tbuckley/cabot-search huggingface dataset:
Abstract SY39-03: Radiation-mediated DNA sensing pathway for immunity and tumor regression
Authors: Yang-xin Fu
Journal: Cancer Research (2015)

Abstract It is thought that ablative radiotherapy (RT), used for rapid control tumor growth, induces genotoxic stress and mitosis crisis leading to prolonged dormancy of irradiated tumor at local and distal site in most patients. We have unexpectedly observed that initial reduction of tumor burden following ablative RT also depends largely on type I IFN for CTL. Targeting tumor with IFN can control tumor growth through initiating a coordinated innate and adaptive immune attack against tumor cells. However, the mechanism for radiation-mediated type I IFN induction remains unclear. Here, we demonstrated that STING, but not MYD88, was required for type I IFN-dependent antitumor effects of radiation. STING in dendritic cells (DCs) controlled radiation-mediated IFN-β induction and was activated by irradiated-tumor cells. The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) mediated DCs sensing of irradiated-tumor cells. Moreover, STING was essential for radiation-induced adaptive immune responses, which relied on type I IFN signaling on DCs. Exogenous IFN-β treatment rescued cGAS/STING-deficient immune responses. Accordingly, enhancing STING signaling by cGAMP administration promoted antitumor efficacy of radiation. Our results reveal that the molecular mechanism of radiation-mediated antitumor immunity depends on a proper cytosolic DNA-sensing pathway, pointing towards a new understanding of radiation and host interactions. Furthermore, we uncover a new strategy to improve radiotherapy by cGAMP treatment. RT induced IFN can also upregulate PD-L1 that suppress T cell-mediated damage and develop radiation resistance for relapse over time. Anti-PDL-1 antibody can greatly reduce radiation resistance leading to complete tumor regression. Furthermore, our study challenges the rationale for current radio/chemotherapy strategies and highlights the importance of immune activation in preventing tumor relapse. Citation Format: Yang-xin Fu. Radiation-mediated DNA sensing pathway for immunity and tumor regression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY39-03. doi:10.1158/1538-7445.AM2015-SY39-03
Advanced Stage Follicular Lymphoma - Watch and Wait or Immunochemotherapy?
Authors: Dulcineia Pereira, Carolina Teixeira, Sofia Ramalheira, Patricia Rocha, Claudia Moreira, Alina Rosinha, Duarte Domingues, Natasha Amaral, Edgar Mesquita, A Brito, Luisa Viterbo, Isabel Oliveira, Nelson Domingues, Ilidia Moreira, Ana Espirito-Santo, Sergio Chacim, Luis Leite, Isabel Cristina Ferreira, Rui Henrique, Angelo Martins, Jose Mario Mariz
Journal: Blood (2014)
Abstract SY16-03: Enterprise-wide clinical sequencing to match patients to personalized cancer treatments
Authors: Michael F. Berger
Journal: Cancer Research (2015)

Abstract Massively parallel sequencing of tumors enables the identification of oncogenomic mutations that correlate with response and resistance to targeted therapies and the prospective detection of these biomarkers in patients with cancer. At Memorial Sloan Kettering Cancer Center, we have developed and optimized a targeted sequencing panel encompassing more than 300 key cancer associated genes (MSK-IMPACT), which we have applied to prospectively profile several thousands of tumors in the clinical setting. The large-scale implementation of our clinical assay has allowed us to identify targetable mutations in patients with many types of cancer and to match patients to the most appropriate clinical trials. I will discuss general challenges and considerations involved in the establishment of an infrastructure for precision oncology at a large center, including challenges in the analysis and management of data and the clinical interpretation of genomic results. I will also present results from our molecular profiling initiative, including several cases in which they have directly influenced patient management. Citation Format: Michael F. Berger. Enterprise-wide clinical sequencing to match patients to personalized cancer treatments. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY16-03. doi:10.1158/1538-7445.AM2015-SY16-03
