Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocyte growth factor (HGF), secreted by mesenchymal cells, has pleiotropic biological activities on several cell types. HGF and its receptor, the c-met proto-oncogene product (c-MET) have been implicated in the genesis and progression of several carcinomas and sarcomas. It has been suggested that MET/HGF autocrine signaling may contribute to tumorigenesis in sarcomas. HGF has been recently found to be a mitogen for rat Schwann cells and to be present in neurofibromas in NF1 patients. In this investigation, we assessed the immunoreactive patterns of HGF and MET in benign and malignant peripheral nerve sheath tumors (PNST) using archival formalin-fixed tissue. The standard avidin-biotin-peroxidase method was used. All benign tumors were negative with HGF. Eight cases of MPNST were positive with both HGF and MET. In some malignant PNST, positivity with both ligand and the receptor may be indicative of an autocrine mediated signal transduction and may implicate HGF/MET in tumor progression. Immunoreactivity with MET was strikingly greater in MPNST in contrast to benign PNST; this finding may prove to be helpful in distinguishing some histologically low-grade MPNST from cellular and atypical benign PNST.
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PMID:Hepatocyte growth factor and c-MET in benign and malignant peripheral nerve sheath tumors. 930 31

Cystatin A (acid cysteine proteinase inhibitor; ACPI) is a natural inhibitor of cysteine proteinases. It has been suggested that an inverse correlation exists between cystatin A and malignant progression. We wanted to assess the biological and clinical significance of cystatin A in infiltrative breast carcinoma by immunohistochemical staining. Formalin-fixed paraffin-embedded material from 440 cases treated during the years 1988-1991 was used in the study. After exclusion of patients with disseminated disease at diagnosis, previous contralateral breast carcinoma, and absence of follow-up data, 384 patients could be included in the survival analysis. For immunohistochemical analysis of cystatin A, we used monoclonal cystatin A antibody WR-23/2/3/3, the binding of which was detected by the avidin-biotin-peroxidase method. Immunohistochemical analysis of Bcl-2 and p53 was also done, and mitotic activity was evaluated. Positive staining for cystatin A was found in 52 of 440 cases. The staining was irregular but showed irrefutably positive areas within neoplastic tissue. Most of the positive tumors were of the ductal infiltrative type, but two were mucinous carcinomas, one medullary and one squamous cell carcinoma. No lobular carcinomas showed positive staining. Focal cystatin A positivity was seen in myoepithelial cells of benign ducts. Occasional apoptotic bodies within the neoplasm showed strong positivity for cystatin A. Tumors positive for cystatin A were of larger size and had higher mitotic activity than cystatin A-negative tumors. Cystatin A was associated with negative Bcl-2 staining, but there was no statistically significant association between axillary lymph node status or p53 immunostaining. The risk for breast cancer-related death was significantly higher in patients with cystatin A-positive tumors than in those with cystatin A-negative ones. The risk increase was significant also in lymph node-negative patients. After adjusting for the effect of tumor size, histological grade, and lymph node status, cystatin A-positive patients still had a higher risk of death. Patients with cystatin A and p53 coexpression had a higher risk of death than the other patients. The findings reveal a new variant of aggressive breast cancer. This type of carcinoma may develop during tumor progression through genetic instability that allows cystatin A expression and gives growth advantage to a clone of tumor cells.
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PMID:Cysteine proteinase inhibitor cystatin A in breast cancer. 945 85

Haptoglobin-related protein (HPR) is a serum protein that is >90% homologous to the acute-phase reactant haptoglobin (Hp). Haptoglobin binds and removes free hemoglobin (Hb) from the circulation. Hpr levels are elevated with tumor progression in the serum of some cancer patients, but the relevance of this observation is not understood. HPR is an integral part of two distinct high molecular weight complexes (trypanosome lytic factor 1 (TLF1) and TLF2) that are lytic for the African parasite Trypanosoma brucei brucei. Previous data indicate that HPR represents the toxic component of both trypanosome lytic factors. It has been proposed that after uptake by the parasite, Hb bound to HPR causes lysis in a peroxidase-dependent process. We report that the molecular architecture of HPR in normal human serum is different from that of Hp and that HPR does not bind Hb in normal human serum. Immunodepletion of all detectable Hb from TLF1 does not deplete TLF1 of HPR or trypanolytic activity, suggesting that the mechanism of parasite lysis is Hb-independent.
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PMID:Characterization of the human serum trypanosome toxin, haptoglobin-related protein. 946 71

