tbuckley/cabot-search huggingface dataset:
Abiraterone acetate followed by enzalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) treated in the US Oncology Community Setting.
Authors: Nicholas J. Vogelzang, Lina Asmar, Jun Tang, Mark Yap, Mary Beth Todd, Yvette Ng, Maneesha Mehra, Debra A. Patt
Journal: Journal of Clinical Oncology (2015)

e16061 Background: Both abiraterone acetate (AA) and enzalutamide (enza) are highly effective in men with chemo naïve mCRPC. AA was FDA approved in this setting in 2012, and enza in 2014 and thus many physicians use AA followed by enza. Although there are published data on sequencing of AA followed by enza, most of these reports are in the post-chemo setting. There are limited data on the effectiveness, of AA followed by enza when both agents are given in the chemo-naive setting. This study was conducted to assess this in 22 sites in a community setting. Methods: This retrospective, observational cohort study used the iKnowMed (iKM) electronic medical record and chart review to evaluate mCRPC pts who received AA followed by enza (both in the chemo-naïve setting) from 1/1/2011 to 12/31/2013 and followed through 4/30/14. 168 pts were identified, 136 pts were evaluable, of whom 24 pts initiated enza before termination of AA. Results: Pt characteristics for 136 pts: median age: 77 yrs (range, 50–93), Caucasian 61%, Gleason 8-10 46%, ECOG PS 0-1 79%, bone/nodal/visceral metastases 90%/21%/30%, respectively. Median PSA/LDH/ALK/HGB at start of AA therapy was 53/208/90/12, respectively. The median follow-up is 16.2 months. Median exposure to AA was 7.4 months (range, < 1-31 mos), PSA reductions of ≥ 30% and ≥ 50% while on AA were 70% and 57%, respectively. Most patients discontinued AA due to progressive disease (PD) (79%). The median exposure to enza was 2.8 months ( < 1-14.7), PSA reductions of ≥ 30% and ≥ 50% while on enza were 46% and 33%, respectively, 39% discontinued enza due to PD, 17% due to death, and 25 (18%) pts were still on enza by the end of study period. For 24 pts (18%) who initiated enza before AA stop, median overlapping period was 2.3 months (0.2 – 16.8). Conclusions: This large multicenter study with short follow-up demonstrates the activity of enza post AA in the chemotherapy-naïve setting. Combination use of the 2 drugs occurred in 18% of patients.
Abstract 2711: Spatiotemporal progression patterns in metastatic lung cancer treated with bevacizumab
Authors: Jeremy M. Mason, Paul K. Newton, Gino K. In, Sonia Lin, Peter Kuhn, Jorge J. Nieva
Journal: Cancer Research (2016)

Abstract We describe a Markov chain mathematical model of lung cancer progression based on a longitudinal dataset of 722 lung cancer patients. Specifically, we investigate the patterns of metastatic spread in lung cancer and how the VEGF inhibitor, bevacizumab, alters these metastatic patterns. Stochastic models were used to simulate metastatic spread by means of random walk processes on directed graphs. We created spatiotemporal diagrams of cancer progression to analyze the differences between patients treated and not treated with bevacizumab. Patients with squamous lung cancer or brain metastases at baseline were ineligible for bevacizumab and excluded from analysis. Our results demonstrated that not only does bevacizumab extend survival, but it also alters patterns of metastatic spread. Patients treated with bevacizumab were characterized by greater heterogeneity in their pathways of metastatic progression, compared to those patients not treated with bevacizumab, which showed more homogeneity in their pathways. Furthermore, we quantify this spread and characterize metastatic sites as ‘spreaders’ and ‘sponges’ based on their probability of spreading the disease. Citation Format: Jeremy M. Mason, Paul K. Newton, Gino K. In, Sonia Lin, Peter Kuhn, Jorge J. Nieva. Spatiotemporal progression patterns in metastatic lung cancer treated with bevacizumab. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2711.
Ofatumumab Based Chemoimmunotherapy (CIT) for Patients with Previously Untreated CLL,
Authors: Tait D. Shanafelt, Mark C Lanasa, Clive S. Zent, Jose F. Leis, Timothy G Call, Betsy R. LaPlant, Han Tun, Deborah A. Bowen, Diane F. Jelinek, Curtis A. Hanson, Neil Kay
Journal: Blood (2011)
Abstract 2867: Functional role of FHL2 in the splicing machinery of liver cells
Authors: Ye Cao, Minghua Liu, Yi Yang, Yinfeng Zhang, Kwok Wing Tsui
Journal: Cancer Research (2016)

