bluuebunny/crossref_metadata_2025 huggingface dataset:
Small Intestinal Obstruction with Intussusception due to Acute Myeloid Leukemia: A Case Report
Authors: Kini Sangeeta , Amarapurkar Anjali , Balasubramanian Meenaskshi
Published: August 2012

Myeloid sarcoma is known to precede the development of acute myeloid leukemia (AML) and can be the only clinical manifestation. Gastrointestinal involvement by AML is rare with the commonest site being small intestine. Patients present with vague abdominal pain and/or obstruction. Prognosis is usually poor as most of them rapidly progress to AML. We report a case of 25-year-old man with complaints of abdominal pain and vomiting of one-year duration. OGD scopy revealed infiltration of lesser curvature of stomach. Subsequently patient came back within a week with signs and symptoms of acute intestinal obstruction for which an ileal resection was done. Although the histology of stomach biopsy and ileal segments showing similar features were thought to be non-Hodgkin's lymphoma, immunohistochemistry confirmed the diagnosis of myeloid sarcoma. Bone marrow investigations confirmed involvement by AML. Patient succumbed to the disease due to extensive involvement of AML. This case highlights the primary gastrointestinal manifestation of AML which can often prove to be a diagnostic difficulty clinically and histologically. Prompt diagnosis is essential to hasten the management.
Homogeneous and Heterogeneous MPSoC Architectures with Network‐On‐Chip Connectivity for Low‐Power and Real‐Time Multimedia Signal Processing
Authors: Saponara Sergio , Fanucci Luca
Published: August 2012

Two multiprocessor system‐on‐chip (MPSoC) architectures are proposed and compared in the paper with reference to audio and video processing applications. One architecture exploits a homogeneous topology; it consists of 8 identical tiles, each made of a 32‐bit RISC core enhanced by a 64‐bit DSP coprocessor with local memory. The other MPSoC architecture exploits a heterogeneous‐tile topology with on‐chip distributed memory resources; the tiles act as application specific processors supporting a different class of algorithms. In both architectures, the multiple tiles are interconnected by a network‐on‐chip (NoC) infrastructure, through network interfaces and routers, which allows parallel operations of the multiple tiles. The functional performances and the implementation complexity of the NoC‐based MPSoC architectures are assessed by synthesis results in submicron CMOS technology. Among the large set of supported algorithms, two case studies are considered: the real‐time implementation of an H.264/MPEG AVC video codec and of a low‐distortion digital audio amplifier. The heterogeneous architecture ensures a higher power efficiency and a smaller area occupation and is more suited for low‐power multimedia processing, such as in mobile devices. The homogeneous scheme allows for a higher flexibility and easier system scalability and is more suited for general‐purpose DSP tasks in power‐supplied devices.
Prevalence and Quality of Life of Slovenian Children with Primary Nocturnal Enuresis
Authors: Karničnik Katja , Koren Alenka , Kos Nastja , Marčun Varda Nataša
Published: August 2012

Aim. To get epidemiologic data about primary nocturnal enuresis (PNE) and its influence on the quality of life of Slovenian children and adolescents and to find out the knowledge about the disorder among school population.Methods. Prospective epidemiologic study was performed in Slovenia in 2011 and supported with two questionnaires. The first questionnaire was distributed among primary school population that included 1248 children. The second questionnaire included 44 children, who have been treated for PNE in Nephrology Unit of our Department of Paediatrics.Results. PNE was diagnosed in 12.4% of children, in 11.8% of girls and in 13.0% of boys. There was evident linkage between the appearance of PNE in children and their relatives. The study showed that PNE influences the quality of life in less than half of the investigated children. Disorder restricts them mostly in relations with coevals. Knowledge about PNE among children in elementary schools was found to be insufficient.Conclusion. We found out that the prevalence of PNE in Slovenia is comparable to prevalence in other countries. More than half of children questioned in a survey think that PNE does not affect their lives significantly. General lack of knowledge about PNE is still a problem.
Moments for Generating Functions of Al‐Salam‐Carlitz Polynomials
Authors: Cao Jian
Published: August 2012

We employ the moment representations for Al‐Salam‐Carlitz polynomials and show how to deduce bilinear, trilinear, and multilinear generating functions for Al‐Salam‐Carlitz polynomials. Moreover, we obtain two terminating generating functions for Al‐Salam‐Carlitz polynomials by the method of moments.
Williams-Beuren's Syndrome: A Case Report
Authors: Zamani Hassan , Babazadeh Kazem , Fattahi Saeid , Mokhtari-Esbuie Farzad
Published: August 2012

