Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factor-I (IGF-I) is a highly conserved 70-residue circulating peptide with diverse biological effects. In mammals IGF-I is an essential mediator of normal postnatal growth and its expression is influenced by hormonal, nutritional, tissue-specific, and developmental factors. Recent studies have demonstrated that the IGF-I gene is more complicated than might have been predicted from its simple protein sequence. In rats and in humans the single-copy six-exon gene is transcribed by adjacent promoters into nascent RNAs with different 5' leader sequences that undergo both alternative RNA splicing and differential polyadenylation to yield multiple mature transcripts. These observations suggest that trophic agents may modulate expression of IGF-I at any of several nodal points. In this report we review several of the mechanisms responsible for regulating production of IGF-I in the rat. During neonatal development IGF-I gene transcription is progressively activated, leading to a rise in both hepatic IGF-I mRNA and in serum IGF-I. The induction of IGF-I expression is limited to mRNAs directed by promoter 1, the more 5' of two rat IGF-I gene promoters, and precedes the ontogenic appearance of liver growth hormone (GH) receptors, indicating that mechanisms independent of GH activate IGF-I expression during early postnatal life. By contrast, in adult GH-deficient rats, a single intraperitoneal injection of GH causes a prompt rise in IGF-I gene transcription that is mediated equivalently by promoters 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1993 Aug
PMID:Multifactorial regulation of IGF-I gene expression. 839 14

The aromatase and estrone sulfatase enzymes are important sources of local synthesis of biologically active estrogens in human breast cancer. Significant intratumoral aromatase activity was detected in 91/145 (63%) of tumors and estrone sulfatase was detected in 93/104 (89%) of tumors. There was no relationship between aromatase activity and tumor size, site, nodal status, menopausal status or estrogen receptor status. There was a significant correlation between the aromatase activity and histological grade, with an excess of aromatase-positive in the high grade tumors (P = 0.03). There was a marginally inverse correlation between the aromatase activity and time to relapse (P < 0.1), a significant correlation between aromatase activity and survival after relapse (P < 0.05) but not with overall survival (P > 0.1). Intratumoral estrone sulfatase activity was not significantly correlated to any putative prognostic factors, nor with time to relapse nor overall survival time.
J Steroid Biochem Mol Biol 1993 Mar
PMID:Prognostic significance of aromatase and estrone sulfatase enzymes in human breast cancer. 847 70

Both during phylogeny and ontogeny the thymus appears as a nodal point between the two major systems of cell-to-cell signaling, the neuroendocrine and immune systems. This review presents the experimental observations which support a dual role in T cell selection played by the thymic repertoire of neuroendocrine polypeptide precursors. Through the mode of cryptocrine intercellular signaling thymic neuroendocrine-related precursors synthesized in thymic epithelial cells have been shown to influence the early steps in T cell differentiation. In addition, thymic neuroendocrine-related polypeptides are a source of self-antigens which are presented by the major histocompatibility system of the thymic epithelium. Preliminary data also suggest that the intrathymic T cell education to neuroendocrine self-antigens is not strictly superimposible to the antigen presentation by dedicated presenting cells. Insulin-like growth factor-II (IGF-II) was identified as one dominant member of the insulin family expressed by thymic epithelial and nurse cells. The intrathymic presentation of IGF-II or IGF-II derived self-antigens is under current investigation. If further confirmed, the central tolerogenic properties of IGF-II could be considered in the elaboration of a strategy for an efficient and safe prevention of insulin-dependent diabetes.
J Mol Med (Berl) 1995 Sep
PMID:Cryptocrine signaling in the thymus network and T cell education to neuroendocrine self-antigens. 852 48

Oestrogen and progesterone receptor (ER and PgR) assay values are frequently used in medical decision-making for breast cancer patients. We have proposed statistical standardization of receptor assay values to improve inter-laboratory comparability, and now report the use of standardized log units (SLU) to investigate the effects of ER and PgR cut-points on time to first recurrence outside the breast (DFS). Between 1980 and 1986, there were 678 primary breast cancer patients treated at the Henrietta Banting Breast Centre (HBBC). The effects of ER and PgR cut-points were examined with multivariate analyses considering the variables: age, tumour size, nodal status, weight and adjuvant treatment. We considered receptor assay cut-points ranging from - 1.0 to + 1.0 SLU (ER between 7 and 166 fmol/mg protein; PgR between 7 and 181 fmol/mg protein). PgR was included in the multivariate prognostic models more often than ER, although patients had a better prognosis with both larger ER and PgR values. There was no best cut-point for ER or PgR, and there was strong evidence that ER and PgR should be considered as continuous rather than dichotomous (negative, positive) variables. Patient prognosis should also be more comparable with SLU.
J Steroid Biochem Mol Biol 1996 Mar
PMID:An investigation of cut-points for primary breast cancer oestrogen and progesterone receptor assays. 863 68

