tbuckley/cabot-search huggingface dataset:
Abstract 1350: Genetic variations in apoptosis pathway are associated with survival in late stage non-small cell lung cancer.
Authors: Xiang Shu, Charles Lu, Joe Y. Chang, Jack A. Roth, Xifeng Wu
Journal: Cancer Research (2013)

Abstract Dysregulation of apoptosis pathway plays an essential role in carcinogenesis, tumor progression, and resistance to chemotherapy. We hypothesized that genetic variations in genes involved in the apoptosis pathway may affect the survival in late stage non-small cell lung cancer (NSCLC) patients. To test this hypothesis, we genotyped 583 tagging SNPs in 598 late stage NSCLC patients and analyzed their associations with survival individually and jointly. Seven SNPs were statistically significantly associated with overall survival after correction for multiple comparisons (q&amp;lt;0.1). The most significant SNP was rs17592236 on FOXO1 gene under the dominant model (OR: 2.54, 95%CI: 1.71-3.78, p=4.15x10−6). We also observed a significant cumulative effect. Compared to the reference group (patients with no more than two risk alleles), those having five or more risk alleles were much more likely to die within seven months (HR: 3.58, 95% CI: 2.55-5.04, p&amp;lt;0.001). Notably, the median survival time (MST) was significantly reduced by up to 15 months in high risk patients when compared to the reference group (MST: 22.2 months, p&amp;lt;0.001). Survival tree analysis revealed potential higher order gene-gene interactions among these SNPs. Our results provided evidence that genetic variations in the apoptosis pathway modulate NSCLC survival and may serve as biomarkers to differentiate NSCLC patients with different prognosis. Citation Format: Xiang Shu, Charles Lu, Joe Y. Chang, Jack A. Roth, Xifeng Wu. Genetic variations in apoptosis pathway are associated with survival in late stage non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1350. doi:10.1158/1538-7445.AM2013-1350
Diagnosis of mass forming lesions in combination with real-time tissue elastography.
Authors: Y Nishiyama, A Kawagoe, U Sakaguchi, R Nishiyama
Journal: Cancer Research (2009)

Abstract Abstract #4013 [Purpose]&amp;#x2028; Although “hardness” is a characteristic of invasive carcinomas, it was not given much importance until now because of its poor quantitative nature and reproducibility. However, due to the development of real-time tissue elastography (EG), the objective measurement of “hardness” is now possible. Moreover, we examined whether mammography (MMG) + B-mode ultrasound (US) in combination with EG improves diagnosability.&amp;#x2028; [Subjects and methods]&amp;#x2028; One hundred and seventy-seven patients with mass-image-forming lesions (135 benign, 42 malignant) whose tissues were diagnosed by core and mammotome biopsies from Oct 2007 to May 2008 were included in the study. Instruments used were Hitachi EUB-8500 and HV-900. The hardness is scored on a scale 1 to 5. Score 1: Distortion appears in the image of the entire low echo tumors, Score 2: Image of most of tumors are distorted but no distortion is seen in certain areas, Score 3: Distortion appears only in the peripheral areas, Score 4: No distortion appears in the entire tumors, and Score 5: No distortion appears even in the peripheral areas. The cases over score 4 are assumed to be malignant. US of category 4 or more, and MMG of category 3 or more were evaluated as malignant.&amp;#x2028; [Results]&amp;#x2028; In 57 patients with lesions of less than 1.1 cm (50 benign, 7 malignant), US + MMG showed sensitivity and specificity of 71.4% and 88.0%, respectively, whereas US + MMG + EG showed sensitivity and specificity of 100% and 80.8%. Moreover, when EG was combined with conventional methods, sensitivity increased from 71.4% to 100%. On the other hand, in 120 patients with lesions of 1.1 cm or more (85 benign, 35 malignant), US + MMG showed sensitivity and specificity of 100% and 55.3%, respectively, whereas US + MMG + EG showed sensitivity and specificity of 100% and 61.2%. There were no significant differences in sensitivity and specificity between the 2 methods, and no additional advantages were observed when EG was used.&amp;#x2028; [Conclusions]&amp;#x2028; Thus, in this study sensitivity could be increased by EG for tumors with a diameter of less than 1.1 cm. Therefore, it was suggested that biopsy may be omissible for low EG scores. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4013.
President's Cancer Panel Nominated
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article President's Cancer Panel Nominated Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 9, 1 May 1991, Page 607, https://doi.org/10.1093/jnci/83.9.607-a Published: 01 May 1991
Abstract LB-22: Gemcitabine resistance is associated with EMT phenotype along with expression of cancer stem cell markers and a specific miRNA profile in the human pancreatic cancer cell line BxPC3
Authors: Alakesh Bera, James W. Freeman, Kolaparthi VenkataSubbaRao, Shujie Zhao
Journal: Cancer Research (2012)

