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Resources to which people expect to represent their social and personal status influence important traveler decisions. Yet we know little about the antecedents and consequences of travelers' behavior under resource fluctuation. Three studies examined how resource status affects travelers' spending propensities in crisis times from the life-history framework. Results presented that travelers with lower childhood backgrounds increased their willingness to pay for international flights to compensate for their resource deficit when their current income is relatively low and travel restriction is severe. Without resource-scarce cues, travel intentions were associated with travelers' childhood travel habits. The research suggests potential customer relationship strategies by showing how and why travelers' life histories affect compensatory behavior that companies may adopt during the industrial crisis. • Identified causal factors for compensatory travel from the life-history aspects • Resource-scarce cues affected low childhood background people on travel behavior. • Compensatory travel tendency was stronger for low childhood background people. [ABSTRACT FROM AUTHOR]

Hearing aids (HAs) are used in everyday life. To improve the subjective satisfaction of HAs, a simple and comprehensive means to adjust the internal parameters to accommodate various situations is required. In this study, we propose a new scalp tapping-based protocol for controlling the parameters of binaural HAs. We then demonstrate the reliability, benefits, and clinical feasibility of the protocol via subjective evaluations from 11 volunteers. In the reliability test, the implemented scalp-tapping detection algorithm showed accuracies above 95.0% in various conditions and no false adjustment of internal parameters occurred from motions or other artifacts. In the benefit test, improvements of signal-to-noise ratio (SNR) and segmental SNR were 2.42–4.04 dB and 1.22–3.95 dB on average for serial connection of beamforming and noise-reduction algorithms. In the feasibility test, the range of control accuracy was 66.67–100% (88.06 ± 10.19%), and the range of latency time was 5.03–22.27 sec (7.25 ± 1.73 s). We expect that the proposed protocol can provide a simple and convenient way to adjust internal parameters of HAs without additional hardware changes and with short-term training. [ABSTRACT FROM AUTHOR]

Background The American Joint Committee on Cancer recently proposed the eighth edition of cancer staging system. Validation studies are required to evaluate the prognostic stratification of ampulla of Vater cancer patients. Methods In the study, 369 operatively resected patients with ampullary cancers were grouped based on the eighth T (T1a, limited to sphincter of Oddi; T1b, invasion to duodenal submucosa; T2, invasion to duodenal proper muscle; T3a, invasion to pancreas ≤0.5 cm; T3b, invasion to pancreas >0.5 cm; and T4, involvement of celiac axis or superior mesenteric artery) and N (N0, no nodal metastasis; N1, 1–3 nodal metastasis; and N2, ≥4 nodal metastasis) category of ampullary cancer staging. Results Overall 5-year survival rates for T and N categories were as followed: T1a, 83%; T1b, 71%; T2, 46%; T3a, 48%; T3b, 28.5%, T4, 7% ( P< . 001); N0, 44.8%; N1, 20%; N2, 4% ( P < . 001). Pair-wise comparisons demonstrated significant differences between T1a-b ( P = .005), T3a-T3b ( P = .03), N0-N1 ( P < . 001), and N1-N2 ( P = .007) tumors, but not between T1b-T2 ( P = .20), T2-T3a ( P = .84), and T3b-T4 ( P = . 17) lesions. Conclusion The eighth edition T category for ampullary cancer does not stratify patients accurately with regard to prognosis. Modification of the current T category with eliminating subcategories (T1, invasion to duodenal submucosa; T2, invasion to duodenal proper muscle; T3, invasion to pancreas or duodenal subserosa) is a better way for determining prognosis of ampullary cancer. The current N category segregates patient survival well. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: This study aimed to develop and validate a method for measuring the depth of tumor invasion (DoI) using magnetic resonance imaging (MRI) and to investigate the diagnostic performance of the measured DoI for stratifying tumor (T) classification in patients with distal bile duct cancer according to the new American Joint Committee on Cancer staging system.Materials and Methods: Fifty-four patients (30 men and 24 women; age range, 43-81 years) with distal bile duct cancer were enrolled. A study coordinator first developed a "provisional method" for measuring DoI on T2-weighted MRI. Subsequently, after compensating for defects, the "improved method" was developed. Two reviewers independently measured DoI and assessed its correlations with the histopathologic reference standard using intraclass correlation coefficient (ICC). The study population was grouped according to the DoI for T classification based on the new staging system for evaluation of diagnostic predictive values.Results: The ICC values between the radiologic and the histopathologic DoI were calculated. Using the "improved method," the ICC for the coordinator's DoI was very good (ICC, 0.885), which was a significantly higher value than that obtained using the "provisional method" (ICC, 0.501, P = .00000); and for two reviewers' DoIs, the ICC values were good (ICC, 0.752 and 0.784, respectively). The overall accuracy of MRI for stratifying bile duct tumors using DoI was 87.0% and 85.2%, respectively.Conclusions: This newly developed method reliably measured DoI on T2-weighted MRI and can be used for preoperative T classification of patients with distal bile duct cancer according to the new staging system. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumors (NETs) are originating from neuroendocrine cells in diffuse endocrine systems. NETs are diagnosed by characteristic histologic features and immunoprofiles. Recent 2010 WHO classification for gastroenteropancreatic NETs introduced grading system based on mitotic count and Ki-67 proliferation index. Gastroenteropancreatic NETs are classified as NET grade 1, NET grade 2, and neuroendocrine carcinoma (NET grade 3). However, the carcinoid is still used in classification of NETs of the lung and uterine cervix. Some issues with grading system such as methodologies for evaluation of Ki-67 index and subclassification of neuroendocrine carcinoma (NET grade 3) are arising. The importance of Ki-67 labeling index is emerging in differential diagnosis of lung carcinoids. In this review, we focus on recent grading and classification of NETs and related issues in various organs, including gastrointestinal tract, pancreas, lung, and female reproductive organs. [ABSTRACT FROM AUTHOR]

