tbuckley/cabot-search huggingface dataset:
Abstract 881: Clinical usefulness of soluble fibrin monomer-fibrinogen complex (SFMC) for the metastasis of malignant neoplasm
Authors: Komatsu Yoshihiro, Shin Koga, Hajime Orita, Mutsumi Sakurada, Hiroshi Maekawa, Minoru Moriwaki, Kouichi Sato
Journal: Cancer Research (2010)

Abstract Objective: SF is a complex coupling fibrin monomer and fibrinogen molecules to be formed in the early-activated state of blood coagulation. The level of SF reflects the thrombin generation activity in plasma. There is increasing evidence that SFMC is expected to serve as a parameter for thrombus formation and DIC, in particular its early stage. Thrombin generation is activated in the metastasis of malignant neoplasm, The aim of this study is to determine whether the SF could be a new marker for the metastasis of malignant neoplasm. Material and Methods: From 2007 to 2008, a total of 86 patients who underwent radical surgery for treatment to the cancer of digestive organs (including cancer of esophagus, stomach, colon, rectum, liver, biliary tract, and pancreas) were enrolled in this study. We measured SF together with established tumor markers before the surgery and every three months after the surgery. Each of them was compared with imaging tests such as CT scan, ultrasounds, MRI, PET-CT, GIF, and CF. Results: There were not admitted the rise of SF neither before nor after surgery in the case of stage1 and 2. No metastasis was admitted with the imaging tests in the cases of stage1 and 2, either. In the cases of stage3 and 4, there were some cases with the rise of SF before the surgery. The decrease of SF and tumor markers were admitted in the cases of excising the radical cure. SF was not high in the some cases with relapse or metastasis which condition was considered to be suppressed by chemotherapy and radiotherapy. Moreover, the rise of SF was admitted in all samples in the case of multiple liver metastasis and multiple peritoneal dissemination. Conclusions: Though this study suggests that SF could be a parameter for the condition of metastatic malignant neoplasm, it has not been systematically studied whether SF is useful for early detection of metastasis and relapse or not. 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 881.
French plan aims to reduce social inequality in cancer prevention and treatment
Authors: P. Benkimoun
Journal: BMJ (2014)

France’s president, Francois Hollande, launched a national plan against cancer for 2014-19 on 4 February, World Cancer Day. While presenting the 152 page document, Hollande explained that the main goal was to reduce social inequalities at all stages for those affected by cancer—namely, in prevention, screening, diagnosis, care, and treatment. 

Hollande’s plan followed the first and second such plans, which covered 2003-13 …
Phase IB pharmacokinetic (PK) study of Src kinase inhibitor AZD0530 plus anastrozole in postmenopausal hormone receptor positive (HR+) metastatic breast cancer (MBC).
Authors: M. D. Pegram, O. E. Silva, C. Higgins, K. Tukia, M. Stuart, J. Slingerland
Journal: Journal of Clinical Oncology (2010)

