bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4316: Suppression of Sp protein expression with Tolfenamic Acid inhibits oral Squamous Cell Carcinoma
Authors: Madero Rafael A. , Lee Chriss M. , Basha Riyaz M. , Abdelrahim Maen A. , Baker Cheryl H. , Shellenberger Thomas D.
Published: July 2012

OBJECTIVE: Upregulation of members of the Sp protein family is associated with cell proliferation and metastasis in multiple cancer types. Tolfenamic acid (TA) is a nonsteroidal anti-inflammatory drug shown to inhibit the expression of Sp proteins. We tested the hypothesis that TA inhibits Sp protein expression in human head and neck squamous cell carcinoma lines to suppress cell growth.

METHODS: An oral Squamous cell carcinoma cell line (UMSCC-1) was screened for Sp-1 expression, a known target for Tolfenamic Acid (TA). To assess the effect of TA on UMSCC-1 cells, in vitro cell proliferation assays were performed at 24, 48, 72, 96 and 120Hrs, in order to correlate the cell growth response to different drug concentrations (25, 50, 75 and 100 µM). In parallel, Western blot analyses were use to measure Sp-1 expression after 72hrs of drug treatment. In subsequent experiments, we analyzed the effect of TA and radiation on UMSCC-1 under two conditions. Experiment 1: Tolfenamic acid was added 24 hrs after the cells were seeded, and underwent different doses of radiation (5, 10 or 20 Gy) 24 hrs after drug treatment was started. Experiment 2: 24 hrs after seeding UMSCC-1 cells were exposed to different doses of radiation (5, 10 and 20 Gy) and TA was added 24 hrs post-radiation. Cell growth was measure ATP assays.

RESULTS: Preliminary results confirmed the presence of Sp-1 expression in the head and neck squamous cell carcinoma cell line, UMSCC-1. In vitro growth analysis showed a direct correlation between cell death and TA concentration. Additionally a synergistic effect was observed when using TA and radiation. Sp-1 has been identified as a transcription factor for the production of Survivin, a protein which is known to be overexpressed in most cancer cells and has been directly linked to the radiation-resistant phenomenon. By regulating the expression of SP-1 using tolfenamic acid, we have demonstrated a reduction and/or complete inhibition of the cancer cells capability to produce Survivin, sensitizing them to radiation.

CONCLUSIONS: Our study suggests that TA bears potential in the treatment of oral squamous cell carcinomas as a concomitant agent for traditional chemotherapeutic regimens. In parallel, preliminary data suggest that TA potentiates radiation sensitivity in human head and neck cancer cells. Animal's studies are warranted to further investigate TA in squamous cell carcinoma.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4316. doi:10.1158/1538-7445.AM2011-4316
Abstract 432: A tissue engineered human extra cellular matrix (hECM) inhibits tumor growth
Authors: Pinney Emmett , Schenone Aaron , Montes-Camacho Mayra , Suetsugu Atsushi , Easter David , Hoffman Robert M. , Naughton Gail
Published: July 2012

A human extracellular matrix (hECM) was extracted from deposits made by neonatal dermal fibroblasts that were seeded on dextran microspheres and cultivated in a stirred bioreactor. The resulting hECM is high in collagen content with reduced hydroxylation as well as proteins found primarily in fetal ECM. These include high concentrations of SPARC, fibulin-2, tenascin, decorin, lumican, and fibromodulin. This hECM was used to treat tumor lines that were introduced onto the CAM of the fertilized chicken egg or growing subcutaneously in the nude mouse. In the CAM model significant tumor inhibition by hECM was seen with the following tumor lines: B16 melanoma was reduced 67%, C6 glioma 58% and MDA-MB-435 breast cancer 78%. Histology indicated that where the cells are in contact with hECM the cells appeared apoptotic. In the nude mouse models similar inhibition by hECM was observed: B16 melanoma was reduced 61%, C6 glioma 60% and MDA-MB-435 breast cancer reduced 58%. Apoptotic pathway activation was confirmed with caspase 9 upregulation in a dose-dependent response to hECM. These data indicate that an ECM rich in fetal proteins is capable of retarding tumor growth.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 432. doi:10.1158/1538-7445.AM2011-432
Abstract 4324: Loss of TGF-beta receptor I and PTEN promotes HNSCC
Authors: Bian Yansong , Hall Bradford , Sun Zhi-Jun , Molinolo Alfredo , Chen Wanjun , Van Waes Carter , Kulkarni Ashok
Published: July 2012

