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G Bertoli

Publications and source records attributed to G Bertoli.

At least 19 recordsLinked to original sources

Pretreatment haemoglobin levels significantly predict the tumour response to primary chemotherapy in human breast cancer.

The purpose of this study was to evaluate whether tumour response to primary chemotherapy in human breast cancer is influenced by baseline haemoglobin (Hb) status. A total of 157 patients with T2-4, N0-1 M0 breast cancer were treated with chemotherapy consisting of either the CMF regimen + tamoxifen (the first 76 cases) or the single-agent epirubicin (the subsequent 81) before definitive surgery. In total, 144 patients were fully assessable. Ki67, p53, bcl-2, c-erbB2, steroid hormone receptor, and microvessel density were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage >50% occurred in 72.1% of patients. Responding patients had higher baseline Hb levels and red blood cell counts than nonresponders (P<0.01 and <0.003, respectively). The distribution of disease response according to increasing cutoffs of baseline Hb status showed that from 12.5 mg l(-1) onwards, patients with Hb levels above the cutoff obtained a greater response rate than those with lower Hb values. The difference attained the statistical significance at 12.5 (76.1 vs 59.5%, P<0.05) and 13.0 g/dl(-1) (81.0 vs 57.6%, P<0.002) cutoffs, respectively. The predictive role of Hb levels was maintained in multivariate analysis after adjustment for clinical and biological characteristics and treatment regimen. Patients with baseline Hb levels </=13 g dl(-1) showed a lower treatment-induced reduction in Ki67 expression (P<0.04) and a higher Ki67 expression at postoperative evaluation (P<0.02) than their counterparts. In conclusion, low Hb levels may negatively influence the response rate of chemotherapy in breast cancer patients. Inhibition of antiproliferative activity could be a possible mechanism.

Antigens, CD↗

Prognostic value of Goseki histological classification in adenocarcinoma of the cardia.

Various histologic classification systems have been proposed as prognostic factors for gastric cancer. We assessed the prognostic value of Goseki classification as well as the TNM staging system, histological tumour grading, Lauren, WHO, Goseki and Siewert classifications in 100 patients with cardia carcinoma undergoing curative surgery. Two patients were lost at follow-up. The median time of follow-up in the remaining patients was 32.9 months after surgery (range: 0.1-142.1 months). No differences in survival rates were observed according to tumour grading, Lauren or WHO histologic or Siewert topographical classification. No differences were found according to Goseki classes, when considering either the mucin content of the carcinoma (types I and III vs II and IV) or the differentiation grade (types I and II vs III and IV). Multivariate analysis showed that the only lymph node positivity was a significant predictor of survival: 7.2% of patients with, but 41.5% of those without nodal involvement were alive after five years (P=0.0001). In conclusion, we found no prognostic role for Goseki or the traditional histological indexes, while the TNM staging system and particularly lymph node positivity were the main predictors of survival in patients with cardia adenocarcinoma.

Adenocarcinoma↗

Sudden improvement of respiratory failure in a woman with carcinoma of the colon.

We present a case of bronchial and endotracheal metastases completely blocking the left main bronchus and partially occluding the middle lobe bronchus contributing to severe respiratory failure. The patient's lack of consent to laser resection of the mass led to the use of chemotherapy; after the first cycle of treatment a neoplastic mass about 3 cm long was spontaneously expelled with a cough. The expulsion of the metastasis caused rapid improvement of the dyspnea and gas exchange; however, the continuation of the chemotherapy did not bring any further benefit to the patient, who died 115 days after diagnosis.

Adenocarcinoma, Mucinous↗

The C-terminal domain of yeast Ero1p mediates membrane localization and is essential for function.

