Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factors (IGF) I and II are potent mitogens for breast carcinoma proliferation. IGF-mediated proliferative activity can be markedly enhanced by the presence of specific IGF-binding proteins (IGFBPs). IGFBP-3 has been shown to enhance IGF-mediated growth in a number of systems. Studies have demonstrated IGFBP-3 secretion only in estrogen receptor (ER)-negative breast carcinoma cell lines while IGFBP-3 could not be detected in media conditioned by ER-positive cell lines. We investigated whether a relationship exists between ER status and IGFBP-3 mRNA expression in human breast carcinoma biopsy specimens. We have detected IGFBP-3 mRNA in breast carcinoma tissue obtained from patients utilizing in situ hybridization. Quantitation of IGFBP-3 mRNA levels was performed utilizing image cytometry. There was a significantly higher expression of IGFBP-3 mRNA in ER-negative breast carcinoma specimens when compared to the ER-positive specimens. Whether this higher expression of IGFBP-3 mRNA and presumed secretion of IGFBP-3 by ER-negative tumors play a role in the rapid proliferation and poor prognosis of these tumors remains to be determined.
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PMID:IGFBP-3 gene expression and estrogen receptor status in human breast carcinoma. 138 Dec 77

The existence of hormone receptors on or within neoplastic tissue has potential diagnostic, therapeutic, and prognostic importance. It has now been demonstrated in many reports that cancers of the breast and prostate often express hormone receptors and can be controlled by hormone manipulation. The fact that larynx is a target organ for androgenic steroids has long been known. The question of whether laryngeal carcinoma expresses hormone receptors has been a matter of interest. We adopted the fluorescent hormone conjugate method to measure the estrogen receptor (ER) and progesterone receptor (PR) in 25 patients with laryngeal cancer. Our findings indicated that in 25 samples of laryngeal cancer 48% were ER positive, and 68% were PR positive. Cells of the laryngeal cancer not only contain ER and PR but also have relationship between the presence of receptors and the degree of histologic differentiation. Low differentiated cancers are inclinable to contain low level receptors. From this initial survey it appears that the hormone receptors could play an important role in the cancer of larynx. The presence of receptors in some laryngeal carcinoma implicates that these tumors are possibly hormone sensitive.
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PMID:[Estrogen and progesterone receptors in laryngeal carcinoma]. 139 30

Breast cancer development is associated with several genetic abnormalities. Loss of heterozygosity in the short arm of chromosome 11 has been observed in 30% of tumors. We found homozygosity at five chromosome 11 polymorphic loci in genomic DNA of the MCF-7 breast carcinoma cell line, suggesting a possible loss of one chromosome 11. We have studied the transformed and tumorigenic phenotypes of MCF-7 cells following introduction of a normal human chromosome 11 via microcell fusion. MCF-7/H11 cell hybrids, containing chromosome 11, showed in vitro characteristics similar to the parental cell line. However, tumorigenicity in athymic mice was completely suppressed. Since tumor formation by MCF-7 cells is estrogen dependent, we have analysed the expression of the estrogen receptor and of the estrogen-activated gene pS2. No difference was detected between the parental MCF-7 cells and the derived chromosome 11 cell hybrids, indicating that the mechanism of MCF-7 tumor suppression by chromosome 11-associated functions does not directly involve the estrogen/estrogen receptor molecular pathway.
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PMID:Suppression of tumorigenesis by the breast cancer cell line MCF-7 following transfer of a normal human chromosome 11. 140 42

The antitumor activity of a newly synthesized triphenylethylene derivative [(E)-4-[1-[4-[2-(dimethylamino)ethoxy-phenyl]-2-(4-isopropyl)phenyl-1- butenyl] phenyl monophosphate] (TAT-59) was investigated against human breast carcinoma xenografts in nude mice with reference to the changes of hormone receptors. Five strains (MCF-7, Br-10, R-27, ZR-75-1, and T-61) used for the experiments possessed cytosol estrogen receptor (ER), and their growth was estradiol dependent. Five mg of TAT-59 and tamoxifen citrate (TAM) per kg were administered p.o. daily except Sunday. TAT-59 showed a positive antitumor effect against MCF-7 and R-27, whereas TAM was effective on MCF-7, and their adverse effects detected by mortality rate, body weight loss, and spleen weight loss were similar to each other. The reduction of ER and production of progesterone receptor (PgR) after the treatment with TAT-59 were more potent than after TAM, suggesting that TAT-59 exerts its antitumor effect through binding to ER. These findings suggest that TAT-59 might merit use in clinical trials with breast cancers.
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PMID:Antitumor effect of triphenylethylene derivative (TAT-59) against human breast carcinoma xenografts in nude mice. 143 57

