Multicenter phase II study of trifluridine/tipiracil for esophageal squamous carcinoma refractory/intolerant to 5-fluorouracil, platinum compounds, and taxanes: the ECTAS study.

BACKGROUND: The standard treatment for unresectable advanced/recurrent esophageal cancer in Japan is 5-fluorouracil plus platinum-containing drugs as first-line chemotherapy and taxanes as second-line chemotherapy. However, the standard regimen after patients become refractory to these treatments remains to be established. Therefore, we investigated the efficacy of trifluridine/tipiracil (FTD/TPI) in patients with esophageal cancer who are refractory or intolerant to 5-fluorouracil, platinum-containing drugs, and taxanes. METHODS: This single-arm phase II trial was conducted in seven hospitals in Japan. Eligible patients were those with unresectable advanced/recurrent esophageal cancer that was refractory or intolerant to 5-fluorouracil, platinum-containing drugs, and taxanes. The primary endpoint was the 3-month progression-free survival rate, and the secondary endpoints were the 6-month progression-free survival rate, progression-free survival, overall survival, response rate, disease control rate, and toxicity. RESULTS: Forty-two patients were enrolled between October 2015 and June 2016. All tumors were squamous cell carcinomas. The progression-free survival rates at 3 and 6 months were 15.4% (90% confidence interval 7.4-26.0%) and 7.7% (90% confidence interval 2.6-16.6%), respectively. The median progression-free survival and median overall survival were 1.3 (95% confidence interval 1.0-1.8) months and 4.5 (95% confidence interval 3.6-5.7) months, respectively. The response rate was 0%, and the disease control rate was 23.8% (95% confidence interval 13.5-38.5%). The major grade 3/4 toxicities were neutropenia (47.6%), leukocytopenia (35.7%), and anemia (21.4%). No treatment-related deaths occurred. Exploratory subgroup analyses showed better progression-free survival in the subgroup without distant metastasis at diagnosis. CONCLUSIONS: Trifluridine/tipiracil monotherapy is feasible and shows modest activity in patients with refractory esophageal squamous cell carcinoma.

A pilot study of regenerative therapy using controlled release of recombinant human fibroblast growth factor for patients with pre-collapse osteonecrosis of the femoral head.

PURPOSE: We evaluated the safety and clinical outcomes of a single local administration of gelatin hydrogel impregnated with recombinant human fibroblast growth factor (rhFGF)-2 for the treatment of the precollapse stage of osteonecrosis of the femoral head (ONFH). METHODS: Patients with ONFH (precollapse stage ≤2) received a single local administration of 800 µg of rhFGF-2-impregnated gelatin hydrogel and were followed up for one year. The surgery was performed using a minimally invasive technique involving a 1-cm skin incision, and walking was allowed from day one postoperatively. The primary outcomes included occurrence of adverse events and complications. The secondary outcomes included changes in the Harris hip scores, visual analog scale for pain scores, University of California, Los Angeles (UCLA) activity scores, and radiological images. RESULTS: We included ten patients, of which five experienced 14 adverse events, including one complication from spinal anesthesia. However, patients completely recovered from all adverse events. The mean clinical scores significantly improved by one year postoperatively compared with the pre-operative scores (before vs. after: visual analog score for pain, 21.2 vs. 5.3 mm; UCLA activity score, 5.5 vs. 6.6; Harris hip score, 81.0 vs. 96.9 points). There was only one case of femoral head collapse; however, this occurred in a hip with extensive necrosis. Stage progression and collapse did not occur in the other nine cases. Computed tomography confirmed bone regeneration in the femoral heads. CONCLUSIONS: Clinical application of rhFGF-2-impregnated gelatin hydrogel for patients with precollapse ONFH was feasible and safe.

A randomized controlled clinical trial of topical insulin-like growth factor-1 therapy for sudden deafness refractory to systemic corticosteroid treatment.

