tbuckley/cabot-search huggingface dataset:
Abstract 3984: Novel t(X;21)(q26;q22) detected in a case of acute unclassifiable leukemia by application of anchored multiplex PCR-based next-generation sequencing
Authors: Laura Johnson, Helen Wang, Katelyn Trifilo, Brian Kudlow, Peter R. Pappenhausen, Mohammad Hussaini
Journal: Cancer Research (2016)

Abstract In this study, we demonstrate real-time clinical application of novel anchored multiplex PCR (AMP) technology in hematologic disease. A 78-year-old man with a history of hairy cell leukemia treated with Cladribine (2013) and bladder cancer (2014) developed dyspnea in August 2015. Work up revealed bicytopenia and leukocytosis. Outside bone marrow biopsy was read as B lymphoblastic leukemia/lymphoma. Rebiopsy was performed at our NCI-designated cancer center with extensive work up resulted in reclassification as acute unclassifiable leukemia (rare) with deferral to molecular diagnostics for guidance regarding classification. MLL, BCR-ABL, and MDS FISH panel were negative. Next generation sequencing (NGS) interrogating more than 400 genes showed FLT3-ITD, truncation of RUNX1 exon 6, ASXL1 p.G646Wfs*12, MLL p.V297L, and EZH2 p.V674M and p.C443Y mutations. The molecular profile favored therapy-related AML. Interestingly, cytogenetics revealed 46,Y,t(X;21)(q26;q22)[20]. FISH confirmed RUNX1 rearrangement but the partner was unknown. The t(X;21)(q26;q22) appears to be novel. However, the rare t(3;21)(q26.2;q22) has been cited to segregate with therapy-related MDS/AML. Subsequent aberrant activation of RUNX1 and MECOM is postulated to be pivotal in pathogenesis. Therefore, it is of great interest to determine the translocation partner associated with RUNX1 in our case. This type of analysis is not easily amenable to either Sanger or conventional NGS approaches. Fortuitously, with the recent advent of AMP technology (Archer FusionPlex) novel fusion detection has become possible. AMP was key in the characterization of this sample and promotes discovery of novel fusions by targeting one (known) of the two genes involved in a translocation event. Application of this cutting edge technology lead to the discovery of the novel fusion RUNX1-G6PD in this case. The identity of the novel fusion partners was supported by the breakpoints originally observed by the karyotype analysis. G6PD has been previously reported to be upregulated in acute leukemia. This discovery raises the possibility convergent pathogenic pathways and carries potential biological, diagnostic, and therapeutic implications. Citation Format: Laura Johnson, Helen Wang, Katelyn Trifilo, Brian Kudlow, Peter R. Pappenhausen, Mohammad Hussaini. Novel t(X;21)(q26;q22) detected in a case of acute unclassifiable leukemia by application of anchored multiplex PCR-based next-generation sequencing. [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 3984.
Abstract 1172: Expression of notch1, numb, and musashi1 in non-small cell lung cancer
Authors: Hajime Kikuchi, Jun Sakakibara-Konishi, Yasuyuki Ikezawa, Taichi Takashina, Hidenori Mizugaki, Eiki Kikuchi, Junko Kikuchi, Naofumi Shinagawa, Satoshi Oizumi, Yasuhiro Hida, Kichizo Kaga, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Masaharu Nishimura
Journal: Cancer Research (2016)

Abstract Background: Deregulation of Notch pathway is associated with carcinogenesis, and Notch signaling is identified as tumor activator in non-small cell lung cancer(NSCLC). The function of Musashi1 has been found to activate Notch signaling through the translational repression of Numb, which represses an intracellular Notch signaling. In NSCLC, the association between Numb or Musashi1 expression and clinicopathological factors or prognosis has remained unclear. In this study, we evaluated the expression of Notch1, Numb, and Musashi1 in NSCLC. Methods: A total of 135 surgically resected NSCLCs were immunohistochemically assessed for Notch1, Numb, and Musashi1 expression. Only cytoplasm and nuclear staining was considered in the evaluation of activated Notch1 expression. The immunoscores were determined, and then its correlation with either the clinicopathological variables or the survival outcomes was analyzed. Results: Immunohistochemical reactivity for Numb, and Musashi1 was detected in the cytoplasm and nuclear of the tumor cells. Notch1 expression was associated with several clinicopathological factors, including pathological histology (p = 0.002), and differentiation of tumor (p = 0.024). Numb expression was also associated with several clinicopathological factors, including sex (p = 0.037), smoking habit (p = 0.033), pathological histology (p = 0.002), and differentiation of tumor (p = 0.015). No correlations were noted between Musashi1 expression and any of the variables. Analysis of cellular biological expression demonstrated a link between low Numb expression and high Notch expression. Multivariate Cox regression analysis showed that positive Numb expression was an independent favorable prognostic factor. Conclusions: We demonstrate that Numb expression was associated with better prognosis in NSCLC. Numb might have the function as tumor suppressor in NSCLC. Citation Format: Hajime Kikuchi, Jun Sakakibara-Konishi, Yasuyuki Ikezawa, Taichi Takashina, Hidenori Mizugaki, Eiki Kikuchi, Junko Kikuchi, Naofumi Shinagawa, Satoshi Oizumi, Yasuhiro Hida, Kichizo Kaga, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Masaharu Nishimura. Expression of notch1, numb, and musashi1 in non-small cell lung cancer. [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 1172.
Abstract 357: Rapid harvesting of highly concentrated circulating tumor cells from bulk human blood with buoyant immuno-microbubbles
Authors: Guankui Wang, Sandeep Pingle, Santosh Kesari, Yu-Tsueng Liu, Dmitri Simberg
Journal: Cancer Research (2016)

