Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunophenotypes of mammary (MPD) and extramammary Paget's disease (EPD) are still not well understood. Thirty-four formalin-fixed paraffin-embedded tissue sections from 33 patients with 6 MPD and 28 EPD were studied immunohistochemically with the use of polyclonal c-erbB-2 and pS2 antisera, and monoclonal nm23, B6.2, GCDFP-15, and p53 antibodies. Cases of MPD expressed a high incidence of c-erbB-2 and nm23 compared with those of EPD (100% vs. 29%; p < 0.01, and 83% vs. 29%; p < 0.05, respectively). Although high expression of B6.2 (> 83%) and moderate expression of GCDFP-15 (33-39%), pS2 (33-46%) and p53 (39-50%) were seen, the positivity was not significantly different between MPD and EPD. These findings indicate that MPD and EPD share immunohistochemical features but partially differ in their patterns of antigen expression.
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PMID:Immunohistochemical study of mammary and extramammary Paget's disease. 776 23

Breast cancer is a complex but increasingly well-understood disease. Clearly, multiple alterations from normal mammary cells are required to achieve a transformed phenotype. Furthermore, there may be several possible alterations within broad categories that will produce the transformations leading to the malignant state. The specific set of alterations within a given cancer may thus provide necessary information about how it is unique and how it may best be treated. Several of the newer biologic markers of breast cancer may provide very specific treatment information. erbB-2 may predict for improved response to doxorubicin, rather than CMF. hsp 27 may predict for failure of doxorubicin. pS2 or EGFR may provide supplemental information predicting response to hormonal therapy. Each of these variables has strong evidence to support its use in this manner, but that evidence has been obtained on limited numbers of patients treated in a limited number of ways. The most established markers, with multiple studies indicating their prognostic benefit, are erbB-2, cathepsin D, and proliferation markers. Of the several proliferation markers there may be no one choice that is best. However, very clearly, any marker must be carefully assessed for appropriate cut-off values, and cut-off values established by one cohort of patients should be verified against another cohort of patients. The oncoproteins associated with cell cycle regulation (cyclin D, p53, Rb, and c-myc) have shown strong promise of providing important prognostic information. The limited studies to date indicate that these markers are independent of one another. Cell cycle regulation may be an area in which any defect may serve to deregulate the cell, and therefore several defects in one cell would be unlikely. The specific nature of the defect in a given cancer may be very important. With the advent of immunohistochemical methods to measure most of the markers, more information may become available. Finally, the burgeoning area of tumor-stromal interactions is replete with potentially important markers of cancer prognosis. The growth factors, which are marginally a part of this area owing to the probable importance of paracrine effects on cancer cell growth, have progressively developed a body of literature supporting their prognostic potential. However, they have rarely been studied in conjunction with the other aspects of tumor-stromal cooperation. The markers of metastatic potential, nm23 and angiogenesis, have been shown in small cohorts to have considerable prognostic import.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Overview of the biologic markers of breast cancer. 815 Jul 84

The recent highlighted points in prognostic factors after breast cancer operation include: 1) the emergence of many genetic and biochemical markers, including c-erbB-2, int-2, EGFR, p53, nm23, LOH, E cadherin, s-phase fraction. The prognostic value of these factors is related to their role in cell cycle regulation, invasion/metastasis mechanisms, etc. The agents related to therapeutic effectiveness, namely p-glycoprotein, pS2, and bcl-2 may become important stratification factors when conducting clinical trials. Pathologic factors, like nodal status, however, are the most useful prognostic factors at the moment. Many newly developed prognostic factors should be examined by multivariate analysis and validated prospectively before clinical use.
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PMID:[Recent prognostic factors for breast cancer]. 912 98