In eukaryotes, members of the Ero1 family control oxidative protein folding in the endoplasmic reticulum (ER). Yeast Ero1p is tightly associated with the ER membrane, despite cleavage of the leader peptide, the only hydrophobic sequence that could mediate lipid insertion. In contrast, human Ero1-Lalpha and a yeast mutant (Ero1pDeltaC) lacking the 127 C-terminal amino acids are soluble when expressed in yeast. Neither Ero1-Lalpha nor Ero1pDeltaC complements an ERO1 disrupted strain. Appending the yeast C-terminal tail to human Ero1-Lalpha restores membrane association and allows growth of ERO1 disrupted cells. Therefore, the tail of Ero1p mediates membrane association and is crucial for function.

Endoplasmic Reticulum↗

Relationship between tumour shrinkage and reduction in Ki67 expression after primary chemotherapy in human breast cancer.

The association between tumour shrinkage and reduction in kinetic cell activity after primary chemotherapy in human breast cancer is still a matter of investigation. 157 patients with T2-4, N0-1, M0 breast cancer received primary chemotherapy consisting of either the CMF regimen + tamoxifen (the first consecutive 76 cases) or the single agent epirubicin (the subsequent 81). Ki67, p53, bcl2, c-erbB2 and steroid hormone receptors were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage of >50% occurred in 72.4% of patients. Ki67 expression significantly decreased after chemotherapy; the reduction correlated with tumour response in both univariate (P < 0.005) and multivariate analysis (P = 0.02). p53, bcl-2, steroid hormone receptor and c-erbB2 immunostaining were scarcely affected. Baseline bcl2 (P = 0.04) and c-erbB2 (P = 0.02) were directly and inversely associated with the reduction in Ki67 immunostaining, respectively. Baseline p53 expression (P < 0.01) was directly related with Ki67 expression at residual tumour, whereas oestrogen receptor expression (P < 0.001) was inversely related. Ki67 at residual tumour was a better predictor for relapse-free survival (RFS) than baseline Ki67. Clinical response (P < 0.03), but not reduction in Ki67, was a significant independent predictor for disease recurrence. Chemotherapy was found to induce tumour shrinkage and to reduce the number of cells in the cell cycle, but its effect on tumour biology/aggressiveness was minimal. Reduction in Ki67 immunostaining correlated with clinical response but failed to be related to RFS. Ki67 expression at surgery rather than at baseline appears to be a better predictor for disease relapse.

Adult↗

Effects of liposome-entrapped annamycin in human breast cancer cells: interference with cell cycle progression and induction of apoptosis.

The effects of liposome-encapsulated annamycin (L-Ann) were investigated in two human breast cancer cell lines, MCF7 and MDA-MB-435. For comparative purposes, doxorubicin (Dx) was used throughout the study. A 4-hour treatment with L-Ann was significantly more active in MDA-MB-435 than in MCF7 cells (IC(50) values of 0.03 and 0.08 microg/ml, respectively), whereas Dx was equally active in the two cell lines (IC(50) 0.12 microg/ml). L-Ann induced an accumulation of cells in G2M phases which was dose-dependent in MDA-MB-435 but not in MCF7 cells. Dx also caused a dose-dependent increase of G2M cell fraction in MDA-MB-435 cells, whereas a G2M cell accumulation was observed only after treatment with the highest Dx concentration in MCF7 cells. G2M phase cell accumulations induced in MCF7 cells by L-Ann or Dx were accompanied by a decrease in cdc2 kinase activity and in cyclin B1 and cdc2 expression. Conversely, in MDA-MB-435 cells exposed to L-Ann or Dx, cdc2 kinase activity, cyclin B1 and cdc2 expression increased in parallel to the increase in the number of cells accumulated in the G2M phase. L-Ann and Dx induced apoptosis in MDA-MB-435 but not in MCF7 cells. In MDA-MB-435 cells exposed to L-Ann or Dx, no change was observed in the expression of bax, but there was a p53-independent increase in p21(waf1) expression. In MCF7 cells, treatment with L-Ann or Dx induced an increase in p53 expression with a consequent transactivation of p21(waf1) and bax. Our results indicate that L-Ann is more cytotoxic than Dx in breast cancer cells and is able to induce apoptosis through p53-independent mechanisms.