The precise molecular mechanisms that contribute to the initiation and progression of head and neck squamous cell carcinoma (HNSCC) have not been clearly delineated. Here, we report that defects in the TGF-β and PI3K/Akt signaling pathways are common in human HNSCCs. Activation of the PI3K/Akt pathway due to PTEN deletion gives rise to hyperproliferation in the head and neck epithelia, but only a few lesions progressed to HNSCCs. Strikingly, PTEN deletion, in combination with a loss of Tgfbr1, caused HNSCC with complete penetrance. Molecular analysis revealed enhanced cell proliferation, increased expression of CCND1 and decreased expression of CDKN1A in the basal layer of the head and neck epithelia, as well as in the tumors of Tgfbr1/PTEN double conditional knockout (2cKO) mice. These tumors displayed pathology and multiple molecular alterations that resembled human HNSCCs. Furthermore, the neoplastic transformation was due to senescence evasion and was associated with an increased number of putative (CD44+, CD133+) cancer stem cells. In addition, myeloid derived suppressor cell (MDSC) infiltration, angiogenesis and immune suppression in the tumor microenvironment also accompanied mouse head and neck carcinogenesis. The Tgfbr1/PTEN 2cKO mouse model is suitable for preclinical intervention and has significant implications in the development of diagnostic cancer biomarkers as well as effective preventive and therapeutic strategies for the treatment of HNSCCs.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4324. doi:10.1158/1538-7445.AM2011-4324
Abstract LB-161: A complete regression and therapeutic vaccination against aggressive malignant rat mesenchymal tumors with “stemness” characteristics obtained by intratumoral injection of LTX-315 (Oncopore®)
Authors: Rekdal Øystein , Wang MengYu , Camilio Ketil , Sveinbjornsson Baldur , Rolstad Bent , Kvalheim Gunnar
Published: July 2012

Background: In order to develop more effective anticancer agents there is a shift from not only treating the bulk of cells in a tumor but also to target the self renewing cancer stem cells (CSCs). Standard treatment with chemotherapy and radiotherapy is unable to eradicate CSCs and therefore other treatment modalites against CSCs are needed. LTX-315 (Oncopore®) is a chemically modified cytolytic peptide which is equally active against drug-sensitive and drug-resistant cancer cells. Earlier animal studies have demonstrated that treatment of syngenic murine A20 B-lymphomas and CT26WT carcinomas with intratumoral (i.t.) injection with LTX-315 resulted in complete tumor regression. The present study was undertaken to investigate whether LTX-315 induced an antitumor response in vivo in a novel malignant rat mesenchymal tumor model with “stemness” properties. Methods: Following long-term culturing of bone marrow-derived rat mesenchymal cells, a transformed mesenchymal cell line (rTMSC) has been been developed. rTMSC has, as the non-malignant rMSC, maintained osteogenic and adipose differentation properties and side population cells from rTMSC are highly clonogenic both in vitro and in vivo. Previously we have shown that s.c. as well as i.v. or i.p. injection of rTMSCs form immature solid sarcomas both in nude rats as well as in PVG rats. In this study the rTMSCs were marked with a dual reporter gene GFP and Luciferase and a CCD camera was used for dynamic living imaging. rTMSCs (5×105 cells) were subcutaneously inoculated into PVG rats and established tumors treated i.t. with LTX-315. Results: Intratumoral treatment with LTX-315 resulted in a complete regression in the majority of the treated animals. Successfully treated mice were protected against s.c. or i.p. re-challenge with rTMSCs. Conclusions: Taken together, our results suggest that LTX-315 treatment induced complete regression and long-term, specific cellular immunity against malignant rat mesenchymal tumor cells with “stemness” properties”. Thus, intratumoral administration of a cytolytic peptide might, in addition to providing local tumor control, confer a novel strategy for therapeutic vaccination against established cancers containing CSCs

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-161. doi:10.1158/1538-7445.AM2011-LB-161
Abstract LB-178: Analysis of restored FFPE samples on Infinium methylation arrays
Authors: Le Jennie , Pokholok Dmitry , Teo Wei Wen , Barnes Brett , Steemers Frank , Hansen Mark , Fan Jian-Bing , Ronaghi Mostafa , Shen Richard , Helm Alex , Fackler Mary Jo , Umbricht Chris , Bibikova Marina , Sukumar Saraswati , Gunderson Kevin L.
Published: July 2012

Millions of Formalin Fixed Paraffin Embedded (FFPE) cancer tissue samples currently present in the US and worldwide provide an enormous, invaluable repository to the discovery of biomarkers in cancer research, drug development, diagnosis and treatment of diseases. However, the processes of fixation and storage of FFPE samples leads to degradation and base modification with chemical residues. This degraded FFPE DNA is inefficiently amplified by the Infinium® whole genome amplification (WGA) step leading to poor performance in genome wide methylation analysis. In this study, purified FFPE DNA or crude lysates (200–500 ng input) were bisulfite converted and restored through Illumina's Infinium HD DNA Restoration kit consisting of a combination of treatment with a DNA polymerase, a repair enzyme, and a ligase. Results of methylation analysis on high density HumanMethylation450 BeadChip®, featuring over 450,000 assays indicated that even highly degraded samples which show initial call rates (genes detected p =0.01) of 50–70% can be successfully restored to a state that achieved call rates of greater than 90%. Direct comparison of frozen and FFPE samples from the same tumors showed an R2 correlation of beta values of greater than 95.0% between fresh frozen (FF) and FFPE samples. We also developed a method to assess FFPE sample quality based on a 90 bp qPCR assay (Infinium HD FFPE QC kit). In this assay FFPE samples exhibiting a Ct (Cq) difference of less than six relative to an intact standard are considered to pass the QC test and generally perform well in the assay.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-178. doi:10.1158/1538-7445.AM2011-LB-178
Abstract LB-424: A genome-wide association study identifies a locus on chromosome 14q21 as a predictor of leukocyte telomere length and as a marker of susceptibility to bladder cancer
Authors: Gu Jian , Chen Meng , Shete Sanjay , Amos Christopher I. , Kamat Ashish , Ye Yuanqing , Lin Jie , Dinney Colin P. , Wu Xifeng
Published: July 2012

