Prevalence of cpe-positive Clostridium perfringens in surface-attached soil of commercially available potatoes and its significance as a potential source of food poisoning.

OBJECTIVE: We aimed to examine the surface-attached soil of commercially available potatoes in Japan to determine the association between foodborne infection and the circulation of Clostridium perfringens through vegetables, soil, and environments. METHODS: C. perfringens spores were isolated from 30 surface-attached soil samples of potatoes obtained from six regions in Japan. We performed multiplex polymerase chain reaction (PCR) and sequencing to detect the presence of six toxin and plasmid-related genes in the isolates. RESULTS: Sulfite-reducing clostridial spores were detected in 28 (93%) of 30 potato samples, and toxin gene PCR was performed using 613 isolates. The C. perfringens α toxin gene (cpa) was detected in 288 isolates (288/613; 47%) from 25 potato samples (83%), and these isolates were presumed to be the strains of C. perfringens. The toxin types of C. perfringens were classified into type A, in which 73% of isolates had only cpa, followed by type F in 20%, type C in 6%, and type E in 0.003% (1 isolate). The enterotoxin gene (cpe) related to food poisoning was detected in 64 isolates from 9 potato samples (3%). Of these, 59 isolates had cpa and cpe, whereas five had cpa, C. perfringens ß toxin gene, and cpe. All tested cpe-positive isolates had plasmid-type cpe. CONCLUSIONS: The isolation of culturable cpe-positive C. perfringens from the surface-attached soil of commercially available potatoes indicates that potatoes are a potential source of foodborne transmission of C. perfringens.

A patient with ALK-positive lung adenocarcinoma who survived alectinib-refractory postoperative recurrence for 4 years by switching to ceritinib.

Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangements are found in ~ 5% of patients with non-small cell lung cancer (NSCLC). Several tyrosine kinase inhibitors (TKIs) have been developed for treatment of so-called ALK-positive NSCLC. In cases of tumor progression during treatment with second-generation ALK-TKIs, such as alectinib, brigatinib, or ceritinib, National Comprehensive Cancer Network guidelines propose a switch to lorlatinib, a third-generation ALK-TKI, or to cytotoxic chemotherapy. However, they do not mention switching to other second-generation ALK-TKIs. Here, we present a rare case of a 53-year-old Japanese woman, who had never smoked, with ALK-positive lung adenocarcinoma who survived alectinib-resistant postoperative recurrence for 4 years by switching to ceritinib. She underwent curative resection for lung adenocarcinoma, but the cancer recurred at the bronchial stump and mediastinal lymph nodes. After platinum-doublet chemotherapy, the patient still had a single growing liver metastasis, but the tumor was found to harbor EML4-ALK rearrangement. Therefore, the patient started to take ALK-TKIs. Alectinib was the second ALK-TKI used to treat this patient. Alectinib shrank the liver metastasis, which was surgically resected. The tumor relapsed again during continued treatment with alectinib, which was switched to ceritinib. Ceritinib was effective for the relapsed tumor and treatment continued well for 4 years. This case report suggests that, in case of tumor progression during treatment with a second-generation ALK-TKI, switching to another second-generation ALK-TKI may be one of the treatment options. Further analyses are warranted to find robust markers to determine which ALK-TKI is best for each patient.

Efficacy of a Glass Membrane Emulsification Device to Form Mixture of Cisplatin Powder with Lipiodol on Transarterial Therapy for Hepatocellular Carcinoma.

