tbuckley/cabot-search huggingface dataset:
CMET-36. DETECTION, MOLECULAR PROFILING AND CULTURE OF CSF-CTCS IN LEPTOMENINGEAL DISEASE (LMDz) IN MELANOMA
Authors: Brittany Evernden, Vincent Law, Rajappa Kenchappa, John Puskas, Elena Ryzhova, Inna Fedorenko, Nam D Tran, Arnold B Etame, Solmaz Sahebjam, Anthony Magliocco, Keiran Smalley, Peter Forsyth
Journal: Neuro-Oncology (2017)

~5% of melanoma-associated brain tumor cases also develop LMDz, which is universally fatal. The aim of this study was to determine whether diagnosis and personalized treatment for melanoma-LMDz could be improved using the Veridex CellSearch® System adapted to enumerate CTCs from CSF. Cell-free DNA (cfDNA) and cell-associated DNA (caDNA) were analyzed. Culturing conditions were optimized for CSF-CTCs expansion ex vivo. Peripheral blood (PB)/CSF-CTCs were detected by Veridex CellSearch® System and the circulating melanoma cell kit. Melanoma cell enrichment and detection was based on anti-CD146 and anti-high molecular weight melanoma associated antigen (HMW-MAA-PE (MEL-PE)). Anti-CD34-APC and anti-CD45-APC were used for ruling out endothelial cells and leukocytes respectively, and DAPI was used for nuclear staining. CfDNA and caDNA were extracted and sequenced with TruSight Tumor 26 panel, Illumina Inc and then profiled in Mela Carta MassArray System. PB-CTCs & CSF-CTCs: 12 patients with definite LMDz and 8 melanoma patients without LMDz were studied. Of the 12 LMDz patients, all but 1 patient (92%) had CSF-CTCs (range, 23 CTCs/ml CSF to 3055 CTCs/ml CSF). 3/12 patients (25%) had PB-CTCs (range, 0.4 CTCS/ml PB to 6.5 CTCs/ml PB). In contrast, only 3/8 (37%) melanoma patients without LMDz had CSF-CTCs detected, with significantly lower CTC counts per ml CSF (range, 0.13 CTCs/ml CSF to 0.6 CTCs/ml CSF). In their PB, 2/8 patients (25%) had PB-CTCs (range, 0.5 CTCs/ml PB to 1.6 CTCs/ml PB). CSF-CTCs Profile: LMDz patients showed GNAQ Q209P mutation (uveal melanoma), NRAS Q61R mutation (nasal melanoma) and also BRAF V600E mutation. Ex vivo culture of CSF-CTCs: We successfully demonstrated ex vivo expansion of isolated CSF-CTCs (possible for ~25% of samples) in the presence of FBS, FGF and EGF. CONCLUSIONS Taken together, the results indicate the potential value of CSF as a biopsy surrogate for assessing genetic makeup of CSF malignancies.
Programmed death ligand-1 (PD-L1) expression in penile squamous cell carcinoma.
Authors: Jennifer Wang, Jaime Rodriguez, Priya Rao, Curtis Alvin Pettaway, Lance C. Pagliaro
Journal: Journal of Clinical Oncology (2015)

393 Background: PD-1 protein is a co-inhibitory receptor expressed on B cells, T cell, and NK cells. Its ligand PD-L1 (B7-H1) leads to inhibition of T cell proliferation and cytokine production and is not expressed on normal tissues other than macrophages, but is expressed on various human carcinomas. Expression of PD-L1 in the HPV-associated disease penile carcinoma is unknown. Methods: Formalin-fixed paraffin-embedded tumor specimens were obtained from 19 patients. PD-L1 staining was done with an E1L3N rabbit monoclonal antibody with the summary of a positive score using H-score membrane staining, which considers both intensity and percentage of cells, with &gt;5% score as a positive. HPV status was also evaluated using FISH or p16 immunohistochemical staining to evaluate for correlation with PD-L1. Results: 23 samples between primaries and lymph nodes were collected from the 19 patients with 5/23 samples (22%) positive for anti-PDL1 staining. 6 samples (26%) were positive for HPV by at least one method of testing with 2/6 (33%) HPV positive patients having positive PD-L1 membrane staining. In both of these samples, there was equivocal peritumoral inflammatory infiltration of PD-L1 cells. Conclusions: This analysis shows that PD-L1 is expressed in penile squamous cell carcinomas and may indicate a role for future anti-PD-L1/PD-1 drugs as therapeutic options. Further analyses of correlated clinical features, survival, and separate PD-L1 staining in peritumoral inflammatory cells are underway.
