Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of three hormonal agents with a different mechanism of action (tamoxifen [TAM], medroxyprogesterone acetate [MPA] and estradiol [E2]) on tumor growth, differentiation and oncogene expression were evaluated using the estrogen-receptor positive human breast carcinoma cell line MCF-7 transplanted into nude mice. In MCF-7 tumors treated with E2, tumor incidence, mean weight of tumors, 3H-thymidine labelling index, differentiation antigen HMFGM (human milk-fat globule membrane) and ras p21, c-myc, neu oncogene products, the level was significantly increased. On the other hand MPA suppressed all of them. TAM increased the level of c-myc expression and HMFGM antigen, but suppressed the others. This evidence indicates that E2 induces both proliferation and differentiation of MCF-7 tumor cells. MPA suppresses both proliferation and differentiation, and TAM induces differentiation and suppresses proliferation.
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PMID:Effects of tamoxifen, medroxyprogesterone acetate and estradiol on tumor growth and oncogene expression in MCF-7 breast cancer cell line transplanted into nude mice. 183 73

A 59-year-old previously oophorectomized woman underwent surgery for a recurrent malignant granulosa cell tumor. Specimens and dispersed cells from the tumor tissue were incubated for 2 hr and cultured for 48 hr, respectively, with and without gonadotropins. Steroids and cyclic AMP (cAMP) concentrations were measured in the incubation and culture media. Incubated specimens from the tumor tissue released measurable amounts of cAMP, progesterone, and estradiol into the medium. Human follicle-stimulating hormone (FSH) 1 microgram/ml significantly stimulated the formation of cAMP and both steroids. Human luteinizing hormone (LH) 1 microgram/ml stimulated cAMP and progesterone but not estradiol release. Human chorionic gonadotropin (hCG) 10 micrograms/ml stimulated cAMP and progesterone formation in tumor tissue but was totally devoid of effect on estradiol release. In the tissue culture experiments progesterone and estradiol were formed in considerable amounts, with a higher capacity for progesterone than for estradiol. Progesterone formation was stimulated by FSH and hCG, while estradiol release was stimulated only by hCG. The addition of testosterone significantly enhanced estradiol formation in both incubation and culture experiments. It is concluded that the steroidogenesis of this granulosa cell tumor is sensitive to gonadotropins.
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PMID:Human granulosa cell tumor: stimulation of steroidogenesis by gonadotropins in vitro. 184 99

Progesterone-binding cyst protein (PBCP) is a secretory protein which has been found in varying concentrations and incidence in cytosols from benign breast tumors, primary breast cancer and metastasis. In order to evaluate its correlation to other prognostic factors, PBCP was analysed in tumor cytosols from 386 women with stage I and stage II breast cancer. The incidence of PBCP negative (i.e. PBCP = 0) tumors was significantly decreased in node negative patients as compared to node positive (p = 0.012). An inverse correlation between estrogen receptor content and PBCP was found (p = 0.001). In a multivariate analysis PBCP category was found to be an independent predictor of the likelihood of axillary nodal involvement (p = 0.015). In spite of this association, PBCP did not reach statistical significance as an independent prognostic factor with regard to relapse-free survival. To evaluate PBCP category as a possible predictive factor for response to adjuvant endocrine treatment, a subpopulation of node positive patients with ER positive tumors was analysed; in patients with PBCP negative tumors, adjuvant treatment with tamoxifen proved to increase the relapse-free survival significantly (p = 0.011). We suggest that PBCP may have a place among other biochemical parameters in breast cancer, to provide an extended basis for understanding of tumor biology and a better selection of patients for endocrine treatment.
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PMID:Progesterone-binding cyst protein (PBCP) in operable breast cancer: correlations with prognostic factors and predictive value for effect of adjuvant tamoxifen treatment. 206 14