We determined the effects of 8-cyclopentyl-3-[3-[[4-(fluorosulfonyl)benzoyl]oxy]propyl]-1-propylxanth ine (FSCPX), a putative irreversible antagonist of the A1-adenosine receptor, on cardiac A1-adenosine receptor-mediated responses and on the specific binding of [3H]-8-cyclopentyl-1,3-dipropylxanthine ([3H]CPX) to guinea pig cardiac and brain membranes. FSCPX (5 microM) completely reversed the increase in K+ current of guinea pig atrial myocytes caused by 100 microM adenosine (259 +/- 30 to 20 +/- 7 pA) but had no significant effect on K+ currents caused by either 0.5 microM carbachol or 100 microM GTP gamma S. The attenuation of K+ current by FSCPX was both time and concentration dependent and persisted after washout of the antagonist. Pretreatment of atrial myocytes with FSCPX (50 nM) markedly attenuated the activation of K+ current and the inhibition of isoproterenol-stimulated I(Ca,L) caused by adenosine by 90.1% and 84.2%, respectively, but did not alter the responses of atrial myocytes to carbachol. FSCPX (1 microM) irreversibly antagonized the A1-adenosine receptor-mediated increase in atrioventricular nodal conduction time of isolated perfused guinea pig hearts from 10.5 +/- 0.5 to 0.7 +/- 0.6 msec but did not significantly alter the A2-adenosine receptor-mediated decrease in coronary resistance. Preincubation of guinea pig cardiac membranes with 0.1, 1.0, or 3.0 microM FSCPX for 30 min reduced the Bmax of [3H]CPX binding by 41 +/- 10%, 67 +/- 6%, and 80 +/- 1% (mean +/- standard error, three experiments), respectively, with no significant change in the Kd. Similarly, 0.1 and 1.0 microM FSCPX irreversibly reduced the binding of [3H]CPX to guinea pig forebrain membranes by 65 +/- 5% and 83 +/- 2% (four experiments), respectively, but did not reduce the binding of [3H]CGS 21680, an A2a-adenosine receptor agonist, to striatal membranes. FSCPX did not affect the potency of 5'-guanylylimidodiphosphate to inhibit the binding of [3H]CCPA, an A1-adenosine receptor agonist, to brain membranes. The results indicate that FSCPX is a specific, irreversible, A1-adenosine subtype-selective receptor antagonist.
Mol Pharmacol 1996 Jul
PMID:A novel irreversible antagonist of the A1-adenosine receptor. 870 Jan 13

Electroporation-mediated gene transfer into intact plant tissues was demonstrated in pea, cowpea, lentil, and soybean plants. Transient expression of a chimeric gus reporter gene was used to monitor the uptake and expression of the introduced DNA in electroporated nodal axillary buds in vivo. The branches that grew out of the nodal meristems were chimeric and expressed the introduced gene up to 20 d after electroporation. Transgenic R1 pea, lentil, and cowpea plants were recovered from seeds originating on these chimeric branches as shown by Southern blot hybridization and GUS expression. Transgenic R2 soybean and lentil plants were also obtained. Segregation ratios in these populations showed a strong bias against transgene presence or expression.
Mol Biotechnol 1996 Apr
PMID:Transgenic grain legumes obtained by in planta electroporation-mediated gene transfer. 873 22

We examined 232 breast carcinomas for c-erbB-2 amplification by Southern analysis using two different cDNA probes. Using these same probes, 95 of these tumors were also examined for mRNA expression by Northern analysis. Amplification was detected in 20 and 17% of the tumors with the probes pHER 2 and pCER 204, respectively, but only 10% showed amplification with both probes. A significantly higher incidence (p < 0.01) of mRNA overexpression was detected with the pHER 2 probe (34%) compared with the pCER 204 probe (16%), with only 11% of tumors demonstrating overexpression with both probes. A total of 10 tumors (11%) exhibited amplification as well as overexpression with pHER 2, whereas significantly fewer (3%) manifested both abnormalities with the larger pCER 204 probe (p < 0.05). Amplification of c-erbB-2, as detected with the pHER 2 probe but not with the pCER 204 probe, was significantly associated with the absence of both estrogen and progesterone receptors (p < 0.05 and p < 0.01, respectively). No relationship was found with other clinical prognostic indicators, such as nodal involvement and metastases. As determined by either probe, overexpression was not associated with prognostic indicators. There was no significant difference in the c-erbB-2 status of tumors from different racial groups.
Diagn Mol Pathol 1996 Sep
PMID:Variations in c-erbB-2 proto-oncogene status in breast cancer tumors as detected by two different cDNA probes. 886 31

