tbuckley/cabot-search huggingface dataset:
Abstract 4612: In breast cancer cells IGF-I induces upregulation of DDR1 by suppressing miR-199a-5p via the PI3K/Akt pathway
Authors: Chiara Palladino, Roberta Matà, Maria Luisa Nicolosi, Anna Rita Lo Presti, Roberta Malaguarnera, Marco Ragusa, Daniela Sciortino, Andrea Morrione, Marcello Maggiolini, Veronica Vella, Antonino Belfiore
Journal: Cancer Research (2016)

Abstract Discoidin Domain Receptor 1 (DDR1) is a collagen receptor tyrosine-kinase that is implicated in tumor progression by contributing to epithelial mesenchymal transition (EMT) and by enhancing tumor cell migration and invasion. We previously demonstrated that, in breast cancer cells, DDR1 functionally cross-talks with IGF-I receptor (IGF-IR), by affecting IGF-IR expression and trafficking. In these cells, DDR1 was able to enhance the stimulatory effects of IGF-I on mitogenesis and invasion suggesting that the DDR1-IGF-IR cross-talk may play a role in cancer progression. Herein, we evaluated whether IGF-I may in turn affect DDR1 expression. Indeed, we demonstrated that in breast cancer cells (MCF-7 and MDA-MB-231), IGF-I was able to upregulate DDR1 protein expression in a time and dose dependent manner. In contrast, DDR1 mRNA levels showed non-significant changes after stimulation with IGF-I. Moreover, we found that DDR1 protein upregulation requires the activation of the PI3K/Akt pathway, while the Erk1/2, the p70/mTOR and the PKC pathways are not involved. Indeed, IGF-I induced DDR1 protein upregulation through a post-trascriptional mechanism involving miR-199a-5p suppression via Akt. We also found that autocrine IGF-II, induced by stable IGF-II cDNA transfection, is also able to elicit significant DDR1 upregulation in breast cancer cells. Similar effects were induced by IGF-II secreted by human cancer associated fibroblasts. Finally, we showed that miR-199a-5p transfection in breast cancer cells, decreased DDR1 expression and affected the response to IGF-I in terms of intracellular signaling through the PI3K/Akt and Erk1/2 pathways, and biological effects such as cell proliferation and migration. These results demonstrate that the protumoral effects of IGF-I include downregulation of miR-199a-5p and consequent upregulation of DDR1 protein. Both these molecules may represent important targets for breast cancers with overactivation of the IGF-IR axis. Citation Format: Chiara Palladino, Roberta Matà, Maria Luisa Nicolosi, Anna Rita Lo Presti, Roberta Malaguarnera, Marco Ragusa, Daniela Sciortino, Andrea Morrione, Marcello Maggiolini, Veronica Vella, Antonino Belfiore. In breast cancer cells IGF-I induces upregulation of DDR1 by suppressing miR-199a-5p via the PI3K/Akt pathway. [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 4612.
Not “just” a shoulder dislocation
Authors: Raghavendra Marappa Ganeshan, Ahmed Ibrahim Bakr
Journal: BMJ (2016)

A 38 year old woman injured her right shoulder during a game of netball. Her shoulder dislocation was reduced under sedation in the emergency department, and her shoulder was immobilised in a sling and she was referred to fracture clinic. She is right handed and has a desk job in an office. She mentioned that she had sustained a similar dislocation …
A phase 3 study of first-line durvalumab (MEDI4736) ± tremelimumab versus standard of care (SoC) chemotherapy (CT) in patients (pts) with unresectable Stage IV urothelial bladder cancer (UBC): DANUBE.
Authors: Thomas Powles, Matt D. Galsky, Daniel Castellano, Michiel Simon Van Der Heijden, Daniel Peter Petrylak, Jon Armstrong, Riccardo Belli, Salvatore Ferro, Yong Ben, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2016)

