Hsin Yi Wang

Clinical value of FDG PET or PET/CT in urinary bladder cancer: A systemic review and meta-analysis

AIM The purpose of the current study was to conduct a systemic review and meta-analysis of the published literature to evaluate the diagnostic accuracy of FDG PET or PET/CT in urinary bladder cancer. MATERIALS AND METHODS The authors conducted a systematic MEDLINE search of articles published between January 2000 and December 2010. Two reviewers independently assessed the methodological quality of each study. We conducted a meta-analysis of pooled sensitivity and specificity in detecting primary and metastatic lesions of bladder cancer. RESULTS Six studies met the inclusion criteria. The pooled sensitivity and specificity of PET/CT for primary lesion detection of bladder cancer were 0.90 (95% CI: 0.70-0.99) and 1.00 (95% CI: 0.74-1.00), respectively. The pooled sensitivity and specificity of FDG PET or PET/CT for staging or restaging (metastatic lesions) of bladder cancer were 0.82 (95% CI: 0.72-0.89) and 0.89 (95% CI: 0.81-0.95), respectively. CONCLUSION The diagnostic accuracy of FDG PET or PET/CT is good in metastatic lesions of urinary bladder cancer. Due to the small number of patients and limited number of studies analyzed, the diagnostic capability of FDG PET or PET/CT in detection of primary bladder wall lesions could not be assessed.

Meta-analysis of the diagnostic performance of [18F]FDG-PET and PET/CT in renal cell carcinoma.

Abstract Objectives: Positron emission tomography (PET) using fluorodeoxyglucose (FDG) is useful for restaging renal cell carcinoma (RCC) and detecting metastatic diseases but is less satisfactory for detecting primary disease. We evaluated whether the integration of computed tomography (CT) scans with the PET system could increase the applicability of FDG-PET for RCC. Methods: The MEDLINE databases were searched for relevant studies published since 2001. Two reviewers independently assessed the methodological quality of each study identified. We then performed a meta-analysis of the sensitivity and specificity of FDG-PET findings as reported in all the selected studies. Results: Fourteen studies were eligible for inclusion. The pooled sensitivity and specificity of FDG-PET were 62% and 88% respectively, for renal lesions. For detecting extra-renal lesions, the pooled sensitivity and specificity of FDG-PET were 79% and 90%, respectively, based on the scans, and 84% and 91% based on the lesions. The use of a hybrid FDG-PET/CT to detect extra-renal lesions increased the pooled sensitivity and specificity to 91% and 88%, respectively, with good consistency. Conclusions: For RCC, combining the FDG-PET and CT systems is helpful for detecting extra-renal metastasis rather than renal lesions. The hybrid PET/CT system has comparable sensitivity and specificity with PET in detecting extra-renal lesions of RCC. Advances in knowledge: The FDG-PET and PET/CT systems are both useful for detecting extra-renal metastasis in renal cell carcinoma.

FDG PET or PET/CT for detecting intramedullary and extramedullary lesions in multiple myeloma: A systematic review and meta-analysis

Aim The purpose of the current study was to conduct a systematic review and meta-analysis of the published literature to evaluate the diagnostic accuracy of FDG PET or PET/CT for intramedullary and extramedullary lesions in multiple myeloma. Methods The authors conducted a systematic MEDLINE search of published articles. Two reviewers independently assessed the methodological quality of each study. We estimated pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR−), and summary receiver operating characteristic curves in the detection of intramedullary and extramedullary lesions in multiple myeloma. Results Fourteen studies with a total of 395 patients met the inclusion criteria. The pooled estimates of sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of FDG PET or PET/CT for the detection of extramedullary lesions in multiple myeloma were 96.0% [95% confidence interval (CI), 79.6%–99.9%], 77.8% (95% CI, 40.0%–97.2%), 3.28 (95% CI, 1.29–8.32), and 0.12 (95% CI, 0.03–0.42), respectively. The pooled estimates of sensitivity, specificity, LR+, and LR− of FDG PET or PET/CT for the detection of intramedullary lesions in multiple myeloma were 61.1% (95% CI, 43.5%–76.9%), 94.1% (95% CI, 71.3%–99.9%), 5.73 (95% CI, 1.53–21.40), and 0.43 (95% CI, 0.28–0.65), respectively. Conclusions Whole-body FDG PET or PET/CT is a valuable imaging tool for the assessment of patients with multiple myeloma, especially for the appraisal of extramedullary involvement.

Emodin and Aloe-Emodin Suppress Breast Cancer Cell Proliferation through ER α Inhibition.

