Synergetic anticancer effect of combined gemcitabine and photodynamic therapy on pancreatic cancer in vivo

AIM:To investigate the anti-tumor effects of combined cytotoxic drug(gemcitabine)and photodynamic therapy(PDT)on human pancreatic cancer xenograft in nude mice. METHODS:Human pancreatic cancer cell line SW1990 was used in the investigation of the in vivo effect of combined gemcitabine and PDT on human pancreatic cancer xenograft in mice.Sixty mice were randomly allocated into a control group(without treatment),photosensitizer treatment group(2 mg/kg photosan,without illumination),chemotherapy group (50 mg/kg gemcitabine i.p.),PDT group(2 mg/kg photosan+laser irradiation)and combined treatment group(photosan+chemotherapy),with 12 mice in each group.Tumor size was measured twice every week.Anti-tumor activity in different groups was evaluated by tumor growth inhibition(TGI). RESULTS:No significant anti-tumor effect was observed either in photosensitizer treatment group or in chemotherapy group.PDT led to necrosis in cancer lesions and significantly reduced tumor volume compared with photosensitizer on day 6 and at the following time points after initialization of therapy (0.24±0.15-0.49±0.08 vs 0.43±0.18-1.25± 0.09,P<0.05).PDT significantly reduced tumor volume in combined treatment group compared with photosensitizer treatment group(0.12±0.07-0.28 ±0.12 vs 0.39±0.15-1.20±0.11,P<0.05),small dose chemotherapy group(0.12±0.07-0.28±0.12 vs 0.32±0.14-1.16±0.08,P<0.05)and control group (0.12±0.07-0.28±0.12 vs 0.43±0.18-1.25±0.09, P<0.05).TGI was higher in the combined treatment group(82.42%)than in the PDT group(58.18%). CONCLUSION:PDT has a significant anti-tumor effect,which is maintained for a short time and can be significantly enhanced by small doses of gemcitabine.

Effect of antidepressants on body weight, ethology and tumor growth of human pancreatic carcinoma xenografts in nude mice

AIM: To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and se- lective serotonin reuptake inhibitor (SSRI) antidepres- sant respectively, on body weight, ingestive behavior, locomotor activity and tumor growth of human pancre- atic carcinoma xenografts in nude mice. METHODS: A subcutaneous xenograft model of hu- man pancreatic cancer cell line SW1990 was estab- lished in nude mice. The tumor-bearing mice were ran- domly divided into mirtazapine group [10 mg/(kg·d)], fluoxetine group [10 mg/(kg·d)] and control group (an equivalent normal saline solution) (7 mice in each group). Doses of all drugs were administered orally, once a day for 42 d. Tumor volume and body weight were measured biweekly. Food intake was recorded once a week. Locomotor activity was detected weekly using an open field test (OFT). RESULTS: Compared to the fluoxetine, mirtazapine significantly increased food intake from d 14 to 42 and attenuated the rate of weight loss from d 28 to 42 (t = 4.38, P < 0.05). Compared to the control group, food intake was significantly suppressed from d 21 to 42 and weight loss was promoted from d 35 to 42 in the fluoxetine group (t = 2.52, P < 0.05). There was a significant difference in body weight of the mice after removal of tumors among the three groups. The body weight of mice was the heaviest (13.66 ± 1.55 g) in the mirtazapine group and the lightest (11.39 ± 1.45 g) in the fluoxetine group (F(2,12) = 11.43, P < 0.01). The behavioral test on d 7 showed that the horizontal and vertical activities were significantly increased in the mirtazapine group compared with the fluoxetine and control groups (F(2,18) = 10.89, P < 0.01). These effects disappeared in the mirtazapine and fluoxetine groups during 2-6 wk. The grooming activity was higher in the mirtazapine group than in the fluoxetine group (10.1 ± 2.1 vs 7.1 ± 1.9 ) (t = 2.40, P < 0.05) in the second week. There was no significant difference in tumor vol- ume and tumor weight of the three groups. CONCLUSION: Mirtazapine and fluoxetine have no effect on the growth of pancreatic tumor. However, mirtazapine can significantly increase food intake and improve nutrition compared with fluoxetine in a pan- creatic cancer mouse model.

Study on Treatment of Polycystic Ovarian Syndrome with Infertility by Combined Therapy of Chinese Herbal Medicine and Compound Cyproterone Acetate

Objective: To evaluate the effect of combined therapy of Chinese herbal medicine and compound cyproterone acetate (CPA) in treating non-obesity polycystic ovarian syndrome (PCOS) and to explore its mechanism in improving withdrawal ovulation. Methods: Eighty-six patients of non-obesity P-COS, typed as Shen-deficiency with blood stasis Syndrome or Shen-deficiency with Phlegm-Dampness Syndrome by Syndrome Differentiation in traditional Chines medicine, were randomly divided into three groups: (1) The TCM group (n = 26) was treated with Chinese drugs for 6 menstrual cycles; (2) The western medicine (WM) group (n=30) was treated with 1 tablet of CPA for 21 days, with the treatment beginning from the 5th day of menstruation. The treatment was given for 3 menstrual cycles by repetitious medication, which stopped and restarted on the 5th day of withdrawal bleeding. Then the ovulation promoting therapy was applied by using clomifene citrate and human chorionic gonadotropin (CC/hCG) for 3 menstrual cycles; (3) The TCM-WM group (n=30) was treated with the medications used for the above two groups. The menstrual cycle, the volume and duration of the menstruation, as well as the improvement of acne and pilosis [Ferriman-Gallway (F-G) scoring] were observed after 3 cycles ended. Moreover, condition of ovulation was monitored by B-ultrasonography at the 4th- 6th cycle and status of pregnancy was observed. Results: Compared with before treatment, the blood level of luteinizing hormone (LH) and testosterone (T) in all 3 groups after treatment significantly decreased (P<0. 05), with its ratio to follicle-stimulating hormone (LH/FSH) recovered to normal, but without markedly change in levels of FSH, estradiol (E2) and prolactin (PRL). The menstrual cycle in most patients got regular and acne significantly alleviated (P<0. 05), and the improvement of infrequent menstruation and acne was better in the WM group and the TCM-WM group than that in the TCM group, but pilosis showed no significant improvement in all three groups. The periodical ovulation rate in the TCM-WM group (73. 1%) and the WM group (68. 3%) was significantly higher than that in the TCM group (40%). The pregnancy rate in the TCM-WM group (53. 8%) was significantly higher than that in the other two groups (26.1% and 25% respectively, all P<0.05). Conclusion: Using combined therapy of TCM and composite CPA followed by o-vulation promoting agents of TCM and WM to treat patients of non-obesity PCOS could relieve the clinical symptoms, improve the abnormal blood level of sex hormones and significantly elevate the pregnancy rate.