Williams-Beuren syndrome is a rare familial multisystem disorder occurring in 1 per 20,000 live births. It is characterized by congenital heart defects (CHD), skeletal and renal anomalies, cognitive disorder, social personality disorder and dysmorphic facies. We present a case of Williams syndrome that presented to us with heart murmur and cognitive problem. A 5-year-old girl referred to pediatric cardiologist because of heart murmurs. She had a systolic murmur (2-3/6) in right upper sternal border with radiation to right cervical region. She also had a bulge forehead. Angiography showed mild supra valvular aortic stenosis and mild multiple peripheral pulmonary stenosis. Fluorescent in situ hybridization (FISH) was performed and the result was: 46.XX, ish del (7q11.2) (ELN X1) (7q22 X2) ELN deletion compatible with Williams syndrome. Peripheral pulmonary artery stenosis is associated with Noonan syndrome, Alagille syndrome, Cutis laxa, Ehler-Danlos syndrome, and Silver-Russel syndrome. The patient had peripheral pulmonary artery stenosis, but no other signs of these syndromes were present, and also she had a supravalvular aortic stenosis which was not seen in other syndromes except Williams syndrome.Conclusion. According to primary symptoms, paraclinical and clinical finding such as dysmorphic facies, cognitive disorder and congenital heart defect, Williams syndrome was the first diagnosis. We suggest a more attention for evaluating heart murmur in childhood period, especially when the patient has abnormal facial features or mental problem.
The Role of HCN Channels on Membrane Excitability in the Nervous System
Authors: Kase Daisuke , Imoto Keiji
Published: August 2012

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels were first reported in heart cells and are recently known to be involved in a variety of neural functions in healthy and diseased brains. HCN channels generate inward currents when the membrane potential is hyperpolarized. Voltage dependence of HCN channels is regulated by intracellular signaling cascades, which contain cyclic AMP, PIP2, and TRIP8b. In addition, voltage-gated potassium channels have a strong influence on HCN channel activity. Because of these funny features, HCN channel currents, previously called funny currents, can have a wide range of functions that are determined by a delicate balance of modulatory factors. These multifaceted features also make it difficult to predict and elucidate the functional role of HCN channels in actual neurons. In this paper, we focus on the impacts of HCN channels on neural activity. The functions of HCN channels reported previously will be summarized, and their mechanisms will be explained by using numerical simulation of simplified model neurons.
A Dependent Hidden Markov Model of Credit Quality
Authors: Korolkiewicz Małgorzata Wiktoria
Published: August 2012

We propose a dependent hidden Markov model of credit quality. We suppose that the "true" credit quality is not observed directly but only through noisy observations given by posted credit ratings. The model is formulated in discrete time with a Markov chain observed in martingale noise, where "noise" terms of the state and observation processes are possibly dependent. The model provides estimates for the state of the Markov chain governing the evolution of the credit rating process and the parameters of the model, where the latter are estimated using the EM algorithm. The dependent dynamics allow for the so-called "rating momentum" discussed in the credit literature and also provide a convenient test of independence between the state and observation dynamics.
The Glomerular Filtration Barrier: Components and Crosstalk
Authors: Menon Madhav C. , Chuang Peter Y. , He Cijiang John
Published: August 2012

The glomerular filtration barrier is a highly specialized blood filtration interface that displays a high conductance to small and midsized solutes in plasma but retains relative impermeability to macromolecules. Its integrity is maintained by physicochemical and signalling interplay among its three core constituents—the glomerular endothelial cell, the basement membrane and visceral epithelial cell (podocyte). Understanding the pathomechanisms of inherited and acquired human diseases as well as experimental injury models of this barrier have helped to unravel this interdependence. Key among the consequences of interference with the integrity of the glomerular filtration barrier is the appearance of significant amounts of proteins in the urine. Proteinuria correlates with kidney disease progression and cardiovascular mortality. With specific reference to proteinuria in human and animal disease phenotypes, the following review explores the roles of the endothelial cell, glomerular basement membrane, and the podocyte and attempts to highlight examples of essential crosstalk within this barrier.
Intensity-Modulated Radiation Therapy for Rectal Carcinoma Can Reduce Treatment Breaks and Emergency Department Visits
Authors: Jabbour Salma K. , Patel Shyamal , Herman Joseph M. , Wild Aaron , Nagda Suneel N. , Altoos Taghrid , Tunceroglu Ahmet , Azad Nilofer , Gearheart Susan , Moss Rebecca A. , Poplin Elizabeth , Levinson Lydia L. , Chandra Ravi A. , Moore Dirk F. , Chen Chunxia , Haffty Bruce G. , Tuli Richard
Published: August 2012

Purpose. To compare the acute toxicities of IMRT to 3D-conformal radiation therapy (3DCRT) in the treatment of rectal cancer.Methods and Materials. Eighty-six patients with rectal cancer preoperatively treated with IMRT (n=30) and 3DCRT (n=56) were retrospectively reviewed. Rates of acute toxicity between IMRT and 3DCRT were compared for anorexia, dehydration, diarrhea, nausea, vomiting, weight loss, radiation dermatitis, fatigue, pain, urinary frequency, and blood counts. Fisher's exact test and chi-square analysis were applied to detect statistical differences in incidences of toxicity between these two groups of patients.Results. There were fewer hospitalizations and emergency department visits in the group treated with IMRT compared with 3DCRT (P=0.005) and no treatment breaks with IMRT compared to 20% with 3DCRT (P=0.0002). Patients treated with IMRT had a significant reduction in grade ≥3 toxicities versus grade ≤2 toxicities (P=0.016) when compared to 3DCRT. The incidence of grade ≥3 diarrhea was 9% among 3DCRT patients compared to 3% among IMRT patients (P=0.31).Conclusions. IMRT for rectal cancer can reduce treatment breaks, emergency department visits, hospitalizations, and all grade ≥3 toxicities compared to 3DCRT. Further evaluation and followup is warranted to determine late toxicities and long-term results of IMRT.
Hermite Polynomials and their Applications Associated withBernoulli and Euler Numbers
Authors: Kim Dae San , Kim Taekyun , Rim Seog-Hoon , Lee Sang Hun
Published: August 2012

