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Biomedical subjects

G Delides

Publications and source records attributed to G Delides.

At least 37 records · Page 2Linked to original sources

Treatment of ovarian cancer with a combination of cis-platinum, adriamycin, cyclophosphamide and hexamethylmelamine.

During the last 2 1/2 years, 38 patients with ovarian cancer were treated with a combination of cisplatinum (CPDD), 50 mg/m2, adriamycin, 30 mg/m2, cyclophosphamide, 300 mg/m2, on day 1; and hexamethylmelamine (HMM), 6 mg/kg daily, for 14 days. Each course was repeated monthly. 2 patients had stage II, 14 stage III and 22 stage IV disease. 14 of the 38 patients were previously treated with chemotherapy, 1 with radiation, 6 with both chemotherapy and radiation, and 17 did not have any treatment before CPDD combination. 31 of the 38 cases (81.5%) demonstrated objective responses lasting for 2 months or more. These responses were partial in 19 and complete in 12 cases. Hematologic toxicity was moderate and with reversible anemia developing in 71% of patients. Gastrointestinal side effects from CPDD were universal. HMM gastrointestinal toxicity necessitated discontinuation of the drug in 5 patients. Severe nephrotoxicity was observed in 2 patients but was reversible. There were no drug-related deaths.

Acute Kidney Injury↗

The significance of enzyme histochemical patterns in carcinomas of the large intestine in man.

The activities of 13 enzymes in 40 carcinomas of the large bowel have been studied using histochemical techniques. Five enzymes-non-specific esterase, monoamine oxidase, succinate dehydrogenase, cytochrome oxidase, and acid phosphatase-commonly show much less activity in the tumours than in adjacent normal colon. The tumours have been classified based upon the number of enzymes which show marked reduction in activity in each tumour (types 1-5). The enzyme histochemical type and the size of the tumours have been jointly correlated with the presence of lymph node metastasis. Small type 1 or 2 tumours do not appear to be associated with metastatic disease. Small type 5 tumours were commonly associated with secondary carcinoma in the lymph nodes. Large tumours (greater than 25 sq cm surface area) of any histochemical type were frequently associated with lymph node metastasis. Discussion of the possible reasons for these findings and their clinical significance is presented.

Acid Phosphatase↗

Metastatic uterine leiomyosarcoma coexisting with papillary carcinoma of the thyroid gland.

Metastatic leiomyosarcoma to the thyroid gland has rarely been described. We report a 54-year-old postmenopausal woman with uterine leiomyosarcoma, who presented with a single "cold" nodule in the right thyroid lobe 3 months after hysterectomy. The lesion was identified as a papillary thyroid carcinoma. In a separate area of the thyroid, a 1.2-mm area of a malignant mesenchymal neoplasm with morphologic and immunohistochemical features of leiomyosarcoma existed. Seven months after thyroidectomy the patient developed micronodular lung disease visible on successive chest computed tomography scans, consistent with metastatic disease from the primary uterine leiomyosarcoma that showed very good and prolonged response to chemotherapy. The thyroid papillary carcinoma was likely the recipient of an early and possibly the first metastasis of the patient's uterine leiomyosarcoma. This is the first report of metastatic leiomyosarcoma coexisting with a primary thyroid carcinoma and supports the possibility of a common pathway connecting thyroid gland neoplasms and sarcomas.

Biopsy, Needle↗

Lens epithelial apoptosis and cell proliferation in human age-related cortical cataract.