e13074 Background: cSrc is overexpressed/activated in ∼70% of primary human BC. Src phosphorylates p27 reducing its inhibitory function toward cyclin E-Cdk2, thereby facilitating p27 degradation. AZD0530 is a potent, orally available inhibitor of Abl and Src family kinases. Preclinical data indicate AZD0530 cooperates with anastrozole to inhibit BC cell growth in vitro and in vivo (Chen, et al., Clin Cancer Res 2009). We hypothesized that Src inhibition will augment p27 to promote antiproliferative effects of anastrozole in HR+ BC. Methods: This is an investigator-initiated, open label phase IB study. Target population: postmenopausal HR+ relapsed or MBC candidates for aromatase inhibitors. Key inclusion: postmenopausal females, age ≥ 18, advanced or locally relapsed HR+ measurable/evaluable (RECIST) disease, ECOG 0-2, informed consent. Cohorts of 3 patients were initiated with AZD0530 175 mg PO/day in combination with anastrozole 1mg PO daily in a planned dose de-escalation study design with subsequent cohort expansion to 12 subjects for PK assessment at 6, 12, 24, 48, and 72 hours, 7, 14 and 21 days after initiation of AZD0530. Results: In 12 patients enrolled, AZD0530 plus anastrozole was well tolerated (no dose limiting toxicities) without need for dose de-escalation. Drug-related adverse events: grade 3 lymphopenia (N=3), neutropenia (N=2), and anemia (N=1); reversible grade 1/2 transaminase elevation (N=9). Serious adverse events were observed in 2 patients (urosepsis and CNS hemorrhage due to CNS metastasis), neither considered drug-related. PK assessment: mean day 21 serum concentration = 298±38.4 ng/ml and 51±5.6 ng/ml for AZD0530 and anastrozole, respectively. Clinical efficacy: There were no objective clinical responses. Notably, patients with bone metastasis reported improvement in bone pain, and 2 patients had prolonged disease stability (>7 and 10 months). Conclusions: Src kinase inhibition with AZD0530 combined with anastrozole was well tolerated without significant PK interaction at the recommended phase II dose. A randomized phase II study of this combination is currently underway in the neoadjuvant setting. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca
AN ALARMING TREND: CHANGE IN RISK PROFILE OF PATIENTS WITH ST ELEVATION MYOCARDIAL INFARCTION OVER THE LAST TWO DECADES
Authors: Amgad G. Mentias, Amr F. Barakat, Mohammad Q. Raza, Haris Riaz, Stephen Ellis, E. Murat Tuzcu, Samir Kapadia
Journal: Journal of the American College of Cardiology (2016)
Abstract 4524: Targeting Bcl-2 family proteins in adult T-cell leukemia/lymphoma: in vitro and in vivo effects of a novel Bcl-2 family inhibitor, ABT-737
Authors: Naoko Kunami, Kenji Ishitsuka, Fusanori Yotsumoto, Chie Ishikawa, Hiroo Katsuya, Shigeki Sawada, Hiroe Tanji, Morishige Takeshita, Naoki Mori, Shingo Miyamoto, Masahide Kuroki, Kazuo Tamura
Journal: Cancer Research (2010)

Abstract Adult T-cell lymphoma/leukemia (ATLL) is a T-cell malignancy caused by the human T-lymphotrophic virus type I (HTLV-I), and its therapeutic outcome still remains extremely poor. Therefore, novel therapeutic strategies are needed to improve treatment outcomes. In this study, we elucidated the therapeutic potential of targeting the anti-apoptotic Bcl-2 family proteins for the treatment of ATLL using ABT-737 (Abbott Laboratories, Abbott Park, IL, USA), a small molecule inhibitor of Bcl-2, Bcl-XL and Bcl-w. We first validated the rationale of this study by immunohistochemically assessing the expression of Bcl-2 family proteins in 25 lymph-node specimens derived from ATLL patients. The Bcl-2 and/or Bcl-XL proteins were expressed in 80% of specimens. We next examined the cytotoxicity of ABT-737 against three ATLL cell lines by the Colorimetric method. ABT-737 significantly inhibited growth of MT-1, MT-2 and HuT 102 cells with concentrations of 50 percent inhibition of 2.4, 0.23 and 0.008μM at 72 h, respectively. We then tried to clarify the mechanism of growth inhibition induced with ABT-737 using MT-1 and MT-2 cells. ABT-737 induced apoptosis in both cells with cleavage of caspases 9 and 3, and PARP. ABT-737 also induced apoptosis in fresh tumor cells derived from patients with ATLL. We also tested if ABT-737 enhances the cytotoxicity induced by conventional chemotherapeutic agents or novel agents. The interactions between them were evaluated using the Chou-Talalay method. ABT-737 synergistically enhanced the cytotoxicity and apoptosis induced by doxorubicin, vincristine or etoposide and bortezomib or suberolyanilide hydroxamic acid, which are current key drugs and promising candidates for the treatment of ATLL, respectively. Finally, we investigated the growth inhibition of ABT-737 in ATLL-xenografted mice. The mean tumor volume and weight, and mean serum level of soluble interleukin-2 receptor α at day 21 of the treated mice with ABT-737 (100mg/kg/day) were significantly lower than those of vehicle-treated mice. Moreover, massive induction of apoptosis was observed in tumors treated with ABT-737 by the TUNEL assay. These results suggest that the use of ABT-737, either alone, or in combination with other conventional cytotoxic and novel drugs, represents a promising novel targeted approach to overcome drug resistance and to improve patient outcome in ATLL. 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 4524.
Case 13-2001
Authors: Paul R. Conlin, William C. Faquin
Journal: New England Journal of Medicine (2001)

