tbuckley/cabot-search huggingface dataset:
Nuclear p16 and p53 expression correlates with cisplatin sensitivity in head and neck squamous cell carcinoma.
Authors: Bharathi Ramamurthy, Mysore S. Veena, Tirunelveli S. Ramalingam, Kei Hirakua, Noriyuki Kasahara, Marilene B. Wang, Eri S. Srivatsan
Journal: Cancer Research (2006)

5093  Head and neck cancer accounts for 4-6% of all human cancers. Squamous cell carcinoma of the head and neck (SCCHN) is a lethal cancer with one of the lowest five-year survival rates. Combination of the chemotherapeutic agent cisplatin and radiation therapy is commonly used as a treatment for this cancer. Analysis of four different SCCHN cell lines for cisplatin sensitivity showed CCL23, a laryngeal carcinoma cell line and CAL27, an oral cancer cell line to be sensitive. The other two oral cancer cell lines, SCC-1 and SCC14A, exhibited relative resistance to cisplatin treatment. While CCL23 showed nuclear expression of p16 and p53, CAL27 cells contained nuclear p53. Expression of p16 was absent in CAL27 cells. These two cell lines were also positive for the expression of CDK4. The resistant cell lines, SCC-1 and SCC14A, contained low level cytoplasmic expression of p16 and p53 and were negative for CDK4. Using gel shift assay and immunoprecipitation studies, we could observe inhibition of NFkB activation mediated by a direct binding of p16 to NFkB in CCL23 cells. There was also a correlation between the nuclear expression of p16 and reduced phosphorylation of the Rb tumor suppressor gene in this cell line. Further, nuclear transport of p53 resulted in an enhanced expression of p21 in CCL23 and CAL27 cell lines. These results suggest that the nuclear expression p16 and/or p53 play an important role in sensitizing the cells to chemotherapeutic agents such as cisplatin. We hypothesize therefore that this sensitivity is associated with the inhibition of CDK4 kinase activity and decreased NFkB transactivation mediated through p16 and p53 tumor suppressor genes.
Development and Characterization of Organic Electronic Scaffolds for Bone Tissue Engineering
Authors: Donata Iandolo, Akhilandeshwari Ravichandran, Xianjie Liu, Feng Wen, Jerry K. Y. Chan, Magnus Berggren, Swee‐Hin Teoh, Daniel T. Simon
Journal: Advanced Healthcare Materials (2016)

Bones have been shown to exhibit piezoelectric properties, generating electrical potential upon mechanical deformation and responding to electrical stimulation with the generation of mechanical stress. Thus, the effects of electrical stimulation on bone tissue engineering have been extensively studied. However, in bone regeneration applications, only few studies have focused on the use of electroactive 3D biodegradable scaffolds at the interphase with stem cells. Here a method is described to combine the bone regeneration capabilities of 3D‐printed macroporous medical grade polycaprolactone (PCL) scaffolds with the electrical and electrochemical capabilities of the conducting polymer poly(3,4‐ethylenedioxythiophene) (PEDOT). PCL scaffolds have been highly effective in vivo as bone regeneration grafts, and PEDOT is a leading material in the field of organic bioelectronics, due to its stability, conformability, and biocompatibility. A protocol is reported for scaffolds functionalization with PEDOT, using vapor‐phase polymerization, resulting in a conformal conducting layer. Scaffolds' porosity and mechanical stability, important for in vivo bone regeneration applications, are retained. Human fetal mesenchymal stem cells proliferation is assessed on the functionalized scaffolds, showing the cytocompatibility of the polymeric coating. Altogether, these results show the feasibility of the proposed approach to obtain electroactive scaffolds for electrical stimulation of stem cells for regenerative medicine.
Abstract 3935: CDKN2A/p16 is inactivated by the combination of inversion and translocation
Authors: Alexis L. Norris, Hirohiko Kamiyama, Ralph H. Hruban, James R. Eshleman
Journal: Cancer Research (2015)

