Search PubMed⌕ Search

Biomedical subjects

M Lopez

Publications and source records attributed to M Lopez.

At least 73 records · Page 4Linked to original sources
PubMed1999

Local and systemic liberation of proinflammatory cytokines in ulcerative colitis.

Determination of plasma and tissue cytokine levels in inflammatory bowel disease have frequently resulted in conflicting data. In the present study we determined in patients with ulcerative colitis (UC), the levels of the proinflammatory cytokines interleukin (IL)-1beta, IL-6, interferon (IFN)-gamma, and tumor-necrosis factor (TNF)-alpha liberated by peripheral blood mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC) after 48-hr culture with pokeweed mitogen (PWM). IL-1beta, IL-6, IFN-gamma and TNF-alpha in the supernatant were detected by ELISA. Results show low basal levels of IL-1beta secretion by PBMC and LPMC, and a considerable increase after mitogen stimulation. Basal IL-6 production by PBMC was higher in UC patients than in controls [2029 pg/ml, CI95(-165 to 4223) vs 572 pg/ml (-383 to 1527) respectively, P = 0.05] and also after PWM activation [14,995 pg/ml (7759-22,230) vs 6598 pg/ml (3240-9956), respectively, P = 0.05]. In LPMC, no differences in IL-6 secretion were observed. TNF-alpha in activated PBMC of patients with UC was not significantly increased in relation to control (P = 0.09). No constitutive secretion of IFN-gamma was observed in mononuclear cells. IFN-gamma levels secreted by activated LPMC were lower in patients with UC than in controls [1571 pg/ml (-108 to 3251) vs 7953 pg/ml (3851-12,055), respectively, P = 0.03]. These results suggest that IL-6, IL-1beta, and TNF-alpha participate as mediators in the inflammatory phenomena observed in UC. Further studies are necessary to evaluate the role of IFN-gamma in this condition.

Adult↗
PubMed1999

Influence of high-grade prostatic intra-epithelial neoplasia on total and percentage free serum prostatic specific antigen.

OBJECTIVE: To analyse the influence of high-grade prostatic intra-epithelial neoplasia (HGPIN) on total and percentage free serum prostatic specific antigen (PSA). PATIENTS AND METHODS: The total and free serum PSA levels were measured (using a double-monoclonal antibody immunoassay, Tandem and Tandem free PSA, Hybritech Inc, Liège, Belgium) in 570 consecutive patients undergoing sextant ultrasound-guided prostatic biopsy because of an abnormal digital rectal examination or a serum PSA concentration of > 4.0 ng/mL. The main diagnosis was benign disease in 321 (56%) and prostate cancer in 249 (44%). HGPIN was detected in 85 (15%) of the patients; in 17 (20%) it was associated with benign tissue and in 68 (80%) with prostate cancer. RESULTS: Patients with benign disease had a median total serum PSA level of 7.2 with no HGPIN and 7.7 ng/mL when HGPIN was present (P>0.05); the corresponding values in patients with prostate cancer were 16.0 and 15.9 ng/mL (P>0.05). The median percentage free serum PSA was 15.8 in patients with HGPIN-free benign disease and 14.1 when HGPIN was present (P>0.05); the corresponding values in patients with prostate cancer were 9.7 and 11.0 (P>0.05). In a multivariate analysis, prostate cancer was the major contributor to total and percentage free serum PSA levels. CONCLUSION: The presence of HGPIN does not contribute significantly to total and percentage free serum PSA levels.

Adult↗
PubMed1999

Cyclic AMP-responsive element binding protein in brain mitochondria.

Cyclic AMP-responsive element binding protein (CREB) is critically involved in many important brain functions, including the formation of long-term memory. CREB is the best characterized member of a family of transcription factors (CREB/ATF family) recognized to be important nuclear targets for intracellular signal transduction systems. Here we show, by using different approaches, that CREB is unexpectedly localized to mitochondria of the rat brain. Controlled subcellular fractionation of hippocampus and cerebral cortex showed that both synaptic and nonsynaptic mitochondria exhibited immunoreactivity to the phosphorylated form of CREB (pCREB). Moreover, CREB extracted from synaptic mitochondria is able to be phosphorylated by the catalytic subunit of protein kinase A and dephosphorylated by protein phosphatase 1 or 2B. DNA mobility shift assays showed the presence of binding activity to the calcium-cyclic AMP-responsive element in mitochondrial extracts from hippocampus; this binding complex was specifically supershifted by an anti-CREB antibody. Immunoelectron microscopic analysis of hippocampal subcellular fractions revealed that pCREB immunoreactivity is localized in close association with the inner mitochondrial membrane. These results, together with recent findings describing the presence and phosphorylation of CREB in developing dendrites, suggest that CREB may participate in different mechanisms involved in the communication between extracellular signals and the expression of genes.

