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Biomedical subjects

V Giachè

Publications and source records attributed to V Giachè.

13 recordsLinked to original sources
PubMed1999

Correlation between DNA content and p53 deletion in colorectal cancer.

OBJECTIVE: To find out whether tumour DNA content correlates with allelic loss of p53 and other pathological features in primary colorectal carcinomas. DESIGN: Ongoing prospective study. SETTING: University hospital, Italy. SUBJECTS: 128 patients who had undergone radical resections for colorectal carcinoma. INTERVENTIONS: Flow cytometric measurement of tumour DNA content and detection of allelic loss on the short arm of chromosome 17 by Southern blot (restriction fragment length polymorphism) analysis in fresh tumour specimens. MAIN OUTCOME MEASURES: Correlation between DNA ploidy and deletion of p53, as well as between these two genetic events and clinicopathological variables. RESULTS: Interpretable DNA histograms were obtained for 122 tumour specimens. Forty-three tumours (35%) were diploid and 79 (65%) aneuploid. The diploid tumours were significantly more common in the proximal colon (from the caecum to the splenic flexure) than in the distal colon (from the descending colon to the rectum) (p = 0.002). The allelic state on the short arm of chromosome 17 was evaluated in 80 heterozygous patients. Forty-four tumour specimens (55%) showed deletion of 17p. Allelic loss of p53 was significantly more common in the distal and rectal tumours than in the proximal ones (p < 0.0001). Aneuploidy was more common among those tumours which had shown deletion of p53 than in those that had not (p = 0.0008). CONCLUSIONS: DNA aneuploidy was significantly associated with the deletion of the p53 gene. This suggests that the functional loss of p53 may favour the growth and establishment of an aneuploid cell population within tumours. Tumours of the proximal and distal colon differ in their genetic nature.

Adenocarcinoma↗
PubMed1998

Colonic cell proliferation in normal mucosa of patients with colon cancer.

Cell kinetics parameters have been analysed in colonic mucosa at different distances from a tumour in patients with colon carcinoma. Total cell number (TCN), 3H thymidine labelling index (TLI), mitotic index (MI), Goblet cell index (GCI) and the distribution of labelled cells along the crypt column (cell position frequency plot) were determined in well-aligned crypts. Total cell number, GCI and the labelled cell position frequency plots were similar in different samples from the same individual. A negative linear correlation between TCN and TLI was observed. The analysis of the cell position plots showed two patterns 1) with a high concentration in the bottom fifth of the crypt and 2) with frequent labelled cells at high positions. Whereas a negative correlation between overall TLI and the percent contribution to the TLI of the lowermost fifth was seen, the correlation was positive for the next 3 fifths and labelling was absent in the last part of the crypt.

Aged↗
PubMed1997

Analysis of HPV16, 18, 31, and 35 DNA in pre-invasive and invasive lesions of the uterine cervix.

AIMS: To analyse the physical state of different human papillomavirus (HPV) DNAs in 55 intraepithelial and invasive HPV associated cervical neoplasms. METHODS: Restriction analysis, using a panel of five HPV type specific enzymes, was carried out for each sample; this was followed by Southern blot analysis. RESULTS: Six (25%) of 24 cervical intraepithelial neoplasms had integrated DNA of different HPV types. In contrast, integration was detected in 25 (81%) of 31 cervical carcinomas. Tumour samples revealed differences in the integration profile of HPV16 and the other HPV types. Six (26%) of 23 HPV16 associated cancers contained only episomal DNA. In contrast, all eight tumours containing HPV18, 31, or 35 revealed integrated DNA exclusively. CONCLUSIONS: The results suggest that in advanced cervical intraepithelial neoplasia lesions, a subset of lesions can be identified in which the viral genome is integrated and there is a greater risk of malignant progression. In addition, HPV16 DNA was not present in the integrated form in 26% of tumours, suggesting that integration and subsequent inactivation of the transcriptional regulator, E2, are not essential steps for the development of HPV16 associated carcinoma. In this respect, the behaviour of HPV16 associated tumours is different from HPV18, 31, and 35 associated tumours, where the viral genome is always present in the integrated form.