PURPOSE: To examine physiochemical characteristics and drug release properties of cisplatin powder and lipiodol mixtures formed by a glass membrane emulsification device compared with a 3-way stopcock. MATERIALS AND METHODS: Seven different types of mixtures were evaluated: cisplatin powder and lipiodol directly mixed (suspension), complete cisplatin solution and lipiodol mixed by a 3-way stopcock or the device (emulsion), incomplete cisplatin solution and lipiodol mixed by a 3-way stopcock or the device (solid-in-water emulsion), and contrast material and cisplatin suspension mixed by a 3-way stopcock or the device (solid-in-oil emulsion). RESULT: The percentages of water-in-oil were 98.08 ± 0.27% in the emulsion formed by the device, while 70.3 ± 4.63% in the emulsion formed by a 3-way stopcock (P = 0.037). Solid-in-water and solid-in-oil emulsions formed by the device showed 98.09 ± 0.38% and 98.70 ± 0.40% of water-in-oil, respectively, whereas both solid-in-water and solid-in-oil emulsions formed by a 3-way stopcock showed 0.00%. Homogenous droplet sizes were shown by using the device. The half release times of cisplatin in the emulsions formed by the device were 197 ± 19, 244 ± 24 and 478 ± 52 min, respectively, which were significantly longer than the emulsion formed by a 3-way stopcock of 8 ± 8 min (P = 0.046-0.050). Suspension showed the longest release time; however, the viscosity was lowest. CONCLUSION: The glass membrane emulsification device formed almost 100% water-in-oil, whereas 3-way stopcock produced 100% oil-in-water when incomplete solution or suspension was mixed. Slower cisplatin release was shown in the emulsions formed by the device.

Intake of Seven Essential Amino Acids Improves Cognitive Function and Psychological and Social Function in Middle-Aged and Older Adults: A Double-Blind, Randomized, Placebo-Controlled Trial.

Background: To delay the onset of dementia, it is important for healthy adults to take preventive actions before the cognitive function clearly declines. Protein malnutrition is a potential risk factor for senile dementia, although the precise link between protein/amino acid nutrition and cognitive function is unknown. The purpose of this study was to examine the effect of the ingestion of seven selected essential amino acids as a granular powder, namely, leucine, phenylalanine, and lysine supplemented with isoleucine, histidine, valine, and tryptophan on cognitive and psychosocial functions in healthy adults. Methods: A double-blind, randomized, placebo-controlled trial was conducted. A total of 105 participants aged 55 years or older were randomly assigned to one of three groups: daily ingestion of 3 g (3gIG) or 6 g (6gIG) of the selected amino acids or daily ingestion of a placebo (PCG). Each group ingested the test powder for 12 weeks. As the main outcome, cognitive function was assessed before and after ingestion by a cognitive test battery. Psychosocial functions were also examined. Results: The numbers of participants excluding dropouts were 35 in PCG and 3gIG and 33 in 6gIG. Analysis of covariance revealed that the 6gIG showed significantly improved cognitive function (Trail Making Test B), social interaction and psychological health scores after ingestion compared to the PCG (multiplicity adjusted p < 0.05). Conclusions: Current findings suggested that ingestion of the seven essential amino acids led to improved attention and cognitive flexibility and psychosocial functioning, which is expected to prevent cognitive decline. Clinical Trial Registration: University Hospital Medical Information Network Clinical Trial Registry (URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000037779, Identifier: UMIN000033174).

Poor outcome with anti-programmed death-ligand 1 (PD-L1) antibody due to poor pharmacokinetic properties in PD-1/PD-L1 blockade-sensitive mouse models.