Abstract LB-290: Multiple distinct mechanisms disrupt let-7 miRNA biogenesis and function in neuroblastoma
Authors: John T. Powers, Kaloyan M. Tsanov, Frederik Roles, Richard Ebright, Marc Seligson, Yvanka de Soysa, Patrick Cahan, Jessica Theissen, Grace S. LaPier, Dan S. Pearson, Frank Berthold, George Q. Daley
Journal: Cancer Research (2015)

Abstract The let-7 microRNA family are known tumor suppressors often deregulated in cancer, yet the underlying mechanisms of let-7 disruption remain poorly understood. Neuroblastoma, a neural crest derived tumor, is defined in part by poor prognosis associated with genetic amplification of MYCN, itself a let-7 target. The let-7 biogenesis inhibitor LIN28B has recently been implicated as a critical regulator of MYCN, but we have employed siRNA and CRISPR-mediated gene disruption to show that LIN28B is dispensable for both MYCN protein expression and growth of MYCN-amplified neuroblastoma cell lines despite robust de-repression of let-7, which prompted us to explore additional mechanisms for let-7 disruption. Consequently, we have found that amplified MYCN mRNA is a potent let-7 sponge that through exceptionally high expression defines a sub-class of self-sponging amplified-competing-endogenous-RNA (aceRNA), which reconciles the dispensability of LIN28B in NB cell lines. In addition, by analyzing a large cohort of tumor samples from patients, we observe frequent genomic loss of let-7 that inversely associates with MYCN-amplification, providing a functional explanation for the known MYCN-amplification-independent pattern of chromosome 3p and 11q loss, which harbor let-7g and let-7a2, respectively. We thus propose a model whereby let-7 disruption by genetic loss, LIN28B expression, or aceRNA sponging is a unifying mechanism of neuroblastoma pathogenesis. Indeed, our data show that the majority of neuroblastomas have at least one let-7 disruption event and that genetic loss in non-MYCN-amplified tumors marks decreased survival, further underscoring its importance. The inverse selective relationship between allelic loss and sponging of let-7 from highly expressed or amplified oncogenes may have broad implications for oncogenesis. Note: This abstract was not presented at the meeting. Citation Format: John T. Powers, Kaloyan M. Tsanov, Frederik Roles, Richard Ebright, Marc Seligson, Yvanka de Soysa, Patrick Cahan, Jessica Theissen, Grace S. LaPier, Dan S. Pearson, Frank Berthold, George Q. Daley. Multiple distinct mechanisms disrupt let-7 miRNA biogenesis and function in neuroblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-290. doi:10.1158/1538-7445.AM2015-LB-290
Neutrophilic eccrine hidradenitis in two patients treated with<i>BRAF</i>inhibitors: a new cutaneous adverse event
Authors: F. Herms, N. Franck, N. Kramkimel, F. Fichel, L. Delaval, S. Laurent-Roussel, A. Carlotti, M.-F. Avril
Journal: British Journal of Dermatology (2016)

Neutrophilic eccrine hidradenitis (NEH) is a rare neutrophilic dermatosis, first described in patients undergoing chemotherapy for a malignant haemopathy. It has polymorphous clinical features and the association of both clinical and histological features is necessary to make a diagnosis. We report the first two cases of NEH in patients treated with a BRAF inhibitor (BRAFi), either dabrafenib or vemurafenib, for a stage IV metastatic melanoma. Disseminated erythematous plaques associated with fever and polyarthralgia occurred early after the initiation of treatment and were badly tolerated. Histological analyses confirmed the diagnosis of NEH. Symptoms disappeared a few days after the cessation of treatment and introduction of topical steroids. The replacement of one BRAFi with another is a therapeutic alternative as it is not necessarily associated with a relapse of NEH. NEH can be added to the spectrum of neutrophilic dermatoses induced by BRAFis. It occurs earlier (3–4 days) than previously described drug‐induced NEH (9–12 days) and may be an earlier stage of eccrine squamous syringometaplasia, which has already been reported in the context of BRAFi‐treated patients.