Telomeres play a critical role in maintaining genome integrity. Telomere shortening is associated with the risk of many aging-related diseases. Classic twin studies have shown that genetic components may contribute up to 80% of the heritability of telomere length. In the study we report here, we used a multi-stage genome-wide association study (GWAS) to identify genetic determinants of telomere length. The mean telomere length in peripheral blood leukocytes was measured by quantitative real-time polymerase chain reaction. We first analyzed 300,000 single-nucleotide polymorphisms (SNPs) in 459 healthy controls, finding 15,120 SNPs associated with telomere length at P < 0.05. We then validated these SNPs in two independent populations comprising 890 and 270 healthy controls, respectively. Four SNPs, including rs398652 on 14q21, were associated with telomere length across all three populations (pooled P-values of < 10−5). The variant alleles of these SNPs were associated with longer telomere length. We then analyzed the association of these SNPs with the risk of bladder cancer in a large case-control study. The variant allele of rs398652 was associated with a significantly reduced risk of bladder cancer (odds ratio = 0.81; 95% confidence interval, 0.67–0.97; P = 0.025), consistent with the correlation of this variant allele with longer telomeres. We then conducted a mediation analysis to examine whether the association between rs398652 and reduced bladder cancer risk is mediated by telomere length, finding that telomere length was a significant mediator of the relationship between rs398652 and bladder cancer (P = 0.013) but that it explains only 14% of the effect. In conclusion, we found that the SNP rs398652 on 14q21 was associated with longer telomere length and a reduced risk of bladder cancer and that a small portion of the effect of this SNP on bladder cancer risk was mediated by telomere length.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-424. doi:10.1158/1538-7445.AM2011-LB-424
Abstract LB-463: Proteomic patterns of colonic submucosa delineates the inflammatory colitides. This could aid understand IBD-related colorectal malignancy
Authors: Schäffer Michael W. , Smith Joan C. , Roy Tanusri Ghosh , Wise Paul E. , Seeley Erin H. , Washington Mary K. , Schwartz David A. , Adunyah Samuel E. , Muldoon Roberta L. , Herline Alan J. , Moses Harold L. , Caprioli Richard M. , M'Koma Amosy E.
Published: July 2012

Purpose: Differentiating Crohn's colitis (CC) and ulcerative colitis (UC) can be challenging even in combination of clinical, endoscopic, radiologic and histopathology examination. Biomarker studies have thus far been unsuccessful for disease delineation. We aim to use unique tissue proteomic methods to evaluate colonic tissue layers for potential biomarkers to identify CC vs. UC. Methods: Fresh-frozen colon specimens from resections for IBD and/or colorectal cancer were retrospectively retrieved. Colitis diagnoses were histologically re-confirmed by a blinded gastrointestinal pathologist. Three sample groups (n=5 each group) were examined: normal colon from CRC specimens (control), UC & CC. MALDI-MS was used to profile mucosal and submucosal compartments individually. Frozen tissues were sectioned at ∼10–15 μm for mounting onto either metal or conductive glass target plates (the glass plates allowing for histologic and MALDI-MS analysis on the same section). Sinapinic acid (20 mg/mL in 50:50 acetonitrile: 0.1% TFA in water) was used to give the best combination of uniform crystal coverage and signal quality for direct tissue protein analysis. Results: MALDI-MS achieved high mass accuracy (±0.01 Daltons) in the lower mass range (<15 kDa). There was distinguishable isotopic resolution of mass-to-charge ratio (m/z) values between normal vs the IBD and more strikingly between CC vs. UC (p< 0.0009) of SAM and FDR tests. There were 5 statistically significant discriminative m/z peaks observed in CC vs UC submucosa. The mucosa did not yield such distinctive peaks. Both the mucosa and submucosa provided signatures that differentiated IBD (CC or UC)) from control tissues (p< 0.001). Conclusions: MALDI-MS tissue profiling as described distinguished the colitides. The methodology revealed 5 m/z peaks of interest. Analyses are underway to identify these IBD discriminative proteins. We hypothesize that these biomarker candidates that distinguish UC from CC will allow delineation of indeterminate colitis into UC or CC. Whether these protein fingerprints play a role in colonic carcinogenesis remains to be elucidated.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-463. doi:10.1158/1538-7445.AM2011-LB-463
Abstract LB-48: Cooperation of NF-κB, STAT3 and p300 on the growth and survival of plasma-cell neoplasia
Authors: Han Seong-Su , Son Dong-Ju , Duncan Kaylia , Janz Siegfried
Published: July 2012

