bluuebunny/crossref_metadata_2025 huggingface dataset:
Financial Development and Money Demand Function: Cointegration, Causality and Variance Decomposition Analysis for Pakistan
Authors: Ahad Muhammad
Published: May 2017

This study has investigated money demand function incorporating financial development, industrial production, income and exchange rate for Pakistan for time span from 1972 to 2012. Bayer–Hanck combined cointegration and Johansen cointegration approaches have been used to test cointegration among variables and vector error correction model (VECM) approach has been applied to explain the direction of causality in the long run and short run. Unit root problem has been tested by augmented Dickey–Fuller (ADF) and Phillips–Perron (PP) unit root tests. The results indicate that feedback effect is found between financial development and money demand. There is a long-run relationship existing among money demand, financial development, income, industrial production and exchange rate. Financial development is the main factor to determine money demand function in both long run and short run.
Exploring Senior Living Alternatives to Institutional Care: Differences between Residents and Non-residents
Authors: Reisenwitz Timothy H.
Published: May 2017

The demand for senior living will continue to increase as America ages. There are various types of senior living facilities, but continuing care retirement communities (CCRCs), or life care communities, have become quite popular. They offer a wide selection of services for residents. This study focused on a particular CCRC and examined the differences between two groups: CCRC residents and non-residents, that is, those who considered CCRC residency but decided against it. First, a consumer profile was developed, detailing the characteristics of the typical CCRC resident. Then, various psychographic variables were analyzed to compare the two groups: cognitive age, advice from friends, family and salespeople, attitude towards the advertising, involvement and self-image or self-concept. T-tests revealed significant differences between groups regarding cognitive age, salespeople advice and self-image or self-concept. Implications for marketers are discussed and directions for future research are provided.
Survival improvement in patients with non–small cell lung cancer between 1983 and 2012: Analysis of the Surveillance, Epidemiology, and End Results database
Authors: Wang Shuncong , Sun Tiantian , Sun Huanhuan , Li Xiaobo , Li Jie , Zheng Xiaobin , Mallampati Saradhi , Sun Hongliu , Zhou Xiuling , Zhou Cuiling , Zhang Hongyu , Cheng Zhibin , Ma Haiqing
Published: May 2017

Non–small cell lung cancer is the most common malignancy in males; it constitutes the majority of lung cancer cases and requires massive medical resources. Despite improvements in managing non–small cell lung cancer, long-term survival remains very low. This study evaluated survival improvement in patients with non–small cell lung cancer in each decade between 1983 and 2012 to determine the impact of race, sex, age, and socioeconomic status on the survival rates in these patients. We extracted data on non–small cell lung cancer cases in each decade between 1983 and 2012 from the Surveillance, Epidemiology, and End Results registries. In total, 573,987 patients with non–small cell lung cancer were identified in 18 Surveillance, Epidemiology, and End Results registry regions during this period. The 12-month relative survival rates improved slightly across three decades, from 39.7% to 40.9% to 45.5%, with larger improvement in the last two decades. However, the 5-year-relative survival rates were very low, with 14.3%, 15.5%, and 18.4%, respectively, in three decades, indicating the urgency for novel comprehensive cancer care. In addition, our data demonstrated superiority in survival time among non–small cell lung cancer patients of lower socioeconomic status and White race. Although survival rates of non–small cell lung cancer patients have improved across the three decades, the 5-year-relative survival rates remain very poor. In addition, widening survival disparities among the race, the sex, and various socioeconomic status groups were confirmed. This study will help in predicting future tendencies of incidence and survival of non–small cell lung cancer, will contribute to better clinical trials by balancing survival disparities, and will eventually improve the clinical management of non–small cell lung cancer.
Ginsenoside 20(S)-Rg3 suppresses ovarian cancer migration via hypoxia-inducible factor 1 alpha and nuclear factor-kappa B signals
Authors: Liu Ting , Zhao Le , Hou Huilian , Ding Lu , Chen Wei , Li Xu
Published: May 2017

Hypoxia-inducible factor 1 is believed to play a prominent role in the survival and developing progress of cancers. As a result, inhibiting α subunit of hypoxia-inducible factor 1 represents an attractive strategy against tumor. Although hypoxia-inducible factor 1α is a hypoxia-regulated subunit, increasing evidence indicates that hypoxia-inducible factor 1α could stable expression under normoxic conditions, regulated by non-hypoxia-mediated mechanisms. However, there are few strategies to target hypoxia-inducible factor 1α under normoxic conditions. Here, we report that ginsenoside 20(S)-Rg3, one of the main active ingredients in red ginseng, restrains hypoxia-inducible factor 1α expression under normal oxygen levels in human ovarian cancer cell lines, SKOV3 and 3AO, which leads to potently inhibits migration of ovarian cancer in vitro and in vivo. 20(S)-Rg3 could decrease the expression of hypoxia-inducible factor 1α by upregulation of prolyl hydroxylase domain protein 1 to promoting hypoxia-inducible factor 1α ubiquitin–proteasome degradation under normal oxygen levels. Furthermore, 20(S)-Rg3 could attenuate the expression of nuclear factor-κ B, which may be another possible mechanism for 20(S)-Rg3 to block ovarian cancer migration. Taken together, our study suggests that 20(S)-Rg3 is a strong inhibitor of hypoxia-inducible factor 1α, which may provide a novel agent for future treatments for ovarian cancer.
Metformin augments doxorubicin cytotoxicity in mammary carcinoma through activation of adenosine monophosphate protein kinase pathway
Authors: El-Ashmawy Nahla E , Khedr Naglaa F , El-Bahrawy Hoda A , Abo Mansour Hend E
Published: May 2017

