tbuckley/cabot-search huggingface dataset:
Abstract SY27-01: Differential efficacy of the angiogenesis inhibitor thrombospondin-1 in different organs
Authors: Kwan-Hyuck Baek, Yoon Jin Lee, Daniel Karl, Alexander Zaslavsky, Sam Yoon, Sandra W. Ryeom
Journal: Cancer Research (2010)

Abstract Tumor angiogenesis is negatively regulated by a number of angiogenesis inhibitors, of which thrombospondin-1 (TSP-1) is one of the most potent. We examined the efficacy of TSP-1 in suppressing tumor growth using both transplantable and inducible tumor and metastasis models in the lung and liver. Although the lung exhibits high levels of endogenous TSP-1, experimental metastases in the lungs of Tsp-1-/- mice showed no differences in growth or microvessel density compared to wild-type mice. However, experimental metastases in the liver were significantly increased in Tsp-1-/- mice versus wild-type mice. Similarly, the growth of tumor cells over-expressing TSP-1 was dramatically inhibited when inoculated into the liver but not in the lung. To further investigate the function of TSP-1 in the lung, we utilized an inducible lung tumor model driven by sporadic activation of oncogenic K-ras. The progression of benign lesions is restrained, in part, by oncogenic activation of cellular senescence. Oncogenic Ras is a prototypical example of this, triggering senescence in many cell types, including lung epithelium. The loss of TSP-1 in this inducible genetically engineered mouse model of lung cancer led to a significant increase in tumor progression. Unexpectedly, we found that TSP-1 plays a critical but previously unidentified role in suppressing K-ras-induced lung tumorigenesis by mediating senescence. Oncogenic ras-induced senescence is abrogated by Tsp-1 deficiency, leading to a marked decrease in overall survival of mice. Similarly, Tsp-1-/- fibroblasts are refractory to oncogenic Ras-induced senescence, which is restored upon TSP-1 re-expression. Moreover, K-ras induces TSP-1 upregulation in a p53-dependent manner. Together, these data indicate that TSP-1 is a critical and cell-autonomous mediator of oncogenic Ras-induced senescence in the lung and suggests a novel role for TSP-1 in the lung, independent of its anti-angiogenic function. Citation Format: Kwan-Hyuck Baek, Yoon Jin Lee, Daniel Karl, Alexander Zaslavsky, Sam Yoon, Sandra W. Ryeom. Differential efficacy of the angiogenesis inhibitor thrombospondin-1 in different organs [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY27-01
Multiple and variant time scales in dynamic information processing
Authors: Hubert R. Dinse
Journal: Behavioral and Brain Sciences (2001)

Single cell receptive field dynamics characterized by highly complicated spatio-temporal activity distributions observable during sensory information processing transforms into much simpler spatio-temporal activity pattern at a population level, indicating a qualitative transformational step of time-variant processing from microscopic to mesoscopic levels. As these dynamics are subject to significant modifications during learning, dynamic information processing is in a permanent state of use-dependent fluctuations.
Abstract B04: Investigating the use of tyrosine kinase inhibitors in Ph-like ALL.
Authors: Kathryn G. Roberts, Yung-Li Yang, Debbie Payne-Turner, Richard C. Harvey, I-Ming Chen, Julie M. Gastier-Foster, Mignon L. Loh, Cheryl L. Willman, Stephen P. Hunger, Charles G. Mullighan
Journal: Clinical Cancer Research (2015)

Abstract This abstract is being presented as a short talk. A full abstract is printed in the Proffered Abstracts section (PR02) of the Conference Proceedings. Citation Format: Kathryn G. Roberts, Yung-Li Yang, Debbie Payne-Turner, Richard C. Harvey, I-Ming Chen, Julie M. Gastier-Foster, Mignon L. Loh, Cheryl L. Willman, Stephen P. Hunger, Charles G. Mullighan. Investigating the use of tyrosine kinase inhibitors in Ph-like ALL. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr B04.
Abstract P4-08-19: Progression-free survival or time to progression in comparative clinical trials of metastatic breast cancer as a potential surrogate for overall survival: A systematic review of 49 trials focusing on breast cancer subtype
Authors: T Tsukioki, N Taira, K Sakamaki, Y Suzuki, Y Kajiwara, M Hatono, Y Takahashi, K Kawata, M Kochi, T Iwamoto, H Ikeda, T Shien, H Doihara
Journal: Cancer Research (2019)

