tbuckley/cabot-search huggingface dataset:
Indocyanine green fluorescence imaging system for sentinel lymph node biopsy in early breast cancer patients.
Authors: H. Abe, T. Umeda, T. Mori, M. Tanaka, Y. Kawai, H. Cho, Y. Kubota, Y. Kurumi, T. Tani
Journal: Journal of Clinical Oncology (2010)

649 Background: Sentinel lymph nodes (SLN) biopsy is a useful method to assess axillary lymph node status in early breast cancer. Indocyanine green (ICG) fluoresces by irradiating the excitation light when it unites with the serum protein. In the study, we present a novel method that allows the detection of SLN with high sensitivity using ICG fluorescence imaging. Methods: A 0.5% ICG solution combined with indigo carmine was intradermally injected for 0.3 mL in the areola closest to a tumor. Fluorescence imaging device (Photodynamic Eye: Hamamatsu Photonics Co.) was obtained using a charge coupled camera and light emitting diodes at 760 nm as the light source. Subcutaneous lymphatic channels draining from the areola to the axilla or other directions were visible by fluorescence imagings immediately. The SLN were then dissected by fluorescence navigation. Results: This study enrolled 175 patients with clinically node-negative breast cancer. Their average age was 52.8 years (ranged from 29 to 82 years). Sixty one patients were premenopausal, and 114 patients were postmenopausal. There were 112 cases with T1 lesions and 63 cases with T2 lesions. Subcutaneous lymphatic channels and SLN were successfully visualized in all patients. One lymphatic channel to the axilla was 55% (95/175), two channels were 29% (51/175), and three channels were 15% (27/175). The channels to other directions were not seen. The number of fluorescence SLN ranged from 1 to 6 (mean: 3.1), and blue dyed SLN ranged from 0 to 3 (mean: 1.2). In the latter, SLN were not identified in 64 patients (identification rate: 63.4%). Twenty three patients had lymph node metastases pathologically. All of them were recognized by fluorescence imagings, but, in 12 patients, lymph nodes with metastases were not identified by a vital dye. A significant correlation was seen between BMI and the time to arrival at the axilla. Conclusions: This ICG fluorescence imaging system presents a novel method for SLN mapping, which allows easy, highly sensitive and real-time imaging-guided SLN mapping in patients with early breast cancer. We hope that this method will provide with detection rate and negative predictive value in SLN navigation surgery. No significant financial relationships to disclose.
Degradation of Aiolos and Ikaros Followed By Downregulation of c-Myc and then IRF4 Leads to Programmed Cell Death in Myeloma Cells Sensitive to IMiDs® Immunomodulatory Compounds
Authors: Chad C Bjorklund, Courtney G. Havens, Patrick R Hagner, Anita K. Gandhi, Maria Wang, Michael D Amatangelo, Ling Lu, Huisheng Wang, Mike Breider, Yan Ren, Antonia Lopez-Girona, Anjan Thakurta, Anke Klippel, Rajesh Chopra
Journal: Blood (2014)
Assessment of Clinical Differences Between Starting Antimyeloma Treatment at Biological Relapse or at Clinical Relapse: Preliminary Results of an Observational Prospective Registry
Authors: Mercedes Gironella, Juan Bergua, Carlos Fernández de Larrea, Fernando Escalante, Maria González, Carmen Martínez Chamorro, Aurelio López, E Pérez-Persona, Juan José Lahuerta, Nieves Somilinos, Alfonso Soler, Yolanda Gonzalez, Alexia Suárez Cabrera, Abelardo Barez, Valentin Cabañas, Antonia Sampol, Ana Pilar Gonzalez, Giselle Lostaunau, David Vilanova, Adrian Alegre
Journal: Blood (2015)
Abstract LB-225: Combination immunotherapy targeting HSP90 DNA-repair client proteins overexpressed in chemotherapy-resistant melanoma
Authors: Subhara Raveendran, Ronald Fecek, Cara Donahue Carey, Walter J. Storkus
Journal: Cancer Research (2016)

