tbuckley/cabot-search huggingface dataset:
Randomized phase II study of best-available 5-fluorouracil (5-FU) versus weekly paclitaxel in gastric cancer (GC) with peritoneal metastasis (PM) refractory to 5-FU-containing regimens (JCOG0407).
Authors: H. Takiuchi, H. Fukuda, N. Boku, Y. Shimada, J. Nasu, Y. Hamamoto, S. Hironaka, K. Yamaguchi, A. Takashima, A. Ohtsu
Journal: Journal of Clinical Oncology (2010)

4052 Background: 5-FU containing regimen is the most commonly used first-line treatment for advanced GC. However, there is no standard treatment after failure of first-line 5-FU-based regimen. In previous phase II trials, it was suggested that paclitaxel was active for GC with PM that was refractory to 5-FU-based chemotherapy. But, the survival and clinical benefit of paclitaxel compared with continuation of another 5-FU beyond progression is not known. Methods: Eligibility criteria included patients with histologically proven gastric adenocarcinoma; PM with radiologically confirmed intestinal stenosis or ascites; 20-75 years old; PS 0-2. One previous 5-FU containing regimen (bolus/continuous infusion[ci]/oral) was permitted, either adjuvant only or for metastatic disease. In the standard arm (Arm A), best- available 5-FU treatments were employed. When the prior chemotherapy included bolus 5-FU, 5-FUci (800 mg/m2/d, d1-5, q4w) was administered. For other cases, MTX/5-FU sequential therapy (MTX 100 mg/m2 followed by bolus 5-FU 600 mg/m2with leucovorin rescue, q1w) was administered. In the test arm (Arm B), weekly paclitaxel (80 mg/m2/d, day 1, 8, 15, q4w) was employed. The primary endpoint was overall survival. The study was designed as a randomized screening trial with one-sided alpha 0.3. Results: 100 pts were randomly allocated Arm A (n = 49) or Arm B (n = 51) between July 2005 and Dec 2008. Median survival time in each arm was the same, 7.7 months and survival at 1 year was 31.4% in Arm B and 27.1% in Arm A, and the 2-year survival was 9.1% and 2.9%, respectively (HR = 0.887 [0.571-1.377], p = 0.298). Median progression-free survival was longer with Arm B (3.7 vs. 2.4 months; HR = 0.568 [0.369-0.873], p = 0.0044). Frequencies (%) of grade 4 neutropenia, grade ≥ 3 febrile neutropenia, appetite loss, diarrhea, and treatment related death (Arm A/Arm B) were 6/2, 4/0, 14/2, 10/0 and 2/0, respectively. Conclusions: Weekly paclitaxel as second-line chemotherapy is feasible, safe and promising, and it can be considered as a good option for the future phase III trial in GC with PM refractory to 5-FU containing regimens. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb
Abstract 1180: Modulation of p73 isoform expression regulates aggressive behavior in NHL cell line model with 1p36 chromosomal disruption
Authors: Hesham M. Hassan, Michelle L. Varney, Shantaram S. Joshi, Rakesh K. Singh, Bhavana J. Dave
Journal: Cancer Research (2012)

