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Biomedical subjects

G Monges

Publications and source records attributed to G Monges.

At least 55 records · Page 3Linked to original sources

Gastrointestinal hormone mRNA expression in human colonic adenocarcinomas, hepatic metastases and cell lines.

Aims-(1) To investigate the expression of the four main hormones of the digestive tract by performing reverse transcription polymerase chain reaction (RT-PCR) on a series of samples, comprising tumoral and healthy colonic tissues, hepatic metastases and colonic cell line samples; and (2) to study the patterns of labelling obtained with serological and morphological markers.Methods-After extraction and reverse transcription, gastrin, somatostatin, cholecystokinin (CCK) and transforming growth factor alpha (TGFalpha) mRNAs were detected by PCR and nested PCR using specific primers. The corresponding proteins were detected by immunohistochemistry.Results-The cell lines expressed all four mRNAs. Gastrin mRNA was present in most tumoral and metastatic samples, while the somatostatin transcript was detected in all samples and was frequently overexpressed in the normal colon. TGFalpha mRNA was expressed systematically in tumours of the right and transverse colon, but not in those located in the left colon; the expression of CCK mRNA was systematically absent in the left colon.Conclusions-The data presented here shed some light on the transcriptional events involved in the production of the various hormones present in the gastrointestinal tract, in both healthy and tumoral tissues. The various mRNAs expressed in cell lines are therefore not systematically expressed in the human pathology.

Journal Article↗

[Pancreatic and duodenal somatostatinoma. Two clinico-pathologic entities].

Somatostatinomas are endocrine tumors with predominant secretion of somatostatin. The majority occur in the pancreas and the duodenum. However, distinctive clinico-pathologic features are reported for both of them. The features of pancreatic somatostatinomas are a larger size, a more frequent clinical expression, a female predominance and a poorer prognosis. Duodenal somatostatinomas are characterized by psammoma bodies at histologic examination. We report here two cases of pancreatic and ampullary somatostatinomas, focusing on the main diagnostic problems and on the characteristics of each tumoral localization.

Aged↗

CD44 expression patterns in breast and colon tumors: a PCR-based study of splice variants.

CD44 cell-surface receptor expresses multiple isoforms, some of which are believed to play a role in tumor growth and metastasis. The CD44 gene is composed of 19 exons, of which 9 (exons 6 to 14) are alternatively spliced to form inclusions in the intervening membrane proximal region. Sequences present in the shortest metastatic variant cloned from a rat metastatic cell line have been shown to correspond to human exons 10 and 11, also called exons v6 and v7. Using RT-PCR, we have addressed in detail the CD44 isoforms produced in human breast and colon tumors. We analyzed 53 breast-tumor- and 58 colon-tumor-related samples as well as 1 benign mastopathy, 1 normal breast, 4 non-invaded lymph nodes and 8 normal colon tissues. All tumors analyzed expressed the hemopoietic CD44 (CD44H) isoform (no alternatively spliced exons added), whereas 81% expressed the CD44E form (addition exons 12, 13 and 14). Furthermore, 85% of tumors presented complex patterns of expression, with an average number of 5 to 6 bands detected. In view of their implication in the metastatic process, we investigated in greater detail the isoforms containing exons 10 and 11 (v6 and v7). Exon 10 was more frequently expressed than exon 11, 80% and 57% of the samples respectively. The great majority of cases showed ladder-like patterns starting from the shortest forms (exons 5-10 or 5-10-11) and larger-molecular-weight bands corresponding predominantly to sequential inclusions of exons from 3' to 5'. Exon-10 and exon-11 variants were also found in one benign mastopathy. The majority of normal tissues (1 breast and 6/8 colon) expressed only the CD44H isoform. These data indicate that expression of metastatic variants is common in human breast and colon tumors and can occur early during cancer progression, as testified by their presence in a benign breast tumor. While expression of exon-10 variants were correlated with presence of distal metastases in colon tumors, exon-11 variants were not (metastatic events were too rare in our breast-tumor series to reach significance). This suggest that exon 10 may correspond to the minimal sequences required to favor metastatic events.

Alternative Splicing↗

Oesophageal cancer and amplification of the human cyclin D gene CCND1/PRAD1.

The human CCND1/PRAD1 gene, located in the 11q13 chromosomal region, encodes a cyclin D protein with potential oncogenic capacity and is involved in several human malignancies. The amplification and expression status of CCND1 was investigated in a series of oesophageal tumours. CCND1 is amplified in 54% and overexpressed in 63% of the tumours of the squamous cell type.

Chromosomes, Human, Pair 11↗

Fine-needle aspiration cytology guided by endoscopic ultrasonography: results in 141 patients.