BACKGROUND: Recently, antiprogrammed cell death protein 1 (aPD-1) and antiprogrammed death-ligand 1 (aPD-L1) monoclonal antibodies (mAbs) have been approved. Even though aPD-1 and aPD-L1 mAbs target the same PD-1/PD-L1 axis, it is still unclear whether both mAbs exert equivalent pharmacological activity in patients who are sensitive to PD-1/PD-L1 blockade therapy, as there is no direct comparison of their pharmacokinetics (PK) and antitumor effects. Therefore, we evaluated the differences between both mAbs in PK and therapeutic effects in PD-1/PD-L1 blockade-sensitive mouse models. METHODS: Herein, murine breast MM48 and colon MC38 xenografts were used to analyze the pharmacological activity of aPD-1 and aPD-L1 mAbs. The PK of the mAbs in the tumor-bearing mice was investigated at low and high doses using two radioisotopes (Indium-111 and Iodine-125) to evaluate the accumulation and degradation of the mAbs. RESULTS: aPD-1 mAb showed antitumor effect in a dose-dependent manner, indicating that the tumor model was sensitive to PD-1/PD-L1 blockade therapy, whereas aPD-L1 mAb failed to suppress tumor growth. The PK study showed that aPD-L1 mAb was accumulated largely in normal organs such as the spleen, liver, and kidney, resulting in low blood concentration and low distributions to tumors at a low dose, even though the tumors expressed PD-L1. Sufficient accumulation of aPD-L1 mAb in tumors was achieved by administration at a high dose owing to the saturation of target-mediated binding in healthy organs. However, degradation of aPD-L1 mAb in tumors was greater than that of aPD-1 mAb, which resulted in poor outcome presumably due to less inhibition of PD-L1 by aPD-L1 mAb than that of PD-1 by aPD-1 mAb. CONCLUSION: According to the PK studies, aPD-1 mAb showed linear PK, whereas aPD-L1 mAb showed non-linear PK between low and high doses. Collectively, the poor PK characteristics of aPD-L1 mAb caused lower antitumor activity than of aPD-1 mAb. These results clearly indicated that aPD-L1 mAb required higher doses than aPD-1 mAb in clinical setting. Thus, targeting of PD-1 would be more advantageous than PD-L1 in terms of PK.

Ubiquinol Improves Endothelial Function in Patients with Heart Failure with Reduced Ejection Fraction: A Single-Center, Randomized Double-Blind Placebo-Controlled Crossover Pilot Study.

BACKGROUND: Endothelial dysfunction is reportedly associated with worse outcomes in patients with chronic heart failure. Ubiquinol is a reduced form of coenzyme Q10 (CoQ10) that may improve endothelial function. OBJECTIVE: We assessed the hypothesis that ubiquinol improves peripheral endothelial function in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: In this randomized, double-blind, placebo-controlled, crossover pilot study, 14 patients with stable HFrEF were randomly and blindly allocated to ubiquinol 400 mg/day or placebo for 3 months. After a 1-month washout period, patients were crossed over to the alternative treatment. Before and after each treatment, we assessed peripheral endothelial function using the reactive hyperemia index (RHI) and analyzed it using the natural logarithm of RHI (LnRHI). RESULTS: Peripheral endothelial function as assessed by LnRHI tended to improve with ubiquinol 400 mg/day for 3 months (p = 0.076). Original RHI values were also compared, and RHI significantly improved with ubiquinol treatment (pre-RHI 1.57 [interquartile range (IQR) 1.39-1.80], post-RHI 1.74 [IQR 1.63-2.02], p = 0.026), but not with placebo (pre-RHI 1.67 [IQR 1.53-1.85], post-RHI 1.51 [IQR 1.39-2.11], p = 0.198). CONCLUSIONS: Ubiquinol 400 mg/day for 3 months led to significant improvement in peripheral endothelial function in patients with HFrEF. Ubiquinol may be a therapeutic option for individuals with HFrEF. Large-scale randomized controlled trials of CoQ10 supplementation in patients with HFrEF are needed. CLINICAL TRIAL REGISTRATION: Japanese University Hospital Medical Information Network (UMIN-ICDR). Clinical Trial identifier number UMIN000012604.

[The influence of types of living alone on 2-year health changes according to elderly adults' marital status: Based on the Comprehensive Regional Studies for Preventing Isolation of the Elderly Who Live in Metropolitan Area (CAPITAL Study)].