Apoptosis↗

[Single-slice and multi-slice computerized tomography: dosimetric comparison with diagnostic reference dose levels].

PURPOSE: The absorbed dose during clinical examinations of the head, thorax, abdomen and pelvis performed with a single-slice CT scanner and a new multi-slice CT system was measured and compared. Technical parameters, defined at installation and memorized on the two CT machines relate to a standard-sized patient and were considered the reference standard. Our experimental data were also been compared with the Diagnostic Reference Levels (D.L. 26/5/2000 n.187, Annex V). MATERIAL AND METHODS: We compared the performance of a multi-slice GE LightSpeed QX/i ADVANTAGE to that of a single-slice GE ProSpeed SX. The radiation beam profiles were measured at isocenter using a phosphor plate. Dose measurements were performed, according to the EUR 16262 EN Guidelines, with a 10-cm long CT pencil ionisation chamber and two PMMA phantoms (CEI EN 61223-2-6) for head and body respectively. RESULTS: The obtained (normalised and weighted) computed tomographic dose index (nCTDIW) values were systematically higher for the multi-slice system (up to 36%) and the dose-length product (DLP) values on the multi-slice scanner exceeded the equivalent single-slice DLP values. The values were, however, always lower than DRLs, except in the case of the head multi-slice protocol, the technical parameters of which need to be improved. Our results allowed moreover to calibrate the automatic dose evaluation system of the multi-slice system, which systematically underestimated DLP values. DISCUSSION AND CONCLUSIONS: The comparison showed that the multi-slice scanner delivers a higher dose compared to the single-slice scanner. This is due to the radiation beam profile which is wider than the total active detector width, to the shorter focal spot-to-isocenter distance and to the effective scan length, which is longer than the nominal irradiated volume because the reconstruction algorithm of a multi-slice helical CT image requires the projection data from all detector rows. Nevertheless, the technology of new CT systems equipped with a multiple row detectors array can improve the protection of the patient thanks to very short irradiation time (less than 1 s) and reduced current values. In order to optimize the dose to the patient some acquisition parameters have been adjusted for head examinations.

Radiation Dosage↗

p53 but not bcl-2 immunostaining is predictive of poor clinical complete response to primary chemotherapy in breast cancer patients.

Preoperative chemotherapy administered to breast cancer (BC) patients is a model for studying in vivo the interaction between cytotoxic treatment and clinical and biological parameters. Apoptosis induced by anticancer agents is a mechanism of treatment activity; therefore, overexpression of genes inhibiting the apoptotic pathway could produce drug resistant tumors. In the present study, the two most studied inhibitors of apoptosis, the bcl-2 gene and the mutant p53, have been evaluated to assess whether they may play a role in modulating response of BC to primary chemotherapy. From August 1990 to January 1997, 143 patients bearing T(2-4)N(0-1)M0 primary BC were submitted to two different chemotherapeutic regimens before surgery. The first 64 received the cyclophosphamide, methotrexate, 5-fluorouracil (CMF) regimen (on days 1 and 8 and every 28 days thereafter) associated with tamoxifen (30 mg daily) in case of estrogen receptor (ER)-positive BC, and the remaining 79 were submitted to single agent epirubicin (120 mg/m2 every 21 days). The expression of p53, bcl-2, Ki67, ER, progesterone receptor, c-erbB2, and the multidrug resistance P-glycoprotein (gp-170) was evaluated in BC specimens obtained at diagnosis by incision biopsy and at postchemotherapy surgery. At the end of chemotherapy administration (median, 3 cycles; range, 2-6), the clinical complete response (cCR) rate was superimposable in the patient subgroups with bcl-2-positive or -negative primary tumors; conversely, p53 expression, at a cutoff of 10% positive cells, was significantly associated with a lower cCR rate (9.4 versus 27.0%; P < 0.04). p53 was a significant predictor for poor cCR in the subset submitted to epirubicin (3.6 versus 25.5%; P < 0.02; in patients with p53+ and p53- BC, respectively); by contrast, only a trend toward lower cCR has been observed in patients with p53+ tumors receiving CMF +/- tamoxifen with respect to p53- ones. The distribution of cCR according to the gp-170-positive or -negative tumors was 8 versus 22% in patients submitted to epirubicin and 29 versus 30% in those receiving CMF +/- tamoxifen, respectively. In a multivariate regression analysis, after adjusting for treatment administered (epirubicin versus CMF +/- tamoxifen), menopausal status, tumor and node status, histology grade, ER, progesterone receptor, c-erbB2, Ki67, bcl-2, and gp-170 expression, the p53 status maintained an independent predictive role for cCR. Most of the tumors undergoing change in percentage of p53 expression after both treatments originally harbored mutant protein, and only four BC specimens that were p53 negative before chemotherapy became positive afterward. These data confirm in vivo the concept that the responsiveness of tumors to chemotherapy in part derives from the capability of BC cells to undergo apoptosis. The role of mutated p53 in preventing response is more evident in patients submitted to epirubicin, and this may be caused by the up-regulation of multidrug resistance gene expression by p53 inactivation. p53 is a stable phenotype and is not inducible by at least three or four chemotherapy cycles.