BACKGROUND: To date, no therapeutic option has been established for sudden deafness refractory to systemic corticosteroids. This study aimed to examine the efficacy and safety of topical insulin-like growth factor-1 (IGF-1) therapy in comparison to intratympanic corticosteroid therapy. METHODS: We randomly assigned patients with sudden deafness refractory to systemic corticosteroids to receive either gelatin hydrogels impregnated with IGF-1 in the middle ear (62 patients) or four intratympanic injections with dexamethasone (Dex; 58 patients). The primary outcome was the proportion of patients showing hearing improvement (10 decibels or greater in pure-tone average hearing thresholds) 8 weeks after treatment. The secondary outcomes included the change in pure-tone average hearing thresholds over time and the incidence of adverse events. RESULTS: In the IGF-1 group, 66.7% (95% confidence interval [CI], 52.9-78.6%) of the patients showed hearing improvement compared to 53.6% (95% CI, 39.7-67.0%) of the patients in the Dex group (P = 0.109). The difference in changes in pure-tone average hearing thresholds over time between the two treatments was statistically significant (P = 0.003). No serious adverse events were observed in either treatment group. Tympanic membrane perforation did not persist in any patient in the IGF-1 group, but did persist in 15.5% (95% CI, 7.3-27.4%) of the patients in the Dex group (P = 0.001). CONCLUSIONS: The positive effect of topical IGF-1 application on hearing levels and its favorable safety profile suggest utility for topical IGF-1 therapy in patients with sudden deafness. TRIAL REGISTRATION: UMIN Clinical Trials Registry Number UMIN000004366, October 30th, 2010.

Effects of zoledronic acid and the association between its efficacy and γδT cells in postmenopausal women with breast cancer treated with preoperative hormonal therapy: a study protocol.

BACKGROUND: Although the efficacy of zoledronic acid in postmenopausal women with breast cancer has been suggested, the underlying mechanism has not been fully clarified. Therefore, which patients may benefit from zoledronic acid and the optimal frequency of zoledronic acid administration are unclear. This study evaluates the effects of zoledronic acid on the tumor response in postmenopausal women with breast cancer and explores the relationship between its efficacy and γδ T cells. METHODS/DESIGN: This study is an open-label, multi-institutional, single-arm, phase II clinical trial. Zoledronic acid will be administered once during preoperative hormonal therapy with letrozole for 24 weeks in postmenopausal women with Estrogen Receptor (ER)-positive , Human Epidermal Growth Factor Receptor 2 (HER2)-negative, clinical T1 or T2 N0M0 breast cancer. The primary endpoint is the objective response rate measured by MRI at 12 and 24 weeks. The secondary endpoints are the associations between the frequency of Vγ2Vδ2 T cells before the administration of zoledronic acid and the objective response, the association between the frequency of Vγ2Vδ2 T cells and the Preoperative Endocrine Prognostic Index score, and the association between the frequency of Vγ2Vδ2 T cells and Ki67 (MIB-1 index). DISCUSSION: This study is designed to determine the add-on effect of zoledronic acid during preoperative hormonal therapy and to investigate the changes of the frequency of Vγ2Vδ2 T cells after the administration of zoledronic acid to explore the potential mechanism of zoledronic acid in breast cancer patients. TRIAL REGISTRATION: This trial was registered at the UMIN Clinical Trials Registry as UMIN000008701.

Clinical effects of ghrelin on gastrointestinal involvement in patients with systemic sclerosis.

The majority of patients with systemic sclerosis (SSc) have gastrointestinal (GI) tract involvement, but therapies using prokinetic agents are usually unsatisfactory. Ghrelin stimulates gastric motility in healthy human volunteers. In this study, we investigated whether ghrelin could improve gastric emptying in patients with gastrointestinal symptoms due to SSc. The study was performed in a randomized, double-blind, placebo-controlled crossover fashion on two occasions. Ten SSc patients with GI tract involvement received an infusion of either ghrelin (5.0 µg/kg) or saline, and gastric emptying rate was evaluated by ¹³C-acetic acid breath test. Gastric emptying was significantly accelerated by ghrelin infusion in patients with SSc (ghrelin vs. saline: 43.3 ± 11.4 min vs. 53.4 ± 5.4 min, P=0.03). No serious adverse effects were observed. Our results suggest that ghrelin might represent a new therapeutic approach for GI tract involvement in patients with SSc.

