tbuckley/cabot-search huggingface dataset:
Abstract 216: Pancreatic cancer fluorescence-­guided surgery with a fluorophore­-conjugated antibody to carcinoembryonic antigen (CEA) improves surgical resection and increases disease-free and overall survival in orthotopic mouse models
Authors: Cristina A. Metildi, Sharmeela Kaushal, George A. Luiken, Robert M. Hoffman, Michael Bouvet
Journal: Cancer Research (2015)

Abstract We established nude­ mouse models of human pancreatic cancer with surgical orthotopic implantation of the human BxPC­3 pancreatic cancer for fluorescence-guided surgery (FGS). After 2 weeks, mice then underwent bright-­light surgery (BLS) or FGS 24 hours after intravenous injection of anti CEA­-Alexa Fluor 488. Completeness of resection was assessed from postoperative imaging. Mice were followed postoperatively until premorbid to determine disease-free survival (DFS) and overall survival (OS). Complete resection was achieved in 92% of mice in the FGS group compared to 45.5% in the BLS group (p = 0.001). FGS resulted in a smaller postoperative tumor burden (p = 0.01). Cure rates with FGS compared to BLS improved from 4.5 to 40%, respectively (p = 0.01), and 1­year postoperative survival rates increased from 0% with BLS to 28% with FGS (p = 0.01). Median DFS increased from 5 weeks with BLS to 11 weeks with FGS (p = 0.0003). Median OS increased from 13.5 weeks with BLS to 22 weeks with FGS (p = 0.001). FGS resulted in greater cure rates and longer DFS and OS using a fluorophore-­conjugated anti ­CEA antibody. The present results demonstrate that FGS has potential to improve the surgical treatment of pancreatic cancer. Citation Format: Cristina A. Metildi, Sharmeela Kaushal, George A. Luiken, Robert M. Hoffman, Michael Bouvet. Pancreatic cancer fluorescence-­guided surgery with a fluorophore­-conjugated antibody to carcinoembryonic antigen (CEA) improves surgical resection and increases disease-free and overall survival in orthotopic mouse models. [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 216. doi:10.1158/1538-7445.AM2015-216
Clonal Evolution of BCR-ABL1 Kinase Domain Mutation In Tyrosine Kinase Inhibitor Treatment Patient
Authors: Hongxing Liu, Ping Zhu, Chunrong Tong, Yanli Zhao, Peng Cai, Juan Zhu, Fang Wang, Jiangying Gu, Jianjun Xie, Xian Zhang, Dao-Pei Lu
Journal: Blood (2010)
Implants for elderly patients
Authors: Martin Schimmel, Frauke Müller, Valérie Suter, Daniel Buser
Journal: Periodontology 2000 (2016)

Abstract In the developed world, the large birth cohorts of the so‐called baby boomer generation have arrived in medical and dental practices. Often, elderly patients are ‘young‐old’ baby boomers in whom partial edentulism is the predominant indication for implant therapy. However, the generation 85+ years of age represents a new challenge for the dental profession, as their lives are frequently dominated by dependency, multimorbidity and frailty. In geriatric implant dentistry, treatment planning is highly individualized, as interindividual differences become more pronounced with age. Nevertheless, there are four typical indications for implant therapy: (i) avoidance of removable partial prostheses; (ii) preservation of existing removable partial prostheses; (iii) stabilization of Kennedy Class I removable partial prostheses; and (iv) stabilization of complete prostheses. From a surgical point of view, two very important aspects must be considered when planning implant surgery in elderly patients: first, the consistent strive to minimize morbidity; and, second, the fact that coexisting medical risk factors are significantly more common in elderly patients. Modern three‐dimensional cone beam computed tomography imaging is often indicated in order to plan minimally invasive implant surgery. Computer‐assisted implant surgery might allow flapless implant surgery, which offers a low level of postoperative morbidity and a minimal risk of postsurgical bleeding. Short and reduced‐diameter implants are now utilized much more often than a decade ago. Two‐stage surgical procedures should be avoided in elderly patients. Implant restorations for elderly patients should be designed so that they can be modified to become low‐maintenance prostheses, or even be removed, as a strategy to facilitate oral hygiene and comfort in the final stage of life.
