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1.  External validation of risk classification in patients with docetaxel-treated castration-resistant prostate cancer 
BMC Urology  2014;14:31.
Background
Castration-resistant prostate cancer (CRPC) patients have poor prognoses, and docetaxel (DTX) is among the few treatment options. An accurate risk classification to identify CRPC patient groups for which DTX would be effective is urgently warranted. The Armstrong risk classification (ARC), which classifies CRPC patients into 3 groups, is superior; however, its usefulness remains unclear, and further external validation is required before clinical use. This study aimed to examine the clinical significance of the ARC through external validation in DTX-treated Japanese CRPC patients.
Methods
CRPC patients who received 2 or more DTX cycles were selected for this study. Patients were classified into good-, intermediate-, and poor-risk groups according to the ARC. Prostate-specific antigen (PSA) responses and overall survival (OS) were calculated and compared between the risk groups. A multivariate analysis was performed to clarify the relationship between the ARC and major patient characteristics.
Results
Seventy-eight CRPC patients met the inclusion criteria. Median PSA levels at DTX initiation was 20 ng/mL. Good-, intermediate-, and poor-risk groups comprised 51 (65%), 17 (22%), and 10 (13%) patients, respectively. PSA response rates ≥30% and ≥50% were 33%, 41%, and 30%, and 18%, 41%, and 20% in the good-, intermediate-, and poor-risk groups, respectivcixely, with no significant differences (p = 0.133 and 0.797, respectively). The median OS in the good-, intermediate-, and poor-risk groups were statistically significant (p < 0.001) at 30.1, 14.2, and 5.7 months, respectively. A multivariate analysis revealed that the ARC and PSA doubling time were independent prognostic factors.
Conclusions
Most of CRPC patients were classified into good-risk group according to the ARC and the ARC could predict prognosis in DTX-treated CRPC patients.
Trial registration
University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) number, UMIN000011969.
doi:10.1186/1471-2490-14-31
PMCID: PMC3997751  PMID: 24742323
Castration-resistant prostate cancer; Docetaxel; Risk classification; Validation study
2.  Acute hepatitis B of genotype H resulting in persistent infection 
A 47-year-old man presented with general fatigue and dark urine. The laboratory data showed increased levels of hepatic transaminases. The patient was positive for hepatitis B virus (HBV) markers and negative for anti-human immunodeficiency virus. The HBV-DNA titer was set to 7.7 log copies/mL. The patient was diagnosed with acute hepatitis B. The HBV infection route was obscure. The serum levels of hepatic transaminases decreased to normal ranges without any treatment, but the HBV-DNA status was maintained for at least 26 mo, indicating the presence of persistent infection. We isolated HBV from the acute-phase serum and determined the genome sequence. A phylogenetic analysis revealed that the isolated HBV was genotype H. In this patient, the elevated peak level of HBV-DNA and the risk alleles at human genome single nucleotide polymorphisms s3077 and rs9277535 in the human leukocyte antigen-DP locus were considered to be risk factors for chronic infection. This case suggests that there is a risk of persistent infection by HBV genotype H following acute hepatitis; further cases of HBV genotype H infection must be identified and characterized. Thus, the complete determination of the HBV genotype may be essential during routine clinical care of acute hepatitis B outpatients.
doi:10.3748/wjg.v20.i11.3044
PMCID: PMC3961985  PMID: 24659896
Acute hepatitis; Chronic hepatitis; Genotyping; Hepatitis B virus; Single nucleotide polymorphisms
3.  HIF-1-mediated metabolic reprogramming reduces ROS levels and facilitates the metastatic colonization of cancers in lungs 
Scientific Reports  2014;4:3793.