Abstract Hepatocellular carcinoma (HCC) is a highly lethal cancer with increasing worldwide incidence. The four-and-a-half LIM domain protein 2 (FHL2) has been identified as an oncogene / tumor suppressor gene in a tissue/cell specific manner by acting as an adaptor protein to form different complexes and involving in various signaling pathways. To clarify the intriguing functions of FHL2, we have identified a batch of interacting partners of FHL2 by immunoprecipitation and liquid chromatography coupling with mass spectrometry. Many of these proteins, including SNRNP70, DAZAP1, SFPQ, TIAL1 and so on, are involved in spliceosome components and mRNA surveillance. The interaction among several proteins and FHL2 has been confirmed by co-immunoprecipitation. To further elucidate the functional role of FHL2 in the splicing process in liver cancer cells, we have studied the transcriptomes of FHL2 overexpression and FHL2 knockdown liver cells, whereas empty vector and scrambled siRNA were used as controls respectively. Followed by bioinformatics analysis, we found significant concordance between the immunoprecipitation and transcriptome datasets. Selected genes were further validated by real-time PCR such as FGFR4. In summary, FHL2 is probably regulating the mRNA splicing by interacting with components of the splicing machinery and modulating splicing related genes at the transcriptional level. Citation Format: Ye Cao, Minghua Liu, Yi Yang, Yinfeng Zhang, Kwok Wing Tsui. Functional role of FHL2 in the splicing machinery of liver cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2867.
New Perspectives in Rheumatology: Avoiding Antimalarial Toxicity
Authors: James T. Rosenbaum, George R. Mount, Jameel Youssef, Phoebe Lin
Journal: Arthritis & Rheumatology (2016)

This report inaugurates New Perspectives in Rheumatology, a series of authoritative articles that focus on recent scientific and clinical developments and their potential to reshape rheumatology practice. Anticipated topics include the implementation of new guidelines and emerging information from clinical and translational research. Richard J. Bucala, MD, PhDEditor-in-ChiefRobert Terkeltaub, MDCo-Editor and Review Article Editor.
Abstract 1277: Neural crest-like gene FOXD1 plays a role in melanoma cell migration and invasion
Authors: Huizi Wu, Lionel Larribere, Kasia Weina, Nathalie Knappe, Christoffer Gebhardt, Viktor Umansky, Jochen Utikal
Journal: Cancer Research (2016)