Leukemia-Induced Alterations in Bone Marrow Cytokine and Chemokine Levels Contribute to Altered Stem Cell Lodgment and Impairment of Normal Stem Cell Growth in CML
Authors: Bin Zhang, Yin Wei Ho, Tessa L. Holyoake, Claudia S Huettner, Ravi Bhatia
Journal: Blood (2011)
New microRNA-based diagnostic test for lung cancer classification.
Authors: Ranit Aharonov, Gila Lithwick Yanai, Hila Benjamin, Mats Olot Sanden, Marluce Bibbo, Craig Thurm, Laurie Horowitz, Yajue Huang, Meora Feinmesser, Iris Barshack, Steve j Hou, Tina B Edmonston, Karin Ashkenazi
Journal: Journal of Clinical Oncology (2012)

10528 Background: Lung cancer is the leading cause of cancer deaths in the US. Treatment options are determined by tumor subtyping, for which there is lack of standardized, objective, and highly accurate techniques. In 20%-30% of cases significant limitations of tumor quantity and quality prevent full classification of the tumor using traditional diagnostic methods. Using microRNA microarray data generated from over a hundred formalin-fixed, paraffin-embedded (FFPE) primary lung cancer samples, we have identified microRNA expression profiles that differ significantly for the main lung cancer types. Based on these findings, we have developed and validated a microRNA-based qRT-PCR assay that differentiates primary lung cancers into four types: squamous cell carcinoma, non-squamous non-small cell lung cancer, carcinoid and small cell carcinoma. Methods: Over 700 primary tumor samples from different histological types of lung cancer were collected. Samples included FFPE blocks from resection or biopsies and cell blocks from cytology specimens including fine needle aspiration, bronchial brushing and bronchial washing. High-quality RNA was extracted from the samples using proprietary protocols. Expression levels of potential microRNA biomarkers were profiled using microarrays followed by a sensitive and specific qRT-PCR platform. An assay for lung tumors classification using 8 microRNAs on qRT-PCR was developed based on data from 261 samples. This assay was validated on an independent blinded set of 451 cytological and pathological samples. Results: Using the expression levels of 8 microRNAs measured in qRT-PCR, accurate classification of the primary lung tumors into the four main cancer types is obtained. The microRNA-based assay reached an accuracy of 94%. Moreover, cytological samples composed over 50% of the validation set and reached an accuracy of 95%. Conclusions: We present here a new microRNA-based assay for the classification of the four main types of lung cancer based only on the expression of 8 microRNAs. This assay displays very high levels of accuracy for both pathological and cytological samples. The assay comprises a standardized, well-tested and objective tool which can assist physicians in the diagnosis of lung cancer.
Increased Risk for EBV-Lymphoma after Allogeneic Hsct in Adult Lymphoma Patients?A Retrospective Study of Reduced Compared to Myeloablative Conditioning.
Authors: Hans G. Hagglund, Mats Brune, Gunnar Oberg, Hans Hagberg, Niklas Theorin, Mats Remberger, Eva Kimby
Journal: Blood (2004)
Sequential Acquisition of Inhibitory NK Cell Receptors After Allogeneic Hematopoietic Stem Cell Transplantation: The Role of Steroids and Other Transplantation-Related Factors.