Multiple genetic and epigenetic alterations in oncogenes, tumour-suppressor genes, cell-cycle regulators, cell adhesion molecules, DNA repair genes and genetic instability as well as telomerase activation are implicated in the multistep process of human stomach carcinogenesis. However, particular combinations of these alterations differ in the two histological types of gastric cancer, indicating that well-differentiated or intestinal-type and poorly differentiated or diffuse-type carcinomas have distinct carcinogenetic pathways. In the multistep process of well-differentiated-type carcinogenesis, the genetic pathway can be divided into three subpathways: an intestinal metaplasia-->adenoma-->carcinoma sequence, an intestinal metaplasia-->carcinoma sequence and de novo. In the multistep process of well-differentiated-type or intestinal-type gastric carcinogenesis, infection with Helicobacter pylori may be a strong trigger for hyperplasia of hTERT-positive 'stem cells' in intestinal metaplasia. Genetic instability and hyperplasia of hTERT-positive stem cells precede replication error at the D1S191 locus, DNA hypermethylation at the D17S5 locus, pS2 loss, RARbeta loss, CD44 abnormal transcripts and p53 mutation, all of which accumulate in at least 30% of incomplete intestinal metaplasias. All of these epigenetic and genetic alterations are common events in intestinal-type gastric cancer. An adenoma-->carcinoma sequence is found in about 20% of gastric adenomas with APC mutations. In addition to these events, p53 mutation and loss of heterozygosity (LOH), reduced p27 expression, cyclin E expression and the presence of c-met 6.0-kb transcripts allow malignant transformation from the above precancerous lesions to intestinal-type gastric cancer. DCC loss, APC mutations, 1q LOH, p27 loss, reduced tumour growth factor (TGF)-beta type I receptor expression, reduced nm23 expression and c-erbB gene amplification are frequently associated with an advanced stage of intestinal-type gastric cancer. The de-novo pathway for carcinogenesis of well-differentiated gastric cancer involves LOH and abnormal expression of the p73 gene that is responsible for the development of foveolar-type gastric cancers with pS2 expression. On the other hand, LOH at chromosome 17p, mutation or LOH of p53 and mutation or loss of E-cadherin are preferentially involved in the development of poorly differentiated gastric cancers. In addition to these changes, gene amplification of K-sam, and c-met and p27 loss as well as reduced nm23 obviously confer progression, metastasis and diffusely productive fibrosis. Mixed gastric carcinomas composed of well-differentiated and poorly differentiated components exhibit some but not all of the molecular events described so far for each of the two types of gastric cancer. Besides these genetic and epigenetic events, well-differentiated and poorly differentiated gastric cancers also organize different patterns of interplay between cancer cells and stromal cells through the growth factor/cytokine receptor system, which plays an important role in cell growth, apoptosis, morphogenesis, angiogenesis, progression and metastasis. Meta-analysis of epidemiological studies and animal models show that both intestinal and diffuse types of gastric cancer are equally associated with H. pylori infection. However, H. pylori infection may play a role only in the initial steps of gastric carcinogenesis. Differences in H. pylori strain, patient age, exogenous or endogenous carcinogens and genetic factors such as DNA polymorphism and genetic instability may be implicated in two distinct major genetic pathways for gastric carcinogenesis.
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PMID:Genetic pathways of two types of gastric cancer. 1505 5

Metastasis of cancer cells from the primary tumor is associated with poor prognosis and decreased overall survival. One protein implicated in inhibiting metastasis is the tumor metastasis suppressor nonmetastatic protein 23 homologue 1 (NM23-H1). NM23-H1 is a multifunctional protein, which, in addition to limiting metastasis, has DNase and histidine protein kinase activities. We have identified new functions for NM23-H1 in influencing estrogen receptor alpha (ER alpha)-mediated gene expression. Using a battery of molecular and biochemical techniques, we show that NM23-H1 interacts with ER alpha and increases the ER alpha-estrogen response element (ERE) interaction. When NM23-H1 expression is increased in U2 osteosarcoma and MDA-MB-231 breast cancer cells, transcription of a transiently transfected, estrogen-responsive reporter plasmid is decreased. More importantly, when endogenous NM23-H1 expression is knocked down in MCF-7 human breast cancer cells using small interfering RNA, estrogen responsiveness of the progesterone receptor (PR), Bcl-2, cathepsin D, and cyclin D1 genes, but not the pS2 gene, is enhanced. Furthermore, NM23-H1 associates with the region of the PR gene containing the +90 activator protein 1 site, but not with the ERE-containing region of the pS2 gene, indicating that NM23-H1 mediates gene-specific effects by association with endogenous chromatin. Our studies suggest that the capacity of NM23-H1 to limit the expression of estrogen-responsive genes such as cathepsin D and Bcl-2, which are involved in cell migration, apoptosis, and angiogenesis, may help to explain the metastasis-suppressive effects of this protein. The complementary abilities of ER alpha and NM23-H1 together to influence gene expression, cell migration, and apoptosis could be key factors in helping to determine tumor cell fate.
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PMID:Interaction of the tumor metastasis suppressor nonmetastatic protein 23 homologue H1 and estrogen receptor alpha alters estrogen-responsive gene expression. 1797 5