Since the incidence of breast cancer increases dramatically all over the world, the search for effective treatment is an urgent need. Metformin has demonstrated anti-tumorigenic effect both in vivo and in vitro in different cancer types. This work was designed to examine on molecular level the mode of action of metformin in mice bearing solid Ehrlich carcinoma and to evaluate the use of metformin in conjunction with doxorubicin as a combined therapy against solid Ehrlich carcinoma. Ehrlich ascites carcinoma cells were inoculated in 60 female mice as a model of breast cancer. The mice were divided into four equal groups: Control tumor, metformin, doxorubicin, and co-treatment. Metformin (15 mg/kg) and doxorubicin (4 mg/kg) were given intraperitoneally (i.p.) for four cycles every 5 days starting on day 12 of inoculation. The anti-tumorigenic effect of metformin was mediated by enhancement of adenosine monophosphate protein kinase activity and elevation of P53 protein as well as the suppression of nuclear factor-kappa B, DNA contents, and cyclin D1 gene expression. Metformin and doxorubicin mono-treatments exhibited opposing action regarding cyclin D1 gene expression, phosphorylated adenosine monophosphate protein kinase, and nuclear factor-kappa B levels. Co-treatment markedly decreased tumor volume, increased survival rate, and improved other parameters compared to doxorubicin group. In parallel, the histopathological findings demonstrated enhanced apoptosis and absence of necrosis in tumor tissue of co-treatment group. Metformin proved chemotherapeutic effect which could be mediated by the activation of adenosine monophosphate protein kinase and related pathways. Combining metformin and doxorubicin, which exhibited different mechanisms of action, produced greater efficacy as anticancer therapeutic regimen.
Beyond circulating microRNA biomarkers: Urinary microRNAs in ovarian and breast cancer
Authors: Gasparri Maria Luisa , Casorelli Assunta , Bardhi Erlisa , Besharat Aris Raad , Savone Delia , Ruscito Ilary , Farooqi Ammad Ahmad , Papadia Andrea , Mueller Michael David , Ferretti Elisabetta , Benedetti Panici Pierluigi
Published: May 2017

Breast cancer is the most common malignancy in women worldwide, and ovarian cancer is the most lethal gynecological malignancy. Women carrying a BRCA1/2 mutation have a very high lifetime risk of developing breast and ovarian cancer. The only effective risk-reducing strategy in BRCA-mutated women is a prophylactic surgery with bilateral mastectomy and bilateral salpingo-oophorectomy. However, many women are reluctant to undergo these prophylactic surgeries due to a consequent mutilated body perception, unfulfilled family planning, and precocious menopause. In these patients, an effective screening strategy is available only for breast cancer, but it only consists in close radiological exams with a significant burden for the health system and a significant distress to the patients. No biomarkers have been shown to effectively detect breast and ovarian cancer at an early stage. MicroRNAs (miRNAs) are key regulatory molecules operating in a post-transcriptional regulation of gene expression. Aberrant expression of miRNAs has been documented in several pathological conditions, including solid tumors, suggesting their involvement in tumorigenesis. miRNAs can be detected in blood and urine and could be used as biomarkers in solid tumors. Encouraging results are emerging in gynecological malignancy as well, and suggest a different pattern of expression of miRNAs in biological fluids of breast and ovarian cancer patients as compared to healthy control. Aim of this study is to highlight the role of the urinary miRNAs which are specifically associated with cancer and to investigate their role in early diagnosis and in determining the prognosis in breast and ovarian cancer.
Cytotoxic effect of celastrol alone or in combination with paclitaxel on anaplastic thyroid carcinoma cells
Authors: Kim Si Hyoung , Kang Jun Goo , Kim Chul Sik , Ihm Sung-Hee , Choi Moon Gi , Yoo Hyung Joon , Lee Seong Jin
Published: May 2017

The influence of celastrol alone or in combination with paclitaxel on survival of anaplastic thyroid carcinoma cells was investigated. In 8505C and SW1736 cells, after treatment of celastrol, cell viability decreased, and cytotoxic activity increased. The protein levels of heat shock protein (hsp) 90, hsp70, Bax, death receptor 5, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase, phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), and phospho-c-Jun N-terminal kinase (JNK) were elevated, and those of Bcl2, phospho-nuclear factor-kappaB (NF-κB), and total and phospho-Akt were reduced. The endoplasmic reticulum stress markers expression and reactive oxygen species production were enhanced. In celastrol-treated cells, N-acetylcysteine increased cell viability and phospho-NF-κB protein levels, and decreased reactive oxygen species production and cytotoxic activity. The protein levels of cyclooxygenase 2, phospho-ERK1/2, phospho-JNK and Bip were diminished. After treatment of both celastrol and paclitaxel, compared with paclitaxel alone, cell viability and the percentage of viable cells were reduced, and death rate and cytotoxic activity were elevated. The protein levels of phospho-ERK1/2, phospho-JNK, Bip, and cyclooxygenase 2, and reactive oxygen species production were enhanced. All of the Combination Index values calculated by Chou–Talalay equation were lower than 1.0, implying the synergism between celastrol and paclitaxel in induction of cell death. In conclusion, our results suggest that celastrol induces cytotoxicity through involvement of Bcl2 family proteins and death receptor, and modulation of phospho-NF-κB, Akt, and mitogen-activated protein kinase in association with endoplasmic reticulum stress and reactive oxygen species production in anaplastic thyroid carcinoma cells. Moreover, celastrol synergizes with paclitaxel in induction of cytotoxicity in anaplastic thyroid carcinoma cells.
Fibroblast growth factor receptors in breast cancer
Authors: Wang Shuwei , Ding Zhongyang
Published: May 2017

