BackgroundThis study aimed to evaluate the prophylactic effect of goshajinkigan (GJG) on paclitaxel (PTX)-induced neuropathy and to elucidate the mechanism of action.ResultsThere was a time-dependent irreversible decrease in pain threshold in PTX group. In PTX/GJG group, pain threshold showed changes in the same level as control. Electron microscope showed that although the ganglion cells of control and PTX/GJG groups were normal, degeneration of the nucleus and swelling of the mitochondria were observed in PTX group. Expression of transient receptor potential vanilloid 4 (TRPV4) gene in PTX group significantly increased compared with that in control and PTX/GJG groups. In TRPV4 knock-out mice, no PTX-induced hyperalgesia was observed, and there was no significant difference in pain threshold between the 3 groups.ConclusionsThese results showed that PTX induced hyperalgesia by enhancing TRPV4 expression, and suggested that GJG might alleviate hyperalgesia by preventing degeneration of the ganglion cells and suppressing TRPV4 expression.

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BackgroundEstrogen causes proliferation of ovarian cancer cells. Although hormone therapy with an anti-estrogen agent is an optional therapy for recurrent epithelial ovarian cancers, both basic and clinical researches are insufficient. We here examine the efficacy of an aromatase inhibitor (AI) for peritonitis carcinomatosa, the late stage of ovarian cancer.MethodsEstrogen receptor (ER)α was assayed in four ovarian cancer cell lines by the RT-PCR method. Using ovariectomized nude mice, peritonitis carcinomatosa consisting of OVCAR-3 cells with the strongest ERα expression or DISS cells with weaker ERα expression was prepared. The survival period was compared between the letrozole group (5 mg/kg/day orally; n = 10) and the control group (n = 10). In addition, the degree of angiogenesis and occurrence of apoptosis were compared using tumor tissue from the abdominal cavity. The expression of aromatase and the protein involving in ERα signaling were examined in tumors immunohistochemically.ResultsSurvival period in OVCAR-3 tumors was significantly prolonged in the letrozole group, compared with the control group (P < 0.05), whereas that in DISS tumors was not different between the both groups. The microvessel density in tumors and expression of VEGF decreased significantly in the letrozole group compared to the control group. The incidence of apoptosis did not differ significantly between these groups. No adverse event was observed accompanying the administration of letrozole. The expressions of aromatase, ERα and FOXP1 that is associated with ERα signaling were reduced in tumors by letrozole administration.ConclusionsLetrozole was effective for ovarian cancers with abundant expression of ERα. Inhibition of angiogenesis and of ascites production appeared to contribute to prolongation of the survival period.

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequently observed treatment-related adverse effect, particularly associated with taxane-based chemotherapy, which affects the quality of life of the patients. To date, CIPN has been subjectively evaluated by patients or physicians. Intraepidermal electrical stimulation (IES) may be applied to evaluate the function of small fibers by measuring pain threshold, and assess the degree of diabetic peripheral neuropathy. The aim of the present study was to evaluate CIPN objectively by using IES. The pain threshold measured by IES in patients with gynecological cancer who underwent taxane-based chemotherapy was compared with the clinical grading scale of peripheral neuropathy (National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0). A total of 57 patients were evaluated (151 measurements). The median age of the patients was 63 years. The number of measurements with clinical grades of 0, 1 and ≥2 was 49, 57 and 45, respectively. The mean pain threshold was 0.1, 0.14 and 0.18 mA for grades 0, 1 and ≥2, respectively. Therefore, the mean pain threshold significantly increased with the progression of the clinical grade. The measurement of pain threshold by using IES may be a reliable indicator for quantitative evaluation of CIPN.

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