Authors: Sebastian Giebel, Joanna Dziaczkowska, Tomasz Czerw, Jerzy Wojnar, Malgorzata Krawczyk-Kulis, Izabela Nowak, Aleksandra Holowiecka, Antonio Segatti, Slawomira Kyrcz-Krzemien, Piotr Kusnierczyk, Jerzy Holowiecki
Journal: Blood (2009)
Abstract 4327: Nek6 and Hif-1α cooperate with the cytoskeletal gateway of drug resistance to drive outcome in serous ovarian cancer
Authors: Marta De Donato, Mara Fanelli, Marisa Mariani, Giuseppina Raspaglio, Deep Pandya, Shiquan He, Paul Fiedler, Marco Petrillo, Giovanni Scambia, Cristiano Ferlini
Journal: Cancer Research (2015)

Abstract Hypoxia selects the most aggressive and drug-resistant clones in solid malignancies. One of the pivotal transcription factors induced by hypoxia is Hif-1α. However, in serous ovarian cancer (SEOC), Hif-1α expression is not a prognostic biomarker. This study aims to assess the hypothesis that the serine-threonine kinase Nek6 functions as a downstream effector cooperating with Hif-1α in driving ovarian cancer aggressiveness. Nek6 was overexpressed and Hif-1α was silenced in A2780 cells. Nek6 was also stably silenced in Hey cells. The dependence of Nek6 expression on Hif-1α was assayed as a function of hypoxic growth conditions. Nek6 interaction with the cytoskeletal gateway of drug resistance was investigated with far western blot. The co-expression of NEK6, HIF1A, TUBB3 and GBP1 transcripts was quantified with qPCR in two cohorts of SEOC patients (346 locally treated patients and 344 from the TCGA dataset). Nek6 expression is induced by hypoxia in a Hif-1α dependent fashion. Nek6 directly interacts with GBP-1, thus being a component of the cytoskeletal gateway of drug resistance. Nek6 overexpression increases and silencing decreases the anchorage-independent growth of cultured cells. In SEOC patients, NEK6 expression is significantly correlated with HIF1A. Co-expression of NEK6, HIF1A, TUBB3 and GBP1 transcripts identifies a subset of SEOC patients characterized by poor outcome and drug resistance. This study demonstrates the functional relevance of Nek6 in the context of the adaptive response to hypoxia in SEOC. This finding may help identify a sub-population of patients at high risk of relapse to standard first-line chemotherapy. Citation Format: Marta De Donato, Mara Fanelli, Marisa Mariani, Giuseppina Raspaglio, Deep Pandya, Shiquan He, Paul Fiedler, Marco Petrillo, Giovanni Scambia, Cristiano Ferlini. Nek6 and Hif-1α cooperate with the cytoskeletal gateway of drug resistance to drive outcome in serous ovarian cancer. [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 4327. doi:10.1158/1538-7445.AM2015-4327
Enrollment insights in the synchronous mRCC population: An update from the ongoing ADAPT* phase 3 study experience.
Authors: Robert A. Figlin, Christopher G. Wood
Journal: Journal of Clinical Oncology (2014)

TPS4599^ Background: AGS-003 is an autologous immunotherapy designed to induce a T-cell response specific to a patient’s tumor antigens. Sunitinib is a TKI and first-line therapy for mRCC that also reverses the immune suppression observed in these patients. In a single arm phase 2 study, AGS-003 plus sunitinib was safe and yielded a median overall survival (OS) of over 30 months in newly diagnosed mRCC patients. Methods: The ADAPT study is a randomized (2:1) international phase 3 study comparing standard targeted therapy plus AGS-003 to standard therapy alone. The primary objective is to compare the median OS between treatment arms. The study is enrolling adults with synchronous, metastatic, clear cell RCC who are good candidates for surgery and standard targeted therapy (initiating with, but not limited to, sunitinib), KPS ≥ 70%, life expectancy of at least 6 months, between 1-4 Heng risk factors, and adequate end organ function. Initial enrollment patterns were investigated in order to gain insight on the features of mRCC patients that are candidates for cytoreductive nephrectomy. More than 105 sites in North America and other select countries have been activated and >200 patients have been consented and tumor samples collected. Approximately 50% of these patients have been excluded from participation in the treatment phase of the ADAPT study after surgery with about half of these being excluded because of non-clear cell histology. Other major reasons include ineligibility for sunitinib and lack of measurable metastatic disease after nephrectomy. Clinical trial information: NCT 1582672.
