Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uterine papillary serous carcinoma (UPSC) is an aggressive malignancy that accounts for a disproportionate number of intraabdominal failures among endometrial carcinoma patients. The histologic appearance and tendency toward intraabdominal spread resemble those of papillary serous adenocarcinoma of the ovary. Because approximately 70% of untreated ovarian carcinoma patients respond to platinum-based chemotherapy, it has been suggested that UPSC patients might respond to similar treatment regimens. Twenty patients with UPSC were treated with cisplatin, doxorubicin (Adriamycin), cyclophosphamide (PAC) chemotherapy between January 1982 and December 1989. They included 9 patients with advanced primary disease, 5 with recurrence, and 6 who received PAC as adjuvant therapy. Patients received a mean of five cycles of PAC. Only 2 of 11 patients with measurable disease greater than 2 cm achieved complete clinical responses of 12 and 31 months duration; there were no partial responses. Actuarial 5-year survival for all patients was 23%. The mean progression-free interval was 9 months. Patients with clinical stages I or II disease had a higher survival rate than those with stage III or IV disease (P = 0.003). Survival did not correlate with depth of myometrial invasion (P = 0.81) or size of residual tumor following initial surgery (P = 0.16). Estrogen or progesterone receptors were detected in 10 of 11 tumors tested. Seven of 9 patients tested had elevated serum levels of CA-125 (greater than 35 U/ml). Correlation between CA-125 value and clinical course was demonstrated in 3 of 5 patients who had serial measurements. Of all patients, 3 are currently alive; 1 has documented disease. Moderate to severe toxicity was seen in 14 patients (70%). There was one possible treatment-related death from cardiomyopathy. UPSC, despite its histologic and clinical similarities to ovarian carcinoma, was relatively resistant to PAC chemotherapy in this mixed group of patients.
 ...
PMID:Uterine papillary serous carcinoma (UPSC) treated with cisplatin, doxorubicin, and cyclophosphamide (PAC). 152 8

The pathophysiological basis of blood coagulation includes hemostatic causes and thrombophilia (protein C deficiency, protein S deficiency, APC resistance, plasminogen deficiency, antithrombin III deficiency, hyperhomocystinemia, lupus anticoagulans and anticardiolipin antibodies). The effect of female sexual steroids on coagulation has been observed: ethinyl estradiol produced an increased risk of thromboembolism. Also, there was a pronounced increase of fibrin division products among users of higher EE doses. The effect of gestagens on coagulation was found to be contradictory. The risk of thrombosis as related to oral contraceptives (OCs) was investigated in several studies. Desogestrel and gestoden-containing OCs produced a higher incidence of thrombosis than levonorgestrel-containing pills. A WHO multinational case-control study was carried out in 21 centers and 17 countries during 1989-93, including a total of 1143 cases and 2998 controls. The risk of thrombosis was 2-3 times higher among women using gestoden or desogestrel-containing OCs than those using LNG-containing OCs. Similarly, there was a 1.58 increased risk according to a case-control study using data from England and Germany. A 1995 study of 700 medical practices in Great Britain involving 238,130 women showed increased risk for gestoden (1.8) and desogestrel (1.9). Another 1995 study used the data of 697,000 women from 398 practices in England and registered 116 cases of thromboembolism. There was a risk three times higher for all ovulation inhibitors among cases compared to controls, as well as a pregnancy risk 5.9 times higher. Nonetheless, no definitive conclusion can be drawn from all of these epidemiological studies, which could challenge the prevailing view on contraceptive behavior.
 ...
PMID:[Contraceptive agents and risk of thrombosis]. 941 70

Gamma-interferon (IFN-gamma) plays an important role in the maintenance of immune homeostasis by regulating the functions of all key cells of the immune system. Pathologically, IFN-gamma has been implicated in several autoimmune diseases. Since estrogens affect autoimmunity, we investigated whether immunomodulatory estrogenic hormones affects IFN-gamma. Concanavalin-A-stimulated splenic lymphocytes from orchiectomized or ovariectomized C57BL/6 mice exposed to estrogen for 3-5 months secreted higher levels of IFN-gamma protein compared to controls. This increase is, in part, due to increased levels of IFN-gamma mRNA. Kinetic studies suggested that splenic lymphocytes from estrogen-treated gonadectomized mice had increased IFN-gamma mRNA and protein as early as 6-12 h of culture. Estrogen also increased the expression of co-stimulatory CD80 (B7-1) molecules on B cells. Since natural estrogen increases IFN-gamma, it became important to test whether diethylstilbestrol (DES, a synthetic estrogen which was given to millions of women) also alters IFN-gamma levels. Our initial investigatory studies show that prenatal mice exposed to DES had a normal ability to secrete IFN-gamma. However, a second exposure of these mice to DES (single dose of 1 microg/g.b.w), as late as 1-1.5 years of age, led to a pronounced increase in the number of IFN-gamma secreting cells and augmented secretion of IFN-gamma. Increased IFN-gamma secretion by splenic lymphocytes from these mice was noted even after stimulation with a submitogenic concentration of anti-CD3 antibodies with or without anti-CD28 antibodies. Cell mixing experiments suggested that the DES-induced increase in IFN-gamma secretion is due to hormonal effects on T cells but not on APC. Together our studies show that: (1) estrogens upregulate IFN-gamma secretion, a vital immunoregulatory cytokine, and (2) inappropriate exposure of developing fetus to DES may permanently alter the "cytokine programming" of lymphocytes.
 ...
PMID:Interferon-gamma levels are upregulated by 17-beta-estradiol and diethylstilbestrol. 1160 Jan 82