Abstract Despite new therapeutic strategies, human pancreatic ductal adenocarcinomas (PDAC) remain one of the greatest oncological challenges, as the rate of incidence almost equals the rate of mortality with a 5-year survival of less than 5%. Gemcitabine is the standard therapy for PDAC and is mostly used alone or in combination with an EGFR inhibitor. While tumors respond to Gemcitabine treatment initially, they generally develop chemoresistance. A thorough understanding of molecular events that promote resistance against Gemcitabine may identify pathways that can be efficiently targeted to reverse chemoresistance. A cell line model resistant to Gemcitabine was generated by transiently exposing BxPC3 cells to increasing concentrations of Gemcitabine. This Gemcitabine resistant cell line, BxPC3-GzR, was compared with untreated BxPC3 control cells. BxPC3-GzR cells showed properties of undergoing epithelial to mesenchymal transition (EMT) and these included a spindle shaped morphology, an increase in expression of vimentin and a decrease in expression of E-cadherin. BxPC3-GzR cells also showed an increase of expression of CD44 and in expression of phosphorylated STAT3TY705, which are characteristic of cancer stem cells. BxPC3 and BxPC3-GzR where further compared by microarray analyses for expression of micro-RNAs (miRNAs). BxPC3-GzR cells showed a specific miRNA expression profile (9 positively and 8 negatively regulated). Thus far seven of eight miRNAs identified as altered in BxPC3-GzR cells were validated by real-time RT-PCR (miR-15b, miR-21, miR-100, miRNA -125b, miRNA-155, miRNA-205 and miRNA-455-3p). These studies suggest that Gemcitabine treatment of PDAC selects for a resistant population of tumor cells that have a mesenchymal/stem cell-like phenotype and that express a distinct miRNA profile. Targeting these miRNAs may provide novel targets for restoring or enhancing anti-tumor response of Gemcitabine. 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 LB-22. doi:1538-7445.AM2012-LB-22
Abstract 3636: The complex mechanism of resistance of human neuroblastoma cells to chemotherapeutic drugs
Authors: Sandra H. Clark, Timothy B. Lautz, Xin Zheng, Janette L. Holub, Yi-Yong Qui, Fei Chu, Mary Beth Madonna
Journal: Cancer Research (2010)

Abstract It has become evident that the biological processes which allow malignant cells to survive in the presence of cytotoxic drugs are extraordinarily complex, and recent findings indicate that a multitude of cellular defense mechanisms may be involved in the development of drug resistance. In order to dissect the dynamic changes in gene expression during the process of acquiring drug resistance, four human neuroblastoma cell lines (IMR 32, BE(2)-C, SK-N-SH and SH-SY5Y) were used to generate drug-resistant cell lines using clinically appropriate chemotherapeutic agents (Doxorubicin and Busulfan). Additionally, in order to understand the physiological role of histone deacetylase (HDACs) in the development of drug resistance in human neuroblastoma and to determine if this development can be delayed or totally suppressed by the HDACs inhibition, the cells were separated into those that were pretreated with a histone deacetylase (HDAC) inhibitor: suberoylanilide hydroxamic acid (SAHA), and those that were not pretreated. Cells were deemed drug-resistant when the cells were able to grow efficiently in drug concentrations of two log concentrations higher than the IC50 level. Neuroblastoma cells were collected at each log phase increase of cytotoxic agent to compare changes in P-glycoprotein and midkine expression; cross-resistance between chemotherapeutic agents, and presence of survival proteins in each group. The creation of these resistant human neuroblastoma cell lines and the determination of the transcriptional changes occurring as the cells become resistant may have important implications for clinical treatment of human neuroblastoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3636.
Abstract P2-14-03: “Ethinylestradiol” is beneficial for postmenopausal advanced breast cancer patients heavily pre-treated with endocrine agents
Authors: H Iwase, Y Yamamoto, K-I Murakami, M Yamamoto-Ibusuki, S Tomita, Y Omoto
Journal: Cancer Research (2012)