Abstract Abnormalities of chromosome 1p36 locus are frequently detected in non Hodgkin lymphoma (NHL) and are associated with aggressive clinical behavior. TP73, a gene at 1p36 locus, is a member of the p53 tumor suppressor gene family, and regulates many important cellular pathways. TP73 gene function is controlled by a balance between two isoforms with opposing functions, the full length TAp73 protein (pro-apoptotic) and the NH2-terminally truncated ΔNp73 protein (anti-apoptotic through antagonizing both TAp73 and p53). Our previous work on diagnostic specimens of NHL cases had shown a differential ΔNp73 up-regulation and increase in ΔNp73:TAp73 expression ratio among NHL cases with 1p36 chromosomal disruption as compared to NHL cases without 1p36 disruption, which correlates with decreased apoptosis, increased cellular proliferation and increased angiogenesis. We hypothesized that modulated expression of the p73 isoforms will alter the aggressive behavior of a NHL cell line containing 1p36 disruption. We used a NHL cell line (Granta-519) that has 1p36 disruption as a model. Granta-519 cells express higher levels of ΔNp73 isoform similar to what was observed in NHL cases with 1p36 abnormality. Next, we stably transfected Granta-519 with a TAp73 mammalian expression vector to modulate the ΔNp73:TAp73 ratio. Cell cycle analysis showed an increase in the percentage of G1 cells and decrease in the percentage of S and G2 cells in TAp73-trasnfected Granta-519 cells as compared to control vector-transfected cells. Serum deprivation significantly inhibited the growth of Granta-519-TAp73- cells as compared to control vector-transfected cells. Moreover, reconstitution of TAp73 expression in Granta-519 cells significantly enhanced their response to Doxorubicin. Together, these results provide an insight on modulation of ΔNp73:TAp73 as a novel therapeutic target in NHL with 1p36 abnormalities. 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 1180. doi:1538-7445.AM2012-1180
Phase 2 Study of Nivolumab (ANTI-PROGRAMMED DEATH-1 [PD-1]) in Patients (PTS) with Advanced, Refractory Squamous (SQ) Non-Small Cell Lung Cancer (NSCLC)
Authors: G. Zalcman, N.A. Rizvi, H. Lena, J. Wolf, J. Mazieres, S.J. Antonia, E. Minenza, D. Planchard, B.J. Lestini, S.S. Ramalingam
Journal: Annals of Oncology (2015)
Abstract P3-01-03: Breast density profile in a prospective large breast cancer screening program in South Brazil.
Authors: M Caleffi, J Zignani, A Clarissa, BJ Ademar, R Ribeiro, DF Dakir
Journal: Cancer Research (2012)