BACKGROUND AND STUDY AIMS: Diagnosis of submucosal lesions, pancreatic tumors, and mediastinal or celiac lymph nodes or masses is possible using endoscopic ultrasonography (EUS), but histological confirmation to differentiate between benign and malignant lesions is still required. The aim of this study was to evaluate the efficacy of a new method of EUS-guided fine-needle aspiration biopsy of intramural and paramural lesions. PATIENTS AND METHODS: From October 1991 to September 1994, EUS-guided fine-needle aspiration biopsy was carried out in 141 patients with findings of mediastinal masses (18 cases), mediastinal lymph nodes (24 cases), submucosal tumors (seven cases), celiac lymph nodes (26 cases), large gastric folds with negative endoscopic biopsy (13 cases), pancreatic tumors (43 cases), a small liver metastasis (five cases), retrorectal tumors (four cases), and an adrenal metastasis (one case). The EUS examination was performed using a Pentax-Hitachi FG 32-UA system. RESULTS: A malignant tumor was diagnosed in 110 of the 141 patients. EUS-guided fine-needle aspiration was positive in 85 cases. In 15 cases, an adequate specimen could not be obtained (10.6%). The sensitivity and specificity of the diagnosis of malignancy were 77.0% and 100%, respectively. Results were better for mediastinal masses (sensitivity 88%), mediastinal lymph nodes (81%), and celiac lymph nodes (80%) than for pancreatic tumors (75%) or submucosal tumors (60%). CONCLUSIONS: These results suggest that EUS-guided fine-needle biopsy using a curved-array transducer represents a step forward in the tissue diagnosis of gastrointestinal lesions.

Adult↗

[Multivariate analysis of the prognostic and predictive factors of response to concomitant radiochemotherapy in epidermoid cancers of the esophagus. Value of immunodetection of protein p53].

OBJECTIVE: The purpose of this study was to determine the prognostic value of the expression of protein p53, EGF receptors (EGR-R), cell proliferation antigen (Ki67) and DNA analysis by flow cytometry on per-endoscopic biopsies as well as the ability of these factors to predict response to concomitant chemoradiation in patients with squamous cell oesophageal carcinoma. METHODS: Sixty-two patients with squamous cell oesophageal carcinoma were prospectively included in this study. For 58 patients (51 men, 7 women; mean age: 59.1 +/- 9.3 years), clinical response to chemoradiation was correlated with the findings of flow cytometry (ploidy, % of cells in S-phase) and immunohistochemistry (p53, EGF-R, Ki67). There were 4 patients in stage I, 14 in stage II, 27 in stage III, and 13 in stage IV. Chemoradiation (2 cycles associating continuous 5FU 800 mg/m2/24 h from D1 to 5 and from D22 to 26, Cisplatyl 70 mg/m2 on D1 and D22; 15 Gy/5d from D1 to 5 and from D22 to 26), was performed prior to surgery in 19 patients (group I) and as the only treatment in 39 patients (group II), with a third cycle from D43. Clinical response was defined as complete or incomplete, ascertained by endoscopy and biopsy, 2 to 3 weeks after the end of chemoradiation. RESULTS: Mean survival in all 58 patients was 13.0 months. Survival was significantly longer in responders than in non responders (14.7 vs 9.6 months; P = 0.03). Among M0 patients, survival was not different in case of exclusive chemoradiation therapy or chemoradiation therapy followed by surgical excision (17.6 vs 13.0 months; NS). Monofactorial analysis showed that, in addition to response, the variables related to survival were stage, non-metastatic status, and absence of p53 surexpression. After multifactorial analysis according to the Cox model, the remaining variables were non-metastatic status, and absence of p53 surexpression. A complete response with negative biopsies was observed in 39 out of 58 patients, i.e. 67.3 +/- 12.1 % (group I: 12 out of 19; group II: 27 out of 39; NS). According to monofactorial analysis, 3 factors were predictive of complete response, i.e. non surexpression of p53 (P < 0.05) and tumour diameter (P = 0.04). After step-by-step logistic regression, non surexpression of p53 and tumour diameter continued to be predictive. The relative risk of a non-complete response was 5.46 if p53 was detected and 1.84 for each cm of added tumour diameter. These two factors were independent. CONCLUSIONS: In this study the predictors of complete response were absence of p53 surexpression and tumour diameter ascertained by CT-scan. Flow cytometry and Ki67 antigen had no prognostic value and were not predictors of response.

Adult↗

Detection of gastrin mRNA in paraffin-embedded samples of normal antral mucosae using polymerase chain reaction technique.