Adult↗
PubMed1991

Gastric cell proliferation kinetics and bile reflux after partial gastrectomy.

Thirty-four randomized, partially gastrectomized subjects (12 with a Billroth II, 11 with a Billroth I, and 11 with a total biliary diversion reconstruction) were studied in order to assess the relationships between bile reflux, gastric histology, and cell proliferation kinetics. Bile acid quantity and concentration in the gastric aspirates progressively decreased from Billroth II to Billroth I to total biliary diversion (after which reflux was almost absent). Perianastomotic mucosa in Billroth II subjects showed the greatest degree of foveolar hyperplasia, and this decreased markedly with increasing distance from the anastomosis. Hyperplastic changes were less evident in Billroth I, and virtually absent in total biliary diversion subjects. The overall foveolar hyperplasia-like behavior of cell kinetic parameters (total pit cell number, labeled pit cell number, and labeling index) was shown. Moreover, subjects with mean bile acid concentration greater than 150 mumol/L had both a greater prevalence of foveolar hyperplasia and greater values of cell kinetic parameters than those with mean bile acid concentration less than or equal to 150 mumol/L. A superficialization of the proliferative compartment was also evident in the former group. These results show a close relationship between postgastrectomy bile reflux, foveolar hyperplasia, and cell kinetic parameters. Histologic and cell kinetic findings are probably the expression of gastric adaptation to chronic bile reflux exposure. Moreover, the type and entity of cell kinetic involvement and its relationship to foveolar hyperplasia and reflux may suggest new "tools" in post-gastrectomy surveillance and help to clarify patterns of gastric carcinogenesis.

Bile Reflux↗
PubMed1987

Circadian phenomena and irradiation. Modifications of enzyme activity in the small intestine after sublethal exposure.

Irradiation effects after a 3 Gy dose administered at four different times of a 24 h light/darkness cycle were studied: the modifications in the brush border enzyme activity of epithelial cells of the small intestine were determined. In controls the activity of these enzymes showed circadian oscillations with the maximum during the dark period and the minimum during the light period. The trend after irradiation in the various groups was very similar but some differences were present specially at the initial intervals when the effect appeared to be different depending on the enzyme level at the time of exposure. Lactase activity in animals irradiated at 0.00 and 18.00 o'clock returned to control levels later than in the other groups.

Animals↗
PubMed1983

Behaviour of lysosomal enzymes in the small intestine after multiple daily fractionation.

Modifications in the activities of some lysosomal enzymes were studied in the small intestine after irradiation on the abdomen by multiple daily fractionation of 3 Gy per fraction every 12 hours. Total doses of 6 and 12 Gy were studied. With lower dose variations were slight. The modifications of acid phosphatase an cathepsin D appeared very low, whereas beta-glucuronidase increased until 72 hours after the last fraction and then returned to control values. With respect to 8 Gy single dose the injury appeared comparatively similar.

Acid Phosphatase↗
PubMed1982

Modifications of small intestine lysosomal enzymes after irradiation at different times of the day.

The modification of lysosomal enzyme activities in animals irradiated with the same sublethal dose at 4 different times of the day is reported. The results confirmed the absence of circadian fluctuations in all the lysosomal enzymes and in protein content. A difference in behaviour between acid beta-galactosidase and beta-glucuronidase on the one hand and between acid phosphatase and cathepsin D on the other was evident in irradiated animals. The results showed that acid beta-galactosidase and beta-glucuronidase increase from the early intervals after irradiation and reach the highest activity between 36 and 48 h. At these intervals autolysis phenomena, heavy cellular alterations and numerous phlogosis cells are present in the epithelium. Only beta-glucuronidase and acid beta-galactosidase indicate the level of radiation injury.

Acid Phosphatase↗
PubMed1982

Modifications in the brush border enzymes of the small intestine after irradiation at different times of the day.

The behaviour of the brush border enzyme activity of the intestinal epithelium after the same sublethal radiation dose to the abdomen at different times of the day was investigated. Three previously observed post-irradiation phases (initial increase of activity, reduction and the return to control values) were confirmed, although with some differences. A later return to normal of lactase was also confirmed. The same dose produced different behaviour of the enzyme activities both during the initial and the recovery phase, depending on the time of the day when irradiation was performed, i.e. on the functional condition of the epithelial cells.