Abstract DNA repair protein (DNA-RP) overexpression has been reported to involve post-translational protein stabilization mediated by the molecular chaperone heat shock protein 90(HSP90), thereby preventing proteasome-dependent degradation of these HSP90 “client” proteins. Overexpression of DNA-RP in a disease-stage associated manner has also been correlated to chemo resistance and poor overall prognosis. Hence, HSP90 inhibitors (HSP90i) have been heralded as co-therapy agents for cancer patients that have developed resistance to first-line treatments such as temozolomide (TMZ). In the presence of HSP90i, HSP90 client proteins rapidly become (poly)ubiquinated and undergo degradation resulting in the improved sensitization of cancer cells to chemo therapy. We observed that HSP90i promote the proteasome-dependent degradation of a broad range of DNA-repair client proteins. We have also identified 9 H-2Kb/Db-presented peptide epitopes derived from DNA-RPs that may be recognized by Type-1 CD8+ T cells after specific vaccination. When combined with adoptive cell therapy using DNA-RP-specific CD8+ T cells, HSP90i cotreatment yielded superior anti-tumor efficacy against established TMZ-resistant B16 tumors in C57BL/6 mice. Citation Format: Subhara Raveendran, Ronald Fecek, Cara Donahue Carey, Walter J. Storkus. Combination immunotherapy targeting HSP90 DNA-repair client proteins overexpressed in chemotherapy-resistant melanoma. [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 LB-225.
Glucose Control and Vascular Outcomes in Type 2 Diabetes: Is the Picture Clear?
Authors: Francesco Giorgino, Philip D. Home, Jaakko Tuomilehto
Journal: Diabetes Care (2016)

The overall impact of glucose lowering on vascular complications and major clinical outcomes, including mortality, in type 2 diabetes is still an open issue. While intensive glucose control has undoubted benefit for microvascular end points, the relationship between glucose-lowering approaches and reduced incidence and/or progression of macrovascular complications is less clear. This review article will discuss the effect of glucose lowering per se as well as the effects of specific glucose-lowering therapies on vascular outcomes in type 2 diabetes. The role of lifestyle changes on cardiovascular outcomes will be also addressed. Recent analyses from large cardiovascular outcome studies (ACCORD, ADVANCE, and VADT) provide new information on factors that modulate the impact of intensive glucose lowering on outcomes, helping to identify the specific clinical characteristics of the patients receiving the intervention that would show a better response. While several studies on cardiovascular outcomes with diabetes drugs are available, they do not clearly highlight a benefit from using a specific medication or will require additional evidence, as for the sodium-glucose cotransporter 2 blockers.
Knowledge needs of nurse practitioners new to oncology care.
Authors: M. Q. Rosenzweig, J. M. Giblin, M. Mickle, A. Morse, P. S. Sheehy, V. Sommer
Journal: Journal of Clinical Oncology (2010)