Animals↗
PubMed1999

Nutritional support in alcoholic cirrhotic patients improves host defenses.

BACKGROUND: Malnutrition is usual in patients with alcoholic liver disease and is associated with a poor outcome. Nutritional support decreases nutrition-associated complications. AIM: To demonstrate that nutritional support in ambulatory alcoholic cirrhotic patients improves host defenses. METHODS: Thirty-one male outpatients with alcoholic cirrhosis CHILD-PUGH B or C were included. Twenty-five subjects completed six months consuming daily a nutritional supplement (Ensure, 1000 Kcal and 35 g protein), in addition to their regular diet. At entrance and every three months, a clinical assessment, nutritional evaluation and indirect calorimetry were performed. Liver function tests and LPS-induced monocyte production of cytokines, salivary secretory IgA, lactulose/mannitol ratio and breath hydrogen tests were also measured in these intervals. Delayed cutaneous hypersensitivity and IgG and IgM antibody response to endotoxin were assessed at entrance and at the end of the study. RESULTS: Patients drank 85% of the provided supplement as an average. REE, total body fat and serum albumin increased, basal breath hydrogen decreased and cellular immunity improved significantly during the follow up period (p< or =0.03). All the other parameters remained unchanged throughout the study. Six patients (16.2%) died during the study, five due to upper gastrointestinal bleeding. CONCLUSION: Nutritional support in alcoholic cirrhotic patients improves nutritional status and cell mediated immunity.

Adipose Tissue↗
PubMed1999

Epirubicin, folinic acid, fluorouracil, and etoposide in the treatment of advanced gastric cancer: phase II study of the Southern Italy Oncology Group (GOIM).

In the authors' previous experience, the addition of epidoxorubicin to the FA-FU regimen obtained a better response rate than that of FA-FU alone in patients with advanced gastric cancer. Furthermore, considering the good efficacy and mild toxicity observed with the addition of etoposide to the FA-FU combination in the German study, the authors conducted a trial to explore the efficacy and tolerability of the ELFE regimen (epirubicin, folinic acid, fluorouracil, and etoposide) in previously untreated advanced gastric cancer patients. Of the 55 patients entered, 51 were evaluable for efficacy. Four complete responses (8%) and 21 partial responses (41%) were observed, with an overall response rate of 49% (95% CI: 35-63%). The median duration of response and survival were 6 and 8 months, respectively. Responder patients showed a significantly better median survival duration than nonresponders (12 vs. 4 months, respectively; p < 0.0001). Toxicity was evaluated in all patients: only 1 patient refused to continue therapy despite low toxicity. As expected, the major toxicities observed were gastrointestinal disturbance, leukopenia, and loss of hair. In conclusion, the ELFE combination regimen appears to be effective and well tolerated for the treatment of advanced gastric cancer patients.

Adult↗
PubMed1999

The Texas Children's Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder.

OBJECTIVES: To develop consensus guidelines for medication treatment algorithms for childhood major depressive disorder (MDD) based on scientific evidence and clinical opinion when science is lacking. The ultimate goal of this approach is to synthesize research and clinical experience for the practitioner and to increase the uniformity of preferred treatment for childhood MDD. A final goal is to develop an approach that can be tested as to whether it improves clinical outcomes for children and adolescents with MDD. METHOD: A consensus conference was held. Participants included academic clinicians and researchers, practicing clinicians, administrators, consumers, and families. The focus was to review and use clinical evidence to recommend specific pharmacological approaches for treatment of MDD in children and adolescents. After a series of presentations of current research evidence and panel discussion, the consensus panel met, agreed on assumptions, and drafted the algorithms. The process initially addressed strategies of treatment and then tactics to implement the strategies. RESULTS: Consensually agreed-upon algorithms for major depressions (with and without psychosis) and comorbid attention deficit disorders were developed. Treatment strategies emphasized the use of selective serotonin reuptake inhibitors. The algorithm consists of systematic strategies for treatment interventions and recommended tactics for implementation of the strategies, including medication augmentation and medication combinations. Participants recommended prospective evaluation of the algorithms in various public sector settings, and many volunteered as sites for such an evaluation. CONCLUSIONS: Using scientific and clinical experience, consensus-derived algorithms for children and adolescents with MDD can be developed.