CBIO-08. DETERMINING THE ROLE OF NICOTINAMIDE METABOLISM IN CHEMOSENSITIVITY IN GLIOBLASTOMA MULTIFORME
Authors: Richard Perryman, Kevin O’Neill, Hector Keun, Nelofer Syed
Journal: Neuro-Oncology (2016)

Glioblastoma multiforme (GBM) is an aggressive brain tumour with a median survival of only 18 months. Standard treatment consists of surgical resection followed by combined radiotherapy and chemotherapy in the form of the DNA alkylating agent temozolomide (TMZ). However, tumour recurrence is common with acquired resistance to both therapies. Novel drug combinations are desperately needed to improve outcomes for patients with GBM. Targeting nicotinamide metabolism in GBM may be one way to achieve this. Cancer cells need to maintain high levels of intracellular NAD to fuel metabolic reactions, maintain redox balance through glutathione synthesis, promote proliferation through regulation of sirtuin activity, and enable DNA repair through PARP activation. Since TMZ is a DNA damaging agent, inhibition of NAD synthesis could improve its efficacy. Moreover, the TCGA data suggests that elevated expression of enzymes involved in nicotinamide metabolism are predictive of survival in patients with GBM. We report that GBM cells are highly sensitive to the NAMPT inhibitor FK866. We observe that sensitivity to FK866 correlates with the expression of NAMPT, NT5E and NAPRT. Cells expressing NAPRT can utilise nicotinic acid to synthesise NAD, and cells expressing NT5E can convert extracellular NMN in to nicotinamide riboside to fuel NAD synthesis. We have shown that inhibition or knockdown of NT5E sensitises GBM cells to FK866 and TMZ. NT5E null cells exhibit decreased proliferation, increased activation of apoptosis and increased cell death in the presence of TMZ and FK866. These effects are enhanced when the two drugs are combined. Finally, we show that FK866 rapidly depletes NAD/NADH levels in GBM cells, and that knockdown of NT5E lowers NAD/NADH levels as well. The use of FK866 and TMZ in combination could be explored to combat GBM recurrence and improve patient survival, stratified on the basis of NT5E and NAPRT status.