Stronger geomagnetic fields may be a risk factor of male suicides.

AIM: Some previous studies have shown a positive relation between geomagnetic disturbances and an increased incidence of suicide. If such a relation exists, stronger geomagnetic fields may affect the number of suicides, because stronger geomagnetic fields generally cause larger geomagnetic field disturbances. Therefore, we here investigated the relation between local geomagnetic field magnetic flux density and the standardized morbidity ratios (SMR) for suicide by each prefecture in Japan. METHODS: Monthly suicide data for each prefecture in the period January 1999 to December 2008 was obtained, and it was found that a total of 216 171 male individuals and 85 154 female individuals committed suicide during this period. A multiple linear regression analysis was carried out with a backward elimination procedure. The SMR for suicide by each prefecture was taken as the response variable and the explanatory variables were each prefecture's local geomagnetic field magnetic flux density (nT), north latitude (°), monthly mean unemployment rate (%), monthly mean air pressure (hPa), monthly mean air temperature (°C), monthly mean humidity (%), and monthly total day length (hours). Analyses were carried out separately for each sex. RESULTS: In the multiple linear regression analysis for male subjects, the local geomagnetic field magnetic flux density (nT), monthly mean unemployment rate (%), and monthly mean humidity (%) were associated with the incidence of suicide, but in the multiple linear regression analysis of female subjects, only north latitude was associated with that. CONCLUSION: In this study, we generated a hypothesis that stronger geomagnetic fields affect the number of cases of male suicide.

Association of geomagnetic disturbances and suicides in Japan, 1999-2010.

OBJECTIVES: Previous studies have shown a positive relationship between geomagnetic disturbances and an increased incidence of suicide. The Japanese suicide rate is the ninth highest in the world, but there have been no reports examining the relationship between geomagnetic disturbance and the number of suicides, and, therefore, this paper examines this relationship. METHODS: The number of Japanese suicides per month from January 1999 to December 2010 was obtained, and it was found that a total of 262,596 males and 102,539 females committed suicide during this period. To adjust the other factors which affect the number of suicides, a multiple linear regression analysis with backward elimination was carried out, with the monthly number of suicides as the response variable and the monthly mean K index value, monthly mean number of sunspots, monthly mean unemployment rate, proportion of elderly people (%), monthly mean air pressure (hPa), monthly mean air temperature (°C), monthly mean humidity (%), and monthly mean day length (h) as the explanatory variables. RESULTS: In the multiple linear regression analysis for males, the monthly mean K index value was associated with the monthly number of suicides, but in females, the monthly mean K index value was not associated with the monthly number of suicides. CONCLUSION: In this study, we generated a hypothesis that geomagnetic disturbances may trigger male suicides.

An exploratory clinical study on the safety and efficacy of an autologous fibroblast-seeded artificial skin cultured with animal product-free medium in patients with diabetic foot ulcers.

Cultured dermal substitutes have been used for the treatment of chronic skin ulcers; however, the biological risks of animal-derived materials in the culture process such as foetal bovine serum (FBS) have been reported. In this study, we prepared an autologous fibroblast-seeded artificial dermis (AFD) using animal-product-free medium supplemented with 2% patient autologous serum and without any animal-derived materials such as trypsin in the culturing process. We applied the AFD in five patients with diabetic ulcers and investigated its safety and efficacy. As the primary endpoint, we defined 'wound bed improvement' according to the percentage of granulation area to the whole wound area on day 21, and 60% or higher was regarded as improved. The mean age of the patients was 60·6 years and the mean duration of the ulcer was 22·6 months. In the evaluation of the primary endpoint, the 'wound bed' was improved in all patients [proportion of improvement: 100%, 95% confidence interval (CI): 48% to 100%]. Three patients had complete wound healing within 12 weeks after application and two patients had >80% wound healing at 12 weeks. Side effects were not serious. Our AFD may be a safe and effective treatment of diabetic ulcers.