Adolescent↗
PubMed1999

Chest illnesses and the decline of FEV1 in steelworkers.

This study relates the impact of various medical conditions to clinically important forced expiratory volume in 1 second (FEV1) declines in a cohort of steelworkers evaluated cross-sectionally and longitudinally. Medical records of 1171 randomly chosen steelworkers were obtained from the medical department of a steel company. We reviewed the medical records for information regarding demographic parameters, smoking status, spirometry indexes, job history, and the worker's respiratory health. These workers had performed annual spirometry from 1980 to 1991 at least once and up to 12 times. We compared the prevalence of medical conditions in 203 male never-smoking steelworkers in this group of 1171 workers by separating workers into three groups on the basis of final predicted FEV1 values (< 65%, between 65% and 79%, and > or = 80%). We also evaluated the prevalence of medical conditions and the association between these conditions and the rate of annual decline in FEV1 in 475 steelworkers who had at least three valid tests and at least 5 years separating the first and last test by multiple logistic regression analysis. Of the 475 steelworkers, 121 were categorized as rapid decliners (an annual rate of decline in FEV1 exceeding the 75th percentile of the slope distribution), whereas the remaining workers served as controls. Three of 203 and 17 of the remaining 200 in the cross-sectional survey had final predicted FEV1 values < 65% or between 65% and 79%, respectively. Among these 20 never-smokers, the accelerated rate of decline could be reasonably explained by factors independent of dust and age in all but two. In the 203 never-smokers, hay fever and trauma occurred more frequently in those with a decreased predicted FEV1. In the longitudinal study of 475 workers, the prevalence of pneumonia was significantly greater in the rapid decliners, whereas the prevalence of allergy, asthma or hay fever, and trauma approached a significant excess in number. Logistic regression models demonstrated that aging, weight gain, smoking, trauma, pneumonia, and a history of allergy, asthma, or hay fever were independently related to the risk of a clinically important decline of FEV1 in this group. In summary, there are multiple risk factors for an accelerated rate of decline in workers with dust exposure. An accurate assessment of the causes for an excessive rate of lung function decline in an individual worker within a population requires an understanding of the relationship between environmental exposures, lung function decline, and the individual worker's underlying health. In addition to the three traditionally recognized variables--age, smoking, and dust exposure--the medical conditions of trauma, pneumonia, and allergy, asthma, or hay fever were related to a clinically important decline of FEV1 in this industrial population.

Adult↗
PubMed1998

The V domain of herpesvirus Ig-like receptor (HIgR) contains a major functional region in herpes simplex virus-1 entry into cells and interacts physically with the viral glycoprotein D.

The herpesvirus entry mediator C (HveC), previously known as poliovirus receptor-related protein 1 (PRR1), and the herpesvirus Ig-like receptor (HIgR) are the bona fide receptors employed by herpes simplex virus-1 and -2 (HSV-1 and -2) for entry into the human cell lines most frequently used in HSV studies. They share an identical ectodomain made of one V and two C2 domains and differ in transmembrane and cytoplasmic regions. Expression of their mRNA in the human nervous system suggests possible usage of these receptors in humans in the path of neuron infection by HSV. Glycoprotein D (gD) is the virion component that mediates HSV-1 entry into cells by interaction with cellular receptors. We report on the identification of the V domain of HIgR/PRR1 as a major functional region in HSV-1 entry by several approaches. First, the epitope recognized by mAb R1. 302 to HIgR/PRR1, capable of inhibiting infection, was mapped to the V domain. Second, a soluble form of HIgR/PRR1 consisting of the single V domain competed with cell-bound full-length receptor and blocked virion infectivity. Third, the V domain was sufficient to mediate HSV entry, as an engineered form of PRR1 in which the two C2 domains were deleted and the V domain was retained and fused to its transmembrane and cytoplasmic regions was still able to confer susceptibility, although at reduced efficiency relative to full-length receptor. Consistently, transfer of the V domain of HIgR/PRR1 to a functionally inactive structural homologue generated a chimeric receptor with virus-entry activity. Finally, the single V domain was sufficient for in vitro physical interaction with gD. The in vitro binding was specific as it was competed both by antibodies to the receptor and by a mAb to gD with potent neutralizing activity for HSV-1 infectivity.