Objectives　The aim of this research is to classify elderly adults who live alone by their marital status type and to clarify how those types affect their higher-level functional capacity and mental health with a 2-year follow-up survey.Methods　This research is based on the results from a survey in 2013. The base-line scores were from 757 participants who completed a survey by mail, carried out in B area of A ward, Tokyo, within the jurisdiction of community general support centers, with people who were not at nursing care levels 4 or 5 and who were not residents of welfare facilities. This study analyzed data for 517 of 527 participants, who answered all questions in the 2015 survey and indicated their marital status. This research categorized the respondents into 4 types of marital status: separation, divorce, bereavement, and unmarried groups. This study adopted the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) as the index of higher-level functional capacity, and the WHO-Five Well-Being Index (WHO-5-J) as the mental health index. In the analysis of the causes of 2-year variations in TMIG-IC total scores and WHO-5-J scores, the dependent variable was each variation. This study used an analysis of covariance in which the fixed factors were types of living alone, sex, annual income, and having children who lived separately in the 2013 survey, and the covariance comprised the base-line scores for the dependent variables, age, and chronic diseases in the 2013 survey.Results　With regards to the variation in TMIG-IC total scores, main effects of the types of living alone were observed. The adjusted variation of covariance decreased most in the separation group (-0.95). For the variation in WHO-5-J scores, main effects of the types of living alone were indicated. In the divorce group, the adjusted variation of covariance was significantly higher than for the unmarried group (2.33 vs. -0.55).Conclusion　The results revealed that the types of marital status: separated, divorced, bereaved, and unmarried, affect changes in the higher-level functional capacity and mental health status of elderly adults living alone, 2 years later. Thus, although previously regarded as a single category, types of marital status should be considered in the analysis of elderly adults who live alone.

Preventive effects of an intergenerational program on age-related hippocampal atrophy in older adults: The REPRINTS study.

OBJECTIVES: A growing body of literature indicates that social engagements, such as intergenerational programs, are effective strategies to improve a range of cognitive abilities. The present study examined whether the intergenerational program-REPRINTS-prevents age-related hippocampal atrophy. METHODS: After comprehensive baseline assessment, participants were allowed to decide whether to participate in the REPRINTS intervention or in the control group, which required only completion of assessments. REPRINTS participants engaged in group activities that involved reading picture books to children at kindergarten and elementary schools, once every 1 to 2 weeks. A follow-up assessment was conducted after 6 years. Two MRI scans were performed, one immediately after baseline assessment and the other after 6 years. Volumes of the hippocampus, thalamus, and caudate nucleus were derived from automated segmentation. The analysis included 17 REPRINTS and 42 control-group participants. RESULTS: There was no significant difference in any variable of participants' characteristics at baseline between the REPRINTS and control groups. Hippocampal volume significantly declined in the control group but was maintained in the REPRINTS group. No significant differences between groups in thalamus or caudate nucleus volume were observed. Although cognitive function was unaffected by the program, greater decreases in hippocampal volume were significantly correlated with greater decreases in cognitive performance scores. CONCLUSIONS: Our results suggest that the REPRINTS intergenerational program has protective effects on age-related hippocampal atrophy in older adults. These changes precede improvements in cognitive performance, suggesting the validity of the concept of brain plasticity in later life following social engagement.

The efficacy of the Kampo medicine rikkunshito for chemotherapy-induced anorexia (RICH trial): study protocol for a randomized controlled trial.

BACKGROUND: Cisplatin is a key drug in lung cancer therapy. However, cisplatin is also well known to induce gastrointestinal disorders, such as chemotherapy-induced nausea and vomiting, anorexia, and weight loss. These symptoms sometimes affect patients' quality of life and make continuation of chemotherapy difficult. Anorexia is a cause of concern for patients with cancer because a persistent loss of appetite progresses to cancer cachexia. Although evidence-based management for chemotherapy has recently been established, there is room for improvement. METHODS/DESIGN: This placebo-controlled, double-blind, randomized trial will aim to determine the efficacy of the traditional Japanese Kampo medicine rikkunshito (TJ-43) for preventing anorexia caused by cisplatin-including chemotherapy in patients with lung cancer. Patients with lung cancer who plan to receive cisplatin-including chemotherapy will be recruited. Patients who provide written consent will be randomly allocated to receive either TJ-43 (arm A) or placebo (arm B) for one course of chemotherapy (21 or 28 consecutive days). Investigators and patients will be masked to the treatment assignment throughout the trial. The primary endpoint will be evaluated as the change in dietary intake from day 0 (the day before the start of chemotherapy) to day 7 of cisplatin-including chemotherapy. The two arms of the trial will comprise 30 patients each. From November 2014, a total of 60 patients will be recruited, and recruitment for the study is planned to be complete by October 2017. DISCUSSION: This trial is designed to examine the efficacy of rikkunshito (TJ-43) for reducing anorexia and maintaining food intake caused by cisplatin-including chemotherapy in patients with lung cancer. TRIAL REGISTRATION: Japan Pharmaceutical Information Center Clinical Trials Information (JAPIC CTI), trial registration: JAPIC CTI-142747 . Registered on 15 December 2014; the RICH trial.