e16532 Background: There is growing evidence that the nation is facing a shortage of providers needed to provide high quality cancer care. Nurse practitioners are increasingly utilized as cancer care providers with no standardized oncology curriculum at practice entry. The purpose of this study was to: 1) Identify the knowledge needs of the Oncology Nurse Practitioner (ONP) on entry to to cancer care; 2) Identify the educational resources used to fill knowledge needs; 3) Describe the impact of ONP knowledge needs on patient care outcomes. Methods: Cross sectional, descriptive study of thirty item electronic survey to assess knowledge needs at entry into and through the first year of practice for ONPs. The questionnaire was randomly distributed (June 21, 2009 through July 27, 2009) via electronic survey to 610 self-described oncology nurse practitioners in the Oncology Nursing Society's data base. Results were tabulated and analyzed in SPSS, V. 14 according to descriptive and correlational statistics. Learning gaps at entry to oncology NP practice were identified and ranked one (not at all prepared) to four (very prepared). Results: One hundred and four (104/607, 17%) ONPs responded. Respondents came to cancer care practice with mean 12.7 years nursing experience. In first year of practice, 90% of ONP's rated themselves as “prepared” or “very prepared” in obtaining patient history, performing physical exam and documenting findings. ONP's rated themselves as “not at all or only “somewhat” prepared” in clinical issues of chemotherapy/biotherapy competency (n = 81, 77.9%); recognizing and managing oncologic emergencies, (n = 77, 70.2%); and recognition and management of drug toxicities, (n = 63, 60.6%). The Primary source of oncology education for ONP's new to practice was almost exclusively collaborating/supervising physician (n = 84, 80.8%). No poor patient outcomes were reported as a result of knowledge deficits. Conclusions: Although highly experienced nurses, ONPs are entering oncology practice adequately prepared as nurse practitioners, but without essential cancer care knowledge. These results hold implication for collaborating physicians, schools of nursing and for continuing education offerings. No significant financial relationships to disclose.
Sixty seconds on . . . Zika and the Olympics
Authors: Susan Mayor
Journal: BMJ (2016)

Can we run rings round Zika?Infectious disease specialists seem to think so.They estimate that, in a worst case scenario, three to 37 of the 500 000 people travelling to Rio for the 2016 Olympic Games (5-21 August) and Paralympic Games (7-18 September) will bring the Zika virus back to their home countries.
Abstract 3948: Lysosomal acid phosphatase 2 is an unfavorable prognostic factor associated with better survival in colorectal cancer patients receiving chemotherapy
Authors: Chi-Long Chen.
Journal: Cancer Research (2016)

Abstract Colorectal cancer (CRC) is one of leading malignancies worldwide. The therapeutic modality for advanced CRC including stage III and IV, is operation following by chemotherapy. For stage II CRC, surgery is the main therapeutic modality but the usage of adjuvant chemotherapy is still controversial and there is no reliable indicator for their purpose. In this study, we found that the expression of lysosomal acid phosphatase 2 (ACP2) in the tumor tissue of CRC was elevated and was correlated with poor outcome in stage II CRC patients, especially. In addition, in CRC patients with high ACP2 expression tended to have more sensitive for 5-FU treatment in our cohort. In CRC of stage II patients, multivariate Cox proportion hazard model analysis revealed that ACP2 expression and T stage are independent prognostic factor for overall survival (HR: 3.274, CI: 1.413-7.586, p = 0.006; HR: 3.742, CI: 1.058-13.233, p = 0.041). Our data indicated that high expression of ACP2 was a negative prognosticator and could predict 5-FU chemotherapy response in stage II CRC. Moreover, we used HCT116 cells transfected with ACP2 lentivirus to create stable shACP2-HCT116 clone. Our results showed knockdown ACP2 could induce chemoresistance and more mesenchymal-like phenotype of CRC cell line. Therefor, targeting ACP2 might be a novel chemotherapy factor and might a new strategy in stage II CRC patients. Citation Format: Chi-Long Chen. Lysosomal acid phosphatase 2 is an unfavorable prognostic factor associated with better survival in colorectal cancer patients receiving chemotherapy. [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 3948.
MONARCH 3: A randomized phase III study of anastrozole or letrozole plus abemaciclib, a CDK4/6 inhibitor, or placebo in first-line treatment of women with HR+, HER2-locoregionally recurrent or metastatic breast cancer (MBC).
Authors: Matthew P. Goetz, Masakazu Toi, Suzanne Klise, Martin Frenzel, Nawel Bourayou, Angelo Di Leo
Journal: Journal of Clinical Oncology (2015)