PURPOSE: To probe the presence of apoptosis in the epithelium of human lenses with age-related cortical cataract as well as to assess cell proliferation, a predicted consequence of apoptotic cell death, in this specific cell population. METHODS: DNA fragmentation was assessed using terminal digoxigenin-labeled dUTP nick end labeling (TUNEL) in capsulotomy specimens obtained from patients who underwent either extracapsular cataract extraction for the removal of adult-onset cortical cataract (n=27) or clear lens extraction for the correction of high myopia (n=25). Cell proliferation was assayed in 23 epithelia of cataractous lenses, and 20 epithelia of non-cataractous lenses with the proliferation marker MIB1, a monoclonal antibody against the nuclear antigen Ki-67 that is detected throughout the cell cycle but is absent in the resting (G0) cell. RESULTS: TUNEL staining was observed in 25 (92.6%) specimens of cataractous lenses, whereas cells undergoing apoptosis were identified in 2 (8%) of the epithelia from non-cataractous lenses. Only two MIB1-positive samples were detected, one of which was a capsule obtained during intracapsular cataract extraction. CONCLUSIONS: The epithelium of human lenses with cortical cataract undergoes low rate apoptotic death. This limited epithelial apoptosis is unlikely to result in any significant cell density decrease since epithelial gaps are likely to be replaced by cell proliferation at the germinative zone of the anterior lens capsule. Nevertheless, the accumulation of small-scale epithelial losses during lifetime may induce alterations in lens fiber formation and homeostasis and result in loss of lens transparency.

Adult↗

Topoisomerase II alpha expression in breast ductal invasive carcinomas and correlation with clinicopathological variables.

Topoisomerase II alpha (topo IIa) is an enzyme that in normal cells is expressed predominantly in the S/G2/M-phase of the cell cycle. In malignant cells, in vitro studies have indicated that the expression of topo II alpha is both higher and less dependent on the proliferation state in the cell. To study the expression of topo IIa and the relationship between that expression-and other variables in cases of breast ductal invasive carcinomas, 50 fine-needle aspiration biopsies were performed from the same number of female patients, diagnosed cytologically and confirmed histologically after surgery. The same cases were studied immunocytochemically using monoclonal antibodies to topo IIa and Her2/neu (CB11) by the alkaline phosphatase method (APAAP). Topo IIa was found in 32 cases (64%) of the carcinomas studied. An overexpression between topo IIa and Her2/neu was found (p < 0.005). A relationship between topo IIa expression, histological grade and lymph node status (LNs) was also found (p < 0.005). Increased topo IIa expression seems to be related to an aggressive form of breast cancer featuring Her2 amplification and lymph node metastasis.

Alkaline Phosphatase↗

Proliferating cell nuclear antigen (PCNA) expression in patients with breast carcinoma in comparison to patients with benign breast diseases.

The proliferating cell nuclear antigen (PCNA) was studied by immunohistochemistry on FNA specimens of 20 breast (ductal) carcinomas, 20 fibroadenomas and 20 atypical fibrocystic lesions of the breast. Sixteen cases of breast carcinomas, eight fibroadenomas but no atypical fibrocystic lesions were found to display nuclear PCNA staining. A significant difference was found, between PCNA index of breast carcinomas (mean PCNA index 56%) and fibroadenomas (mean PCNA 21, 25%). This suggests that breast carcinomas display a higher proliferation index than fibroadenomas and fibrocystic disease. Furthermore, we found variations in PCNA among individual cases of breast carcinomas. This suggests that PCNA index can help in the individual approach of the proliferation rate of each tumour, a parameter of potentially importance for predicting the biological behaviour of the tumour in association with other proliferation markers.

Biopsy, Needle↗

A new expert system for histopathological diagnosis of human ovarian epithelial cancer.

A new rule-based expert system designed to assist pathologists in the histological diagnosis of human ovarian epithelial cancer has been developed. The system was implemented using the INSIGHT II+ EXPERT System Shell and runs on IBM compatible microcomputers. It operates using knowledge acquired through the literature, research and experience, formulated into a total of 195 IF-THEN rules. The WHO International Histological Classification of Tumours is being used throughout. The system can quickly focus on a differential problem, thereby reducing the time necessary to reach a conclusion. It has been tested on a set of 34 cases, previously examined by pathologists of the Metaxas Memorial Cancer Institute, and has been found to reach good agreement with the pathologists' diagnoses.