Abstract Purpose and Methods: Estrogen deprivation therapy using aromatase inhibitors is a standard therapy in postmenopausal hormone-dependent breast cancer. Paradoxically, low-dose estradiol was reported to be beneficial for the postmenopausal patients who have been heavily pre-treated with long-term sequential anti-estrogen therapies. To determine efficacy and safety of ethinylestradiol (3mg/day oral), a phase 2 study has been performed for the postmenopausal patients with advanced or recurrent breast cancer who became resistant to sequential endocrine treatments. The primary endpoint was clinical benefit rate, secondary were safety, objective response rate and time to progression. The interim data will be reported because of the extremely beneficial results. Results: Eighteen cases with ER-positive tumor which showed resistance to previous sequential-endocrine therapies including SERMs and/or aromatase inhibitors were registered from Oct 2010 to May 2012. Their mean age was 62 years-old and the mean observation time was 9.2 months. Nine cases were evaluated as partial response, 1 case as long NC, 3 cases as stable disease, and another 2 cases as progressive disease. In three cases of all 18 cases, the estradiol administration was withdrawn within 1 week with their early endocrine-related symptoms, such as nausea, general fatigue and fever. Duration of effect in the case of the PR (including the 4 ongoing cases) was more than 24 weeks. All of 9 responders had high ER expression in the primary or metastatic tumor and had a history of long-term endocrine therapies in metastatic setting and had response to previous endocrine therapies. Serum estradiol levels elevated as 30–100pg/mL, and FSH was suppressed below premenopausal levels in 4 weeks later administration. Although the weight gain, irregular vaginal bleeding, or endometrial thickening was observed in patients treated with long-term treatment, there was no severe adverse event, such as deep venous thrombosis or other malignancies in this series. Discussion: The mechanism of low-dose estrogen treatment can be considered the estrogen-induced apoptosis. The high ER expression and the response to previous endocrine therapies might be recognized as predictive factor of this treatment. This low-dose estrogen therapy may contribute to overturn the common sense of the endocrine therapy for breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-14-03.
Anaphylaxis Associated with Blue Dye
Authors: Antonio Gil-Moreno, Assumpcio Perez-Benavente
Journal: New England Journal of Medicine (2012)

A 33-year-old woman was admitted to the hospital for surgery for early squamous-cell cervical cancer (stage IB1, with a tumor <2 cm in diameter). Magnetic resonance imaging showed neither lymphadenopathy nor paracervical involvement.
The Role of Stromal Cells in Tumor Metastases.
Authors: A. Pieters, D. Duda, E. Steller, D. Fukumura, R. Jain
Journal: Cancer Research (2009)

Abstract Background: In 1889, Stephen Paget hypothesized that metastatic cells - the “seeds” - only grow in the secondary sites - the “soil” - with a permissive microenvironment. Here, we show that the “seeds” can carry their own “soil” - activated fibroblasts from primary site of metastatic tumors. Moreover, we report that carryover of these non-malignant host-derived cells during metastatic cell colonization in the lungs can increase cancer's metastatic efficiency.Materials and Methods: We use multiple animal models and two metastatic tumor cell lines (LLC1 and LA-P0297) to study the composition, origin and role of fragments shed by tumors in the metastatic process.Results: we have shown that, in addition to single cells (81%), tumors shed fragments consisting of both tumor and host cells. We show that these fragments are more viable in the circulation compared to tumor cells alone (p&amp;lt;0.05). When we selectively deplete the host cells in the tumor microenvironment the spontaneous formation of metastases is significantly reduced three weeks after primary tumor resection compared to control mice (p&amp;lt;0.05). Next, survival was significantly increased in mice with metastases after co-implantation of carcinoma-associated fibroblasts (CAFs) isolated from breast cancer patients together with LLC1 cells, but had no effect in mice implanted with LLC1 cells alone (p&amp;lt;0.01) Lastly, we have assessed the nature of these host stromal cells using immunohistochemistry and RT-PCR and indentified the majority of them as being of mesenchymal/fibroblast lineage.Discussion: We found that tumor-associated stromal cells can escape primary tumors along with cancer cells, survive in blood circulation and in metastatic nodules. Pre-existence of a tissue-like structure in the form of heterotypic cell fragments may increase the viability of cancer cells in blood circulation and modulate metastasis efficiency. How this mechanism contributes to the organo-tropism of certain metastatic tumors is not known. But demonstration of the involvement of some of the same tumor “soil” in both local and distant tumor invasion has important conceptual and clinical implications for colonization during metastasis progression. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6151.
Inborn Error in the Terminal Step of Aldosterone Biosynthesis
Authors: Johannes D. Veldhuis, Howard E. Kulin, Richard J. Santen, Thomas E. Wilson, James C. Melby
Journal: New England Journal of Medicine (1980)