Hypoxia-inducible factor 1 (HIF-1) has been associated with distant tumor metastasis; however, its function in multiple metastatic processes has not yet been fully elucidated. In the present study, we demonstrated that cancer cells transiently upregulated HIF-1 activity during their metastatic colonization after extravasation in the lungs in hypoxia-independent and reactive oxygen species (ROS)-dependent manners. Transient activation induced the expression of lactate dehydrogenase A and phosphorylation of the E1α subunit of pyruvate dehydrogenase, which indicated the reprogramming of glucose metabolic pathways from mitochondrial oxidative phosphorylation to anaerobic glycolysis and lactic acid fermentation. The administration of the HIF-1 inhibitor, YC-1, inhibited this reprogramming, increased intratumoral ROS levels, and eventually suppressed the formation of metastatic lung tumors. These results indicate that HIF-1-mediated metabolic reprogramming is responsible for the survival of metastatic cancers during their colonization in lungs by reducing cytotoxic ROS levels; therefore, its blockade by HIF-1-inhibitors is a rational strategy to prevent tumor metastasis.
doi:10.1038/srep03793
PMCID: PMC3899644  PMID: 24452734
4.  Evaluation of Hepatic Tissue Blood Flow Using Xenon Computed Tomography with Fibrosis Progression in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis C 
Aims
The present study evaluated the utility of xenon computed tomography (Xe-CT) as a noninvasive diagnostic procedure for the measurement of hepatic tissue blood flow (TBF) in patients with nonalcoholic fatty liver disease (NAFLD) or chronic hepatitis C (CH-C).
Methods
Xe-CT was performed in 93 patients with NAFLD and in 109 patients with CH-C. Subjects were classified into one of three groups, based on fibrosis stage: group 1, no bridging fibrosis; group 2, bridging fibrosis; and group 3, liver cirrhosis. Correlations between hepatic TBFs in each fibrosis stage were examined.
Results
In group 1, portal venous TBF (PVTBF), hepatic arterial (HATBF), and total hepatic TBF (THTBF) were significantly lower in patients with in nonalcoholic steatohepatitis (NASH) than in those with CH-C (p < 0.001, p < 0.05, p < 0.001, respectively). In group 2, PVTBF and THTBF were significantly lower in patients with in NASH than in those with CH-C (p < 0.001, p < 0.05, respectively). In group 3, hepatic TBFs were not significantly different when comparing patients with NASH and those with CH-C.
Conclusions
PVTBF decreased due to fat infiltration. Therefore, hemodynamic changes occur relatively earlier in NAFLD than in CH-C. Patients with NASH should be monitored carefully for portal hypertensive complications in the early fibrosis stage.
doi:10.3390/ijms15011026
PMCID: PMC3907854  PMID: 24424317
nonalcoholic steatohepatitis; chronic hepatitis C; hepatic tissue blood flow; Xe computed tomography
5.  Involvement of magnitude of ambient temperature change in nonspecific effect in perceived placebo effect on lower urinary tract symptoms: study on switching of naftopidil in patients with benign prostatic hyperplasia 
Purpose
To determine if switching from one brand of the α1-adrenoceptor antagonist naftopidil (Avishot™) to another brand (Flivas™) under the same conditions causes the same changes in lower urinary tract symptoms (LUTS) and quality of life (QOL) as the perceived placebo effect, and if ambient temperature as a nonspecific factor is related to those changes in benign prostatic hyperplasia (BPH) patients.
Patients and methods
A retrospective study was carried out on 217 BPH patients who had received Avishot™ for more than 6 months and then were switched to Flivas™ at the same dose and timing. The two drugs contain the same principal ingredient and display the same pharmacokinetic properties. The International Prostate Symptom Score (IPSS), QOL score, and average monthly ambient temperature at the patients’ residence area from the Automated Meteorological Data Acquisition System in Japan were used for the evaluation.
Results
A significant change in urinary storage symptoms (P = 0.006), and especially in nighttime frequency (P< 0.001), was observed by switching drugs, suggesting the perceived placebo effect. There was significant improvement of daytime frequency (P< 0.05), nighttime frequency (P< 0.001), storage symptoms (P< 0.001), and total IPSS (P< 0.05) when the magnitude of ambient temperature change from before and 3 months after switching drugs was higher than 10°C, while no significant improvement was noted in any of the parameters examined when the same was lower than 10°C.