We derive some interesting identities and arithmetic properties of Bernoulli and Euler polynomials from the orthogonality of Hermite polynomials. Let Pn = {p(x) ∈ ℚ[x]∣deg p(x) ≤ n} be the (n + 1)‐dimensional vector space over ℚ. Then we show that {H0(x), H1(x), …, Hn(x)} is a good basis for the space Pn for our purpose of arithmetical and combinatorial applications.
Obstetric Management of a Patient with Narcolepsy and Cataplexy: A Case Report
Authors: Ajayi S. , Kinagi R. , Haslett E.
Published: August 2012

We report the management of a patient who suffers from narcolepsy and cataplexy and presented to the clinic at 14 weeks of gestation. Her symptoms were resistant to modafinil but controlled with clomipramine and amphetamine. Discussion concerning mode of delivery for these patients is scarce in the literature. We discuss some issues surrounding the antenatal management and counselling regarding mode of delivery and postpartum care.
Cognitive Outcome of Status Epilepticus in Children
Authors: Sheppard Emilie , Lippé Sarah
Published: August 2012

Epileptic encephalopathy encompasses conditions in which cognitive, motor, or sensory deficits result as a consequence of epileptic activity defining certain syndromes. It therefore represents a more severe subset of epilepsy, which can be generally characterized as frequent or severe seizures leading to cerebral dysfunction. This disturbance in cerebral functioning can in turn hinder, somewhat dramatically, cognitive development and further impact the future lives of patients. In this paper, we describe the cognitive consequences of status epilepticus in children and in adults in the context of plasticity theories. Recent studies maintain that consequences of SE may be severe cognitive sequelae, especially in early life. Since the residual consequences of SE in adulthood seem less detrimental and long-lasting, we argue that early life insults, such as those created by SE, during a rapid period of development and functional specialization, result in specific cognitive deficits dependent on the sensitive period at which SE occurred.
Effect of Mixing on Microorganism Growth in Loop Bioreactors
Authors: Al Taweel A. M. , Shah Q. , Aufderheide B.
Published: August 2012

The impact of mixing on the promotion of microorganism growth rate has been analyzed using a multiphase forced-circulation pipe-loop reactor model capable of identifying conditions under which it is possible to convert natural gas into Single-Cell Protein. The impact of mixing in the interphase mass transfer was found to exert a critical role in determining the overall productivity of the bioreactor, particularly at the high cell loadings needed to reduce the capital costs associated with the large-scale production needed for the production of relatively low-value SCP in a sustainable manner.
Tin(II) Selective PVC Membrane Electrode Based on Salicylaldehyde Thiosemicarbazone as an Ionophore
Authors: Chandra Sulekh , Sharma Kusum , Kumar Adarsh
Published: August 2012

A polymeric membrane‐based tin selective electrode was developed by using salicylaldehyde thiosemicarbazone (STSC). The best performance was recorded with a membrane composition of PVC : TBP : ionophore : NaTPB as 28 : 59 : 8 : 5 (w/w%). The Nernstian slope calculated from the calibration curve for Sn2+ sensor was 28.8 ± 0.4 mV/decade. The detection limit of the sensor was 2.10 × 10−8 M, in the linear concentration range of 1.0 × 10−2 − 1.1 × 10−7 M. It was relatively fast response time (<8 s for concentration ≥1.0 × 10−4 and <12 s for concentration of ≥1.0 × 10−6 M) and can be used for 9 months without any considerable divergence in potentials. The proposed sensor exhibit relatively good selectivity and high sensitivity for tin(II) as other mono‐, di‐, and trivalent cations and can be used in a pH range of 2.0–8.5. The analytical usefulness of the proposed electrode has been evaluated by its application in the determination of stannous in artificially made samples.
Synthesis and Antibacterial, Antimycobacterial Activity of 7‐[4‐{5‐(2‐Oxo‐2‐p‐substituted‐phenylethylthio)‐1,3,4‐thiadiazol‐2yl}‐3′‐methylpiperazinyl] Quinolone Derivatives
Authors: Agrawal Kapil M. , Talele Gokul S.
Published: August 2012

Currently we screened 9 newer synthesized fluoroquinolone derivatives 5(a–i) against two gram positive, two gram negative bacterial strains, and mycobacterium tuberculosis H37Rv. These analogues were confirmed by IR, 1H NMR, 13C NMR, and elemental analysis. Selected compounds were confirmed by mass spectral study. Compounds 5(b–d) showed comparable biological activities and other analogues of the series showed moderate‐to‐weak activity, as compared to the reference marketed drugs.
Abstract 1084: Naturally occurring variants of human α9 nicotinic receptor differentially affect bronchial cell proliferation and transformation
Authors: Chikova Anna , Grando Sergei
Published: August 2012