Presentation of CaseA 19-year-old man was admitted to the hospital because of headaches and hypertension.The patient had been well until two years earlier, when he began to have episodic mild headaches that resolved spontaneously. Two months before admission, the headaches became much more severe and frequent, occurring almost daily, and were accompanied by throbbing chest pain, sweating, dizziness, palpitations, and a greenish pallor. The episodes occurred during both waking hours and sleep and were often heralded by an epigastric “uneasiness” that radiated to the head.Four weeks before admission, hypertension was diagnosed. A computed tomographic (CT) scan of . . .
Abstract 1588: Canonical Wnt signaling mediates resistance of colorectal cancer cells to radiation therapy.
Authors: Georg Emons, Janneke Möller, Melanie Spitzner, Emil Kendziorra, Jochen Gaedcke, Margret Rave-Fränk, Tobias Pukrop, Michael Ghadimi, Thomas Ried, Marian Grade
Journal: Cancer Research (2013)

Abstract Background: The clinical response of locally advanced rectal cancers to preoperative chemoradiotherapy is very heterogeneous. We previously identified TCF4, the key downstream effector of the Wnt/β-catenin signaling pathway, as over-expressed in tumors that were resistant to chemoradiotherapy. The aim of this study was to explore the potential functional relevance of Wnt/ß-catenin signaling for mediating treatment resistance. Methods: Using RNA interference, TCF4 and β-catenin were inhibited in the colorectal cancer cell lines SW837 and SW480. Subsequently, these cell lines were irradiated with varying doses of X-rays. In addition, normal retinal epithelial cells (RPE) were stimulated with Wnt-3a for 28 hours, and also irradiated. Wnt/β-catenin activity was assessed using the TOPFLASH/FOPFLASH reporter assay, and induction of Axin2 was confirmed by Western blotting. Results: Protein levels of both TCF4 and β-catenin were considerably reduced following RNAi, accompanied by a decreased TOP/FOP reporter activity. Importantly, silencing of both proteins led to a pronounced radiosensitization in SW837 and SW480 cells. Exogenous stimulation of canonical Wnt signaling in RPE cells using Wnt-3a resulted in an increased Axin2 expression and an increased TOP/FOP reporter activity. Importantly, however, this activation of canonical Wnt signaling was associated with significant increase in resistance to radiation therapy. Conclusion: TCF4 was found to be over-expressed in resistant rectal carcinomas, and its RNAi-mediated silencing caused a significant radiosensitization. To determine whether this effect was dependent on canonical Wnt signaling, we inhibited ß-catenin, another key factor of this pathway and binding partner of TCF4, and observed a similar sensitization to radiation therapy. Follow-up experiments show that external stimulation of canonical Wnt signaling confers radiation resistance in normal cells. These data suggest that targeting canonical Wnt signaling may represent a potential therapeutic strategy for sensitizing tumor cells to radiation. In vivo studies are ongoing to validate these results. Citation Format: Georg Emons, Janneke Möller, Melanie Spitzner, Emil Kendziorra, Jochen Gaedcke, Margret Rave-Fränk, Tobias Pukrop, Michael Ghadimi, Thomas Ried, Marian Grade. Canonical Wnt signaling mediates resistance of colorectal cancer cells to radiation therapy. [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 1588. doi:10.1158/1538-7445.AM2013-1588
THU0262 Off-Label Use of Rituximab for SLE in Europe: A Comparison to Patients Treated with Conventional Immunosuppressive Medications
Authors: R. F. van Vollenhoven, M. Mild, T. Dörner, E. Gremese, F. Houssiau, T. Huizinga, D. A. Isenberg, L. Kovács, G. Ruiz-Irastorza, D. Squatrito, L. Emmi, A. Voskuyl, M. Mosca, A. Castro, A. Iuliano, M. Inanc, G. Szücs, A. Doria, S. Jacobsen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rituximab (Mabthera; RTX) has not been approved for use in SLE, but uncontrolled observations have suggested efficacy in some patients and the medication can be used off-label in many European countries. We previously reported that based on data from the International Registry for Biologics in SLE (IRBIS), and additional data from investigators, between 0.5 and 1.3% of European patients with SLE have been treated, off-label, with