Abstract Introduction: Women involved in breast cancer (BC) screening of NMPOA cohort, in South Brazil, are undergoing their 8th year of follow up. As mammography breast density is a well-established risk factor for breast cancer, since the beginning of this study, all mammograms were characterized according to breast density Birads pattern. Recently, a study published in the JNCI showed an association of this pattern of breast density with tumors that presented more aggressive characteristics. Objective: To characterize the mammography density patterns of women involved in a prospective NMPOA cohort, and describe the mammography density appearance of those diagnosed with BC, correlating it with genomic classification and stages. Methods: First screening mammogram of all women in the cohort was reviewed. All mammograms were classified according to BIRADS® patterns of density, which take into account the percentage of fibroglandular tissue (A: less than 25%; B: from 25 to 50%; C: from 50% to 75%, and D: more the 75%). Also, we compared breast density among the 17 incidental breast cancers diagnosed during follow up. Genomic classification and staging of the diagnosed cancers was described. Results: A total of 2943 first mammograms were done until the end of women accrued inclusion in the cohort (April of 2006). Women's age ranged from 40 to 69 years. From these, 820 were A density, 893 B, 970 C and 260 D (graphic 1). Until November 2011, 17 cancer cases were found in the screening population. From these, 04 were A, 06 were B, 06 were C and 1 were D (graphic 2). Cancer staging and genomic classification according to each mammogram density are summarized on Tables 1 and 2. No differences were observed in BC staging when we compared the A and B density with C and D (p = 1.0). The same occurred with the genomic classification (p = 0.48). Conclusion: Our screening population has a predominance of low mammogram densities, probably due to the high body mass index observed in previous studies of this cohort. With respect to cancer cases, the absence of statistical significance results suggests that longer follow up will be necessary for definitive conclusions. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-01-03.
FRI0574-HPR The Effect of Kinesiophobia on Physical Activity in Individuals with Chronic Neck Pain
Authors: I. Demirbüken, O. Aydoğdu, T. Kuru Çolak, B. Özgül, Z. Sarı, S.U. Yurdalan
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> 9Avoidance behavior due to fear9 called 9kinesiophobia9, is being increasingly recognized as an important contributor to disability among individuals with chronic pain [1]. While physical activity is a common management strategy for musculoskeletal pain [2], individuals with chronic pain avoid their daily physical activities and become less active. Neck pain is a fairly common musculoskeletal condition within chronic pain problems in the community [3]. Although the relation between kinesiophobia and disability, muscle strength and range of motion was investigated [4], the effect of kinesiophobia over the physical activity level of the individuals with neck pain has not been investigated yet. <h3>Objectives</h3> The aim of this study was to explore the relationship between level of kinesiophobia and level of physical activity in individuals suffering from chronic neck pain. <h3>Methods</h3> Fifty-seven subjects of mean age 44.8±13.4 years who admitted with chronic neck pain to a Private Physiotherapy Clinic between September and December 2013 participated in this study. Visual Analog Scale was used for pain assessment. Level of kinesiophobia was determined by using Tampa Kinesiophobia Scale and level of physical activity was assessed by using the short form of The International Physical Activity Questionnaire. Pearson correlation test was used to determine the relationships between kinesiophobia and chronic neck pain &amp; level of physical activity. <h3>Results</h3> It was found that level of kinesiophobia was not correlated to level of physical activity (r=0.213, p=0.097). The neck pain was not associated with level of kinesiophobia (r=-0.054, p=0.677) and physical activity (r=-0,166, p=0.197). <h3>Conclusions</h3> The findings of this study showed that avoidance behavior due to fear did not influence physical activity levels of individuals with chronic neck pain. The lack of statistically significant findings on relationship between the intensity of neck pain and physical activity suggests more research in this field. Further research with larger sample sizes investigating the effect of kinesiophobia on physical activity is warranted. <h3>References</h3> Geisser, M.E., A.J. Haig, and M.E. Theisen. Activity avoidance and function in persons with chronic back pain. J Occup Rehabil 2000;10(3):215-27. Bergman, S. Management of musculoskeletal pain. Best Practice &amp; Research in Clinical Rheumatology 2007;21(1):153-66. Fejer, R., K.O. Kyvik, and J. Hartvigsen. The prevalence of neck pain in the world population: a systematic critical review of the literature. Eur Spine J 2006;15(6):834-48. Hudes, K., The Tampa Scale of Kinesiophobia and neck pain, disability and range of motion: a narrative review of the literature. J Can Chiropr Assoc 2011;55(3):222-32. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4597
AB1136 Nailfold Capillaroscopic Findings and Other Unique Laboratory Characteristics in A Single Centre Cohort of anti PL-12 Positive Antisynthetase Syndrome: Table 1
Authors: S. Kumar
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Anti-synthetase syndromes (ASS) are a subset of idiopathic inflammatory myositis (IIM). Patients present with varying combinations of myositis, interstitial lung disease (ILD), Raynaud9s phenomenon and arthritis.Anti Jo-1is the prototypical form of ASS.Non Jo-1 forms are increasing being recognized with anti PL-12 syndrome constituting around 2-3% of IIM patients. Data regarding anti PL-12 is rare and most cohorts report a nearly universal presence of ILD as well as infrequent muscle involvement which is mostly subclinical.The aim of this retrospective review was to determine diagnostic utility of various tests in anti PL-12 ASS patients seen in a single centre. <h3>Objectives</h3> To determine nailfold capillaroscopic findings as well as identify unique laboratory characteristics in patients diagnosed with anti PL-12 ASS. <h3>Methods</h3> A search was made among the database of all patients seen in the newly instituted department of rheumatology.Patients identified as having anti PL-12 ASS were identified and details recorded. <h3>Results</h3> Three patients (Two women and one man) were diagnosed with anti PL-12 antisynthetase syndrome in a short span of 7 months. (July 2013 to December 2013). Their clinical and laboratory characteristics are detailed in the table. Mean age of the patients was 44.3 years.(46,36 &amp; 51 yrs) All three patients had a symptom duration of around 1 month. All patients had fever, myalgia and arthralgia, though only the male patient had objective arhtritis.Objective muscle weakness varied from absent to moderately significant, however all patients demonstrated a normal CPK level.MRI (performed in 2 patients) demonstrated significant muscle oedema.Nailfold capillaroscopy demonstrated significantly high number of microhemorrhages and capillary dropouts. There were a number of megacapillaries as well. None of the patients demonstrated Raynaud9s phenomenon.Despite a normal CPK, patients had a high LDH and borderline high ALT/AST.Patients demonstrated a significantly elevated level of inflammatory markers and leucocytosis.They also demonstrated a hyperglobulinemia (absolute or relative to serum albumin level), though there was an absence of reactive thrombocytosis. <h3>Conclusions</h3> As in previous literature, patients with anti PL-12 ASS in this single centre cohort demonstrated minimal to moderate myositis.Similar to previous literature they demonstrated an elevated serum LDH level though the serum CPK level was uniformly normal.Nail fold capillaroscopic abnormalities and laboratory features of significant systemic inflammation except for absence of reactive thrombocytosis are described for the first time. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5810
Abstract 4250: A novel thrombospondin-1 mimetic peptide, ABT-898, decreases angiogenesis in a mouse model of glioblastoma multiforme
Authors: Ryosuke Yamada, Ichiro Nakano
Journal: Cancer Research (2011)