Estrogen receptor status was determined by immunocytochemical examination of fine-needle aspirates in 109 cases of primary invasive breast carcinoma. The results were compared with those from biochemical determination performed on tumor cytosols. Positive agreement was found between qualitative determination (positive/negative) by the two methods in 83% of the cases, and after semiquantitative stratification into three groups the results corresponded in 76%. The predictive value of a positive result on fine-needle aspirate was 96%, and 57% of a negative result. It is concluded that immunocytochemical determination of estrogen receptor status of breast carcinomas on fine-needle aspirate with the applied technique cannot replace the current standard biochemical method.
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PMID:[Determination of estrogen receptor status in breast cancer by immunocytochemical examination of fine-needle aspirates]. 146 48

Ninety-two women with advanced, unilateral breast cancer were classified according to the Wolfe and Nottingham classifications of mammographic parenchymal pattern (MPP). Both classifications of MPP were significantly correlated to the estrogen receptor (ER) status of the breast carcinoma, but could not be used for prediction of response to hormonal therapy. Age distribution was significantly different among Wolfe types as well as between ER groups, but a multiple regression analysis showed that both age and Wolfe pattern were significant and independent predictors of the ER status.
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PMID:Prediction of hormone responsiveness by mammographic parenchymal pattern in advanced primary breast cancer. 146 61

The 5'-flanking region of the human lactoferrin gene was isolated from a human placental genomic library. This genomic clone contains a 16-kilobase pair (kbp) insert and produces seven fragments when digested with the SacI restriction enzyme. We sequenced one of the fragments that comprises 1294 bp of the 5'-flanking sequence, 79 bp of the first exon, and 690 bp of the first intron. A major transcription start site was mapped by primer extension. The region immediately upstream from the transcription initiation site following the first exon is abundant in G and C nucleotides. In the promoter and 5'-flanking region within a 300-bp stretch (-465 to -165) of the DNA, we found a noncanonical TATA box (ATAAA), CAAT-like sequence (CAAC) and sequences homologous to the consensus SP1 binding site, Pu.1/Sp.1 binding element (PU box), two half-palindromic estrogen response elements (EREs; GGTCA), an imperfect ERE (GGTCAAGGCGATC), and a sequence resembling the chicken ovalbumin upstream promoter transcription factor (COUP-TF) binding site (GTCTCACAGGTCA). The COUP-TF binding site and the imperfect ERE shared five nucleotides (GGTCA). With the exception of the two half-palindromic EREs, the elements with very well matched sequences were also found in the corresponding positions in the mouse lactoferrin gene. The synthetic oligonucleotide, including the 26 bp of COUP/ERE sequence, was cloned before the SV40 promoter in a chloramphenicol acetyltransferase reporter construct. These chimeric plasmids were transiently transfected into human endometrium carcinoma RL95-2 cells to assess hormone responsiveness. We found that the COUP/ERE element acted as an enhancer in response to estrogen stimulation. In vitro DNase I footprinting analysis showed binding of the estrogen receptor on the imperfect ERE. In contrast to the mouse lactoferrin COUP/ERE element, COUP-TF does not interact with this element, as demonstrated by band shift assay and site-directed mutagenesis. Therefore, the molecular mechanisms of the estrogen action that govern the lactoferrin gene expression differ between mouse and human.
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PMID:Differential molecular mechanism of the estrogen action that regulates lactoferrin gene in human and mouse. 148 Jan 83

