Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Tn determinant (GalNAcalpha-O-Ser/Thr), normally a cryptic structure in mucin-type O-glycans, is a tumor-associated marker which has attracted particular interest in cancer biology. We herein report the characterization of N-nitrosomethylurea (NMU)-induced breast cancer in rats as a new model for the study of aberrant O-glycosylation products. Tn-antigen expression is detectable not only in mammary carcinoma induced by NMU but also in carcinogen-initiated mammary epithelium, indicating that Tn could be a pre-cancerous biomarker in rats treated with NMU. Serum Tn levels were followed up longitudinally in 30 rats from the time of the first injection of NMU to the development of advanced breast cancer. Tn antigen increased in serum several weeks before tumor development, and became highly positive after 56 days of carcinogenesis (prior to breast-cancer occurrence), and the levels correlated with Tn expression in mammary tissues. However, during the follow-up after detection of mammary cancer, all animals displayed a significant decrease of serum Tn antigen, and low levels were observed in animals with advanced breast cancer. We have shown that the humoral immune response to cancer, with the production of anti-Tn antibodies, could hamper the detection of Tn antigen in animals with advanced breast cancer. These results suggest that NMU-induced rat mammary carcinogenesis is a useful experimental model to study the regulation of O-glycosylation at the cellular level during malignant transformation.
 ...
PMID:Tn antigen is a pre-cancerous biomarker in breast tissue and serum in n-nitrosomethylurea-induced rat mammary carcinogenesis. 1084 87

In the present study we examined the localization and overexpression of heat shock proteins (hsps), mainly hsp90, in pancreatic carcinoma tissue compared with control tissue (including chronic pancreatitis and normal pancreas tissue), with the aid of immunohistochemical staining, in situ hybridization and reverse transcriptase polymerase chain reaction. Hsp90 alpha mRNA was overexpressed more highly in pancreatic carcinoma than in the control tissue. The proliferating-cell-nuclear-antigen labeling index was also high in pancreatic carcinoma tissue compared with the other tissue. These findings suggest that the overexpression of hsp90 alpha mRNA in carcinomas may be correlated with cell proliferation. However, hsp90 beta was constitutively overexpressed almost equally in all groups of pancreatic tissue including pancreatic carcinoma, chronic pancreatitis and normal pancreas tissue. Immunohistochemical staining demonstrated a differentiation in the expression of hsp90 between histological types of pancreatic carcinoma. These findings suggest that hsp90 alpha is involved in carcinogenesis and that hsp90 beta is correlated to structural conformation. Hsp90 alpha and hsp90 beta seem to perform different functions in tissue containing malignant cells. P53, MDM2 and WAF1, that were cell-cycle-related oncogene product were more strongly expressed in the nuclei of the cancer cells of the cancer tissue. Especially, MDM2 was more strongly expressed in mucinous carcinoma and the mucin secreting tissues surrounding pancreatic carcinoma tissue. The expression of MDM2 protein might also be correlated to secretion systems during structural conformation and be correlated to hsp90 beta.
 ...
PMID:Overexpression and localization of heat shock proteins mRNA in pancreatic carcinoma. 1085 51

In the gastrointestinal tract, epithelial dysplasia is defined as an "unequivocal neoplastic transformation, confined within the boundaries of the basement membrane" or "the presence of unequivocally neoplastic cells that replace a variable proportion of the normal epithelium". It can be recognized by microscopy because of cytological and architectural changes. Reactive changes or equivocal changes should thus not be called "dysplasia". As dysplasia is confined within the basement membrane, it is a noninvasive neoplastic transformation. In the lower esophagus lined by columnar epithelium (Barrett's esophagus) dysplasia is classified as negative, indefinite or positive. Positive lesions are subdivided into low-grade and high-grade dysplasia according to the severity of the lesions. Carcinoma in situ (intraepithelial carcinoma) is included in the category of high-grade dysplasia. The presence of dysplasia can be recognized on biopsies and on cytological preparations. Several techniques have been introduced with the purpose to improve the diagnostic yield. These include special stains for the assessment of mucin, enzymehistochemistry and immunohistochemistry for tumor markers such as CEA and CA 19-9 and molecular techniques. Mucin histochemistry, enzymehistochemistry and immunohistochemistry for traditional markers have limited practical value. The nuclear presence of abnormal products such as mutant p53 can be identified using immunohistochemistry and appropriate antibodies. Flow cytometry can identify aneuploid cell populations and Fluorescent In Situ Hybridization (FISH) can identify chromosomal gains and losses. These techniques provide additional information but they identify other phenomena which do not necessarily appear at the same moment as dysplasia during the process of carcinogenesis. Application of these techniques can however certainly help to support a diagnosis of dysplasia while negative results do not necessarily disproof such a diagnosis. The temporal course of the progression of dysplasia and the development of carcinoma is not well known and seems to be variable. Low-grade dysplasia may persist for long periods. A direct progression towards carcinoma has been noted although more often an increase in the severity of the dysplasia, before the development of carcinoma, was seen during the observation period. High-grade dysplasia can also persist for many months, sometimes even years without obvious evolution but it can also progress rapidly to carcinoma.
 ...
PMID:Barrett's esophagus: the metaplasia-dysplasia-carcinoma sequence: morphological aspects. 1090 13