Abstract Circulating tumor cells (CTCs) are the extremely rare cells shed from primary tumor during metastatic disease. A technology to quickly and inexpensively isolate viable CTCs will enable widespread clinical utilization of CTCs for cancer prognosis and drug testing. The lipid-shelled microbubble is a biocompatible material that has been used as ultrasound contrast media. We have previously shown that MB is a promising vehicle to isolate rare cells from biological fluids by flotation. Here we investigated the role of lipid composition, MB/cell ratio, and type of tumor surface marker [epithelial cell adhesion molecule (EpCAM), receptor tyrosine-protein kinase erbB-2 or human epidermal growth factor receptor 2 (HER2/neu) and epithelial growth factor receptor (EGFR)] on MB stability and binding efficiency to breast cancer cells. Optimized MBs coated with anti-EpCAM antibody showed 95% binding efficiency to human breast carcinoma SKBR-3 cells. Cells were able to proliferate in culture with MBs attached to them. We further developed an inverted setup in order to harvest (skim) highly concentrated tumor cells in a microliter volume on a nitrocellulose membrane. Using vacuum-assisted harvesting we demonstrated a high efficiency (∼80%) of isolation of rare tumor cells spiked in 7 ml blood by anti-EpCAM MBs. A blinded study using anti-EpCAM MBs detected epithelial CTCs in samples of metastatic breast and ovarian cancers with brain metastases, but not in samples from non-epithelial brain malignancies, including primary glioblastoma multiforme, hemangioblastoma and metastatic melanoma. The simple and robust MB approach can be developed into an inexpensive tool for batch CTC isolation in basic research and clinical applications. Citation Format: Guankui Wang, Sandeep Pingle, Santosh Kesari, Yu-Tsueng Liu, Dmitri Simberg. Rapid harvesting of highly concentrated circulating tumor cells from bulk human blood with buoyant immuno-microbubbles. [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 357.
Abstract 1802: ER-positive breast cancer prevention with the use of hormone replacement therapy
Authors: Anna G. Dembo, Geoffrey L. Greene
Journal: Cancer Research (2016)

