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T Aparicio

Publications and source records attributed to T Aparicio.

17 recordsLinked to original sources
PubMed2005

Leptin stimulates the proliferation of human colon cancer cells in vitro but does not promote the growth of colon cancer xenografts in nude mice or intestinal tumorigenesis in Apc(Min/+) mice.

BACKGROUND AND AIMS: Leptin, the product of the ob gene, has been suggested to increase the risk of colon cancer. However, we have shown that although leptin stimulates epithelial cell proliferation it reduces the development of carcinogen induced preneoplastic lesions in the rat colon. Here, we explored the effect of leptin in vitro on proliferation of human colon cancer cells, and in vivo on the growth of HT-29 xenografts in nude mice and the development of intestinal tumours in Apc(Min/+) mice. METHODS: Proliferation of HT-29, LoVo, Caco2, and SW 480 cells was assessed in the absence or presence of leptin (20-500 ng/ml) by 3H-thymidine incorporation and cell count. Leptin (800 microg/kg/day) or its vehicle was delivered for four weeks to nude mice, inoculated with HT-29 cells on day 0, and for six weeks to Apc(Min/+) mice. RESULTS: Leptin dose dependently stimulated cell DNA synthesis and growth in all cell lines. In nude mice, leptin caused a 4.3-fold increase in plasma leptin levels compared with pair fed controls. This hyperleptinaemia, despite leptin receptor expression in tumours, did not induce significant variation in tumour volume or weight. Tumour Ki-67 index was even inhibited. In leptin treated Apc(Min/+) mice, a 2.4-fold increase in plasma leptin levels did not modify the number, size, or distribution of intestinal adenomas compared with pair fed controls. CONCLUSIONS: Leptin acts as a growth factor on colon cancer cells in vitro but does not promote tumour growth in vivo in the two models tested. These findings do not support a pivotal role for hyperleptinaemia in intestinal carcinogenesis.

Adenoma↗
PubMed2004

Prognostic factors after surgery of primary resectable gastrointestinal stromal tumours.

AIMS: To analyse the prognostic factors of gastrointestinal stromal tumours (GIST) after a complete resection of the primary tumour. PATIENTS AND METHODS: Fifty-nine patients who underwent a complete initial resection of a GIST were studied. Peritumoral resections (PTR) were compared to segmental organ resections (SOR). Overall survival (OS) and the disease-free survival (DFS) were calculated using the Kaplan-Meier method. RESULTS: Primary sites were: stomach (25), small intestine (22), rectum (7), duodenum (5). Two patients had nodal involvement. The median follow-up was 45 months. Local DFS was significantly better after SOR compared to PTR (median 63 vs. 11 months, respectively, p<0.001). Univariate analysis for OS identified the grade (p=0.005) and size (p=0.02) as prognostic factors. Only a high histologic grade was an independent factor (p=0.02) in the multivariate analysis. Out of 49 patients who relapsed, the first recurrence was local only in 12, local and distant in 10 and distant only in 27; only one had a lymph node failure. Recurrences were accessible to curative surgery in 22 cases. OS of patients submitted to complete resection of their recurrence was significantly better than patients whose recurrence could not be resected (median 52 vs. 12 months, respectively, p<0.001). CONCLUSION: Complete surgery without rupture remains the mainstay of treatment in patients with localized, resectable disease. A peri-tumoral resection confers a high risk of local recurrence and should be avoided. Lymphadenectomy is not systematic. Grade is the main prognostic factor for OS and can be a decision marker for adjuvant treatment with Gleevec.

Adult↗
PubMed2003

Oxaliplatin- or irinotecan-based chemotherapy for metastatic colorectal cancer in the elderly.

The tolerance and efficacy of oxaliplatin and irinotecan for metastatic colorectal cancer are unknown in elderly patients. Methods. All consecutive patients over 74 years treated with oxaliplatin or irinotecan for metastatic colorectal cancer were enrolled. The tumour response was assessed every 2-3 months and toxicity was collected at each cycle according to World Health Organisation criteria. A total of 66 patients were enrolled from 12 centres. The median age was 78 years (range, 75-88 years); 39 patients had no severe comorbidity according to the Charlson score. In total, 44 and 22 patients received oxaliplatin or irinotecan, respectively, in combination with 5-fluororuracil+/-folinic acid or raltitrexed in 64 patients. A total of 545 chemotherapy cycles were administered in first (41%), second (51%) or third line (8%). A dose reduction occurred in 190 cycles (35%). Complete response, partial response and stabilisation occurred in 1.5, 20 and 47% of patients, respectively. The median time to progression and overall survival were 6.8 and 11.2 months in first line and 6.3 and 11.6 months in second line, respectively. Grade 3 and 4 toxicity occurred in 42% of patients: neutropenia 17%, diarrhoea 15%, neuropathy 11%, nausea and vomiting 8% and thrombopenia 6%. There was no treatment-related death. In selected elderly patients, chemotherapy with oxaliplatin or irinotecan is feasible with manageable toxicity.