Profound salt wasting developed in a male infant who had marked reductions in serum and urinary aldosterone concentrations despite striking hyperreninemia. Coincident elevations in plasma and urinary levels of specific 18-hydroxysteroids localized the defect to corticosterone methyl oxidase Type II, the adrenal enzyme responsible for the final step of aldosterone synthesis. Salt replacement but not hydrocortisone ameliorated the clinical and metabolic abnormalities. Evaluation of 33 other family members disclosed the biochemical disorder in six other subjects who were affected in an autosomal-recessive pattern with variably severe clinical manifestations and abnormal ratios of 18-hydroxycorticosterone (or its metabolites) to aldosterone. This inborn error in aldosterone biosynthesis must be distinguished from other heritable, salt-losing defects in adrenal steroidogenesis.
Acute Nonlymphocytic Leukemia
Authors: Philip J. Fialkow, Jack W. Singer, John W. Adamson, Roger L. Berkow, Jan M. Friedman, Robert J. Jacobson, John W. Moohr
Journal: New England Journal of Medicine (1979)

Two patients with acute nonlymphocytic leukemia who were heterozygous for the X-chromosome-linked enzyme glucose-6-phosphate dehydrogenase were studied to determine the number and type of cells in which the disease arises. Both type A and B isoenzymes were found in normal tissues, but the myeloblasts showed only one enzyme type, indicating that at the time of study, the disease had a clonal origin. The observation in one patient that erythroid cells did not arise from this clone contrasts with conclusions reached in patients previously studied with chromosomal markers. The results suggest that in this patient, the leukemic clone suppressed expression of normal granulopoiesis but did not inhibit erythroid differentiation from normal progenitors. They suggest also that the disease is heterogeneous. In some patients, the disease is expressed in cells with differentiation restricted to the granulocyte-macrophage pathway; in others, it involves stem cells that also differentiate into erythrocytes. This heterogeneity may reflect differences in causation and could have prognostic importance.
Glioma Recurrence Versus Radiation Necrosis
Authors: Amarnath Jena, Sangeeta Taneja, Aashish Gambhir, Anil Kumar Mishra, Maria Mathew D'souza, Sapna Manocha Verma, Puja Panwar Hazari, Pradeep Negi, Ganesh Krishna Rao Jhadav, Shanti Kumar Sogani
Journal: Clinical Nuclear Medicine (2016)