Gastrin, a peptide hormone produced by the G cells of the gastric antrum, plays a major role in the regulation of digestive mucosal growth. Although some light has been shed on the peptidic aspects of this hormone's mode of action and the co-regulatory activity in which it is involved along with the other gastrointestinal hormones, little is known at present about the modes of expression of its mRNA at the tissue level. A few attempts have been made so far to detect the transcript, mostly using molecular hybridization techniques. Here it was proposed to detect gastrin mRNA using a RT-PCR technique on a series of paraffin-embedded samples of normal human antrum processed with various fixatives commonly used in histology. The transcript was detectable in all the 7-microns sections of the samples treated with either formalin or Carnoy's solution, whereas Bouin's solution, which is also used as a fixative in histology, was found to have inhibitory effects on the method described here.

Acetates↗

Detection of gastrin mRNA in fresh human colonic carcinomas by reverse transcription-polymerase chain reaction.

To investigate the hypothesis that gastrin might be synthesized by tumour tissues in cancer of the colon, samples from six human colon tumours, one hepatic metastasis, four normal colonic mucosal samples and two antral and one fundic gastric mucosal samples from nine patients were analysed to determine whether gastrin mRNA was present. RNA was extracted from surgical specimens by ultracentrifugation on a CsCl cushion, purified using the guanidinium thiocyanate method, reverse-transcribed and amplified by polymerase chain reaction. Gastrin mRNA was detected in each colonic carcinoma sample (including the hepatic metastasis), while no such signal was observed in normal colon biopsies. Positive and negative controls (gastric antrum and fundus respectively) gave the expected results. In each of the positive samples, the chemiluminescent revelation of amplified products after Southern blotting corresponded to gastrin mRNA without the intron. These findings demonstrate the ability of primary and metastatic human colonic tumours to produce gastrin mRNA. Since malignant cell lines have been reported to produce gastrin peptide, and since gastrin receptors were present in some cases, our results support the idea that gastrin may be involved in an autocrine mechanism.

Base Sequence↗

[Guided puncture-cytology under electronic sectorial ultrasound endoscopy. Results in 26 patients].

The diagnosis of submucosal tumors, extrinsic lesions of gastrointestinal tract and mediastinal or celiac masses can be made by endoscopic ultrasonography (EUS) but histological confirmation (benign or malignant lesion) is still required. The aim of this study was to determine the efficacy of a new method, enabling EUS (curved array transducer)--guided fine needle aspiration of deep lesions. From October 1991 to August 1992, EUS-guided fine needle aspiration was performed in 26 patients in whom a mediastinal mass (6 cases), mediastinal lymph nodes (4 cases), submucosal tumor (5 cases), extrinsic masses (4 cases) and large fold gastric disease with negative endoscopic biopsy (7 cases) was detected by EUS. Diagnostic results were obtained in 19 of 26 patients (73.1%). A malignant tumor was detected in 21 of 26 patients. The EUS-guided fine needle aspiration was positive in 16 cases. The sensitivity for diagnosis of malignancy was 76.2% while specificity was 100%. The development of this new technique in the future needs further study.

Abdominal Neoplasms↗

[Gastric adenocarcinoma with an endocrine component. Report of nine cases].

Nine gastric adenocarcinomas containing endocrine cells were retrospectively studied to evaluate anatomo-clinical and immunohistochemical features, and the out-come of the patients. These gastric tumors were bulky with frequently lymph node metastasis. The immunohistochemical analysis had shown that all tumors contain EC cells, two tumors D cells, one tumor PP cells, but neither G cells nor A cells were detected. Five-years survival rate of these gastric tumors was slightly but not significantly increased as compared to usual adenocarcinomas (45.5% vs 36.5%). However, one can raise the question of possible control of local hormonal secretions on tumoral growth, particularly the anti-trophic part of the somatostatin.

Adenocarcinoma↗

Detection of gastrin mRNA by in situ hybridization using radioactive- and digoxigenin-labelled probes: a comparative study.

The hormone gastrin is mainly produced by the G cells of the antral mucosa and plays a major role in the regulation of digestive mucosal growth. Since it permits identification of cell types containing mRNA, in situ hybridization (ISH) appears to be an interesting method for studying gastrin-producing tissues. In this study, in situ detection of gastrin mRNA has been carried out on frozen sections of four human normal antral mucosa samples and of six colonic carcinomas removed from patients with high levels of plasma gastrin, using a gastrin oligonucleotidic DNA probe. We have compared the results provided respectively by the [35s] labelling and the digoxigenin labelling of the synthetic probe. Positive cells were found in each normal sample analysed with radioactive- as well as digoxigenin-labelled antisense probes. The total number of cells expressing gastrin mRNA appeared slightly higher with the [35s]-labelled probe, while the digoxigenin-labelled probe gave a better definition of positive signals. In contrast, neither radioactive nor cold probes gave positive signals in the six colonic carcinoma samples, although gastrin expression had been demonstrated in these tumours using a reverse transcriptase-PCR method. These results show that, although ISH does not seem sensitive enough to allow the detection of very low levels of gastrin expression, it would appear to be a reliable method for visualizing gastrin mRNA in human antral mucosa.