Abstract Menopause occurs in women between the ages of 45 and 55 and often results in undesirable vasomotor symptoms. Hormone replacement therapy (HRT) alleviates these symptoms, including hot flashes, difficulty sleeping, fatigue, and vaginal atrophy. HRT also prevents osteoporosis. PremPro, a currently available HRT formulation that combines conjugated equine estrogens (CE) with medroxyprogesterone acetate, increases the risk of breast cancer. Due to the perceived risk based largely on the results of the Women's Health Initiative (WHI) trial, the number of women taking HRT has decreased dramatically. Duavee, a new form of HRT that combines CE and bazedoxifene (BZA), a selective estrogen receptor modulator (SERM) and degrader (SERD), has recently been approved by the FDA for treatment of moderate to severe hot flashes and to reduce the risk of osteoporosis. Importantly, this CE/BZA mixture not only relieves symptoms associated with menopause, but it also does not stimulate the breast or uterus. Although several preclinical studies suggest that CE/BZA might be protective in the breast, the mechanism of action of this new combination therapy is not known. Our goal, therefore, is to elucidate the underlying molecular mechanisms by which CE/BZA differentially affects estrogen receptor alpha (ERα) action in the mammary gland, using transcriptome and whole genome occupancy analysis in breast cancer cell lines. We are also studying the effects of CE/BZA on early mammary cancer progression in the polyoma middle T antigen (PyMT) transgenic mouse model, which has been shown to be sensitive to estrogens. In addition, we are studying the effects in an ERα-positive patient-derived xenograft mouse model. We have determined that CE modulates gene expression in MCF7 cells similar to 17β-estradiol (E2), and that BZA is able to inhibit these effects. We have also observed that CE increases ERα occupancy versus E2 at response elements associated with some estrogen target genes, whereas CE/BZA decreases this occupancy. In the PyMT mouse model, we have determined that CE/BZA significantly delays the onset of mammary tumors in ovariectomized mice and prolongs their survival when compared to E2 and CE treatment alone. An improved understanding of the molecular mechanisms of CE/BZA action in hormone sensitive breast cancer cell and animal models should have important implications for women considering HRT. Citation Format: Anna G. Dembo, Geoffrey L. Greene. ER-positive breast cancer prevention with the use of hormone replacement therapy. [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 1802.
Genomic Analisys of Notch Mutations in a Case of Alagille Syndrome with Acute Lymphoblastic Leukemia
Authors: Simona Bernardi, Paola Tononi, Sergio Marin Vargas, Giulio Bassi, Paul Takam Kamga, Omar Perbellini, Achille Ambrosetti, Vittorio Meneghini, Luigi Scaffidi, Giovanni Martinelli, Ilaria Iacobucci, Giovanni Pizzolo, Massimo Delledonne, Mauro Krampera
Journal: Blood (2014)
SARC 028: A phase II study of the anti-PD1 antibody pembrolizumab (P) in patients (Pts) with advanced sarcomas.
Authors: Melissa Amber Burgess, John Crowley, Denise K. Reinke, Richard F. Riedel, Suzanne George, Sujana Movva, Brian Andrew Van Tine, Lara Emily Davis, Scott Schuetze, James Hu, Steven Attia, Dennis A. Priebat, Damon R. Reed, Sandra P. D'Angelo, Scott H. Okuno, Robert G. Maki, Shreyaskumar Patel, Laurence H. Baker, Hussein Abdul-Hassan Tawbi
Journal: Journal of Clinical Oncology (2015)

TPS10578 Background: Immune checkpoint inhibition with antibodies (abs) to cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death 1 (PD-1), and programmed death ligand 1 (PD-L1) have made a significant therapeutic impact in metastatic melanoma. Abs targeting the PD-1/PD-L1 axis also exhibited clinical activity in solid tumors that are not considered "immunogenic", e.g., lung and bladder cancer. The significance of the PD-1/PD-L1 axis is currently being elucidated in sarcoma. Over 150 sarcomas of various histologic subtypes have been analyzed for PD-L1 tumor expression and the presence of PD-1+ tumor infiltrating lymphocytes (TIL): up to 65% of sarcomas expressed PD-L1 which, along with PD-1 TIL positivity, correlated with poorer overall survival and aggressive tumor features. We seek to determine the efficacy of PD-1 blockade with the anti-PD-1 ab pembrolizumab in pts with advanced soft tissue (STS) and bone sarcomas. Methods: This is an open label, multicenter, single stage, phase II study of P in pts with advanced STS (Arm A) or bone sarcomas (Arm B). P will be given intravenously at 200 mg every 3 weeks. The primary efficacy endpoint is objective response rate (ORR) by RECIST 1.1. 40 pts/arm will provide 82% power to detect an improvement in ORR from 10 to 25% with a one-sided type I error of 4.2%. This design will also have 87% power to detect an improvement in the 4-months progression-free survival rate from 20% to 40% with a one-sided type I error of 4%. Key eligibility criteria include ≥ 12 years of age, ECOG PS of 0 or 1, up to 3 prior therapies, and at least one tumor site accessible for biopsy. Exclusion criteria include low grade sarcoma, prior immunotherapies, and chronic use of corticosteroids or other immunosuppression. Secondary endpoints are safety, overall and progression free survival, and response rates by immune-related response criteria (ir-RC). Mandatory tumor biopsies pre and post-treatment will be obtained to determine PD-L1 expression as well as to perform immune monitoring in the tumor microenvironment. Peripheral blood will also be collected for immune monitoring in the circulation. Enrollment will occur at 10 SARC participating institutions and is expected to be completed in 2015. NCT02301039. Clinical trial information: NCT02301039.
The Emergence of the Randomized, Controlled Trial
Authors: Laura E. Bothwell, Scott H. Podolsky
Journal: New England Journal of Medicine (2016)