This study aimed to investigate the potential of hybrid gadolinium (Gd)-enhanced F-fluoroethyl-L-tyrosine (F-FET) PET/MRI in distinguishing recurrence from radiation necrosis using simultaneously acquired multiple structural and functional parameters.Twenty-six patients (5 female and 21 male patients; mean ± SD age, 51.58 ± 15.97 years) with single or multiple contrast-enhancing brain lesions (n = 32) on MRI after surgery and radiation therapy were evaluated with simultaneously acquired Gd-enhanced F-FET PET/MRI. They were then followed up with resurgery and histopathological diagnosis (n = 9) and/or clinical/MRI- or PET/MRI-based imaging follow-up (n = 17). PET/MR images were analyzed using manually drawn regions of interest over areas of maximal contrast enhancement and/or FET uptake. Maximum target-to-background ratio (TBRmax), mean target-to-background ratio (TBRmean), and choline-to-creatine (Cho/Cr) ratios as well as normalized mean relative cerebral blood volume (rCBVmean) and mean apparent diffusion coefficient (ADCmean) were determined. The accuracy of each parameter individually and in various possible combinations for differentiating recurrence versus radiation necrosis was evaluated using 2-tailed independent samples Student t test, multivariate analysis of variance, and multivariate receiver operating characteristic analysis. Positive histopathological finding and long-term imaging/clinical follow-up suggestive of disease progression served as criterion standard.Of 26 patients, 19 were classified as recurrence, with 7 patients showing radiation necrosis. Individually, TBRmax, TBRmean, ADCmean, and Cho/Cr ratios as well as normalized rCBVmean was significant in differentiating recurrence from radiation necrosis, with an accuracy of 93.8% for TBRmax, 87.5% for TBRmean, 81.3% for ADCmean, 96.9% for Cho/Cr ratio, and 90.6% for normalized rCBVmean. The accuracy of both normalized rCBVmean and ADCmean was improved in combination with TBRmax or Cho/Cr ratio. However, TBRmax (or TBRmean) with Cho/Cr ratio yielded the highest accuracy, approaching up to 97%. Furthermore, maximum area under the curve is achieved with the combination of TBRmean, CBV, and Cho/Cr values.Our findings suggest that FET uptake with Cho/Cr ratio and normalized rCBVmean could be most useful to distinguish primary glioma recurrence from radiation necrosis. Hybrid simultaneous multiparametric F-FET PET/MRI might play a significant role in the evaluation of patients with suspected glioma recurrence.
MIDDLE OR OLDER AGE AT THE TIME OF BARIATRIC SURGERY FOR MORBID OBESITY IS ASSOCIATED WITH A HIGHER RISK FOR CARDIOVASCULAR EVENTS
Authors: Maharaj Singh, Ahmed Dalmar, Zoe Heis, Michael N Katzoff, Thomas Y. Chua, A. Jamil Tajik, Arshad Jahangir
Journal: Journal of the American College of Cardiology (2016)
Upregulation of Fra-1 and Fra-2 in breast cancer cells results in changes in adhesion, migration, invasion and stem cell markers.
Authors: C Schroeder, S Janke, S Krenkel, T Streichert, F Jaenicke, K Milde-Langosch
Journal: Cancer Research (2009)

Abstract Abstract #2058 Background: Fra-1 and Fra-2 (Fos-related antigen1 and 2) are members of the Fos family of AP-1 transcription factors which are often up-regulated in human mammary carcinomas. The results of previous studies with clinical tumor tissues and experimental studies of breast cancer cell-lines suggested that they might be involved in the regulation of tumor invasion and metastasis in breast cancer.&amp;#x2028; Materials and Methods: In order to analyze the impact of Fra-1 and Fra-2 on the aggressive behavior of breast cancer cells, we established stable transfectants of the weakly invasive MCF-7 cells and as well in the highly invasive MDA-MB231 breast cancer cells with Fra-1 and Fra-2 overexpression. Additionally we generated MCF-7 stable transfectants with inducible Fra-2 transcription controlled by the tetracycline-inducible tetON-system. The consequences of Fra-1 and Fra-2 upregulation on the biology of the breast cancer cells were analysed by MTT assays (proliferation) and Matrigel invasion assays (invasion and motility). In addition, possible target genes which were differentially regulated in stable transfectants with Fra-1 and Fra-2 overexpression were identified by microarray analysis and, partly Western blots.&amp;#x2028; Results: Cell proliferation was not influenced by Fra-1 and Fra-2. In contrast, the invasive potential of the cells was increased by Fra-1 and Fra-2 in MDA-MB231 and MCF7 cells. In addition, there was a similar effect on cell motility. By using the GeneChip Human Genome U133A 2.0 array (Affymetrix), we identified several genes which are known to be involved in cell adhesion, migration or invasion and which were up- or downregulated in stable transfectants, i.e. ICAM, L1CAM, ALCAM, CX43 etc. Moreover, Fra-2 overexpression in MDA-MB231 cells resulted in CD44 upregulation and CD24 downregulation, which is characteristic of breast cancer stem cells.&amp;#x2028; Discussion: In clinical breast cancer tissues, up-regulation of Fra-2 and Fra1 protein expression has been observed and was shown to be associated with a more aggressive phenotype. Our data of the experimental studies with breast cancer cell-lines indicates that Fra-2 as well as Fra-1 may play an important role in tumor progression by transcriptional regulation of genes which are involved in cell adhesion, invasion and motility. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2058.