Abstract Prognostic outlook for patients with glioblastoma multiforme (GBM) still appears bleak in spite of medical advances in treatment of other malignant tumors in the past decades. With optimal therapy, of surgical resection, radiation therapy, and chemotherapy, a median survival merely approximates to 12 months. However, a recent dogma that the microvascular niche of such tumors plays a critical role in their maintenance has led to development of “anti-angiogenenic” therapies that target it. To evaluate the apoptotic effect of ABT-898, a TSP-mimetic, anti-angiogenic peptide on endothelial cells, we used human umbilical vein endothelial cells (HUVEC) to model human brain microvasculature. Furthermore, to then assess its clinical applicability, an orthotopic xenograft mouse model was established using human-derived GBM cells lines, and its therapeutic effect evaluated in vivo. We found that ABT-898 induced apoptosis on HUVEC as evidenced by increased fraction of annexin-V positive cells on flow cytometry. Systemic treatment of BTSC-derived immunodeficient mouse tumors with ABT-898, either alone or in combination with temozolomide, significantly reduced tumor size at day 14 post-injection of GBM cells, compared with that of a vehicle, which was used as a control. In addition, treatment with ABT-898 allowed increase in median survival in the xenograft models compared to the control mice. These observations suggest that ABT-898 is a plausible candidate for use in future treatment of GBM. 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 4250. doi:10.1158/1538-7445.AM2011-4250
Abstract 4326: Responses of a direct in vivo xenograft model of melanoma to MKK1/2 inhibitor
Authors: Jyothi Sethuraman, Yuchun Luo, Hyojin Sung, Mayumi Fujita, Natalie G. Ahn
Journal: Cancer Research (2011)

Abstract Metastatic melanoma is the most aggressive form of skin cancer, accounting for 80% of skin cancer deaths due to its high resistance to conventional chemotherapy. Recent studies have shown that metastatic melanomas are susceptible to targeted therapeutics using inhibitors of BRAF or MKK1/2 protein kinases. Here, we study the effect of the MKK1/2 inhibitor, AZD6244, on a direct in vivo xenograft model of melanoma, as well as the effect of MKK1/2 inhibitors, AZD6244 and CI1040 and the BRAF-V600E inhibitor, PLX4720, on established cell lines and cells from direct in vivo xenografts grown in 2D culture. Treatment with CI1040 elicited strong cell death responses in six of nine established melanoma cell lines, reaching 65-80% apoptosis after 48 h. Xenografts of established melanoma cell lines were also responsive to MKK1/2 inhibitor, showing suppressed tumor growth in animals treated with CI1040 in the presence or absence of temozolomide. Likewise, MKK1/2 inhibitor suppressed tumor growth in a direct in vivo xenograft model of melanoma, where tumors harboring BRAF-V600E mutations showed complete growth inhibition in response to AZD6244. One tumor harboring BRAF-WT showed partial growth suppression with AZD6244 alone, but complete suppression was achieved when AZD6244 was combined with temozolomide. Unexpectedly, cells derived from direct in vivo xenografts and grown in 2D culture showed relatively low apoptotic responses when treated with MKK1/2 or BRAF inhibitors. The results suggest that tumor and cell growth conditions might influence mechanisms underlying the oncogene addiction response to constitutive activation of the BRAF/MKK/ERK pathway. 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 4326. doi:10.1158/1538-7445.AM2011-4326
American Cancer Society Commemorates 20th Anniversary of National Cancer Act
Authors: L. F. Anderson
Journal: JNCI Journal of the National Cancer Institute (1991)