Isolation of polyadenilated mRNA from human immortalized bronchial epithelial cell line BEP2D revealed the presence of multiple isoforms of RNA coded by the CHRNA9 gene for α9 nicotinic acetylcholine receptor (nAChR). BEP2D cells were homozygous for the rs10009228 polymorphism encoding for N442S amino-acid substitution, and also contained mRNA coding for several truncated isoforms of α9 protein. To elucidate the biologic significance of the naturally occurring variants of α9 nAChR, we compared the biologic effects of overexpression of full-length α9 N442 and S442 proteins, and the truncated α9 variant occurring due to a loss of the exon 4 sequence that causes frame shift and early termination of the translation. These as well as control vector were overexpressed in the BEP2D cells that were used in the assays of proliferation rate, spontaneous vs. tobacco nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced cellular transformation, and tumorigenicity in cell culture and mice. Overexpression of the S442 variant significantly increased cellular proliferation, and spontaneous and NNK-induced transformation. The N442 variant significantly decreased cellular transformation, without affecting proliferation rate. Overexpression of the truncated α9 significantly decreased proliferation and suppressed cellular transformation. These results suggested that α9 nAChR plays important roles in regulation of bronchial cell growth by endogenous acetylcholine and exogenous nicotine and susceptibility to NNK-induced carcinogenic transformation. The biologic activities of α9 nAChR may be regulated at the splicing level, and genetic polymorphisms in CHRNA9 affecting protein levels, amino-acid sequence and RNA splicing may influence the risk for lung cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1084. doi:1538-7445.AM2012-1084
Abstract 109: CSE1L, a 20q gain passenger that drives colorectal adenoma to carcinoma progression
Authors: Sillars-Hardebol Anke H. , Carvalho Beatriz , Belien Jeroen A.M. , de Wit Meike , Delis-van Diemen Pien M. , Tijssen Marianne , van de Wiel Mark A. , Ponten Fredrik , Meijer Gerrit A. , Fijneman Remond J. A.
Published: August 2012

Background ‘Driver genes’ are defined as genes that promote the tumorigenic process upon acquirement of somatic alterations. Gain of chromosome 20q is an important factor in the progression of colorectal adenomas to carcinomas. Previously we identified TPX2 and AURKA as two genes that drive 20q amplification in colorectal adenoma to carcinoma progression, based on correlation of mRNA and protein expression levels with 20q DNA copy number status while functionally influencing cancer processes. These findings are consistent with the hypothesis that the selection advantage imposed by 20q gain in colorectal adenoma to carcinoma progression is achieved by gain-of-function of multiple cancer-related genes at chromosome 20q, rather than affecting a single driver gene. In addition to TPX2 and AURKA, other 20q genes such as CSE1L may further contribute to tumor progression. Aim We here investigated whether CSE1L is another 20q located gene that drives colorectal adenoma to carcinoma progression, in a 20q gain-dependent manner. Methods Functional effects of CSE1L on cell viability, anchorage-independent growth and invasion were investigated upon gene knockdown using the SW480 colorectal cancer cell line. CSE1L protein expression levels were examined by immunohistochemical evaluation of tissue microarrays containing a series of colorectal adenoma and carcinoma samples, which were characterized by genome-wide (microarray-based) DNA and mRNA profiling. Results CSE1L knockdown affected cell viability and anchorage-independent growth. CSE1L mRNA expression levels correlated with chromosome 20q DNA copy number status. However, CSE1L protein expression was not associated with 20q gain, although its expression was increased in carcinomas compared to adenomas. Conclusion CSE1L appears to be a driver of colorectal tumor progression based on its functional effects combined with increased protein expression levels in carcinomas compared to adenomas. However, the lack of correlation between CSE1L protein expression levels and 20q DNA copy number status in colorectal adenoma to carcinoma progression implies that CSE1L is merely a passenger rather than a driver of chromosome 20q amplification, suggesting that CSE1L protein levels are subject to post-transcriptional regulation in a 20q gain-independent manner.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 109. doi:1538-7445.AM2012-109
Abstract 1090: Impact of CXCL1/CXCR2 signaling in ovarian cancer proliferation
Authors: Dong Yuanlin , Kabir Syeda M. , Son Deok-Soo
Published: August 2012