The objective of the present investigation was to compare the effects of three ornithine decarboxylase inhibitors on tumoricidal macrophage and antitumor activities in vivo. alpha-Difluoromethylornithine (DFMO), (2R,5R)-6-heptyne-2,5-diamine, and alpha-(fluoromethyl)dehydroornithine methyl ester (delta MFMOme) were administered continuously in drinking water starting on Day 1 to B16F1 tumor-bearing mice. DFMO, (2R,5R)-6-heptyne-2,5-diamine, and delta MFMOme reduced B16F1 tumor growth, measured on Day 18, up to 87, 79, and 95%, respectively. Similarly, all three ornithine decarboxylase inhibitors reduced B16F1 putrescine and spermidine levels. delta MFMOme was substantially more effective both as an antitumor agent and in reducing polyamines. Both DFMO and delta MFMOme augmented macrophage tumoricidal activity directed against B16F1 target cells. MAP had no effect on macrophage tumoricidal activity. Lipopolysaccharide-stimulated macrophages from delta MFMOme-treated mice also exhibited an increase in interleukin and tumor necrosis factor levels. Furthermore, treatment with a known macrophage activator, gamma-interferon, enhanced the antitumor activity of delta MFMOme. delta MFMOme did not alter natural killer cell activity; however, cytolytic T-lymphocyte induction was reduced by 40 to 50%. These results demonstrate that, in addition to their established antitumor activity, ornithine decarboxylase inhibitors may also potentiate specific tumoricidal effector cell generation in vivo.
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PMID:Effects of three irreversible inhibitors of ornithine decarboxylase on macrophage-mediated tumoricidal activity and antitumor activity in B16F1 tumor-bearing mice. 211 41

The success of renal cell carcinoma (RCC)-nephrectomy with radical lymph node dissection in stage I and II disease is undisputed. Through these measures 23% of metastases are controlled. The five-year survival time in stage III disease, however, stagnates at 35% +/- 14% despite radical surgery. Also, the additional tumor-vaccine-therapy of the Mainz-Joint-Study-Group was successful only in stage I and II disease, whereas stage III disease did not benefit from this therapy. As 50% of all radically operated patients developed metastases within three years after surgery, the call by radio-oncologists for supplementary radiotherapy beginning with stage III disease must be put foreward. The problems of therapy and chances of survival in generalized disease are demonstrated in 100 of our cases treated by surgery, radiotherapy and with MPA (medroxyprogesteroneacetate). Whereas Schmiedt et al. show a total survival time of 10,3 months after diagnosis of metastatic disease, the Offenbach patients achieved 16,5 months with a median survival time of 11,75 months. The necessity of therapeutic intervention is confirmed by the fact that the most favorable median survival time, 15,75 months, was achieved in metastatic disease involving three organs. We present here the special features of the individual organ manifestations and point out that not only the mean and median survival time, but also the very widely varying survival times in individual cases, make conscientious oncological post-treatment follow up and management a requirement.
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PMID:[Long-term results in the treatment of 100 metastatic hypernephroid carcinomas]. 213 18

The efficacy and side-effects of megestrol acetate and medroxyprogesterone acetate in postmenopausal patients with advanced breast cancer were compared in a prospectively randomized study. The dosage of MA was 2 X 80 mg p.o. or MPA 2 X 500 mg p.o. daily, given as a secondary hormonal treatment, mostly after previous treatment with tamoxifen. Ninety-eight patients entered the study and 92 were evaluable for effect, 48 patients on MA and 44 on MPA. Age, main tumor site and prior treatment were not different, but there was a preponderance of ER-negative tumors in the MA group. Responses appeared to be more frequent in the MPA-treated group (25% vs. 43%), predominantly in bone lesions, 12% for MA and 45% for MPA. Median progression-free survival was comparable, 15 vs. 10 months, and overall survival was not different (20 vs. 16 months). Toxicity was frequent, occurring in 83% vs. 74% of patients: increased appetite, nausea and dizziness in more than 20%, and a preponderance of pyrosis and breathlessness on MA and hot flashes, sweating and tremors on MPA. Cushingoid symptoms were present in about a quarter of the patients treated for more than 3 months. The occurrence of thrombo-embolic episodes and cardiovascular events was evenly distributed. Patients on MPA had more often increase in body weight, systolic blood pressure and serum creatinine than those treated with MA. It is concluded that MPA may be more effective for treatment of bone metastases, at the expense of more progestational side-effects. The occurrence of Cushingoid effects is frequent but similar in both arms, while the incidence of cardiovascular or thrombo-embolic events cannot be related to the use of either compound.
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PMID:A randomized comparison of megestrol acetate (MA) and medroxyprogesterone acetate (MPA) in patients with advanced breast cancer. 214 91