Collaboration of pro-inflammatory cytokine, interleukin 6 (IL-6), with oncogenic transcription factor, MYC, has been implicated in the natural history of human B-cell and plasma-cell neoplasms such as multiple myeloma (MM) and Waldenström's macroglobulinemia (WM). To generate a mouse model of IL-6/MYC-driven B-lineage tumors, we intercrossed strain C.H2-Ld-IL6 mice, which carry a human IL6 cDNA gene under control of the major histocompatibility complex (MHC) H2-Ld promoter, with strain C.iMycEμ and C.iMycCα mice, which harbor a gene-insertion mutation that recapitulates the chromosomal T(12;15) translocation leading to deregulated expression of MYC in mouse plasmacytoma (PCT). Double-transgenic C.IL6/iMycEμ and C.IL6/iMycCα mice develop PCT with full penetrance (100% tumor incidence), short latencies (3–6 months) and remarkable phenotypic consistency. To test the hypothesis that nuclear factor-κB (NF-κB) signaling plays a role in malignant plasma-cell transformation in these mice, we performed electrophoretic mobility shift assays (EMSA) using splenic B cells from C.IL6/iMycΔEμ mice. We found that the splenocytes contained elevated levels of NF-κB and signal transducer and activator of transcription 3 (STAT3) DNA-binding activities compared to normal splenic B cells used as control. Super-shift assays demonstrated that in addition to p50, p65 and c-Rel (indicators of canonical NF-κB pathway activation), RelB was involved. This suggested the additional activation of alternative NF-kB signaling. NF-kB, pSTAT3 and co-transcription factor, p300, were shown to be physically associated in transgenic B cells. Ongoing studies are aimed at elucidating whether NF-κB/STAT3/p300 signaling underlies up-regulation of c-myc level in the course of PCT development. Using qPCR we also found that p21 – which is usually known as a tumor suppressor and direct target of NF-κB, STAT3, p53 and MYC – exhibited increased p53-independent expression in B cells obtained from C.IL6/iMycΔEμ mice, but not from C.IL6 or iMycΔEμ mice. In contrast, the expression of Aurora kinase A, a direct upstream regulator of both NF-kB and E2F1, was strongly up-regulated in B cells from C.IL6/iMycΔEμ, C.IL6 and iMycΔEμ mice. Likewise, E2F1, a direct upstream regulator of p21, and E2F3, a direct upstream regulator of both p21 and Aurora kinase A, were upregulated. Our findings suggest that p21 is up-regulated, either directly or indirectly, through Aurora kinase A and/or NF-κB/STAT3/p300 complex. Furthermore, they indicate the usefulness of the newly developed IL-6/MYC mouse tumor model for identifying potential targets for the treatment and prevention of MM and WM.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-48. doi:10.1158/1538-7445.AM2011-LB-48
Abstract LB-52: Integrative protein and transcriptomic analysis identified an EMT-associated secretory phenotype that correlates with metastasis and predicts survival in lung adenocarcinoma patients
Authors: Reka Ajaya Kumar , Chen Guoan , Jones Richard , Kim Sinae , Michailidis George , Kuick Rork , Pisano Michael , Beer David , Omenn Gilbert , Keshamouni Venkateshwar
Published: July 2012

The epithelial-mesenchymal transition (EMT) confers many clinicaly relevant properties to cancer cells, including migratory and invasive capacity, resistance to apoptosis, drug resistance, evasion of host immune surveillance, and tumor stem cell traits. Therefore, we reasoned that characterizing the secretome of cultured cells in EMT may identify biomarkers which allow monitoring of EMT in tumors and provide a signature to predict metastasis and survival in patients with cancers. Utilizing aTGF-β-induced EMT model with A549 lung adenocarcinoma cells, we harvested serum-free conditioned media from control and EMT cells (5 ng/ml TGF-β, 72h) to quantitatively profile differentially expressed proteins by GeLC-MS/MS and spectral counting. We identified >2000 proteins, >70% of which were putative secretory proteins. Corresponding transcriptomic analysis was performed by Affymetrix U133-plus microarray which identified ∼3,500 genes as differentially expressed. By integrating these two data sets we derived an EMT-associated secretory phenotype (EASP) comprising 97 genes of secretory proteins that were differentially up-regulated by at least two-fold during EMT both for protein and mRNA levels. Several of these proteins were validated by MRM. Analysis of EASP expression in a gene expression dataset from 443 human lung adenocarcinoma tumors revealed strong positive correlations with lymph node metastasis (p<0.05), advanced tumor stage (p=0.006) and histological grade (p<0.00001). After splitting the 443 tumors into a training (n=254) and test (n=189) sets, random forest survival analysis, including age, sex and stage as variables, stratified the test-set into low, medium and high-risk groups with significant differences in overall survival (p=0.0002). For further validation we tested EASP in two independent histologically distinguished lung cancer data sets. Interestingly, EASP predicted survival only in the dataset with adenocarcinomas (n=111, p=0.03), not in the dataset with squamous tumors (n=130). This result indicates that integrative analysis of relevant biological processes in cell-culture models may provide mechanism-related, tumor type-specific, clinically-relevant biomarkers with significant prognostic value.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-52. doi:10.1158/1538-7445.AM2011-LB-52
Abstract LB-64: Hitting Testicular Cancer Where It Hurts: Through Public Awareness and Post-Treatment Support
Authors: Buckland Timothy
Published: July 2012