Introduction: Chemokine network plays a critical role in the development and progression of cancer. Human ovarian tumors express chemokine CXCL1 and its receptor CXCR2, but its role in ovarian cancer development and progression remains unclear. In this study, we investigate whether CXCL1/CXCR2 have functional significance in ovarian cancer cell proliferation. Methods: CXCR2 was overexpressed by stable transfection into the human ovarian surface epithelial cancer cell lines A2780, OVCAR3, and SKOV3. The influence of CXCL1 and CXCR2 on cell proliferation, cell cycle progression, and changes in related proteins and gene expression were determined by using confocal image analysis, MTT assay, Western blotting, flow cytometry, and PCR array. Results: CXCR2 was mainly expressed on the cell surface and intracellular localization, and these expressions were profoundly enhanced in CXCR2 overexpressed cell lines when compared to controls. CXCR2 significantly increased the proliferation of A2780, OVCAR3 and SKOV3 cells in a time-dependent manner, and these increases were abolished by the CXCR2 inhibitor, SD 225002. Furtermore, CXCR2-induced cancer cell proliferation was suppressed by Gefitinib, an inhibitor of epidermal growth factor receptor (EGFR), indicating crosstalk between CXCR2 and EGFR in ovarian cancer cell proliferation. CXCR2 induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and NF-kappa B, probably contributing to ovarian tumor growth and metastatic progression. CXCL1 significantly stimulates the cell proliferation in CXCR2 overexpressed cell lines, and the stimulations were substantially blocked by the ERK1/2 inhibitor, PD 98059, further confirming the involvement of MAPK signaling. CXCR2 reduced cell cycle arrest in the G0-G1 phase and increased the cell population in the S and G2-M phase, and these changes were associated with enhanced expression for CDK6, a G1-S cell cycle transition regulatory gene. Chemokine specific PCR array revealed that CXCR2 enhances proinflammatory chemokines CCL2, CXCL1, CXCL2, CXCL3, and CXCL6, suggesting that CXCR2 accelerates proinflammatory tumor microenvironment to provide the suitable condition for ovarian cancer progression. Conclusions: Taken together, this study demonstrated that CXCL1/CXCR2 signaling plays critical roles in ovarian cancer growth and progression through the activation of ERK1/2 and NF-kappa B. Thus, CXCL1/CXCR2 signaling may be important in the pathogenesis of ovarian cancer, providing a basis for the therapeutic targets in ovarian cancer patients.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1090. doi:1538-7445.AM2012-1090
Abstract 1091: Cannabinoids inhibit epidermal growth factor receptor transactivation in lung cancer cells
Authors: Moody Terry W. , Mantey Samuel , Jensen Robert T. , Wink David , Mukhopadhyay Partha , Pacher Pal
Published: August 2012

The cannabinoid receptors CB1 and CB2 are present on non-small cell lung cancer (NSCLC) biopsy specimens (Preet et al., 2011, Cancer Prev. Res. 4:65). CP55,940 and Win55,212-2 are mixed agonists which stimulate CB1 and CB2 cannabinoid receptors. G-protein coupled receptors (GPCR) for pituitary adenylate cyclase activating polypeptide (PACAP) regulate epidermal growth factor receptor (EGFR) tyrosine phosphorylation in NSCLC cells. Here the ability of cannabinoids to alter EGFR transactivation was investigated. PACAP stimulated EGFR tyrosine phosphorylation (PY1068) 4-fold using NCI-H838 and H1299 cells. CP55,940 and Win55,212-2 inhibited the ability of PACAP to increase EGFR tyrosine phosphorylation in lung cancer cells. By Western blot, cell lines NCI-H838 and NCI-H1299 had both CB1 and CB2 receptors. PACAP increased cAMP levels in NCI-H838 cells and CP55,940 inhibited the increase in cAMP caused by PACAP. In contrast, PACAP increased cytosolic Ca2+ in lung cancer cells, but CP55,940 did not alter the ability of PACAP to increase calcium in lung cancer cells. These results suggest that CP55,940 may inhibit adenylyl cyclase activity but not phosphatidylinositol turnover caused by addition of PACAP to lung cancer cells. Previously we found that PACAP increased tyrosine phosphorylation of focal adhesion kinase, paxillin and ERK in lung cancer cells (Moody et al., 2002, Reg. Peptides 109:135). CP55,940 inhibited the increase in tyrosine phosphorylation of focal adhesion kinase, paxillin and ERK caused by PACAP addition to lung cancer cells. Also, CP55.940 and Win55,212-2 inhibited the growth of NCI-H1299 and NCI-H838 cells. CP55,940 potentiated the growth inhibitory effects of gefitinib, an EGFR tyrosine kinase inhibitor. These results indicate that cannabinoids inhibit EGFR transactivation in lung cancer cells and potentiate gefitinib cytotoxicity.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1091. doi:1538-7445.AM2012-1091
Abstract 11: A requirement for SOCS-1 and SOCS-3 phosphorylation in BCR-ABL-mediated transformation
Authors: Chen Jilong , Qiu Xiaoxue , Guo Guijie , Chen Ke
Published: August 2012

