Androstadienes ; therapeutic use ; Antineoplastic Agents, Hormonal ; administration & dosage ; Aromatase Inhibitors ; administration & dosage ; Breast Neoplasms ; drug therapy ; Drug Administration Schedule ; Female ; Humans ; Nitriles ; administration & dosage ; Postmenopause ; Triazoles ; administration & dosage

OBJECTIVETo investigate the effect of two different doses of letrozole in promoting ovulation in infertile women with polycystic ovarian syndrome (PCOS).

METHODSSeventy-six PCOS infertile women undergoing intrauterine insemination (IUI) or with anovulation were divided into two groups and received oral letrozole at the daily dose of 2.5 (n=36) or 5.0 mg (n=40) from the 3rd to the 7th day of the menstrual cycle. Three days after discontinuation of the medication (the 10th day of the menstrual cycle ), ultrasound scanning was performed to monitor the follicle development. When the diameter of the biggest follicle reached 14 mm, the presence of luteinizing hormone (LH) was monitored; when LH positivity was detected, blood samples were drawn to test follicle-stimulating hormone (FSH), LH, estradiol (E2) and testosterone (T) levels. Human chorionic gonadotropin (hCG, 10 000 U) was then injected to induce ovulation.

RESULTSThe ovulation rate, stimulation follicle days, diameter of the biggest follicle on the day of LH positivity and the thickness of endometrium were all similar between the two groups (P>0.05). But in women receiving 5.0 mg letrozole, both the number of mature follicles and pregnancy rate were significantly higher than those in women having the half dose (P<0.05). The levels of FSH, LH, E2, and T on the third day of menstruation and on the day of HCG injection were similar between the two groups (P<0.05).

CONCLUSIONLetrozole at the dose of 5.0 mg/day produces higher pregnancy rate and more mature follicles in fertile women with PCOS.

Adult ; Aromatase Inhibitors ; administration & dosage ; Female ; Fertility Agents, Female ; administration & dosage ; Humans ; Infertility, Female ; drug therapy ; etiology ; Insemination, Artificial ; Nitriles ; administration & dosage ; Ovulation Induction ; methods ; Polycystic Ovary Syndrome ; complications ; Triazoles ; administration & dosage

OBJECTIVETo evaluate the inhibitory effect of genistin combined with anastrozole on the growth and apoptosis of breast tumor tissue, and to study their anti-cancer mechanism by using the model of 7,12-dimethylbenz [alpha] anthracene (DMBA)-induced mammary tumors following ovariectomy in Sprague-Dawley (SD) rats.

METHODSThe DMBA induced postmenopausal SD rats were randomly divided into the control group, the genistein group, the anastrozole group, and the genistein combined with anastrozole group. The growth of tumors was observed in each group. The proliferation index and apoptosis index of tumor cells were determined. Moreover, estradiol (E2) and 17beta-HSD1 mRNA levels were determined by ELISA and RT-PCR respectively.

RESULTSThe tumor growth was inhibited in the genistein group and the anastrozole group. The inhibitory ratio was significantly higher in the genistein combined with anastrozole group (P < 0.05). Compared with the control group, levels of E2 and 17beta-HSD1 mRNA decreased more significantly in the genistein combined with anastrozole group (P < 0.05).

CONCLUSIONSGenistein could suppress the growth of mammary tumors in postmenopausal rats. It showed synergistic effect when combined with anastrozole, which resulted in reduced levels of E2 and 17beta-HSD1 mRNA. It had inhibitory effect on the growth of breast tumors.