Overall survival (OS) of EGFR mutation-positive non-small cell lung cancer (NSCLC): 1,660 Japanese patients (pts)
Authors: Hiroshige Yoshioka, Shunichi Sugawara, Kazushi Yoshida, Shuji Murakami, Young Hak Kim, Shinji Atagi, Fumio Imamura, Koji Takeda, Takashi Seto, Satoshi Morita, Yuichiro Ohe
Journal: Annals of Oncology (2016)
Number and Type of TET2 Mutations in Chronic Myelomonocytic Leukemia: Clinical and Prognostic Correlates
Authors: Mrinal M Patnaik, Mohammad Faizan Zahid, Terra L. Lasho, Ezequiel Tolosa, Christy Finke, Curtis A. Hanson, Rhett P. Ketterling, Eric Solary, Keith D Robertson, Naseema Gangat, Martin E. Fernandez-Zapico, Ayalew Tefferi
Journal: Blood (2016)
Decisions Taken in Children and Adolescents with Chronic Myeloid Leukemia (CML) at Failure of Imatinib Treatment
Authors: Meinolf Suttorp, Josephine Tabea Tauer, Manuela Krumbholz, Nils von Neuhoff, Brigitte Schlegelberger, Markus Metzler, Christian Thiede
Journal: Blood (2014)
Hand-foot syndrome (HFS) in patients receiving capecitabine: A pharmacological explanation
Authors: J. M. Ferrero, S. Lassalle, M. Mari, J. L. Formento, M. Francoual, J. P. Lacour, M. C. Etienne-Grimaldi, P. Hofman, G. Milano
Journal: Journal of Clinical Oncology (2006)

2019 Background: Use of the oral fluoropyrimidine capecitabine, which generates 5FU in tumor tissues, is currently expanding. HFS is frequently associated with administration of capecitabine. However, the underlying pharmacological mechanism of HFS is still not elucidated. In a previous experimental study, we ruled out a possible implication of 5FU catabolites (FUH2 and FBAL) in the etiology of HFS (Anti-Cancer Drugs 15: 969, 2004). The aim of this study was to investigate expression levels of thymidine phosphorylase (TP, the main activating enzyme of capecitabine) and dihydropyrimidine dehydrogenase (DPD, the rate-limiting enzyme of 5FU catabolism) in skin samples from the palm area of the hand (target zone) and from the back (control zone). Methods: Paired-skin biopsies have been planned in 12 healthy volunteers, in agreement with the local ethical committee. Expressions of TP, DPD, and Ki67 (cell proliferation marker) were analyzed by a two-step immunohistochemical method using specific monoclonal antibodies (from Calbiochem for TP, Roche for DPD and Dako for Ki67) and immunoperoxydase revelation (kit ABC Vectastain). Results: Data from the first four subjects indicate no significant difference in the strong Ki67 staining between control and target zones. TP was markedly expressed in the basal layer of the epidermis (BLE), with similar staining in control and target zones. Interestingly, in 3 cases out of 4, DPD was strongly expressed (2+, 3+) in the BLE of the control zone and much less (0, 1+) in the paired-target zone. Definitive data on 12 subjects will be presented. Conclusions: This preliminary original observation suggests that capecitabine may be locally activated in the skin due to high TP expression. The relative absence of DPD expression in the palm area may explain the specificity of HFS, which may result from a lack of local 5FU catabolism. These new data open the way to a possible pharmacological approach to limit HFS. No significant financial relationships to disclose.
Premature Aging of Hematopoietic Cells in Long Term Survivors after HSCT with Chronic GVHD and a Female Donor.
Authors: Gabriela M. Baerlocher, Alicia Rovo, Astrid Mueller, Sybille Matthey, Martin Stern, Joerg Halter, Jan Dirk, Caroline Arber, Alois Gratwohl, Andre Tichelli
Journal: Blood (2007)
The Role of Donor CMV Serostatus on Outcome after T-Cell Replete Haplo-SCT and Post-Transplant Cyclophosphamide: A Cohort Analysis on 207 Consecutive Adult Patients
Authors: Roberto Crocchiolo, Luca Castagna, Sabine Furst, Raynier Devillier, Barbara Sarina, Stefania Bramanti, Jean ElCheikh, Angela Granata, Samia Harbi, Lucio Morabito, Catherine Faucher, Andrea Rimondo, Bilal Mohty, Pierre Weiller, Carmelo Carlo-Stella, Christian Chabannon, Reda Bouabdallah, Armando Santoro, Norbert Vey, Didier Blaise
Journal: Blood (2015)
Mechanisms of 2-Methoxyestradiol-Induced Apoptosis on Myelodysplastic Syndrome MUTZ-1 Cell Lines.
Authors: Bao-An Chen, Guo-Hua Xia, Hui-Xia Lu, Ze-Ye Shao, Chong Gao, Hua-Jia Ding, Ping-Pei Xiao, Ning-Na Chen, Gang Zhao, Feng Gao, Jian Chen, Jun Wang
Journal: Blood (2007)
Long-Term Safety and Efficacy of Oral Eltrombopag for the Treatment of Subjects with Idiopathic Thrombocytopenic Purpura (ITP): Preliminary Data from the EXTEND Study.