Previous studies have demonstrated that constitutive activation of JAK/STAT signaling is required for efficient transformation by the Abelson murine leukemia virus (A-MuLV), which expresses v-Abl oncoprotein. Importantly, there is increasing evidence that deregulation of the JAK or STAT activity plays a critical role in BCR-ABL-induced malignant transformation. SOCS-1 and SOCS-3 are inhibitors of JAK-STAT pathway and as such are involved in a negative feedback loop of cytokine signaling. However, the mechanism by which Abl oncogene bypasses SOCS inhibitory regulation remains poorly defined. Here, we found that co-expression of BCR-ABL with SOCS-1 or SOCS-3 resulted in tyrosine phosphorylation of these SOCS proteins. Interestingly, tyrosine-phosphorylated SOCS-1 was detected in three of five primary CML samples which express BCR-ABL. BCR-ABL-dependent phosphorylation of SOCS-1 and SOCS-3 occurred mainly on Tyr 155 and Tyr 204 residues of SOCS-1, and Tyr 221 residue of SOCS-3. Phosphorylation of these SOCS proteins was associated with its binding to BCR-ABL, and this interaction was disrupted by mutation of the sites of SOCS phosphorylation. We demonstrated that BCR-ABL-dependent phosphorylation of SOCS-1 and SOCS-3 alters their inhibitory effects on the activation of JAK1 and JAK2 and thereby enhances JAK-STAT signaling. Moreover, disrupting the tyrosine phosphorylation of SOCS-1 or SOCS-3 promotes K562 leukemic cells to undergo apoptosis and blocks tumor formation in mouse model. Together, these results reveal a requirement for tyrosine phosphorylation of SOCS-1 and SCOCS-3 in BCR-ABL-mediated transformation in the presence of these SOCS proteins.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 11. doi:1538-7445.AM2012-11
Abstract 110: Role of CARD 10 mediated NF-kB activation in colorectal carcinoma cells
Authors: Bu Rong , Ahmed Maqbool , Bavi Prashant , Sultana Mehar , Al-Haqawi Wael , Uddin Shahab , Al-Kuraya Khawla S.
Published: August 2012

Colorectal carcinoma is the fourth most common cancer in men and the third in women worldwide, accounting for 8% of all cancer deaths. NF-κB gene plays a role in tumorgenesis through the transcriptional activation of genes associated with cell proliferation, angiogenesis, metastasis, tumor promotion, inflammation and suppression of apoptosis. NF-κB protein activation, defined as nuclear expression of NF-κB by immunohistochemistry was an independent prognostic marker for poor survival. CARD10 gene is known positive regulator of the NF-κB activation pathway and can activate the NF-κB activity. CARD10 is an enzyme that is encoded by the CARD10 gene and it associates with IKK complex resulting in NF-κB activation. Considering the potential therapeutic utility of targeting NF-κB and its key modulators, we previously studied CARD10 genetic alterations and immunohistochemical expression of CARD10 in a large cohort cases1. CARD10 protein expression associated significantly with NF-κB activation, and CARD10 amplification was significantly associated with CARD10 protein expression and presence of distance metastasis. To extend and confirm our clinical finding, we performed in vitro studies using a panel of CRC cell lines to investigate the biological role of CARD10 alterations in CRC carcinogenesis. Our data showed that TNF-α treatment caused efficient translocation of p56 in CARD 10 muatation harboring cell line -DLD-1 cells to nucleus as compared to HCT-15 cells. Furthermore, the luciferase activity was significantly higher in CARD 10 amplified HCT-116 cells as compared to DLD1 and HCT-15 cells which carry normal CRAD10 gene copy number after 48 hours of transfection with an NF-κB reporter. In addition, it was also observed that the formation of colonies was significantly higher in HCT-116 as compared to DLD-1 and HCT-15. Finally CARD 10 siRNA transfection knocked down the expression of CARD10 and abrogated the expression of NF-κB, and resulted in apoptosis through activation of caspase-3. These data suggest that CARD10 mutation and amplification mediated NFκB activation play an important role in cellular transformation of CRC cells. Thus, the study raises the possibility that inhibition of CARD10 might have significant therapeutic value in CRC. Reference: 1: Jehad Abubaker, Prashant Bavi, Zeenath Jehan, Maqbool Ahmed, Wael Al-Haqawi, Mehar Sultana, Sarita Prabhakaran, Nasser Al-Sanea, Alaa Abduljabbar, Luai H Ashari, Samar Alhomoud, Fouad Al-Dayel, Shahab Uddin, Khawla S. Al-Kuraya. Clinicopathological significance of CARD10 alterations in Middle Eastern colorectal cancer. 102nd AACR Annual Meeting, April2-6, 2011, Orlando, Florida.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 110. doi:1538-7445.AM2012-110
Abstract 1110: Effect of miR-29 on cisplatin sensitivity of ovarian cancer cells
Authors: Yu Pei-Ning , Lin Wen-Chi , Kuo Chih-Chi , Huang Rui-Lan , Yan Ming-De , Shih Yu-Lueng , Chou Yu-Ching , Lai Hung-Cheng , Lin Ya-Wen
Published: August 2012