Abstract Homozygous deletions (HDs) are a common mechanism by which tumor suppressor genes (TSG) are inactivated in cancer. Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A/p16) is the most commonly deleted TSG, with HDs in 40% of pancreatic ductal adenocarcinomas (PDAC) harboring p16 deletions. HDs create novel junctions, which can be exploited for sensitive early detection and minimal residual disease testing, using the PAtient-specific REarrangement (PARE) method. Here we characterize the underlying structural rearrangements that produce p16 HDs in a panel of PDAC cancer cell lines using pair-end whole genome sequencing (WGS) and high density SNP microarray analyses. Rearrangements were defined as simple interstitial deletions when the segment of a chromosome arm was deleted and the ends joined. The complex rearrangements causing the HD were categorized at both breakpoints as inversions and/or translocations. Sanger sequencing confirmed novel junctions, and breakpoints were assessed for non-templated base insertions and microhomology. We report that complex rearrangements underlie half of p16 HDs in PDAC (3 of 5). Most striking, the combination of an inversion and inter-chromosomal translocation (INV+TRANS) was exclusively responsible for these complex rearrangements. Inversions ranged in size from 47 to 3,373bp and translocations were non-recurrent and were often non-reciprocal (2 of 3). All HDs were resolved (either by interstitial deletion or INV+TRANS) without the addition of any non-templated bases inserted at the novel junction, arguing against the involvement of error-prone non-homologous end joining (NHEJ). Microhomology was seen at most rearrangement junctions (8 of 9), but with a median of only 2 bases. Further work is needed to elucidate the mechanism responsible for INV+TRANS rearrangements. Citation Format: Alexis L. Norris, Hirohiko Kamiyama, Ralph H. Hruban, James R. Eshleman. CDKN2A/p16 is inactivated by the combination of inversion and translocation. [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 3935. doi:10.1158/1538-7445.AM2015-3935
RISC-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells
Authors: Luca Pandolfini, Ettore Luzi, Dario Bressan, Nadia Ucciferri, Michele Bertacchi, Rossella Brandi, Silvia Rocchiccioli, Mara D’Onofrio, Federico Cremisi
Journal: Genome biology (2016)

Embryonic stem cells are intrinsically unstable and differentiate spontaneously if they are not shielded from external stimuli. Although the nature of such instability is still controversial, growing evidence suggests that protein translation control may play a crucial role. We performed an integrated analysis of RNA and proteins at the transition between naïve embryonic stem cells and cells primed to differentiate. During this transition, mRNAs coding for chromatin regulators are specifically released from translational inhibition mediated by RNA-induced silencing complex (RISC). This suggests that, prior to differentiation, the propensity of embryonic stem cells to change their epigenetic status is hampered by RNA interference. The expression of these chromatin regulators is reinstated following acute inactivation of RISC and it correlates with loss of stemness markers and activation of early cell differentiation markers in treated embryonic stem cells. We propose that RISC-mediated inhibition of specific sets of chromatin regulators is a primary mechanism for preserving embryonic stem cell pluripotency while inhibiting the onset of embryonic developmental programs.
Delays in diagnosis and initiating treatment for patients with lung cancer
Authors: R. L. Vandermeer, S. J. Dimitry, A. Arnold, P. M. Ellis
Journal: Journal of Clinical Oncology (2006)