The effect of recombinant human interferon-alpha 2a (rhIFN-alpha 2a) on the hormone receptor level and antitumor activity of tamoxifen (TAM) was investigated in nude mice using ZR-75-1, an estrogen receptor (ER)-positive, and progesterone receptor (PgR)-negative human breast carcinoma xenograft. ER levels (maximum binding sites) of tumors treated with rhIFN-alpha 2a at a dose of 6 x 10(5) U/mouse/day for 1 or 3 wk were not significantly different from the control, whereas those with rhIFN-alpha 2a at a dose of 6 x 10(4) U/mouse/day for 1 or 3 wk were higher than the control (3.9- to 4.4-fold) with a significant difference at P < 0.01. The increase of ER by rhIFN-alpha 2a was investigated using a sucrose density gradient method. The peak was only seen at 8S in both rhIFN-alpha 2a-treated tumor and control ER, and the sedimentation patterns were almost the same, suggesting that both ERs were essentially equivalent. On the other hand, PgR of all the treated groups could be detected, while that of the control group was undetectable. The antitumor effect of the combination treatment of rhIFN-alpha 2a and TAM was compared with those of single treatments. While rhIFN-alpha 2a at a dose of 6 x 10(5) U/mouse/day and TAM did not show a combination effect, rhIFN-alpha 2a at a dose of 6 x 10(4) U/mouse/day and TAM showed a synergistic combination effect, and ER was decreased to the threshold of detection by the combination treatment. These findings indicated that a low dose of rhIFN-alpha 2a increased the ER levels of ER-positive human breast cancer in vivo as well as in vitro and enhanced the anti-proliferative effect of TAM, and the newly synthesized ER was essentially the same as the original ER.
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PMID:Recombinant human interferon-alpha 2a increases hormone receptor level of a human breast carcinoma xenograft in nude mice and enhances the anti-proliferative activity of tamoxifen. 148 48

Recent reports have suggested that tissue-type plasminogen activator activity is regulated by estrogen in 7,12-dimethylbenz[a]anthracene-induced rat mammary carcinoma type I cells but is not necessarily regulated by estrogen in type II mammary carcinoma cells. We have compared the biological features of these two types of mammary carcinoma cells and have found that, although there is no difference in estrogen receptor content between these two cell types, the plasminogen activator activity markedly differs. Tissue-type plasminogen activator activity is significantly higher in type I carcinoma than in type II carcinoma, urokinase-type activity is significantly higher in type II carcinoma than in type I carcinoma. When these two types were compared in terms of rate of tumor growth, type II carcinomas clearly showed more rapid growth than type I carcinomas. Survival studies showed significantly shorter survival of type II tumor-bearing rats compared with type I tumor-bearing rats. Furthermore, type II carcinomas contained a greater proportion of aneuploid cells than type I carcinomas. These results suggest that type II carcinoma cells, in which estrogen is unable to regulate tissue-type plasminogen activator activity, are considered to be of a higher grade of malignancy than type I carcinoma cells.
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PMID:Demonstration of a possible link between high grade malignancy in dimethylbenz[a]anthracene-induced rat mammary carcinoma and increased urokinase plasminogen activator content. 152 Sep 14

We have recently demonstrated that physiological levels of androgens exert direct and potent inhibitory effects on the growth of human breast cancer ZR-75-1 cells in vivo in nude mice as well as in vitro under both basal and estrogen-stimulated conditions. The inhibitory effect of androgens has also been confirmed on the growth of dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat. Such observations are in close agreement with the clinical data showing that androgens and the androgenic compound medroxyprogesterone acetate (MPA) have beneficial effects in breast cancer in women comparable to other endocrine therapies, including tamoxifen. Although the inhibitory action of androgens on cell proliferation in estrogen-induced ZR-75-1 cells results, in part, from their suppressive effect on expression of the estrogen receptor, the androgens also exert a direct inhibitory effect independent of estrogens. Androgens cause a global slowing effect on the duration of the cell cycle. These observations support clinical data showing that androgenic compounds induce an objective remission after failure of antiestrogen therapy as well as those indicating that the antiproliferative action of androgens is additive to that of antiestrogens. We have also recently demonstrated in ZR-75-1 human breast cancer cells the antagonism between androgens and estrogens on the expression of GCDFP-15 and GCDFP-24 which are two major proteins secreted in human gross cystic disease fluid. The effects of androgens and estrogens as well as those of progestins and glucocorticoids on GCDFP-15 and GCDFP-24 mRNA levels and secretion are opposite to those induced by the same steroids on cell growth in ZR-75-1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Androgens and breast cancer. 155 Nov 35


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