Fibroblast growth factor receptors are growth factor receptor tyrosine kinases, exerting their roles in embryogenesis, tissue homeostasis, and development of breast cancer. Recent genetic studies have identified some subtypes of fibroblast growth factor receptors as strong genetic loci associated with breast cancer. In this article, we review the recent epidemiological findings and experiment results of fibroblast growth factor receptors in breast cancer. First, we summarized the structure and physiological function of fibroblast growth factor receptors in humans. Then, we discussed the common genetic variations in fibroblast growth factor receptors that affect breast cancer risk. In addition, we also introduced the potential roles of each fibroblast growth factor receptors isoform in breast cancer. Finally, we explored the potential therapeutics targeting fibroblast growth factor receptors for breast cancer. Based on the biological mechanisms of fibroblast growth factor receptors leading to the pathogenesis in breast cancer, targeting fibroblast growth factor receptors may provide new opportunities for breast cancer therapeutic strategies.
Grainyhead-like 2 in development and cancer
Authors: Ma Lijun , Yan Hongli , Zhao Hui , Sun Jianmin
Published: May 2017

Grainyhead-like 2 is a human homolog of Drosophila grainyhead. It inhibits epithelial-to-mesenchymal transition that is necessary for cell migration, and it is involved in neural tube closure, epithelial morphogenesis, and barrier formation during embryogenesis by regulation of the expression of cell junction proteins such as E-cadherin and vimentin. Cancer shares many common characters with development such as epithelial-to-mesenchymal transition. In addition to its important role in development, grainyhead-like 2 is implicated in carcinogenesis as well. However, the reports on grainyhead-like 2 in various cancers are controversial. Grainyhead-like 2 can act as either a tumor suppressor or an oncogene with the mechanisms not well elucidated. In this review, we summarized recent progress on grainyhead-like 2 in development and cancer in order to get an insight into the regulation network of grainyhead-like 2 and understand the roles of grainyhead-like 2 in various cancers.
Next-generation sequencing for endocrine cancers: Recent advances and challenges
Authors: Suresh Padmanaban S , Venkatesh Thejaswini , Tsutsumi Rie , Shetty Abhishek
Published: May 2017

Contemporary molecular biology research tools have enriched numerous areas of biomedical research that address challenging diseases, including endocrine cancers (pituitary, thyroid, parathyroid, adrenal, testicular, ovarian, and neuroendocrine cancers). These tools have placed several intriguing clues before the scientific community. Endocrine cancers pose a major challenge in health care and research despite considerable attempts by researchers to understand their etiology. Microarray analyses have provided gene signatures from many cells, tissues, and organs that can differentiate healthy states from diseased ones, and even show patterns that correlate with stages of a disease. Microarray data can also elucidate the responses of endocrine tumors to therapeutic treatments. The rapid progress in next-generation sequencing methods has overcome many of the initial challenges of these technologies, and their advantages over microarray techniques have enabled them to emerge as valuable aids for clinical research applications (prognosis, identification of drug targets, etc.). A comprehensive review describing the recent advances in next-generation sequencing methods and their application in the evaluation of endocrine and endocrine-related cancers is lacking. The main purpose of this review is to illustrate the concepts that collectively constitute our current view of the possibilities offered by next-generation sequencing technological platforms, challenges to relevant applications, and perspectives on the future of clinical genetic testing of patients with endocrine tumors. We focus on recent discoveries in the use of next-generation sequencing methods for clinical diagnosis of endocrine tumors in patients and conclude with a discussion on persisting challenges and future objectives.
The long noncoding RNA urothelial carcinoma-associated 1 overexpression as a poor prognostic biomarker in clear cell renal cell carcinoma
Authors: Wang Yang , Gao Wen , Xu Jiali , Zhu Yizhi , Liu Lingxiang
Published: May 2017

Long noncoding RNA urothelial carcinoma-associated 1 has previously played important roles in cancer. However, its role is still unknown in clear cell renal cell carcinoma. We utilized the most recent molecular and clinical data of clear cell renal cell carcinoma from The Cancer Genome Atlas project, and the relationship between urothelial carcinoma-associated 1 expression and the clinicopathological features was analyzed. Our results indicated that urothelial carcinoma-associated 1 overexpression was associated with male ( p = 0.003), wild-type PBRM1 ( p = 0.021), and BAP1 mutation ( p = 0.022) in clear cell renal cell carcinoma, although lower expression was found in tumors compared with normal controls, validated in tumor tissues from The Cancer Genome Atlas and 21 clear cell renal cell carcinoma patients at our hospital. Moreover, urothelial carcinoma-associated 1 overexpression indicated poor prognosis independently (Hazard Ratio [HR]: 1.92, p = 0.000) in clear cell renal cell carcinoma; it might be a potential detrimental gene considered as a predictive biomarker involved in clear cell renal cell carcinoma.
microRNAs: Emerging players in oral cancers and inflammatory disorders
Authors: Kulkarni Varun , Uttamani Juhi Raju , Naqvi Afsar Raza , Nares Salvador
Published: May 2017