Authors: James B. Bussel, Gregory Cheng, Lidia Kovaleva, Mansoor N. Saleh, Balkis Meddeb, Bhabita Mayer, J. Lee Fraser, Manuel Aivado
Journal: Blood (2007)
Prognostic Significance of Unbalanced Chromosome Abnormalities Used by 2008 World Health Organization (WHO) Classification to Define “Acute Myeloid Leukemia (AML) with Myelodysplasia-Related Changes” in Adults: a Cancer and Leukemia Group B (CALGB) Study.
Authors: Krzysztof Mrózek, Kelsi B. Holland, Mark J. Pettenati, Kati Maharry, Guido Marcucci, Maria R. Baer, Jonathan E. Kolitz, Dean Margeson, Colin G. Edwards, Andrew J. Carroll, Richard A. Larson, Clara D. Bloomfield
Journal: Blood (2009)
hsTRAIL/Apo2L Induces Apoptosis in Enteropathy-Associated T-Cell Lymphoma
Authors: Marijn Radersma, Laura R de Baaij, Nathalie J Hijmering, Gert Ossenkoppele, Chris JLM Meijer, Chris JJ Mulder, Saskia AGM Cillessen
Journal: Blood (2011)
KRAS mutations of colorectal cancer -clinical analysis as a prognostic factor and in vitro assay of proliferation-
Authors: Yuta Yamamoto, Masato Kitazawa, Makoto Koyama, Shinichiro Imai, Satoshi Sugiyama, Yusuke Miyagawa, Akira Suzuki, Shinichi Miyagawa
Journal: Annals of Oncology (2016)
E-SHAP for refractory and relapsing lymphoma: Influence of patient selection on response rate
Authors: J. Aparicio Urtasun, J. Gómez Codina, C. Molins Palau, M. Pastor Borgon¯ón, I. Maestu Maiques, B. Mun№arriz Gandia, J. Montalar Salcedo
Journal: Annals of Oncology (1993)
Bone Marrow Cellularity, but Not Dysplasia, Is An Additional Prognostic Factor for Patients with Acute Myeloid Leukemia After Allogeneic Stem Cell Transplantation
Authors: Maximilian Christopeit, Karolin Miersch, Evgeny Klyuchnikov, Mascha Binder, Francis Ayuk, Tatjana Zabelina, Philippe Schafhausen, Carsten Bokemeyer, Torsten Haferlach, Nicolaus Kroeger, Ulrike Bacher
Journal: Blood (2011)
The Amount of Spontaneous Apoptosis Is An Independent Strong Disease Progression Indicator in B-Cell Chronic Lymphocytic Leukemia (B-CLL)
Authors: Giovanni Del Poeta, Maria Ilaria Del Principe, Francesco Buccisano, Daniela Piccioni, Luca Maurillo, Chiara Sarlo, Maria Irno Consalvo, Pietro Bulian, Antonella Zucchetto, Laura Giannì, Cristina Simotti, Paolo de Fabritiis, Adriano Venditti, Valter Gattei, Sergio Amadori
Journal: Blood (2009)
Prognostic impact of the cumulative dose and dose intensity of everolimus in patients with pancreatic neuroendocrine tumors (PNETs)
Authors: R. Berardi, S. Pusceddu, F. Spada, T. Ibrahim, M.P. Brizzi, L. Antonuzzo, P. Ferolla, M. Rinzivillo, N. Silvestris, F. Freddari, E. Testa, A. Bongiovanni, C. Zichi, F. Di Costanzo, G. Delle Fave, N. Fazio, F. de Braud, M. Falconi, S. Cascinu
Journal: Annals of Oncology (2016)
Effect of 2 Years of Treatment With Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at 3 Years Among Patients With Moderate to Severe Seasonal Allergic Rhinitis
Authors: Guy W. Scadding, Moises A. Calderon, Mohamed H. Shamji, Aarif O. Eifan, Martin Penagos, Florentina Dumitru, Michelle L. Sever, Henry T. Bahnson, Kaitie Lawson, Kristina M. Harris, Audrey G. Plough, Joy Laurienzo Panza, Tielin Qin, Noha Lim, Nadia K. Tchao, Alkis Togias, Stephen R. Durham
Journal: JAMA (2017)

Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment.To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up.A randomized double-blind, placebo-controlled, 3-parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015.Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 µg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation).Total nasal symptom scores (TNSS; range; 0 [best] to 12 [worst]) were recorded between 0 and 10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy vs placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy.Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS score for the sublingual immunotherapy group was 6.36 (95% CI, 5.76 to 6.96) at pretreatment and 4.73 (95% CI, 3.97 to 5.48) at 3 years, and for the placebo group, the score was 6.06 (95% CI, 5.23 to 6.88) at pretreatment and 4.81 (95% CI, 3.97 to 5.65) at 3 years. The between-group difference (adjusted for baseline) was -0.18 (95% CI, -1.25 to 0.90; [P = .75]).Among patients with moderate to severe seasonal allergic rhinitis, 2 years of sublingual grass pollen immunotherapy was not significantly different from placebo in improving the nasal response to allergen challenge at 3-year follow-up.clinicaltrials.gov Identifier: NCT01335139; EudraCT Number: 2010-023536-16.