Age Factors↗
PubMed2001

Antitumour activity of somatostatin analogues in progressive metastatic neuroendocrine tumours.

A few studies have suggested an antitumour activity of somatostatin analogues in neuroendocrine tumours (NET). The aim of this study was to evaluate the antitumour efficacy of somatostatin analogues in patients with documented progressive tumours. 35 consecutive patients with documented tumour progression were treated with somatostatin analogues. Patients were classified into two groups. In Group 1, tumours were progressing rapidly (an increase of 50% or more in the lesion surface area in 3 months) and in Group 2, tumours were progressing more slowly (an increase of less than 50% in the lesion surface area in 3 months but greater than 25% in 6 months). Treatment consisted of subcutaneous (s.c.) octreotide, 100 microg thrice daily for 17 patients, intramuscular lanreotide, 30 mg/every 14 days for 11 patients and for 7 patients both somatostatin analogues were used successively during the follow-up. Primary tumour sites were the small intestine (n=12), pancreas (n=13), lungs (n=5), and other sites (n=5). 18 patients had the carcinoid syndrome with flushing and/or diarrhoea. The median duration of treatment was 7 months. Treatment was discontinued in 3 patients due to side-effects. One patient (3%) achieved a partial response and the disease was stabilised in 20 patients (57%) for a median duration of 11 months (6-48 months). Stabilisation of patients in Group 1 was significantly less frequent at 6 months than that of patients in Group 2 (4/12 and 13/17 respectively, P<0.02). Somatostatin analogue treatment resulted in one partial response (3%) and 20 cases of stabilisation (57%) in 35 patients with progressive NET. A slow tumour growth rate before treatment is predictive of a good response to somatostatin analogues which could be considered an option for first-line treatment.

Adult↗
PubMed2001

Hepatocyte growth factor induces colonic cancer cell invasiveness via enhanced motility and protease overproduction. Evidence for PI3 kinase and PKC involvement.

Tumour progression to the metastatic phenotype is mainly dependent on tumour cell invasiveness. Cell migration is a crucial step in this process. Here we investigate the effect of hepatocyte growth factor (HGF) on the induction of in vitro invasiveness of poorly aggressive Caco-2 colonic cancer epithelial cells. Invasion assays through a Matrigel barrier were performed. Proteases were assessed by zymography, reverse transcription-polymerase chain reaction and immunoblotting. Caco-2 cells were found to express HGF receptor but not HGF and to secrete several proteases, namely matrix metalloproteinase-1 (MMP-1), MMP-2, possibly MMP-9 and urokinase plasminogen activator (uPA). Exogenous HGF promoted invasiveness of Caco-2 cells through an artificial basement membrane matrix and enhanced their production of proteases. In addition, analyses of media at the end of invasion assays indicated that anti-HGF antibody inhibited protease production in parallel with cell invasion. The involvement of proteases in the HGF-induced invasion process was further investigated using either a synthetic general MMP inhibitor or neutralizing antibodies against MMPs or uPA. All components significantly inhibited HGF-promoted cell invasion. Moreover, specific inhibitors of PKCalpha/beta1 and PI3 kinase also decreased both HGF-promoted cell invasion and protease expression in invasion assay media. Thus, our findings provide evidence that the process of HGF-activated invasiveness of Caco-2 cells involves PI3 kinase and PKC and results from close association of two events, stimulation of cell motile activity and concomitant overproduction of proteases, which permits cell migration through a degraded extracellular matrix.

Caco-2 Cells↗
PubMed2001

[Evaluation of three testing strategies for detection of hepatitis C in a hospital medical consultation and in an HIV testing center].