Abstract Melanoma is a highly aggressive skin cancer arising from transformed melanocytes. Despite tremendous efforts and considerable progress in clinical treatment, melanoma remains a deadly disease characterized by abundant treatment resistance due to high phenotype plasticity of melanoma cells. In order to evade therapy, melanoma cells can undergo phenotype switching from a differentiated state towards a dedifferentiated and more stem cell-like state. Recently, some melanoma cells with neural crest-like characteristics were shown to be able to sustain tumor growth and to give rise to distant metastases. Here, we use the technique of directed differentiation of human induced pluripotent stem cells (hiPSCs) to characterize the human neural crest cell population in vitro and to identify potential genes that are reactivated during melanoma progression. We differentiated hiPSCs towards melanocytes via the neural crest stage. Expression analyses revealed an overexpression of the Forkhead Box D1 (FOXD1) transcription factor in neural crest cells and importantly, increased FOXD1 expression was also found in melanoma cells compared to normal human melanocytes. Interestingly, in invasive and less proliferative melanoma cells, FOXD1 expression was elevated compared to highly proliferative and less motile cells, indicating a potential role of this factor in motility acquisition. To gain deeper insight into the expression pattern of FOXD1 in clinical samples, a protein expression analysis using tissue microarrays was performed determining FOXD1 expression in melanocytic nevi, primary and metastatic melanoma samples. Surprisingly, in benign melanocytic nevi, FOXD1 was dominantly localized in the nucleus whereas a shift towards a cytoplasmic localization was observed in both, primary and metastatic melanomas. Loss of FOXD1 gene in melanoma cells also revealed the importance of this gene in melanoma cell migration and invasion. Further characterization of FOXD1 and its role in melanoma progression may help to understand the phenotypic plasticity of melanoma cells, which is required for overcoming resistance in anti-melanoma therapy. In conclusion, FOXD1 is overexpressed and aberrantly localized in malignant melanoma cells compared to melanocytes. Our data indicate its function in melanoma migration and invasion. FOXD1 might be an interesting target in melanoma therapy. Citation Format: Huizi Wu, Lionel Larribere, Kasia Weina, Nathalie Knappe, Christoffer Gebhardt, Viktor Umansky, Jochen Utikal. Neural crest-like gene FOXD1 plays a role in melanoma cell migration and invasion. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1277.
Abstract 2699: A cancer treatment based on synergy between anti-angiogenic and immune cell therapies
Authors: Luis F. Soto-Ortiz
Journal: Cancer Research (2016)

Abstract A mathematical model integrating tumor angiogenesis and tumor-targeted cytotoxicity by immune cells was developed to identify the therapeutic window of two distinct modes to treat cancer: 1) an anti-angiogenesis treatment based on the monoclonal antibody bevacizumab that targets tumor vasculature, and 2) immunotherapy involving the injection of unlicensed dendritic cells to boost the anti-tumor adaptive response. The angiogenic cytokine Vascular Endothelial Growth Factor (VEGF) contributes to the immunosuppressive tumor microenvironment, which is responsible for the short-lived therapeutic effect of cancer-targeted immunotherapy. The effect of immunosuppression on the width of the therapeutic window of each treatment was quantified. Experimental evidence has shown that neutralizing immunosuppressive cytokines results in an enhanced immune response against infections and chronic diseases. The model was used to determine treatment protocols involving the combination of anti-VEGF and unlicensed dendritic cell injections that enhance tumor regression. The model simulations predicted that the most effective method to treat tumors involves administering a series of biweekly anti-VEGF injections to disrupt angiogenic processes and limit tumor growth. The simulations also verified the hypothesis that reducing the concentration of the immunosuppressive factor VEGF prior to an injection of unlicensed dendritic cells enhances the cytotoxicity of CD8+ T cells and results in complete tumor elimination. Feasible treatment protocols for tumors that are diagnosed late and have grown to a relatively large size were identified. Citation Format: Luis F. Soto-Ortiz. A cancer treatment based on synergy between anti-angiogenic and immune cell therapies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2699.
Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist
Authors: Peter Kühnen, Karine Clément, Susanna Wiegand, Oliver Blankenstein, Keith Gottesdiener, Lea L. Martini, Knut Mai, Ulrike Blume-Peytavi, Annette Grüters, Heiko Krude
Journal: New England Journal of Medicine (2016)

Patients with rare defects in the gene encoding proopiomelanocortin (POMC) have extreme early-onset obesity, hyperphagia, hypopigmentation, and hypocortisolism, resulting from the lack of the proopiomelanocortin-derived peptides melanocyte-stimulating hormone and corticotropin. In such patients, adrenal insufficiency must be treated with hydrocortisone early in life. No effective pharmacologic treatments have been available for the hyperphagia and obesity that characterize the condition. In this investigator-initiated, open-label study, two patients with proopiomelanocortin deficiency were treated with setmelanotide, a new melanocortin-4 receptor agonist. The patients had a sustainable reduction in hunger and substantial weight loss (51.0 kg after 42 weeks in Patient 1 and 20.5 kg after 12 weeks in Patient 2).
Abstract 5141: Determinants of metastatic competence in breast carcinoma: a role for immune cells
Authors: Robiya Joseph, Rama Soundararajan, Anurag Paranjape, Sendurai Mani
Journal: Cancer Research (2016)