The molecular events regulating the development and progression of colonic neoplasia are currently being delineated. Recent studies have implicated c-Src protein kinase activation as an early event in the malignant transformation of colonic epithelial cells. However, increased c-Src activity has also been reported in colon carcinomas as well as in metastatic hepatic and extrahepatic colon carcinomas. To further investigate the potential role of c-Src in the progression of colonic neoplasia, we analyzed c-Src levels by immunohistochemistry in 27 colorectal resection specimens. Mouse monoclonal antibody to c-Src protein was applied to 3-micron sections from formalin-fixed, paraffin-embedded tissues using the avidin-biotin-peroxidase method. The combination of adenomatous (AD) and adjacent carcinomatous mucosa (CA) specimens were present in 20 of 27 patients. In 15 cases, synchronous metastatic (MT) lesions were available for evaluation. Strong c-Src expression was evident in 95% of AD (n = 20), in contradistinction to 32% of MT (n = 19) and 14% of CA (n = 22). Weak-to-moderate c-Src expression was seen in adjacent normal colonic mucosa (NM) in 96% of cases. Signed rank test univariate analysis revealed a statistically significant difference in c-Src expression between NM/AD (p = 0.0001), NM/CA (p = 0.0001), NM/MT (p = 0.0006), AD/CA (p = 0.0001), and AD/MT (p = 0.0002). No significant correlation between levels of c-Src expression and patient survival, tumor size, histologic grade, or tumor configuration was observed using the Cox's Regression Model. Similar results were obtained by analysis of c-Src protein levels and c-Src kinase activity as measured by Western blot and in vitro kinase assays of representative cases. Our results indicate that: (a) elevated c-Src expression is an important early event during colorectal carcinogenesis; (b) its activation may be involved in tumor progression in a subset of colonic carcinomas; and (c) additional molecular events are necessary for invasion to occur.
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PMID:Elevated c-Src protein expression is an early event in colonic neoplasia. 952 Sep 49

There are many arguments for considering a specific fully habituated (auxin and cytokinin-independent) and fully heterotrophic non-organogenic (HNO) sugarbeet callus cell line as terminating a neoplastic progression, and thus to be made of cancerous cells. The similarities with animal tumour and cancer cells are recalled. All types of habituated tissues examined in the literature share at least three common biochemical characteristics: low apparent peroxidase activity, high content of polyamines (PAs) and low production of ethylene. However, results concerning their auxin and cytokinin levels are not consistent. Peroxidase synthesis in the achlorophyllous HNO callus appears to arise from aminolevulinic acid (ALA) synthesis through the Shemin pathway, commonly used by animals and fungi. This pathway is limited by disturbed nitrogen metabolism that diverts glutamate (directly used for ALA synthesis in green higher plants) from the Kreb's cycle into PA synthesis. There is no argument to suggest that the low ethylene production is caused by a competition with PAs for their common precursor, S-adenosylmethionine. The results we report here indicate modified anabolic and catabolic pathways of auxins and cytokinins but also the possibilities of unusual compounds playing similar roles (dehydrodiconiferyl alcohol glucosides, for instance). A higher turnover of PAs is shown in the HNO callus, which could suggest a role for H2O2 and gamma-aminobutyric acid, products or intermediates in the PA catabolic pathway, as secondary messengers. The habituated cells retain some sensitivity towards exogenous auxins and cytokinins. Their increased sensitivity to PAs and ethylene suggests modified hormonal balances for the control of these actively dividing cells.
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PMID:Shemin pathway and peroxidase deficiency in a fully habituated and fully heterotrophic non-organogenic sugarbeet callus: an adaptative strategy or the consequence of modified hormonal balances and sensitivities in these cancerous cells? A review and reassessment. 1061 88

Tumour progression is currently believed to result from genetic instability. Chromosomal patterns specific of a type of cancer are frequent even though phenotypic spatial heterogeneity is omnipresent. The latter is the usual cause of histological grading imprecision, a well documented problem, without any fully satisfactory solution up to now. The present article addresses this problem in breast carcinoma. The assessment of a genetic marker for human tumours requires quantifiable measures of intratumoral heterogeneity. If any invariance paradigm representing a stochastic or geostatistic function could be discovered, this might help in solving the grading problem. A novel methodological approach using geostatistics to measure heterogeneity is used. Twenty tumours from the three usual (Scarff-Bloom and Richardson) grades were obtained and paraffin sections stained by MIB-1 (Ki-67) and peroxidase staining. Whole two-dimensional sections were sampled. Morphometric grids of variable sizes allowed a simple and fast recording of positions of epithelial nuclei, marked or not by MIB-1. The geostatistical method is based here upon the asymptotic behaviour of dispersion variance. Measure of asymptotic exponent of dispersion variance shows an increase from grade 1 to grade 3. Preliminary results are encouraging: grades 1 and 3 on one hand and 2 and 3 on the other hand are totally separated. The final proof of an improved grading using this measure will of course require a confrontation with the results of survival studies.
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PMID:Breast carcinoma, intratumour heterogeneity and histological grading, using geostatistics. 1115 11