17-Hydroxysteroid Dehydrogenases ; metabolism ; Animals ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Estradiol ; metabolism ; Female ; Genistein ; administration & dosage ; pharmacology ; Mammary Neoplasms, Experimental ; chemically induced ; pathology ; Nitriles ; administration & dosage ; pharmacology ; Ovariectomy ; Postmenopause ; Rats ; Rats, Sprague-Dawley ; Triazoles ; administration & dosage ; pharmacology

PURPOSE: To evaluate the efficacy of minimal stimulation using discretely administered gonadotropin combined with clomiphene citrate (CC) or letrozole (LTZ) for intrauterine insemination (IUI) cycles. MATERIALS AND METHODS: Total 257 IUI cycles from 158 infertile couples were assessed. A CC dose of 100 mg/day (n=126 cycles) or a LTZ dose of 5 mg/day (n=131 cycles) was administered on days 3-5 of the menstrual cycle for 5 days. Each group received human menopausal gonadotropin at a dose of 150 IU by two or three alternative day: CC combined with alternate-day regimen for 2 or 3 days (CC+300, n=37; CC+450, n=89) and LTZ combined with alternate-day regimen for 2 or 3 days (LTZ+300, n=36; LTZ+450, n=95). RESULTS: The clinical pregnancy rate was comparable between the CC and LTZ groups (18.3% vs. 13.0%, p=0.243). The clinical pregnancy rate also showed no significant difference among the 4 groups (21.6% vs. 16.9% vs. 11.1% vs. 12.6%, p=0.507). The multiple pregnancy rate was significantly higher in LTZ compared to CC group (37.5% vs. 8.7%, p=0.028) and in the LTZ+450 compared to CC+450 group (50% vs. 13.3%, p=0.038). Overall, there were 15 cases of ovarian hyperstimulation syndrome (OHSS), with the prevalence being significantly lower in the LTZ compared to CC group (1.5% vs. 10.3%, p=0.003). OHSS was more prevalent in the CC+450 compared to the LTZ+450 group (12.4% vs. 1.1%, p=0.002). CONCLUSION: Our findings suggest that minimal stimulation using two alternate-day gonadotropin with LTZ decreases the development of OHSS and multiple pregnancies, while maintaining comparable pregnancy rates in IUI cycles.
Adult ; Aromatase Inhibitors/administration & dosage ; Clomiphene/*administration & dosage/therapeutic use ; Drug Administration Schedule ; Drug Combinations ; Female ; Fertility Agents, Female/administration & dosage/therapeutic use ; Fertilization in Vitro ; Gonadotropins/*administration & dosage ; Humans ; Infertility, Female/*drug therapy ; Insemination, Artificial/*statistics & numerical data ; Nitriles/*administration & dosage ; Ovulation Induction/methods/*statistics & numerical data ; Pregnancy ; Pregnancy Rate ; Treatment Outcome ; Triazoles/*administration & dosage

PURPOSE: To evaluate the efficacy of minimal stimulation using discretely administered gonadotropin combined with clomiphene citrate (CC) or letrozole (LTZ) for intrauterine insemination (IUI) cycles. MATERIALS AND METHODS: Total 257 IUI cycles from 158 infertile couples were assessed. A CC dose of 100 mg/day (n=126 cycles) or a LTZ dose of 5 mg/day (n=131 cycles) was administered on days 3-5 of the menstrual cycle for 5 days. Each group received human menopausal gonadotropin at a dose of 150 IU by two or three alternative day: CC combined with alternate-day regimen for 2 or 3 days (CC+300, n=37; CC+450, n=89) and LTZ combined with alternate-day regimen for 2 or 3 days (LTZ+300, n=36; LTZ+450, n=95). RESULTS: The clinical pregnancy rate was comparable between the CC and LTZ groups (18.3% vs. 13.0%, p=0.243). The clinical pregnancy rate also showed no significant difference among the 4 groups (21.6% vs. 16.9% vs. 11.1% vs. 12.6%, p=0.507). The multiple pregnancy rate was significantly higher in LTZ compared to CC group (37.5% vs. 8.7%, p=0.028) and in the LTZ+450 compared to CC+450 group (50% vs. 13.3%, p=0.038). Overall, there were 15 cases of ovarian hyperstimulation syndrome (OHSS), with the prevalence being significantly lower in the LTZ compared to CC group (1.5% vs. 10.3%, p=0.003). OHSS was more prevalent in the CC+450 compared to the LTZ+450 group (12.4% vs. 1.1%, p=0.002). CONCLUSION: Our findings suggest that minimal stimulation using two alternate-day gonadotropin with LTZ decreases the development of OHSS and multiple pregnancies, while maintaining comparable pregnancy rates in IUI cycles.
Adult ; Aromatase Inhibitors/administration & dosage ; Clomiphene/*administration & dosage/therapeutic use ; Drug Administration Schedule ; Drug Combinations ; Female ; Fertility Agents, Female/administration & dosage/therapeutic use ; Fertilization in Vitro ; Gonadotropins/*administration & dosage ; Humans ; Infertility, Female/*drug therapy ; Insemination, Artificial/*statistics & numerical data ; Nitriles/*administration & dosage ; Ovulation Induction/methods/*statistics & numerical data ; Pregnancy ; Pregnancy Rate ; Treatment Outcome ; Triazoles/*administration & dosage