6102 Background: Many patients with lung cancer report delays in the diagnosis of their disease. This situation may contribute to advanced stage at diagnosis and poor long term survival. This study explores the delays experienced by patients referred to a regional cancer centre with lung cancer. Methods: A prospective cohort of patients referred to a regional cancer centre with newly diagnosed lung cancer were surveyed over a 3 month period. Surgically resected patients were not included as they were treated at another site. Patients were asked when they first experienced symptoms, when they saw their doctor, what tests were done, when they saw a specialist and when they started treatment. A medical record review was employed to validate the data patients provided. Descriptive statistics were used to summarize the different time intervals. Results: 56 of 73 patients consented (RR 77%). However, only 52 patients (30M, 22F) were interviewed as two expired before being interviewed and two could not be contacted. The mean age was 68 yrs. Stage distribution was as follows: IB/IIA 10%, IIIA 20%, IIIB/IV 70%. The initial treatment was as follows: 10% of patients supportive care alone, 19% chemotherapy, 44% radiation and 27% had combined chemoradiation. Patients waited a median of 21 days (IQR 7–51d) before seeing a doctor and a further 22d (IQR 0–38d) to complete any investigations. The median time from presentation to specialist referral was 27d (IQR 12–49d) and a further 63d (IQR 44–102d) to complete investigations. The median wait time to start treatment once patients were seen at the cancer centre was 10d (IRQ 2–28d). The overall time from development of first symptoms to starting treatment was 139d (IQR 100–174d). Conclusions: Lung cancer patients experience substantial delays from development of symptoms to first initiating treatment. There is a need to develop and evaluate rapid assessment clinics for patients with suspected lung cancers. No significant financial relationships to disclose.
A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2− Metastatic Breast Cancer
Authors: Ingrid A. Mayer, Vandana G. Abramson, Luigi Formisano, Justin M. Balko, Mónica V. Estrada, Melinda E. Sanders, Dejan Juric, David Solit, Michael F. Berger, Helen H. Won, Yisheng Li, Lewis C. Cantley, Eric Winer, Carlos L. Arteaga
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Alpelisib, a selective oral inhibitor of the class I PI3K catalytic subunit p110α, has shown synergistic antitumor activity with endocrine therapy against ER+/PIK3CA-mutated breast cancer cells. This phase Ib study evaluated alpelisib plus letrozole's safety, tolerability, and preliminary activity in patients with metastatic ER+ breast cancer refractory to endocrine therapy. Experimental Design: Twenty-six patients received letrozole and alpelisib daily. Outcomes were assessed by standard solid-tumor phase I methods. Tumor blocks were collected for DNA extraction and next-generation sequencing. Results: Alpelisib's maximum-tolerated dose (MTD) in combination with letrozole was 300 mg/d. Common drug-related adverse events included hyperglycemia, nausea, fatigue, diarrhea, and rash with dose-limiting toxicity occurring at 350 mg/d of alpelisib. The clinical benefit rate (lack of progression ≥6 months) was 35% (44% in patients with PIK3CA-mutated and 20% in PIK3CA wild-type tumors; 95% CI, 17%–56%), including five objective responses. Of eight patients remaining on treatment ≥12 months, six had tumors with a PIK3CA mutation. Among evaluable tumors, those with FGFR1/2 amplification and KRAS and TP53 mutations did not derive clinical benefit. Overexpression of FGFR1 in ER+/PIK3CA mutant breast cancer cells attenuated the response to alpelisib in vitro. Conclusions: The combination of letrozole and alpelisib was safe, with reversible toxicities. Clinical activity was observed independently of PIK3CA mutation status, although clinical benefit was seen in a higher proportion of patients with PIK3CA-mutated tumors. Phase II and III trials of alpelisib and endocrine therapy in patients with ER+ breast cancer are ongoing. Clin Cancer Res; 23(1); 26–34. ©2016 AACR.
Uppsala Consensus Statement on Environmental Contaminants and the Global Obesity Epidemic
Authors: Lars Lind, P. Monica Lind, Margareta H. Lejonklou, Linda Dunder, Åke Bergman, Carlos Guerrero-Bosagna, Erik Lampa, Hong Kyu Lee, Juliette Legler, Angel Nadal, Youngmi Kim Pak, Richard P. Phipps, Laura N. Vandenberg, Daniel Zalko, Marlene Ågerstrand, Mattias Öberg, Bruce Blumberg, Jerrold J. Heindel, Linda S. Birnbaum
Journal: Environmental Health Perspectives (2016)

