Efficacy and safety of standard of care with/without bevacizumab for platinum-resistant ovarian/fallopian tube/peritoneal cancer previously treated with bevacizumab: The Japanese Gynecologic Oncology Group study JGOG3023.

We investigated the efficacy and safety of further bevacizumab therapy in patients with platinum-resistant ovarian cancer whose disease had progressed after bevacizumab plus chemotherapy. In this multicenter, open-label, phase II trial (JGOG3023), patients were randomized 1:1 to a single-agent chemotherapy alone (either pegylated liposomal doxorubicin [40 or 50 mg/m2 administered intravenously], topotecan [1.25 mg/m2 intravenously], paclitaxel [80 mg/m2 intravenously], or gemcitabine [1000 mg/m2 intravenously]) or single-agent chemotherapy + bevacizumab (15 mg/m2 intravenously). The primary endpoint was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Secondary endpoints were overall survival (OS), objective response rate (ORR), and response rate according to Gynecological Cancer Intergroup cancer antigen 125 criteria. In total, 103 patients were allocated to chemotherapy (n = 51) or chemotherapy + bevacizumab (n = 52). Median investigator-assessed PFS was 3.1 and 4.0 mo in each group, respectively (hazard ratio [HR] = 0.54, 95% confidence interval [CI]: 0.32-0.90, P = .0082). Median OS was 11.3 and 15.3 mo in each group, respectively (HR = 0.67, 95% CI: 0.38-1.17, P = .1556). Respective ORRs were 13.7% and 25.0% (P = .0599) and response rates were 16.7% and 21.4% (P = .8273). The incidence of grade ≥3 treatment-related AEs was 42.0% in the chemotherapy group and 54.9% in the chemotherapy + bevacizumab group; AEs were well tolerated, with only 2 and 12 events leading to discontinuation of therapy, respectively. Bevacizumab was effective beyond progressive disease and AEs were manageable. The observed improvement in PFS requires further verification.

Protective effect of taurine on UVB-induced skin aging in hairless mice.

Taurine, a sulfur-containing amino acid derivative, exists at a high concentration in the skin and is considered to play an important role in maintaining moisture homeostasis. This study investigated the effects of oral taurine supplementation on epidermal moisture content and wrinkle formation, as well as skin taurine content, using ultraviolet B (UVB)-irradiated hairless mice. Wrinkles were induced by exposing hairless mice to UVB radiation (70-100 mJ/cm2). Taurine was dissolved in drinking water at a concentration of 0.3 or 3% (w/v) and given to the mice ad libitum for 2-10 weeks. Taurine was then extracted from the dorsal skin, and the skin taurine content was determined using high-performance liquid chromatography (HPLC). The wrinkles were evaluated using a wrinkle score and the quantitative wrinkle area ratio. The exposure of the mice to UVB radiation for 4 weeks resulted in a decreased moisture content and increased transepidermal water loss (TEWL) in the skin, while taurine supplementation suppressed these changes. Oral supplementation with taurine for 8 weeks ameliorated the development of UVB-induced wrinkle formation. Furthermore, oral taurine supplementation for 4 weeks decreased pre-stablished wrinkles in a dose-dependent manner. Although the UVB radiation reduced the epidermal taurine content, oral taurine supplementation partly restored the taurine content in the epidermis. The present study showed that oral taurine supplementation is able to suppress UVB-induced wrinkle formation, which may be associated with the regulation of moisture content in the epidermis. The beneficial effects of taurine on skin aging may be attributed to its osmoregulatory role.

Age-related decline in the taurine content of the skin in rodents.

Taurine, a sulfur-containing amino acid, occurs at high concentrations in the skin, and plays a role in maintaining the homeostasis of the skin. We investigated the effects of aging on the content and localization of taurine in the skin of mice and rats. Taurine was extracted from the skin samples of hairless mice and Sprague Dawley rats, and the taurine content of the skin was determined by high-performance liquid chromatography (HPLC). The results of the investigation revealed that the taurine content in both the dermis and epidermis of hairless mice declined significantly with age. Similar age-related decline in the skin taurine content was also observed in rats. In contrast, the taurine content in the sole remained unchanged with age. An immunohistochemical analysis also revealed a decreased skin taurine content in aged animals compared with younger animals, although no significant differences in the localization of taurine were observed between the two age groups. Supplementation of the drinking water of aged mice with 3% (w/v) taurine for 4 weeks increased the taurine content of the epidermis, but not the dermis. The present study showed for the first time that the taurine content of the skin decreased with age in mice and rats, which may be related to the impairment of the skin homeostasis observed with aging. The decreased taurine content of the epidermis in aged animals was able to be rescued by taurine supplementation.

Bevacizumab combined with platinum-taxane chemotherapy as first-line treatment for advanced ovarian cancer: a prospective observational study of safety and efficacy in Japanese patients (JGOG3022 trial).

BACKGROUND: This was the first large-scale prospective observational Japanese study evaluating the safety and efficacy of bevacizumab combined with paclitaxel and carboplatin for newly diagnosed advanced ovarian cancer. METHODS: Patients were prospectively enrolled in the primary analysis cohort if they had Stage III or IV epithelial ovarian/fallopian tube/primary peritoneal cancer and were scheduled to receive paclitaxel plus carboplatin every 3 weeks in Cycles 1-6 and bevacizumab every 3 weeks in Cycles 2-22. Primary endpoints were bevacizumab-specific adverse events and adverse events ≥ Grade 3. Secondary endpoints were progression-free survival (PFS) and the response rate. RESULTS: Among 346 patients enrolled, 293 patients formed the primary analysis cohort. Regarding bevacizumab-specific adverse events ≥ grade 3, incidence rates of thromboembolic events (1.4%), gastrointestinal perforation (0.3%), fistula (0.7%), wound dehiscence (0%), and bleeding (0%) were very low. While incidence rates of hypertension (23.2%) and proteinuria (12.6%) were high, all such events were tolerable. No patient with prior bowel resection developed perforation or fistula. Median PFS was 16.3 months (95% CI 14.5-18.9). The response rate was 77.5% (95% CI 67.4-85.7). The response rate was 63.6% in patients with clear cell carcinoma, which tended to be better than previously reported. The median platinum-free interval was 11.5 months, and the platinum-resistant recurrence rate was 24.5%. CONCLUSIONS: Combining bevacizumab with chemotherapy was tolerable and efficacy was acceptable in Japanese patients with advanced epithelial ovarian cancer. Bevacizumab seems to reduce platinum-resistant recurrence and is promising for clear cell carcinoma.

[Effects of ethanol extracts of herbal medicines on dermatitis in an atopic dermatitis mouse model].

Atopic dermatitis is a chronic and relapsing inflammatory skin disease that is characterized by highly pruritic, eczematous skin lesions. Our previous study elucidated that nerve growth factor (NGF) plays an important role in the pathogenesis of skin lesions and inhibition of the physiological effects of NGF can moderate skin lesions in atopic dermatitis. In this study, we investigated the effects of ethanol extracts of herbal medicines on neuritic outgrowth induced by NGF. Four herbal extracts (Geranium thunbergii, Humulus lupulus, Rosmarinus officinalis and Salvia officinalis L.) inhibited NGF-induced neuritic outgrowth in PC12 cells. We also investigated the effects of each herbal extract on dermatitis in NC/Nga, an atopic dermatitis mouse model. The skin lesions of the NC/Nga mice were significantly inhibited by repeated applications of each herbal extract. These results suggested that the four herbal extracts can prevent and moderate the symptoms of atopic dermatitis, and these effects might be appeared by inhibiting the effect of NGF on neuritic outgrowth in lesional skin.