Gastrointestinal stromal tumors associated with other malignancies. Chance phenomenon or causal relationship? A series of 75 patients
Authors: E. Orlandi, P. mordenti, R. porzio, E. zaffignani, E.M. stroppa, P. capelli, R. delfanti, A. zangrandi, E. nobili, L. cavanna
Journal: Annals of Oncology (2016)
Potentially Avoidable Hospitalizations in Older Patients with Acute Myeloid Leukemia (AML)
Authors: Areej El-Jawahri, Tanya Keenan, Gregory Abel, David P. Steensma, Thomas W. LeBlanc, Lara Traeger, Amir T. Fathi, Daniel J. DeAngelo, Martha Wadleigh, Gabriela Hobbs, Philip C. Amrein, Richard M. Stone, Karen K. Ballen, Yi-Bin Chen, Jennifer S. Temel
Journal: Blood (2015)
Platinum-fluoropyrimidine (PF) and paclitaxel (PTX)-based chemotherapy (CT) in advanced anal cancer (AC)
Authors: F. Sclafani, F. Morano, C. Baratelli, E. Kalaitzaki, D. Watkins, N. Starling, I. Chau, D. Cunningham, S. Rao
Journal: Annals of Oncology (2016)
QLIF-21. QUALITY OF LIFE DOMAINS IN RELATION TO GLIOMA GRADE
Authors: Paige Bracci, Susan Chang, Jennifer Clarke, Elizabeth Claus, Daniel Lachance, Tracy Luks, Lucie McCoy, Annette Molinaro, Jennie Taylor, Joseph Wiemels, John Wiencke, Margaret Wrensch
Journal: Neuro-Oncology (2016)

Cancer-related quality of life (QOL) factors, some of which are unique to brain tumor patients with glioma, have not been well-studied by glioma grade. To examine potential differences in QOL factors among patients with primary glioma, the validated self-administered instrument, FactBr (Functional Assessment of Cancer Therapy for patients with Brain cancer) version 3, was used to collect QOL data from 754 participants with histologically confirmed WHO (World Health Organization) grade II (n=150), grade III (n=149) or grade IV (n=455) glioma in the San Francisco Bay Area Adult Glioma Study. Time since diagnosis and treatments received varied because patients were recruited as they came to the UCSF Neuro-oncology clinic. QOL domains were computed for physical [7 questions], social [7 questions], emotional [6 questions], functional [7 questions]) and brain/neurocognitive (19 questions) well-being. Analysis of variance methods adjusted for age-group at diagnosis and days from diagnosis to interview (quartiles) were employed to examine differences in well-being scores by grade. Physical, social, emotional and functional well-being, and composite scores for total well-being and general well-being (brain score excluded) did not differ by grade. Brain well-being differed by grade (p=0.02) with post-hoc multiple comparisons of marginal means showing that compared with grade IV patients, brain well-being scores were higher for patients with grade II but not with grade III glioma (Tukey-Kramer p=0.04, p=0.07 respectively). Previous reports also have reported cognitive QOL effects for glioma patients. Overall, results show that patient self-identified brain/neurocognitive well-being is the QOL domain most associated with glioma grade in recently diagnosed glioma patients. This heterogeneity in patient QOL factors by glioma grade might help to inform development of patient support programs. Further investigation of QOL measures over time, by extent of surgery, radiation, and chemotherapy treatments and other tumor characteristics such as tumor location is also needed.