Abstract Background: Overall survival (OS) is the established endpoint to evaluate the effects of drug treatment in comparative clinical trials of metastatic breast cancer. But assessing OS requires long follow-up periods and large sample size, which raise costs and create long delays in the drug approval process. Progression-free survival (PFS) or time to progression (TTP) is considered as a surrogate for OS and is often used as an alternative to OS. In some cancers the two endpoints are highly correlated, but in others they are not. Furthermore, the effect of breast cancer (BC) subtypes on the surrogacy of PFS/TTP for OS has not been completely defined. Method: A systematic literature review of randomized control trials was conducted to identify studies that reported both the hazard ratio (HR) of PFS/TTP and OS for BC subtypes {i.e. estrogen receptor (ER) positive, HER2 positive, and triple negative (TN)}. The correlation between the HR of PFS/TTP and OS was evaluated using weighted Spearman's rank correlation. Results: A total of 49 trials (34 phase III trials and 15 phase II trials) were selected for analysis. Among these trials, there were 8 comparison trials between one chemotherapy and another chemotherapy regimen, 18 comparison trials between chemotherapy and chemotherapy plus molecularly-targeted therapy, 9 comparison trials between one endocrine therapy and another endocrine therapy, and 5 comparison trials between endocrine therapy and endocrine therapy plus molecularly-targeted therapy. There were 17 trials reporting the HR of PFS/TTP and OS for ER positive, 16 trials for HER2 positive, and 9 trials for TN BC. Weighted Spearman's rank correlation revealed that coefficient between the HR of PFS/TTP and OS was 0.721(p&amp;lt;.0001) for all trials, 0.873(p&amp;lt; .0001) for ER positive, 0.642(p=0.0055) for HER2 positive, and 0.615(p=0.078)for TN BC. Conclusion: There was a strong correlation between the HR of PFS/TTP and OS for ER positive BC, and a weak correlation between the HR of PFS/TTP and OS for HER2 positive and TN BC. The validity of using PFS/TTP as an OS surrogate marker was shown for metastatic BC, especially for ER positive BC. Citation Format: Tsukioki T, Taira N, Sakamaki K, Suzuki Y, Kajiwara Y, Hatono M, Takahashi Y, Kawata K, Kochi M, Iwamoto T, Ikeda H, Shien T, Doihara H. Progression-free survival or time to progression in comparative clinical trials of metastatic breast cancer as a potential surrogate for overall survival: A systematic review of 49 trials focusing on breast cancer subtype [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-19.
Abstract 21066: Cardiac Specific Knockdown of <i>Hsl</i> , a Candidate Gene From Human Studies at High Altitude, Improves Hypoxia Tolerance in <i>Drosophila</i>
Authors: Madlina Babakhanlou, Tsering Stobdan, Gabriel G Haddad
Journal: Circulation (2017)

Rationale: Human adaptation to high altitude hypoxia can potentially enlighten us for better therapeutic modalities for sea level diseases that involve hypoxia and ischemia in their pathogenesis. Using whole genome sequencing, we identified LIPE (Lipase E, Hormone Sensitive Type), as a candidate gene involved in HA adaptation. This gene is highly conserved and the ortholog in Drosophila i.e., Hsl , when globally knocked down and tested for hypoxia tolerance, significantly improves survival rates in low oxygen. Objective: To understand the hypoxia tolerance mechanism in Hsl- knockdown Drosophila . Methods and Results: We knocked down Hsl in individual tissue-types by crossing tissue specific Gal4 drivers with UAS- RNAi(Hsl) lines. To elucidate its potential role in hypoxia tolerance, we measured the eclosion rate (%) at 5% O 2 and compared with controls kept at room air (21% O 2 ). Remarkably, the eclosion rate for Hsl , at 5% O 2 , when knocked down specifically in heart (UAS- RNAi(Hsl) X Hand-Gal4 ) was significantly higher (86.02%; P&lt;0.05) when compared to the background controls (42.2% for w1118 , 50.06% for Hand-Gal4 and 39.72% for UAS- RNAi(Hsl) ). Conclusion: These data indicate that a lower level of Hsl in the heart significantly improves hypoxia tolerance in Drosophila . Interestingly, also during cardiac-ischemic-hypoxia, the cardiomyocytes strategically knockdown LIPE , preventing lipid metabolism and therefore reduce oxygen consumption when the supply is limited.
Fragmented attractor boundaries in the KIII model of sensory information processing: A potential evidence of Cantor encoding in cognitive processes
Authors: Robert Kozma
Journal: Behavioral and Brain Sciences (2001)