TPS624 Background: Abemaciclib (LY2835219), a cell cycle inhibitor of CDK4/CDK6, demonstrated a clinically manageable safety profile and single-agent anti-tumor activity in MBC; all tumor responses were observed in hormone receptor positive (HR+) disease (Tolaney SM, Rosen LS, Beeram M, et al. San Antonio Breast Cancer Symposium, 2014, Abstract P5-19-13). Non-steroidal aromatase inhibitors (NSAI, letrozole and anastrazole), approved in the first-line setting for postmenopausal women with HR+ MBC, are being evaluated in combination with abemaciclib for safety and tolerability in a phase Ib study (NCT02057133) and in the present study (NCT02246621) to assess clinical efficacy. Methods: MONARCH 3 is a randomized, double-blind, placebo-controlled, phase III study of abemaciclib + NSAI vs placebo + NSAI in locoregionally recurrent (not amenable to curative treatment) breast cancer or MBC, with no prior systemic therapy in this disease setting. Patients will be randomized 2:1, and stratified by nature of disease (visceral vs bone-only metastases vs other) and prior (neo)adjuvant endocrine therapy (aromatase inhibitor vs other vs none). Abemaciclib 150 mg or placebo will be given continuously PO every 12 hours until progression, along with anastrozole 1 mg or letrozole 2.5 mg once daily at the investigator’s discretion, and assessments will occur every 28 days. Postmenopausal women with HR+, HER2- disease, a disease-free interval &gt; 12 mos after completion of (neo)adjuvant endocrine therapy, ECOG PS ≤ 1, adequate organ function, and measurable disease or nonmeasurable bone-only disease (RECIST v1.1) are eligible. The primary endpoint is progression-free survival (PFS); a key secondary endpoint is overall survival (OS). The study has 80% power to detect an increase in PFS of approximately 40% (hazard ratio = 0.714). Assuming a median PFS of 10 mos in the control arm, this corresponds to a 4-mo increase in the median PFS. PFS and OS will be hierarchically tested to maintain an overall type I error rate of 2.5%. Enrollment began November 2014; planned enrollment is 450 patients. Clinical trial information: NCT02246621.
Phase II study of pazopanib plus interferon alfa as first-line therapy of advanced renal cell carcinoma: A Spanish Oncology Genitourinary Group (SOGUG) study.
Authors: Xavier Garcia del Muro, Miguel Angel Climent, Jose Luis Perez-Gracia, Begona Mellado, JA Virizuela, Daniel E. Castellano, Iciar Garcia Carbonero, Aranzazu Gonzalez del Alba, Carlos Alvarez Fernandez, Nuria Mulet, Ignacio Duran
Journal: Journal of Clinical Oncology (2016)

4571 Background: Combination of a VEGF receptor inhibitor with immunotherapy could be a strategy to enhance antitumor efficacy in advanced RCC. A phase I trial by our group showed that pazopanib plus interferon alfa (IFN) is feasible and safe (J Clin Oncol 32, 2014; suppl 4 abstr 450). The purpose of this study is to assess the activity and toxicity of this combination in patients (pts) with advanced renal cell carcinoma (RCC). Methods: Untreatedpts with clear cell RCC, ECOG PS 0-1 and adequate hematological, cardiac, renal and hepatic function, were included in this phase II study, receiving pazopanib at 800mg daily plus IFN 3 million U subcutaneously 3 times a week. Primary endpoint was response rate (RECIST v.1.1). A Simon’s two-stage sequential design was used (P0 = 20%, P1 = 40%, α = 0.05, β = 0.20), requiring at least 10 responses for the study to be considered positive. Results: Thirty three pts were enrolled at 10 centers. Median age was 59 (37-75). PS: 0-21,1-12 pts. 25 were males. Heng prognostic group: favorable-12, intermediate- 21 pts. 90% had undergone prior nephrectomy. The median number of cycles administered per patient was 7.4, although at the time of the analysis 18 pts remained on therapy. With a median follow-up of 9.3 months, 9 (27%) pts achieved partial response and 20 (61%) had stable disease. Median progression-free survival (PFS) was 14.8 months (95% CI, 4.35-25.2) and median overall survival was not reached. Most common grade 3-4 toxicities were hypertension (18%), asthenia (12%), mucositis (12%), hepatotoxicity (9%) and diarrhea (6%). Other toxicities of varying grades included fever, arthralgia, headache, hand-foot syndrome, emesis and dysgeusia. Conclusions: The combination ofpazopanib and IFN is safe and provides promising PFS. These results support the further exploration of alternative combinations of pazopanib with new immunotherapeutic agents, which are more active and better tolerated than IFN. Clinical trial information: NCT01513187.
ATNT-16PHASE 1 DOSE ESCALATION AND EXPANSION SAFETY STUDY OF BLZ-100 FOR FLUORESCENCE GUIDED RESECTION OF GLIOMA IN ADULTS
Authors: Chirag Patil, David Walker, Pramod Butte, Kate Nufer, David Kittle, Tarl Prow, Dennis Miller, Keith Black, Adam Mamelak
Journal: Neuro-Oncology (2015)