Abstract 1065: RASSF- 1A methylation in squamous cell carcinoma of the lower lip using pyrosequencing technique
Authors: Estela Kaminagakura, Cláudia Coutinho-Camillo, Luciana Strieder, Danyel Perez, Fernando Soares, Kátia Oliveira, Luiz Paulo Kowalski
Journal: Cancer Research (2015)

Abstract Background: Chronic exposure to UVB radiation can cause hypermethylation and silencing of the tumor suppressor gene RASSF-1A. The protein encoded by this gene has multiple important functions in cell cycle control. Objective: to investigate the clinical significance of the methylation profile of RASSF-1A and of its protein expression in lower lip squamous cell carcinoma (SCC). Methods: The demographic and clinical-pathological data of 87 patients with a confirmed diagnosis were collected from the medical records. DNA was extracted from paraffin-embedded tissue samples and treated with sodium bisulfite. 2ug of treated and intact DNA was submitted to PCR amplification using a specific primer targeting the RASSF-1A promoter segments 1 and 2. RASSF1A methylation was investigated by pyrosequencing; the complementary strand was synthesized automatically and the signal emitted during the reaction was detected with a camera and transformed into peaks on a pyrogram. Results: Lower lip SCC was more frequent in men than women, with a proportion of 2.4:1. The mean patient age was 63.3 years. Lymph node involvement was absent (N0) in 73 (83.1%) of cases and present (N+) in 14 (16.1%). In group N0, most patients (n = 49, 67.1%) were in an early clinical stage (CS I and II). Analysis of the methylation of RASSF1A_01 was possible in 29 of the SCC cases. Hypermethylation was observed in 15 (51.7%) cases, one (3.4%) of them being associated with metastasis to regional lymph nodes. Analysis of RASSF1A_02 was possible in 20 cases and hypermethylation was observed in only 9 (45.0%). No significant correlation was found between the clinical-pathological parameters (age, gender, clinical stage) and aberrant methylation of the promoter region studied (p&amp;gt;0.05). Conclusions: Hypermethylation of the two RASSF-1A segments studied was observed in approximately 50% of SCC cases, but was not correlated to clinicopathologic parameters. Citation Format: Estela Kaminagakura, Cláudia Coutinho-Camillo, Luciana Strieder, Danyel Perez, Fernando Soares, Kátia Oliveira, Luiz Paulo Kowalski. RASSF- 1A methylation in squamous cell carcinoma of the lower lip using pyrosequencing technique. [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 1065. doi:10.1158/1538-7445.AM2015-1065
Association of Langerhans Cell Histiocytosis with Erdheim-Chester Disease: How Close Monocyte/Macrophage and Dendritic Cell Lineages Are?
Authors: Baptiste Hervier, Julien Haroche, Olivier Hermine, Jean Donadieu, Frederic Charlotte, Nicole Brousse, Eric Hachulla, Zahir Amoura
Journal: Blood (2010)
Activation of the PI3K-Akt Pathway by Activated Protein C Occurs Via a Novel Receptor, Apolipoprotein E Receptor 2 (ApoER2)
Authors: Xia V. Yang, Yajnavalka Banerjee, Jose A. Fernandez, Hiroshi Deguchi, Xiao Xu, Laurent O. Mosnier, Rolf T Urbanus, Phillip G deGroot, Tara C White, Owen J.T. McCarty, John H. Griffin
Journal: Blood (2008)
Encouraging Activity of Obinutuzumab (GA101) Monotherapy in Relapsed/Refractory Aggressive Non-Hodgkin's Lymphoma: Results From a Phase II Study (BO20999),
Authors: Franck Morschhauser, Guillaume Cartron, Catherine Thieblemont, Philippe Solal-Celigny, Corinne Haioun, Reda Bouabdallah, Thierry Lamy, Noel Milpied, Steven Le Gouill, Pierre Feugier, Michael K. Wenger, Elisabeth Wassner-Fritsch, Elina Asikanius, Gilles Andre Salles
Journal: Blood (2011)
Hepatic artery infusion for recurrentor chemoresistant hepatic malignancy.