Summary: From the lectures presented at the 2nd International Workshop on Obesity and Environmental Contaminants, which was held in Uppsala, Sweden, on 8–9 October 2015, it became evident that the findings from numerous animal and epidemiological studies are consistent with the hypothesis that environmental contaminants could contribute to the global obesity epidemic. To increase awareness of this important issue among scientists, regulatory agencies, politicians, chemical industry management, and the general public, the authors summarize compelling scientific evidence that supports the hypothesis and discuss actions that could restrict the possible harmful effects of environmental contaminants on obesity.
Impact Of Rabbit Anti-Thymocyte Globulin-Containing Reduced-Intensity Conditioning Regimens On Outcomes Of Adults Undergoing Unrelated Cord Blood Transplantation For Hematological Malignancies
Authors: Laurent B Pascal, Luciana Tucunduva, Annalisa Ruggeri, Didier Blaise, Mohamad Mohty, Patrice Ceballos, Patrice Chevallier, Jan Cornelissen, Natacha Maillard, Reza Tabrizi, Eefke J Petersen, Werner Linkesch, Henrik Sengeolev, Chantal Kenzey, Eliane Gluckman, Vanderson Rocha, Ibrahim Yakoub-Agha
Journal: Blood (2013)
Sustainable improvement in quality indicators in Ontario's surgical oncology program (SOP)
Authors: H. Stern, M. Fung-Kee-Fung, D. Urbach, A. Smith, M. Brouwers, B. Langer
Journal: Journal of Clinical Oncology (2007)

6638 Traditional approaches to quality improvement (QI) have in general utilized performance data against benchmarks, and pay for performance to drive quality. In 2002 the SOP of Ontario, Canada, population 12 million, combined such a QI strategy with philosophical, cultural change aimed on the development of a workforce capable of setting and implementing improvements through communities of practice (CoPs) and application of evidence. The objective was to facilitate implementation of a rigorously developed set of performance indicators, guidelines and standards of care. The most tangible examples of early success include the reduction in operative mortality of pancreatic cancer and the improvement in harvesting lymph nodes in colorectal cancer. A series of indicators, guidelines and standards for colorectal, prostate, thoracic, and hepatobiliary cancers, were developed in partnership with the program in evidence-based care utilizing a rigorous and transparent methodological framework. A value-based purchasing contract (volume-based funding dependent on submission of wait time data). Health service delivery research to identify gaps and evaluate success. CoPs approach to engaging surgeons in solving quality gaps, including opinion leaders, workshops, multidisciplinary teamwork and website tools. Significant improvements have been seen in colorectal and pancreatic caancer indicators. In pancreatic cancer they include a reduction in 30 day operative mortality, in Ontario from a mean of 10.2% in 1988–1996 to 4.5% in 2002–2004, a reduction in numbers of surgeons and hospitals performing pancreatic surgery, and an increase in volumes performed in high volume institutions. In colorectal cancer the compliance with the NCI guideline of 12 lymph nodes harvested increased from 27% in 1997–2000 to 69% in 2005. Oncologists have been engaged in solving system gaps through participation in guideline and standard development and implementation using the CoPs approach. Our experience supports the hypothesis that guidelines, standards and performance indicators, value- based purchasing, and CoPs social influence elements are essential components that can change practice and improve quality in a large jurisdiction cancer system. No significant financial relationships to disclose.
Somatic ERCC2 mutations are associated with a distinct genomic signature in urothelial tumors
Authors: Jaegil Kim, Kent W Mouw, Paz Polak, Lior Z Braunstein, Atanas Kamburov, Grace Tiao, David J Kwiatkowski, Jonathan E Rosenberg, Eliezer M Van Allen, Alan D D'Andrea, Gad Getz
Journal: Nature Genetics (2016)
Safety and efficacy of the combination of pegylated interferon-α2b and dasatinib in newly diagnosed chronic-phase chronic myeloid leukemia patients
Authors: H Hjorth-Hansen, J Stentoft, J Richter, P Koskenvesa, M Höglund, A Dreimane, K Porkka, T Gedde-Dahl, B T Gjertsen, F X Gruber, L Stenke, K M Eriksson, B Markevärn, A Lübking, H Vestergaard, L Udby, O W Bjerrum, I Persson, S Mustjoki, U Olsson-Strömberg
Journal: Leukemia (2016)
Age-Dependent Pancreatic Gene Regulation Reveals Mechanisms Governing Human β Cell Function
Authors: H. Efsun Arda, Lingyu Li, Jennifer Tsai, Eduardo A. Torre, Yenny Rosli, Heshan Peiris, Robert C. Spitale, Chunhua Dai, Xueying Gu, Kun Qu, Pei Wang, Jing Wang, Markus Grompe, Raphael Scharfmann, Michael S. Snyder, Rita Bottino, Alvin C. Powers, Howard Y. Chang, Seung K. Kim
Journal: Cell Metabolism (2016)
Long‐term efficacy and safety results of taliglucerase alfa up to 36 months in adult treatment‐naïve patients with Gaucher disease
Authors: Ari Zimran, Gloria Durán, Atul Mehta, Pilar Giraldo, Hanna Rosenbaum, Fiorina Giona, Dominick J. Amato, Milan Petakov, Eduardo Terreros Muñoz, Sergio Eduardo Solorio‐Meza, Peter A. Cooper, Sheeba Varughese, Raul Chertkoff, Einat Brill‐Almon
Journal: American Journal of Hematology (2016)