Epithelium↗

Information retrieval for pathology information systems.

In a medical information system there is a serious need for assessing patient information in various ways. There is also a need for summarizing information in simple statistical tabular form. In this part we present and evaluate different techniques for query formulation, such as: QBE (Query-by-Example), SQL (Structured Query Language), GCL (Graphical Query Language). We also present a query processor for use in a pathology information system. This software system incorporates: a) A semi graphical tree structure interface (SGTSI) for query formulation, and b) Summary tables handling.

Adult↗

C-erbB-2: expression in patients with breast carcinoma in comparison to patients with benign breast diseases.

C-erbB-2 (Her-2 or c-neu) expression was studied by immunohistochemistry on FNA specimens of 20 breast ductal carcinomas, 20 fibroadenomas and 20 atypical fibrocystic lesions of the breast. Twelve cases of breast carcinomas, six fibroadenomas and five atypical fibrocystic lesions were found to display c-erbB-2 staining. A significant difference was found among c-erbB-2 index of breast carcinomas (mean 70,25), fibroadenomas (mean 43,83) and atypical fibrocystic disease (mean 37,4). We also found variations in c-erbB-2 expression, among individual cases of breast carcinomas, concerning the number and the intensity of carcinoma cells. It would be interesting to correlate these variations in c-erbB-2 expression with the prognosis of breast carcinomas.

Breast Neoplasms↗

Aspiration biopsy (FNA) in patients with various lung lesions.

Percutaneous fine needle aspiration biopsy for cytologic examination of lung lesions, is an accepted and safe diagnostic procedure, especially in cases of primary and metastatic lung tumors. This study includes 348 cases of patients with 172 cases of primary and 50 cases of metastatic lung tumors, 16 suspicious for malignancy, 49 negative for malignancy (2 false negatives), 9 inconclusive and 52 with inadequate material. In many tumor cases, immunochemistry was performed and the diagnosis was evaluated by comparison of the cytological diagnosis to the histological one. A statistical analysis was also performed. Sensitivity, specificity, positive predictive value and negative predictive value were respectively, 99.1%, 100%, 100% and 95.9%. This suggests that percutaneous FNA biopsy is a reliable method and finally, we believe that it can help the physicians in the approach of the diagnostic problems of lung lesions.

Biopsy, Needle↗

Expression of p53 and mdm-2 proteins in Hodgkin's Disease. Absence of correlation with the presence of Epstein-Barr virus.

The expression of p53 and mdm-2 proteins was analysed in parrafin sections from 39 cases of Hodgkin's disease (HD) and compared to the presence of Epstein-Barr Virus (EBV). P53 protein was found in Hodgkin and Reed-Sternberg (HRS) cells in 12/39 cases. Mdm-2 protein was found in HRS cells in 10/39 cases. EBV-encoded EBER1-2 mRNAs and LMP-1 protein expression were found in HRS cells in 16/39 cases. In view of the LMP-1 oncogenic potential in vitro, these findings suggest that EBV may be involved in the pathogenesis of a proportion of HD cases. The coexpression of mdm-2 and p53 proteins was found in HRS cells in 10 cases, whereas in 27 cases neither was identified and in 2 cases there was no coexpression of mdm-2/p53. The simultaneous p53/mdm-2 protein expression, in view of previous findings which showed that most cases of HD display no p53 gene mutations, suggests that mdm-2 protein expression may be one of the factors responsible for the stabilisation of p53 protein in these cases. This could be important, in the pathogenesis of these cases of HD, since mdm-2 may deregulate the p53 dependent growth suppressive pathway. Mdm-2-/ p53+ protein expression may reflect the stabilisation of p53 protein by proteins other than mdm-2, mutations in the p53 gene making it unable to activate mdm-2, or the deregulation of the mdm-2 gene. No relationship was found between the presence of EBV and the expression of p53 and/or mdm-2 proteins.