Association of oral diseases and disorders with altered microRNA profiles is firmly recognized. These evidences support the potential use of microRNAs as therapeutic tools for diagnosis, prognosis, and treatment of various diseases. In this review, we highlight the association of altered microRNA signatures in oral cancers and oral inflammatory diseases. Advances in our ability to detect microRNAs in human sera and saliva further highlight their clinical value as potential biomarkers. We have discussed key mechanisms underlying microRNA dysregulation in pathological conditions. The use of microRNAs in diagnostics and their potential therapeutic value in the treatment of oral diseases are reviewed.
Laparoscopic subperitoneal injection of chemo-loaded particles lowers tumor growth on a rabbit model of peritoneal carcinomatosis
Authors: Pascale Florentina , Fazel Afshin , Namur Julien , Ghegediban Saida-Homayra , D’Inca Hadrian , Wassef Michel , Moine Laurence , Laurent Alexandre
Published: May 2017

The purpose of our study was to assess the effect of controlled-release chemotherapy on the growth and viability of peritoneal carcinomatosis treated by subperitoneal injection in a rabbit VX2 model. A model of peritoneal carcinomatosis was created by laparoscopic injection of VX2 tumor in the left and right broad ligaments of 12 White New Zealand rabbits. At day 12, each tumor was randomly treated with a peritumoral injection of 0.5 mL microspheres loaded with doxorubicin (DEM-DOX) or unloaded (DEM-BLAND). Seven days after treatment, tumor volume, tumor viability in histology, local tumor necrosis in contact with DEM, and doxorubicin concentration profile around the drug eluting microspheres (DEM) were measured. Tumor volume was significantly lower in the DEM-DOX group (3.6 ± 3.2 cm3) compared with the DEM-BLAND group (8.9 ± 5.4 cm3) (p = 0.0425). The percentage of viable tumor tissue was significantly lower in the DEM-DOX group (38% ± 17%) compared with the DEM-BLAND group (56% ± 20%) (p = 0.0202). Tissue necrosis was observed around all DEM-DOX up to a distance of 1.094 ± 0.852 mm and never observed around DEM-BLAND. Drug concentration was above the therapeutic level of 1.0 µM up to a distance of 1.4 mm from the DEM to the tumor. Laparoscopic subperitoneal injection of chemo-loaded particles is feasible and lowers tumor growth and viability in a rabbit model of peritoneal carcinomatosis after 1 week.
Upregulated Vav2 in gastric cancer tissues promotes tumor invasion and metastasis
Authors: Tan Bi-bo , Li Yong , Fan Li-qiao , Zhao Qun , Liu Qing-wei , Liu Yü , Wang Dong , Jia Nan
Published: May 2017

Several studies have proved that Vav2 gene is associated with the carcinogenesis of some tumors, but the relationship between Vav2 gene and gastric cancer remains unclear. Purpose of this study is to detect the expression of Vav2 protein in gastric cancer tissues and to evaluate the clinical value of Vav2. Furthermore, both effect of Vav2 gene on invasion and metastasis of gastric cancer cells and its mechanism are investigated in vitro. Results showed that positive rate of Vav2 protein was significantly higher in gastric cancer tissues than in adjacent tissues and notably higher in metastatic lymph nodes than in gastric cancer tissues. Results of western blot were consistent with immunohistochemistry. Expression of Vav2 protein in gastric cancer tissues was related to degree of tumor differentiation, lymph node metastasis, and clinical stages. Inhibition of endogenous Vav2 in BGC823 cells led to significantly decreased cell activity, migration, and invasion ability in vitro, and expression of Rac1, MMP-2, and MMP-9 decreased, whereas expression of TIMP-1 increased. We concluded that Vav2 might promote invasion and metastasis of gastric cancer by regulating some invasion and metastasis-related genes.
Altered expression of small leucine-rich proteoglycans (Decorin, Biglycan and Lumican): Plausible diagnostic marker in urothelial carcinoma of bladder
Authors: Appunni Sandeep , Anand Vivek , Khandelwal Madhuram , Seth Amlesh , Mathur Sandeep , Sharma Alpana
Published: May 2017

Small leucine-rich proteoglycans are components of extracellular matrix that regulates neoplastic transformation. Among small leucine rich proteoglycans, Decorin, Biglycan and Lumican are most commonly implicated markers, and their expression is well studied in various malignancies. In this novel study, we have collectively evaluated expression of these three molecules in urothelial carcinoma of bladder. Thirty patients of confirmed untreated bladder cancer, 30 healthy controls for blood and 30 controls for adjacent non-tumour tissue were enrolled. Blood was collected from all subjects and tumour/adjacent normal tissue was obtained from the patients. Circulatory levels were estimated by enzyme-linked immunosorbent assay, relative messenger RNA expression by quantitative polymerase chain reaction and protein expression by immunohistochemistry and western-blotting. Circulatory levels of Biglycan (p = 0.0038) and Lumican (p < 0.0001) were significantly elevated, and that of Decorin (p < 0.0001) was significantly reduced in patients as compared with controls. Protein expression by immunohistochemistry and western-blotting showed elevated expression of Lumican and Biglycan and lower expression of Decorin in urothelial carcinoma of bladder. Quantitative polymerase chain reaction for messenger RNA expression from tissue specimens revealed significantly higher expression of Biglycan (p = 0.0008) and Lumican (p = 0.01) and lower expression of Decorin (p < 0.0001) in urothelial carcinoma of bladder. Out of all molecules receiver operating characteristic curve showed that the 0.207 ng/ml cut-off of serum Lumican provided optimum sensitivity (90.0%) and specificity (90.0%). Significant alteration of matrix small leucine-rich proteoglycans in urothelial carcinoma of bladder was observed. Higher expression of Lumican in Bladder cancer patients with the cut-off value of highest optimum sensitivity and specificity shows its importance as a potential non-invasive marker for early detection of UBC following further validation in large patient cohort.
Study of the TP53 codon 72 polymorphism in oral cancer and oral potentially malignant disorders in Argentine patients
Authors: Zarate Ana Maria , Don Julieta , Secchi Dante , Carrica Andres , Galindez Costa Fernanda , Panico Rene , Brusa Martin , Barra José Luis , Brunotto Mabel
Published: May 2017