AIMS: Testing for hepatitis C virus (HCV) is recommended. The purpose of this study was to evaluate the efficacy of HCV testing in a medical consultation without an appointment and in an HIV testing center based on three testing strategies: 1997 French Consensus Conference, "Lettre de la Direction Générale de la Santé" (January 1996), and extension to other risk factors. PATIENTS AND METHODS: For 6 months a free blood test was offered to any patient with a risk factor according to the literature. RESULTS: There were 1 736 new patients at the medical consultation and 1 616 at the testing center. The patients were younger at the testing center than at the medical consultation (31.1 vs 43.3 years; P<0.001). Acceptance of screening was better at the testing center (97.8% vs 75.2%; P<0.001). There were more patients exposed to one of the risk factors at the testing center (31.2% vs 13.9%; P<0.001). Tests were more efficient at the testing center: 30 HCV positive patients/1 616 (1.86%) vs 11/1 736 (0.63%, P<0.01). Tests based on the 1997 French Consensus Conference provided detection in 27/30 (90%) of HCV positive patients at the testing center but only 4/11 (36.3%) at the medical consultation (P<0.01). CONCLUSION: Testing was effective in both places but was more efficient at the testing center. Efficacy of the testing strategies differs significantly according to the place of screening. At the testing center, screening can be restricted to patients with a history of intravenous drug use and blood transfusion. At the medical consultation, screening should be extended to other risk factors.

Adult↗
PubMed2000

pT3.2I, the smallest plasmid of Thiobacillus T3.2.

The whole nucleotide sequence of pT3.2I, the smallest plasmid of the acidophilic bacterium Thiobacillus T3.2, has been determined. pT3.2I is 15,390 bp long with a 53.7% GC content. Different regions can be defined in it: one 2569-bp putative insertion sequence similar to other insertion sequences of some Agrobacterium Ti plasmids; and a longer sequence, which occurs in two almost identical copies, differing only in a 1-bp deletion (6406 and 6405 bp). Several open reading frames and some smaller sequences were found in this duplicated region: ORFA and ORFG, encoding a putative polyol dehydrogenase and a putative RepA replication protein, respectively, an 83-bp sequence which could code for an antisense RNA, and a 36-bp region highly homologous to ori sequences of ColE2- and ColE3-related plasmids. Another putative gene, ORFH, is only present in the longer copy of this region (it is deleted in the short copy) and might encode a 90-amino-acid polypeptide which could act as a second replication protein, RepB. Based on sequence comparisons, pT3. 2I can be related to plasmids in the pColE2-CA42 incB incompatibility group.

Amino Acid Sequence↗
PubMed2000

Dihydropyrimidine dehydrogenase activity in normal, inflammatory and tumour tissues of colon and liver in humans.

BACKGROUND/PURPOSE: Dihydropyridmidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5FU). Although this catabolism is likely to occur in the liver in humans, there may be a local inactivation in tumours, modifying the efficacy of 5FU. The aim of this study was to examine the DPD activity in normal, inflammatory and malignant tissues from both the colon and the liver to assess the modifications of DPD activity in the process of tumourigenesis. METHODS: DPD activity was evaluated in 107 patients, corresponding to 194 samples (70 colorectal tumour and normal colon, nine metastases secondary to a colon cancer, ten inflammatory colon, 20 samples of normal liver, seven from primary liver cancer, and eight from inflammatory liver). DPD activity was determined using an enzymatic reaction followed by analysis of 5FU and its catabolite dihydro-5FU by high-performance liquid chromatograph. Results were expressed as pmol of 5FU catabolized/min x mg protein. RESULTS: DPD was highly variable in tumour and normal tissues, both from colon and liver. In colon, the correlation between DPD activity in tumour and normal mucosa was weak, even if it was statistically significant due to the higher number of samples. In inflammatory colon tissue (ulcerative colitis or Crohn's disease), DPD activity was significantly higher than in normal tissue (P = 0.006). In liver metastases from colon cancer, DPD activity was not significantly different from that observed in primary colon tumour (P = 0.32). In liver, DPD activity was significantly lower in primary liver tumour than in uninvolved liver specimens (P = 0.001). In inflammatory liver tissue (hepatitis), DPD activity ranged between normal and tumour tissues, and did not differ significantly either from normal tissue or primary liver cancer. CONCLUSIONS: DPD activity was modified in colon and in liver during a pathological process and the dysregulation of DPD increased from a benign to a malignant tissue.

Adolescent↗
PubMed1999

Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin.