BLZ-100 is an intraoperative, fluorescent near-infrared imaging agent designed to specifically label tumor tissue and enable more complete surgical resection. The chlorotoxin (CTX) peptide portion of BLZ-100 targets the tumor, and the coupled fluorescent dye, indocyanine green, provides the fluorescent signal. CTX has been shown to target brain cancer in humans and BLZ-100 uptake has been shown in animal tumor models. This study characterizes the safety and fluorescence imaging potential of BLZ-100 in subjects with newly diagnosed or recurrent glioma. BLZ-100 is given as a slow bolus IV injection approximately 1 day before neurosurgery. Adequate bone marrow, liver and kidney function are required to participate. Dose escalation utilized a “3 + 3” design with 3 pre-specified dose levels. Dose limiting toxicity is defined as any related adverse event (AE) of ≥ Grade 3 severity occurring within 7 days of BLZ-100 administration. Safety measures include adverse events, laboratory measures of hematology, liver and kidney function, vital signs and electrocardiograms (ECG). Fluorescent images in situ are taken prior to and at the completion of tumor resection. Portions of excised tumor are also imaged ex vivo. Three subjects received 3 mg BLZ-100 in the first cohort; four subjects received 9 mg in the second. No dose limiting toxicity or BLZ-100 related adverse events have been observed. Two subjects had pathologically confirmed Grade II tumors, two had Grade III, and three had Grade IV. Two of the 7 cases were newly diagnosed. Fluorescent signal from portions of the resected tumor has been observed using ex vivo techniques and was concordant with pathology confirmed tumor. In situ imaging has been achieved in two cases with readily accessible tumors. These data suggest BLZ-100 is well tolerated and tumor-specific fluorescence can achieved in vivo. Dose escalation is continuing to 18 mg.
Abstract 3109: The TERT variant rs2736100_AC is associated with reduced risk of upper track urothelial carcinomas
Authors: Xiaotian Yuan, Ping Li, Magnus Björkholm, Dawei Xu
Journal: Cancer Research (2016)