Taliglucerase alfa is an intravenous enzyme replacement therapy approved for treatment of type 1 Gaucher disease (GD), and is the first available plant cell-expressed recombinant therapeutic protein. Herein, we report long-term safety and efficacy results of taliglucerase alfa in treatment-naïve adult patients with GD. Patients were randomized to receive taliglucerase alfa 30 or 60 U/kg every other week, and 23 patients completed 36 months of treatment. Taliglucerase alfa (30 U/kg; 60 U/kg, respectively) resulted in mean decreases in spleen volume (50.1%; 64.6%) and liver volume (25.6%; 24.4%) with mean increases in hemoglobin concentration (16.0%; 35.8%) and platelet count (45.7%; 114.0%), and mean decreases in chitotriosidase activity (71.5%; 82.2%). All treatment-related adverse events were mild to moderate in intensity and transient. The most common adverse events were nasopharyngitis, arthralgia, upper respiratory tract infection, headache, pain in extremity, and hypertension. These 36-month results of taliglucerase alfa in treatment-naïve adult patients with GD demonstrate continued improvement in disease parameters with no new safety concerns. These findings extend the taliglucerase alfa clinical safety and efficacy dataset. www.clinicaltrials.gov identifier NCT00705939. Am. J. Hematol. 91:656-660, 2016. © 2016 Wiley Periodicals, Inc.
Universal influenza vaccines: a realistic option?
Authors: R.D. de Vries, A.F. Altenburg, G.F. Rimmelzwaan
Journal: Clinical Microbiology and Infection (2016)

The extensive antigenic drift displayed by seasonal influenza viruses and the risk of pandemics caused by newly emerging antigenically distinct influenza A viruses of novel subtypes has raised considerable interest in the development of so-called universal influenza vaccines. We review options for the development of universal flu vaccines and discuss progress that has been made recently.
Epidemiological Aspects of Neoplastic Disorders in Israeli Migrant Population. V. The Lymphomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: B Modan, B Goldman, M Shani, D Meytes, B S Mitchell
Journal: JNCI Journal of the National Cancer Institute (1969)

Records of all patients diagnosed as having malignant lymphoma in Israel between 1960 and 1964 were reviewed. The mean annual incidence for all cases was 8.3 per 100,000: 9.5 per 100,000 in males and 7.2 per 100,000 in females. The incidence rates and age distribution of lymphosarcoma and reticulum cell sarcoma were similar, with an abrupt rise around the age of 50 and steady increase in older age groups, in contrast with Hodgkin's disease where a bimodal age distribution was present. Lymphoma incidence was higher among patients of North African origin in younger age groups and among European patients in older age groups, but no differences were observed in incidence between the newly arrived and more veteran immigrants. A significant June peak was found in the first diagnosis of lymphosarcoma and reticulum cell sarcoma among adult males, but not among females, nor in childhood. This finding remains largely unexplained.
Expression of protein kinase C beta (PKCß) as a prognostic marker in non-small cell lung cancer (NSCLC) and mesothelioma
Authors: L. Faoro, S. Loganathan, A. Husain, M. Westerhoff, V. Janamanchi, E. Vokes, R. Salgia
Journal: Journal of Clinical Oncology (2007)