The anthraquinones emodin and aloe-emodin are abundant in rhubarb. Several lines of evidence indicate that emodin and aloe-emodin have estrogenic activity as phytoestrogens. However, their effects on estrogen receptor α (ERα) activation and breast cancer cell growth remain controversial. The goal of this study is to investigate the effects and molecular mechanisms of emodin and aloe-emodin on breast cancer cell proliferation. Our results indicate that both emodin and aloe-emodin are capable of inhibiting breast cancer cell proliferation by downregulating ERα protein levels, thereby suppressing ERα transcriptional activation. Furthermore, aloe-emodin treatment led to the dissociation of heat shock protein 90 (HSP90) and ERα and increased ERα ubiquitination. Although emodin had similar effects to aloe-emodin, it was not capable of promoting HSP90/ERα dissociation and ERα ubiquitination. Protein fractionation results suggest that aloe-emodin tended to induce cytosolic ERα degradation. Although emodin might induce cytosolic ERα degradation, it primarily affected nuclear ERα distribution similar to the action of estrogen when protein degradation was blocked. In conclusion, our data demonstrate that emodin and aloe-emodin specifically suppress breast cancer cell proliferation by targeting ERα protein stability through distinct mechanisms. These findings suggest a possible application of anthraquinones in preventing or treating breast cancer in the future.

Increased subsequent risk of erectile dysfunction in patients with irritable bowel syndrome: a nationwide population‐based cohort study

This retrospective population‐based study aimed to investigate associations between erectile dysfunction (ED) and the irritable bowel syndrome (IBS) using a Taiwanese cohort. We identified 17 608 male patients who were newly diagnosed with IBS from 1997 to 2010. The date that the diagnosis of IBS had been made was the index date. IBS patients with a history of ED before the index date or with incomplete demographic information were excluded. 70 432 age‐matched subjects without IBS were selected as comparison cohort. Both cohorts were followed until the end of 2010 or censored. Cox proportional hazard regression model was used to estimate the effects of IBS on ED risks. The incidence rate ratio of ED in the IBS cohort was 2.92 times higher than that in the non‐IBS cohort (29.5 vs. 10.1 per 10 000 person‐years), with an adjusted hazard ratio (aHR) of 2.58 (95% confidence interval [CI]: 2.24–2.98). The risk of ED increased with increasing age and number of comorbidities. Patients with depression were at a higher risk of ED (aHR: 1.97; 95% CI: 1.49–2.63) compared with the subjects without depression. IBS patients had a higher risk of developing ED compared with non‐IBS subjects. Ageing and comorbidities including diabetes, cardiovascular disease, chronic kidney disease and depression were associated with the risk of ED.

Inhibitory effects of Rhenium-188-labeled Herceptin on prostate cancer cell growth: A possible radioimmunotherapy to prostate carcinoma

Abstract Purpose: Herceptin is widely used in treating Her2-overexpressing breast cancer. However, the application of Herceptin in prostate cancer is still controversial. Our previous results have indicated the relevance of Her2 in the transition of the androgen requirement in prostate cancer cells. In this study, the effects of radioimmunotherapy against Her2 in prostate cancer were investigated. Materials and methods: DU145, an androgen receptor-negative prostate cancer cell line, was used in vitro and in vivo to evaluate the effects of Herceptin labeled with a beta emitter, Rhenium-188 (Re-188). Its effects on cell growth, extent of apoptosis, the bio-distribution of Re-188 labeled Herceptin (Re-H), and protein levels were determined. Results: Treatments with Re-188 and Re-H reduced the proliferation of DU145 cells in dose- and time-dependent manners compared to the Herceptin-treated group. Growth inhibition and apoptosis were induced after Re-H treatment; growth inhibition was more distinct in cells with high Her2/p-Her2 levels. Our in vivo xenograft studies revealed that Re-H treatment significantly retarded tumor growth and altered the levels of apoptosis-related proteins. The bio-distribution of Re-H in mice demonstrated a tissue-specific pattern. Importantly, the levels of p35 protein, which is related to cancer cell survival and invasion, dramatically decreased after Re-H treatment. Conclusions: Our data demonstrate that Re-188-labeled Herceptin effectively inhibited the growth of DU145 cells compared to the Herceptin- and Re-188-treated cohorts. This implies that targeting Her2 by both radio- and immuno- therapy might be a potential strategy for treating patients with androgen-independent prostate cancer.

18F-FDG PET/CT in detection of gynecomastia in patients with hepatocellular carcinoma

OBJECTIVE We retrospectively investigate the prevalence of gynecomastia as false-positive 2-[18F]fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging in patients with hepatocellular carcinoma (HCC). METHODS Among the 127 male HCC patients who underwent 18F-FDG PET/CT scan, the 18FDG uptakes at the bilateral breasts in 9 patients with gynecomastia were recorded as standard uptake value (SUVmax) and the visual interpretation in both early and delayed images. RESULTS The mean early SUVmax was 1.58/1.57 (right/left breast) in nine gynecomastia patients. The three patients with early visual score of 3 had higher early SUVmaxs. CONCLUSION Gynecomastia is a possible cause of false-positive uptake on 18F-FDG PET/CT images.