There are two well-defined pathways for colorectal carcinogenesis, the suppressor and the mutator pathways. The latter is characteristic of hereditary non-polyposis colorectal cancer (HNPCC), but can also be found in a subset of sporadic colorectal cancer (SCC) possessing distinctive clinical and pathological features, namely early age of onset, location in the right colon, poor differentiation, and a predominant mucinous component. This mutator pathway results from inactivation of mismatch repair (MMR) genes, namely MSH2 and MLH1. The aim of this study was to ascertain if abnormal MMR protein gene expression is a good indicator for identifying tumours from the mutator pathway. Seventy-six cases of SCC were studied by immunohistochemistry using two monoclonal mouse antibodies that react against MSH2 and MLH1 protein gene products. Immunoexpression was assessed both in tumour and in non-neoplastic, adjacent and distant mucosa. Microsatellite instability (MSI) was detected by evaluating the length of poly(CA) repeated sequences at seven loci, or by the detection of small unstable alleles in a poly(A) repeat - BAT-26. Except for BAT-26, in which only tumour DNA was used, MSI analysis was performed in both tumour and normal mucosal DNA. MSI was classified as high (MSI-H), low (MSI-L) or stable (MSS). Abnormal protein expression was found in 9/76 (12%) tumours. Immunohistochemistry for hmlh1 and hmsh2 detected 75% of MSI-H. There was also a highly significant correlation between the observed immunoexpression and several clinical and pathological characteristics described as the phenotypic profile of the mutator pathway, such as right-sided location (p=0.003), mucin production (p=0.008), and a peritumoural lymphoid infiltrate (p=0.009). Non-neoplastic adjacent mucosa showed normal hMSH2 expression in all cases, but in ten cases there was no hMLH1 expression in this transitional mucosa, which is known to display an alterated mucin pattern and a high proliferative rate. These results demonstrated a good correlation between hMLH1 and hMSH2 gene immunoexpression and the clinico-pathological features characteristic of the mutator phenotype and support the use of this method as a rapid and efficient way to detect tumours arising from this pathway.
 ...
PMID:Immunohistochemical detection of mismatch repair gene proteins as a useful tool for the identification of colorectal carcinoma with the mutator phenotype. 1091 9

The proper staging of colorectal cancer was discussed with emphasis on the most relevant pathological parameters. Standard staging classifications i.e. Dukes', Astler-Coller's and international TNM classifications are defined by a few basic parameters, namely local invasion and lymph node metastasis, along with the histological grade of differentiation. Advances in diagnosis and treatment and modern aspects of tumor biology introduced other prognostic factors regarding proliferative activity of tumor, its local and systemic effects, host defense mechanisms and metastatic potential. Independent prognostic significance was shown and/or new criteria recommended for: resection margin and peritoneal involvement, vascular invasion, tumoral mucin production activity, presence of extranodal (micro) metastasis, extent of presented (extra) mural tumor spread, peritumoral lymphocytic infiltration, character of tumoral invasive margin and presence of peritumoral Crohn's-like lymphoid reaction. The se pathological parameters, discussed in detail, were partly contained in new revision of TNM or other classifications, not widely accepted, such as Jass', Japanese JSCCR, British UKCCCR classification, or new prognostic categories proposed by Harrison and coworkers. Our own first experiences and primary results showed variable agreement most of the mentioned parameters with special respect to reproducibility of Harrison's new prognostic categories. Many newly developed methods and novel tumor markers with some predictive values on clinical outcome are recently recognized, still uncertain for routine clinical usage. We reviewed in brief most important and/or most studied pathobiological predictors, such as: DNA ploidy, markers of proliferative activity, expression of tumor-specific and tumor-associated antigens or receptors. Among many of hereditary and genetic markers we stressed the importance of RER phenotype, mutations of tumor suppressor genes and some oncogenes, allelic loss of 18q, 17p and other chromosomal alleles as prognostic and screening tools or therapeutic targets. In conclusion, more new insights in carcinogenesis and new therapeutic agents will require new classification systems, never considered as definitive.
 ...
PMID:[New prognostic parameters and categories of colorectal carcinoma--correlation with standards]. 1095 90