Lurbinectedin (PM01183) exhibits antitumor activity in PARP-inhibitor resistant germline BRCA PDX and lacks cross-resistance with cisplatin
Authors: C. Cruz, G. Caratu, A. Llop-Guevara, M. Castroviejo, S. Gutierrez-Enriquez, B. Morancho, E. Álvarezdela Campa, L. Prudkin, P. Nuciforo, J. Arribas, A. Vivancos, Xdela Cruz, C. Galmarini, P.M. Avilés, C. Saura, O. Díez, V. Serra, J. Balmaña
Journal: Annals of Oncology (2016)
Medical Liability Reform in a New Political Environment
Authors: Anand Parekh, G. William Hoagland
Journal: JAMA (2017)

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Maintenance treatment with cetuximab in a series of patients treated with standard chemotherapy and cetuximab in metastatic colorectal cancer.
Authors: G. Quintero-Aldana, S. Varela, B. Campos, S. Vazquez-Estevez, O. Maseda, E. Santos, C. Iglesias, I. Torres, A. Lancho, J. Mel
Journal: Journal of Clinical Oncology (2011)

624 Background: New strategies are needed to improve outcomes and reduced toxicities of currently treatments for patients with advanced colorectal cancer. Nowadays maintaining treatment until disease progression is the standard option for these patients. Cetuximab is a recombinant humanized monoclonal antibody that neutralizes epidermal growth factor receptor and it has shown benefit not only in combination with standard chemotherapy in first- and second-line treatment or as a single agent in progression to standard chemotherapy in KRAS wild-type metastatic colorectal cancer (mCRC). Methods: This data describes patients who received standard chemotherapy with cetuximab every two weeks. For patients with response or stable disease, cetuximab was continued until disease progression or unacceptable toxicity. Results: Twelve patients are reported, nine were male (75%). The median age was 62 years (range, 46 to 78 years). All patients had stage IV, and liver was the most common location (75%). The majority of patients (75%) received FOLFOX VI as a first-line treatment in combination with cetuximab; only two patients were treated with FOLFIRI. Cetuximab was maintained after the first line of treatment in the 75% of patients. The median of cycles of chemotherapy and cetuximab was 12. Best response achieved in this setting was complete response (58.3%, 7/12). Median of monotherapy with cetuximab treatment was 7.5 cycles (range 3 to 12). At the moment of this analysis seven of twelve patients continued with the maintenance. In the rest of patients the treatment was followed until progression (33%, 3/12). No grade 3-4 toxicities were seen during maintenance cetuximab. The most common adverse effect during maintenance was cutaneous toxicity but the majority of patients had minor toxicity (50% grade 1). Conclusions: Cetuximab has significant antitumor activity not only as a single agent or in combination with standard chemotherapy but may also when it is used as maintenance therapy after a complete or partial response to first or second line based chemotherapy in mCRC. Maintenance cetuximab is feasible, safe, and worthy of future study in advanced colorectal cancer. No significant financial relationships to disclose.