Efficacy and Safety of Branched Chain Amino Acids on Retinitis Pigmentosa: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Purpose: The aim of this study was to investigate the efficacy and safety of orally administered branched-chain amino acids (BCAAs) on disease progression in patients with retinitis pigmentosa (RP). Methods: A double-blind, randomized, placebo-controlled study was conducted at the Kyoto University Hospital. Seventy patients with RP aged 20 years or above were randomly assigned to the TK-98 (a combination of BCAAs in granule form) or placebo group. One packet (4.15 g) of the study drug was administered orally thrice daily for 78 weeks. Results: There was no significant difference in the rate of change in the total point score, the primary endpoint, between the TK-98 (-52.4 ± 10.3 dB/year) and placebo (-42.9 ± 13.8 dB/year) groups. Ellipsoid zone length decreased by -76.5 ± 8.9 and -95.5 ± 12.2 µm/year in the TK-98 and placebo groups, respectively; although this difference was not significant, the TK-98 group showed slower degeneration. No serious adverse events were associated with the oral administration of TK-98 in patients with RP. Conclusions: This study did not yield conclusive evidence supporting BCAA combination granules' effectiveness in slowing visual field progression in patients with RP. An insignificant trend toward a slower reduction in ellipsoid zone length was found in morphological tests. Further studies are required to fully understand the potential benefits of BCAA supplementation in RP. Translational Relevance: Our study demonstrates the safety of administering BCAAs to patients with RP. Accordingly, larger, more homogeneous clinical studies with longer durations may suggest their potential as therapeutic agents.

A high-hydrostatic pressure device for nevus tissue inactivation and dermal regeneration for reconstructing skin defects after giant congenital melanocytic nevus excision: a clinical trial.

Background: A novel treatment has been developed to reconstruct large skin defects caused by the excision of giant congenital melanocytic nevi. It involves the reimplantation of high-hydrostatic pressurized nevus tissue as a cell-inactivated autologous scaffold for dermal regeneration, followed by the implantation of cultured epithelial autografts on the regenerated dermis. Because this treatment has shown promise in a first-in-human clinical trial which used a prototype pressure machine, a novel pressure device was specifically designed for clinical use. Methods: In a prospective investigator-initiated clinical trial involving three patients, we evaluated the safety and efficacy of the skin regeneration treatment using a pressure device. All three patients underwent surgical excision of the nevus tissue, primary reimplantation of the inactivated nevus tissue, and secondary implantation of cultured epithelial autografts. Results: Engraftment of inactivated nevus tissue and cultured epithelial autografts was successful in all three cases, with over 90% epithelialization at 8 weeks post-surgery. No serious adverse events or device malfunction were observed during the trial. Conclusion: The novel pressure device safely and effectively enabled dermal regeneration using the nevus tissue as an autologous scaffold. This innovative approach offers several advantages, including reduced invasiveness due to minimal sacrifice of normal skin for skin grafting and high curative potential resulting from full-thickness removal of the nevus tissue.

Clinical Utility of Germline Genetic Testing in Japanese Men Undergoing Prostate Biopsy.