Spatio-temporal neuro-dynamics is a quickly developing field of brain research and Tsuda's work is a significant contribution toward establishing theoretical foundations in this area. It is conceivable that the fragmented attractor landscapes and dynamical memory patterns identified earlier in various K-sets are biologically plausible manifestations of attractor ruins, chaotic itinerancy, and Cantor encoding as applied to sensory information processing.
Subsequent Breast Cancer in Female Childhood Cancer Survivors in the St Jude Lifetime Cohort Study (SJLIFE)
Authors: Matthew J. Ehrhardt, Carrie R. Howell, Karen Hale, Malek J. Baassiri, Carol Rodriguez, Carmen L. Wilson, Surekha S. Joshi, Thomas C. Lemond, Sheila Shope, Rebecca M. Howell, Zhaoming Wang, Deokumar Srivastava, Daniel A. Mulrooney, Jinghui Zhang, Leslie L. Robison, Kirsten K. Ness, Melissa M. Hudson
Journal: Journal of Clinical Oncology (2019)

Anthracycline-associated risk for subsequent breast cancer in childhood cancer survivors is hypothesized to be mediated by
Recognising the deteriorating patient
Authors: Hannah Jethwa, Fiona Morcom, Andy Cohen
Journal: BMJ (2014)

A 75 year old man is admitted to hospital with severe chest pain. The figure⇓ shows his observation chart.



Observation chart of patient with severe chest infection





### 1 What is the first sign on this chart of important clinical deterioration?

An increasing respiratory rate is the first and most important indicator of severe illness, although anecdotally it is the vital sign least accurately calculated. Extensive research into predictors of mortality based on observation charts has shown that a respiratory rate greater than 27 breaths per minute is an important predictor of cardiopulmonary arrest.1

Interestingly, at first glance the vital sign that stands out the most on this observation chart is the decrease in blood pressure; a fall in blood pressure is, however, a late sign of deterioration.

Another relevant sign of clinical deterioration is an increasing requirement for oxygen to maintain adequate saturations—in other words, a change from room air to 2 L/min of oxygen …
Heparin-like Effect Associated With Risk of Bleeding, Sepsis, and Death in Patients With Severe Alcohol-Associated Hepatitis
Authors: Madhumita Premkumar, Chhagan Bihari, Priyanka Saxena, Devaraja Rangegowda Devurgowda, Tanmay Vyas, Roshni Mirza, Priyanka Jain, Guresh Kumar, Puja Bhatia, Sukriti Baweja, Ashok Choudhury, Shiv Kumar Sarin
Journal: Clinical Gastroenterology and Hepatology (2019)
Abstract P6-05-06: Estrogen induced miR-489 acts as a negative feedback to confine uncontrolled estrogen signaling and cell proliferation in breast cancer
Authors: M Soni, Y Patel, R Shealy, H Chen
Journal: Cancer Research (2019)