Base Sequence↗

[Serum gastrin levels in colorectal cancers. Evolution after treatment].

Increased basal serum gastrin level has been described in patients presenting with colorectal cancer. The aim of this work was to study the evolution of serum gastrin levels after cancer treatment. We measured basal serum gastrin levels before and 1 to 2 months after treatment in 15 patients (7 men, 8 women; mean age: 61.6 years). There were 3 malignant polyps, 4 Dukes A, 3 Dukes B, 4 Dukes C and 1 Dukes D colonic cancers. Treatment included 3 endoscopic polypectomies, 2 laser photodestructions, and 10 surgical resections, Mean basal gastrin level after treatment (49.07 +/- 12.65 mIU/l) was significantly lower (P less than 0.002) than before treatment (104.47 +/- 26.98 mIU/l). In the 2 patients treated by laser therapy, recurrences were associated with reincreasing serum gastrin levels. These results suggest an "autocrine" secretion of gastrin.

Adenocarcinoma↗

[Obstruction of pancreatic ducts with a fibrin glue. Study after segmentary autotransplantation in dogs].

The effects of the main pancreatic duct with a fibrin sealant have been investigated on an experimental model of segmental pancreatic transplantation in the dog. Fourteen segmental pancreatic transplantations were performed. A cephalic pancreactectomy was performed during the same operating time. The main duct was obstructed with a fibrin sealant (Tissucol modified by addition of a solution of aprotinine concentrated at 10,000 KUI per mL). Biological follow-up consisted in: 1) Intravenous Glucose Tolerance Testing at Day 0 and Day 28 with glycaemia's integral calculus and K V Alues. 2) Measurements of glycaemia and serum amylase every three days from day 0 to day 28. Histological examination of the pancreatic tissue before and after transplantation involved a microscopy analysis reporting the degree of fibrosis and necrosis. The areas of the Langherans islets and of the fibrosis were calculated with informatic area analysis. The study was carried on non diabetic dogs at Day 28. The glycaemia's calculus of IVGTT were not significantly different before and after transplantation (p = 0.291). On the other hand, there was a significant difference of the K Values before and after transplantation (p = 0.006). Histology after transplantation revealed important lesions of fibrosis and normal or hypertropic Langherans islets in most cases. Pancreatic ducts presented with linings thickened with fibrosis. There was no fibrin sealant in the lumen. Obstruction of pancreatic ducts with a fibrin sealant induces an important fibrosis of the pancreatic exocrin tissue allowing the preservation of a satisfactory endocrine function. This technic may be used in clinical practice during the segmental pancreatic transplantations or after cephalic pancreatico-duodenectomy.

Amylases↗

[Pancreatic conservation after autotransplantation in dogs. Value of histologic surface analysis].

A study of an artificial conservation fluid (hyperosmolar, pH = 8, rich in lactobionate and raffinose) was carried out by means of an experimental procedure involving segmental pancreatic autotransplants in dogs. The study covers 14 transplants, seven carried out without conservation and seven with 24-hour conservation at 4 degrees C. The caudal pancreas was removed after splenectomy and either transfused with 250 ml of 4 degrees C Euro-Collins before immediate transplant or with 250 ml of 4 degrees C conservation fluid for 24 hours before the transplant. The caudal pancreas was transplanted onto the right iliac vessels, while an arterio-venous fistula was created on the distal splenic vessels and the pancreatic duct was injected with modified tissucol. At the same time as the transplant, a cephalic pancreatectomy was performed. Laboratory tests included an intra venous glucose tolerance test monitored on days 0 and 28 and blood glucose and serum amylase measured every three days from days 1 to 28. The histological study of the pancreatic tissues 28 days after the transplants involved the light microscopic evaluation of the degree of fibrosis, inflammation of the pancreas, cystosteatonecrosis and peripancreatic inflammation. We used a computerized method to measure the surface area of the islets of Langerhans, as revealed by immunocytochemistry, and the surface area of fibrosis. The blood glucose and the serum amylase analyses from days 1 to 28, and the blood glucose variations during the intra venous glucose tolerance test, showed no differences between the two groups. Standard laboratory parameters were similar in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