TPS4574 Background: Cisplatin-based CT is the standard first-line treatment for metastatic UBC and carboplatin-based regimens are utilized for cisplatin-ineligible pts. Despite a relatively high response rate, responses are generally short-lived and almost all pts experience disease progression highlighting a major unmet medical need in UBC. Immune checkpoint blockade has shown activity in pts with CT-resistant UBC, and evidence suggests targeting both programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) checkpoints provides for non-redundant pathway blockade and synergy. Durvalumab is a selective, high affinity, engineered human IgG1 mAb that blocks programmed cell death ligand-1 (PD-L1) binding to PD-1 and CD80. Tremelimumab is an anti-CTLA-4 mAb of the lgG2 kappa isotype. In a Phase 1/2 study (NCT01693562), single-agent durvalumab showed preliminary evidence of antitumor activity across several tumor types, including UBC. Encouraging clinical activity and manageable tolerability were reported in a Phase 1b study of durvalumab + tremelimumab in NSCLC (NCT02000947). Methods: DANUBE is a randomized, open-label, multicenter, global Phase 3 study (NCT02516241) of durvalumab ± tremelimumab versus SoC CT in treatment-naïve pts with unresectable and/or metastatic UBC. Pts will be randomized 1:1:1 to receive durvalumab 1500 mg i.v. every 4 wks (q4w) for up to 12 mos; durvalumab 1500 mg i.v. q4w + tremelimumab 75 mg i.v. q4w for 4 doses, followed by durvalumab 1500 mg i.v. q4w for up to 12 mos; or SoC (cisplatin + gemcitabine or carboplatin + gemcitabine) for up to 6 cycles. Pts will be stratified according to cisplatin eligibility, PD-L1 status (PD-L1+: ≥ 25% tumor membrane or tumor-associated immune cells stained), and visceral metastasis. The primary endpoint is PFS using investigator assessment (RECIST v1.1). Secondary endpoints include OS; proportion of pts alive and progression free at 12 mos, ORR, DOR, and DCR using investigator assessment; time to second progression; HRQOL; PK; immunogenicity; and safety and tolerability. Recruitment is ongoing. Clinical trial information: NCT02516241.
Abstract 1193: Treatment of breast cancer xenografts with paclitaxel enriches for cancer stem cells that can be targeted by a ROR1-specific antibody
Authors: Suping Zhang, Grace Liu, Sam H. Lai, Han Zhang, Emanuela M. Ghia, Bing Cui, Rongrong Wu, George Widhopf, Jian Yu, Richard Schwab, Karen Messer, Barbara Parker, Thomas J. Kipps
Journal: Cancer Research (2016)

Abstract Although initially responsive to hormone therapy and chemotherapy, many patients with metastatic breast cancer develop resistant and potentially fatal disease. One of the mechanisms of resistance is the emergence of post-treatment survival of a small number of breast cancer stem cells (CSC), which are relatively resistant to chemotherapy, have self-renewal capacity, and can repopulate the tumor and spread to distal sites. New therapies are required to eliminate breast CSC that could be used alone or in combination with standard therapy to mitigate the risk of developing relapsed disease. In this study, treatment of immune-deficient mice bearing breast-cancer patient-derived xenografts (PDX) with paclitaxel reduced tumor volumes, but enhanced the proportion of tumor cells that expressed ROR1, an RTK-like orphan receptor that is ordinarily expressed during embryogenesis. We found that breast cancer tumors with high levels of ROR1 expression were enriched for stem-cell gene-expression signatures. Moreover, cells isolated from breast cancer PDX that were positive for CSC markers such as aldehyde dehydrogenase 1 (ALDH1) were enriched for ROR1 expression, and ROR1+-cells isolated from breast cancer PDX had a greater capacity to form spheroids in vitro or re-engraft immune-deficient mice, than did ROR1-negative (ROR1Neg) cells isolated from the same tumor population. Treatment of breast cancer cells with a humanized anti-ROR1 mAb, UC-961, suppressed expression of the polycomb-ring-finger oncogene Bmi-1, and genes encoding proteins implicated in the epithelial-mesenchymal transition. UC-961 also impaired the capacity of breast-cancer cells to form spheroids or to re-engraft immune-deficient mice. Finally, combined therapy with UC-961 and paclitaxel appeared more effective in reducing re-engraftment potential than either agent alone (Table1). Collectively, this study implies that patients with advanced breast cancer may benefit from anti-CSC therapy, either alone or in combination with conventional anti-cancer drugs. Citation Format: Suping Zhang, Grace Liu, Sam H. Lai, Han Zhang, Emanuela M. Ghia, Bing Cui, Rongrong Wu, George Widhopf, Jian Yu, Richard Schwab, Karen Messer, Barbara Parker, Thomas J. Kipps. Treatment of breast cancer xenografts with paclitaxel enriches for cancer stem cells that can be targeted by a ROR1-specific antibody. [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 1193.
P89 Transarterial chemoembolization as neo-adjuvant therapy pre-transplantation in patients with hepatocellular carcinoma
Authors: E Tsochatzis, M Garcovich, L Marelli, G Fede, G Germani, J O'Beirne, A Burroughs
Journal: Gut (2010)

