tbuckley/cabot-search huggingface dataset:
Treatment of newly diagnosed, inner-city multiple myeloma patients with low-dose thalidomide and dexamethasone and zoledronate
Authors: U. H. Klueppelberg, D. M. Kahn, M. Braunstein, E. L. Smith, I. Shapira, O. Batuman
Journal: Journal of Clinical Oncology (2006)

17555 Background: The incidence of multiple myeloma (MM) is high in African Americans (AA), who are underrepresented in clinical trials. This Phase II trial assessed thalidomide (100 mg/day), dexamethasone (10–40 mg for 4 days/week x3 for 6 months, then 4 days/month), and zoledronate (4 mg/4 weeks) (TDZ) in newly diagnosed AA patients with MM. TDZ was designed to be non-myelotoxic and compatible with HAART because of the high HIV infection rate in our patients. Because it mitigates tumor growth and angiogenesis and bone resorption, zoledronate was expected to boost the therapeutic effects of thal and dex. All newly diagnosed patients were eligible. Methods: Of 45 enrollees, 38 (22F/16M; median age = 61 years) were evaluable. All had bone disease, and baseline serum beta2-microglobulin (4.9 mg/dL) and albumin (3.3 mg/dL) indicated advanced disease. Eight patients (21%) were HIV+ (7F/1M; median age = 47 years). Patients with HIV were younger (P &lt; .001) and had higher β2-microglobulin levels (P = .003), and 6 were on HAART. Patients were treated for 24 months or until disease progression. Results: Mean duration of treatment was 18 months (range = 3–24). Age-adjusted one-year survival was 74.4%, identical to SEER data (73.7%). Near-CR was achieved in 30% (7 HIV-/4 HIV+) and partial remission in 68% (22 HIV-/3 HIV+) of patients. Median time to maximum response was 4.5 months in HIV- patients and 2.5 months in HIV+ patients (P &lt; .05). Overall cumulative survival at 24 months was 68% by Kaplan-Meier analysis, and was unaffected by HIV status, age, or sex. Creatinine clearance both for HIV+ and HIV- patients was normal, and was unaffected by TDZ. Despite daily ASA, thromboembolism occurred in 13% of patients. No other significant toxicity was observed. Ten patients died (9 HIV- and 1 HIV+); deaths were due to MM progression (n = 3), MM complications (n = 3), and causes unrelated to MM (n = 4). Conclusions: TDZ is safe and effective in the long-term management of MM, and is comparable to high-dose chemotherapy with stem cell rescue for both HIV- and HIV+ patients. TDZ is without renal or osteonecrotic side effects. The faster response to TDZ in HIV+ MM patients on HAART suggests a cooperative interaction between the two regimens. No significant financial relationships to disclose.
Proteomic signatures of acute myeloid leukemia (AML) distinguishes different outcome groups across cytogenetics and identified potential therapy targets
Authors: R. Tibes, Y. Qiu, K. Coombes, B. Hennessy, H. Kantarjian, F. Giles, E. Estey, G. Mills, S. Kornblau
Journal: Journal of Clinical Oncology (2006)