Gastrointestinal and cutaneous AIDS-related Kaposi's sarcoma: Different activity of liposomal doxorubicin according to location of lesions
Authors: D. E. Hernandez-Morales, A. E. Hernàndez-Zaccaro
Journal: Journal of Clinical Oncology (2004)

9030 Background: Kaposi's sarcoma (KS) continuous being a frequent neoplasm in third world AIDS patients. Liposomal doxorubicin (LD) is the drug of choice for advanced KS; nevertheless, it is very expensive for third world countries. In addition, we believe that the greatest usefulness of LD is in patients with visceral KS and that there is a different activity of the drug according to the location of the lesions. Due to this, we carried out a prospective study to evaluate the effectiveness of LD in gastrointestinal KS patients as well as its differential clinical activity, depending on the location of the lesions. Methods: The study included thirteen AIDS male patients with ages between 25 and 35 years (mean: 27 years), a performance status > 70, with more than 25 cutaneous lesions and extensive gastrointestinal KS. They were treated with LD, 20 mg/m2 every 21 days, during 6 cycles, and half of them were under highly active antiretroviral therapy. Results: Ten patients (77%) were able to obtain a complete response of the gastrointestinal KS lesions and three (23%) a partial response. Regarding the cutaneous lesions, there was only one patient (8%) who showed a complete response, five (38%) showed partial responses and seven (54%) stabilized their disease. By applying Fisher's test we found a significant difference (p< 0.00035) when comparing the effectiveness of LD in gastrointestinal lesions in relation to cutaneous ones. Conclusions: It can be concluded that LD has a different activity in KS lesions, being more effective in gastrointestinal KS, which is very relevant since gastrointestinal KS can compromise the life of patients due to the massive bleeding risk. Due to this, we can recommend LD in patients from third world countries with extensive gastrointestinal KS. No significant financial relationships to disclose.
Diffuse large B cell lymphoma with mediastinal mass at presentation
Authors: A. Deshpande, P. Bierman, J. Vose, M. Bast, G. Bociek, J. Lynch, J. Armitage
Journal: Journal of Clinical Oncology (2004)

6585 Background: Primary mediastinal B cell lymphoma (PMBL) has been recognized as a subtype of diffuse large B cell lymphoma (DLBCL) with distinct characteristics (e.g.: seen most often in young females) and is thought to be of thymic origin. Other subtypes of DLBCL may involve the mediastinum and may be confused with PMBL. The value of radiotherapy in DLBCL with a mediastinal mass is debated. We conducted this retrospective analysis to study clinical characteristics and treatment outcomes in patients with DLBCL and a mediastinal mass at presentation. Methods: This is an analysis of 61 patients diagnosed with diffuse large B-cell lymphoma presenting with a mediastinal mass> 5 cms who received their initial treatment between June 1984 and October 2000. Results: The median age was 41 years and 50% were females. 66% presented with elevated LDH and 63% had limited stage disease (stage I and II). 46 % of the patients presented with mediastinal mass >10cms and 69% had B symptoms. 27% received adjuvant radiation therapy. All patients received anthracycline-containing chemotherapy. A complete remission was achieved in 62% and partial remission in 22% of the patients. The median follow-up of surviving patients is 7.6 years and the 5-year overall (OS) and event-free survival (EFS) is 55% and 38%, respectively. Older patients had significantly poorer OS (p = 0.016), but age was not associated with EFS. Stage III and IV patients had poorer outcome compared to stage I and II (EFS 58% vs. 24%, p = 0.025 and OS 84% vs. 30%, p < 0.001). Tumor size, B symptoms, LDH and number of extra nodal sites were not significantly associated with outcome. Patients who received adjuvant radiation therapy compared to those who did not had better EFS (65% vs. 32%, p< 0.01), and OS (72% vs. 45%, p = 0.081). The use of radiation therapy improved outcome in patients with stages I and II and not in III and IV. The advantage was most pronounced for stage II patients (EFS p = 0.014 and OS p= 0.013). Conclusions: Patients with DLBCL with mediastinal mass who present with limited stage disease benefit from adjuvant radiation therapy. No significant financial relationships to disclose.
Maintenance Therapy (MT) for non-squamous advanced NSCLC: a multicenter Italian survey about patients (pts)' perspectives and physicians' awareness
Authors: M.V. Pacchiana, E. Capelletto, A. Rossi, D. Galetta, P. Bordi, A. Ceribelli, V. Scotti, D. Cortinovis, G. Valmadre, O. Martelli, A. Miccianza, A. Del Conte, R. Morena, F. Rosetti, L. Ostacoli, S. Novello
Journal: Annals of Oncology (2015)
Clinical and Molecular Results of the Multicenter Randomized GITMO-IIL Trial in Poor Risk Follicular Lymphoma (FL) at Diagnosis: Rituximab-Supplemented High-Dose Sequential Chemotherapy (R-HDS) Is Superior to CHOP-R in Molecular Remissions Rate, EFS and PFS.