In clinical practice, the main dilemma to a successful ovarian cancer therapy is the development of drug resistance. The mounting evidence demonstrated that microRNAs (miRNAs) not only controlled cell proliferation, invasion and metastasis but also therapeutic resistance of ovarian cancer cell. Recently, we isolated CP70sps(CP70 side population spheres) from CP70 ovarian cancer cell line and proved that CP70sps exhibited more resistant to cisplatin than CP70. This phenomenon was correlated to other study which supported that side population of cancer cells was responsible for chemoresistance. In this study, we compared the expression of miRNAs between CP70sps and CP70 to investigate the role of miRNAs in cisplatin resistance of ovarian cancer cells. Our miRNA array and quantitative RT-PCR data showed that CP70sps expressed lower level of miR-29a/b/c family than CP70 cells and CP70sps4wks cells which were repopulation of CP70sps in attached condition. After knockdown of miR-29a/b/c family by miRNA inhibitors, reduction of miR-29a/b/c family enhanced cisplatin resistance of CP70 cells. However, there was no effect on cell cycle and proliferation rate in both CP70 cells and A2780, a parental cisplatin-sensitive cell line of CP70 cells. Downregulation of miR-29a/b/c family contributed cells to escape cisplatin-induced cell death through COL1A1 upregulation. Moreover, reduction of miR-29a/b/c increased phosphorylation of ERK1/2 and GSK3β to transduce survival signaling and reduced active form casepase-9 to avoid cell apoptosis. Furthermore, we found that either ectopic expression of miR-29 alone or combination of miR-29 with cisplatin treatment efficaciously reduced tumorigenicity of CP70 cells in immunodeficiency mice. Finally, we ascertained that the ovarian cancer patients with high expression of miR-29a had better overall survival rate. Taken together, our data demonstrated that the miR-29 family was a sensitizer for cisplatin treatment and might be associated with tumorigenecity of ovarian cancer cells.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1110. doi:1538-7445.AM2012-1110
Abstract 1130: API 31510 induced shift in mitochondrial metabolism in cancer cells is characterized by increased mitochondrial efficiency and induction of apoptosis
Authors: Jing Enxuan , Vishnudas Vivek , Jimnenez Joaquin J. , Narain Niven R. , Sarangarajan Rangaprasad
Published: August 2012

API 31510 is an ubidecarenone-based small molecule currently in late stage clinical development for skin cancers and early stage for solid tumors. Mechanism of action studies demonstrate that there is induced metabolic shift that occurs via modulation of the pentose phosphate shunt. The current study focused on delineating further insight into the relationship of mitochondrial metabolism and API 31510 induced apoptosis on different cancer cell lines. Use of Berg Interrogative Biology™ Platform of high thorough-put “omic” data demonstrated presence of coordinated alterations on gene expression and substrate metabolism in the cells in response to treatment with API 31510. Detection of apoptotic responses in different cancer cell lines revealed a significant elevation of different markers such as Bcl2, BcL-xL, BIRC3, and GADD45. Hence, the treatment induced significant increases in the intrinsic apoptosis networks in pancreatic (PaCa-2), breast (SKBr3), and liver (Hep3B) cancer cell lines. Furthermore, treatment with API 31510 is associated with increase in the ATP/oxygen consumption rate (OCR) ratios, suggesting increased mitochondrial efficiency in API 31510 treated cancer cells. Conversely, in normal fibroblasts, aortic smooth muscle, cardiomyocytes, and liver cells, the cells exhibited a more homeostatic phenotype and were not adversely affected by administration of API 31510. This observation suggests that the oncogenic phenotype secondary to mitochondrial dysfunction alters the metabolic machinery in a manner that confers an evasion of intrinsic apoptotic potential in cancer. Increased ATP/OCR is accompanied by altered intracellular reactive oxygen species (ROS) production in cancer cell lines. Taken together, the data suggest that the data demonstrate that treatment with API 31510 is associated with induction of significantly increased cell death triggered by increased mitochondrial efficiency, altered ROS and apoptosis activation in cancer cells.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1130. doi:1538-7445.AM2012-1130
Abstract 1142: The expression profile of cancer/testis antigens (CTAs) in head and neck cancer
Authors: Karia Bruno Takao R. , Zamuner Fernando Tadeu , Nani Luiz Augusto S. , Rodrigues Dorival M. , Carvalho Andre L. , Vettore Andre Luiz
Published: August 2012

Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the most frequent types of cancer. Despite significant improvements in the therapeutic strategies, the overall survival rate in 5 years is around 50%. The development of new therapies and their integration into the current forms of treatment (surgery, radiotherapy and chemotherapy) is of great interest to improve the therapeutic efficacy. Immunotherapy may provide an alternative for current treatment approach, since the natural immune response can be stimulated by active immunotherapeutic interventions which may help in the control of the tumor progression and recurrence. A requirement for the development of immunotherapeutic approaches is the identification of immunogenic gene products expressed predominantly in tumor cells. Cancer/testis antigens (CTAs) fulfill this prerequisite as their expression is restricted to tumors with no expression in normal tissues, except germ line cells. In this study we performed a search on Oncomine, SAGE Anatomic Viewer, CTdatabase and PubMed databases to select among the 153 CTAs genes those that might be expressed in HNSCC. This in silico analysis allowed the selection of 60 CTAs genes to have their expression evaluated in 89 tumors and in 20 normal mucosa by RT-PCR. According this analysis, 13 CTAs were specificaly expressed in HNSCC samples (>25% sensitivity) The expression of CTA1 was significantely associated with perineural invasion (p=0,023) and vascular invasion (p=0,003), whereas the presence of CTA2 or CTA3 was correlated with the presence of tumor cells in the lymph nodes (p=0,023 and p=0,037, repectively). Moreover, the CTA4 expression showed to be associated with capsular rupture (p=0,005). We report here the identification of 13 CTAs frequently expressed in HNSCC and the expression of some of them was significantly associated with poor prognostic factors. These results could be important for the development of immunotherapy strategies for treating HNSCC patients.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1142. doi:1538-7445.AM2012-1142
Abstract 1144: Overexpression of Tripartite Motif-containing 24 contributes to human epithelium cell carcinoma and correlates with poor prognosis of patient with local advanced head and neck squamous cell carcinoma
Authors: Lu Yan , Cao Wei , Cui Zhibin , Chen Wantao
Published: August 2012