Abstract Upper tract urothelial carcinomas (UTUCs) are originated from urothelium, and consist predominantly of renal pelvic carcinomas (RPCs) and ureter carcinomas (UTs). The UTUC incidence has increased over the past two decades, and most UTUCs have become invasive when diagnosed. Therefore, it is urgently needed to identify high-risk populations for the preventive intervention and monitoring. Recent genome-wide association study has provided strong evidence that common single nucleotide polymorphisms (SNPs) are associated with susceptibility of various malignancies. However, little is known about the susceptibility loci to UTUC. Here we genotyped the telomerase reverse transcriptase (TERT) SNPs rs2736100 and rs2736098, two SNPs associated with a risk of other malignancies, in Han Chinese patients with UTUC (n = 217) and evaluated the relationship between the rs2736100 polymorphism and UTUC risk by comparing with that in 289 healthy controls. Genotyping was performed using a TaqMan® SNP Genotyping Assays kit. Neither AA nor CC genotypes differed significantly between cases and control subjects, while the AC carriers were associated with the reduced risk of UTUC (OR = 0.6043; 95% CI: 0.4039 - 0.9042; P = 0.0185). When RPCs (n = 100) and UTs (n = 117) were analyzed separately, such protective effect remained significant in UTs (OR = 0.5728; 95% CI: 0.3540 - 0.9269; P = 0.031). The AC genotype was lower in RPC patients than in controls, but the difference was not statistically significant (OR = 0.6484; 95% CI: 0.3811 - 1.103; P = 0.142). In conclusion, we show for the first time that the rs2736100 AC genotype is protective against UTUC development. Citation Format: Xiaotian Yuan, Ping Li, Magnus Björkholm, Dawei Xu. The TERT variant rs2736100_AC is associated with reduced risk of upper track urothelial carcinomas. [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 3109.
Capecitabine (CAPE) +/- Bevacizumab (BEV) in the Adjuvant Treatment of Colorectal Cancer (CRC) - First and Final Toxicity Results from the International Phase III QUASAR2 Trial
Authors: R.S. Midgley, S. Love, V. Potter, E. Segelov, D.R. Ferry, A. Weaver, C. Scudder, P. Julier, S. Grumett, D.J. Kerr
Journal: Annals of Oncology (2012)
Terminal digit preference biases polyp size measurements at endoscopy, computed tomographic colonography, and histopathology
Authors: Andrew Plumb, Claire Nickerson, Katherine Wooldrage, Paul Bassett, Stuart Taylor, Douglas Altman, Wendy Atkin, Steve Halligan
Journal: Endoscopy (2016)

<b>Background and study aims:</b> Terminal digit preference bias for "pleasing" numbers has been described in many areas of medicine. The aim of this study was to determine whether endoscopists, radiologists, and pathologists exhibit such bias when measuring colorectal polyp diameters. <b>Methods:</b> Colorectal polyp diameters measured at endoscopy, computed tomographic colonography (CTC), and histopathology were collated from a colorectal cancer screening program and two parallel multicenter randomized trials. Smoothing models were fitted to the data to estimate the expected number of polyps at 1-mm increments, assuming no systematic measurement bias. The difference between the expected and observed numbers of polyps was calculated for each terminal digit using statistical modeling. The impact of measurement bias on per-patient detection rates of polyps ≥ 10 mm was estimated for each modality. <b>Results:</b> A total of 92 124 individual polyps were measured by endoscopy (91 670 screening and 454 from trials), 2385 polyps were measured by CTC (1664 screening, 721 trials), and 79 272 were measured by histopathology (78 783 screening, 489 trials). Clustering of polyp diameter measurements at 5-mm intervals was demonstrated for all modalities, both in the screening program and the trials. The statistical models estimated that per-patient detection rates of polyps ≥ 10 mm were over-inflated by 2.4 % for endoscopy, 3.1 % for CTC, and 3.3 % for histopathology in the screening program, with similar trends in the randomized trials. <b>Conclusion:</b> Endoscopists, radiologists, and pathologists all exhibit terminal digit preference when measuring colorectal polyps. This will bias trial data, referral rates for further testing, adenoma surveillance regimens, and comparisons between tests.
The Use Of Tevagrastim (Biosimilar Filgrastim XMO2) For Hematopoietic Stem Cell Mobilization In HLA Matched Sibling Donors For Allogeneic Stem Cell Transplantation To AML/MDS Patients
Authors: Ivetta Danylesko, Rina Sareli, Nira Bloom-Varda, Ronit Yerushalmi, Noga Shem-Tov, Yulia Volchek, Avichai Shimoni, Arnon Nagler
Journal: Blood (2013)