The aim of this work was to evaluate the prevalence of TP53Arg72Pro mutations and their possible relationship with oral carcinoma and oral potentially malignant disorders in Argentine patients. A cross-sectional study was performed on 111 exfoliated cytologies from patients with oral cancer (OC), oral potentially malignant disorders (OPMD) and controls. The TP53Arg72Pro mutations were determined using conventional PCR. We evaluated univariate and multivariate study variables, setting p < 0.05. We found: (a) a low frequency of Pro72 variant in control group and a high frequency in OC and OPMD, as well in OC and oral leukoplakia (OL) diagnosis; (b) multivariate association among the TP53CC genotype and females over 45 years with no tobacco nor alcohol habits with oral lichen planus pathology; (c) multivariate association between the TP53GC genotype and males with alcohol and tobacco habits and OC and OL pathologies. Our results showed that the wild-type Arg72variant was related to control patients and Pro72variant was related to OC and OPMD, in Argentine patients.
The c-Met receptor: Implication for targeted therapies in colorectal cancer
Authors: Safaie Qamsari Elmira , Safaei Ghaderi Sepideh , Zarei Bahareh , Dorostkar Ruhollah , Bagheri Salman , Jadidi-Niaragh Farhad , Somi Mohammad Hossein , Yousefi Mehdi
Published: May 2017

c-Met (mesenchymal–epithelial transition factor) is a tyrosine kinase receptor activated by hepatocyte growth factor and regulates multiple biological processes, such as cell scattering, survival, and proliferation. Aberrant c-Met signaling has been implicated in a variety of cancer types, including colorectal cancer. c-Met is genetically altered through various mechanisms that is associated with colorectal cancer progression and metastasis. Especially, in colorectal cancer, preclinical evidence for the aberrant activation of the c-Met signaling exists. Accordingly, molecular targeting of c-Met receptor could be a promising strategy, in the treatment of colorectal cancer patients. Recently, it was also shown that crosstalk between c-Met and other cell surface receptors attributes to tumorigenesis and development of therapeutic resistance. Characterization of the molecular mechanisms through which c-Met crosstalks with other receptors in favor of tumor formation and progression remains to explore. This review will describe the mechanisms of aberrant c-Met signaling in colorectal cancer and discuss on additional roles for c-Met receptor through crosstalk with other tyrosine kinase receptors and cell surface proteins in colorectal cancer. Novel therapeutic approaches for c-Met pathway targeting will also be discussed.
Focal adhesion kinase inhibitor PF573228 and death receptor 5 agonist lexatumumab synergistically induce apoptosis in pancreatic carcinoma
Authors: Zhao Xiangxuan , Sun Wei , Puszyk William M , Wallet Shannon , Hochwald Steve , Robertson Keith , Liu Chen
Published: May 2017

Pancreatic cancer has one of the lowest survival rates of all cancers. The mechanism underlying chemo-resistance of pancreatic cancer is not well understood. Our previous article reported that small molecule YM155 induced apoptosis in pancreatic cancer cells via activation of death receptor 5. In this study, we aim to continuously address death receptor 5–mediated apoptosis in chemo-resistant pancreatic carcinoma. We found that in comparison to paired pancreatic cancer tissues and adjacent normal tissues, five of the six cancer tissues had downregulated death receptor 5 and upregulated Bcl-xL. Mono treatment with lexatumumab was not sufficient to induce apoptosis in pancreatic cancer cells, whereas focal adhesion kinase inhibitor PF573228 significantly sensitized lexatumumab-induced apoptosis. Western blotting analysis revealed that lexatumumab and PF573228 combination treatment increased death receptor 5 but decreased Bcl-xL expression. Interestingly, pre-treatment with Bcl-xL inhibitor ABT263 reversed the insensitivity of panc-1 cells to lexatumumab or PF573228-induced apoptosis. Specific small interfering RNA-mediated gene silencing of Bcl-xL effectively sensitized pancreatic cancer cells to lexatumumab or PF573228-induced apoptosis. Furthermore, lexatumumab and PF573228 combination was shown to exhibit significant xenograft pancreatic tumor growth inhibition in SCID mice. Our data provide fundamental evidence to support the notion that lexatumumab and PF573228 co-treatment could be a potentially effective regime for patients with pancreatic cancer.
Leptin acts on neoplastic behavior and expression levels of genes related to hypoxia, angiogenesis, and invasiveness in oral squamous cell carcinoma
Authors: Sobrinho Santos Eliane Macedo , Guimarães Talita Antunes , Santos Hércules Otacílio , Cangussu Lilian Mendes Borborema , de Jesus Sabrina Ferreira , Fraga Carlos Alberto de Carvalho , Cardoso Claudio Marcelo , Santos Sérgio Henrique Souza , de Paula Alfredo Maurício Batista , Gomez Ricardo Santiago , Guimarães André Luiz Sena , Farias Lucyana Conceição
Published: May 2017