The American Cancer Society estimated that in 2010 there were 8480 American men diagnosed with testicular cancer. Within this population, the vast majority of those diagnosed were young males between the ages of 15 and 29. Although treatment of this disease has been highly effective, there are two key areas where support is lacking: public awareness and post-treatment care. Many young males that notice something wrong do not seek immediate medical attention due to a lack of education regarding the signs and symptoms of testicular cancer, as well as the embarrassing stigma of this disease. As in all cancer cases, finding and treating this disease early is crucial. Although this group has a high survival rate (bordering on 95%), the goal of early detection is to minimize exposure to harmful treatments and promote survival of all patients. Through the work of The Canadian Testicular Cancer Association, increasing awareness is being addressed in Canada. The goals of this Ontario-based organization are to make people aware of the early warning signs of testicular cancer and to encourage males that suspect something is wrong to seek medical attention. A recent campaign designed to combat these issues occurred last January. ‘Manuary’ is a month-long nationwide awareness campaign, with events occurring throughout the month.

The second underrepresented area of support for testicular cancer patients is in post-treatment care. As can be said for many young adult cancers, when patients are diagnosed, their lives are in a stage of transition. This fast-paced transitionary phase can be abruptly stalled with administration of treatment, creating a gap between a patient's pre-cancer life and where they have been left. Many young testicular cancer patients have trouble coping with this issue, creating feelings of isolation and depression. From a patient's stand point, there is a significant lack of support from the health care system in helping them deal with these issues. By creating support groups and making them nationally or even internationally available, the goal is to empower patients to see that they are not alone and develop strategies to overcome these emotions. Through connections within The Canadian Testicular Cancer Association, one-on-one patient interactions have been established. Mr. Buckland's goal is to make these resources easily accessible to all testicular cancer patients in any support group.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-64. doi:10.1158/1538-7445.AM2011-LB-64
Abstract LB-76: Services of a Cancer Center
Authors: Mapara Virginia
Published: July 2012

The Cancer Center in Harare is part of the Cancer Association in Zimbabwe. It is a nonprofit organization supported by donations from the public. The outreach programs and cancer assistance services are given free to the patients, institutions and the community. The association was formed in Bulawayo, its headquarters, in 1959, and then in Harare in 1961. The center is committed to empowering clients and their families to cope with the crisis of dealing with cancer through a holistic approach which will enable the client to develop a positive attitude to the disease throughout their treatment. The center provides the community with information to promote healthy lifestyle choices and to increase public awareness on the prevention and early detection of cancer.

The center seeks also seeks to: promote prevention of cancer through public awareness, talks and lectures; carry out counseling services and give psychological support; provide complimentary health therapies to those diagnosed of cancer; teach breast care, breast self examination and manages a breast care clinic; give nutritional advice to the cancer patients; and serve as a resource centre for patients through use of the library. The activities of the center include giving lectures, talks and print media to schools, corporate organizations and communities. Information on cancer is also given over radio, television and through the distribution of quarterly newsletters. Counseling services are provided to those diagnosed of cancer and their families. The organization also offers counseling services to patients in hospitals during chemotherapy and radiotherapy. The center provides a wide range of complimentary health therapies such as relaxation and meditation classes, aromatherapy (massage) reflexology, Reiki, shiatsu and use of rife therapy. Awareness campaigns are recognized and health education programs are intensified such as the worldwide recognized No Tobacco Day, Breast Cancer Awareness Month, and World Cancer Day.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-76. doi:10.1158/1538-7445.AM2011-LB-76
Abstract PL01-01: Effective translation of cancer discoveries to cancer treatment
Authors: Hait William N.
Published: July 2012

The objective of this presentation is to analyze the current status of translational research to understand the reasons for success, the barriers to further progress, and the insights that will continue to accelerate the enterprise. I will postulate that the most impactful drugs were developed because of specific observations about a type of malignancy rather than by studying targets in isolation. This will be tested by reviewing major scientific breakthroughs throughout the modern era of cancer treatment and will focus on the importance of biomarkers and companion diagnostic tests. Examples of how the merging of a deep understanding of a particular tumor type with modern cancer biology and cancer genomics will be presented. I will begin by attempting to define translation as the application of discoveries to the practice of medicine, a process that begins with a clinical observation that leads to a discovery, whose significance to a specific medical problem is recognized and acted upon. Each step in the process requires critical skill sets that span basic biology, pathology, pharmacology, clinical, and regulatory science. The challenges confronting those who participate have been carefully described and a variety of approaches to break down barriers are being continuously tested and upgraded. Although the success rate for drug development in oncology is lower than hoped, the number of new medical and biological entities moving into the clinic and on track for approval is immense, outpaces any other therapeutic area, and offers enormous hope to patients, physicians, and investigators alike.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr PL01-01. doi:10.1158/1538-7445.AM2011-PL01-01
Abstract SY12-01: Stem cell approaches dissect lung cancer biology
Authors: Kim Carla F.
Published: July 2012