Background: Multiple common variants and also rare variants in monogenic risk genes such as BRCA2 and HOXB13 have been reported to be associated with risk of prostate cancer (PCa); however, the clinical setting in which germline genetic testing could be used for PCa diagnosis remains obscure. Herein, we tested the clinical utility of a 16 common variant-based polygenic risk score (PRS) that has been developed previously for Japanese men and also evaluated the frequency of PCa-associated rare variants in a prospective cohort of Japanese men undergoing prostate biopsy. Methods: A total of 1336 patients undergoing first prostate biopsy were included. PRS was calculated based on the genotype of 16 common variants, and sequencing of 8 prostate cancer-associated genes was performed by multiplex polymerase chain reaction based target sequencing. PRS was combined with clinical factors in logistic regression models to assess whether addition of PRS improves the prediction of biopsy positivity. Results: The top PRS decile was associated with an odds ratio of 4.10 (95% confidence interval = 2.46 to 6.86) with reference to the patients at average risk, and the estimated lifetime absolute risk approached 20%. Among the patients with prostate specific antigen 2-10 ng/mL who had prebiopsy magnetic resonance imaging, high PRS had an equivalent impact on biopsy positivity as a positive magnetic resonance imaging finding. Rare variants were detected in 19 (2.37%) and 7 (1.31%) patients with positive and negative biopsies, respectively, with BRCA2 variants being the most prevalent. There was no association between PRS and high-risk rare variants. Conclusions: Germline genetic testing could be clinically useful in both pre- and post-PSA screening settings.

Quality-of-life evaluation for advanced non-small-cell lung cancer: a comparison between vinorelbine plus gemcitabine followed by docetaxel versus paclitaxel plus carboplatin regimens in a randomized trial: Japan Multinational Trial Organization LC00-03 (BRI LC03-01).

BACKGROUND: A randomized trial of vinorelbine plus gemcitabine followed by docetaxel (VGD) versus paclitaxel plus carboplatin (PC) in patients with advanced non-small-cell lung cancer showed no difference in overall survival (median survival time: 13.6 versus 14.1 months) between the two treatment groups. We report here the results of quality-of-life (QOL) study initiated in the mid-course of this randomized trial. METHODS: The patients themselves assessed the Functional Assessment of Cancer Therapy (FACT)-Lung (FACT-L), FACT-Taxane and the Functional Assessment of Chronic Illness Therapy - Spirituality (FACIT-Sp) QOL instruments at baseline and 6, 12 and 18 weeks after the treatment. The primary endpoint was a comparison of total QOL score for each assessment instrument between the two groups. RESULTS: Sixty-eight patients from the trial (VGD, 34; PC, 34) who submitted baseline questionnaires and at least one questionnaire over the course of treatment were eligible. Longitudinal analysis showed a significant difference in slope of the FACT-Taxane score (p = 0.004) between treatment regimens over time, but no difference was found in FACT-L score (p = 0.311) and FACIT-Sp score (p = 0.466) between the two groups. CONCLUSIONS: The significant difference in slope of FACT-Taxane score favored the VGD regimen. These data should be considered in treatment decision-making for patients with advanced non-small-cell lung cancer. TRIAL REGISTRATION: NCT00242983.

Safety of Silk-elastin Sponges in Patients with Chronic Skin Ulcers: A Phase I/II, Single-center, Open-label, Single-arm Clinical Trial.

BACKGROUND: Although traditional wound dressings such as collagen scaffolds promote granulation tissue formation, the efficacy of these dressings in chronic wounds is limited because of high susceptibility to bacterial growth. Biomaterials that can be applied to chronic wounds should have an anti-bacterial function. We previously reported that administering a silk-elastin solution that forms moisturizing hydrogels to wound surfaces of diabetic mice reduced bacterial growth and promoted granulation tissue formation compared with control or carboxymethyl cellulose hydrogels. We hypothesized that silk-elastin promotes wound healing in human chronic wounds by suppressing bacterial growth. METHODS: An open-label, clinical case series was conducted with a prospective, single-arm design at Kyoto University Hospital in Kyoto, Japan. In this study, 6 patients with chronic skin ulcers of any origin (2 < ulcer area (cm2) < 25) on their lower extremities were included; patients with critical ischemia were excluded. Silk-elastin sponges were applied and covered with a polyurethane film without changing the dressing for 14 days. Inflammation triggered treatment discontinuation due to fear of infection. The primary study endpoint was adverse events, including inflammation and infection. RESULTS: Poor hydrogel formation, possibly due to continuous exudation, was observed. No serious adverse events were noted. Two patients discontinued treatment on day 6 and day 7, respectively, due to inflammation, but they were not infected. The other 4 patients completed the 14-day silk-elastin sponge treatment without infection. CONCLUSION: Silk-elastin sponge is safe for chronic skin ulcers, and its ability to promote wound healing should be determined by confirmatory clinical trials.