Abstract Dynamic interactions between cancer cells and their surrounding microenvironment influence tumor survival, growth and metastasis. The tumor microenvironment harbors a complex variety of cells including T lymphocytes and macrophages that produce a host of cytokines, chemokines, growth factors or interleukins, all of which presumably work in coordination to determine net tumor biology. Immune cells can offer a critical check-point in tumor progression. Interestingly however, infiltration of the tumor by immune cells appears to have dual functionality - they can reportedly either be pro-metastatic or anti-metastatic in their contribution. These clearly conflicting roles of immune cells limit our comprehension of their actual input to tumor advancement. Tumor infiltrating lymphocytes, in particular, the infiltration by T cells, has emerged as a good prognostic marker for a variety of cancers. However, the key molecular factors that regulate the cross-talk between tumor cells and T lymphocytes, and the underlying signaling pathways are still ill-defined. Moreover, the impact of T lymphocytes of the inflammatory tumor microenvironment, on the epithelial-mesenchymal plasticity and associated metastatic traits in breast cancer cells, is incompletely understood. We previously demonstrated that two key EMT/CSC factors - FOXC2 and Twist - are critical requirements for breast carcinoma cells to metastasize. The objective of the current study is to systematically investigate the role of regulatory T cells in EMT/CSC-dictated breast tumor progression, using two isogenic breast cancer cell lines (67NR and 4T1) that form primary mammary tumors similarly, but differ drastically in their ability to metastasize. Citation Format: Robiya Joseph, Rama Soundararajan, Anurag Paranjape, Sendurai Mani. Determinants of metastatic competence in breast carcinoma: a role for immune cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5141.
Thrombomodulin-Dependent Protein C Activator Treatment Improves the Short-Term Outcome of Experimental Ischemic Stroke in Mice.
Authors: Andras Gruber, Patricia D. Hurn, Sawan Hurst, Leslie Bush, Ulla M. Marzec, Erik Tucker, Stephen R. Hanson, Enrico Di Cera
Journal: Blood (2006)
Incidence and prevalence of basal cell carcinoma (BCC) and locally advanced BCC (LABCC) in a large commercially insured population in the United States: A retrospective cohort study
Authors: Gary Goldenberg, Tom Karagiannis, Jacqueline Blanche Palmer, Juzer Lotya, Caitriona O'Neill, Renata Kisa, Vivian Herrera, Daniel M. Siegel
Journal: Journal of the American Academy of Dermatology (2016)
A phase II study of weekly docetaxel/cisplatin and concurrent radiotherapy followed by surgery in patients with stage III non-small cell lung cancer (NSCLC)
Authors: K. W. Maas, E. C. Phernambucq, S. Y. Sharouni, J. A. Stigt, H. J. Groen, B. E. van den Borne, S. Senan, E. F. Smit, R. A. Paul, F. M. Schramel
Journal: Journal of Clinical Oncology (2007)