Binding Sites↗
PubMed1998

The human poliovirus receptor related 2 protein is a new hematopoietic/endothelial homophilic adhesion molecule.

We have recently described Poliovirus Receptor Related 2 (PRR2), a new cell surface molecule homologous to the poliovirus receptor (PVR/CD155). Both molecules are transmembrane glycoproteins belonging to the Ig superfamily (IgSF). They contain 3 Ig domains of V, C2, and C2 types in their extracellular regions that share 51% aa identity. The PRR2 gene encodes two mRNA isoforms of 3.0 kb (hPRR2 [short form]) and 4.4 kb (hPRR2delta [long form]), both widely expressed in human tissues, including hematopoietic cells. To further characterize PRR2 expression during hematopoiesis and to analyze its function, we have developed a monoclonal antibody (MoAb) directed against its extracellular region (R2.477). PRR2 was expressed in 96% of the CD34(+), 88% of the CD33(+), and 95% of the CD14(+) hematopoietic lineages and faintly in the CD41 compartment. Ectopic expression of both PRR2 cDNAs induced marked cell aggregation. A soluble chimeric receptor construct with the Fc fragment of human IgG1 (PRR2-Fc) as well as a fab fragment of the anti-PRR2 MoAb (R2.477) inhibit aggregation. PRR2-Fc binds specifically to PRR2-expressing cells. These results suggest that PRR2 is a homophilic adhesion receptor. PRR2 was also expressed at the surface of endothelial cells at the intercellular junctions of adjacent cells but not at the free cellular edges. Homophilic interactions are associated with dimerization of isoforms of PRR2 and lead to the tyrosine phosphorylation of PRR2delta. Altogether, these results suggest that homophilic properties of PRR2 could participate to the regulation of hematopoietic/endothelial cell functions.

Animals↗
PubMed1998

Characterization of a UDP-Gal:Galbeta1-3GalNAc alpha1, 4-galactosyltransferase activity in a Mamestra brassicae cell line.

The binding of Bandeiraea simplicifolia lectin-I isolectin B4 on the endogenous glycoproteins of different insect cell lines led us to characterize for the first time a UDP-Gal:Galbeta1-3GalNAc alpha1, 4-galactosyltransferase in a Mamestra brassicae cell line (Mb). The study of the acceptor specificity indicated that the Mb alpha-galactosyltransferase prefers Galbeta1-3-R as acceptor, and among such glycans, the relative substrate activity Vmax/Km was equal to 20 microliters.mg-1.h-1 for Galbetal-3GlcNAcbeta1-O-octyl and to 330 microliters.mg-1.h-1 for Galbeta1-3GalNAcalpha-1-O-benzyl, showing clearly that Galbeta1-3GalNAc disaccharide was the more suitable acceptor substrate for Mb alpha-galactosyltransferase activity. Nuclear magnetic resonance and mass spectrometry data allowed us to establish that the Mb alpha-galactosyltransferase synthesizes one unique product, Galalpha1-4Galbeta1-3GalNAcalpha1-O-benzyl. The Galbeta1-3GalNAc disaccharide is usually present on O-glycosylation sites of numerous asialoglycoproteins and at the nonreducing end of some glycolipids. We observed that Mb alpha1,4-galactosyltransferase catalyzed the transfer of galactose onto both natural acceptors. Finally, we demonstrated that the trisaccharide Galalpha1-4Galbeta1-3GalNAcalpha1-O-benzyl was able to inhibit anti-PK monoclonal antibody-mediated hemagglutination of human blood group PK1 and PK2 erythrocytes.

Animals↗
PubMed1998

Relation between variation in copy number of ribosomal RNA encoding genes and size of harbouring chromosomes in Leishmania of subgenus Viannia.