Objective: To investigate the clinical effects of integrated traditional Chinese and Western medicine in the treatment of castration-resistant prostate cancer (CRPC). METHODS: A total of 54 CRPC patients were randomly divided into a control and a trial group, all treated by endocrine therapy (oral Bicalutamide at 50 mg per d plus subcutaneous injection of Goserelin at 3.6 mg once every 4 wk) and chemotherapy (intravenous injection of Docetaxel at 75 mg/m2 once every 3 wk plus oral Prednisone at 5 mg bid), while the latter group by Fuyang Huayu Prescription (a Traditional Chinese Medicine ［TCM］ prescription for tonifying yang and dispersing blood stasis) in addition, for a course of 24 weeks. Comparisons were made between the two groups of patients in the level of serum prostate-specific antigen (PSA), Karnofsky physical condition scores, function assessment of cancer therapy-prostate (FACT-P) scores, and TCM symptoms scores before and after 12 or 24 weeks of treatment. RESULTS: Compared with the baseline, the serum PSA level was significantly decreased after 12 weeks of treatment both in the control (［25.9 ± 39.3］ vs ［20.0 ± 21.1］ μg/L, P <0.05) and in the trial group (［22.1 ± 33.9］ vs ［17.9 ± 19.1］ μg/L, P <0.05), with no statistically significant differences between the two groups (P >0.05). At 24 weeks, however, the PSA levels in the control and trial groups were slightly increased to (23.1 ± 28.4) and (19.6 ± 23.5) μg/L, respectively, with no statistically significant differences in between (P >0.05). Karnofsky, FACT-P and TCM symptoms scores were all markedly improved in the trial group after 12 weeks of treatment (P <0.05) and remained stable at 24 weeks, but not in the control group either at 12 or at 24 weeks (P >0.05). CONCLUSIONS TCM Fuyang Huayu Prescription combined with endocrine therapy and chemotherapy is effective for CRPC.
Anilides ; administration & dosage ; Antineoplastic Agents, Hormonal ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Docetaxel ; Drug Administration Schedule ; Goserelin ; administration & dosage ; Humans ; Male ; Nitriles ; administration & dosage ; Prednisone ; administration & dosage ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms, Castration-Resistant ; blood ; drug therapy ; Taxoids ; administration & dosage ; Tosyl Compounds ; administration & dosage ; Treatment Outcome

OBJECTIVETo investigate the role of extracellular signal-regulated kinase1/2 (ERK1/2) pathway in the regulation of aquaporin 4 (AQP4) expression in cultured astrocytes after scratch-injury.

METHODSThe scratch-injury model was produced in cultured astrocytes of rat by a 10-μL plastic pipette tip. The morphological changes of astrocytes and lactate dehydrogenase (LDH) leakages were observed to assess the degree of scratch-injury. AQP4 expression was detected by immunofluorescence staining and Western blot, and phosphorylated-ERK1/2 (p-ERK1/2) expression was determined by Western blot. To explore the effect of ERK1/2 pathway on AQP4 expression in scratch-injured astrocytes, 10 µmol/L U0126 (ERK1/2 inhibitor) was incubated in the medium at 30 min before the scratch-injury in some groups.