Lung cancer is the major cause of death from cancer worldwide. The five-year survival rate for the majority of lung cancer patients is only 16% because their tumors are refractory to chemotherapeutics or quickly become resistant to therapeutic response. Also contributing to morbidity, most lung cancer patients already have advanced, metastatic disease at the time of diagnosis or develop metastases after surgical removal of early-stage primary lung tumors. The cancer stem cell (CSC) hypothesis is an attractive explanation for tumor growth, recurrence after treatment, and metastasis in some cancers, yet the precise role of CSCs in lung tumors has not been established. Since successful cancer therapy requires the elimination or incapacitation of all tumor cells capable of regenerating a tumor, it is crucial to characterize the cells that are able to propagate a tumor in vivo. We refer to these functionally important cancer cells as tumor-propagating cells (TPCs). Importantly, understanding the identity and molecular nature of TPCs will provide new opportunities for early detection, treatment and prevention of metastatic disease, whether or not they fit the CSC model in each type of cancer. My laboratory recently showed that murine lung adenocarcinomas, the most prevalent lung cancer subtype, contain a TPC population. In mice bearing tumors initiated with oncogenic Kras and deletion of p53, the cell surface marker Sca1 identifies cancer cells with stem cell properties. In contrast, TPCs are Sca1-negative in lung tumors that express a mutant EGFR. Thus, the predominant driving oncogenotype is an important determinant in the identification of TPC phenotype in lung cancer. This finding suggests that treatments directed against cancer stem cells should be targeted to subsets of patients grouped according to their oncogenotype. We have recently obtained global gene expression data from the Sca1-sorted populations of murine lung tumor cells, as well as their normal wild-type counterparts, to uncover the molecular pathways responsible for tumor propagation in lung adenocarcinoma. I will also discuss new avenues we have taken to understand the connections between TPCs and metastasis in mouse models as well as translating the importance of our findings in human lung cancer cells and patient samples.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY12-01. doi:10.1158/1538-7445.AM2011-SY12-01
Abstract SY12-03: Getting abreast of the mammary epithelial hierarchy and breast cancer
Authors: Visvader Jane E. , Asselin-Labat Marie-Liesse , Vaillant François , Lim Elgene , Bouras Toula , Pal Bhupinder , Wu Di , Smyth Gordon , Lindeman Geoff
Published: July 2012

To understand relationships between breast tissue, cells of origin and cancer stem cells in breast tumors, it is necessary to dissect the normal mammary epithelial hierarchy. We have isolated discrete populations of mouse and human mammary epithelial cells on the basis of cell-surface markers and defined subpopulations that are highly enriched for mammary stem, luminal progenitor and mature luminal cells. Transcriptome analyses of mouse and human mammary epithelial populations has led to the identification of multiple conserved genes and pathways. Analysis of different mouse models of mammary tumorigenesis using syngeneic transplantation assays and interrogation of molecular profiles has revealed potential cells of origin in preneoplastic tissue and the presence of a definitive cancer stem cell subset in different mouse mammary tumors. The role of the zinc finger transcription factor Gata-3, a critical regulator of luminal cell differentiation and a favourable prognostic indicator in breast cancer, has recently been explored in tumor initiation using mouse models. Gata-3 deficiency was found to increase the tumorigenicity of different epithelial subpopulations, with accompanying cell-fate changes. In the context of human breast tissue, analogous studies have enabled us to pinpoint the cellular defect occurring in precancerous tissue from BRCA1 mutation carriers. These carriers were shown to harbor aberrant luminal progenitor cells. Combined with interrogation of the molecular profiles of the different subtypes of breast cancer, the luminal progenitor was identified as the likely cell of origin for BRCA1-associated basal cancers.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY12-03. doi:10.1158/1538-7445.AM2011-SY12-03
Ventricular Access Devices Are Safe and Effective in the Treatment of Posthemorrhagic Ventricular Dilatation prior to Shunt Placement
Authors: Tian Ashley G. , Hintz Susan R. , Cohen Ronald S. , Edwards Michael S.B.
Published: July 2012

Intraventricular hemorrhage of prematurity (IVH) is a diagnosis that has become more frequent in recent years. Advances in medical care have led to survival of increasingly premature infants, as well as infants with more complex medical conditions. Treatment with a ventricular access device (VAD) was reported almost 3 decades ago; however, it is unclear how effective this treatment is in the current population of premature infants. At our institution (from 2004 to present), we treat posthemorrhagic hydrocephalus (PHH) with a VAD. In order to look at safety and efficacy, we retrospectively combed the medical records of premature children, admitted to Lucile Packard Children’s Hospital from January 2005 to December 2009, and identified 310 premature children with IVH. Of these, 28 children required treatment for PHH with a VAD. There were no infections associated with placement of these devices and a very low rate of other complications, such as need for repositioning (7.41%) or replacement (3.75%). Our data show that treatment with a VAD is very safe, with few complications and can be used to treat PHH in this very complex infant population.
Vertebral Choristoma in Lipomyelomeningocele: A Case Report
Authors: Joshua S.P. , Singh Pankaj Kumar , Mahapatra A.K.
Published: July 2012