BACKGROUND: To identify new and useful candidate biomarkers in head and neck squamous cell carcinoma (HNSCC), we performed a genome-wide survey and found that Tripartite motif-containing 24(TRIM24) was a gene that was markedly up-regulated in HNSCC. TRIM24 is a member of transcriptional intermediary factor 1 family, functions as a co-regulator that modulate transcriptional activities of several nuclear receptors, either positively or negatively. Here, we investigated the effects of TRIM24 on proliferation, invasion and apoptotic potential in HNSCC cell lines as well as its clinical significance in HNSCC. METHODS: The expressions of TRIM24 were examined through real-time PCR and western blot in 56 pairs of HNSCC and adjacent normal samples, as well as in 8 HNSCC cell lines and primary normal keratinocytes. Three TRIM24 high-expressed cell line were transfected with TRIM24 siRNA, then the proliferation, invasion and apoptotic potential was assessed by cell-counting kit-8, colony formation, matrigel invasion chambers and flow cytometry. In addition, the clinical implication of TRIM24 was investigated in another independent 91 locally advanced HNSCC by immunohistochemistry. RESULTS: TRIM24 mRNA expression were up-regulated remarkably in HNSCC samples and cell lines through real-time PCR. Correspondingly, elevated TRIM24 translation levels were found in 2 of 3 (67%) HNSCC tissues that were selected randomly from the 56 paired HNSCC tissues and 6 of 8 HNSCC cell lines using Western blot analysis. A significant reduction in cell proliferation and increase in population of apoptotic cells were observed in TRIM24 siRNA transfected cell lines in p53-dependent manner. Moreover, 55%(50/91) of HNSCC samples show high expression of TRIM24 by immunohistochemistry and survival analyses indicated a significant association between TRIM 24 high expression and a reduced overall survival in patients with locally advanced HNSCC (log rank test, P = 0.020). CONCLUSION: Our data indicated that overexpression of TRIM24 may play an important role in HNSCC tumorigenesis and serve as an independent prognostic predictor for patients with locally advanced HNSCC. ACKNOWLEDGMENTS: This study was supported by the National Natural Science Foundation of China (Grant No. 30973343), Projects of the Shanghai Science and Technology Committee (Grant No. 08JC1414400 and 10XD1402500) and the Shanghai Leading Academic Discipline Project (S30206). *Yan Lu and Wei Cao contributed equally to this work.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1144. doi:1538-7445.AM2012-1144
Abstract 116: Targeting hypoxia for the identification of novel biomarkers for prostate cancer
Authors: Gomez Christian R. , Munz Jan Marie , Kosari Farhad , Karnes Jeffrey , Cheville John , Ida Cristiane , Sebo Thomas , Vasmatzis George , Vuk-Pavlovic Stanimir
Published: August 2012

Tumor-associated hypoxia has been associated with malignant progression, metastasis, resistance to therapy, and poor clinical outcome in prostate cancer (CaP). Prompted by the evidence that hypoxia affects CaP, we studied global gene expression in 100 CaP tissues and 71 samples of adjacent benign tissues. RNA was extracted from cancer cells isolated by laser-capture microdissection (LCM) or without isolation (“bulk tissue”). We found 24 hypoxia-associated genes significantly overexpressed in CaP (p≤0.02), both in bulk tissue and LCM. Among hypoxia-associated genes, the disc large (drosophila) homolog-associated protein 5 (DLG7), hyaluronan-mediated motility receptor (HMMR) and cyclin B1 (CCNB1) were associated with Gleason score and systemic progression. Since the products of HMMR and CCNB1 have been recently identified as molecular markers of CaP progression, we postulated that DLG7 has prognostic value also. To test this hypothesis we measured transcript levels for DLG7 in a 150-pair case-control cohort. The cases (progression to systemic disease within five years of surgery) and controls (no progression within seven years) were matched for clinical and pathologic prognostic variables, including grade, stage, and preoperative serum levels of PSA. The overall prognostic ability of DLG7, as tested in receiver operating characteristic analysis was of 0.74 (95% CL, 0.68 to 0.8), independent of the for ERG status. Overall, our data indicate that DLG7, a hypoxia-controlled gene have a prognostic value in high-risk CaP. To better define the value of DLG7 as a molecular predictor of CaP progression, we are currently assessing DLG7 protein levels by immunohistochemistry. Then we will analyze the association of DLG7 levels with clinical parameters. Introduction of oxygen tension as a variable may constitute a tool for the identification of novel biomarkers for CaP. Present address CRG: University of Mississippi Cancer Institute, Jackson, MS, USA. Support: DOD PC094680 (CRG), PCF Creativity Award (CRG), Mayo Clinic Prostate SPORE 5P50CA091956 (SV-P); Mrs. Adelyn L. Luther, Singer Island, Florida and Mayo Clinic Cancer Center (SV-P).

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 116. doi:1538-7445.AM2012-116