RTX. <h3>Objectives</h3> To compare characteristics of SLE patients treated off-label with RTX to those of SLE patients treated with conventional, non-biologic immunosuppressives (ISs) at the same specialty centers. <h3>Methods</h3> Investigators participating in IRBIS, initiated by the SLICC group, provided the data for this study. Data previously submitted to the IRBIS registry by 28 centers in 11 European countries were complemented with additional clinical information from the participating sites. Comparator patients were those started on any conventional IS; not necessarily naïve for previous ISs. <h3>Results</h3> In this European study, 175 patients were analyzed; 103 were treated off-label with RTX and 72 with conventional ISs. The most frequently used ISs were mycophenolate mofetil (43%) and azathioprine (33%). For both groups, about 90% were female, 90% were Caucasians and 85% were non-smokers. Organ manifestations leading to treatment with RTX were lupus nephritis in 58%, hematological lupus in 16%, musculoskeletal in 11%, skin disease in 6%, CNS in 7%, and other manifestations in 7%. For patients started on ISs, the corresponding percentages were 53%, 11%, 22%, 6%, 7%, and 6%. These distributions were not statistically different. Reason for treatment initiation with RTX was mainly disease control while steroid sparing was frequently the main reason for conventional ISs. At treatment initiation mean disease duration (±SD) was 9.1±7.0 for RTX-treated patients and 4.1±6.6 for patients on ISs (p&lt;0.0001); mean ages were 41.2±12.5 and 36.1±11.3, respectively (p=0.007). There were significant differences between the groups for SLEDAI scores (12.2±7.0 vs. 9.4±7.0, p=001) and SLICC damage index (1.6±3.4 vs. 0.57±1.0, p=0.014). <h3>Conclusions</h3> Both RTX and conventional ISs are used mostly in lupus nephritis. No organ manifestion was more likely to be treated with RTX, however, patients started on RTX were somewhat older, had significantly longer disease duration, higher disease activity and more damage compared to patients started on conventional ISs. These data support the view that RTX is used for selected patients with later-stage, more severe SLE. <h3>Acknowledgements</h3> Supported by a research grant from Roche <h3>Disclosure of Interest</h3> None Declared
Stat Bite: Leading Causes of Death in the United States
Authors: B. Miller
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Stat Bite: Leading Causes of Death in the United States Get access Barry Miller Barry Miller Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 9, 4 May 1994, Pages 659–660, https://doi.org/10.1093/jnci/86.9.659 Published: 04 May 1994
431 PRE-EMPTIVE OR PROPHYLACTIC THERAPY FOR REACTIVATION OF HEPATITIS B VIRUS IN PATIENTS WHO RECEIVED IMMUNOSUPPRESSIVE OR CYTOTOXIC THERAPY: EVALUATION OF BOTH HBsAg-POSITIVE AND HBsAg-NEGATIVE COHORTS
Authors: A. Tamori, T. Koike, H. Goto, M. Tada, H. Morikawa, M. Enomoto, T. Nakatani, M. Hino, N. Kawada
Journal: Journal of Hepatology (2013)
579 ENDOTHELIAL DYSFUNCTION IN CIRRHOSIS AND ITS RELATIONSHIP WITH PORTAL HYPERTENSION AND LIVER FAILURE
Authors: M. Garcovich, A. Lupascu, D. Roccarina, E.B. Annicchiarico, M.E. Ainora, G. Caracciolo, F.R. Ponziani, M. Siciliano, A. Gasbarrini, M.A. Zocco
Journal: Journal of Hepatology (2013)
A Clinical Trial of a Chest-Pain Observation Unit for Patients with Unstable Angina
Authors: Michael E. Farkouh, Peter A. Smars, Guy S. Reeder, Alan R. Zinsmeister, Roger W. Evans, Thomas D. Meloy, Stephen L. Kopecky, Marvin Allen, Thomas G. Allison, Raymond J. Gibbons, Sherine E. Gabriel
Journal: New England Journal of Medicine (1998)

Nearly half of patients hospitalized with unstable angina eventually receive a non–cardiac-related diagnosis, yet 5 percent of patients with myocardial infarction are inappropriately discharged from the emergency department. We evaluated the safety, efficacy, and cost of admission to a chest-pain observation unit (CPU) located in the emergency department for such patients.
Dietary n-3 Polyunsaturated Fatty Acids and Smoking-Related Chronic Obstructive Pulmonary Disease
Authors: Eyal Shahar, Aaron R. Folsom, Sandra L. Melnick, Melvyn S. Tockman, George W. Comstock, Valerio Gennaro, Millicent W. Higgins, Paul D. Sorlie, Wen-Jene Ko, Moyses Szklo
Journal: New England Journal of Medicine (1994)