Leptin, one of the main hormones controlling energy homeostasis, has been associated with different cancer types. In oral cancer, its effect is not well understood. We investigated, through in vitro and in vivo assays, whether leptin can affect the neoplastic behavior of oral squamous cell carcinoma. Expression of genes possibly linked to the leptin pathway was assessed in leptin-treated oral squamous cell carcinoma cells and also in tissue samples of oral squamous cell carcinoma and oral mucosa, including leptin, leptin receptor, hypoxia-inducible factor 1-alpha, E-cadherin, matrix metalloproteinase-2, matrix metalloproteinase-9, Col1A1, Ki67, and mir-210. Leptin treatment favored higher rates of cell proliferation and migration, and reduced apoptosis. Accordingly, leptin-treated oral squamous cell carcinoma cells show decreased messenger RNA caspase-3 expression, and increased levels of E-cadherin, Col1A1, matrix metalloproteinase-2, matrix metalloproteinase-9, and mir-210. In tissue samples, hypoxia-inducible factor 1-alpha messenger RNA and protein expression of leptin and leptin receptor were high in oral squamous cell carcinoma cases. Serum leptin levels were increased in first clinical stages of the disease. In animal model, oral squamous cell carcinoma–induced mice show higher leptin receptor expression, and serum leptin level was increased in dysplasia group. Our findings suggest that leptin seems to exert an effect on oral squamous cell carcinoma cells behavior and also on molecular markers related to cell proliferation, migration, and tumor angiogenesis.
Glioblastoma-synthesized G-CSF and GM-CSF contribute to growth and immunosuppression: Potential therapeutic benefit from dapsone, fenofibrate, and ribavirin
Authors: Kast Richard E , Hill Quentin A , Wion Didier , Mellstedt Håkan , Focosi Daniele , Karpel-Massler Georg , Heiland Tim , Halatsch Marc-Eric
Published: May 2017

Increased ratio of circulating neutrophils to lymphocytes is a common finding in glioblastoma and other cancers. Data reviewed establish that any damage to brain tissue tends to cause an increase in G-CSF and/or GM-CSF (G(M)-CSF) synthesized by the brain. Glioblastoma cells themselves also synthesize G(M)-CSF. G(M)-CSF synthesized by brain due to damage by a growing tumor and by the tumor itself stimulates bone marrow to shift hematopoiesis toward granulocytic lineages away from lymphocytic lineages. This shift is immunosuppressive and generates the relative lymphopenia characteristic of glioblastoma. Any trauma to brain—be it blunt, sharp, ischemic, infectious, cytotoxic, tumor encroachment, or radiation—increases brain synthesis of G(M)-CSF. G(M)-CSF are growth and motility enhancing factors for glioblastomas. High levels of G(M)-CSF contribute to the characteristic neutrophilia and lymphopenia of glioblastoma. Hematopoietic bone marrow becomes entrained with, directed by, and contributes to glioblastoma pathology. The antibiotic dapsone, the lipid-lowering agent fenofibrate, and the antiviral drug ribavirin are Food and Drug Administration– and European Medicines Agency–approved medicines that have potential to lower synthesis or effects of G(M)-CSF and thus deprive a glioblastoma of some of the growth promoting contributions of bone marrow and G(M)-CSF.
Impact of viral and host DNA methylations on HPV16-related cervical cancer pathogenesis
Authors: Sen Shrinka , Mandal Paramita , Bhattacharya Amrapali , Kundu Sudip , Roy Chowdhury Rahul , Mondal Nidhu Ranjan , Chatterjee Tanmay , Chakravarty Biman , Roy Sudipta , Sengupta Sharmila
Published: May 2017

Epigenetic alterations within human papillomavirus (HPV) and host cellular genomes are known to occur during cervical carcinogenesis. Our objective was to analyse the influence of (1) methylation within two immunostimulatory CpG motifs within HPV16 E6 and E7 genes around the viral late promoter and their correlation, if any, with expression deregulation of host receptor (TLR9) and DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) and (2) global DNA methylation levels within CpGs of the repetitive Alu sequences, on cervical cancer (CaCx) pathogenesis. Significantly higher proportions of CaCx samples portrayed methylation in immunostimulatory CpG motifs, compared to HPV16-positive non-malignant samples, with cases harbouring episomal HPV16 showing decreased methylation compared to those with viral integration. A significant linear trend of TLR9 upregulation was recorded in the order of HPV–negative controls < HPV16-positive non-malignant samples < HPV16-positive CaCx cases. TLR9 upregulation in cases with episomal HPV16 was again higher among those with non-methylated immunostimulatory CpG motifs. Comparison of cases with HPV–negative controls revealed that DNMT3A was significantly downregulated only among integrated cases, DNMT3B was significantly overexpressed among both categories of cases, although at variable levels, while DNMT1 failed to show any deregulated expression among the cases. Global host DNA hypomethylation, also showed a significant linear increasing trend through the progressive CaCx development stages mentioned above and was most prominently higher among cases with episomal HPV16 as opposed to viral integration. Thus, HPV16 and host methylations appear to influence CaCx pathogenesis, with differential molecular signatures among CaCx cases with episomal and integrated HPV16.
Single-chain antibody–delivered Livin siRNA inhibits human malignant melanoma growth in vitro and in vivo
Authors: Wang Hao , Yang Yifei , Wang Wei , Guan Bing , Xun Meng , Zhang Hai , Wang Ziling , Zhao Yong
Published: May 2017