[Display omitted] • Riptortus pedestris acquires bacterial symbiont, Burkholderia spp., from soil. • We investigated Burkholderia clade compositions using PCR analysis in South Korea. • Triple clade (SBE + PBE + BCC) of Burkholderia was dominantly detected in soil. • Riptortus pedestris mainly acquired single BCC clade when reared on the soil samples. • From wild R. pedestris collected, the insects mainly harbored single BCC clade. Riptortus pedestris (Hemiptera: Alydidae) is known to acquire the genus Burkholderia , symbiotic bacteria, from soil. Therefore, symbiont acquisition of R. pedestris would be directly affected by bacterial diversity in soil. Soil typically harbors diverse microbes including different Burkholderia clades such as SBE (stinkbug-associated beneficial and environmental), PBE (plant-associated beneficial and environmental), and BCC (Burkholderia cepacia and complex). Nevertheless, little is known about Burkholderia acquisition patterns of R. pedestris in nature, especially in the context of bacteria clade compositions in soil. Therefore, based on diagnostic PCR analysis, we investigated Burkholderia clade compositions in field-collected soil itself and R. pedestris when the insects were provided with the soil. Also, wild R. pedestris were surveyed to characterize their Burkholderia compositions. First, 88.44% of soil samples were detected with the genus Burkholderia , and triple clade (SBE + PBE + BCC) was most frequently detected. Second, R. pedestris nymphs readily acquired Burkholderia bacteria from field-collected soil where 91.25% of the reared insects harbored the bacteria in their midguts. In contrast to soil, the detection of single BCC clade was the most dominant among the three identified Burkholderia clades. Third, from wild R. pedestris , 80.62% of the insects were found to harbor the genus Burkholderia , and single BCC clade was most frequently detected. Finally, 29.13% and 47.06% of the reared and wild R. pedestris were detected with unidentified Burkholderia clade, which does not belong to any of the three identified clades. Our findings provide baseline information to better understand ecological associations between R. pedestris and Burkholderia bacteria in different clades. [ABSTRACT FROM AUTHOR]