18050 Background: Concurrent chemoradiotherapy treatment is standard of care for patients with stage III NSCLC in good performance. Optimal chemotherapy have yet to be defined and the role of surgery is still unclear. This prospective phase II study analysed the feasibility and efficacy of weekly docetaxel/cisplatin (DC) and concurrent involved-field thoracic radiotherapy (CRT) followed by surgery in good performance status patients with stage IIIA/B NSCLC. Primary endpoint is radiological response of DC and CRT. Secondary endpoints included toxicity, efficacy of surgery, postoperative morbidity and mortality, time to progression and overall survival. Methods: DC consisted of IV docetaxel 20 mg/m 2 and cisplatin 20mg/m 2 at days 1,8,15,22,29 and 36. CRT was given in once-daily fractions of 1.8 Gy, 5 fractions a week to a total dose of 45 Gy during days 8 to 36. CT-based planning was used to minimise radiation to the contralateral lung. Invasive and non-invasive investigations were performed after induction treatment in order to restage the mediastinum. when mediastinal downstaging was achieved, surgery was performed in order to achieve radical resection. Results: Between January 2005 until August 2006, 45 patients were included, of whom 43 patients were evaluable. Stage IIIB disease was present in 18 patients (cT4N2=9, cT4N0/N1=5 and cN3=4) and 25 had stage IIIA-N2 disease. Radiologic response was seen in 20 patients (47%) and 8 (19%) showed progressive disease. Toxicity was mild. Explorative thoracotomy was performed in 24 (56%) patients. Of these, 14 were initially staged as IIIA and ten as stage IIIB (4 of whom had N3 metastases). Twenty patients (47%) underwent a radical resection without residual mediastinal malignant disease, and ten pneumonectomies (8 left sided) were performed. Three patients showed complete pathological response. The 30 days mortality after operation was 4% (one patient) due to ARDS. Conclusions: Weekly DC and CRT is possible in stage III NSCLC, with limited toxicity and nearly half of the treated patients (47%) could undergo a radical surgical resection (R0) without residual mediastinal malignant disease. This promising tri-modality regimen should be tested in future phase II or III trials. No significant financial relationships to disclose.
Abstract 1724: Pancreatic cancer stem cell metastasis and mitochondrial respiration is dependent on the the ISG15-mediated ubiquitin-like modification process known as ISGylation
Authors: Bruno Sainz, Sonia Alcala Sanchez, Mireia Vallespinos
Journal: Cancer Research (2016)

Abstract We recently discovered that CSCs of distinct solid tumors (e.g. pancreatic, colon, and liver) contain intracellular vesicles coated in the ATP-dependent transporter ABCG2, which act as a sink for the accumulation of riboflavin (vitamin B2). Using autofluorescence and other CSC markers, such as CD133, we have begun to dissect CSCs at the genetic and protein level. Using RNAseq to transcriptionally distinguish CSCs from non-CSCs, we observed that pancreatic CSCs of different primary PDAC tumors exhibit a transcriptional gene activation signature belonging to the Type I interferon (IFN) signaling pathway. In particular, CSCs up-regulate the interferon-stimulated gene 15, a 165 amino acid (17kDa) protein that is induced by Type I IFN treatment and functions to ISGylate proteins, a ubiquitin-like modification process whereby ISG15 can be covalently linked to cytoplasmic and nuclear proteins. We have discovered that CSCs not only upregulate the expression of monomeric ISG15, but numerous proteins within CSCs are ISGylated, the level of ISGylation correlates with their metastatic capacity and knockdown of ISG15 ablates pancreatic CSCs functions, such as self-renewal, migration and invasion in vivo and mitochondrial respiration. Thus, our data indicate that the ISGylayion pathway is active in CSCs and plays an important role in the “stem-like” properties of these cells. We have also elucidated the mechanism underlying the differential regulation of ISG15 in CSCs versus non-CSCs. Specifically, using over expression lentiviral vector systems and pharmacological inhibitors (i.e. BRD4 inhibitor JQ-1), we show that MYC controls the expression of miR22, a micro-RNA that targets, among others transcripts, a number of Interferon Regulatory Factors (IRFs) that are essential for intracellular IFN signaling, including ISG15 expression. CSCs express low levels of MYC and miR-22, relieving the inhibitory block on IRFs and subsequent ISG15 signaling. As expected, over expression of MYC increases miR-22 levels and blocks IRF-mediated ISG15 expression. While the intricacies of these complex and distinct pathways still need to be unraveled at the CSC level, our data suggest that MYC may be a key universal player in these pathways, and targeting ISG15 in CSCs may represent a unique approach to altering the biology of CSCs. Citation Format: Bruno Sainz, Sonia Alcala Sanchez, Mireia Vallespinos. Pancreatic cancer stem cell metastasis and mitochondrial respiration is dependent on the the ISG15-mediated ubiquitin-like modification process known as ISGylation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1724.