anderson Cancer Center. Patient demographics, radiographic studies, fine-needle aspiration biopsy findings, operative procedures, and other treatment data were reviewed. RESULTS: The median age of the 11 patients was 64 years (range, 37 to 74 years). Abdominal pain was the most common symptom at presentation. Five patients had an elevated lactate dehydrogenase level, and only two patients had hyperbilirubinemia. Computed tomography scan demonstrated encasement of the superior mesenteric artery or superior mesenteric-portal vein confluence in six patients. Seven patients underwent computed tomography-guided fine-needle aspiration; five had findings of lymphoma. Two patients underwent distal pancreatectomy and splenectomy, and one underwent pancreaticoduodenectomy. All patients were treated with combination chemotherapy, and seven received radiotherapy. Only two patients have died of disease (12 and 16 months after diagnosis) at a median follow-up time of 67 months. CONCLUSIONS: In the majority of patients, pancreatic lymphoma can be distinguished from pancreatic adenocarcinoma on the basis of symptoms, laboratory and radiographic findings, and fine-needle aspiration biopsy results. Once the diagnosis is established, all patients should undergo systemic chemotherapy followed by involved-field radiotherapy if the tumor has not been resected.

Adult↗
PubMed1998

Improved sentinel lymph node localization in patients with primary melanoma with the use of radiolabeled colloid.

BACKGROUND: The purpose of this study was to determine whether the sentinel lymph node (SLN) localization technique, which uses blue dye and 99mTc-labeled sulfur colloid, provides advantages over blue dye alone in the management of patients with stages I and II cutaneous melanoma. METHODS: The records of 626 consecutive patients with melanoma who underwent lymphatic mapping and SLN biopsy between 1991 and 1997 at the M.D. Anderson Cancer Center were reviewed. Lymphatic mapping was performed with isosulfan blue dye alone (n = 252) or in combination with 99mTc-labeled sulfur colloid accompanied by a hand-held gamma probe (n = 374). SLNs were defined as those that stained blue or demonstrated increased focal radiotracer uptake. RESULTS: SLN identification rates improved from 87% (dye alone) to 99% (dye and colloid) (P < .0001) with the combined technique in all anatomic sites examined. The mean number of SLNs harvested from each basin was significantly greater in the patients mapped with dye and colloid (1.74 vs 1.31; P < .0001). Occult metastatic disease was identified in 17.5% of all patients and did not significantly differ between groups. In 92% of patients who had at least one positive SLN and were mapped with both agents, lymphatic metastases were identified in the SLN that contained the greatest radiotracer uptake. CONCLUSIONS: SLN identification is enhanced by the addition of radiolabeled sulfur colloid and intraoperative use of the hand-held gamma probe and may identify SLNs missed by the blue dye alone. These data support the combined use of radiolabeled sulfur colloid and blue dye in lymphatic mapping procedures to improve the nodal staging of stages I and II melanoma.

Adolescent↗
PubMed1998

Reduction mammaplasty: its role in breast conservation surgery for early-stage breast cancer.

Segmental resection and radiotherapy is an accepted alternative over mastectomy for small, staged breast malignancies. However, women with large, pendulous breasts have been documented to have poorer cosmetic outcomes when undergoing irradiation after breast conservative surgery compared with women with small- or medium-size breasts, thought to be caused by dose inhomogeneity. The purpose of this study was to evaluate the efficacy of combining reduction mammaplasty with breast conservative surgery to facilitate postoperative irradiation. Between 1988 and 1996, 10 women have undergone bilateral reduction mammaplasty for breast malignancy followed by radiation therapy at our center. All women wished to avoid mastectomy (average age, 59 years). All lesions were detected preoperatively on mammography. The average amount of tissue removed was 945 g per breast. A variety of reduction techniques were employed to include the malignant lesions. All patients received 50 Gy of radiation therapy delivered in 25 fractions following reduction mammaplasty during a 5-week period. Radiation therapy was usually initiated within 4 weeks following surgery. Follow-up is currently 37 months, with all patients being followed for at least 8 months. No patients have had complications from the surgery or radiation therapy. No local recurrent malignancies have been detected. Cosmesis has been good to excellent in all patients. Despite equivalent survival outcomes for mastectomy for early-stage breast cancer, certain women are not good candidates for breast conservation and radiation therapy. An alternative for women with large, pendulous breasts that combines breast conservation therapy and concurrent bilateral reduction mammaplasty should be considered. This combination, in selected women, provides good functional and cosmetic results, and at the same time minimizes the potential difficulties of radiation therapy.

Breast Neoplasms↗
PubMed1997

A packaging system for SV40 vectors without viral coding sequences.

SV40 vectors have been used as expression vectors for mammalian cells since the early 1980s. More recently, they have been used as gene transfer vectors in mice and in human peripheral blood cells. Here we described a system for packaging SV40 vectors without viral coding sequences. Recombinant adenovirus-expressing SV40 capsids can effectively package plasmids that contain the SV40 replication origin. The final yield of infectious SV40 vector is about 3 x 10(5), with a SV40 to adenoviral vector ratio of about 1000:1. Helper adenoviruses can be effectively heat-inactivated with no effect on the infectivity of SV40 vectors.