6523 Background: Cytogenetics (CG) guide AML treatment but reliable markers predicting response and relapse within CG groups are missing. We therefore determined whether functional proteomic signatures can classify AML into groups with different outcomes and risk of relapse. Method: Using Reverse Phase Protein Array, total and phospho-site specific expression of 37 proteins in 73 primary AML was measured. Outcomes in the set were comprised equally of primary refractory (PR), relapsed (Rel) and continuous complete remission (CCR) patients. Cell lysates were spotted on nitrocellulose coated slides, probed with validated antibodies, expression intensities were quantified, data was standardized and analyzed for correlations using different clustering approaches. Results: Unsupervised hierarchical clustering based on Pearsons’ correlation distance yielded 4 large clusters. Subsequent perturbation bootstrap re-sampling arranged samples into four classes that correlated with initial response to therapy and risk of relapse (see Table ). Protein profiles in each of he 4 classes differed. Cytogenetic marker distribution were similar across the 4 clusters. Class 1 and 4 demonstrated a similar predictive value of patient outcome as cytogenetics. In classes at highest risk of relapse (2, 3) different proteins were predictive of response. In class 2, the most discriminatory proteins predicting CCR were elevated AMPK, p27, 4-EBP1, BclXL. In class 3, relapsed patients had elevated PTEN, phospho-Stat3, total Stat3, and phospho-PKCα compared to CCR patients. Conclusion: Pretreatment protein expression signatures divide AML into classes that predict for initial achievement of CR and subsequent relapse independent of CG. Poteomic profiling may suggest potential therapy targets as opposed to CG or transcriptional profiling. These preliminary results need to be confirmed in formal training and test sets prior to changing patient management. [Table: see text] No significant financial relationships to disclose.
Accurate Classification of Diffuse Large B Cell Lymphoma Into Germinal Center and Activated B Cell Subtypes Using a Nuclease Protection Assay On Formalin Fixed Paraffin Embedded Tissue: A Study From the Lymphoma and Leukemia Molecular Profiling Project.
Authors: Lisa M. Rimsza, George Wright, Mark Schwartz, Wing C. Chan, Elaine S Jaffe, Randy D. Gascoyne, Elias Campo, Andreas Rosenwald, German Ott, James R. Cook, Raymond R. Tubbs, Rita M. Braziel, Jan Delabie, Thomas P. Miller, Richard I Fisher, Louis M. Staudt
Journal: Blood (2009)
Abstract A36: Resistance to IGF-1R targeted therapy by insulin-like growth factor 2-mediated tumor microenvironment network
Authors: Ji-Sun Lee, Ho-Young Lee
Journal: Cancer Research (2016)

Abstract Drug resistance is a major impediment in medical oncology. Recent studies have emphasized the importance of the tumor microenvironment (TME) to innate resistance to molecularly targeted therapies. In this study, we investigate the role of TME in resistance to cixutumumab, an anti-IGF-1R mAb that has shown limited clinical efficacy. We show that treatment with cixutumumab accelerates tumor infiltration of stromal cells and metastatic tumor growth and, ultimately, decreases overall survival of mice. Cixutumumab treatment stimulates recruitment of macrophages and fibroblasts via STAT3-dependent transcriptional up-regulation of IGF2 in cancer cells and paracrine IGF2/IGF-2R activation, resulting in the stroma-derived CXCL8 production and thus angiogenic and metastatic environment. Silencing IGF2 or STAT3 expression in cancer cells or IGF-2R or CXCL8 expression in stromal cells significantly inhibits the cancer-stroma communication and angiogenic activities of vascular endothelial cells. These findings suggest that blocking the STAT3/IGF-2/IGF-2R intercellular signaling network may overcome the adverse consequences of anti-IGF-1R mAb-based therapies. Citation Format: Ji-Sun Lee, Ho-Young Lee. Resistance to IGF-1R targeted therapy by insulin-like growth factor 2-mediated tumor microenvironment network. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A36.
Patient Choice and Lack of Medicare Coverage for HCT Are the Major Reasons Why Transplant Eligible Myelofibrosis Patients Do Not Undergo Transplant
Authors: Parth Desai, Julianne Chen, Diane Liu, Jimin Wu, Sairah Ahmed, Betul Oran, Stefan O. Ciurea, Amin M. Alousi, Srdan Verstovsek, Richard E. Champlin, Uday R. Popat
Journal: Blood (2015)
Genomic alterations in upper tract urothelial carcinoma (UTUC) versus urothelial carcinoma of the bladder (UBC).
Authors: Stephanie A. Mullane, Guillermo de Velasco, Toni K. Choueiri, Philip W. Kantoff, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2016)

431 Background: Defining the landscape of genomic alterations in UTUC as well as identifying the genomic differences from UBC, may provide insights into the treatment of UTUC. Methods: We interrogated our enterprise-wide institutional targeted next generation tumor sequencing data to compare genomic alterations in patients with UTUC (n = 25) with UBC (n = 72), irrespective of tumor stage. We described differences in frequencies of somatic mutations and copy number alterations in 300 relevant cancer-associated genes. Results: UTUC and UBC demonstrated differences in somatic alterations. Genes more commonly found in UTUC included FGFR3 (20% v. 7.5%), STAG2 (16% v. 7.5%), RB1 (24% v. 16%), TSC1 (16% v. 5.4%), EP300 (12% v. 5.4%), IGFIR (20% v. 0%), and Notch1 (24% v. 0%) (see table). Alterations in FGFR3 and TP53 co-existed in only on patient. We did identify two UTUC patients with MSH2 alterations, both of whom had previously been diagnosed with Lynch Syndrome. Conclusions: Biologically relevant differences exist between UTUC and UBC. We observed an enrichment of potentially targetable mutations including TSC1 and FGFR3. Findings in the genomic profile underline the need to consider these two locations as unique entities for future biologically driven trials. [Table: see text]
Collaboration, consensus and consideration
Authors: Eleanor J Tillett
Journal: British Journal of Sports Medicine (2016)