Full-grown Xenopus laevis oocytes resume meiosis from prophase arrest in response to progesterone stimulation. Recent studies have shown that the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA), a very potent activator of protein kinase C, can also induce the resumption of meiosis in amphibian oocytes. We have investigated the possibility that sn-1,2-diacylglycerol (DAG), the intracellular activator of protein kinase C, may be involved in the pathway normally used by progesterone. We have found that full-grown oocytes arrested in meiotic prophase contain 48 +/- 5 pmoles DAG/oocyte. This level increases within the first 5 minutes following the addition of progesterone and reaches a maximum of 75 +/- 10 pmoles following 60 minutes of steroid stimulation. Progesterone induces the up-regulation of a Na+/H+ antiport in the plasma membrane of the oocyte causing an increase in pHi following 60 minutes of steroid stimulation. We have found that the addition of 200 microM DAG (1,2-dioctanoylglycerol, diC8) to the culture medium can cause a partial up-regulation of this Na+/H+ pump in the absence of hormonal stimulation. These results suggest that DAG and protein kinase C may be involved in regulating certain aspects of meiotic maturation in progesterone-stimulated Xenopus oocytes.
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PMID:sn-1,2-diacylglycerol levels increase in progesterone-stimulated Xenopus laevis oocytes. 216 19

From 114 patients treated with local radiotherapy after nephrectomy up to now 46 patients are alive. 59 patients died; 55 patients died because of the tumor, 4 patients died because of other genesis. At 4 patients, who are alive, a secondary therapy because of pulmonary metastasis was performed. Three times a solitary metastasis of the lung was removed surgically. One female patient came into a CR under therapy with Gestagen (Depo Provera). Three patients (2.6%) died because of a local recidive. There was no change of survival rates and local recidive rates compared to surgery alone.
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PMID:[Results following radiotherapy for hypernephroma]. 226 23

The proliferative activity of 163 primary breast cancers was assessed by immunocytochemistry with the mouse monoclonal antibody Ki-67, which recognizes a nuclear antigen expressed in all phases of the cell cycle except for Go. The overall frequency distribution of Ki-67 staining was of exponential type, with percentage of positive staining cells ranging from 0.3 to 88.3%, with a median value of 10.1%. No relationship was observed between Ki-67 values and menopausal status of patients. A significant positive correlation was found between Ki-67 values and tumor grade, especially mitotic grade. Estrogen Receptors (ER) were assayed by immunocytochemistry with ER-ICA method and by dextran-coated charcoal method (DCC) in 129 and 141 tumors, respectively. A negative correlation was found between the ER content by both methods and Ki-67 score. Eighty-nine percent of cases with Ki-67 value less than 10.1% contained more than 10% ER-ICA-positive cells. Progesterone receptors (PgR) were assayed by immunocytochemistry with PgR-ICA method and by DCC in 62 and 141 tumors, respectively. A negative correlation was observed between the PgR content by both methods and Ki-67 score. No correlation was found between Ki-67 score and lymph node involvement by tumor. These findings suggests that Ki-67 score could be used as an independent prognostic marker, useful to distinguish different risk for recurrence within the two clinically heterogeneous groups of N- and N+ patients.
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PMID:Assessment of proliferative rate of breast cancer by Ki-67 monoclonal antibody. 230 19

In order to clarify possible alterations of membrane-, and cytoplasma-glycoconjugates of laryngeal cancer cells in metastatic process, a histochemical study was performed on laryngeal squamous carcinoma, using seven lectins conjugated with horseradish peroxidase (HRP); PNA, UEA-I, WGA, RCA-I, DBA, SBA and MPA. The author studied 32 primary tumors and 32 corresponding metastatic tumors obtained from 32 patients and primary tumors from 8 patients without histological evidence of lymph node metastasis. None of the patients underwent irradiation or chemotherapy before operation. The specimens were provided for routine lectin histochemistry. The present study revealed some significant differences in lectin-binding as follows. Primary tumor vs. metastatic tumor: There was a significant difference in lectin-binding between primary and metastatic cancer cells. 29 (90.0%) of 32 primary tumors were positive for MPA-staining. On the other hand, 21 (65.6%) of 32 metastatic tumors were positive for MPA-staining. There was a statistically significant (p less than 0.05) difference between primary and metastatic tumors with regard to MPA-binding. Primary tumor cells tended to more bind with lectins than with metastatic tumor cells. Well-differentiated primary tumor vs. moderately differentiated primary tumor: There was a significant difference in lectin-binding between these two types of tumors. Of 15 well-differentiated primary tumors, 13 (86.7%) showed SBA binding. The percentage of SBA-binding was significantly higher in well-differentiated tumor than in moderately differentiated primary tumors (50%, 8/16). Keratinization vs. non-keratinization: There was a significant difference in lectin-binding between keratinized and non-keratinized tumor cells in both primary and metastatic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Lectin histochemistry of primary and metastatic tumor cells of laryngeal cancer]. 234 78


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