Adenoviridae↗
PubMed1997

Role of conservation therapy for invasive lobular carcinoma of the breast.

BACKGROUND: Invasive lobular carcinoma (ILC) accounts for 5% to 10% of all invasive breast cancers. Although breast conservation therapy using local excision and postoperative irradiation is a standard therapy for early invasive ductal breast cancer, the result of this strategy in ILC is not well documented. We sought to determine the rate of locoregional recurrence after breast conservation therapy in patients with ILC. METHODS: A retrospective review of 74 patients with ILC treated with breast conservation therapy at The University of Texas M. D. Anderson Cancer Center (n = 43) or The John Wayne Cancer Institute (n = 31) between 1977 and 1993 was performed. RESULTS: The median age of patients was 60 years, and median follow-up was 56 months (range 1 to 207 months). Thirty-nine patients had American Joint Committee on Cancer stage I disease, 30 had stage IIa disease, and five had stage IIb disease. All patients underwent surgical resection and postoperative radiation therapy. Twelve patients received postoperative adjuvant chemotherapy, and 27 patients were treated with adjuvant hormonal therapy. The 5-year actuarial locoregional recurrence rate was 9.8%, and the median time to recurrence was 77 months (range 41 to 113 months). Patients with positive or close (< or = 1 mm) surgical margins were at increased risk for local recurrence on univariate analysis (p = 0.034). Of the nine patients with breast recurrence, six underwent salvage therapy with total mastectomy and are disease free at the time of this writing, two patients died of distant disease, and one is alive with local disease at the time of this report. The 5-year disease-specific survival rate was 93.7%. CONCLUSIONS: Breast conservation therapy for ILC achieves locoregional control in the majority of patients. However, long-term follow-up of patients is important because many local recurrences following breast conservation therapy are late events.

Adult↗
PubMed1997

Splenectomy in the accelerated or blastic phase of chronic myelogenous leukemia: a single-institution, 25-year experience.

BACKGROUND: Patients in the accelerated or blastic phases of chronic myelogenous leukemia (CML) often have painful splenomegaly and secondary thrombocytopenia. We tested the hypothesis that splenectomy can be performed with minimal complications in advanced CML, thereby alleviating pain, reversing thrombocytopenia, and minimizing transfusion requirements. METHODS: We reviewed the records of 53 patients in the accelerated or blastic phases of CML who underwent splenectomy between 1970 and 1995 at the U. T. M. D. Anderson Cancer Center. RESULTS: Twenty-eight patients were in accelerated phase and 25 in blastic phase at the time of splenectomy. The most common indications for splenectomy were symptomatic splenomegaly (median splenic weight, 1000 gm; range, 120 to 6700 gm) or thrombocytopenia (platelet count less than 100,000/microliter) or both. There was 1 death within 30 days of splenectomy. The preoperative platelet count increased 3.72-fold +/- 0.53-fold (mean +/- SEM) by postoperative day 7 (p < 0.001; paired t test). Patients with transfusion-dependent thrombocytopenia had significantly fewer platelet and red blood cell transfusions in the 6 months after splenectomy than in the 6 months before splenectomy (p = 0.016; sign test). CONCLUSIONS: Splenectomy can be performed with minimal morbidity and mortality in advanced CML, thereby relieving symptomatic splenomegaly, reversing thrombocytopenia, and minimizing transfusion requirements.

Adolescent↗
PubMed1994

Congenital microgastria in a premature infant.

The authors report the case of a 1,500-g baby boy with microgastria, vascular ring, tracheoesophageal fistula (TEF), and the VATER association. Despite repair of the TEF and placement of a gastrostomy tube, he failed to thrive and had recurrent bouts of aspiration pneumonia. Gastric augmentation at 8 months of age resolved the feeding problems, and he now has a normal diet.

Abnormalities, Multiple↗
PubMed1992

Surgical management of the thyroid nodule: patient selection based on the results of fine-needle aspiration cytology.

To determine whether the routine use of fine-needle aspiration (FNA) cytology reduces the rate of unnecessary surgery, the surgical pathology of 54 thyroidectomy patients who had preoperative FNA was compared to the results obtained with 24 thyroidectomy patients who did not have preoperative FNA. Twenty-nine (85.3%) of the 34 patients who had a positive FNA were confirmed by histology to have a thyroid neoplasm; in 24 patients, the neoplasm was malignant. Two of the 17 patients who had a negative FNA but underwent thyroidectomy based on other factors were found to have thyroid cancer. Only 8 (33.3%) of the 24 surgical specimens of patients who did not have an FNA were found to be malignant. FNA had a sensitivity of 93.5% and a specificity of 75.0%. The results indicate that the routine use of FNA for patients with thyroid nodules reduces the incidence of unnecessary surgery. Furthermore, FNA alone is sufficient to identify most patients at risk and is, therefore, cost-effective. However, the presence of other findings suspicious of malignancy should preclude clinical decision making based on FNA alone.

Adolescent↗