Lipomeningocele is a type of occult spinal dysraphism characterized by a subcutaneous lipomatous mass that protrudes through a midline bony defect. We report a rare presentation of this condition – a vertebral choristoma wherein the lipomatous mass displaced the normally formed posterior elements – lamina and spinous process of L4 vertebra dorsally to an abnormal location in the absence of a bony defect.
Capecitabine plus Cisplatin as First-Line Chemotherapy for Advanced Biliary Tract Cancer: A Retrospective Single-Center Study
Authors: Woo Sang Myung , Lee Woo Jin , Han Sung-Sik , Park Sang-Jae , Kim Tae Hyun , Koh Young Hwan , Kim Hyun Bum , Hong Eun Kyung , Park Joong-Won , Kim Chang-Min
Published: July 2012

Background: Palliative chemotherapy is currently the primary therapeutic approach in the treatment of advanced biliary tract cancer (BTC). Our aim was to assess the efficacy and safety of capecitabine plus cisplatin as first-line chemotherapy for patients with advanced BTC and to analyze the relationship between the level of CA19-9 and clinical outcome. Methods: We retrospectively reviewed the records of patients who had unresectable, metastatic or recurrent BTC who were treated with capecitabine plus cisplatin. Capecitabine was administered orally at a dose of 1,000 mg/m2 twice a day for 14 days, followed by a 1-week rest period. Cisplatin was administered intravenously on days 1 and 8 at a dose of 30 mg/m2 for 60 min every 3 weeks. Results: A total of 176 patients were enrolled. Among the 143 assessable patients, 24 (17%) had a partial response. A complete response was radiologically confirmed in 1 patient who had gallbladder cancer. Sixty-two patients (43%) had stable disease and 56 patients (39%) had progressive disease. With a median follow-up of 5.7 months, the median time-to-progression (TTP) was 3.7 months (95% CI 3.1–4.3) and the median overall survival (OS) was 7.4 months (95% CI 6.1–8.7). There was a significant positive correlation between CA19-9 response and TTP (r = 0.66, p = 0.01). CA19-9 response was also significantly correlated with OS (r = 0.57, p < 0.01). The most common grade 3/4 toxicities were nausea/vomiting [12 patients (6.8%)]. Conclusions: Our results indicate that the capecitabine/cisplatin regimen is well tolerated and has moderate activity against advanced BTC. The CA19-9 response may be a suitable surrogate marker for patients with BTC who are treated with capecitabine/cisplatin.
Intake of Liquid and Solid Sucrose in Relation to Changes in Body Fatness over 6 Years among 8- to 10-Year-Old Children: The European Youth Heart Study
Authors: Olsen Nanna Julie , Andersen Lars Bo , Wedderkopp Niels , Kristensen Peter Lund , Heitmann Berit Lilienthal
Published: July 2012

Objective: To examine if intake of soft drinks is more closely associated with weight gain than other energy sources and if these associations are mediated through differences in energy intake or insulin level. Methods: Data derived from the Danish part of the European Youth Heart Study (n = 359). Height, weight, and waist circumference (WC) were measured in 1997-1998 and again in 2003-2004. Results: Intake of liquid sucrose was associated with changes in waist circumference (ΔWC) (β = 0.226, p = 0.07, R2 = 0.17) as well as BMI z-scores (ΔBMIz) (β = 0.031, p = 0.05, R2 = 0.30). Associations attenuated slightly after adjusting for energy intake, but were substantially reduced when adjusting for insulin. Adjustment for both insulin and energy intake attenuated the effect of soft drinks intake on ΔBMIz, but not on ΔWC. Conclusion: Liquid sucrose seemed more clearly associated with ΔWC and ΔBMIz than other energy sources. For ΔWC, the association seemed to be based on decreases in insulin sensitivity rather than increases in energy intake, whereas for ΔBMIz the association seemed to be based on both increases in energy intake and decreases in insulin sensitivity.
Circulation: Cardiovascular Quality and Outcomes
Editors' Picks
Authors:   The Editors
Published: July 2012

The following articles are being highlighted as part of
Circulation's
Topic Review series. This series summarizes the most important manuscripts, as selected by the editors, published in
Circulation
and the
Circulation
subspecialty journals. The studies included in this article represent the Editors' Picks for each
Circulation: Cardiovascular Quality and Outcomes'
issue published in 2011.
Effect of Addition of Clopidogrel to Aspirin on Mortality
Authors: Palacio Santiago , Hart Robert G. , Pearce Lesly A. , Benavente Oscar R.
Published: July 2012

Background and Purpose—

In the Secondary Prevention of Small Subcortical Strokes (SPS3) trial, addition of clopidogrel to aspirin was associated with an unexpected increase in mortality in patients with lacunar strokes. We assessed the effect of the addition of clopidogrel to aspirin on mortality in a meta-analysis of published randomized trials.