According to studies on a variety of malignant tumors from different organs MUC1 mucin antigen presents as a valuable marker of cancer progression and prognosis. During recent years, a great number of monoclonal antibodies (mabs) directed to MUC1 was generated. Their epitopes can be classified according to their position within the tandem repeat domain of the mucin and with respect to effects exerted by site-specific glycosylation. In this study, eight mabs from different clusters were selected to correlate their epitope specificity with their binding pattern in human cancer specimens. By applying an immunohistochemical ABC-peroxidase method, ten carcinomas derived from breast, pancreas, stomach and colon were characterized. A positive reaction of all mabs could be observed in the majority of the carcinomas, however, the extent of the stained tumor area varied significantly. In general, mabs M38, VA1 and BC3 exhibited the strongest staining reaction. Mab BW835 showed a similar binding intensity, especially in pancreatic and gastric carcinomas. It is tempting to speculate that the different binding patterns may reflect differences in epitope specificity. In conclusion, future immunohistochemical, immunoserological and therapeutic studies involving MUC1 antigen should prefer well-characterized and highly reactive mabs detecting defined peptide epitopes.
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PMID:Epitope-dependent differential immunoreactivities of anti-MUC1 monoclonal antibodies in human carcinomas. 1117 79

A sandwich-type ELISA has been developed for quantification of the complex between the cysteine proteinase cathepsin B (CB) and its reversible tight-binding inhibitor cystatin C (CC) in normal and pathological sera. The assay is based on a combination of catching Ab (3E1), raised against CB, and a horseradish peroxidase-labelled detection Ab (1A2), raised against CC. Only the CB/CC complex is able to evoke a signal in this assay. The detection limit of the assay was 15.5 nM and the working range between 31.3-200 nM. The within and between-run coefficients of variance (CV) varied from 4.7% to 9.4% and 11% to 12.8%, respectively, demonstrating satisfactory reproducibility of the method. The concentration of the CB/CC complex was determined in sera from 90 healthy controls, 32 patients with non-cancerous lung diseases, 148 patients with lung and 32 patients with colorectal cancer. The CB/CC complex was significantly less abundant in sera of patients bearing malignant lung tumours than in those with non-cancerous lung diseases or healthy controls (p<0.001). In colorectal cancer sera its level was significantly lower in advanced stages C and D than in early Dukes' stages A and B (p=0.02). Our results show that the increased levels of CB in malignant sera are not impaired effectively by CC and support the hypothesis of hindered inhibitory capability during cancer progression.
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PMID:Cathepsin B/cystatin C complex levels in sera from patients with lung and colorectal cancer. 1151 34

CD44 is an adhesion molecule involved in cell-to-cell and cell-to-matrix interactions. Recent evidence indicates a role of CD44 in tumor growth and metastatic potential of tumor cells. Moreover, it is widely known that the p53 tumor suppressor gene controls cell proliferation and loss of its normal function may lead to carcinogenesis. To investigate the role of these biomarkers in renal cancer, we analyzed the immunohistochemical distribution of CD44's expression on formalin fixed paraffin embedded tissue from 67 renal cell carcinomas and correlated with clinicopathologic parameters as well as with p53 suppressor gene expression. The monoclonal antibodies CD44 and p53 were applied to the tissues using the streptavidin biotin peroxidase method after microwave antigen retrieval. For CD44 and p53 more than 10% membranous and 5% nuclear staining, respectively, were estimated as positive. CD44's membranous immunoreactivity was detected in 24/67 tumors (35%) and mostly in carcinomas of clear/granular cell type. Nine tumors expressed nuclear immunoexpression of p53 protein (13.4%). Statistically significant correlation was noted between CD44 expression and nuclear grade (P < 0.001), tumor stage (P < 0.001), vascular invasion (P < 0.05) and p53 expression (P < 0.01). These results suggest that CD44s and p53 are markers of tumor progression in renal cell cancer.
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PMID:Expression of CD44 protein in renal cell carcinomas: association with p53 expression. 1247 36

CD44s is a cell adhesion molecule, which belongs to the family of hyaluronan binding proteins. Anti-body to CD44s is used to establish the association of its expression with the clinicopathological characteristics of colorectal cancer using immunohistochemical methods. The aim of this study is to investigate the expression of the standard form of CD44 (CD44s) in colorectal cancer tissues as compared to adjacent normal colonic tissues. Furthermore, the level of expression of CD44s in colorectal cancer tissues was correlated with the degree of histological differentiation, Duke s classification, sex, size and site of the tumor. Immunohistochemical analysis for CD44s was carried out in 49 paraffin-fixed sections of neoplastic colorectal tissues and non-neoplastic ones adjacent to the lesion, by the standard peroxidase-antiperoxidase method. Expression of these antigens were compared in normal and malignant epithelium and stromal cells. The results show that the level of CD44s in the epithelial and stromal cells was significantly higher in the colorectal cancer tissues than the normal ones. However, there was no association between the percentages of expressions of CD44s and the degree of histological differentiation, Duke s classification, sex or size of the tumor. There was however, a significantly higher expression of CD44s in the epithelium of rectal cancer than that of colonic cancer. This study indicates that the expression of CD44s is significantly higher in colorectal cancer tissues. However, further studies are required to understand its role in tumor progression and metastasis of this disease.
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PMID:Expression of CD44s in human colorectal cancer. 1251 96


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