Abstract Estrogen induced miR-489 acts as a negative feedback to confine uncontrolled estrogen signaling and cell proliferation in breast cancer. Mithil Soni1,2, Yogin Patel1,2,3, Ryann Shealy1, Hexin Chen1,2,4. 1Dept. of Biological Sciences, University of South Carolina, 2Center for colon cancer research, 3current location, National cancer institute, surgery branch, 4corrosponding author. Approximately 75% of diagnosed breast cancer tumors are Estrogen receptor positive tumors and are associated with better prognosis due to response to hormonal therapies. However, around 40% of patients relapse after hormonal therapies. Identification of novel molecular targets is necessary to combat such resistant tumors. In the current study, using microarray, qRT-PCR, western blot, luciferase reporter assay and immunofluorescence, we found that miR-489 is an estrogen regulated miRNA that negatively regulates estrogen signaling. Depletion of miR-489 using Anti-miR-489 siRNA or CRISPR-Cas9 significantly increased estrogen induced proliferation, colony formation ability and stem like cell population. Loss of miR-489 also induced estrogen independent proliferation. Mechanistically we found that depletion of miR-489 enhanced nuclear localization of estrogen receptor while restoration of miR-489 increased cytosolic ER and inhibited estrogen induced transcription. Furthermore, we found that miR-489 depletion also increases estrogen independent growth through activation of MAPK and PI3K-AKT pathway. We also observed loss of miR-489 in tamoxifen resistance breast cancer cell line and found increased resistance to tamoxifen upon miR-489 inhibition while miR-489 restoration sensitized Tamoxifen resistant cell lines. Clinical analysis of estrogen receptor positive breast cancer patient showed that ER+ve breast cancers with low miR-489 expression represents aggressive cancers with significant reduction in survival time. In summary, these results indicate potential role of miR-489 as a biomarker to predict aggressiveness of ER+ve breast cancer and response to tamoxifen therapy and can potentially be used as a therapeutic agent to treat or sensitize tamoxifen resistant tumors. Citation Format: Soni M, Patel Y, Shealy R, Chen H. Estrogen induced miR-489 acts as a negative feedback to confine uncontrolled estrogen signaling and cell proliferation in breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-05-06.
Abstract P1-18-06: First-line treatment for endocrine sensitive bone-only metastatic breast cancer: Is more always better?
Authors: A Toss, M Venturelli, I Sperduti, C Isca, E Molinaro, E Barbieri, F Piacentini, C Omarini, L Cortesi, S Cascinu, L Moscetti
Journal: Cancer Research (2019)

Abstract The standard first-line for endocrine sensitive metastatic breast cancer (BC) is represented by endocrine therapy. Several phase III clinical trials searched for more effective endocrine strategies. Nevertheless, the use of combinations for the first-line treatment of bone-only disease (BoD) is widely discussed, due to its indolent course. Our meta-analysis aims to explore the role of new endocrine strategies in BoD. A systematic review of electronic databases was conducted to identify the phase III clinical trials comparing the standard AI to novel experimental strategies. The hazard ratios (HR) for PFS were pooled in a meta-analysis. The heterogeneity of the data was evaluated by Chi-square Q test and I2 statistic. 8 studies were included in the analyses. 4 trials explored the role of CDK4/6 inhibitors (Monaleesa2 and 7, Monarch3 and Paloma2), 2 trials analyzed Fulvestrant + AI (SWOG and FACT), one trial studied Fulvestrant monotherapy (FALCON), while one trial evaluated the association between Bevacizumab and Letrozole (ALLIANCE). 6 trials reported data regarding the BoD, while 2 trials included the BoD in the non-visceral disease. Overall, the meta-analyses showed a PFS advantage for the experimental arms [HR 0.70 p 0.012], with a significant moderate/high heterogeneity [I2 66.48% p 0.004]. Only the FALCON and Paloma2 showed a significant improvement in PFS, respectively for Fulvestrant and Palbociclib + Letrozole. Considering only trials reporting data for BoD, the experimental arms significantly improved the PFS [HR 0.66 p 0.005], with a low/moderate non-significant heterogeneity [I2 44.95% p 0.106]. The novel strategies showed to be able to improve the PFS of BoD. Nonetheless, only Palbociclib + Letrozole provided statistically significant data of advantage in this setting. In clinical trials, BoD is often included in the non-visceral disease subgroup. Future clinical trials should take into account the differences in natural history and better prognosis of BoD, in order to define the best approach to these patients. Citation Format: Toss A, Venturelli M, Sperduti I, Isca C, Molinaro E, Barbieri E, Piacentini F, Omarini C, Cortesi L, Cascinu S, Moscetti L. First-line treatment for endocrine sensitive bone-only metastatic breast cancer: Is more always better? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-18-06.
Mesenteric Vein Thrombosis Associated to Elevated Factor VIII in a Patient Treated with Adjuvant Tamoxifen
Authors: Juan Herrada, Ethan A Reiter, Anuradha Gupta, Carmen Arango, Mark M Landeros, Lorenzo-Medina Mercedes, Jesus A Gomez, Sacramento Vargas-Sanz, Angel F Campos-Gines, Melissa Madrid, Jeannette Briceno
Journal: Blood (2014)
Abstract P2-01-25: Not presented
Authors: W Xing, Q Li, R Cao, G Sun, C Jiang
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Xing W, Li Q, Cao R, Sun G, Jiang C. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-25.
The medical zoo
Authors: Eva Dumann
Journal: BMJ (2014)