RESULTSIncreases in LDH leakage were observed at 1, 12, and 24 h after scratch-injury, and AQP4 expression was reduced simultaneously. Decrease in AQP4 expression was associated with a significant increase in ERK1/2 activation. Furthermore, pretreatment with U0126 blocked both ERK1/2 activation and decrease in AQP4 expression induced by scratch-injury.

CONCLUSIONThese results indicate that ERK1/2 pathway down-regulates AQP4 expression in scratch-injured astrocytes, and ERK1/2 pathway might be a novel therapeutic target in reversing the effects of astrocytes that contribute to traumatic brain edema.

Animals ; Aquaporin 4 ; metabolism ; Astrocytes ; enzymology ; metabolism ; Butadienes ; administration & dosage ; Cells, Cultured ; Down-Regulation ; Enzyme Activation ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; MAP Kinase Signaling System ; Nitriles ; administration & dosage ; Rats ; Rats, Wistar ; Skin ; injuries

OBJECTIVETo search for an effective hormonal therapy for delaying the progression of prostate cancer to androgen-independent prostate cancer (AIPC).

METHODSThis study included 93 cases of prostate cancer confirmed by transrectal ultrasound-guided biopsy, 22 treated by bilateral orchiectomy plus bicalutamide as a continuous androgen deprivation (CAD) therapy, and the other 71 by the intermittent androgen deprivation (IAD) therapy, the latter divided into a standard IAD group (n = 29) and a modified IAD group (n = 42) to be treated by maximum androgen blockage (MAB) until the serum PSA level decreased to less than 0.2 microg/L and the medication was maintained for 3 months. Entering the intermittent period, the patients of the standard IAD group discontinued medication, while those in the modified IAD group withdrew luteinizing hormone-releasing hormone analogue (LHRH-a) but continued the use of bicalutamide. MAB was resumed in these two groups when serum PSA manifested a continuous rise and went up to 4 microg/L until prostate cancer progressed to AIPC. Comparisons were made among the CAD, standard IAD and modified IAD groups in the follow-up time, time of progression to CRPC and treatment cycles.

RESULTSThe three groups of patients were well balanced in terms of demographics, baseline characteristics and follow-up time. The median times of progression to AIPC in the CAD, standard IAD and modified IAD groups were (26.50 +/- 4.15), (30.00 +/- 7.83) and (34.93 +/- 5.08) months, respectively, with statistically significant differences between the modified IAD group and the CAD (P = 0.001) and standard IAD (P = 0.032), but not between the latter two groups (P = 0.143). Kaplan-Meier survival curves showed a significantly longer median time of progression to AIPC in the modified than in the standard IAD group (P = 0.01). The mean cycle length was (16.13 +/- 3.33) months for the standard IAD group and (19.58 +/- 4.30) months for the modified IAD group, and the time off treatment of the first cycle was (9.6 +/- 3.2) months in the former and (14.2 +/- 3.7) months in the latter, with significant difference between the two groups (P = 0.001).

CONCLUSIONCompared with CAD and standard IAD, modified IAD therapy can significantly prolong the time of progression to AIPC in patients with prostate cancer.

Aged ; Aged, 80 and over ; Androgen Antagonists ; administration & dosage ; therapeutic use ; Anilides ; administration & dosage ; therapeutic use ; Antineoplastic Agents, Hormonal ; administration & dosage ; therapeutic use ; Disease Progression ; Humans ; Male ; Middle Aged ; Nitriles ; administration & dosage ; therapeutic use ; Prognosis ; Prostatic Neoplasms ; diagnosis ; drug therapy ; Tosyl Compounds ; administration & dosage ; therapeutic use ; Treatment Outcome