The purpose of this study was to evaluate by a retrospective analysis of 53 patients the efficacy of chemotherapy combining etoposide and cisplatin in the treatment of neuroendocrine tumours. The regimen was a combination of etoposide 100 mg m(-2) day(-1) for 3 days and cisplatin 100 mg m(-2) on day 1, given by 2-h intravenous infusion, administered every 21 days. Twelve patients had a well-differentiated and 41 a poorly differentiated neuroendocrine tumour. Toxicity of treatment was assessed in 50 patients and efficacy in 52 patients. Among the 11 patients with a well-differentiated tumour evaluable for tumoural response, only one (9.4%) had a partial response for 8.5 months. Forty-one patients with a poorly differentiated tumour showed an objective response rate of 41.5% (four complete and 13 partial responses); the median duration of response was 9.2 months, the median overall survival 15 months and the median progression-free survival 8.9 months. Haematological grade 3-4 toxicity was observed in 60% of the cases with one treatment-related death, digestive grade 3-4 toxicity in 40% and grade 3 alopecia was constant. No severe renal, hearing and neurological toxicities were observed (grade 1 in 6%, 14%, 72% respectively and no grade >1). We confirm that poorly differentiated neuroendocrine tumours are chemosensitive to the etoposide plus cisplatin combination. However, the prognosis remains poor with a 2-year survival lower than 20% confirming that new therapeutic strategies have to be developed.

Adult↗
PubMed1999

Matrix metalloproteinase inhibition prevents colon cancer peritoneal carcinomatosis development and prolongs survival in rats.

Matrix metalloproteinases (MMP) are enzymes responsible for extracellular matrix degradation which play a role in cancer progression and metastatic spreading. We investigated the effects of the MMP inhibitor, batimastat, in vitro on the proliferation and invasiveness of the rat colon cancer cell line DHD/K12, and in vivo on the growth of an aggressive model of peritoneal carcinomatosis producing haemorrhagic ascites and metastases, obtained in the rat by i.p. injection of DHD/K12 cells. MMP production was studied in conditioned culture media, solid tumors and ascitic fluid. In vivo, after injection of tumor cells on day 0, rats received i.p. daily either batimastat (30 mg/kg) or equal volume of vehicle from day 2 until killing on day 43 (series I) or from day 13 until death (series II). The grade of peritoneal carcinomatosis, ascite volume, number and size of liver metastases were evaluated in both series, and survival in series II. MMPs-1, -2 and -9 were identified in culture media, tumors and ascites. In vitro, batimastat did not modify DHD/K12 cell proliferation and slightly reduced cell invasion. In vivo, in series I, batimastat treatment totally prevented peritoneal carcinomatosis and liver metastasis development. In series II, it significantly prolonged survival (P < 0.0002) and reduced peritoneal carcinomatosis (P < 0.001) and hepatic metastases number as compared with controls. However, batimastat-treated rats of the two series had peritoneal inflammation with marked ascites. Nevertheless, inhibition of MMP is a new therapeutic approach which may be promising in treatment of microtumors as in more advanced cancer stages.

Animals↗
PubMed1998

[Effects of HGF on the production of matrix metalloproteinases by colonic cancer cells DHD/K12].

Matrix metalloproteinases (MMPs) and growth factors such as hepatocyte growth factor (HGF) are implicated in tumoral progression of several digestive cancers. The rat DHD/K12 colonic cancer cell line is very invasive in vivo. We showed by RT-PCR and western immunoblotting the presence of HGF receptor, c-Met, in DHD/K12 cells. Then, we detected by zymography and western blots the secretion of MMP-2 and MMP-9 in the conditioned medium of these cells. After 24 or 48 h of culture in medium supplemented with HGF, transforming growth factor-alpha (TGF-alpha) or sodium butyrate, MMP production by DHD/K12 cells was stimulated by HGF and TGF-alpha and inhibited by sodium butyrate. Knowing the capacity of MMPs to degrade the extracellular matrix and thus to favour tumoral invasion, results suggest that HGF is implicated in the aggressive behaviour of DHD/K12 cells since it increased MMPs secretion by these cells.

Animals↗
PubMed1995

[Sero-epidemiology of hepatitis A: alcoholic patients are a group at risk].

OBJECTIVES: The possibility of "community-acquired" viral infection has been suggested in alcoholics. In order to assess this hypothesis, we evaluated the prevalence of antibodies against hepatitis A virus, a oro-fecally transmitted virus, in heavy drinkers. PATIENTS AND METHODS: We retrospectively studied 258 heavy drinkers, 188 males and 70 females, divided into sub-groups of increasing age, and compared them to 277 similarly classified blood donors. RESULTS: The prevalence of serum anti-hepatitis A antibodies was significantly higher in alcoholics than in controls (64.7 vs 52.3%, P < 0.01). The difference was particularly marked in patients younger than 45 years old (56.2 vs 39.1%, P < 0.01). In the alcoholics, there was no correlation between the prevalence of anti-hepatitis A antibodies and the socioeconomic level, the quantity of alcohol ingested, or the severity of the underlying liver disease. CONCLUSION: These results suggest that alcoholism is, per se, a risk factor for viral infections.

Adolescent↗