Animals↗
PubMed1982

Unconventional dose administrations: modifications of body and small intestine weights.

The modifications of body and small intestine weight were analyzed after abdominal irradiation in rats. Different doses were administered in single sessions, in two equal fractions with different splits, in multiple daily fractionations, varying the amount of the dose and the intervals among fractions. The results show that body weight gradually decreased after irradiation and only after many days it returned to control levels. Small intestine weight decreased starting from early intervals, and a rapid increase over controls was observed at 5 days. A return to control levels was reached later. Multiple-daily-fractionation (MDF) irradiation with 12 Gy (1200 rad) produced modifications less evident that the same dose administered in single session and appeared more similar to those observed after 6 or 8 Gy, according to the different splits used. The more marked the damage the lower the interval between fractions when a total dose of 12 Gy was administered in two fractions. The modifications after 6 Gy MDF were less marked than after a single session of the same magnitude, both in body and small-intestinal weight. In conclusion the MDF used in these experiments produced a damage very easily recovered by the organism in spite of the short time of dose administration.

Abdomen↗
PubMed1979

Circadian activity of rat kidney enzymes.

Alkaline phosphatase, LAP, beta-glucuronidase and cathepsin D activities and protein content of the kidney homogenate did not show any circadian rhythm in animals sacrificed at different hours of the day. The fluctuations of maltase appear modest and not dependent on a ligh/dark cycle.

Animals↗
PubMedDate not supplied

A method for measuring microquantities of DNA.

Quantitative analysis of DNA content represents a critical step when only very small amounts of nucleic acids are available. The DNA content of a small RNA-free sample can be measured in a simple and precise way using a two-dimensional approach. DNA samples are spotted on the surface of an agarose gel containing ethidium bromide (EtBr) and the ultraviolet-induced low-light fluorescence emitted by EtBr molecules intercalated into the DNA is evaluated. The high sensitivity and reproducibility of this quantitative method has been obtained using an advanced analysis system capable of distinguishing low-light fluorescent patterns, as in the case of DNA stained with EtBr, from the background. Use of an internal standard is necessary because the intensity of the signal is due to the aperture of camera diaphragm and to gel conditions. Using this two-dimensional analysis system it is possible to obtain rapid and precise quantitation of as little as 2 ng of DNA.

Animals↗
PubMedDate not supplied

[Cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV) infection].

Many studies have shown a strong correlation between CIN and HPV infection. Molecular biology has allowed identification of types of HPV which seem to be connected, more frequently than others, to dysplastic lesions. Physical state of HPV-genome seems to play an important role in the development of cervical cancer. In this study the HPV-genome has been searched in tissue specimens obtained from 34 women affected by CIN II and III. All patients underwent laser conization. Immediately before treatment, colposcopically directed biopsies of the cervical lesion and of the areas with no colposcopically apparent disease were taken and on these samples, HPV-DNA has been searched, isolated and analysed for HPV types and physical state. Histologic examination on cones showed 6 cases of CIN II (3 with HPV), 24 cases of CIN III (14 with HPV), 1 microinvasive carcinoma and 3 with no residual lesion. Southern blot analysis detected HPV-DNA in 4 cases of CIN II (16.7%) and in 20 cases of CIN III (70.6%). In 50% of CIN II and 85% of CIN III HPV 16 DNA has been found and in the remaining 50% of CIN II and 15% of CIN III HPV 31 DNA has been detected. All CIN II and 14 cases of CIN III showed episomal HPV-DNA. Integrated HPV-DNA has been found in 3 cases of CIN III and the other 3 cases of CIN III showed both integrated and episomal HPV-genome. Integrated form has been noticed only for HPV 16 type. In no case of colposcopically normal tissue has HPV-DNA been found. These data seem to confirm the strong correlation between HPV 16 type, which often has integrated form, and CIN III strengthening the hypothesis of its potential oncogenic action.

Adult↗