Chromosomal size polymorphism in Leishmania of subgenus Viannia has been correlated with eco-geography. The sizes of chromosomes bearing rDNA genes were determined in 69 isolates. A considerable size-variation was observed, ranging from 1100 to 1500 kb. Chromosomes of L.(V.). braziliensis, L.(V.)guyanensis and L.(V.) peruviana from northern Peru were significantly larger (200 kb) than those of L.(V.) peruviana from southern Peru. In addition, 31 out of 69 isolates presented each two different-sized homologues of the rDNA chromosome. Long range restriction mapping of three different-sized rDNA chromosomes from L.(V.)braziliensis M2903 and L.(V.)peruviana HB31 (north) and LC106 (south) each revealed three fragments delimited by PmeI restriction sites: two constant in size (the centre and one extremity of the chromosome) and one variable (the other extremity, containing a single cluster of rDNA genes). Further analysis of the M2903 rDNA chromosome allowed the localization of its 140 kb rDNA cluster at 85 kb from the telomeric end. Two arguments indicated that size-variation of the rDNA chromosome is partially due to amplification/deletion of the clustered rDNA genes: (i) size-variation of the cluster-containing fragment was proportional to the size-variation of the whole chromosome, and (ii) hybridization signal intensity of the rDNA chromosome with a small subunit rDNA probe strongly correlated with chromosomal size. Nevertheless, DNA sequences present between the rDNA cluster and the telomere might also play a role in chromosomal size polymorphism. In addition, our data suggest that rDNA gene copy number (20-40 copies cell(-1) under a diploid hypothesis) in subgenus Viannia is lower than reported previously.

Animals↗
PubMed1998

Electrocautery as a factor in seroma formation following mastectomy.

BACKGROUND: Electrocautery has been postulated as a factor in the risk of seroma formation after mastectomy. METHODS: Eighty consecutive mastectomies in 74 patients were randomly assigned to dissection of the mastectomy flaps with either scalpel (n = 38) or electrocautery (n = 42). Total volume of fluid output through drains and aspirated from seromas was recorded. Other factors investigated included the type of drain utilized, estimated blood loss, and complications. RESULTS: Seromas developed in 16 wounds in the electrocautery group compared with 5 in the scalpel group (38% and 13%, respectively; P = 0.01). Other factors with an independent risk for seroma included use of Jackson-Pratt drains compared with Blake drains (P = 0.006), and lower estimated blood loss (P = 0.006). No differences in characteristics of patients or in other complications were noted. CONCLUSIONS: Use of electrocautery to create skin flaps in mastectomy reduced blood loss but increased the rate of seroma formation.

Aged↗
PubMed1998

Conservative surgery and radiotherapy in early stage breast cancer: a comparison between tumourectomy and quadrantectomy.

BACKGROUND AND PURPOSE: This study analyses and compares the results of local regional control, distant metastases and survival in two series of patients irradiated from 1986 to 1992 in our radiation oncology centre following quadrantectomy or tumourectomy for early stage breast cancer. MATERIALS AND METHODS: The quadrantectomy group consisted of 152 women, 109 (72%) with T1 and 43 (28%) with T2 tumours. Axillary nodes in this group were positive in 51 (33%) patients. The tumourectomy group included 123 women, 71 (58%) with T1 and 52 (42%) with T2 tumours. Positive axillary nodes were found in 56 (46%) of these patients. All quadrantectomy and tumourectomy patients received a dose of 50 Gy in 5 weeks to the whole breast, followed by a 10-16 Gy electron boost. Node positive patients in the tumourectomy group also received 50 Gy to the axillary apex and supraclavicular region. In both surgical groups, node positive premenopausal and postmenopausal patients received adjuvant CMF or tamoxifen therapy, respectively. RESULTS: After a median follow-up of 58 months, 89% of women in the tumourectomy group and 87% in the quadrantectomy group were alive and 80 and 73%, respectively, were free of disease. Breast and nodal failures were detected in 4.9 and 0.8% of cases, respectively, in the tumourectomy group, as compared to 5.9 and 3.3% of cases, respectively, in the quadrantectomy group. Distant relapses were observed in 16 and 18% of patients in the former and latter groups, respectively. Actuarial overall and disease-free survival was similar in the two series, with 5-year rates of 90 and 72%, respectively, in the tumourectomy group, and of 91 and 78%, respectively, in the quadrantectomy group. The differences in survival are not statistically different. CONCLUSIONS: Our findings show that tumourectomy and quadrantectomy, followed by adequate radiotherapy, provide comparable results in terms of local-regional control and survival.

Adult↗
PubMed1998

Clinical psychology in the management of pediatric skin disease.

The role of psychological factors in certain dermatological conditions is not disputed; however, these processes have been much more thoroughly explored in adult populations than in pediatric populations. Therefore, this article reviews relevant adult and child studies. This article explores three aspects of psychological functioning as they relate to dermatological conditions and their treatment, specifically stress and emotional regulation, behavioral and environmental issues, and compliance. The goal of this article is to give the practicing dermatologist a working overview of psychological factors in pediatric skin disease which will facilitate good communication with families around these issues and referral for adjunctive psychological treatment as needed.