Adult↗

Comparative study on the acceptability of two modern monophasic oral contraceptive preparations: 30 microgram ethinyl estradiol combined with 150 microgram desogestrel or 75 microgram gestodene.

Cycle control and tolerability of two monophasic oral contraceptive pills containing 30 microg ethinyl estradiol (EE) with either 150 microg desogestrel (DSG) or 75 microg gestodene (GSD) were compared in women starting oral contraception. A minimum of 200 healthy women at risk for pregnancy were to be treated for a total of 6 cycles per patient in a prospective, randomized open parallel-group multicenter trial. Two hundred and forty-one subjects were randomized, 115 to DSG/EE and 126 to GSD/EE. Compliance to the study preparation was high (around 95%) in both groups and no pregnancies occurred during the study. Cycle control was excellent; there were no differences between the two groups with regard to incidence of spotting and breakthrough bleeding or duration and intensity of withdrawal bleeding. Side-effects were mild and in general comparable in the two groups. Both at baseline and during treatment, a higher proportion of women taking GSD/EE complained about breast tenderness. This resulted in more early withdrawals because of breast tenderness in the GSD/EE group. It was concluded that monophasic DSG/EE and GSD/EE are equally effective, have similar cycle control and both are generally well tolerated.

Adolescent↗

Distribution of mobilized progenitor cells in the buffy coat of the haemonetics MCS3p cell separator: a study to optimize the collection of progenitors by leukapheresis.

Hematopoietic progenitor and stem cells for transplantation can be mobilized into the circulation and collected by leukapheresis. In this procedure, the leukocytes are distributed in the buffy coat along a density gradient, and the composition of the final product depends on which layer was collected. For the Haemonetics MCS3p Cell Separator, the manufacturer recommended starting the progenitor cell collection at a light transmission of 30%-40% (compared with plasma) and continue it for 40-50 ml. To optimize the use of this machine, the buffy coat it produces was studied in 12 patients by collecting it in fractions of increasing specific weight. Each fraction was analyzed by morphology, immunocytometry, and cell culture. We found that the buffy coat uniformly contains 8 times more leukocytes than blood, but the proportion of each white cell type varies along a gradient. The lymphocyte-predominant lighter layers are richer in CD34+ cells when compared with the granulocyte-predominant denser layers (6-14 times versus 2-4 times more than blood). The majority of CD34+ cells are found at a light transmission of 10%-70% (hematocrit 6-9). We conclude that cells for transplantation should be collected in a lighter fraction of the buffy coat than originally suggested by the manufacturer.

Antigens, CD↗

Evidence of higher insulin resistance in NIDDM patients with ischaemic heart disease.