Hodgkin Disease↗

Cigarette smoking and vaginal atrophy in postmenopausal women.

The atrophy of the vaginal epithelium was studied clinically and cytologically on vaginal smears of 1638 healthy postmenopausal female non smokers and 531 healthy postmenopausal smokers (over 30 years), with a mean age of 58 years. A very strong statistically significant difference (p < 0.0001) in the atrophical vaginal changes between smokers and nonsmokers to the disadvantage of the smokers. Also a very statistically significant association (p < 0.0001) was observed between the cytological expression of the vaginal atrophy and duration at menopause of the non-smokers but no association in the cases of the smokers. Another important result of this study was that the smokers women had an early menopause (p < 0.0001), on average by 2 years sooner (mean age 48.5 years) than non-smokers (mean age 50.5 years). These results suggest that cigarette smoking has an effect on the vaginal squamous epithelium, increasing the atrophical changes and causing early menopause by mechanisms, some of which remain unclear.

Age of Onset↗

Cigarette smoking as a risk factor for intraepithelial lesion of the cervix uteri.

Cervical intraepithelial lesions were diagnosed cytologically, and confirmed histologically in 328 patients from 1990 to 1996 at the University Hospital of Heraklion. The women were grouped according to the grade of the cervical intraepithelial lesion as low grade cases (LSIL) on high grade cases (HSIL) (Bethesda classification). They were also grouped according to their smoking status as non-smokers or smokers. A very strong statistically significant difference (p < 0.0001) in the incidence of the disease between non-smokers and smokers was found, to the disadvantage of smokers. Also a very statistically significant (p approximately 0.001) association was found between the number of cigarettes per day, duration of exposure (years of use) and the grade of cervical intraepithelial lesion. Our results indicate that cigarette smoking is a risk factor in the development of cervical intraepithelial lesions and possibly cervical squamous cancer. Further studies are required to prove this hypothesis and to document the biological plausibility of this relationship.

Cervix Uteri↗

MIB1 (Ki-67) expression in non-Hodgkin's lymphomas.

The MIB1 monoclonal antibody which is used as a marker of cell proliferation was studied by immunohistochemistry on formalin-fixed and paraffin embedded biopsy specimens of lymph nodes in 40 high- and 46 lowgrade cases of non-Hodgkin's lymphomas (NHL) classified according to the Kiel classification. All cases were found to display nuclear MIB1 staining. A statistically significant difference (P < 0.005) was found between high- and low grade NHLs and this indicates that the high- grade NHL display a higher proliferation rate than low grade. In addition, remarkable variations in MIB1 expression were found among individual cases of the same histological group. These data may suggest that MIB1 index can help in the individual approach of the proliferation rate of each tumour and this may be an important parameter in association with clinical and other laboratory parameters for predicting the biological behaviour of non-Hodgkin's lymphomas.

Antibodies, Monoclonal↗

p53 protein expression in breast carcinomas. Comparative study with the wild type p53 induced proteins mdm2 and p21/waf1.

The aim was to investigate the pattern of expression of p53 protein and two wild-type (wt) p53-induced proteins (mdm2 and p21/waf1), as an indirect way of assessing p53 gene status in breast carcinomas. Formalin-fixed paraffin embedded tissue from 102 cases of breast carcinomas comprising mostly ductal carcinomas (88 cases) was stained by immunohistochemistry for p53, mdm2 and p21/waf1 proteins. We found p53, mdm2 and waf1/p21 protein expression in 33/102, 20/102 and 38/102 breast carcinomas, respectively. Parallel p53/mdm2 protein expression was found in 9 cases. Five were also p21/waf1 positive. Discordant p53+/ mdm2-protein expression was found in 24 cases. Nine were p21/waf1 positive and the remaining fifteen were p21/waf1 negative. The patterns mdm2+/p53-/p21- and p21+/p53-(+)/mdm2- were found in 6 and 20 cases, respectively. Parallel p53/mdm2/p21 protein expression may represent breast carcinomas with wt p53 gene since mdm2 and p21 proteins are inducible by wt p53 gene. In these cases p53 protein expression may be due to stabilisation to mdm2 protein. This could be important in the pathogenesis of these cases since mdm2 may deregulate the p53-dependent growth suppressive pathway. Discordant p53+/mdm2-/p21- protein expression may represent breast carcinomas with p53 gene mutations unable to activate expression of mdm2 and p21 proteins. Breast carcinomas with p53+/mdm2/p21+ protein expression may have either wt p53 with deregulated mdm2 gene expression or mutated p53 gene with p53-independent p21 expression. Cases with only mdm2 expression may represent tumours with mdm2 gene amplification or overexpression and cases with only p21 expression may reflect p53-independent regulation of p21 protein.