Conclusion
The present study showed the nonspecific effect of magnitude of ambient temperature change was involved in the perceived placebo effect on LUTS, especially on storage symptoms, by switching drugs. The nonspecific effect on LUTS with BPH needs to be considered when evaluating subjective treatment efficacy of drugs for LUTS with BPH in routine clinical practice. The present study supports the lifestyle advice “avoid exposing the lower body to cold temperature” or “keep warm when it is cold” for LUTS with BPH.
doi:10.2147/RRU.S42583
PMCID: PMC3826939  PMID: 24400239
ambient temperature; benign prostatic hyperplasia; lower urinary tract symptoms; naftopidil; nonspecific effect; placebo effect
6.  Docetaxel with or without estramustine for estramustine refractory castration-resistant prostate cancer: a single institution experience 
BMC Urology  2012;12:3.
Background
The significance of combination of docetaxel (DTX) with estramustine phosphate (EMP) in castration-resistant prostate cancer (CRPC) patients remains unclear. In this study, we aimed to retrospectively evaluate the efficacy and toxicity of DTX with or without EMP and to elucidate the significance of DTX and EMP combination therapy in Japanese EMP-refractory CRPC patients.
Methods
To compare the efficacy and toxicity of DTX and EMP, we divided CRPC patients, who were confirmed to be resistant to EMP, into the following two groups: group D (n = 28), which included patients treated with DTX (60 mg/m2, once in every four weeks) alone, and group DE (n = 33), which included patients treated with a combination of DTX (60 mg/m2, once in every four weeks) and EMP (twice daily oral administration at 280 mg).
Results
Prostate specific antigen (PSA) response (> 50% decline in PSA) was observed in six patients (21%) in group D and eight patients (24%) in group DE. The median time to progression (TTP) was 12.0 months and 6.2 months and the median overall survival (OS) was 26.4 months and 24.3 months in group D and DE, respectively. There was no statistical difference between the two groups in terms of PSA response, TTP, and OS. The incidence of adverse events of grade 3/4 was low in both the groups, and there was no statistical difference between the two groups.
Conclusions
Although treatment with DTX at 60 mg/m2 was effective and highly tolerated in EMP-refractory Japanese CRPC patients, the DTX and EMP combination therapy might not exhibit any survival benefit for CRPC patients.
doi:10.1186/1471-2490-12-3
PMCID: PMC3305626  PMID: 22353627
7.  Insufficient radiofrequency ablation therapy may induce further malignant transformation of hepatocellular carcinoma 
Hepatology International  2008;2(1):116-123.
Background
Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is a thermoablative technique to kill tumor tissue by generating areas of coagulative necrosis. Recent reports have raised concern that RFA may lead to a local recurrence of HCC with an aggressive phenotype and unfavorable prognosis, suggesting that RFA may induce further malignant transformation of HCC. However, the biological effects of RFA on HCC cells have not been directly analyzed. The aim of this study was to determine whether heat stress of the type associated with RFA induces malignant transformation of HCC.
Methods
We assessed the sensitivity of three HCC cell lines (HepG2, Alexander, and Huh7) to heat treatment for 10 min. We then determined the temperature at which a heat-resistant subline can be generated. We established and expanded sublines that survived heat treatment. And their proliferation rates, heat sensitivities, and invasive capacities were further examined.
Results
All HepG2 died after 48°C treatment, whereas 49°C treatment was required to kill all Alexander and HuH7. We generated 20 sublines for each parental cell line. A HepG2 subline, HepG2#18, proliferated 100% faster than parental HepG2. Moreover, HepG2#18 survived after 50°C treatment, whereas all parental HepG2 died after heat treatments at 48°C or higher.
Conclusion
Our results showed that even a single heat treatment could induce further transformation of an HCC cell line. Our results suggest that an insufficient treatment of HCC by RFA that enables survival of some cells might induce further malignant transformation in vivo.
doi:10.1007/s12072-007-9040-3
PMCID: PMC2716878  PMID: 19669287
Hepatocellular Carcinoma (HCC); Radiofrequency Ablation (RFA); Malignant transformation

Results 1-7 (7)