American Cancer Society Commemorates 20th Anniversary of National Cancer Act Get access Linda F. Anderson Linda F. Anderson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 20, 16 October 1991, Pages 1445–1446, https://doi.org/10.1093/jnci/83.20.1445 Published: 16 October 1991
HG-06 * INHIBITION OF EPIGENETIC REGULATION AS A THERAPY FOR PEDIATRIC HIGH GRADE GLIOMA
Authors: S. Dombrowski, T. Abou-Antoun, S. Mack, X.-N. Li, P. Houghton, D. Bigner, J. Rich, V. Recinos
Journal: Neuro-Oncology (2015)

Pediatric high grade glioma (HGG), which ranks among the most lethal of cancers among children, contain two recurrent mutations within the histone H3.3 gene H3F3A (K27M and G34R/V).Recent studies have now shown Overall survival
Sustained Reduction of Cardiac Impedance and Preload in Congestive Heart Failure with the Antihypertensive Vasodilator Prazosin
Authors: Richard R. Miller, Najam A. Awan, Kevin S. Maxwell, Dean T. Mason
Journal: New England Journal of Medicine (1977)

To elucidate the hemodynamic effects of prazosin, an antihypertensive agent, in congestive heart failure, we studied 10 patients with ischemic cardiomyopathy and severe ventricular dysfunction. After an oral dose of 2 to 7 mg, heart rate was unchanged (P greater than 0.05). One hour after prazosin administration, mean arterial pressure declined from 95 to 78 mm Hg (P less than 0.001); left ventricular filling pressure declined from 30 to 18 mm Hg (P less than 0.001), cardiac index increased from 2.1 to 2.9 liters per minutes per square meter (P less than 0.001), and systemic vascular resistance fell from 2074 to 1156 dynes sec cm-5 (P less than 0.001). In both forearms vascular resistance and venous tone were reduced (86 to 48 mm Hg per ml per 100 g per minute, and 59 to 18 mm Hg per ml, respectively [P less than 0.001]). All responses persisted for a least six hours (P less than 0.01). Prazosin benefits severe congestive heart failure by inducing a sustained fall of both cardiac preload and impedance.
Abstract 2150: The role of SHP2 in HER2+ breast cancer
Authors: Xiaonan Wang
Journal: Cancer Research (2012)

Abstract Breast cancer is the most common malignancy and the second most common cause of cancer related death in women. HER2+ over-expressing (HER2+) tumors comprise 20% to 25% of all cases and are associated with a poor prognosis. The discovery of HER2 monoclonal antibody-based therapeutics has greatly improved patient prognosis. However, patients suffer relapse and de novo resistance. Thus it is important to determine additional therapeutic targets in HER2+ breast cancer that might be used in combination with current therapies to improve patient survival. SHP2 (PTPN11) is a non-receptor protein-tyrosine phosphatase (PTP) that contains two SH2 domains at its N-terminus, a central PTP domain and a C-terminal proline-rich tail. Previous studies suggest that Shp2 is required for Ras/Erk signaling downstream of most growth factor receptors and integrins. Heterozygous germ-line PTPN11 mutations cause Noonan Syndrome and LEOPARD syndrome, which are associated with leukemia and cancer predisposition. Somatic PTPN11 mutations cause juvenile myelomonocytic leukemia (JMML) and several other neoplasms. We have discovered that Shp2 is required in Neu-mediated tumorigenesis in the MMTV-NIC mouse model; furthermore, SHP2-depleted human HER2+ BT-474 has defective tumorigenesis in nude mice. SHP2 is required in anchorage-independent growth in 4 HER2+ breast cancer cell lines, though its effect on growth on plastics appears minimal. I hypothesize that SHP2 is required for HER2+ breast tumor initiation and maintenance. I further hypothesize that SHP2 functions through specific substrates/interacting proteins in HER2+ breast cancer cells, possibly molecules that are involved in anchorage-independent proliferation. 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 2150. doi:1538-7445.AM2012-2150