Introduction  Hepatocellular carcinoma (HCC) is the main indication for 15% of liver transplants. Currently the criteria used for listing patients are the Milan criteria. However, as waiting time is increasing, patients may fall out these criteria while on the waiting list.  Aim  We retrospectively evaluated the effect of neo-adjuvant transarterial chemoembolization (TACE) in consecutive patients transplanted for HCC.  Method  We analysed data from consecutive patients who were transplanted for HCC between 1990 and 2010 as main indication in our unit. Laboratory, epidemiological, radiological and histological data were analysed. Survival was evaluated using multiple regression analysis.  Results  In total 148 patients were transplanted for HCC, of which 74 had TACE as neo-adjuvant therapy. Mean follow-up post-transplant was 31±29 months (range 1–145). Patients had a mean of 1.6±0.9 (range 1–5) TACE sessions and had a mean waiting list time of 2.5±2.4 months (range 0.5–12.3). TACE response was evaluated in explanted livers as follow: no response in 10 (16%), partial tumour necrosis in 35 (55%) and complete tumour necrosis in 19 (30%). Tumour recurred in 21 (14%) patients in a mean time of 5.1±14 months. Recurrence happened in 2/10 patients who did not respond to TACE, 1/35 who had a partial response and 0/19 who had a complete response (p=0.040). TACE as neo-adjuvant therapy was associated with less recurrence irrespective of histological response (18.3% recurrence in patients who did not have TACE vs 5.6% in patients who had, p=0.037). No serious adverse effects of TACE were noted.  Conclusion  TACE is an effective neo-adjuvant therapy in patients listed for liver transplantation, as it is associated with significantly less post-transplantation tumour recurrences. As waiting lists are getting longer, its use as a standard neo-adjuvant therapy should be further explored.
A Retrospective Study of Elderly Patients with Diffuse Large B-Cell Lymphoma (DLBCL): Clinical Significance of Treatment Intensity and Comprehensive Geriatric Assessment (CGA)
Authors: Masahiro Yoshida, Mirei Horiuchi, Hideya Ueda, Kiyoyuki Hagihara, Hiroshi Kanashima, Takafumi Nakao, Takahisa Yamane
Journal: Blood (2014)
Temozolomide dose-dense regimen in high grade gliomas: dose-finding/phase II study
Authors: L. Napoleoni, G. Bruera, M.I. Adinolfi, A. Catalucci, P. Bonfili, M. Di Staso, A. Ricci, E. Di Cesare, R.J. Galzio, E. Ricevuto
Journal: Annals of Oncology (2015)
PSA surveillance in men with localized prostate cancer.
Authors: D. N. Yeboa, K. Liao, T. Guzzo, N. B. Haas, J. P. Christodouleas, N. Vapiwala, R. Sunderland, N. Mitra, K. Armstrong, J. E. Bekelman
Journal: Journal of Clinical Oncology (2010)