Immunohistochemical profiling of receptor tyrosine kinases, MED12, and TGF-ßRII of surgically resected small cell lung cancer, and the potential of c-kit as a prognostic marker.

The limited number of available treatments for patients with small-cell lung cancer (SCLC) has prompted us to further investigate the biology of SCLC by molecular profiling. We collected formalin-fixed paraffin-embedded tumor samples from 127 patients with SCLC, who had undergone surgery at 16 institutions between January 2003 and January 2013, and analyzed the association between disease-specific survival and protein expression of c-kit, c-Met, epidermal growth factor receptor, human EGFR-related 2, vascular endothelial growth factor receptor II, anaplastic lymphoma kinase, mediator complex subunit 12 (MED12), and transforming growth factor beta receptor II (TGF-ßRII) by immunohistochemistry (IHC). Of the 125 evaluable samples, all tumors expressed MED12, and 123 samples (98.4%) expressed TGF-ßRII. MED12 was highly expressed in the nucleus in 92% of the positive samples while TGF-ßRII was highly expressed in the cytoplasm in 55% of the positive samples. High c-kit expression was an independent favorable prognostic marker confirmed by multivariate analysis (hazard ratio: 0.543, 95% confidence interval: 0.310-0.953, p = 0.033). Both the relapse free-survival and overall survival of patients who underwent adjuvant chemotherapy were statistically longer in those with high c-kit expression (n = 38) than those with intermediate, low, or no c-kit expression (n = 19) (not reached vs 11.6 months, p = 0.021; not reached vs 25.9 months, p = 0.028). IHC for c-kit may offer a prognostic marker for early-stage SCLC, and the results for MED12 and TGF-ßRII may suggest the biological characteristics of SCLC. Further investigation of the roles of their related molecules in early stage SCLC is required.

Monitoring Serum Levels of Sorafenib and Its N-Oxide Is Essential for Long-Term Sorafenib Treatment of Patients with Hepatocellular Carcinoma.

Sorafenib, an oral multi-kinase inhibitor, is the final therapy prior to palliative care for advanced hepatocellular carcinoma (HCC). However, due to its adverse effects, 20% of patients must discontinue sorafenib within 1 month after first administration. To identify ways to predict the adverse effects and administer the drug for longer periods, we explored the relationship between the duration of sorafenib treatment and the pharmacokinetics of sorafenib and its major metabolite, sorafenib N-oxide. Twenty-five subjects enrolled in the study were divided into two groups: patients with dosage reduced or withdrawn due to adverse effects (n = 8), and patients with dosage maintained for 1 month after initial administration (n = 17). We evaluated early sorafenib accumulation as the area under the curve of sorafenib and sorafenib N-oxide concentrations during days 1-7 (AUC(sorafenib) and AUC(N-oxide), respectively). Inter-group comparison revealed that AUC(N-oxide) and AUC ratio (AUC(N-oxide)/AUC(sorafenib)) were significantly higher in the dosage reduction/withdrawal group (P = 0.031 and P = 0.0022, respectively). Receiver operating characteristic analysis indicated that AUC(N-oxide) and AUC ratio were reliable predictors of adverse effects. When patients were classified by cut-off points (AUC(N-oxide:) 2.0 µg ∙ day/mL, AUC ratio: 0.13), progression-free survival was significantly longer in patients with AUC(N-oxide) ≤ 2.0 µg ∙ day/mL (P = 0.0048, log-rank test). In conclusion, we recommend to simultaneously monitor serum levels of sorafenib and its N-oxide during the early stage after the first administration, which enables us to provide safe and long-term therapy for each HCC patient with sorafenib.

[Two cases of thymic carcinoid treated with octreotide long-acting repeatable].

