Quantitative evaluation of chemotherapy-induced peripheral neuropathy by using intraepidermal electrical stimulation.

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.

The prophylactic effects of a traditional Japanese medicine, goshajinkigan, on paclitaxel-induced peripheral neuropathy and its mechanism of action.

BACKGROUND: This study aimed to evaluate the prophylactic effect of goshajinkigan (GJG) on paclitaxel (PTX)-induced neuropathy and to elucidate the mechanism of action. RESULTS: There 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. CONCLUSIONS: These 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.

Inhibitory effects of aromatase inhibitor on estrogen receptor-alpha positive ovarian cancer in mice.

BACKGROUND: Estrogen 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. METHODS: Estrogen 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. RESULTS: Survival 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. CONCLUSIONS: Letrozole 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.

Is omentectomy mandatory in the operation for ovarian cancer? Preliminary results in a rat study.

OBJECTIVE: To investigate whether omentectomy is required in the operation for ovarian cancer, in particular at the early stage. STUDY DESIGN: F344 nude rats were divided into two groups: one in which laparotomy and omentectomy were performed (primary omentectomy group, n=6) and one without omentectomy (n=12). Concurrently, DISS cells derived from ovarian cancer were transplanted intraperitoneally. After three weeks, the 12 rats without omentectomy were divided into two more groups: one in which the omentum was resected together with the tumor (sham operation/omentectomy group, n=6) and one without omentectomy (sham operation alone group, n=6). RESULTS: The survival of the sham operation alone group was shortest with a median of 35 days, while the median of the primary omentectomy group was 42 days. In the sham operation/omentectomy group, four rats survived beyond Day 90, which was significant compared with other two groups. The intraperitoneal findings in the primary omentectomy group revealed extensive disseminated foci on the mesentery and under the abdominal wall. The sham operation alone group was characterized by jaundice resulting from the compression of the biliary system at the liver hilum by the omental mass. Disseminated foci were not observed in the peritoneal cavity from the sham operation/omentectomy group. CONCLUSIONS: This study suggests the possibility that the omentum has a role in capturing cancer cells and suppressing further peritoneal dissemination. Therefore, although omentectomy is rewarding if disseminated foci are present in the omentum, it is suggested that the timing of omentectomy requires reconsideration in the absence of omental metastasis.

[Successful optimal debulking surgery following chemotherapy combined with irinotecan hydrochloride and cisplatin for advanced clear cell carcinoma of the ovary].

BACKGROUND: Clear cell carcinoma of the ovary is known to be resistant to chemotherapy. CASE: A 59-year-old woman was diagnosed with advanced clear cell carcinoma of the ovary after an exploratory laparotomy. Large disseminated foci expanded from diaphragm to omentum to liver. Three courses of chemotherapy combined with irinotecan hydrochloride (CPT-11) and cisplatin (CDDP)(CPT-P) remarkably reduced the volume of the primary tumor and disseminated foci. These diseases could be extirpated completely by the subsequent interval debulking surgery. CONCLUSION: CPT-P may become a promising regimen for clear cell carcinoma of the ovary.

Dietary Garcinia cambogia does not modify skin properties of mice with or without excessive sucrose intake.

The influence of 3.3% Garcinia cambogia extract on the properties of mouse skin with or without 10% sucrose water loading was investigated. Mice (7-week-old) were given free access to a control diet or a diet containing Garcinia cambogia extract. They were also given water alone or both water and sucrose water. Their skin was compared by both biochemical and histological methods. The collagen and triacylglycerol contents were not significantly different among the four groups. Similarly, electron microscopy revealed no differences in the thickness of the dermis layer or the subcutaneous tissue layer. Mice given the diet containing Garcinia cambogia tended to have a reduced total number of adipocytes, but not significantly. These results suggest that Garcinia cambogia supplementation for at least 4 weeks does not induce a negative effect on skin properties in mice irrespective of excessive sucrose intake.

Gamma-linolenic acid prevents conjugated linoleic acid-induced fatty liver in mice.

OBJECTIVE: The present study was done to clarify the mechanism by which conjugated linoleic acid (CLA) induces fatty liver in mice and to attenuate this symptom by adding other dietary fatty acids. METHODS: Mice were given CLA short (12 h) or long (4 wk) term or given CLA with linoleic acid (LA) or gamma-linolenic acid (GLA) in the long term (4 wk). Total lipids, triacylglycerol, and prostaglandin E(2) (PGE(2)) levels in the liver were determined. RESULTS: A single administration of CLA significantly increased PGE(2) levels in the liver 12 h after administration. However, long-term administration of CLA significantly decreased the liver PGE(2) level and induced fatty liver. GLA increased PGE(2) levels, and coadministration with GLA, but not with LA, prevented the CLA-induced fatty liver. CONCLUSIONS: These data suggest that CLA initially stimulates PGE(2) production followed by depletion of PGE(2) sources in the liver. The fatty liver associated with PGE(2) reduction by CLA ingestion can be attenuated by GLA in mice.