Methods—

Randomized trials in which clopidogrel was added to aspirin in subjects with vascular disease or vascular risk factors were identified. Trials were restricted to those with a mean follow-up of ≥14 days in which both the combination of aspirin and clopidogrel was tested and mortality was reported.

Results—

Twelve trials included 90 934 participants (mean age, 63 years; 70% men; median follow-up, 1 year) with 6849 observed deaths. There was no significant increase in mortality with the combination therapy either in 4 short-term (14 days–3 months; OR, 0.93; 95% CI, 0.87–0.99) or in 7 long-term (>3 months; hazard ratio, 0.97; 95% CI, 0.91–1.04) trials after 1 long-term trial (the SPS3 trial) was excluded because of heterogeneity. Addition of clopidogrel was associated with an increase in fatal hemorrhage (OR, 1.35; 95% CI, 0.97–1.90) and a reduction in myocardial infarction (OR, 0.82; 95% CI, 0.74–0.91).

Conclusions—

The addition of clopidogrel to aspirin has no overall effect on mortality. The SPS3 trial results are outliers, possibly because of a lower prevalence of coronary artery ischemia. Addition of clopidogrel to aspirin increases fatal bleeding and reduces myocardial infarction.

Clinical Trial Registration—

URL:
http//www.clinicaltrials.gov
. Unique identifier: NCT00059306.
Costs and Cost-Effectiveness of Carotid Stenting Versus Endarterectomy for Patients at Standard Surgical Risk
Authors: Vilain Katherine R. , Magnuson Elizabeth A. , Li Haiyan , Clark Wayne M. , Begg Richard J. , Sam Albert D. , Sternbergh W. Charles , Weaver Fred A. , Gray William A. , Voeks Jenifer H. , Brott Thomas G. , Cohen David J.
Published: July 2012

Background and Purpose—

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated similar rates of the primary composite end point between carotid artery stenting (CAS) and carotid endarterectomy (CEA), although the risk of stroke was higher with CAS, and the risk of myocardial infarction was higher with CEA. Given the large number of patients who are candidates for these procedures, an understanding of their relative cost and cost-effectiveness may have important implications for health care policy and treatment guidelines.

Methods—

We performed a formal economic evaluation alongside the CREST trial. Costs were estimated from all trial participants over the first year of follow-up using a combination of resource use data and hospital billing data. Patient-level health use scores were obtained using data from the SF-36. We then used a Markov disease-simulation model calibrated to the CREST results to project 10-year costs and quality-adjusted life expectancy for the 2 treatment groups.

Results—

Although initial procedural costs were $1025/patient higher with CAS, postprocedure costs and physician costs were lower such that total costs for the index hospitalization were similar for the CAS and CEA groups ($15 055 versus $14 816; mean difference, $239/patient; 95% CI for difference, −$297 to $775). Neither follow-up costs after discharge nor total 1-year costs differed significantly. For the CREST population, model-based projections over a 10-year time horizon demonstrated that CAS would result in a mean incremental cost of $524/patient and a reduction in quality-adjusted life expectancy of 0.008 years compared with CEA. Probabilistic sensitivity analysis demonstrated that CEA was economically attractive at an incremental cost-effectiveness threshold of $50 000/quality-adjusted life-year gained in 54% of samples, whereas CAS was economically attractive in 46%.

Conclusions—

Despite slightly lower in-trial costs and lower rates of stroke with CEA compared with CAS, projected 10-year outcomes from this controlled clinical trial demonstrate only trivial differences in overall healthcare costs and quality-adjusted life expectancy between the 2 strategies. If the CREST results can be replicated in clinical practice, these findings suggest that factors other than cost-effectiveness should be considered when deciding between treatment options for carotid artery stenosis in patients at standard risk for surgical complications.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique Identifier: NCT00004732.
A Characterization of the Variation in Relative Humidity across West Africa during the Dry Season
Authors: Seefeldt Mark W. , Hopson Thomas M. , Warner Thomas T.
Published: July 2012

The variation of relative humidity across West Africa during the dry season is evaluated using the Modern Era Retrospective Analysis for Research and Applications (MERRA) dataset and the method of self-organizing maps. Interest in the dry season of West Africa is related to the connection between near-surface atmospheric moisture and the occurrence of meningitis across West Africa, most notably in the region known as the meningitis belt. The patterns in relative humidity are analyzed in terms of frequency of each pattern as well as the sequencing from one pattern to the next. The variations in relative humidity are characterized subannually for individual years from 1979 to 2009 as well as decadally over the entire 30-yr duration of dry seasons in West Africa. The progression from relatively moist patterns to relatively dry patterns and back to the moist patterns over the course of the dry season corresponds to the northward and then southward migration of the intertropical convergence zone. The results indicate distinctly different frequency and sequencing of relative humidity patterns from year to year. The year-to-year changes in relative humidity patterns are gradual. There is some indication of a larger, possibly decadal, pattern to the year-to-year changes in the variation of relative humidity over the course of the dry season. The results are reflective of the reanalysis data including potentially unusual and erroneously dry conditions in central Africa after the mid-1990s.