Thymic carcinoid is a rare disease that accounts for 3.1% of thymic tumors and 1.8-6% of all carcinoid tumors in Japan. Advanced thymic carcinoid has a 5-year survival rate of 28-31%.Compared with carcinoid tumors that arise in other organs, thyroid carcinoid tumors carry a relatively worse prognosis, and the most effective therapeutic strategy is thought to be surgical resection.However, for patients with recurrence and distant metastases, multimodal therapy including radiotherapy and/or chemotherapy is usually applied.No chemotherapy treatment regimen has been established in Japan, although the National Comprehensive Cancer Network Guidelines proposed the application of octreotide long-acting repeatable(LAR).In this report, we present two cases of thymic carcinoid that were treated with octreotide LAR and achieved long-term survival.

Effects of a comprehensive intervention program, including hot bathing, on physical function in community-dwelling healthy older adults: a pilot randomized controlled trial.

BACKGROUND AND AIMS: To study the effects of a comprehensive intervention program comprising exercise, diet, and hot bathing in community-dwelling older adults by using a randomized controlled trial. METHODS: The program included 61 community-dwelling healthy older adults (mean [SD] age, 69.9 [5.3] years) who were using a hot bath facility. The participants were randomly assigned to four groups as follows: an exercise, diet, and hot bath intervention group (A); an exercise and diet intervention group (B); a hot bath intervention group (C); and a control group (D). Individuals in groups A and B participated in a comprehensive intervention program (including exercise and diet classes) twice a week for 3 months, and those in groups A and C took hot baths. RESULTS: After 3 months, the participants in groups A and B showed a significantly greater improvement in their timed up and go test and stepping test scores than the participants in groups C and D. However, the participants in groups A and C did not show any dependent or independent effects of hot bathing. Three months after the intervention, a follow-up assessment indicated that the group A participants maintained the effect of the intervention and showed improved lower extremity function and health-related quality of life. CONCLUSIONS: The present study suggests that a comprehensive intervention program involving hot bathing may improve lower extremity function and that its effects can be maintained even in healthy older adults. However, the dependent or independent effects of hot bathing may not be expected for healthy older adults.

No enhancing effects of diacylglycerol oil on tumor development in a medium-term multi-organ carcinogenesis bioassay using male F344 rats.

The modifying potential of diacylglycerol (DAG) oil on tumor development was investigated in a medium-term multi-organ carcinogenesis bioassay. DAG oil is a cooking oil that contains >80% diglycerides, <20% triglycerides and <5% monoglycerides. Male 6-week-old F344 rats (20 in each group) were sequentially treated with five carcinogens for initiation in different organ target sites for 4 weeks (DMBDD treatment), and then administered DAG oil at dietary levels of 0% (control), 1.375%, 2.75% or 5.5% [triacylglycerol (TGs), with the same fatty acid composition as DAG oil were also added at dietary levels of 5.5%, 4.125%, 2.75% and 0%, respectively, to maintain the same lipid level], or 5.5% high linoleic acid TG (HLTG), 5.5% high oleic acid TG (HOTG), or 5.5% medium-chain TG (MCTG) (as reference substances, mostly consisting of triacylglycerols) admixed into AIN-93G semi-synthetic diet, for an additional 24 weeks. Controls received standard diet without any supplementation as non-treated control. All animals were killed at the end of week 28, and the major organs were carefully examined for preneoplastic and neoplastic lesions. No DAG oil treatment-related changes were noted in survival, general conditions, body weights, food consumption and organ weights. Upon quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci of the liver, DAG oil was not found to exert any effects. The incidence of colon adenomas was significantly increased in rats given 1.375% DAG oil, but not 2.75% and 5.5% DAG oil, when compared to the control (5.5% TG group) value. Furthermore, incidences and multiplicity of hyperplasias and adenomas and/or adenocarcinomas were comparable across all DAG oil-treated groups. In contrast, incidences of colon adenomas and/or adenocarcinomas were significantly increased in rats given 5.5% HOTG, and adenomas with MCTG, but not 5.5% HLTG, as compared to the 5.5% TG value. Preneoplastic and neoplastic lesions induced by DMBDD treatment in various organs other than the large intestine were comparable in all cases. Thus, the current results indicate that DAG oil may not exert modifying potential on tumor development, even in the colon because of the lack of dose-dependence. DAG oil was equivalent to HOTG (standard cocking oil composed of naturally occurring fatty acids), with regard to colon tumor development. Further dose-response study concerning HOTG may be needed to confirm whether the enhancing effect of large intestine carcinogenesis exert or not.

