Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.23.5 (cathepsin D)
4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We conducted a trial in 42 benign and malignant meningiomas to assess a possible influence of preoperative dexamethasone therapy on mitotic index, labelling indices of proliferating cell nuclear antigen (PCNA), progesterone receptor, epidermal growth factor receptor (EGF-R), c-erbB-2 oncoprotein, cathepsin D, gamma-gamma enolase as well as the mean number of silver-stained nucleolar organizer region-associated proteins (AgNORs). Tumors with preceding dexamethasone therapy for more than 1 day display significantly less immunohistochemical staining for PCNA. A correlation between the labelling index of PCNA and the degree of malignancy could not be identified. There was no significant effect of preoperative dexamethasone therapy on the other parameters. Our data suggest that dexamethasone may selectively inhibit the expression of PCNA in the G1/S-phase of the cell cycle. Thus, we emphasize the necessity to heed factors, e.g. dexamethasone, which may affect the expression of proliferating markers.
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PMID:Influence of preoperative dexamethasone therapy on proliferating cell nuclear antigen (PCNA) expression in comparison to other parameters in meningiomas. 136 Aug 48

The purpose of this study was to characterize the clinical and histological features of intraoral squamous cell carcinoma in men who were seropositive for the human immunodeficiency virus and to evaluate viral cofactors (human papillomavirus, herpes simplex virus, Epstein-Barr virus), proliferative index (proliferating cell nuclear antigen), a factor associated with invasion (cathepsin D), and mutated tumor suppressor gene and proto-oncogene products (mutated p53, c-erbB-2). Four men who were seropositive for the human immunodeficiency virus and had acquired immunodeficiency syndrome presented with painful oral lesions of variable duration. Oral cancer risk factors included heavy tobacco use (four of four), heavy alcohol use (three of four), and previous radiotherapy (one of four). The lesions consisted of ulcers (two of four), a fungating mass (one of four), and papillary erythroplakia (one of four). Incisional biopsy specimens were obtained. High-stringency in situ hybridization was performed with DNA probes to the human papillomavirus (types 6/11; 16/18; 31/33/35) and Epstein-Barr virus: Immunocytochemical studies for the herpes simplex virus, proliferating cell nuclear antigen, cathepsin D, mutated p53, and c-erbB-2 were performed. Two lesions were moderately differentiated squamous cell carcinoma, one lesion was a basaloid squamous cell carcinoma, and one was carcinoma in situ. Stage of disease at diagnosis was II (one of four), III (two of four), and IV (one of four). Three cases were positive for the human papillomavirus, one case was positive for Epstein-Barr virus, and three cases were positive for the herpes simplex virus. C-erbB-2 was focally positive in one case, and mutated p53 was positive in a separate case.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraoral squamous cell carcinoma in human immunodeficiency virus infection. A clinicopathologic study. 755 63

Elective cervical lymphadenectomy often is performed for laryngeal carcinoma to eliminate metastatic disease that escapes clinical and radiographic detection. We investigated characteristics of the primary tumor that might predict cervical lymph node status. We obtained archival tissue from 88 laryngectomies--65 with concurrent cervical lymphadenectomies. Of the 40 clinically negative necks that were dissected, 17% showed lymph node metastasis by pathologic examination. The primary tumors were examined immunohistochemically for expression of epidermal growth factor receptor (EGFR), p53, cathepsin D, proliferating cell nuclear antigen (PCNA), and Ki-67-specific antigen, and by flow cytometry for DNA ploidy-cell cycle analysis. Seventy-seven percent of the cases showed aberrant p53 staining, 99% expressed EGFR, 40% produced cathepsin D, 29% were aneuploid, and 54% had a moderate or high synthesis phase fraction (SPF). High grade, aneuploidy, and tumor vascular invasion independently predicted cervical node metastasis (p < .04 each). Supraglottic locale (p < .16) and a raggedly infiltrating invading margin (p < .13) were weakly associated with node positivity. Advanced clinical T status, the expression of EGFR, p53, and cathepsin D, the PCNA and Ki-67 indices, and SPF did not correlate with node metastasis. The presence of cervical node metastasis predicted poor disease-free (p < .005) and overall survival (p < .04). Advanced clinical T status correlated with brief overall survival (p < .02). Tumor site, histopathologic parameters, ploidy, SPF, PCNA and Ki-67 indices, and the expression of p53, EGFR, and cathepsin D did not affect survival. The presence of vascular invasion, high grade, and aneuploidy may help identify which patients would benefit from elective cervical lymphadenectomy. The correlation of cervical lymph node status and clinical T category with survival confirms the results of previous studies.
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PMID:Cervical lymph node status and survival in laryngeal carcinoma: prognostic factors. 766 16