Dr. Scott Podolsky on the evolution of the essential methods of randomized, controlled trials. (08:07)Download Randomized, controlled trials date back much farther than is usually recognized, and their history offers insights into the intellectual and social forces shaping what would become a medical research standard and a mechanism for taming the therapeutic marketplace.
Abstract 3515: MiR-320b-regulated TRIAP1 prevents mitochondria fragmentation and apoptosis by controlling cytochrome c release in nasopharyngeal carcinoma
Authors: Ying-Qin Li, Na Liu, Jun Ma
Journal: Cancer Research (2016)

Abstract Mitochondria play critical roles in apoptosis. Imbalance of mitochondria fusion/fission leads to mitochondrial fragmentation and initiates intrinsic apoptosis, but the regulation of mitochondrial fragmentation in nasopharyngeal carcinoma (NPC) remains undefined. Here we show that TRIAP1 is aberrantly overexpressed and associated with poor survival in NPC patients. TRIAP1 overexpression promotes cell growth and suppresses NPC cell death in vitro and in vivo, whereas TRIAP1 knockdown inhibits cell tumorigenesis and enhances apoptosis through induction of mitochondrial fragmentation, membrane potential alteration and release of cytochrome c from mitochondria to cytosol. In intersection with our previous miRNA data and available bioinformatics algorithms, we identified miR-320b as a negative regulator of TRIAP1 expression. Further studies show that miR-320b suppresses NPC cell proliferation and enhances mitochondrial fragmentation and apoptosis by targeting TRIAP1. Moreover, loss of miRA-320b expression is conversely correlated with TRIAP1 overexpression and poor prognosis in NPC patients. This study reveals the regulation of miR-320b/TRIAP1 in mitochondrial fragmentation and apoptosis, and suggests potential therapeutic targets for NPC treatment. Citation Format: Ying-Qin Li, Na Liu, Jun Ma. MiR-320b-regulated TRIAP1 prevents mitochondria fragmentation and apoptosis by controlling cytochrome c release in nasopharyngeal carcinoma. [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 3515.
Single Nucleotide Polymorphism Array Analysis Of Bone Marrow Failure Patients Reveals Characteristic Patterns Of Genetic Changes
Authors: Daria V. Babushok, Hongbo M. Xie, Jacquelyn J. Roth, Nieves Perdigones, Timothy S. Olson, Joshua D. Cockroft, Xiaowu Gai, Juan C. Perin, Yimei Li, Michele E. Paessler, Hakon Hakonarson, Gregory M. Podsakoff, Philip J. Mason, Jaclyn A. Biegel, Monica Bessler
Journal: Blood (2013)
Phase I study evaluating high dose ADXS11-001 treatment in women with carcinoma of the cervix.
Authors: Sharad A. Ghamande, Robin Dobbins, Lisa Marshall, Donna Wheatley, Cheryl Prince, David J. Mauro, John Edward Janik, Samir Khleif
Journal: Journal of Clinical Oncology (2015)

TPS3096 Background: This is a phase I, dose-escalation, open-label, single-center study, in subjects with carcinoma of the cervix who have failed conventional therapy. ADXS11-001 is a live attenuated Listeria monocytogenes (Lm)-LLO immunotherapy bioengineered to secret an antigen-adjuvant fusion protein (fused to HPV16 E7). The primary objective of the study is to evaluate the tolerability and safety of ADXS11-001. Secondary objectives are tumor response, progression-free survival and correlative immunologic studies. Methods: Subject eligibility: Women ≥ 18 years of age with histologically-confirmed, measurable and/or evaluable (defined by RECIST 1.1) persistent, metastatic, or recurrent squamous or adenocarcinoma of the cervix with documented disease progression that is not amenable to surgery or standard radiotherapy. Subjects must have received ≤ 2 prior regimens for treatment of their metastatic disease. Planned sample size is approximately 6-12 subjects. Subjects will receive ADXS11-001 every 3 weeks during a 12- week treatment cycle. Doses will be escalated in the standard 3 + 3 fashion, in two doses, starting with 5 x 109 colony forming units (cfu) to a maximum dose level of 1 x 1010 cfu. If DLT is seen in one of 3 subjects, another 3 subjects will be treated at that same dose. If DLT is seen in 2 of 6 subjects, then that dose level will be considered maximum tolerated dose (MTD) and the previous dose level will be selected as the recommended phase II dose (RP2D). Blood samples will be evaluated for immunologic effects in cycle 1 only. Treatment cycles can be repeated at the RP2D (or less) for an individual subject until a discontinuation criterion is met, including documented disease progression, intolerable side effects. The end of study will be defined as 1 year after the last subject’s first treatment or until that subject has met a discontinuation criterion. Assessment of the RP2D level may be further explored in an expansion cohort of 15 subjects. Clinical trial information: NCT02164461.
The implementation of a rapid response team at Memorial Sloan-Kettering Cancer Center: A preliminary report
Authors: A. D. Klotz, E. Thattassery, D. Graham
Journal: Journal of Clinical Oncology (2007)