Adolescent↗
PubMed1998

Evaluation of an innovative program to address the health and social service needs of drug-using women with or at risk for HIV infection.

Drug-using women with or at risk for HIV infection have many competing unmet needs, especially for social services, drug treatment, and medical care. High-risk drug-using women were recruited through street outreach, at needle exchange sites, a prison, and local community based organizations in New Haven, Connecticut for a study of the service needs of out-of-treatment drug users and the ability of an interactive case management intervention (ICM) to address those needs. These women were administered baseline and follow-up interviews to identify their health and social service needs and the degree to which these needs were resolved. The women who chose to enroll in the interactive case management intervention (n = 38) did not differ demographically nor in their HIV risk behaviors from those not receiving case management (n = 73). Provision of ICM was most successful in meeting needs for supportive mental health counseling, basic services, and long term housing. The impact of interactive case management was less evident for the acquisition of medical and dental services, which were accessed comparably by women not receiving the intervention. Overall, the women who enrolled in the ICM intervention showed a significant decrease in the number of unmet service needs as compared to those who did not enroll. Multiple contacts were required by the case manager to establish trust and to resolve the unmet service needs of these high-risk women. Women with or at risk for HIV infection can be effectively engaged in an ICM intervention in order to meet their multiple unmet service needs, although such interventions are time-and-labor intensive.

Adult↗
PubMed1998

Cell culture bags allow a large extent of ex vivo expansion of LTC-IC and functional mature cells which can subsequently be frozen: interest for a large-scale clinical applications.

The aim of this study was to evaluate the ex vivo expansion of normal CD34+ cells in gas-permeable polypropylene bags suitable for clinical use. Cells were cultured for 14 days in serum-free medium supplemented with SCF, IL3, IL6, FLT3-1, G-CSF + MGDF or Epo. The bags supported the expansion of hematopoietic cells in a similar manner to small scale well or flask systems, allowing mean expansions of up to 2193-fold for total nucleated cells, 140-fold for CFU-GM and 66-fold for LTC-IC. Increasing the initial cell concentration from 5 x 10(3) to 1 x 10(5)CD34+ cells/ml induced the production of granulocytic cells with terminal differentiation while simultaneously decreasing the overall extent of expansion of the white blood cells produced. We tested the phagocytic activity and oxidative metabolism of the white blood cells produced. The percentage of phagocytic cells was 39+/-0.5% in expanded cultures derived from fractions initiated at 5 x 10(3), 10(4) or 10(5) cells/ml and 45+/-6% in cultured cells obtained from starting fractions containing 5 x 10(4) cells/ml, as compared to 58+/-4% in normal controls. A study of the potential for oxygen-dependent microbe killing showed that the expanded cells produced H2O2, although in lesser quantities than control cells. We subsequently investigated the possibility of freezing expanded cells. Total cell recovery after thawing was 45+/-4%, while recoveries of progenitors and stem cells ranged from 65 to 90%, without any influence of the initial cell concentration. This new approach could be of major interest for clinical practice, as it would allow evaluation of the quality of a graft prior to its infusion and employs experimental conditions which meet the criteria for potential clinical use.

Blood Preservation↗
PubMed1998

Repeated cycles of retrovirus-mediated HSVtk gene transfer plus ganciclovir increase survival of rats with peritoneal carcinomatosis.

Peritoneal carcinomatosis is a common clinical situation that requires novel therapeutic approaches. We investigated the efficiency of an HSVtk gene therapy for the treatment of peritoneal carcinomatosis induced in syngeneic rats by DHD/K12 colon carcinoma cells. In this setting, the efficiency of two different retrovirus producing cell lines (GP+AmEnv12 and FLYA13) was compared. Rats treated with a single injection of retrovirus producing cells followed by a 5-day course of ganciclovir treatment showed an increased survival as compared with control animals. Animals treated with three injections of producing cells, each followed by a 4-5-day course of ganciclovir treatment, showed an increased survival as compared with control rats and with those treated with a single cycle of retrovirus producing cells plus ganciclovir. However, only a few animals remained tumor-free after day 180. There was no difference between the two producing cell lines in any of the experiments. RT-PCR demonstrated a faint expression of the tk transgene in the liver, spleen, epiploon, bowels and the lung of the animals injected with the HSVtk producing cells, reflecting most likely the transduction of only a limited number of cells.

Animals↗