Although gene therapy has brought new insights into the treatment of malignant melanoma, targeting delivery of nucleic acid which targets critical oncogene/anti-oncogene in vivo is still a bottleneck in the therapeutic application. Our previous in vitro studies have found that the oncogene Livin could serve as a potential molecular target by small interfering RNA for gene therapy of malignant melanoma. However, how to transport Livin small interfering RNA into malignant melanoma cells specifically and efficiently in vivo needs further investigation. Cumulative evidence has suggested that single-chain antibody–mediated small interfering RNA targeted delivery is an effective way to silence specific genes in human cancer cells. Indeed, this study designed a protamine–single-chain antibody fusion protein, anti-MM scFv-tP, to deliver Livin small interfering RNA into LiBr cells. Further experiments confirmed the induction of cell apoptosis and suppression of cell proliferation by anti-MM scFv-tP in LiBr cells, along with efficient silence of Livin gene both in vitro and in vivo. Altogether, our findings provide a feasible approach to transport Livin small interfering RNA to malignant melanoma cells which would be a new therapeutic strategy for combating malignant melanoma.
Empowerment in Latina Immigrant Women Recovering From Interpersonal Violence: A Concept Analysis
Authors: Page Robin L. , Chilton Jenifer , Montalvo-Liendo Nora , Matthews Debra , Nava Angeles
Published: May 2017

Latina immigrant women are vulnerable and may experience higher levels of interpersonal or intimate partner violence (IPV) due to their immigrant status and cultural emphasis on familism. The concept of empowerment within the cultural context of Latina immigrant women experiencing IPV was analyzed using a modified version of Walker and Avant’s concept analysis technique. The technique considers usage and definitions in the literature, antecedents, attributes, empirical referents, and the inclusion of a model and contrary case. This analysis encompasses a comparative approach and includes a discussion of how the definition of empowerment compares across the nursing literature. Defining attributes include reciprocal relationships, autonomy, and accountability. Antecedents comprise willingness to learn and motivation to create change. Consequences encompass self-esteem, self-efficacy, and competence for making life decisions. Empowerment has the potential to improve total well-being, having a positive and profound impact on the lives of women experiencing IPV.
Adjustable fluid and particle permeation through hydrogel composite membranes
Authors: Ehrenhofer Adrian , Wallmersperger Thomas
Published: May 2017

Membranes act as smart structures in respect to their permeation abilities. Control of particle and fluid permeation through a synthetic membrane can be achieved by using different effects like size-exclusion or electromagnetic interactions that occur between the particles and membrane pores. The simulation of controlled permeability provides an insight into the smart behavior of membranes for chemical signal processing, sensing interfaces or lab-on-a-chip devices. In the current work, we model the underlying physical processes on a microfluidic level using the engineer’s approach of laminar flow through pipes. Different pore geometries inside a composite membrane system consisting of a polyethylene terephthalate support membrane and a poly(N-isopropylacrylamide) hydrogel-layer are investigated. Simulations for different states of thermally induced pore opening are performed for free and blocked states. From the results we derive paradigms for the design of a membrane system for microfluidic cell-size profiling considering stimulus-range, pore shape and measurement setup.
Hybrid energy harvesting based on cymbal and wagon wheel inspiration
Authors: Ganilova Olga , Awaludin Aiman , Dong Riguang
Published: May 2017

The demand for self-sufficient electronic devices is increasing as well as the overall energy use, and such demands are pushing technology forward, especially in effective energy harvesting. A novel hybrid energy harvesting system has been proposed and analysed in this article. It has been demonstrated that the energy harvesting system is capable of converting enough energy to power a typical micro-electro-mechanical system device. This has been achieved through unification of the nine–cymbal energy harvester array, as an energy harvesting core, and shape memory alloy active elements, acting as a source of force stimulated by the environmental changes. A finite element model was developed for the cymbal energy harvester, which was verified and used for the analysis of cymbal energy harvester’s response to the change of the end-cap material. This was followed by the finite element model for the energy harvesting system used for analysis of the location of shape memory alloy wires and force generated by each wire individually and then all together. As a further optimisation of the energy harvesting system, a novel wagon wheel design was explored in terms of its energy harvesting capabilities. As expected, due to the increased displacement, an increase in the power output was achieved.
Power and frequency bandwidth improvement of piezoelectric energy harvesting devices using phase-shifted synchronous electric charge extraction interface circuit
Authors: Lefeuvre Elie , Badel Adrien , Brenes Alexis , Seok Seonho , Yoo Chan-Sei
Published: May 2017

This article presents a new way to control the synchronous electric charge extraction interface circuit, which was formerly developed to improve the performances of piezoelectric vibration energy harvesting devices. An analytical model for energy harvesting systems including this new technique, called phase-shift synchronous electric charge extraction, is proposed. This model is then used to study the properties of this new control scheme in the cases of low and high electromechanical coupling. Contrary to the synchronous electric charge extraction technique which exhibited significant improvements in terms of harvested power for piezoelectric devices with low electromechanical coupling, the phase-shift synchronous electric charge extraction technique shows capability to increase the harvested power up to the theoretical limit for piezoelectric devices with high electromechanical coupling. In addition, the presented theoretical results show that the frequency bandwidth of piezoelectric energy harvesting devices may be substantially increased.
Size-dependent free vibration analysis of functionally graded piezoelectric plate subjected to thermo-electro-mechanical loading
Authors: Jandaghian Ali Akbar , Rahmani Omid
Published: May 2017