Background and purpose The efficacy of prophylactic extended-field irradiation (EFI) plus concomitant cisplatin in patients with locally advanced uterine cervical cancer (LAUCC) is unknown, nor is it known whether tumor carbonic anhydrase IX (CA9) expression level, a hypoxia marker, influences survival outcome. Material and methods We recruited patients with UCC, FIGO stage IB1 with pelvic lymph node (LN) metastases to IVA with negative para-aortic LN on PET/CT. CA9 expression was examined and patients were randomized to either EFI or pelvic only radiotherapy (PRT) in each CA9 group. The primary outcomes were para-aortic recurrence-free survival (PARFS) and disease-free survival (DFS). Results Between 2006 and 2011, 79 patients with CA9-positive and 37 with CA9-negative tumors were enrolled, respectively. The median follow-up period was 69.2 months (range 6.8–102.1). For CA9-positive patients, 5-year PARFS was 100% and 81.7% for those receiving EFI and PRT ( p = 0.007), respectively. DFS was 78.6% for EFI and 71.3% for PRT patients ( p = 0.353). For CA9-negative patients, 5y PARFS was 100% and 94.1% for EFI and PRT ( p = 0.317), respectively. DFS was 100% for EFI and 70.7% for PRT ( p = 0.018). Conclusion EFI significantly reduced recurrences in PAN in patients with CA9-positive tumors, but survival outcome was not improved, due to high local recurrence and high distant metastases rates. This study indicates the necessity for new therapeutic strategies for LAUCC patients whose tumors show high CA9 expression. [ABSTRACT FROM AUTHOR]

Highlights: [•] Methoxychlor (MXC) and triclosan (TCS) increased ovarian cancer cell growth. [•] MXC or TCS resulted in upregulation of cyclin D1 and downregulation of p21 and Bax genes. [•] In addition, they regulated these proteins as well in ovarian cancer cells. [•] MXC and TCS may stimulate ovarian cancer growth via an ER-dependent pathway. [Copyright &y& Elsevier]

Abstract: Background and purpose: Lymph node (LN) metastasis is a well-known prognostic factor of the cervical cancer. In the current study, the size of metastatic LN was evaluated for its significance in the patients treated with definitive radiotherapy. Materials and methods: LN metastasis was evaluated for the 268 consecutive patients. The short-axis diameters of the largest LN were measured on magnetic resonance images for the 155 patients with LN metastasis. All the patients were classified into three groups: the negative lymphadenopathy (group N), the small (<15mm) lymphadenopathy (group SP), and the large (⩾15mm) lymphadenopathy (group LP). Results: Patients in the group LP showed significantly lower survival rates than the groups N and SP (5-year overall survival rates of 89%, 82%, and 58%, for groups N, SP, and LP, respectively, P <0.001; 5-year disease-free survival rates of 80%, 67%, and 50%, respectively, P <0.001). Regarding the pattern of failure, patients in the group LP showed inferior regional control rates and higher distant metastasis. Conclusion: The current study shows that the patients with large metastatic LNs are at increased risk of dying from early distant metastasis with substantial number of combined regional failures. Adoption of more effective systemic treatment as well as high radiotherapy dose for LNs may improve cure rates for these patients. [Copyright &y& Elsevier]

Purpose: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with curative intent in patients with stage IVB cervical cancer initially presenting with paraortic and left supraclavicular lymph node metastases. Methods and Materials: The medical records of 25 patients with both paraortic and left supraclavicular lymph nodal metastases (group I) were reviewed and compared with those of 101 women with paraortic lymph node metastases alone (group II). Group I received a mean 59.4 Gy to the paraortic and left supraclavicular areas and 50.4 Gy to the pelvis, followed by 30 Gy of high-dose-rate brachytherapy in 6 fractions. Group II received the same dose to the paraortic area and pelvis followed by intracavitary brachytherapy. All patients received platinum-based chemotherapy simultaneously. Results: Of the 25 patients in group I, 16 (64%) experienced acute grade 3-4 hematologic toxicities, and 1 had a late grade 3 genitourinary toxicity. Complete responses, including the primary mass and pelvic, paraortic, and left supraclavicular lymph nodes, were observed in 13 patients (52%). At a median follow-up of 32 months for surviving patients, 3 experienced in-field failure, 6 showed distant failure, and 9 showed both. The 3-year overall and disease-free survival rates were 49% and 33%, respectively. In comparison, of the 101 patients in group II, 16 showed in-field failure, 14 experienced distant failure, and 11 showed both. The 3-year overall and disease-free survival rates were 69% and 57%, respectively. Conclusions: Curative CCRT is feasible in patients with stage IVB cervical cancer presenting with paraortic and left supraclavicular lymph nodal metastases, with acceptable late toxicity and high response rates, despite high rates of acute hematologic toxicity. [Copyright &y& Elsevier]