This year's British Association of Sport and Exercise Medicine (BASEM) issue for the British Journal of Sports Medicine ( BJSM ) illustrates what can be achieved when we combine the ‘best of the best’ experts and research. Collaboration is something we at BASEM are increasingly exploring with our fellow medical and paramedical organisations. This may take the form of combining for conferences, sharing teaching platforms or teaming up for initiatives. While we are generally ‘better together’, we are also mindful that the voices of individual groups are heard and that we remember the lessons from our recent past.

That international expert researchers spend their time reviewing and condensing the literature for us is something clinicians who access BJSM benefit from again and again. This process is very nicely illustrated by …
Frequency and Dynamics of Bcr1/Bcr3 Isoforms of PML/RARA Fusion Gene - Results of Russian APL Multicenter Trial.
Authors: Valeri Savchenko, Elena Parovitchnikova, Irina Demidova, Elena Shuravina, Valentin Isaev, Andrey Miyurin, Sergei Kulikov
Journal: Blood (2004)
TGF-β inhibitors stimulate red blood cell production by enhancing self-renewal of BFU-E erythroid progenitors
Authors: Xiaofei Gao, Hsiang-Ying Lee, Edroaldo Lummertz da Rocha, Cheng Zhang, Yi-Fen Lu, Dandan Li, Yuxiong Feng, Jideofor Ezike, Russell R. Elmes, M. Inmaculada Barrasa, Patrick Cahan, Hu Li, George Q. Daley, Harvey F. Lodish
Journal: Blood (2016)
Impact of biomarker dynamic profile and pathological response induced by neoadjuvant chemoradiotherapy in rectal cancer
Authors: A. L. Gentile, C. Pinto, C. Ceccarelli, F. Di Fabio, C. Funaioli, C. Longobardi, M. L. Tardio, D. Cuicchi, B. Iacopino, A. A. Martoni
Journal: Journal of Clinical Oncology (2006)