6024 Background: PSA surveillance is an important component of active surveillance for men with clinically localized prostate cancer who do not receive initial treatment. We describe use and determinants of PSA surveillance in a population-based cohort. Methods: Using data from the linked Surveillance, Epidemiology, and End Results (SEER) Medicare program, we evaluated 7,148 men age 65 to 84 years with AJCC stage T1 or T2 prostate cancer and Gleason ≤ 7 who did not receive treatment within 12 months of diagnosis. We included patients diagnosed from January 1, 1997 to December 31, 2002. For all patients, Medicare claims were observed until a secondary cancer treatment event (radiation, surgery, hormone therapy, chemotherapy), death, or December 31, 2006. The primary outcome was receipt of at least annual PSA tests, a minimum requirement of NCCN recommended active surveillance since 1997. We performed multivariable logistic regression to examine the relationship between receipt of annual PSA tests and patient, clinical and demographic characteristics. Results: Of men with Gleason ≤ 7 prostate cancer who did not receive initial treatment, only 36% undergo at least annual PSA tests. As shown in the Table, men 75 years or older and men with medical comorbidities had higher rates of annual PSAs. Men identified as African American and those residing in lower income areas had lower rates of annual PSAs. Conclusions: Annual PSA surveillance of men with localized prostate cancer who do not receive initial treatment is uncommon. Further research is necessary to clarify the benefits and harms of increased surveillance among older men and those with medical comorbidities. Multivariable analysis of annual PSA surveillance* Variable N = 7,148 Annual PSA (%) OR (95% CI) Age 65-74 3,430 30 1 (Ref) 75-84 3,718 41 1.28 (1.15, 1.42) Comorbidity 0 1,561 16 1 (Ref) 1 1,165 40 3.22 (2.68, 3.88) ≥2 4,422 42 3.46 (2.95, 4.04) Race White 5,879 37 1 (Ref) Black 844 22 0.53 (0.43, 0.65) Other 144 30 0.72 (0.48, 1.08) Unknown 281 52 1.60 (1.06, 2.40) Census tract median income 0-25K 1,240 26 1 (Ref) >25-40K 2,314 32 1.16 (0.98, 1.37) >40-60K 2,110 38 1.40 (1.16, 1.69) >60K 1,336 46 1.79 (1.44, 2.23) Unknown 148 45 2.32 (1.54, 3.48) * Adjusted for patient, clinical, and demographic characteristics. No significant financial relationships to disclose.
Evaluation by patients with heart failure of the effects of enalapril compared with hydralazine plus isosorbide dinitrate on quality of life: V-HeFT II
Authors: T. S. Rector, G. Johnson, W. B. Dunkman, G. Daniels, L. Farrell, A. Henrick, B. Smith, J. N. Cohn
Journal: Circulation (1993)

Background. Two new questionnaires concerning the quality of life of patients with heart failure were used in a randomized, controlled trial to determine if the patients' perceptions of the effects of enalapril on their daily activities and sense of well-being were different from those of a group treated with hydralazine and isosorbide dinitrate. Methods and Results. The questionnaires were completed at baseline and at 3 months, 6 months, and subsequently every 6 months during follow-up, which averaged 2.5 years (range, 0.5-5.7 years). Data from the questionnaires were reliable as indicated by correlation coefficients between repeated baseline scores of 0.88 and 0.87. Both treatment groups showed a progressive deterioration in quality of life as measured by both questionnaires
Abstract 2151: Development of reference reagents to accelerate research on the RAS pathway
Authors: Dominic Esposito
Journal: Cancer Research (2015)

Abstract The Ras Reference Reagents program within the NCI national Ras mission is designed to produce and distribute qualified DNA vectors, cell lines, and viruses to supply to the external community to facilitate research into Ras biology and development of Ras cancer therapeutics. Initial sets of reagents include sequence-verified libraries of Ras mutants and Ras pathway genes in Gateway combinatorial cloning vectors in multiple formats. An associated library of combinatorial components is also available to permit simple generation of expression vectors with various promoters, fusion tags, and plasmid backbones. Additional reagents under construction validated plasmid and lentiviral reagents for shRNA and CRISPR delivery, qualified cell lines, and systems for the generation of highly purified and characterized Ras and Ras-related proteins. All of these resources are readily available to the academic community through simple mechanisms, and can be licensed to industry as well. The Ras Reference Reagents program is also interested in identifying the needs of the community for additional Ras-related resources, and is developing methods for vetting requests from the outside to provide additional reagents. Citation Format: Dominic Esposito. Development of reference reagents to accelerate research on the RAS pathway. [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 2151. doi:10.1158/1538-7445.AM2015-2151
Abstract 1580: Cancer-associated fibroblasts potentiates tumor relapse after radiotherapy
Authors: Jun Mi, Yongbin Wang, Guifang Gan, Jiangmin Zhao
Journal: Cancer Research (2016)