Abstract: Background and purpose: To investigate the dosimetric impact of beamlet size in the leaf travel direction for the spinal treatment using intensity-modulated radiosurgery (IMRS). Materials and methods: The IMRS plans of ten patients (11 lesions – 6 thoracic, 2 cervical, 3 lumbar) were re-planned using four different beamlet sizes (1, 2, 5, and 10mm) – in the leaf travel direction, while keeping the Y-dimension by multi-leaf collimator (MLC) width fixed, and compared to the reference plan with beamlet size of 3mm. To evaluate the beamlet size effect, target volumes (coverage, conformity, and size effect), organ at risks (OARS) (doses to the spinal cord, lung and kidneys), and integral dose, and monitor units (MUs) were calculated. Results: Target coverage and dose conformity for planning target volume (PTV) were not correlated with beamlet size. Maximum (p =0.000) and mean (p =0.000) spinal cord doses decreased by 4.0% and 3.4% from 23.4% and 28.6% as beamlet size decreased from 10 to 1mm. The integral doses, MUs and doses to other organs increased at smaller beamlet sizes. MUs for a beamlet size of 10mm decreased by 31.4%, as compared with that at the reference beamlet size. Conclusions: Despite no dosimetric benefits with respect to target volume and an MU increase, a definite dose reduction was observed at the spinal cord for smaller beamlet sizes. Treatment with IMRS planning for the spine will benefit from the use of a beamlet size between 2 and 4mm. [Copyright &y& Elsevier]

Abstract: Rhabdoid tumors have been reported in many different anatomic sites as an aggressive tumor and usually present with a rhabdoid tumor component (a composite tumor) rather than a pure rhabdoid tumor. Rhabdoid tumor in the prostate has been described only once in the prostatic region as a possible epithelial origin. Rhabdoid features in prostatic stromal sarcomas (PSSs) have never been described in the literature. Here, we report a case of a PSS with rhabdoid features. A 31-year-old man presented with a 4-month history of voiding difficulty and anal pain. Computed tomography of the abdomen revealed an ovoid mass in the prostate invading rectum and urinary bladder. A needle biopsy was diagnosed as an unclassified spindle cell sarcoma, and 2 cycles of adriamycin-based neoadjuvant chemotherapy were given, followed by radical prostatectomy. The prostatectomy specimen revealed a high-grade sarcoma with fascicles of highly cellular spindle cells and numerous mitoses with hemorrhage and necrosis. In areas, the tumor also contained sheets of loosely cohesive epithelioid cells with rhabdoid tumor component. Both spindle and rhabdoid tumor cells were positive for vimentin, CD34, and progesterone receptor and negative for desmin and cytokeratin immunostainings. The rhabdoid tumor cells retained INI1 expression. The tumor recurred in the bladder, and the patient died of sepsis. To the best of our knowledge, this is the first case of PSS with rhabdoid features. The tumor showed an aggressive clinical behavior with a short-term survival (7 months after diagnosis). [Copyright &y& Elsevier]

Abstract: We isolated a galectin-9 (Gal-9) homologue gene (Tl-gal) from an adult worm of the canine gastrointestinal nematode parasite, Toxascaris leonina, via random cDNA library sequencing. The deduced amino acid sequence of the Tl-gal genes evidenced an identity of 89% with the galectin of Dirofilaria immitis, 87% identity with the galectin of Brugia malayi, and 35% identity with the human GAL-9 gene. To evaluate immune modulate function of Tl-GAL in host inflammatory response, we constructed recombinant Tl-GAL (rTl-GAL) using an Escherichia coli expression vector system and treated to intestinal inflammation mice. Although the carbohydrate-binding ability of rTl-GAL was less than that of rat galectin, we confirmed that recombinant rTl-GAL has carbohydrate-binding activity. The clinical symptoms of dextran sulfate sodium (DSS)-treated mice after rTl-GAL pre-treatment were found to be minimized, or less profound, as compared to those of the rTl-GAL untreated group. Additionally, the DSS-treated mice exhibited a significant shortening of the colon, but the large intestines of the rTl-GAL pre-treated mice were longer than those of the control group (P <0.05). Additionally, the rTl-GAL treated group exhibited significantly increased the levels of TGF-β and IL-10 (P <0.05). The production of these regulatory cytokines may ameliorate intestinal inflammation. These findings demonstrate that rTl-GAL could inhibit inflammation reactions via the inhibition of Th1 and Th2 cytokine production by increasing the production of TGF-β and IL-10 cytokines. The rTl-GAL may induce TGF-β expression, primarily via the activation of the p38 pathway. In conclusion, rTl-GAL may function like a host galectin, thus functioning as a regulatory molecule in the host immune system; rTl-GAL may prove useful in the design of novel therapeutic intervention strategies for the treatment of allergic and immune diseases. [ABSTRACT FROM AUTHOR]

Purpose: We analyzed outcomes of simultaneous integrated boost (SIB) intensity-modulated radiotherapy (IMRT) in patients with high-grade gliomas, compared with a literature review. Methods and Materials: Forty consecutive patients (WHO grade III, 14 patients; grade IV, 26 patients) treated with SIB-IMRT were analyzed. A dose of 2.0 Gy was delivered to the planning target volume with a SIB of 0.4 Gy to the gross tumor volume with a total dose of 60 Gy to the gross tumor volume and 50 Gy to the planning target volume in 25 fractions during 5 weeks. Twenty patients received temozolomide chemotherapy. Results: At a median follow-up of 13.4 months (range, 3.7–55.9 months), median survival was 14.8 months. One- and 2-year survival rates were 78% and 65%, respectively, for patients with grade III tumors and 56% and 31%, respectively, for patients with grade IV tumors. Age (≤50 vs. >50), grade (III vs. IV), subtype (astrocytoma vs. oligodendroglioma or mixed), and a Zubrod performance score (0–1 vs. >2) were predictive of survival. Of 25 (63%) patients who had recurrences, 17 patients had local failure, 9 patients had regional failure, and 1 patient had distant metastasis. Toxicities were acceptable. Conclusions: SIB-IMRT with the dose/fractionation used in this study is feasible and safe, with a survival outcome similar to the historical control. The shortening of treatment time by using SIB-IMRT may be of value, although further investigation is warranted to prove its survival advantage. [Copyright &y& Elsevier]

Background & Aims: Pancreatic bicarbonate (HCO3 −) secretion is important for a healthy pancreas as well as digestive physiology. However, how human pancreatic duct cells secrete copious amounts of HCO3 − has long been a puzzle. Here, we report that a dynamic increase in the cystic fibrosis transmembrane conductance regulator (CFTR) HCO3 − permeability by intracellular Cl− concentration ([Cl−]i)-sensitive mechanisms plays a pivotal role in pancreatic HCO3 − secretion. Methods: The role of [Cl−]i-sensitive kinases in CFTR-mediated HCO3 − transport was examined in heterologous expression systems, PANC1 human pancreatic duct cells, and human and guinea pig pancreatic tissues using an integrated molecular and physiologic approach. Results: In human pancreatic tissues, CFTR-positive duct cells abundantly expressed with-no-lysine (WNK1) kinase, oxidative stress-responsive kinase 1 (OSR1), and sterile 20/SPS1-related proline/alanine-rich kinase (SPAK), which are known to be activated by low [Cl−]i. Interestingly, CFTR activation rapidly decreased [Cl−]i in response to luminal Cl− depletion in polarized PANC1 human pancreatic duct cells. Notably, the WNK1-mediated OSR1 and SPAK activation by low [Cl−]i strongly increased CFTR HCO3 − permeability in CFTR-transfected HEK 293T, PANC1, and guinea pig pancreatic duct cells, making CFTR primarily an HCO3 − channel, which is essential for the secretion of pancreatic juice containing HCO3 − at a concentration greater than 140 mmol/L. In contrast, OSR1 and SPAK activation inhibited CFTR-dependent Cl−/HCO3 − exchange activity that may reabsorb HCO3 − from the high HCO3 −-containing pancreatic juice. Conclusions: These results indicate that the [Cl−]i-sensitive activation of the WNK1-OSR1/SPAK pathway is the molecular switch to generate HCO3 −-rich fluid in the human pancreatic duct. [Copyright &y& Elsevier]

Abstract: BLT2, a low-affinity leukotriene B4 (LTB4) receptor, is a member of the G-protein coupled receptor (GPCR) family and is involved in the pathogenesis of inflammatory diseases such as asthma. Despite its clinical implications, however, no pharmacological inhibitors are available. In the present study, we screened for small molecules that interfere with the interaction between the third intracellular loop region of BLT2 (BLT2iL3) and the Gαi3 protein subunit (Gαi3), using a high-throughput screening (HTS) assay with a library of 1040 FDA-approved drugs and bioactive compounds. We identified two small molecules—purpurin [1,2,4-trihydroxy-9,10-anthraquinone; IC50 =1.6μM for BLT2] and chloranil [tetrachloro-1,4-benzoquinone; IC50 =0.42μM for BLT2]—as specific BLT2-blocking agents. We found that blockade of the BLT2iL3-Gαi3 interaction by these small molecules inhibited the BLT2-downstream signaling cascade. For example, BLT2-signaling to phosphoinositide-3 kinase (PI3K)/Akt phosphorylation was completely abolished by these molecules. Furthermore, we observed that these small molecules blocked LTB4-induced chemotaxis by inhibiting the BLT2-PI3K/Akt-downstream, Rac1-reactive oxygen species-dependent pathway. Taken together, our results show that purpurin and chloranil interfere with the interaction between BLT2iL3 and Gαi3 and thus block the biological functions of BLT2 (e.g., chemotaxis). The present findings suggest a potential application of purpurin and chloranil as pharmacological therapeutic agents against BLT2-associated inflammatory human diseases. [Copyright &y& Elsevier]

Abstract: Although the role of the actin cytoskeleton has become increasingly elucidated, the role of actin polymerization in inflammatory processes remains poorly understood. Here, we examine the role of the actin cytoskeleton during LPS-mediated inflammatory events in RAW264.7 cells and peritoneal macrophages. We observed that actin cytoskeleton disruption by cytochalasin B and siRNA to cytoplasmic actin strongly down-regulated LPS-mediated inflammatory responses such as NO production, PGE2 release, and TNF-α secretion. Actin cytoskeleton disruption by cytochalasin B down-regulated a series of signaling cascades including PI3K, Akt, and IKK, but not MAPKs, necessary for NF-κB activation without down-regulating total forms of the proteins as assessed by measuring their phosphorylation levels. In particular, cytochalasin B significantly inhibited LPS-induced both phosphorylation and kinase activity of Src without altering total level, implying that Src may be a potential pharmacological target of actin cytoskeleton rearrangement. Moreover, the direct association of Src with actin was actin polymerization-dependent according to immunoprecipitation analysis performed with a GFP-actin wild type and HA-tagged Src. Therefore, our data suggest that actin cytoskeleton rearrangement may be a key event during the regulation of inflammatory responses that modulates the activity of Src and its downstream signaling molecules. [Copyright &y& Elsevier]

Background: A TH1-specific transcription factor, T-box–containing protein expressed in T cells (T-bet), controls the production of both TH1 and TH2 cytokines in TH cell differentiation by means of distinct mechanisms. T-bet–deficient mice overproduce TH2 cytokines and have spontaneous airway inflammation. Objectives: We tested whether T-bet overexpression could protect against the development or progression of asthma. Methods: We generated a T cell–specific and inducible line of T-bet–transgenic mice on a T-bet–deficient genetic background and used it to study the function of T-bet in an ovalbumin (OVA)–induced asthma model. Results: Induction of T-bet in a T cell–specific manner in an OVA model of asthma concomitant with OVA injection prevented airway hyperresponsiveness, eosinophilic and lymphocytic inflammation, and IL-5 and IL-13 production in bronchoalveolar lavage fluid and also reduced serum IgE and TH2 cytokine production by peripheral T cells. Even when T-bet expression was induced during later stages of asthma progression, T-bet overexpression still attenuated airway hyperresponsiveness and goblet cell hyperplasia, as well as TH2 cytokine production. Conclusions: Our results suggest that T-bet expression in T cells can prevent the initiation of airway inflammation and progression of chronic inflammation and might be extrapolated to human asthma. [Copyright &y& Elsevier]

Summary: Carbonic anhydrase IX (CA9) is reportedly overexpressed in several types of carcinomas, but little is known about the expression pattern of CA9 in oral cavity cancer and the corresponding normal tissues. We aimed to assess the prevalence of CA9 expression and its prognostic implications in patients with oral cavity squamous cell carcinoma (SCC). Immunohistochemical staining with anti-CA9 antibody was performed in 117 oral SCC samples. Clinicopathologic factors were correlated with the results of CA9 expression. CA9 expression was restricted to tumor cells and did not appear in the corresponding normal tissue. Among 117 samples, 68 (58.1%) tumors displayed CA9 overexpression. CA9 expression was significantly associated with postoperative recurrence (P = .05) and poor overall survival (P = .02). CA9 expression was also associated with male sex, lymph node metastasis, and smoking history, but these correlations did not reach statistical significance. In conclusion, CA9 expression was a frequent and tumor-specific event in oral SCC. CA9 demonstrated significant associations with disease recurrence and poor clinical outcome and shows potential as a prognostic factor for oral SCC. [Copyright &y& Elsevier]

Abstract: Activating transcription factor 3 (ATF3) is an early-induced gene involved in diverse cellular functions in response to various stresses including viral infection. Here we observed marked reduction of ATF3 by coxsackievirus B3 (CVB3) infection and investigated the regulation and functional role of ATF3 in HeLa cells for the understanding of biological significance of ATF3 downregulation. CVB3 infection markedly reduced ATF3 expression at mRNA and protein levels in parallel with p53 degradation, and preservation of p53 expression rescued CVB3 infection-induced ATF3 downregulation. ATF3 overexpression stimulated apoptotic cell death following CVB3 infection, accompanying with augmentation of CVB3 infection-induced eIF2α phosphorylation. However, ATF3 overexpression did not affect viral protein production but promoted virus progeny release. Taken together, our results suggest that ATF3 is under control of p53 in part and that the ATF3 downregulation via p53 degradation may contribute to effective viral production as a modulation mechanism of CVB3 infection-induced cell death. [Copyright &y& Elsevier]

Abstract: Homers are scaffolding proteins that bind Ca2+ signaling proteins in cellular microdomains. The Homers participate in targeting and localization of Ca2+ signaling proteins in signaling complexes. However, recent work showed that the Homers are not passive scaffolding proteins, but rather they regulate the activity of several proteins within the Ca2+ signaling complex in an isoform-specific manner. Homer2 increases the GAP activity of RGS proteins and PLCβ that accelerate the GTPase activity of Gα subunits. Homer1 gates the activity of TRPC channels, controls the rates of their translocation and retrieval from the plasma membrane and mediates the conformational coupling between TRPC channels and IP3Rs. Homer1 stimulates the activity of the cardiac and neuronal L-type Ca2+ channels Cav1.2 and Cav1.3. Homer1 also mediates the communication between the cardiac and smooth muscle ryanodine receptor RyR2 and Cav1.2 to regulate E–C coupling. In many cases the Homers function as a buffer to reduce the intensity of Ca2+ signaling and create a negative bias that can be reversed by the immediate early gene form of Homer1. Hence, the Homers should be viewed as the buffers of Ca2+ signaling that ensure a high spatial and temporal fidelity of the Ca2+ signaling and activation of downstream effects. [Copyright &y& Elsevier]

Abstract: Receptor-activated Ca2+ influx is mediated largely by store-operated channels (SOCs). TRPC channels mediate a significant portion of the receptor-activated Ca2+ influx. However, whether any of the TRPC channels function as a SOC remains controversial. Our understanding of the regulation of TRPC channels and their function as SOCs is being reshaped with the discovery of the role of STIM1 in the regulation of Ca2+ influx channels. The findings that STIM1 is an ER resident Ca2+ binding protein that regulates SOCs allow an expanded and molecular definition of SOCs. SOCs can be considered as channels that are regulated by STIM1 and require the clustering of STIM1 in response to depletion of the ER Ca2+ stores and its translocation towards the plasma membrane. TRPC1 and other TRPC channels fulfill these criteria. STIM1 binds to TRPC1, TRPC2, TRPC4 and TRPC5 but not to TRPC3, TRPC6 and TRPC7, and STIM1 regulates TRPC1 channel activity. Structure–function analysis reveals that the C-terminus of STIM1 contains the binding and gating function of STIM1. The ERM domain of STIM1 binds to TRPC channels and a lysine-rich region participates in the gating of SOCs and TRPC1. Knock-down of STIM1 by siRNA and prevention of its translocation to the plasma membrane inhibit the activity of native SOCs and TRPC1. These findings support the conclusion that TRPC1 is a SOC. Similar studies with other TRPC channels demonstrate their regulation by STIM1 and indicate that all TRPC channels, except TRPC7, function as SOCs. [Copyright &y& Elsevier]

Abstract: Codonopsis lanceolata L. has long been used as a folk medicine in Korea, Japan and China for the treatment of lung inflammatory diseases. In this study, therefore, we aimed to demonstrate its ethnopharmacological activity by examining macrophage-function regulating effects. The total methanol extracts of fresh leaves (l-TME) or roots (r-TME) of Codonopsis lanceolata L. significantly suppressed the production of pro-inflammatory mediators (nitric oxide [NO] and tumor necrosis factor [TNF-α]) without altering mRNA levels. The expression of interleukin (IL)-3 and IL-6, however, was strongly diminished. According to the analysis of signaling enzyme activation by immunoblotting, phospho-IκB levels, a representative pro-inflammatory gene activation pathway, were not affected by the TMEs. By contrast, the Raf-ERK signaling pathway, which was involved in regulation of post-translational modification of pro-inflammatory gene products, was strongly blocked after 6-h of exposure. Moreover, l-TME down-regulated LPS-mediated phagocytic uptake and CD29-mediated cell–cell adhesion, while r-TME strongly up-regulated these two cellular events as well as fibronectin-cell adhesion. The surface levels of the costimulatory molecules (CD80 and CD86) of RAW264.7 cells were also enhanced by these extracts. l-TME also diminished functional activation (assessed by NO production) and the surface level of dectin-1, but not toll-like receptor (TLR)-2. Taken together, these data suggest that Codonopsis lanceolata may have the ability to modulate macrophage-mediated immune responses, thus contributing to its anti-inflammatory activity. [Copyright &y& Elsevier]

Abstract: Chemically synthesized small interfering RNA (siRNA) has been used as an anti-coxsackievirus B3 (CVB3) agent. Herein, we investigated whether vector-derived short hairpin RNAs (shRNA) targeting CVB3 can exert antiviral activities, prior to their further application to viral vector system for efficient in vivo administration. Employing transient transfection assays to in vivo mouse models as well as to in vitro Cos-7 cell cultures, we directly demonstrated the potential antiviral activity of shRNAs following challenges with infectious CVB3. Of the six shRNAs that we designed, three prevented cell death from CVB3 infection by suppressing viral replication and viral production in Cos-7 cells. These were shRNA 2, which targeted the capsid protein VP1, and shRNAs 4 and 5, which targeted two different regions of the RNA-dependent RNA polymerase 3D. Furthermore, shRNAs 2 and 5 also exerted strong antiviral effects in viral replication in vivo, accompanied by attenuated pancreatic tissue damage. Through this direct evaluation system we addressed the development and application of vector-derived shRNAs as an anti-CVB3 agent, revealing new target sequences. [Copyright &y& Elsevier]

Abstract: Based on the functional approximation of a target volume DVH (TV-DVH) to a modified step function, we propose a new index that indicates the degrees of dose coverage and homogeneity for target volume reached in clinical routines. Forty-seven IMRT patient plans are included in the analysis to explore the efficiency of the proposed method. The new index, named s-index, was defined to vary from 0:05 for clinically acceptable TV-DVH at our institution and showed the ability to give the user an idea whether the degree of dose coverage and homogeneity for target volume were adequate when the user-defined criteria had been in place. The result shows that the lower value of s-index indecates the higher dose coverage for the tumor volume and/or the higher dose homogeneity showing the faster fall-off rate at the percentage dose higher than 100%. In addition to the quantification of dose coverage and homogeneity is has been also shown that s-index is more accurate in evaluating the dose homogeneity in tumor volume than the conventional method. The proposed method has demonstrated the effectiveness in evaluating TV-DVH in terms of simple index and supplements currently used indices by providing complete information of a DVH curve in a treatment plan. [ABSTRACT FROM AUTHOR]