A Standardized Wedelia chinensis Extract Overcomes the Feedback Activation of HER2/3 Signaling upon Androgen-Ablation in Prostate Cancer

Crosstalk between the androgen receptor (AR) and other signaling pathways in prostate cancer (PCa) severely affects the therapeutic outcome of hormonal therapy. Although anti-androgen therapy prolongs overall survival in PCa patients, resistance rapidly develops and is often associated with increased AR expression and upregulation of the HER2/3-AKT signaling pathway. However, single agent therapy targeting AR, HER2/3 or AKT usually fails due to the reciprocal feedback loop. Previously, we reported that wedelolactone, apigenin, and luteolin are the active compounds in Wedelia chinensis herbal extract, and act synergistically to inhibit the AR activity in PCa. Here, we further demonstrated that an herbal extract of W. chinensis (WCE) effectively disrupted the AR, HER2/3, and AKT signaling networks and therefore enhanced the therapeutic efficacy of androgen ablation in PCa. Furthermore, WCE remained effective in suppressing AR and HER2/3 signaling in an in vivo adapted castration-resistant PCa (CRPC) LNCaP cell model that was insensitive to androgen withdrawal and second-line antiandrogen, enzalutamide. This study provides preclinical evidence that the use of a defined, single plant-derived extract can augment the therapeutic efficacy of castration with significantly prolonged progression-free survival. These data also establish a solid basis for using WCE as a candidate agent in clinical studies

Location-based Data Analysis of Visitor Structure for Recreational Area Management

This work presents a location-based data analysis framework for profiling visitors structures. In terms of recreational area management, understanding visitors’ structure and popularity is important. Traditionally, visitors monitoring with automatic counting devices has drawbacks of inaccurate visitors counting. In this work, compared to automatic counting devices, we use Wi-Fi tracking as the main method to count visitors, which provides a fairly precise picture of visitor structures. Moreover, we deliver rich analytic functions in this framework and we present the functionality with visitor data collected from Guanyinshan Visitor Center. This framework not only standardizes visitor counting process but also facilitates a profound analysis of visitor structures. Key Words: Guanyinshan Visitor Center, Wi-Fi trackin

Bifid mandibular canals and their cortex thicknesses: A comparison study on images obtained from cone-beam and multislice computed tomography

AbstractBackground/purposeHigh prevalence of bifid mandibular canals has been visualized with various types of computerized tomography (CT). Along the canals, a various ranged corticalization was recently reported. The depiction of the fine anatomic structures on multislice and cone-beam CT images was compared.Material and methodsThe presence or absence of the bifid canal was assessed on 327 images obtained by multislice CT (MSCT; n = 173) or by cone-beam CT (CBCT; n = 154), according to the configuration. The cortex thickness and distribution were also assessed.ResultsThe prevalence of bifid canal detected by CBCT was significantly greater than that detected by MSCT (42.2% vs. 18.7% for hemi-mandibles and 58.4% vs. 30.6% for patients). Cortical thickness recorded by CBCT was significantly thinner than that recorded by MSCT (0.48 mm vs. 0.65 mm, P < 0.001); however, the distributions of corticalization detected by the two tomography methods were similar. There was a significant association of cortex thickness with CT type and corticalization degree (R2 = 0.530, P < 0.001).ConclusionThinner cortices, but greater prevalence of bifid canals recorded by CBCT, compared to MSCT, suggests that clinicians should be cautious when using CT to interpret this fine anatomic structure

Volumetric intensity-modulated Arc (RapidArc) therapy for primary hepatocellular carcinoma: comparison with intensity-modulated radiotherapy and 3-D conformal radiotherapy