What can we learn from animal models? If you are a preclinical student, the chances are you will be encountering a vast array of biological terms and concepts this year. But how many of you will take this knowledge for granted? Model organisms, defined as species that have been widely studied usually because they are easy to maintain and breed in a laboratory setting and have particular experimental advantages, have been fundamental for improving our understanding of how life works.1 Knowledge in cell biology, genetics, metabolism, and many other aspects of life comes from the study of these organisms, and they can be of great benefit in looking at the genetic or developmental origins of human disease.23 These strategies are based on the principles of the common descent of life, and the highly conserved nature of essential biological processes through evolution summarised by the Nobel prize winning biologist Jacques Monod when he said “what is true for Escherichia coli is true for an elephant.” We’ve all heard of the laboratory mouse, but there are plenty of other creatures that have provided vital insights to the medical world. So next time you talk about polyglutamine repeats in Huntington’s disease, for example, spare a thought for the humble fruit flies who have contributed to this knowledge. #### Fruit fly ( Drosophilia ) ##### What is it used for? ##### Why?
Abstract SY02-04: Regulation of invadopodia formation and cancer cell invasion
Authors: Barbara Blouw, Matt Buschman, Pilar Cejudo-Martin, Begoña Diaz, Christine Gould, Danielle Murphy, Manuela Quintavalle, Susanne Heynen, Behrad Azimi, Jeff Price, Sara A. Courtneidge
Journal: Cancer Research (2010)

Abstract Cell invasion plays a central role in a wide variety of biological phenomena, and is the cause of tumor growth and metastasis. Understanding the biochemical mechanisms that control cell invasion is one of the major goals of our laboratory. Podosomes and invadopodia are specialized cellular structures present in cells with physiological or pathological invasive behaviors. These transient structures are localized at the ventral cell surface, contain an array of different proteins, and facilitate cell-substrate adhesion as well as the local proteolytic activity necessary for extracellular matrix remodeling and subsequent cellular invasion. We have previously shown that the adaptor protein and Src substrate Tks5 is required for both podosome and invadopodia formation, and for tumor growth in vivo. More recently we also defined a role for the Tks5-mediated generation of reactive oxygen species (ROS). We have developed a high content, cell-based high throughput screening assay that allows us to identify inhibitors and activators of invadopodia formation. As a proof of principle, we tested the LOPAC1280 collection of small molecules and found 7 inhibitory compounds and 2 activators. Of the 7 inhibitors, 4 are cyclin-dependent kinase (Cdk) inhibitors. Loss-of-function experiments demonstrated that Cdk5 is the responsible kinase. On the other hand, paclitaxel was one of the two compounds that increased invadopodia formation. We have also used our high content assay to screen a large compound collection as well as an siRNA library targeting the entire kinome. The mechanisms by which Cdk5 and tubulin regulate invadopodia formation, and the nature of the other regulators, are the subjects of our current investigations. Citation Format: Barbara Blouw, Matt Buschman, Pilar Cejudo-Martin, Begoña Diaz, Christine Gould, Danielle Murphy, Manuela Quintavalle, Susanne Heynen, Behrad Azimi, Jeff Price, Sara A. Courtneidge. Regulation of invadopodia formation and cancer cell invasion [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY02-04