Increased risk of organic erectile dysfunction in patients with chronic fatigue syndrome: a nationwide population‐based cohort study

Chronic fatigue syndrome (CFS) is a complex disorder characterized by profound and persistent fatigue and several comorbidities. CFS was previously reported to be associated with female sexual dysfunction. We propose that CFS might also be associated with organic erectile dysfunction (organic ED). We conducted a retrospective cohort study by using data from the National Health Insurance (NHI) Research Database. We identified 2156 male patients who were newly diagnosed with CFS between January 1, 2003 and December 31, 2006. After excluding those younger than 20 years and prevalent cases, 1976 patients were subjected to analysis, and 7904 people served as healthy controls. All study subjects were followed up from the index date to the date of organic ED diagnosis, withdrawal from the NHI program, or the end of 2011. Compared with the non‐CFS cohort, the incidence density rate of organic ED was 1.88‐fold higher than that in the CFS cohort (3.23 vs. 1.73 per 1000 person‐years) with an adjusted hazard ratio (HR) of 1.88 (95% CI = 1.26–2.81) when adjusting for sex and comorbidities. The combined impacts of patients with CFS and cardiovascular disease (CVD), diabetes mellitus (DM), chronic kidney disease (CKD), depression, and anxiety showed a significant by joint association with organic ED risk compared with patients with no CFS and no counterpart comorbidity. The greatest magnitude of adjusted HR of ED for CFS was observed in individuals without any comorbidity (3.87, 1.95–7.66). The incidence of organic ED is higher among males aged 40 years and over for both CFS and non‐CFS cohorts. As the number of comorbidity increases, the incidence of organic ED increases in males without CFS. Higher incidence of organic ED was observed in males with CVD, DM, CKD, depression, or anxiety for both CFS and non‐CFS cohorts.

Increased subsequent risk of erectile dysfunction among middle and old age males with chronic osteomyelitis: a nationwide population-based cohort study

Chronic inflammation may cause endothelial dysfunction and atherosclerosis, resulting in subsequent erectile dysfunction (ED). We examined the relationship between chronic osteomyelitis, which is a chronic inflammatory disease, and ED. A retrospective cohort study was conducted using data from the National Health Insurance Research Database. After excluding patients <40 years of age, 677 male patients newly diagnosed with chronic osteomyelitis (COM) from 1 January 2000 to 31 December 2011 were identified for the study. The non-osteomyelitis comparison cohort consisted of 2706 male participants. The incidence of ED was 2.66-fold higher in the COM cohort than in the non-osteomyelitis cohort (4.01 vs 1.51 per 10 000 person-years). After adjusting for age and comorbidities of coronary heart disease, hypertension, hyperlipidemia, depression, stroke, diabetes, peripheral vascular disease, chronic kidney disease, chronic obstructive pulmonary disease and asthma, the patients with COM had a 2.82-fold risk of ED (95% confidence interval=1.44–5.56). The incidence of ED increased with that of comorbidities in both cohorts. The highest hazard ratio was in patients between 40 and 59 years of age who had COM. Our data showed, for the first time, that COM is a possible risk factor for the development of ED.

Cdk5 Directly Targets Nuclear p21CIP1 and Promotes Cancer Cell Growth

The significance of Cdk5 in cell-cycle control and cancer biology has gained increased attention. Here we report the inverse correlation between the protein levels of Cdk5 and p21CIP1 from cell-based and clinical analysis. Mechanistically, we identify that Cdk5 overexpression triggers the proteasome-dependent degradation of p21CIP1 through a S130 phosphorylation in a Cdk2-independent manner. Besides, the evidence from cell-based and clinical analysis shows that Cdk5 primarily regulates nuclear p21CIP1 protein degradation. S130A-p21CIP1 mutant enables to block either its protein degradation or the increase of cancer cell growth caused by Cdk5. Notably, Cdk5-triggered p21CIP1 targeting primarily appears in S-phase, while Cdk5 overexpression increases the activation of Cdk2 and its interaction with DNA polymerase δ. The in vivo results show that Cdk2 might play an important role in the downstream signaling to Cdk5. In summary, these findings suggest that Cdk5 in a high expression status promotes cancer growth by directly and rapidly releasing p21CIP1-dependent cell-cycle inhibition and subsequent Cdk2 activation, which illustrates an oncogenic role of Cdk5 potentially applied for future diagnosis and therapy. Cancer Res; 76(23); 6888-900. ©2016 AACR.