Authors: Harold J. Wanebo, Charu Taneja, Francis Cummings, Giovanni Begossi, James Belliveau
Journal: Journal of Clinical Oncology (2013)

295 Background: Previously treated Hepatic Colorectal Metastases (CRC) and advanced hepato cellular cancer (HCC) are tumor challenges frequently unresponsive to systemic chemo therapy (CT). We reviewed survival outcome in chemo resistant / high risk patients following hepatic artery infusion (HAI) in 21 CRC pts, 10 HCC pts, and 6 miscellaneous metastatic cancers. Methods: Patient groups: 21 CRC pts (16M, 5 F), mean age 63: 16 had metachronous (DFI-17 mos), and 5 Synchronous CA; liver extent: 76% multiple (&gt;5) mets or extensive bilateral; CEA (ng/m), &gt;100, 8 pts &gt; 50 (3 pts) ;&lt; 5 (3 pts),UNK(7 pts). Previous CT:FU/LV (11pts), Oxaliplatin (OX) or Irinotecan (IR) (10 pts). Liver surgery: Partial Resection/RFA – 9 pts. HCC – (9 PTS), cholangioCA(1pt); M/F 5/5; av.age 63yr.. Previous RX Hepatic lobectomy 4 pts, RFA/TACE – 3 patients. Miscellaneous GP (therapy): Hepatic lobectomy + HAI were in metastatic lung (1), Breast (1), advanced gall bladder Ca (GBCA) (T 3-4) (2 pts); HAI alone was done in Br. CA (1) carcinoid (1) Treatment Protocols: CRC: HAI-FUDR 12/15mg/kg/d, dexamethasone 2mg.kg/d, leukovorin (20mg/M 2 /d) X14 d plus bolus (d1), oxaliplatin OX 130 mg/M 2 cisplatin CIS, 100 mg/M 2 ; Systemic RX: d20-30. OX I.V. 130mg/M 2 , capecitabine 750-1,000 mg/M 2 /d x 10 days (also used in Miscel. Grp.) HCC Protocol: HAI-14 d as in CRC Protocol. Bolus infusion d1-doxorubicin 75mg/M 2 or OX or CIS as in CRC schema. Results: CRC:OS-CRC post start HAI = med/16 mos., 2yr/5yr = 27%/6%. HCC OS = 9 mos.( Median); 3-&gt;41mos in 9 evaluable pts.; 1 HCC pt with recurrence 2 yr. post hepatectomy survived over 3.5 yrs. with HAI + RFA/TACE – (OS-67mo).Miscellaneous group included lung (11 mos) Br CA (23, 9 mos) adv. Carcinoid (3 mos), GBCA (2 pts &gt; 60 mos), Major Complications; Pump malfunction (4 pts), misperfusion (2) pts, infected pocket (2) pt, duodenal fistula (1) pt. Conclusions: Hepatic artery infusion alternating with systemic chemo therapy has apparent survival benefit in selected patients with persistent or progressive chemo resistant malignancy from metastatic CRC, HCC, or selected miscellaneous cancers (breast, lung, liver, gall bladder cancer) and warrants further study.
Comparison of Immune Reconstitution after Umbilical Cord Blood (UCB) and Allogenic Peripheral Blood Stem Cell (APBSC) Transplantation in Patients with Advanced Multiple Myeloma (MM) and Acute Myeloid Leukemia (AML).