6-O-Sulfation of beta-GlcNAc is an initial step in the biosynthesis of N-linked and O-linked sulfated glycans, which are widely distributed in colonic tissues. However, the biochemical mechanism of this sulfation in human colonic carcinogenesis was still unclear. In this study, we found two types of GlcNAc:-->6sulfotransferases (SulT) in human colonic adenocarcinomas and the adjacent normal mucosa, and we determined their enzymatic characteristics. One SulT, named SulT-a, was present in the adjacent normal mucosa and in non-mucinous adenocarcinomas, whereas the other SulT, named SulT-b, was present only in mucinous adenocarcinomas and adenocarcinomas with a mucinous component. SulT-a preferentially acted on Galbeta1-->3(GlcNAcbeta1-->6)GalNAc(alpha1)-p-nitrophenyl (pNP) and GlcNAcbeta1-->2Man, whereas SulT-b could act not only on these two glycans, but also on GlcNAcbeta1-->3GalNAc(alpha1)-pNP and GlcNAcbeta1-->3Galbeta1-->4Glc. The levels of SulT-a activity were significantly lower in non-mucinous adenocarcinomas than in the adjacent mucosa. In contrast, SulT-b was expressed in mucinous adenocarcinomas and in adenocarcinomas with a mucinous component. These results indicate that there are at least two types of GlcNAc:-->6SulT, SulT-a and -b, in colonic mucosa and adenocarcinomas, and that the occurrence of these enzymes is closely correlated with colonic cancer and the presence of areas of mucin accumulation.
 ...
PMID:Biochemical differences between two types of N-acetylglucosamine:-->6sulfotransferases in human colonic adenocarcinomas and the adjacent normal mucosa: specific expression of a GlcNAc:-->6sulfotransferase in mucinous adenocarcinoma. 1098 53

Mucins and simple mucin-type carbohydrates are cancer-associated antigens in several human tumors. Expression of Tn, sialosyl-Tn, Thomsen-Friedenreich (T), sialosyl-T and of a recently identified mucin-like glycoprotein (gp230) has not yet been thoroughly investigated in human cervix carcinogenesis. In the present study sections from normal cervix (n=10), CIN III lesions (n=10), and invasive carcinomas (n=47) were evaluated immunohistochemically using monoclonal antibodies. In normal cervix there was: cytoplasmatic expression of Tn in 1 case (10%); membranous expression of STn in 8 cases (80%); no expression of T and cytoplasmatic expression of ST in 1 case (10%); gp 230 was expressed in all cases with a membranous pattern. In CIN III lesions there was cytoplasmatic and membranous expression of Tn in 3 cases (30%) and of STn in 9 cases (90%); T and ST were not expressed; gp 230 was expressed in 5 cases (50%) both in the cytoplasm and at the cell membrane. In invasive carcinomas we observed Tn expression in 30 cases (63.8%) and STn in 31 cases (66%); T antigen was not expressed; expression of both ST and gp 230 in 24 cases (51.1%); all antigens showed membranous and cytoplasmatic staining. Our results show that Tn and ST are good markers of invasive carcinomas of the human cervix. We have also shown that loss of expression of the mucin-like glycoprotein gp 230 is associated with malignant transformation at a preinvasive stage.
 ...
PMID:Simple mucin-type carbohydrate antigens (Tn, sialosyl-Tn, T and sialosyl-T) and gp 230 mucin-like glycoprotein are candidate markers for neoplastic transformation of the human cervix. 1099 78