Abstract Cancer-associated fibroblasts (CAFs) are a major component of cancer stromal cells, about 40∼50% of total cell population in cancer. Our data show that CAFs are distributed into larger area than tumor image revealed by MRI or CT since MRI- or CT- images only represent the core region containing cancer cells. Although the image-guided stereotactic body radiation therapy (SBRT) can precisely deliver radiation does to cancers and decreases radiation side effects, compared to the conventional external beam radiotherapy (EBRT), the data from our retrospective study showed that cancer recurrence including local and remote in patients with conventional EBRT was more frequent than patients with SBRT, and the survival time of patients with EBRT was also longer than patients with SBRT. We also demonstrated that CAFs could promote cancer cells recovery from radiation-induced damage through secreting cytokines/chemokines and exporting intermediate metabolites, which induce cancer cell dormancy and enhance DNA damage repair capacity. Citation Format: Jun Mi, Yongbin Wang, Guifang Gan, Jiangmin Zhao. Cancer-associated fibroblasts potentiates tumor relapse after radiotherapy. [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 1580.
Is the Chronic Myeloproliferative Disease Prognosis Really Different in Geriatric Patients?
Authors: Osman Ilhan, Pinar Ataca, Erden Atilla, Selami Kocak Toprak, Gulsah Kaygusuz, Isinsu Kuzu, Sinem Civriz Bozdag, Pervin Topcuoglu, Onder Arslan, Muhit Ozcan, Meral Beksac, Taner Demirer, Hamdi Akan, Nahide Konuk, Gunhan Gurman
Journal: Blood (2014)
Abstract 5134: Evaluation of immune tolerance mechanisms in pulmonary squamous cell and adenocarcinomas - how to interfere beyond PDL1 blockade
Authors: Helmut H. Popper, Luka Brcic, Gudrun Absenger, Barbara Prietl, Joerg Lindenmann, Marija Balic
Journal: Cancer Research (2016)

Abstract Introduction: Immunotherapy has emerged as a new tool to treat patients with NSCLC. Programmed death ligand 1 (PDL1) expressed on carcinoma cells serve as a marker predicting the response of anti-PDL antibody therapy. However, the results of clinical studies are conflicting as patients might profit from therapy despite not expressing PDL1 on their tumors, and also some tumors expressing PDL1 do not respond to therapy. It is evident that NSCLC cells use other mechanisms of immunotolerance. Methods: Surgically removed specimen of lung cancer are evaluated for infiltrating innate as well as specific immune cell in tumor centers and invasive front. In addition bronchoalveolar lavage is taken simultaneously and evaluated by flow cytometry for the same immune cells as the tissues. These cell types are evaluated: dendritic cells (classical, plasmocytoid, monocytoid), macrophages (M1 and M2), lymphocytes of Bcell lineage, lymphocytes of Tcell lineage, regulatory Tcells, natural killer cells. In addition tumor cells and lymphocytes are studied for their expression of PD1, PDL1, and PDL2, respectively Results and discussion: Within lung cancer several different mechanisms of inducing immune tolerance emerged: PD1-PDL1 interaction of tumor cells and CD8 lymphocytes, plasmocytoid as well as monocytoid dendritic cell induced downregulation of cytotoxic Tcell action, influx of myeloid derived cells inducing immune tolerance against tumor cells, M2 macrophage polarization with enhancement of stroma remodeling for tumor cell invasion and reduced Tcell reaction, increase of Treg cells inducing immune tolerance. Some of these mechanisms are seen in combination with PD1-PDL1 induced immune tolerance. This might explain, why some patients do not benefit from anti-PDL1 therapy. BAL emerged as a powerful tool in the evaluation of the immune reaction in NSCLC patients and might be a tool for evaluation of immune responses as well as a diagnostic tool to evaluate resistance mechanisms. Citation Format: Helmut H. Popper, Luka Brcic, Gudrun Absenger, Barbara Prietl, Joerg Lindenmann, Marija Balic. Evaluation of immune tolerance mechanisms in pulmonary squamous cell and adenocarcinomas - how to interfere beyond PDL1 blockade. [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 5134.
A Phase 2 Study of Ofatumumab in Combination with a Pan-AKT Inhibitor (Afuresertib) in Previously Treated Patients with Chronic Lymphocytic Leukemia (CLL)
Authors: Christine I Chen, Susi Snitzler, Olga Levina, Tong (Trina) Wang, Lisa W Le, Harminder Paul, Ellen Nong Wei, Anthea Lau, Michelle Queau, James B Johnston, Suzanne Trudel, Deborah A Smith
Journal: Blood (2015)