Authors: Jean-Come Meniane, Patrice Ceballos, Maud Condomines, Jean-françois Eliaou, Nathalie Fegueux, Bernard Klein, Jean-françois Rossi
Journal: Blood (2007)
Detection of locally advanced breast cancer in the I-SPY TRIAL (CALGB 150007/150012, ACRIN 6657) in the interval between routine screening
Authors: C. Lin, D. Moore, A. DeMichele, D. Ollila, L. Montgomery, M. Liu, H. Krontiras, R. Gomez, L. Esserman
Journal: Journal of Clinical Oncology (2009)

1503 Background: It is assumed that most locally advanced breast cancers (LABC) could be detected at an earlier stage with routine screening. However, LABCs may present between screens as interval cancers (IC). ICs present at an earlier age, with higher grade, larger size, and are associated with lower survival, compared to screen-detected cancers (SDC), and comprise 17% of cancers from population-based screening programs. We evaluated the screening history in patients with LABCs from the I SPY TRIAL, to determine the frequency of screening and ICs. Methods: Of 221 pts enrolled in the I-SPY TRIAL, a multisite neoadjuvant study for women with LABCs &gt; 3cm in size, screening history and presentation were retrospectively collected for 154. Two groups, screened (S), defined as a mammogram within 2 years, or non screened (NS), previous mammogram more than 2 years prior, were evaluated (Table). The frequency of ICs at 1 and 2 years was determined in S pts. Frequency of mammographically occult (MO) tumors was determined for all. Results: Of the total, 99 (64%) and 55 (36%) were NS and S, respectively. Mean tumor size for all pts was 6.7cm. Only 11 (20%) of S pts were SDCs and 44 (80%) were ICs, with 24 (63%) diagnosed within 1 year and 14 (37%) between 1 and 2 yrs of their last normal mammogram. 24 (24%) NS patients were younger than the recommended screening age of 40; in the remaining 75 pts, 9 (12%) were MO. Only 20% of IC tumors were MO. ICs were of higher grade (44% vs 11% grade III), and tumor size (7.0cm vs 4.4cm) than their SDC counterparts. 80% of cancers detected in I SPY were NKI70 gene test poor prognosis. Relationship to breast density and subtype is currently being assessed. Conclusions: Women presenting with LABCs have a high likelihood (80%) of an IC. This suggests that the growth rate of LABCs precludes early detection by conventional screening. Understanding the biology of ICs will be important to develop better strategies for prevention and early detection. [Table: see text] No significant financial relationships to disclose.
314. Mathematical Modeling of Erythrocyte Chimerism Informs Clinical Strategies for Sickle Cell Disease
Authors: Philipp M. Altrock, Christian Brendel, Raffaele Renella, Stuart H. Orkin, David A. Williams, Franziska Michor
Journal: Molecular Therapy (2016)

Recent advances in gene therapy and genome-engineering technologies offer the opportunity to correct sickle cell disease (SCD), which originates from a point mutation in the gamma-globin gene. The developmental switch from fetal gamma-globin to adult beta-globin is governed in part by the transcription factor (TF) BCL11A. This TF can be a therapeutic target for reactivation of corrected gamma-globin and concomitant reduction of sickling beta-globin. Genetic alteration of a portion of the hematopoietic stem cell (HSC) compartment would lead to a mixture of sickling and corrected peripheral red blood cell (RBC) populations. The degree of HSC alteration required to achieve a desired stable fraction of corrected RBCs with high gamma-gobin remained unclear. We developed a mathematical model that describes aging and survival of normal and sickling RBCs: a survival advantage of non-sickled RBCs over sickled RBCs leads to their overrepresentation in periphery. The math model considers HSC and age-structured RBC populations, and we aimed to validate it in an experimental mouse model by transplanting mixtures of Berkeley SCD mouse model and normal murine bone marrow cells to establish chimeric grafts in murine hosts. The math model identified the level of bone marrow chimerism required for successful stem cell-based gene therapies in SCD. We found an equation for the stable fraction of normal RBCs in periphery as a function of the fraction of genetically altered HSCs, predicting that gene therapy leading to 40% altered HSCs results in 55% non-sickling RBCs in periphery (Figure 1A, line). These findings were confirmed in the experimental mouse setting, where we achieved altered HSC mixtures between 0.5 and 38%, leading to RBC fractions between 7 and 62% (Figure 1A, data points). We found that a mathematical model incorporating a constant RBC selection approach was sufficient to predict pheripheral chimerism. This approach was then used to make SCD patient-predictions: 10% HSC alteration leads to 40% normal RBCs in periphery, 30% leads to over 70% normal RBCs (medians, assuming variable S cell life span, Figure 1B), which depend on the mean life spans of sickling (median 20 days) and normal (110 days) RBCs. Our integrative approach informs the target frequency of HSC genetic alterations likely required for effective treatment of sickling syndromes in humans.