An 80 year old Japanese man had adenosquamous carcinoma of the gall-bladder characterized by an adenocarcinoma (AC) in the gall-bladder lumen and a squamous cell carcinoma (SCC) in the invaded region of the liver. In the AC, the tumor cells consisted of atypical columnar epithelium with pseudostratification, mimicking gastric foveolar epithelium, while atypical signet-ring cells were scattered within the SCC. There was an abrupt transition between the AC and SCC areas. The tumor cells in the AC area were intensely positive for galactose oxidase-Schiff staining, and paradoxical concanavalin A staining revealed these tumor cells to have Class II mucins. Immunohistochemically, the tumor cells in foveolar-type adenocarcinoma were diffusely positive for cathepsin D. Flow cytometrical analysis of DNA content showed the AC area to be diploid and the SCC area to be aneuploid. The S-phase fraction of the SCC area (46.9%) was larger than that of the AC area (19.5%). The positive rate of immunostaining for proliferating cell nuclear antigen in the SCC area (mean 50.627%) was larger than that of the AC area (mean 3.048%, P < 0.01). These results suggest that the AC area of this tumor, histochemically and immunohistochemically, showed gastric foveolar-type characteristics, the SCC component was squamous cell metaplasia of the pre-existing AC, and that the SCC area had a greater proliferating capacity than the AC area.
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PMID:Adenosquamous carcinoma of the gall-bladder with gastric foveolar-type epithelium. 778 97

Endometrial cancers have been considered to be less prevalent in Japan than in Western countries. However, with the increase in life expectancy, the Westernization of the Japanese diet, and changes in the hormonal environment, the prevalence of the disease has gradually increased even in our country. Similar increases in cancers of the breasts, lungs, colons, and ovaries have been noted in recent years. Much is still unknown regarding the pathogenesis and natural history of endometrial cancer. Although endometrial hyperplasia is considered to be a precancerous lesion of endometrial carcinoma, the relationship between those diseases has not been elucidated to the same degree as that between cervical cancer and cervical dysplasia, or carcinoma in situ. Research findings in genetic oncology have revealed that tumorigenesis involves a multi-step process. It is probable that activation of multiple genes, inactivation of anti-oncogenes, and disappearance of normal inhibitor genes occur in the process of the development of endometrial cancer. The purpose of this study is to elucidate the relationship between oncogenes and the development of endometrial cancer. In addition, the significance of endometrial hyperplasia as a clinical entity is also be evaluated. The roles played by oncogenes in endometrial cancers and endometrial hyperplasias were examined using the most recent molecular biological and immunohistochemical methods. Also, the differences in cellular proliferation and tissue invasiveness were discussed. Results obtained were as follows. Evaluation of cell proliferation (PCNA, FCM) revealed that there was no difference in proliferative activity between atypical hyperplasia and well differentiated adenocarcinoma. Evaluation of oncogene abnormalities (c-myc,c-erbB-2,K-ras,p53) revealed that the development of endometrial cancer was a multistep process involving several oncogenes, as it has been noted in the development of other cancers. Evaluation of extracellular matrix and related factors (cathepsin D, laminin, type IV collagen, tenascin, CD44) showed that tissue invasiveness differed between atypical hyperplasia and well differentiated adenocarcinoma.
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PMID:[Evaluation of the degree of biological behavior in endometrial hyperplasia and endometrial carcinoma: an investigation of proliferative activity, oncogene, and extracellular matrix]. 810 84

Within the past few years, the measurement of serum and tissue markers, especially the latter, has assumed a more significant role influencing clinical decisions about treatment and follow-up of patients with malignant disease. Breast cancer is a useful paradigm to illustrate the types and importance of these various markers. Tissue markers, including nuclear grade, steroid hormone receptors, DNA index, ploidy, expression of oncogenes or tumor-suppressor genes, epidermal growth factors, cathepsin D, proliferating cell nuclear antigen (PCNA), Ki-67, p32, and others, may influence choices of initial treatment as well as adjuvant chemotherapy and (or) hormone administration. The serial measurement of serum markers, those currently available and those on the horizon, for example, may offer a way to monitor patients at risk for recurrent cancer. Although the current role of these markers may be controversial, as information about them is collected and refined, in the future perhaps a panel of such studies could be incorporated into forthcoming clinical staging systems for carcinoma of the breast and other malignancies to define both treatment and outcome.
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PMID:Clinical applications of serum and tissue markers in malignant disease: breast cancer as the paradigm. 822 51

Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and cathepsin D was performed on 60 transitional cell carcinoma (TCC) specimens from 60 patients with bladder cancer. The percentage of PCNA-positive cells (PCNA-labelling index) was determined by counting 500 or 1,000 cells, and cathepsin D expression was graded according to the extent of immunoreactivity to anti-cathepsin D antibody. The PCNA-labelling index was significantly higher in high-grade and high-stage tumors compared to that in low-grade and low-stage tumors. Cathepsin D was highly positive in grade-1 tumors. In contrast, 82% of grade-3 tumors and 76% of advanced tumors showed negative or low reactivity to anti-cathepsin D. Groups of high PCNA-labelling index and negative cathepsin D had significantly poorer prognoses compared to those of the low PCNA group and cathepsin D highly positive group, respectively, in univariate analyses. However, neither of these two factors were independent prognostic factors in multivariate analyses. These results suggest that the PCNA-labelling index and cathepsin D expression may indicate the malignant potential of TCC and may be able to provide additional information for predicting survival when stratifying for grade of bladder cancer.
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PMID:Immunohistochemical studies of proliferating cell nuclear antigen and cathepsin D in transitional cell carcinoma of the urinary bladder. 939 54