Prospective studies have shown a relationship between hyperinsulinaemia, an indirect index of insulin resistance, and IHD in men with normal glucose tolerance. In NIDDM this association is less clear possibly due to the poor significance of insulin and C-peptide concentrations as an index of insulin resistance. Therefore, only a direct measurement of insulin sensitivity could clarify the possible relationship between insulin resistance and IHD in NIDDM. We have evaluated insulin sensitivity, by means of an ITT, and some risk factors for IHD in 72 men with NIDDM, 36 with and 36 without IHD, attending our out-patient Diabetic Clinic. The two groups were of similar age, duration of diabetes, glycaemic control and body composition. Subjects with IHD were more insulin resistant (K(ITT) index 2.45 +/- 0.18 vs 3.12 +/- 0.13% per min, in patients with and without IHD, respectively, p < 0.004), had higher total (p = 0.011) and LDL serum cholesterol levels (p = 0.010) and greater prevalence of hypertension (p = 0.001) compared to subjects without IHD. Using step-wise logistic regression analysis, insulin resistance (odds ratio 2.57, 95% CI 1.87-3.28, p = 0.008), hypertension (odds ratio 8.17, 95% CI 6.86-9.48, p = 0.002), total serum cholesterol levels (odds ratio 1.02, 95% CI 1.005-1.035, p = 0.015) and BMI (0.79, 95% CI 0.67-0.97, p = 0.049) were independently associated with IHD. After adjustment for age and duration of diabetes, only insulin sensitivity was directly related to the age of onset of IHD, independently from other clinical and metabolic parameters (p < 0.015).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Multicentre evaluation of a biphasic culture system for recovery of mycobacteria from clinical specimens.

A new biphasic system (MB Check, Roche) for isolation of mycobacteria from clinical specimens was evaluated by eight different microbiological laboratories in comparison with methods routinely used in the respective laboratories. Altogether 1125 clinical specimens were processed; pretreatment, if performed, was by a variety of methods. Mycobacteria were recovered from 167 specimens with the biphasic system and 165 specimens with the other methods. The average time required for isolation of Mycobacterium tuberculosis was 22.6 days with the biphasic system and 24.7 days with egg-based media; for other mycobacterial species it was 23.5 versus 20.8 days. The inclusion of a chocolate agar section in the biphasic system facilitated the early detection of contaminants, while the NAP-containing section appeared unable to differentiate Mycobacterium tuberculosis from other mycobacterial species. The biphasic system, which enables recovery of mycobacteria in small laboratories without specialized equipment, is more practical than conventional methods and at least as sensitive.

Bacteriological Techniques↗

Clinical significance of gastric dysplasia: a multicenter follow-up study. Gastrointestinal Endoscopic Pathology Study Group.

The evolution of gastric moderate and severe dysplasia was examined in a prospective multicenter study. One-hundred-and-nine of 141 patients with the endoscopic-bioptic diagnosis of moderate or severe dysplasia had an adequate follow-up and were included into the study. After revision of the initial slides by a gastrointestinal pathologist, 57 patients whose lesions did not meet the histological criteria for dysplasia were excluded, being reclassified as hyperplastic or metaplastic lesions (group 2). The 52 patients with confirmed moderate or severe dysplasia (group 1) were followed up for at least six months or underwent surgery for confirmed dysplasia or cancer. Thirty-two cancers were found in group 1 (33% in patients with moderate and 81% in patients with severe dysplasia). Among them, about half (n = 17) were early gastric cancers. Neither severe dysplasia nor cancer were found during the follow-up in group 2. Mean follow-up time was 13 months in group 1 and 16 months in group 2. Our results indicate that: 1) Confirmed moderate dysplasia shows a high risk of cancer development and requires strict bioptic follow-up; 2) Surgery is indicated in confirmed severe gastric dysplasia seen in the early detection of gastric cancer.

Adult↗

[Phytobezoar].

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Adult↗