Stromelysin-3 (ST-3) mRNA expression was studied in 28 colorectal carcinomas and compared with that of adjacent nontumorous tissue. By Northern blot analysis, levels of ST-3 mRNA were significantly increased in the carcinomas compared with ST-3 expression was seen with degree of invasion, nodal or distant metastases, or histologic grade. In situ hybridization of nontumorous tissue showed no significant ST-3 expression. In tumor tissue, ST-3 mRNA was localized adjacent to colon carcinoma cells in irregular foci within the stoma. No significant difference in ST-3 expression was found between the center and periphery of the colon tumors. Most of the colon carcinomas (26 of 28) induced an expression of ST-3 in the directly adjacent stroma. No significant correlation between ST-3 mRNA expression and tumor stage and grade was seen. By Northern blot, we also saw expression of ST-3 in noncarcinomatous tissue, further supporting the concept that ST-3 expression is a tumor-induced but not a tumor-specific phenomenon.
Diagn Mol Pathol 1996 Dec
PMID:Stromelysin-3 (ST-3) mRNA expression in colorectal carcinomas. Localization and clinicopathologic correlations. 895 21

In order to improve the cytomorphologic diagnosis of malignant lymphoma on lymph node fine-needle aspiration (FNA), and to make a confident discrimination between low-grade follicular non-Hodgkin's lymphoma (NHL) and lymphoid hyperplasia, polymerase chain reaction (PCR) analysis was performed of the Ig CDR3 region and BCL2 breakpoint region in 25 nonselected cases of malignant lymphoma (17 NHL and 8 Hodgkin's disease [HD]) with histologic control, and 22 cases of lymph nodal hyperplasia with histologic and/or clinical control. Among lymphomas, IgH monoclonality was detected in 7 (77%) of 9 NHLs and BCL2 rearrangement in 3 (17.6%) of 17 NHLs, all of which were follicular centroblastic-centrocytic (FCBCC). Three BCL2/JH negative FCBCC cases were monoclonal for CDR3. Neither IgH monoclonality nor BCL2 rearrangement were found in HD. Among cytologically diagnosed lymphoid hyperplasias, one IgH polyclonal case was considered false-negative, being histologically diagnosed as lymphoplasmacytic NHL on the subsequent excisional biopsy. Another 4 cases (2 BCL2 rearranged and 2 monoclonal for IgH) were considered false-positive on the basis of histologic features or clinical control. These data indicate that the combined PCR analysis of IgH and BCL2 rearrangements can confirm a cytologic diagnosis of lymphoma in FNAs while, due to the occurrence of both false-positive and false-negative results, it is of limited value in the distinction between follicular lymphoma and lymphoid hyperplasia without morphologic or clinical support.
Diagn Mol Pathol 1997 Jun
PMID:PCR analysis of IgH and BCL2 gene rearrangement in the diagnosis of follicular lymphoma in lymph node fine-needle aspiration. A critical appraisal. 927 87

In order to clarify critical events during bronchial carcinogenesis, and to evaluate a possible prognostic role for p21 immunohistochemical detection, we assessed the immunohistochemical expression of p21 protein in 60 surgically resected non-small-cell lung cancers (NSCLCs) that had been investigated previously for their p53 protein status. We found that p21 protein was expressed in both normal and neoplastic tissue. In normal tissue, p21 immunoreactivity was detectable in a low percentage of well-differentiated cells. We found immunostaining for p21 in 80% of the investigated neoplasms. In 73.3% of the neoplasms, p21 was considered to be overexpressed. No relationship was found between p21 overexpression and tumor stage or tumor-nodal-metastatic (TNM) status. The histologic grading was slightly correlated with the p21 status (P = -0.51), with no significant differences noted between squamous carcinomas and adenocarcinomas. Survival percentage curves for our lung-cancer patients, based on a comparison of different p21 expression levels and constructed through a Kaplan-Meier analysis, showed significant differences in mean (P < 0.001) and overall (P < 0.001) survival time between patients of different p21 status, suggesting a favorable prognostic value of p21 immunostaining for NSCLC patients.
Am J Respir Cell Mol Biol 1998 Feb
PMID:p21waf1/cip1mda-6 expression in non-small-cell lung cancer: relationship to survival. 947 8


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