Uridine diphosphate (UDP)-GalNAc: polypeptide N-acetylgalactosaminyltransferase (GalNAc transferase) catalyzes the initial step in mucin type O-glycosylation, and its expression has been assumed to be altered between normal epithelial cells and cancer cells. We studied the alteration of GalNAc transferase expression during the carcinogenesis of human colorectal epithelial cells. We produced polyclonal antibodies against synthetic polypeptides with specific sequence to two GalNAc transferase isozymes, T1 and T2. Surgically resected specimens from 50 patients with colorectal cancer were immunohistochemically stained, and the staining grade (percentage of positively stained cells) was compared between cancer and its normal counterpart in the same specimen. Significant signals for both T1 and T2 expression were seen in the supranuclear region of normal and cancer cells, indicating the subcellular localization of the enzymes in the Golgi apparatus. The prevalence of positive staining for T1 and T2 expression in colorectal cancer was significantly higher than that in normal epithelium (P < 0.05). However, the difference in staining grades between cancer and normal tissues varied in each patient. These results indicate that there is variability in the expression patterns of GalNAc transferase isozymes in normal and cancerous cells colorectal among individuals.
 ...
PMID:Expression of UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase isozymes T1 and T2 in human colorectal cancer. 1108 93

PA2.26 antigen is a small mucin-type transmembrane glycoprotein induced in mouse epidermal keratinocytes during carcinogenesis. It is located at plasma membrane projections, such as microvilli and ruffles, where it interacts with the actin cytoskeleton. Previous studies revealed that ectopic expression of PA2.26 in epidermal MCA3D keratinocytes induces cell surface extensions and increased motility. Here, we show that PA2.26-expressing MCA3D (3D2.26) cell transfectants undergo a phenotypic conversion linked to the acquisition of malignant characteristics. The 3D2.26 cells down-regulate basal keratin K14 and up-regulate vimentin and keratin K8 expression. Immunofluorescence analysis in 3D2.26 cell cultures showed loss of cortical actin filaments and destabilization of adherens junctions mediated by E- and P-cadherin, although both cadherin mRNAs were expressed in the transfectants. When the cadherin protein levels were analyzed in Western blots, no P-cadherin protein or smaller polypeptide E-cadherin forms were detected, suggesting that E- and P-cadherin synthesized in 3D2.26 cells was unstable and proteolytically degraded. Transplantation of 3D2.26 cells into athymic nude mice induced tumors, whereas MCA3D cells and control (3DN) transfectants were not tumorigenic after 72 days postinjection. The phenotype of the tumors was undifferentiated, with mixed regions exhibiting a glandular differentiation pattern in which the presence of numerous surface microvilli was observed at the ultrastructural level. Interestingly, PA2.26 antigen was highly expressed in these microvillous cell surfaces. Tumor cells were vimentin- and K8-positive and showed an aberrant pattern of E-cadherin protein expression in which large cytoplasmic aggregates were found close to the nucleus. Infiltration of tumor cells into lymphatic vessels and the presence of frequent regional lymph node metastases were also observed in the tumors. These results indicate that expression of PA2.26 antigen in premalignant keratinocytes induces a fully transformed and metastatic phenotype, and they suggest an involvement of PA2.26 in malignant progression.
 ...
PMID:Ectopic expression of PA2.26 antigen in epidermal keratinocytes leads to destabilization of adherens junctions and malignant progression. 1109 35

Seventy cases of cancer of the gastric remnant were divided into three groups: 33 cases following surgery for benign disease (group A), and 15 cases occurring more than 10 years and 22 cases occurring within 10 years after the first gastrectomy for malignant disease (groups B and C, respectively). Then mucin histochemical and immunohistochemical studies were undertaken. Billroth-II procedure for anastomosis was most frequently performed in group A. Intestinal metaplasia within the mucosa surrounding the carcinomas was more frequently present in groups A and C with a diffuse distribution. Intestinal-type surrounding mucosa was significantly more frequent in group C. The immunohistochemical expression of p53 protein was most frequently expressed in group B. We conclude that a different mechanism of carcinogenesis exists in these three groups; i) group A: the reflux of duodenal juice especially following B-II procedures leads to progression of the carcinoma. ii) group B: some genetic factor such as p53 may be related to the metachronous multiple carcinogenesis. iii) group C: metachronous multiple carcinogenesis within the short interval may be closely associated with diffuse intestinal metaplasia in the surrounding mucosa.
 ...
PMID:Different characteristics of carcinoma in the gastric remnant: histochemical and immunohistochemical studies. 1111 63


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>