Authors: Marco Ladetto, Federica de Marco, Fabio Benedetti, Umberto Vitolo, Caterina Patti, Alessandro Rambaldi, Anna Marina Liberati, Maurizio Musso, Alessandro Pulsoni, Attilio Olivieri, Enzo Pavone, Enrico Pogliani, Delia Rota Scalabrini, Andrea Gallamini, Vincenzo Callea, Irene Ricca, Mario Boccadoro, Ignazio Majolino, Paolo Corradini, Alessandro M. Gianni, Corrado Tarella
Journal: Blood (2006)
Abstract A44: Coordination of stress signals by the lysine methyltransferase SMYD2 promotes pancreatic cancer
Authors: Pawel K. Mazur, Nicolas Reynoird, Timo Stellfeld, Natasha M. Flores, Shane M. Lofgren, Scott M. Carlson, Elisabeth Brambilla, Pierre Hainaut, Ewa B. Kaznowska, Cheryl H. Arrowsmith, Purvesh Khatri, Carlo Stresemann, Or Gozani, Julien Sage
Journal: Cancer Research (2016)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal form of cancer with few therapeutic options. We find that levels of the lysine methyltransferase SMYD2 are elevated in precancerous lesions and PDAC and that SMYD2 normally promotes Ras-driven development of PDAC. Notably, loss of SMYD2 correlates with diminished inflammation in PDAC and we identify the stress-response kinase MAPKAPK3 as a new and physiologically relevant SMYD2 substrate. Inhibition of MAPKAPK3 impedes PDAC growth, identifying a potential new kinase target in PDAC. Finally, we show that inhibition of SMYD2 cooperates with standard chemotherapy to treat PDAC cells and tumors. Together, our findings suggest new roles for SMYD2 in inflammation and stress responses, and identify SMYD2 and MAPKAPK3 as potential therapeutic targets to treat pancreatic cancer. Citation Format: Pawel K. Mazur, Nicolas Reynoird, Timo Stellfeld, Natasha M. Flores, Shane M. Lofgren, Scott M. Carlson, Elisabeth Brambilla, Pierre Hainaut, Ewa B. Kaznowska, Cheryl H. Arrowsmith, Purvesh Khatri, Carlo Stresemann, Or Gozani, Julien Sage.{Authors}. Coordination of stress signals by the lysine methyltransferase SMYD2 promotes pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A44.
Bcr-Abl Inhibition by Imatinib Restores Lyn Trafficking to Lipid Rafts and Promotes CXCR4 Surface Expression of CML Cells in BM Microenvironment
Authors: Yoko Tabe, Linhua Jin, Naoki Ichikawa, Marina Konopleva, Michael Andreeff, Takashi Miida
Journal: Blood (2008)
A Single Legionella Effector Catalyzes a Multistep Ubiquitination Pathway to Rearrange Tubular Endoplasmic Reticulum for Replication
Authors: Kristin M. Kotewicz, Vinay Ramabhadran, Nicole Sjoblom, Joseph P. Vogel, Eva Haenssler, Mengyun Zhang, Jessica Behringer, Rebecca A. Scheck, Ralph R. Isberg
Journal: Cell Host & Microbe (2016)
625. RNAi Therapy for Dominant Limb Girdle Muscular Dystrophy Type 1A
Authors: Lindsay M. Wallace, Carlee R. Giesige, Danielle A. Griffin, Louise R. Rodino-Klapaca, Scott Q. Harper
Journal: Molecular Therapy (2016)

Limb Girdle Muscular Dystrophy (LGMD) refers to a group of disorders characterized by progressive wasting and weakness of pelvic and shoulder girdle muscles. Patients commonly require wheelchair assistance, and individuals with some forms of LGMD may have cardiac and respiratory muscle involvement. Modest improvements in a limited set of muscles may dramatically improve patients' quality of life, but currently no effective treatment exists. There are 8 dominant forms of LGMD (LGMD1) that would benefit from gene therapy strategies to reduce their pathogenic alleles. We previously showed the first RNAi-based pre-clinical treatment for LGMD1A, which is caused by dominant mutations in one allele of the myotilin (MYOT) gene. Our strategy involved delivering MYOT targeted artificial microRNAs (miMYOT) to muscles of the T57I transgenic mouse model of LGMD1A using AAV6 vectors. Both 3 months (short-term) and 9 months (long-term) time points showed significant reduction of mutant myotilin mRNA and soluble protein expression. MYOT gene silencing resulted in histological improvements that were accompanied by significant functional correction including increased muscle weight and improved specific force. While the initial study showed proof-of-principle for this therapy, translation of miMYOT