Safety and Efficacy of FIT039 for Verruca Vulgaris: A Placebo-Controlled, Phase I/II Randomized Controlled Trial.

TRIAL DESIGN: Human papillomavirus infection causes verruca vulgaris. CDK9 inhibitor FIT039 inhibits DNA virus proliferation in animal models. We conducted a multicenter, single-blind, placebo-controlled, randomized phase I/II clinical trial evaluating the safety and efficacy of FIT039 against verruca vulgaris. METHODS: Target lesions were treated with liquid nitrogen once, and a FIT039 patch or placebo patch was applied for 14 days. The primary endpoint was lesion disappearance. The secondary endpoints were safety and changes in dimension, cross-sectional area, and the number of petechial lesions. RESULTS: A total of 24 participants were randomly allocated to the FIT039 (n = 13, median age, 54 years) and placebo (n = 11, median age, 62 years) groups. Verruca vulgaris did not disappear. FIT039 decreased the dimension to 76% of the initial value on day 29, followed by an increase to 98% on day 57. Placebo showed a monotonic increase to 107% on day 57. Changes in the cross-sectional area and petechiae number were comparable between the groups. CONCLUSIONS: No drug-related adverse reactions occurred. FIT039 efficacy was not determined in this study.

Repurposing bromocriptine for Aß metabolism in Alzheimer's disease (REBRAnD) study: randomised placebo-controlled double-blind comparative trial and open-label extension trial to investigate the safety and efficacy of bromocriptine in Alzheimer's disease with presenilin 1 (PSEN1) mutations.

INTRODUCTION: Alzheimer's disease (AD) is one of the most common causes of dementia. Pathogenic variants in the presenilin 1 (PSEN1) gene are the most frequent cause of early-onset AD. Medications for patients with AD bearing PSEN1 mutation (PSEN1-AD) are limited to symptomatic therapies and no established radical treatments are available. Induced pluripotent stem cell (iPSC)-based drug repurposing identified bromocriptine as a therapeutic candidate for PSEN1-AD. In this study, we used an enrichment strategy with iPSCs to select the study population, and we will investigate the safety and efficacy of an orally administered dose of bromocriptine in patients with PSEN1-AD. METHODS AND ANALYSIS: This is a multicentre, randomised, placebo-controlled trial. AD patients with PSEN1 mutations and a Mini Mental State Examination-Japanese score of ≤25 will be randomly assigned, at a 2:1 ratio, to the trial drug or placebo group (≥4 patients in TW-012R and ≥2 patients in placebo). This clinical trial consists of a screening period, double-blind phase (9 months) and extension phase (3 months). The double-blind phase for evaluating the efficacy and safety is composed of the low-dose maintenance period (10 mg/day), high-dose maintenance period (22.5 mg/day) and tapering period of the trial drug. Additionally, there is an open-labelled active drug extension period for evaluating long-term safety. Primary outcomes are safety and efficacy in cognitive and psychological function. Also, exploratory investigations for the efficacy of bromocriptine by neurological scores and biomarkers will be conducted. ETHICS AND DISSEMINATION: The proposed trial is conducted according to the Declaration of Helsinki, and was approved by the Institutional Review Board (K070). The study results are expected to be disseminated at international or national conferences and published in international journals following the peer-review process. TRIAL REGISTRATION NUMBER: jRCT2041200008, NCT04413344.

Topical insulin-like growth factor 1 treatment using gelatin hydrogels for glucocorticoid-resistant sudden sensorineural hearing loss: a prospective clinical trial.