Sequence-specific DNA damage induced by ultraviolet A-irradiated folic acid via its photolysis product.

DNA damage mediated by photosensitizers participates in solar carcinogenesis. Fluorescence measurement and high-performance liquid chromatography analysis demonstrated that photoirradiated folic acid, one of the photosensitizers in cells, generates pterine-6-carboxylic acid (PCA). Experiments using 32P-labeled DNA fragments obtained from a human gene showed that ultraviolet A-irradiated folic acid or PCA caused DNA cleavage specifically at consecutive G residues in double-stranded DNA after Escherichia coli formamidopyrimidine-DNA glycosylase or piperidine treatment. The amount of 8-oxo-7,8-dihydro-2(')-deoxyguanosine formed through this DNA photoreaction in double-stranded DNA exceeded that in single-stranded DNA. Kinetic studies suggested that DNA damage is caused mainly by photoexcited PCA generated from folic acid rather than by folic acid itself. In conclusion, photoirradiated folic acid generates PCA, which induces DNA photooxidation specifically at consecutive G residues through electron transfer. Excess intake of folic acid supplements may increase a risk of skin cancer by solar ultraviolet light.

Survival advantage of using autologous blood transfusion during surgery for esophageal cancer.

PURPOSE: There is evidence that blood transfusion is associated with an increased rate of tumor recurrence. This study was conducted to assess the survival advantage of giving autologous blood instead of allogeneic blood during surgery for esophageal cancer. METHODS: We retrospectively analyzed 62 patients who underwent esophagectomy for thoracic esophageal cancer between January 1991 and February 1995 and received allogeneic blood transfusion, and 61 patients operated on between March 1995 and February 1998, who received autologous blood transfusion. The clinicopathological factors and survival rates were compared between the two groups. RESULTS: The clinicopathological factors that influenced prognosis were similar in the two groups; however, a definite survival advantage was evident in the autologous blood transfusion group. According to multivariate analyses, the transfusion of allogeneic blood was an independent prognostic factor ( P = 0.0222), as was the presence of metastatic lymph nodes. Patients who received allogeneic blood transfusions perioperatively had more than a twofold greater risk (Hazard ration 2.406) of death over patients who received autologous blood transfusions. CONCLUSION: Autologous blood transfusion appears to be an independent prognostic factor for the survival of patients with esophageal cancer.

Constituents of Compositae plants III. Anti-tumor promoting effects and cytotoxic activity against human cancer cell lines of triterpene diols and triols from edible chrysanthemum flowers.

Fifteen pentacyclic triterpene diols and triols, consisting of: six taraxastanes, faradiol (1), heliantriol B0 (2), heliantriol C (3), 22alpha-methoxyfaradiol (4), arnidiol (5), and faradiol alpha-epoxide (6); five oleananes, maniladiol (7), erythrodiol (8), longispinogenin (9), coflodiol (10), and heliantriol A(1) (11); two ursanes, brein (12) and uvaol (13); and two lupanes, calenduladiol (14) and heliantriol B2 (15), isolated from the non-saponifiable lipid fraction of the edible flower extract of chrysanthemum (Chrysanthemum morifolium) were evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate, in Raji cells as a primary screening test for anti-tumor-promoters. All of the compounds tested showed inhibitory effects against EBV-EA activation with potencies either comparable with or stronger than that of glycyrrhetic acid, a known natural anti-tumor-promoter. Evaluation of the cytotoxic activity of six compounds, 1-3 and 5-7, against human cancer cell lines revealed that compound 5 possesses a wide range of cytotoxicity, with GI50 values (concentration that yields 50% growth) of mostly less than 6 microM.