requires additional work. Mouse knockout studies suggested MYOT is a non-essential gene, as animals lacking MYOT develop normally. In the case of LGMD1A this would suggest the mutation is harmful but complete loss would be tolerated. However, we do not currently know if haploinsufficiency of wild-type MYOT is tolerated in other organisms, including humans. To address this question, we delivered morpholinos or AAV.miRNAs to multiple species. We found knockdown of endogenous MYOT to be safe in developing Xenopus, adult mice and non-human primates, suggesting that a non-allele-specific silencing approach for MYOT would be tolerated in LGMD1A-targeted treatments. We also performed dose escalations to assess the safety parameters of AAV.miMYOT vectors and utilized microarray data to identify potential biomarkers for clinical outcome measures. We then validated that some of our lead biomarkers were significantly normalized in miMYOT-treated T57I mice. Together these data provide additional data to support the further translation of miMYOT therapy for LGMD1A.
P0134 : Complications of endoscopic retrograde cholangiopancreatography in patients with cirrhosis
Authors: C. Leal, A. Fernandez Simon, O. Sendino, C. Zulli, C. Rodriguez de Miguel, A. Mendez-Bocanegra, D. Balderramo, J. Fernández, J. Llach, A. Cardenas
Journal: Journal of Hepatology (2015)
Abstract 839: Effects of occupational exposure to carbon black on peripheral white blood cell counts
Authors: Yufei Dai, Rong Zhang, Yong Niu, Huawei Duan, Tao Meng, Meng Ye, Meili Shen, Ping Bin, Shanfa Yu, Roel Vermeulen, Nathaniel Rothman, Qing Lan, Yuxin Zheng
Journal: Cancer Research (2015)

Abstract Carbon black (CB) is a material produced by the combustion of hydrocarbon gases or liquids and widely used in various industrial settings. The International Agency for Research on Cancer has classified CB as possibly carcinogenic to humans. Previous studies suggest that CB might induce lung inflammation and injury and it is well known that inflammation can play an important role in tumor development. However, the relationship between CB exposure and peripheral white blood cell counts is still not clear. To address this issue, we conducted a cross-sectional molecular epidemiology study of 106 CB-exposed male workers responsible for packing CB in a CB manufacturing facility that produced very high purity CB and 112 unexposed male control workers from the same geographic region who were frequency-matched to the exposed workers by age. The average number of years worked in the factory for the exposed workers was 12.5 years. Peripheral blood samples were collected and a complete blood cell count (CBC) and lymphocyte subset analysis were conducted. There was a borderline significant increase in eosinophil count, and a significant decrease in total lymphocyte and NK cell counts, among the exposed vs. control workers. Among non-smokers (35 exposed and 29 controls), CB exposure was associated with a borderline significant increase in total white blood cell and neutrophil counts, a significant increase in eosinophil counts, and a significant decrease in total lymphocyte, CD3+ T cell, CD8+ T cell and NK cell counts. There were no significant differences between exposed and control workers for any white blood cell measure among smokers. Also, there was some evidence of an interaction between carbon black exposure and smoking status for neutrophil, total lymphocyte, CD3+ T cell, and CD8+ T cell counts. Our results suggest that CB exposure may be associated with altered levels of cells that play an important role in the inflammatory process among non-smokers. Also, there was evidence for an interaction between CB exposure and tobacco use. These findings may provide new insights into particulate-associated disease. Citation Format: Yufei Dai, Rong Zhang, Yong Niu, Huawei Duan, Tao Meng, Meng Ye, Meili Shen, Ping Bin, Shanfa Yu, Roel Vermeulen, Nathaniel Rothman, Qing Lan, Yuxin Zheng. Effects of occupational exposure to carbon black on peripheral white blood cell counts. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 839. doi:10.1158/1538-7445.AM2015-839