The effects of diclazuril on the bursa of Fabricius (BF) structure and secretory IgA (SIgA) expression in chickens infected with Eimeria tenella were examined. The morphology of the BF was observed by hematoxylin and eosin staining, while ultrastructural changes were monitored by transmission electron microscopy. E. tenella infection caused the BF cell volumes to decrease, irregularly arranged, as well as, enlargement of the intercellular space. Diclazuril treatment alleviated the physical signs of damages associated with E. tenella infection. The SIgA expression in BF was analyzed by immunohistochemistry technique. The SIgA expression increased significantly by 350.4% (P<0.01) after E. tenella infection compared to the normal control group. With the treatment of diclazuril, the SIgA was relatively fewer in the cortex, and the expression level was significantly decreased by 46.7% (P<0.01) compared with the infected and untreated group. In conclusion, E. tenella infection in chickens induced obvious harmful changes in BF morphological structure and stimulated the expression of SIgA in the BF. Diclazuril treatment effectively alleviated the morphological changes. This result demonstrates a method to develop an immunological strategy in coccidiosis control.
Animals ; Bursa of Fabricius/anatomy & histology/*parasitology ; Chickens ; Coccidiosis/drug therapy/metabolism/parasitology/*veterinary ; Coccidiostats/administration & dosage/*adverse effects ; Eimeria tenella/*physiology ; Female ; Immunoglobulin A, Secretory/*genetics/metabolism ; Male ; Nitriles/administration & dosage/*adverse effects ; Poultry Diseases/*drug therapy/genetics/metabolism/parasitology ; Triazines/administration & dosage/*adverse effects

BACKGROUND AND OBJECTIVELetrozole is an aromatase inhibitor that is used in the treatment of estrogen-sensitive tumors such as endometrial carcinoma, however, its therapeutic effect is still to be further improved. It is reported that curcumin has antitumor capability and can enhance the sensitivity of tumor cells to anticancer agents. This study was to investigate the inhibitory effect of letrozole combination with curcumin on the implanted endometrial tumor growth.

METHODSNude mice were implanted with endometrial carcinoma RL-952 cells. All tumor-bearing mice were randomly divided into 5 groups: control(without treatment), Let(1) (letrozole, 1 microg/d), Let(10) (letrozole, 10 microg/d), Cur [ curcumin, 300 mg/kg.d)], and Let + Cur group [10microg/d letrozole + 50mg/ (kg.d) curcumin]. The tumor growth was monitored. Tumor cells apoptosis was detected in both control and treated groups. The expressions of bcl-2 mRNA and bcl-2 protein were detected using RT-PCR and Western blot, respectively.

RESULTSFifty mice were successfully implanted with the endometrial tumor. Treatment with letrozole markedly inhibited tumor growth; the inhibitory effect was further enhanced by the combination of letrozole and curcumin. The inhibitory rates in Let (1), Let (10), the Cur, and the Let + Cur groups were 15.95%, 22.49%, 21.57%, and 35.89%, respectively. Treatment with curcumin inhibited the expression of bcl-2 in tumor cells at the mRNA and protein levels. The apoptosis rates in the control group and the four experimental groups mentioned above were 16.97%, 32.90%, 35.80%, 34.16%, and 47.24%, respectively. Tumor cells apoptosis were observed in mice treated with either letrozole or curcumin; however, combination of letrozole and curcumin further enhanced the inhibitory rate in tumor growth.

CONCLUSIONSTreatment with letrozole or curcumin could inhibit the xenografted endometrial tumor growth by inducing apoptosis in tumor cells. Combination of letrozole and curcumin further enhanced the inhibitory effect of tumor growth.

Adenocarcinoma ; metabolism ; pathology ; Animals ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Curcumin ; administration & dosage ; pharmacology ; Drug Synergism ; Endometrial Neoplasms ; metabolism ; pathology ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Nitriles ; administration & dosage ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Random Allocation ; Receptors, Estrogen ; metabolism ; Triazoles ; administration & dosage ; pharmacology ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays