bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA‐PKcs‐dependent NHEJ pathway supports the progression of topoisomerase II poison‐induced chromosome aberrant cells
Authors: Elguero Maria Eugenia , de Campos‐Nebel Marcelo , González‐Cid Marcela 
Published: September 2012

AbstractThe role of DNA double strand break (DSB) repair pathways, non‐homologous end joining (NHEJ), and homologous recombination (HR) was evaluated to prevent the chromosome instability induced by the topoisomerase II (Top2) poisons, idarubicin, and etoposide in Chinese hamster cell lines. XR‐C1 (DNA‐PKcs deficient) and V‐C8 (BRCA2 deficient) showed higher sensitivity to increased concentrations of Top2 poisons compared with their normal counterparts, CHO9 and V79. Both proficient and deficient cells exhibited a marked DSB induction in all phases of the cell cycle. Additionally, deficient cells showed persistent DNA damage 24 hr post‐treatment. Chromosomal aberrations increased in the first mitosis following Top2 poison‐treatments in G1 or G2 in proficient and deficient cells. CHO9 and V79 demonstrated chromosome and chromatid exchanges following treatments in G1 and G2 phases, respectively. Deficient cells showed high frequencies of chromatid exchanges following treatments in G1 and G2. Simultaneously, we analyzed the micronuclei (MN) induction in interphase cells after treatments in G1, S, or G2 of the previous cell cycle. Both Top2 poisons induced an important increase in MN in CHO9, V79, and V‐C8 cells. XR‐C1 exhibited an increased MN frequency when cells were treated in G1 phase but not in S or G2. This MN reduction was due to a cell accumulation at G2/M and death in G2‐treated cells. Our data suggest that NHEJ and HR operate differentially throughout the cell cycle to protect from Top2 poison‐induced chromosome instability, and that DNA‐PKcs‐dependent NHEJ pathway allows the survival of chromosome damaged cells during S/G2 to the next interphase. Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc.
Bcl‐xL protein: Predictor of complete tumor response in patients with oral cancer treated with curative radiotherapy
Authors: Mallick Sanchita , Agarwal Jaiprakash , Kannan Sadhana , Pawar Sagar , Kane Shubhada , Teni Tanuja 
Published: September 2012

BackgroundWe earlier observed altered expression of p53 and Bcl‐xL in oral cancer cell lines/tissues and wanted to evaluate these proteins for prediction of radiotherapy response and outcome.MethodsThirty‐nine paraffin‐embedded, pretreatment oral cancer biopsies were analyzed for protein expression using immunohistochemistry and correlated with tumor response to radiotherapy and disease‐free survival (DFS).ResultHigh p53 (p = .040) was observed in female versus male patients. Increased p53 intensity (p = .063) was observed in tobacco habitués (chewers ± smokers) versus patients with no habits. In univariate analysis, nodal positivity (p = .044) and favorable/complete tumor response (p = .002) exhibited a significant correlation with DFS, whereas tumor response emerged as an independent predictor of DFS in multivariate analysis. Significantly high Bcl‐xL (p = .048) was observed in the unfavorable versus favorable responders.ConclusionOur study suggests that Bcl‐xL expression along with clinical parameters may be useful for identifying patients with oral cancer likely to draw maximum benefit from curative radiotherapy. © 2012 Wiley Periodicals, Inc. Head Neck 35: 1448–1453, 2013
Vagal nerve stimulation without dissecting the carotid sheath during intraoperative neuromonitoring of the recurrent laryngeal nerve in thyroid surgery
Authors: Wu Che‐Wei , Dionigi Gianlorenzo , Chen Hui‐Chun , Chen Hsiu‐Ya , Lee Ka‐Wo , Lu I‐Cheng , Chang Pi‐Ying , Hsiao Pi‐Jung , Ho Kuen‐Yao , Chiang Feng‐Yu 
Published: September 2012

BackgroundVagal nerve stimulation (VNS) has been recommended as a routine procedure during intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN). However, many surgeons have been discouraged from performing VNS because of the need for opening the carotid sheath. The purpose of this study was to investigate the feasibility and reliability of VNS without carotid sheath dissection.MethodsTwo hundred twenty patients with 376 nerves at risk were enrolled in this study. VNS without nerve exposure during IONM was applied by simply pressing a ball‐tip stimulator on the space between the carotid artery and jugular vein.ResultsVNS without nerve exposure was feasible in all cases and did not result in any morbidity. All VNS signals were successfully obtained within 30 minutes of the start of the operation and all showed a clear and reliable laryngeal electromyography (EMG) response that was similar to that from the conventional method in which nerve exposure for VNS is applied.ConclusionsVNS without dissecting the carotid sheath is feasible and reliable, rendering it a simple, safe, and surgeon‐friendly procedure during IONM. © 2012 Wiley Periodicals, Inc. Head Neck 35: 1443–1447, 2013
Deletion of the RNA‐editing enzyme ADAR1 causes regression of established chronic myelogenous leukemia in mice
Authors: Steinman Richard A. , Yang Qiong , Gasparetto Maura , Robinson Lisa J. , Liu Xiaoping , Lenzner Diana E. , Hou Jingzhou , Smith Clayton , Wang Qingde 
Published: September 2012

AbstractPatients with chronic myelogenous leukemia (CML) respond well to tyrosine kinase inhibitors (TKIs) of the Bcr‐Abl oncoprotein. However, intolerance and resistance to these agents remains a challenge, and TKIs are unable to eradicate rare leukemia‐initiating cells. Leukemia treatment would benefit from a better understanding of molecular signals that are necessary for the survival of leukemia‐initiating cells but dispensable for normal hematopoietic stem cells. Leukemia‐initiating cells in CML can arise from myeloid progenitor cells, a population that we have reported in normal hematopoiesis to depend on the RNA‐editing enzyme adenosine deaminase acting on RNA‐1 (ADAR1). We now report that Bcr‐Abl transformed leukemic cells were ADAR1‐dependent in a conditional ADAR1 knockout mouse model. ADAR1 deletion reversed leukocytosis and splenomegaly, and preferentially depleted primitive Lin‐Sca+Kit+ (LSK) leukemic cells but not LSK cells lacking the leukemic oncoprotein. ADAR1 deletion ultimately normalized the peripheral white blood count, eliminating leukemic cells as assessed by PCR. These results uncover a novel requirement for ADAR1 in myeloid leukemic cells and indicate that ADAR1 may comprise a new molecular target for CML‐directed therapeutics.
18β‐glycyrrhetinic acid inhibits hepatocellular carcinoma development by reversing hepatic stellate cell‐mediated immunosuppression in mice
Authors: Kuang Penghao , Zhao Wenxiu , Su Weixue , Zhang Zhengqi , Zhang Lei , Liu Jianming , Ren Guangli , Yin Zhenyu , Wang Xiaomin 
Published: September 2012

AbstractHepatic stellate cells (HSCs) have immunosuppressive capabilities and contribute to the occurrence and development of hepatocellular carcinoma (HCC). Thus, activated HSCs may be a suitable target for HCC therapy. Our study used mixed leukocyte reactions (MLR) in vitro to demonstrate that 18β‐glycyrrhetinic acid (GA) could reverse HSC‐mediated immunosuppression by reducing T‐cell apoptosis and regulatory T (Treg) cells expression, thereby enhancing the ability of T cells to attack tumor cells and attenuating HCC cell invasiveness. Moreover, we established a HCC orthotopic implantation model in immunocompetent C57BL/6 mice, which suggested that GA played a protective role in HCC development by reducing immunosuppression mediated by HSCs in the tumor microenvironment.
Potassium citrate supplementation results in sustained improvement in calcium balance in older men and women
Authors: Moseley Kendall F , Weaver Connie M , Appel Lawrence , Sebastian Anthony , Sellmeyer Deborah E 
Published: September 2012

Abstract
The dietary acid load created by the typical Western diet may adversely impact the skeleton by disrupting calcium metabolism. Whether neutralizing dietary acid with alkaline potassium salts results in sustained improvements in calcium balance remains controversial. In this randomized, double-blind, placebo-controlled study, 52 men and women (mean age 65.2 ± 6.2 years) were randomly assigned to potassium citrate 60 mmol/d, 90 mmol/d, or placebo daily with measurements of bone turnover markers, net acid excretion, and calcium metabolism, including intestinal fractional calcium absorption and calcium balance, obtained at baseline and at 6 months. At 6 months, net acid excretion was significantly lower in both treatment groups compared to placebo and it was negative, meaning subjects' dietary acid was completely neutralized (−11.3 mmol/d on 60 mmol/d; −29.5 mmol/d on 90 mmol/d, p &lt; 0.001 compared to placebo). At 6 months, 24-hour urine calcium was significantly reduced in persons taking potassium citrate 60 mmol/d (−46 ± 15.9 mg/d) and 90 mmol/d (−59 ± 31.6 mg/d) compared with placebo (p &lt; 0.01). Fractional calcium absorption was not changed by potassium citrate supplementation. Net calcium balance was significantly improved in participants taking potassium citrate 90 mmol/d compared to placebo (142 ± 80 mg/d on 90 mmol/d versus −80 ± 54 mg/d on placebo; p = 0.02). Calcium balance was also improved on potassium citrate 60 mmol/d, but this did not reach statistical significance (p = 0.18). Serum C-telopeptide decreased significantly in both potassium citrate groups compared to placebo (−34.6 ± 39.1 ng/L on 90 mmol/d, p = 0.05; −71.6 ± 40.7 ng/L on 60 mmol/d, p = 0.02) whereas bone-specific alkaline phosphatase did not change. Intact parathyroid hormone was significantly decreased in the 90 mmol/d group (p = 0.01). Readily available, safe, and easily administered in an oral form, potassium citrate has the potential to improve skeletal health. Longer-term trials with definitive outcomes such as bone density and fracture are needed. © 2013 American Society for Bone and Mineral Research.
Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia
Authors: Barros Nilana MT , Hoac Betty , Neves Raquel L , Addison William N , Assis Diego M , Murshed Monzur , Carmona Adriana K , McKee Marc D 
Published: September 2012

Abstract
X-linked hypophosphatemia (XLH/HYP)—with renal phosphate wasting, hypophosphatemia, osteomalacia, and tooth abscesses—is caused by mutations in the zinc-metallopeptidase PHEX gene (phosphate-regulating gene with homologies to endopeptidase on the X chromosome). PHEX is highly expressed by mineralized tissue cells. Inactivating mutations in PHEX lead to distal renal effects (implying accumulation of a secreted, circulating phosphaturic factor) and accumulation in bone and teeth of mineralization-inhibiting, acidic serine- and aspartate-rich motif (ASARM)-containing peptides, which are proteolytically derived from the mineral-binding matrix proteins of the SIBLING family (small, integrin-binding ligand N-linked glycoproteins). Although the latter observation suggests a local, direct matrix effect for PHEX, its physiologically relevant substrate protein(s) have not been identified. Here, we investigated two SIBLING proteins containing the ASARM motif—osteopontin (OPN) and bone sialoprotein (BSP)—as potential substrates for PHEX. Using cleavage assays, gel electrophoresis, and mass spectrometry, we report that OPN is a full-length protein substrate for PHEX. Degradation of OPN was essentially complete, including hydrolysis of the ASARM motif, resulting in only very small residual fragments. Western blotting of Hyp (the murine homolog of human XLH) mouse bone extracts having no PHEX activity clearly showed accumulation of an ∼35 kDa OPN fragment that was not present in wild-type mouse bone. Immunohistochemistry and immunogold labeling (electron microscopy) for OPN in Hyp bone likewise showed an accumulation of OPN and/or its fragments compared with normal wild-type bone. Incubation of Hyp mouse bone extracts with PHEX resulted in the complete degradation of these fragments. In conclusion, these results identify full-length OPN and its fragments as novel, physiologically relevant substrates for PHEX, suggesting that accumulation of mineralization-inhibiting OPN fragments may contribute to the mineralization defect seen in the osteomalacic bone characteristic of XLH/HYP. © 2013 American Society for Bone and Mineral Research.
The US postmarketing surveillance study of adult osteosarcoma and teriparatide: Study design and findings from the first 7 years
Authors: Andrews Elizabeth B , Gilsenan Alicia W , Midkiff Kirk , Sherrill Beth , Wu Yun , Mann Beth H , Masica Daniel 
Published: September 2012

Abstract
The Osteosarcoma Surveillance Study, an ongoing 15-year surveillance study initiated in 2003, is a postmarketing commitment to the United States (US) Food and Drug Administration to evaluate a potential association between teriparatide, rhPTH(1–34), a recombinant human parathyroid hormone analog (self-injectable medication to treat osteoporosis), and development of osteosarcoma in response to a finding from preclinical (animal) studies. Incident cases of primary osteosarcoma diagnosed in adults (aged ≥40 years) on or after January 1, 2003, are identified through population-based state, regional, and comprehensive cancer center registries in the US. Information on possible prior treatment with teriparatide, on demographics, and on risk factors is ascertained by patient or proxy telephone interview after patient consent. Between June 2004 and September 30, 2011, 1448 cases (diagnosed 2003 to 2009) were identified by participating cancer registries (estimated to be 62% of all adult cases in the US for that time period); 549 patients or proxies were interviewed. Interviewed patients were similar to noninterviewed patients with regard to mean age, sex, race, and geographical distribution and tumor type and site of tumor. Mean age of those interviewed was 61 years, 46% were female, 86% were white, and 77% were alive when the case was reported to the study investigators. Data collected in the study provide descriptive information on a large number of adults with osteosarcoma, an uncommon malignant bone tumor. After 7 years of the study, there were no osteosarcoma patients who had a prior history of teriparatide treatment. Thus, approximately halfway through this 15-year study, the study has not detected a pattern indicative of a causal association between teriparatide treatment and osteosarcoma in humans. © 2012 American Society for Bone and Mineral Research.
miR‐200c enhances radiosensitivity of human breast cancer cells
Authors: Lin Jing , Liu Cong , Gao Fu , Mitchel R.E.J. , Zhao Luqian , Yang Yanyong , Lei Jixiao , Cai Jianming 
Published: September 2012

AbstractDue to the intrinsic resistance of many tumors to radiotherapy, current methods to improve the survival of cancer patients largely depend on increasing tumor radiosensitivity. It is well‐known that miR‐200c inhibits epithelial–mesenchymal transition (EMT), and enhances cancer cell chemosensitivity. We sought to clarify the effects of miR‐200c on the radiosensitization of human breast cancer cells. In this study, we found that low levels of miR‐200c expression correlated with radiotolerance in breast cancer cells. miR‐200c overexpression could increase radiosensitivity in breast cancer cells by inhibiting cell proliferation, and by increasing apoptosis and DNA double‐strand breaks. Additionally, we found that miR‐200c directly targeted TANK‐binding kinase 1 (TBK1). However, overexpression of TBK1 partially rescued miR‐200c mediated apoptosis induced by ionizing radiation. In summary, miR‐200c can be a potential target for enhancing the effect of radiation treatment on breast cancer cells. J. Cell. Biochem. 114: 606–615, 2013. © 2012 Wiley Periodicals, Inc.
Diethyl Hexyl Phthalate (DEHP) is associated with insulin resistance in adipose tissue of male rat: Protective role of antioxidant vitamins (C & E)
Authors: Rajesh Parsanathan , Sathish Sampath , Srinivasan Chinnapaiyan , Selvaraj Jayaraman , Balasubramanian Karundevi 
Published: September 2012

AbstractDiethyl hexyl phthalate (DEHP) is a plasticizer, commonly used in a variety of products, including lubricants, perfumes, hairsprays and cosmetics, construction materials, wood finishers, adhesives, floorings and paints. DEHP is an endocrine disruptor and it has a continuum of influence on various organ systems in human beings and experimental animals. However, specific effects of DEHP on insulin signaling in adipose tissue are not known. Adult male albino rats of Wistar strain were divided into four groups. Control, DEHP treated (dissolved in olive oil at a dose of 10, and 100 mg/kg body weight, respectively, once daily through gastric intubations for 30 days) and DEHP + vitamin E (50 mg/kg body weight) and C (100 mg/kg body weight) dissolved in olive oil and distilled water, respectively, once daily through gastric intubations for 30 days. After the completion of treatment, adipose tissue was dissected out to assess various parameters. DEHP treatment escalated H2O2 and hydroxyl radical levels as well as lipid peroxidation in the adipose tissue. DEHP impaired the expression of insulin signaling molecules and their phosphorelay pathways leading to diminish plasma membrane GLUT4 level and thus decreased glucose uptake and oxidation. Blood glucose level was elevated as a result of these changes. Supplementation of vitamins (C & E) prevented the DEHP‐induced changes. It is concluded that DEHP‐induced ROS and lipid peroxidation disrupts the insulin signal transduction in adipose tissue and favors glucose intolerance. Antioxidant vitamins have a protective role against the adverse effect of DEHP. J. Cell. Biochem. 114: 558–569, 2013. © 2012 Wiley Periodicals, Inc.
A novel tumor metastasis suppressor gene LASS2/TMSG1 interacts with vacuolar ATPase through its homeodomain
Authors: Yu Wenjuan , Wang Leiming , Wang Yuewei , Xu Xiaoyan , Zou Pengcheng , Gong Miaozi , Zheng Jie , You Jiangfeng , Wang Hua , Mei Fang , Pei Fei 
Published: September 2012

AbstractLASS2/TMSG1 was a novel tumor metastasis suppressor gene, which was first cloned by our laboratory from non‐metastatic and metastatic cancer cell variants of human prostate carcinoma PC‐3M using mRNA differential display in 1999. LASS2/TMSG1 could interact with the C subunit of vacuolar ATPase (V‐ATPase, ATP6V0C) and regulate V‐ATPase activity. In an attempt to provide molecular mechanism of the interaction between LASS2/TMSG1 and V‐ATPase, we constructed four variant transfectants containing different functional domain of LASS2/TMSG1 and stably transfected the variants to human prostate cancer cell line PC‐3M‐1E8 cell with high metastatic potential. Results showed that there were no obvious differences of V‐ATPase expression among different transfected cells and the control. However, V‐ATPase activity and intracellular pH was significantly higher in the variant transfectants with Homeodomain of LASS2/TMSG1 than that in the control using the pH‐dependent fluorescence probe BECEF/AM. Immunoprecipitation, immunofluorescence and immuno‐electron microscope alone or in combination demonstrated the direct interaction of Homeodomain of LASS2/TMSG1 and ATP6V0C. Loss of Homeodomain markedly enhanced the proliferation ability but weakened the apoptotic effect of LASS2/TMSG1 in PC‐3M‐1E8 cells. These lines of results for the first time contribute to the conclusion that LASS2/TMSG1 could regulate V‐ATPase activity and intracellular pH through the direct interaction of its Homeodomain and the C subunit of V‐ATPase. Their interaction could play important roles in the apoptosis of tumor cells. J. Cell. Biochem. 114: 570–583, 2013. © 2012 Wiley Periodicals, Inc.
Role of inflammatory mechanisms in pathogenesis of type 2 diabetes mellitus
Authors: Akash Muhammad Sajid Hamid , Rehman Kanwal , Chen Shuqing 
Published: September 2012

AbstractType 2 diabetes mellitus (T2DM) is characterized by progressive β‐cell dysfunctioning and insulin resistance. This article reviews recent literature with special focus on inflammatory mechanisms that provoke the pathogenesis of T2DM. We have focused on the recent advances in progression of T2DM including various inflammatory mechanisms that might induce inflammation, insulin resistance, decrease insulin secretion from pancreatic islets and dysfunctioning of β‐cells. Here we have also summarized the role of various pro‐inflammatory mediators involved in inflammatory mechanisms, which may further alter the normal structure of β‐cells by inducing pancreatic islet's apoptosis. In conclusion, it is suggested that the role of inflammation in pathogenesis of T2DM is crucial and cannot be neglected. Moreover, the insight of inflammatory responses in T2DM may provide a new gateway for the better treatment of diabetes mellitus. J. Cell. Biochem. 114: 525–531, 2013. © 2012 Wiley Periodicals, Inc.
Signet ring cell mixed histology may show more aggressive behavior than other histologies in early gastric cancer
Authors: Huh Cheal Wung , Jung Da Hyun , Kim Jie‐Hyun , Lee Yong Chan , Kim Hyunki , Kim Hoguen , Yoon Sun Och , Youn Young Hoon , Park Hyojin , Lee Sang In , Choi Seung Ho , Cheong Jae‐Ho , Noh Sung Hoon 
Published: September 2012

AbstractBackgroundSignet ring cell carcinoma (SRC) of the stomach is known to have different microscopic and biologic characteristics compared to non‐SRC. The pathologic report has documented partly SRC component with main histologies. However, the clinical significance of SRC mixture has not been reported. Aim was to investigate clinicopathologic features of mixed‐SRC histology in early gastric cancer (EGC).MethodsTwo thousand two hundred eight patients were diagnosed with EGC and underwent surgery. The patients were divided into three groups such as adenocarcinoma with partly SRC (mixed‐SRC group), only adenocarcinoma (adenocarcinoma group), and SRC (SRC group). Clinicopathologic characteristics were compared.ResultsThe SRC group was more associated with younger age, female, mid‐body, mucosa‐confined, depressed type, lower lymph node metastasis (LNM), lower lymphovascular invasion, and better survival rate than adenocarcinoma group. The mixed‐SRC group was more associated with younger age, female, upper‐body, and depressed type than adenocarcinoma group, similar to SRC group. However, the mixed‐SRC group showed more submucosal invasion, larger size, and higher LNM than other groups. The mixed‐SRC component was one of the independent risk factors of LNM.ConclusionsMixed‐SRC histology in EGC showed more aggressive behavior than other histologies. Clinical considerations of mixed‐SRC histology may be helpful to decide on a specific cancer treatment. J. Surg. Oncol. 2013;107:124–129. © 2012 Wiley Periodicals, Inc.
Rheological and thermal behaviors of commercial poly(aryletherketone)s
Authors: White Kevin L. , Jin Lin , Ferrer Nangelie , Wong Minhao , Bremner Tim , Sue Hung‐Jue 
Published: September 2012

AbstractThe mechanical properties and thermal stability of several grades of poly(aryletherketone)s (PAEKs) were investigated using thermal, rheological, and dynamic mechanical characterization. Detailed rheological characterization revealed that several grades of poly(etheretherketone) (PEEK) exhibit relaxation behavior characteristic of a long‐chain branched structure. The potentially branched PEEKs showed greater mechanical damping behavior than the linear‐chain PEEKs. The molecular weight dependence on zero‐shear viscosity for several linear‐chain polymers indicates that the PEEKs behave as rigid chains in the melt. Differences in chain structure do not significantly influence dynamic mechanical behavior in the solid state but affect stability at elevated temperatures. The potentially branched PEEKs are most susceptible to oxidation in air, but exhibit much greater stability in nitrogen. Poly(etherketone) is highly susceptible to degradation in both air and nitrogen environments. Implications of this study for development of high‐performance PAEKs are discussed. POLYM. ENG. SCI. 2013. © 2012 Society of Plastics Engineers