6627 Background: The implementation of a rapid response team (RRT) has become a popular patient safety initiative at many health care institutions during the past decade. To date, there are no studies evaluating the utilization or impact of a rapid response team in a population of cancer patients. We report on our experience implementing such a team at Memorial Sloan-Kettering Cancer Center. Methods: A consecutive cohort of all consults performed by the RRT between July 1st and December 31th, 2006 had the following variables recorded: primary cancer diagnosis, reason for consult, RRT intervention. Outcomes measured were survival to discharge and 30 day survival. Hospital mortality and hospital codes were compared to historical data from 2005 and were adjusted for hospital census. Results: There were 195 consults requested between July 1st and December 31st, 2006. The majority of these patients were on the medical service (124 vs 66 on surgical service). The most common primary malignancies for which the RRT was called arose from the gastrointestinal tract (30.2%), thoracic cavity (12.8%), urologic tract (9.3%), and breast (7.6%). Most consults were requested for compromised respiratory function (n=76), cardiovascular (n=72, 34 hypotension, 23 tachycardia), and neurologic derangements (n=13). 33 patients (16.9%) required transfer to an alternate level of care such as telemetry or the intensive care unit. 121 patients (65%) seen by the RRT survived to discharge however 92 (47%) died within 30 days of an RRT consult. Hospital codes decreased 21% (55 vs 70, p&lt;0.10) and hospital mortality decreased 22% (3.43 deaths per 1,000 discharges vs 4.43 deaths per 1,000 discharges) following implementation of the RRT although these results did not achieve statistical significance. Conclusions: The Rapid Response Team at MSKCC assists in the acute management of hospitalized cancer patients. Many of these patients are critically-ill and are near the end of their oncologic course. Further studies are necessary to better characterize the impact of this resource and determine how it can be utilized most effectively. No significant financial relationships to disclose.
Increased hepatic cholesterol synthesis in mdr2 P-glycoprotein deficient mice with impaired biliary cholesterol and phospholipid secretion
Authors: F Kuipers, H Wolters, R Havinga, Rj Vonk, Hmg Princen, Rpjo Elferink, Ak Groen
Journal: Circulation (1995)

Abstracts From the 68th Scientific Sessions, Anaheim Convention Center Anaheim, California November 13-16, 1995
High-throughput Phenotyping of Lung Cancer Somatic Mutations
Authors: Alice H. Berger, Angela N. Brooks, Xiaoyun Wu, Yashaswi Shrestha, Candace Chouinard, Federica Piccioni, Mukta Bagul, Atanas Kamburov, Marcin Imielinski, Larson Hogstrom, Cong Zhu, Xiaoping Yang, Sasha Pantel, Ryo Sakai, Jacqueline Watson, Nathan Kaplan, Joshua D. Campbell, Shantanu Singh, David E. Root, Rajiv Narayan, Ted Natoli, David L. Lahr, Itay Tirosh, Pablo Tamayo, Gad Getz, Bang Wong, John Doench, Aravind Subramanian, Todd R. Golub, Matthew Meyerson, Jesse S. Boehm
Journal: Cancer Cell (2016)
Birth Weight and Breast Cancer
Authors: Bianca L De Stavola, Isabel dos Santos Silva, Michael J Wadsworth
Journal: New England Journal of Medicine (2005)

Amory and Amory correctly note that grapefruit juice inhibits CYP3A4.Indeed, the same phenomenon may be seen with intact grapefruit segments. 4 This effect is confined to intestinal rather than hepatic CYP3A4, and significant increases in drug levels are most likely with CYP3A4 substrates that normally undergo a high degree of presystemic metabolism. 5With the exception of cisapride (which is no longer in widespread use), this is not the case for most of the CYP3A4 substrates implicated in the genesis of torsades de pointes.Nevertheless, a recognition of the potential effects of grapefruit on drug bioavailability is essential, given the multitude of drugs metabolized by CYP3A4.
Premature Infants Rehospitalized because of an Apparent Life-Threatening Event Had Distinctive Autonomic Developmental Trajectories
Authors: Gustavo Nino, R. B. Govindan, Tareq Al-Shargabi, Marina Metzler, An N. Massaro, Geovanny F. Perez, Robert McCarter, Carl E. Hunt, Adre J. du Plessis
Journal: American Journal of Respiratory and Critical Care Medicine (2016)