In 87 breast cancer patients, the immunohistochemical expression of the basement membrane (BM)-degrading enzyme cathepsin D (CD) was correlated with the expression of extracellular matrix components, with growth fraction, steroid receptor content and with the other conventional prognostic variables in breast cancer. Only 6.25% of tumours had laminin-defined BM, while 86.8% showed staining for fibronectin. CD was also identified in carcinoma cells (cancer cell CD; CCCD) and in stromal cells (stromal cell CD; SCCD). Forty-five percent of tumours showed CCCD and 47.5%, SCCD expression. CCCD expression was significantly correlated with positive oestrogen receptor content, with low Ki-67 and high PCNA score and with SCCD expression. There was no correlation with collagen type IV, laminin or fibronectin. SCCD expression was positively correlated with collagen type IV, laminin expression and tumour grade. The data suggest that the CD of tumour cells and the CD of tumour-associated macrophages have different roles in breast cancer. CCCD correlates with cell proliferation and is regulated by oestrogens, while SCCD relates to cell differentiation, is oestrogen-independent, and has a proteolytic role in the breakdown of BM components.
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PMID:Immunohistochemical expression of cathepsin D in correlation with extracellular matrix component, steroid receptor status and proliferative indices in breast cancer. 946 71

Matrix metalloproteinases (MMPs) are a group of enzymes thought to be responsible for both normal connective tissue matrix remodelling and accelerated breakdown associated with tumour development. The current study aimed to investigate the immunohistochemical expression of matrix metalloproteinase 3 (MMP-3, stromelysin-1) in correlation with the expression of Basement Membrane (BM) antigen (type IV collagen, laminin), fibronectin, cathepsin D, p53, c-erbB-2, proliferative activity (Ki-67, PCNA), steroid receptor content as well as to the other conventional clinicopathological parameters in breast cancer. This study was performed on a series of frozen and paraffin sections from 84 breast cancer specimens by immunohistochemistry using the monoclonal antibody MMP-3 (Ab-1). Stromelysin-1 (ST1) was observed in about 10% of epithelial cells in the control groups (cases of fibrocystic and benign proliferative breast disease), while expression (> 10% of expression) was detected in 89.7% of tumours. The expression of ST1 in carcinoma cells was strongly associated with its presence in the stroma (p < 0.001). A significantly positive correlation was found between ST1 expression, and p53 tumour suppressor gene product (p = 0.004), and a relationship with c-erbB-2 protein and progesterone receptor status was also indicated. These findings suggest that ST1 expression in breast cancer tissue is irrespective of the expression of the extracellular matrix component, the proteolytic enzyme cathepsin D and the growth fraction of the tumour, and that it could be a potential new prognostic marker in breast cancer.
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PMID:Matrix metalloproteinase expression in human breast cancer: an immunohistochemical study including correlation with cathepsin D, type IV collagen, laminin, fibronectin, EGFR, c-erbB-2 oncoprotein, p53, steroid receptors status and proliferative indices. 967 87

The expression of BCL-2 protein was evaluated immunohistochemically in 23 intracystic papillary carcinomas (IPCs) of the breast. Twenty-two patients were female and one male, aged 49-90 years (median 72). Twenty-one cases had a benign behaviour, while two cases developed local recurrence. Of the 23 tumours, 19 (82%) were immunoreactive for BCL-2, the majority of positive carcinomas showing intense cytoplasmic staining of more than 50% neoplastic cells. The intensity of BCL-2 expression was significantly correlated with prognostic markers such as estrogen receptor (ER) positivity (p = 0.001), cathepsin D (CD) reactivity in the neoplastic cells (p = 0.001) and low growth fraction, evaluated by proliferating cell nuclear antigen (PCNA) immunostaining (p = 0.008). An inverse relationship was also found between BCL-2 and p53 protein (p = 0.001). Three cases of high grade (G3) IPC expressed p53, high PCNA index, and CD (the latter only in the stromal cells), but no immunostaining for BCL-2 and ER. Thus, absence of BCL-2 expression in high grade IPC was associated with ER-negative, rapidly proliferating and p53-positive immunophenotype. All high grade tumours showed invasion of the cystic wall. Local recurrence developed in one of these. The authors conclude that BCL-2 immunoreactivity in IPC is related with tumour grade and with a range of molecular markers of favourable prognosis such as ER positive status, CD expression in the neoplastic cells, and low PCNA index. These findings are consistent with the indolent clinical course and the very favourable prognosis of IPC of the breast.
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PMID:Correlated expression of BCL-2 protein, estrogen receptor, cathepsin D and low growth fraction (PCNA) in intracystic papillary breast carcinoma. 977 88


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