3614 Background: The aim of this study was to evaluate the correlation among biomarkers, pathological response and clinical outcomes in patients (pts) with rectal cancer submitted to neoadjuvant chemoradiotherapy. Methods: Pts entering the study had rectal adenocarcinoma, uT3/4N-/+ or uT2N-/+ with inferior location. Chemotherapy consisted of oxaliplatin 60 mg/m 2 weekly infusion IV for 6 times and 5-fluorouracil 225 mg/m 2 /die continuous infusion IV d 1–38. Radiotherapy was delivered up to a dose of 50.4 Gy in daily fractions of 1.8 Gy d 1–38. Rectal surgery with TME was performed 6–8 weeks after neoadjuvant treatment. Immunohistochemical determination of Ki67, p53, bcl2, TS, EGFR, MLH1 and MSH2 was performed in pretreatment biopsy and operative specimen. Results: Between March 2002 and May 2005, 32 pts had completed neoadjuvant therapy and surgery. Pt characteristics: 24 (75%) men and 8 (25%) women; median age 64 (33–80) years; stage uT2N-M0 3 (9.4%) pts, uT3N-M0 14 (43.8%), uT3N+M0 10 (31.2%), uT3NXM0 2 (6.2%), uT4N+M0 3 (9.4%). Surgery consisted of abdominal-perineal amputation in 12 (37.5%) and low-anterior resection in 17 (53.1%) pts, with negative circumferential resection margins in 86.2%. Laparoscopic local excision was performed in 3 (9.4%) pts. Pathological down-staging occurred in 18 (56.2%) pts, including 7 (21.9%) pT0N0, with sphincter preservation in 40%. Tumor Regression Grade (TRG) (according to Mandard) evaluation of operative specimen was: 7 TRG1, 11 TRG2, 11 TRG3 and 3 TRG4. Expression mean value in pretreatment biopsy and operative specimen was: Ki67 88.8% and 31.7%; p53 49.7% and 40.7%; TS 12.6% and 10.0%; MLH1 89.7% and 76.4%; MSH2 84.3% and 72.2%. The evaluation of biomarker profile in operative specimen of TRG2 pts vs TRG3–4 showed: Ki67 16.6% vs 46.2% (p=0.03); TS 4.5% vs 12.9% (ns); MSH2 82.3% vs 65.6% (ns); p53 52.3% vs 34.8% (ns). Median DFS was 19 (3–35) months. At a median follow-up of 22 (5–41) months, 100.0% of TRG1 pts, 90.9% of TRG2, 73.3% of TRG3–4 had no-evidence of disease relapse. Conclusions: These preliminary results suggest a correlation between Ki67 and pathological response in rectal cancer pts treated with neoadjuvant therapy. Moreover, DFS appears to be related to TRG. No significant financial relationships to disclose.
Outcome of Patients with Acute Myeloid Leukemia Treated with Salvage High-Dose Cytarabine Monotherapy
Authors: Jonathan Canaani, Marlise R. Luskin, Alison Loren, Colleen Timlin, James Mangan, Elizabeth O. Hexner, Noelle V. Frey, David L Porter, Edward A. Stadtmauer, Selina Luger
Journal: Blood (2015)
A Novel PF4-Dependent Platelet Activation Assay Identifies Patients Likely to Have Heparin-Induced Thrombocytopenia/Thrombosis (HIT)
Authors: Anand Padmanabhan, Curtis Jones, Brian R Curtis, Daniel W. Bougie, Mia Sullivan, Namrata Peswani, Janice McFarland, Daniel Eastwood, Demin Wang, Richard H. Aster
Journal: Blood (2015)
Arsenic Trioxide (ATO) and MEK1 Inhibitor Activate Apoptotic p73 Pathway in Primary Acute Myelogenous Leukemia Blasts.
Authors: Paolo Lunghi, Antonio Costanzo, Luigi Salvatore, Nelida Noguera, Antonio Tabilio, Francesco Lo Coco, Massimo Levrero, Antonio Bonati
Journal: Blood (2005)
Mortalin-2 (mthsp70/PBP74/Grp75), a Novel Mediator of Erythropoietin Signal.
Authors: Rie Ohtsuka, Yasunobu Abe, Tomomi Fujii, Eriko Nagasawa, Hirotoshi Shimada, Yoshimichi Tachikawa, Koichiro Muta
Journal: Blood (2005)
On Materials for Cardiac Tissue Engineering
Authors: Ibrahim J. Domian, Hanry Yu, Nikhil Mittal
Journal: Advanced Healthcare Materials (2016)

In this essay the authors argue that chamber pressure dominates the biomechanics of the contraction cycle of the heart, while tissue stiffness dominates the relaxation cycle. This appears to be an under-recognized challenge in cardiac tissue engineering. Optimal approaches will involve constructing chambers or modulating the stiffness of the scaffold/substrate in synchrony with the beating cycle.
Precision Medicine, Genomics, and Public Health
Authors: Donna K. Arnett, Steven A. Claas
Journal: Diabetes Care (2016)

Despite the advances in molecular genetics and… as genetic tests are proliferating in the U.S. population, their appropriate usage in the public health setting needs careful scrutiny.—Muin J. Khoury

The issues that Muin J. Khoury (1) identified as relevant in the intersection of genomics and public health—rapid advances in the molecular technologies available for interrogating the genome, the proliferation of genetic and genomic testing in the clinical setting, uncertainties surrounding the use and value of such tests—are far from surprising. These issues form the basis of much discussion in today’s scientific, professional, and popular literature. What is perhaps surprising about the statement, however, is that it was made nearly 20 years ago. As advances in molecular genetics have marched steadily forward and genetic epidemiologists have attempted to generate useful public health knowledge, paradigms have meanwhile shifted and developing disciplines (e.g., epigenetics, metabolomics) now contribute substantively to the conversation. The challenges faced by public health practitioners in this context have stemmed from the shifting landscape upon which the discipline is built. President Barack Obama's Precision Medicine Initiative (PMI), unveiled during his 2015 State of the Union Address, represents a concerted effort to lay the scientific foundation for the careful scrutiny Khoury called for.