Breast Neoplasms↗

Immunohistochemical expression of p53, bcl-2, mdm2 and waf1/p21 proteins in colorectal adenocarcinomas.

The present study was undertaken to examine the distribution of p53, p21, mdm-2 and bcl-2 protein expression in human colorectal adenocarcinomas in order to obtain combined information about the immunophenotypes characterising these tumours. Formalin-fixed, paraffin-embedded tissue sections from 52 cases of colorectal adenocarcinomas were stained using immunohistochemical methods for the detection of p53, p21/waf1, mdm2 and bcl-2 proteins. P53, p21/waf1, mdm2 and bcl-2 proteins were expressed in 35/52, 45/52, 9/52 and 27/52 cases, respectively. All nine mdm2+ cases expressed p53 and p21 proteins as well. The three patterns observed in p53/p21 expression were: p53+/p21+, p53+/p21- and p53-/p21+ in 28, 7, and 17 cases, respectively. Consequently, p53+/mdm2-/p21+, p53+/mdm-/p21- and p53-/mdm2-/p21+ immunophenotypes were expressed in 19, 7, and 17 cases respectively. Four patterns of p53/bcl2 expression were identified: p53+/bcl2+, 20 cases; p53+/bcl2-, 15 cases; p53-/bcl2+, 7 cases; p53-/bcl2-, 10 cases. It was noteworthy that 9 of the 10 p53-/bcl2-tumours had negative lymph node status. The present results suggest that both p53 dependent and p53-independent induction of p21 expression may be involved in the molecular mechanisms controlling these tumours. High expression of the p53 protein in colorectal carcinomas could be due not only to p53 gene mutations but also to binding to mdm2 protein which leads to p53 protein stabilisation. In addition, tumours with p53-/bcl2- immunophenotype are frequently associated to negative lymph node status and seem to be less aggressive.

Adenocarcinoma↗

P21/waf1 protein expression in nasopharyngeal carcinoma. Comparative study with PCNA, p53 and MDM-2 protein expression.

We investigated the immunohistochemical expression of p21/waf1 protein in 59 cases of nasopharyngeal carcinomas (NPC) and compared p21 expression with PCNA, p53 and mdm2 protein expression. We found p21, PCNA, p53 and mdm2 in 59/59, 59/59, 18/59 and 12/59 nasopharyngeal carcinomas, respectively. We observed a tendency to a relationship between high expression of PCNA (> 25% positivity in tumour cells) and low expression of p21 protein. Parallel p53/p21 protein expression was found in 18 cases. Twelve were also mdm2 positive. This pattern may represent NPC with wild type (wt) p53 since mdm2 and p21 proteins are inducible by wt p53 gene. In these cases p53 protein expression may be due to stabilisation to mdm2 protein. This could be important in the pathogenesis of these cases since mdm2 may deregulate the p53-dependent growth suppressive pathway. Discordant p53-/p21+ protein expression was found in 41 cases. All were also mdm2 negative. This pattern suggests immunohistochemically undetectable wt p53 gene which is able to induce p21 protein expression.

Carcinoma↗