BACKGROUND: Sudden sensorineural hearing loss (SSHL) is a common condition in which patients lose the hearing in one ear within 3 days. Systemic glucocorticoid treatments have been used as standard therapy for SSHL; however, about 20% of patients do not respond. We tested the safety and efficacy of topical insulin-like growth factor 1 (IGF1) application using gelatin hydrogels as a treatment for SSHL. METHODS: Patients with SSHL that showed no recovery to systemic glucocorticoid administration were recruited. We applied gelatin hydrogels, impregnated with recombinant human IGF1, into the middle ear. The primary outcome measure was the proportion of patients showing hearing improvement 12 weeks after the test treatment. The secondary outcome measures were the proportion of patients showing improvement at 24 weeks and the incidence of adverse events. The null hypothesis was that 33% of patients would show hearing improvement, as was reported for a historical control after hyperbaric oxygen therapy. RESULTS: In total, 25 patients received the test treatment at a median of 23 days (range 15-32) after the onset of SSHL, between 2007 and 2009. At 12 weeks after the test treatment, 48% (95% CI 28% to 69%; P = 0.086) of patients showed hearing improvement, and the proportion increased to 56% (95% CI 35% to 76%; P = 0.015) at 24 weeks. No serious adverse events were observed. CONCLUSIONS: Topical IGF1 application using gelatin hydrogels is well tolerated and may be efficacious for hearing recovery in patients with SSHL that is resistant to systemic glucocorticoids.

Lizards respond to an extremely low-frequency electromagnetic field.

Animals from a wide range of taxa have been shown to possess magnetic sense and use magnetic compasses to orient; however, there is no information in the literature on whether lizards have either of these abilities. In this study, we investigated the behavioral responses of a diurnal agamid lizard (Pogona vitticeps) to a sinusoidal extremely low-frequency electromagnetic field (ELF-EMF; 6 and 8 Hz, peak magnetic field 2.6 microT, peak electric field 10 V m(-1)). Fourteen adult lizards were divided randomly into two groups (the EMF and control groups; each group had three males and four females). The EMF group received whole-body exposure to ELF-EMF and the control group did not. Lizards in the EMF group were exposed to ELF-EMF for 12 h per day (during the light period). The number of tail lifts was monitored beginning 3 days before exposure and ending after 5 days of exposure. For each individual, the average number of tail lifts per day was calculated. The average number of tail lifts per individual per day was greater in the EMF group than in the control group (20.7+/-6.3 and 9.1+/-4.5 tail lifts, respectively, N=7 each, P=0.02). We confirmed the reproducibility of this response by a cross-over trial. These results suggest that at least some lizards are able to perceive ELF-EMFs. Furthermore, when the parietal eye of the lizards was covered with a small round aluminum 'cap' which could block light, the tail-lifting response to ELF-EMF disappeared. Our experiments suggest that (1) lizards perceive EMFs and (2) the parietal eye may be involved in light-dependent magnetoreceptive responses.

Medical mushrooms used for biochemical failure after radical treatment for prostate cancer: an open-label study.

OBJECTIVE: The aim of this study was to assess the efficacy and safety of two different types of medical mushrooms in patients with prostate cancer in Japan. METHODS: Patients with biochemical failure after radical treatment for non-metastasized prostate cancer were enrolled in this open-label study. For 6 months they ingested one of the two following supplements: Senseiro, containing extracts from the Agaricus blazei Murill mushroom; and Rokkaku Reishi, containing the Ganoderma lucidum mushroom. Levels of serum prostate-specific antigen (PSA) level and PSA doubling time were examined before and after study entry to assess the impact of these supplements on disease progression. The primary end-point of this study was partial response rate (50% or more decrease of serum PSA). Hormonal status, represented by serum testosterone levels, and toxicity were also assessed. RESULTS: A total of 51 patients were enrolled following radical prostatectomy. Forty-seven completed the protocol and could be assessed. Thirty-two patients received Senseiro and the remaining 15 received Rokkaku Reishi. No partial response in terms of PSA was observed. Alteration of PSA doubling time did not correlate with that of serum testosterone levels. Serious adverse effects were not observed. CONCLUSIONS: No significant anticancer effects were observed with the intake of these two medical mushrooms.