<p>Abstract</p> <p>Background</p> <p>To compare the RapidArc plan for primary hepatocellular carcinoma (HCC) with 3-D conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) plans using dosimetric analysis.</p> <p>Methods</p> <p>Nine patients with unresectable HCC were enrolled in this study. Dosimetric values for RapidArc, IMRT, and 3DCRT were calculated for total doses of 45~50.4 Gy using 1.8 Gy/day. The parameters included the conformal index (CI), homogeneity index (HI), and hot spot (V_107%) for the planned target volume (PTV) as well as the monitor units (MUs) for plan efficiency, the mean dose (D_mean) for the organs at risk (OAR) and the maximal dose at 1% volume (D_1%) for the spinal cord. The percentage of the normal liver volume receiving ≥ 40, > 30, > 20, and > 10 Gy (V_{40 Gy}, V_{30 Gy}, V_{20 Gy}, and V_{10 Gy}) and the normal tissue complication probability (NTCP) were also evaluated to determine liver toxicity.</p> <p>Results</p> <p>All three methods achieved comparable homogeneity for the PTV. RapidArc achieved significantly better CI and V_107%values than IMRT or 3DCRT (<it>p </it>< 0.05). The MUs were significantly lower for RapidArc (323.8 ± 60.7) and 3DCRT (322.3 ± 28.6) than for IMRT (1165.4 ± 170.7) (<it>p </it>< 0.001). IMRT achieved a significantly lower D_meanof the normal liver than did 3DCRT or RapidArc (<it>p </it>= 0.001). 3DCRT had higher V_{40 Gy}and V_{30 Gy}values for the normal liver than did RapidArc or IMRT. Although the V_{10 Gy}to the normal liver was higher with RapidArc (75.8 ± 13.1%) than with 3DCRT or IMRT (60.5 ± 10.2% and 57.2 ± 10.0%, respectively; <it>p </it>< 0.01), the NTCP did not differ significantly between RapidArc (4.38 ± 2.69) and IMRT (3.98 ± 3.00) and both were better than 3DCRT (7.57 ± 4.36) (<it>p </it>= 0.02).</p> <p>Conclusions</p> <p>RapidArc provided favorable tumor coverage compared with IMRT or 3DCRT, but RapidArc is not superior to IMRT in terms of liver protection. Further studies are needed to establish treatment outcome differences between the three approaches.</p

Phyllanthus urinaria Induces Apoptosis in Human Osteosarcoma 143B Cells via Activation of Fas/FasL- and Mitochondria-Mediated Pathways

Phyllanthus urinaria (P. urinaria), in this study, was used for the treatment of human osteosarcoma cells, which is one of the tough malignancies with few therapeutic modalities. Herein, we demonstrated that P. urinaria inhibited human osteosarcoma 143B cells growth through an apoptotic extrinsic pathway to activate Fas receptor/ligand expression. Both intracellular and mitochondrial reactive oxygen species were increased to lead to alterations of mitochondrial membrane permeability and Bcl-2 family including upregulation of Bid, tBid, and Bax and downregulation of Bcl-2. P. urinaria triggered an intrinsic pathway and amplified the caspase cascade to induce apoptosis of 143B cells. However, upregulation of both intracellular and mitochondrial reactive oxygen species and the sequential membrane potential change were less pronounced in the mitochondrial respiratory-defective 143Bρ0 cells compared with the 143B cells. This study offers the evidence that mitochondria are essential for the anticancer mechanism induced by P. urinaria through both extrinsic and intrinsic pathways

Concurrent image-guided intensity modulated radiotherapy and chemotherapy following neoadjuvant chemotherapy for locally advanced nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>To evaluate the experience of induction chemotherapy followed by concurrent chemoradiationwith helical tomotherapy (HT) for nasopharyngeal carcinoma (NPC).</p> <p>Methods</p> <p>Between August 2006 and December 2009, 28 patients with pathological proven nonmetastatic NPC were enrolled. All patients were staged as IIB-IVB. Patients were first treated with 2 to 3 cycles of induction chemotherapy with EP-HDFL (Epirubicin, Cisplatin, 5-FU, and Leucovorin). After induction chemotherapy, weekly based PFL was administered concurrent with HT. Radiation consisted of 70 Gy to the planning target volumes of the primary tumor plus any positive nodal disease using 2 Gy per fraction.</p> <p>Results</p> <p>After completion of induction chemotherapy, the response rates for primary and nodal disease were 96.4% and 80.8%, respectively. With a median follow-up after 33 months (Range, 13-53 months), there have been 2 primary and 1 nodal relapse after completion of radiotherapy. The estimated 3-year progression-free rates for local, regional, locoregional and distant metastasis survival rate were 92.4%, 95.7%, 88.4%, and 78.0%, respectively. The estimated 3-year overall survival was 83.5%. Acute grade 3, 4 toxicities for xerostomia and dermatitis were only 3.6% and 10.7%, respectively.</p> <p>Conclusion</p> <p>HT for locoregionally advanced NPC is feasible and effective in regard to locoregional control with high compliance, even after neoadjuvant chemotherapy. None of out-field or marginal failure noted in the current study confirms the potential benefits of treating NPC patients by image-guided radiation modality. A long-term follow-up study is needed to confirm these preliminary findings.</p

The nucleolar protein NIFK promotes cancer progression via CK1α/β-catenin in metastasis and Ki-67-dependent cell proliferation.