Analytical solutions are presented to study the thermo-electro-mechanical vibration problem of functionally graded piezoelectric materials’ nanoscale rectangular plates based on the size-dependent Kirchhoff plate theory. The plate is under an applied electric voltage, a biaxial force, and a uniform temperature rise. The material properties vary continuously along the thickness direction. To check the validity of the method, the results are compared with the results obtained in previous studies for the special cases. Finally, a parametric study is accompanied to survey the effects of the gradient index, length scale parameter, length-to-thickness ratio, external electric, and temperature change on the vibration of functionally graded piezoelectric nanoplates.
Malignant PEComa With Metastatic Disease at Diagnosis and Resistance to Several Chemotherapy Regimens and Targeted Therapy (m-TOR Inhibitor)
Authors: Machado Isidro , Cruz Julia , Lavernia Javier , Rayon José M. , Poveda Andrés , Llombart-Bosch Antonio
Published: May 2017

Perivascular epithelioid cell tumors (PEComas) are infrequent neoplasms with peculiar myomelanocytic differentiation. The aggressive abdominopelvic variant is rare, with only a small number of published cases. We present an additional case of this unusual variant, which showed an aggressive histologic and clinical behavior with multiple liver metastases and resistance to several therapies. We also discuss the histological and immunohistochemical profiles as well as the differential diagnosis.
Development of an Atypical Teratoid Rhabdoid Tumor in a Meningioma
Authors: Lach Boleslaw , Kameda-Smith Michelle , Singh Sheila , Ajani Olufemi
Published: May 2017

We describe an atypical teratoid rhabdoid tumor (AT/RT) with a component of low-grade and anaplastic rhabdoid meningioma in a 7-year-old child. The AT/RT was uniformly negative for INI1 and displayed immunoreactivity for vimentin, P53, CD99, cytokeratins with AE1/AE3 antibodies, epithelial membrane antigen, β-catenin, smooth muscle actin, E-cadherin, and S-100 protein. AT/RT was continuous, with small foci of recognizable low-grade and anaplastic meningioma. The low-grade meningioma was INI1 positive with scattered INI1-negative nuclei, whereas the remaining tumor components were INI1 negative. A recurrent tumor 6 months after partial resection contained only INI1-negative AT/RT. This case supports the hypothesis that rare examples of AT/RT may emerge from a preexisting “parent” neoplasm as a result of a second hit mutation.
Paratesticular Soft-Tissue Masses in Orchiectomy Specimens: A 17-Year Survey of Primary and Incidental Cases From One Institution
Authors: Priemer David S. , Trevino Karen , Chen Shaoxiong , Ulbright Thomas M. , Idrees Muhammad T.
Published: May 2017

The paratestis (PT) is defined by the testicular tunics, epididymis, spermatic cord, rete testis, and embryonic remnants. It gives rise to a large diversity of pathologies, including those of soft tissue, which may prompt orchiectomy. We performed a 17-year search of our database for orchiectomies for a PT soft-tissue mass. In a total of 4741 orchiectomy specimens, 138 orchiectomies were performed for primary neoplastic or nonneoplastic masses of the PT soft tissue or had an incidental PT soft-tissue mass. Of these, 65.9% were neoplastic. The mean age was 40.2 years (range: <1 to 87 years) and was similar for neoplastic and nonneoplastic lesions. The most common malignancies were rhabdomyosarcoma (31/63 malignancies), liposarcoma (19/63), and leiomyosarcoma (5/63), with the former occurring in younger patients (average: 18.3 years). No malignancies were incidental. The most common benign neoplasm was spermatic cord lipoma (24/28 of benign neoplasms); however, most were incidental. This was followed by leiomyoma (3/28) and hemangioma (1/28). The most common nonneoplastic lesions were adrenal rests (22/47 nonneoplastic cases); however, all were incidental findings. Of 47 nonneoplastic masses, 22 prompted orchiectomy, and of these, the most common diagnosis was fibrous/nodular periorchitis (11/47). Of 88 nonincidental lesions, 25 were either benign neoplasms (3/25) or nonneoplastic (22/25). These data indicate that PT soft-tissue neoplasms prompting orchiectomy are disproportionately rhabdomyosarcomas, though these are principally in young patients. In older patients, malignancies are more frequently liposarcomas. However, almost one-third of orchiectomies performed for PT soft-tissue masses yield benign lesions, indicating an opportunity to reduce unnecessary procedures.
Fractional-order Boubaker functions and their applications in solving delay fractional optimal control problems
Authors: Rabiei Kobra , Ordokhani Yadollah , Babolian Esmaeil
Published: May 2017

In this paper, a new set of functions called fractional-order Boubaker functions is defined for solving the delay fractional optimal control problems with a quadratic performance index. To solve the problem, first we obtain the operational matrix of the Caputo fractional derivative of these functions and the operational matrix of multiplication to solve the nonlinear problems for the first time. Also, a general formulation for the delay operational matrix of these functions has been achieved. Then we utilized these matrices to solve delay fractional optimal control problems directly. In fact, the delay fractional optimal control problem converts to an optimization problem, which can then be easily solved with the aid of the Gauss–Legendre integration formula and Newton’s iterative method. Convergence of the algorithm is proved. The applicability of the method is shown by some examples; moreover, a comparison with the existing results shows the preference of this method.