Fish contain n-3 polyunsaturated fatty acids, principally eicosapentaenoic acid and docosahexaenoic acid, which are known to interfere with the body's inflammatory response and may be of benefit in chronic inflammatory conditions.
Abstract 271: Heregulin internalization to the nucleus is mediated via binding to nucleolin
Authors: Lin Yang, Ruth Lupu
Journal: Cancer Research (2010)

Abstract Heregulin internalization to the nucleus is mediated via binding to Nucleolin Lin Yang, and Ruth Lupu. Department of Laboratory Medicine and Pathology, Mayo Clinic Foundation, Rochester, Minnesota 55902 Heregulin (HRG) is known as a soluble secreted growth factor of EGF-like family, which binds and activates HER3 and HER4 and transactivates HER2 and HER1 receptors. It has been shown that HRG translocates to the nucleus in triple negative breast cancer cells that express high level of HRG. The mechanism by which HRG translocates to the nucleus is still unknown. We have recently uncovered that Nucleolin binds to Heregulin and allows HRG to translocate to the nucleus. Mass spectrometry analysis revealed that multifunctional protein Nucleolin is a major HRG-associated protein. Using co-immunoprecipitation we confirmed HRG interacts with Nucleolin in both endogenous and ectopic levels. Then, we made deleted mutants of HRG to map the Nucleolin binding domain on HRG and we found that Nucleolin binds to HRG on its N-terminus which contains a putative nuclear localization signal (NLS). Remarkably, in these cells we found a striking peri-nuclear accumulation when Nucleolin was knocked down. These results show for the first time that HRG translocate to the nucleus mediated by Nucleolin binding in breast cancer cells. Importantly, the nuclear function of HRG remains as a positive regulator of chemosensitization. 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 271.
Surgical Treatment of Aneurysms of the Ascending Aorta in the Marfan Syndrome
Authors: Vincent L. Gott, Reed E. Pyeritz, George J. Magovern, Duke E. Cameron, Victor A. McKusick
Journal: New England Journal of Medicine (1986)

The life expectancy of patients with the Marfan syndrome is reduced by complications caused by dilatation of the ascending aorta. Because surgical therapy with a composite graft may alter this natural history, we analyzed the preoperative and long-term postoperative status of 50 consecutive patients who received such a graft. At surgery, the patients had a mean age of 32.2 years and a mean aortic diameter of 7.1 cm (range, 5.3 to 10). Dissection of the ascending aorta was present in 14 patients and was acute in 5. None of the 44 patients who underwent elective repair, and only one of the six patients who had emergency surgery, died in the hospital; thus, the overall hospital mortality was 2 percent. Five of the 49 survivors died during a follow-up period of up to eight years (10.2 percent late mortality). During the most recent four years of evaluation of this series (38 patients), no postoperative deaths due to intrathoracic problems occurred. Actuarial survival was 87 percent at both two and five years. Composite-graft repair of the ascending aorta in patients with the Marfan syndrome can be performed with low operative and long-term mortality. Because of the unfavorable natural history of the Marfan syndrome and the potential for dissection in moderately dilated aortic roots, we recommend prophylactic repair when the aneurysm reaches a diameter of 6 cm. (N Engl J Med 1986; 314: 1070–4.)
FDG PET/CT in Type I Glycogen Storage Disease
Authors: Chloé Manca, Marine Claudin, Arthur Belle, Pierre Yves Marie, Antoine Verger
Journal: Clinical Nuclear Medicine (2015)

Type I glycogen storage disease (GSD) is a rare autosomal recessive disorder caused by glucose-6-phosphatase deficiency. We report herein the particular pattern provided by FDG PET imaging in a 33-year-old patient with type Ib GSD. PET images yielded evidence of a pulmonary infectious focus as well as of: (1) a dramatically enlarged liver leading to a high global FDG uptake, (2) increased bone marrow activity, (3) splenomegalia leading to a high global spleen uptake, (4) a diffuse enhancement in muscle FDG uptake.