Nucleolar protein interacting with the FHA domain of pKi-67 (NIFK) is a Ki-67-interacting protein. However, its precise function in cancer remains largely uninvestigated. Here we show the clinical significance and metastatic mechanism of NIFK in lung cancer. NIFK expression is clinically associated with poor prognosis and metastasis. Furthermore, NIFK enhances Ki-67-dependent proliferation, and promotes migration, invasion in vitro and metastasis in vivo via downregulation of casein kinase 1α (CK1α), a suppressor of pro-metastatic TCF4/β-catenin signaling. Inversely, CK1α is upregulated upon NIFK knockdown. The silencing of CK1α expression in NIFK-silenced cells restores TCF4/β-catenin transcriptional activity, cell migration, and metastasis. Furthermore, RUNX1 is identified as a transcription factor of CSNK1A1 (CK1α) that is negatively regulated by NIFK. Our results demonstrate the prognostic value of NIFK, and suggest that NIFK is required for lung cancer progression via the RUNX1-dependent CK1α repression, which activates TCF4/β-catenin signaling in metastasis and the Ki-67-dependent regulation in cell proliferation

Lessons Learned of NSPO’s Picosatellite Mission: Yamsat - 1A, 1B & 1C

The YamSat is the first developed picosatellite in National Space Program Office’s (NSPO), Taiwan, R.O.C. It is scheduled to flight in the CubeSat launch in 2003. The rapid-prototyping system engineering different from the past formal discipline opens a new satellite development model in NSPO. The YamSat Test Readiness Review Meeting was successfully held in January 2002 and the environmental tests were completed by end March 2002. Besides the breadboard model and engineering test bed to prove of operation concept are built, three YamSats (1A, 1B, & 1C) instead of one are manufactured with slightly different configurations and purposes. The YamSat- 1A is for flight with ambitious and novel R.O.C. made components, including 15 domestic organizations and companies’ participation. The YamSat-1B is basically for backup purpose and demonstration, whereas the YamSat-1C is for amateur communication experiment end-to-end field test, and for public education purpose. This new experience gives fruitful lessons learned and provides low cost space experimentation and education to the next built picosatellites in Taiwan’s universities. Detailed mission and lessons learned are addressed in this paper

Inhibition of FAK Signaling Elicits Lamin A/C-Associated Nuclear Deformity and Cellular Senescence

Focal adhesion kinase (FAK) is a non-receptor kinase that facilitates tumor aggressiveness. The effects of FAK inhibition include arresting proliferation, limiting metastasis, and inhibiting angiogenesis. PF-573228 is an ATP-competitive inhibitor of FAK. Treating lung cancer cells with PF-573228 resulted in FAK inactivation and changes in the expressions of lamin A/C and nuclear deformity. Since lamin A/C downregulation or deficiency was associated with cellular senescence, the senescence-associated β-galactosidase (SA-β-gal) assay was used to investigate whether PF-573228 treatment drove cellular senescence, which showed more SA-β-gal-positive cells in culture. p53 is known to play a pivotal role in mediating the progression of cellular senescence, and the PF-573228-treated lung cancer cells resulted in a higher p53 expression level. Subsequently, the FAK depletion in lung cancer cells was employed to confirm the role of FAK inhibition on cellular senescence. FAK depletion and pharmacological inhibition of lung cancer cells elicited similar patterns of cellular senescence, lamin A/C downregulation, and p53 upregulation, implying that FAK signaling is associated with the expression of p53 and the maintenance of lamin A/C levels to shape regular nuclear morphology and manage anti-senescence. Conversely, FAK inactivation led to p53 upregulation, disorganization of the nuclear matrix, and consequently cellular senescence. Our data suggest a new FAK signaling pathway, in that abolishing FAK signaling can activate the senescence program in cells. Triggering cellular senescence could be a new therapeutic approach to limit tumor growth