7656 Background: The protein kinase C (PKC) family of serine-threonine protein kinases has been shown to be involved in tumor cell growth, survival, and progression. Tumor-induced angiogenesis requires activation of PKCs, particularly PKCβ, through vascular endothelial growth factor (VEGF) pathways. PKCβ-2 appears to be a major down-stream signaling protein for the VEGFR. This makes PKCβ an attractive target in treatment of malignancies, including lung cancer. Methods: 135 tumor samples (111 Non-small cell lung cancer tissues (52 adenocarcinomas (AC), 34 large cell (LC), 25 squamous cell carcinoma (SCC)) and 24 mesotheliomas (MT)) arranged in tumor microarrays (TMAs) were subject to immunohistochemical staining of PKCβ-1 and PKCβ-2. Results were analyzed manually and scored for intensity (1+, 2+, 3+). Clinical information was available for the AC, LC, and SCC group. Survival curves were generated and median survival between groups was compared utilizing the Log-rank methodology. Results: In NSCLC the expression of PKCβ1 was negative in 1% (1/107), 1+ in 14% (15/107), 2+ in 43% (46/107), 3+ in 42% (45/107); PKCβ2 immunostaining was negative in 28.4% (29/102), 1+ in 12.7% (13/102), 3+ in 23.6% (24/102) and 3+ in 35.3% (36/102). Median survival was superior for patients who expressed PKCβ1 (2+ or 3+) as compared to non-expressors (median survival 1258 days versus 124 days, p&lt;0.001). There was no difference in median survival in patients whose tumors expressed PKCβ2 and those that did not express it. In mesothelioma, staining for PKCβ1 was negative in 0, 1+ in 0, 2+ in 8.3% (2/24) and 3+ in 91.7% (22/24). For PKCβ2, tissues stained negative in 56.5% (13/23), 1+ in 21.8% (5/23), 2+ in 8.7% (2/23), 3+ in 13% (3/23). Median survival was superior for patients whose tumors did not express PKC-beta 2 (0 or 1+) as compared to expressors (median survival 604 days versus 103 days, p&lt;0.001). Conclusions: PKCβ is expressed in NSCLC and mesothelioma. PKCβ1 expression is a favorable prognostic factor in NSCLC, whereas expression of PKCβ2 is an adverse prognostic factor in mesothelioma. Therapeutic targeting of this molecule would be useful for the future. No significant financial relationships to disclose.
Stable Expression Of Chimeric Antigen Receptors (CARs) By Sleeping Beauty-Mediated Gene Transfer and Efficient Expansion Of Leukemia-Specific Cytokine-Induced Killer (CIK) Cells
Authors: Chiara Francesca Magnani, Nice Turazzi, Fabrizio Benedicenti, Greta Maria Paola Giordano Attianese, Sarah Tettamanti, Eugenio Montini, Laurence J N Cooper, Alessandro Aiuti, Andrea Biondi, Ettore Biagi
Journal: Blood (2013)
TCTAP A-094 The Sensitivity of Dobutamine Stress Echocardiography and Carotid Artery Ultrasound in Correlation with Coronary Angiography in the Distinction Between Ischemic and Non-Ischemic Dilated Cardiomyopathy
Authors: Mahmoud Mohamed Soliman, Mona Ibrahim Abu El Souod, Zainab Abd Elslam Fahmy, Haitham Galal Mohammed, Mohamed Gamal El Din Abdelmutaleb
Journal: Journal of the American College of Cardiology (2016)