How does this PMI impact the prevention and treatment of diabetes? As public health practitioners, we must face the current reality of the high and increasing global prevalence of diabetes. Between 1980 and 2008, the global age-standardized diabetes prevalence increased from 8.3 to 9.8% in men and from 7.5 to 9.2% in women (2). Precision medicine (PM) may offer new strategies to prevent and reduce diabetes in populations. PM seeks to integrate a bounty of data from each person's genome—combined with data from his or her environment and lifestyle (i.e., behaviors)—to tailor medical treatment to the individual …
What is the place of clinical variables in advanced non-small cell lung cancer (NSCLC) patients treated with chemotherapy?
Authors: M. Berhoune, E. Fabre-Guillevin, E. Banu, F. Scotte, B. Bonan, J. Medioni, O. Cojocarasu, K. Rideller, J. Ayllon, E. Levy
Journal: Journal of Clinical Oncology (2007)

18197 Background: Chemotherapy (CT) has shown its effectiveness in symptom control and quality of life improvement in advanced NSCLC patients. The therapeutic strategy and some clinical variables could have a major impact on outcome. Methods: Our retrospective analysis evaluated the impact on overall survival (OS) of the clinical benefit (CB), ECOG performance status (PS) and toxicity, function of treatment. CB was defined as disease-related symptoms improvement according to hospitalization report. Only grade III-IV CTC-NCI version 2 toxicities have been considered. OS was calculated between start of CT and death or last follow-up. Multivariate Cox regression analysis including CB, PS, toxicity and age, stratified by AJCC initial stage was used. Results: Data of 68 consecutive stage IIIB-IV patients treated in a single French centre were analyzed. Chemotherapy was platinum-salt based in 88, 45 and 25% of pts for the first, second and third-line, respectively. Median age was 61 years, 37% were women. More than half (66%) were metastatic and 14% were previously irradiated. Median survival was 14 months (95% CI, 6.1–21.8), 53 % of patients are dead. The risk of death PS-related was multiplied by 2.3, 2.4 and 5.3 for the first, second and third-line of CT, respectively. PS and CB were initially associated with OS (first and second-line CT), but after the third-line of CT only PS was significantly related with OS. The risk of death reduction induced by a CB was 59, 82 and 29%, respectively. Less toxicities during CT were associated with a better OS (an unsignificant 20- 30% risk of death reduction), independently of the chronology of CT. Older pts &gt;70 years have a higher risk of death (HR=1.87), independently of the CB and treatment-related toxicities in the multivariate analysis (P=0.18), sex-adjusted. Conclusions: No matter how many lines of CT are used for a specified patient, the ECOG PS was a patient-related variable with a dominant impact on the outcome. CT must be less toxic in order to achieve a CB and ameliorate the PS. No significant financial relationships to disclose.
Oral capecitabine in gemcitabine-pretreated patients with advanced pancreatic cancer: A single-center study
Authors: S. H. Boeck, R. Wilkowski, C. J. Bruns, R. D. Issels, C. Schulz, N. Moosmann, D. Laessig, A. Golf, V. Heinemann
Journal: Journal of Clinical Oncology (2007)

15085 Background: To date, no standard regimen for salvage chemotherapy after gemcitabine (Gem)-failure is defined in patients with advanced pancreatic cancer (PC). Methods: Within this study we prospectively collected clinical data of 37 patients (pts) with advanced PC who were treated with capecitabine (Cape) at our center. Cape was offered to patients who already had received at least one previous treatment regimen containing full-dose Gem (either as single- or combination chemotherapy or sequentially within a radio- chemotherapy (RCT) protocol), who presented with a KPS = 70% and had adequate organ function. Cape was administrated orally at a daily dose of 2 x 1250 mg/m 2 for 14 consecutive days followed by 7 days of rest (in pts &gt; 65 years: 2 x 1000 mg/m 2 /d). Treatment cycles were repeated every 3 weeks and continued until disease progression or unacceptable toxicity. Results: A median number of 3 treatment cycles (range 1–36) was given to 37 pts (54% male, median age 63 yrs, 97% with metastatic disease); 15 pts previously underwent RCT, 20 pts had received one previous treatment regimen and 17 pts 2 or more previous regimens. After a median follow- up of 6.1 months, 10 pts are still alive including 4 pts still on Cape. Currently, 35 pts are evaluable for response: no complete or partial response was observed, but 13 pts (37%) had stable disease (SD). A CA19–9 reduction &gt; 20% after 8 weeks of Cape was determined in 6 pts (16%), all of them had SD. Median TTP was 2.2 months, median overall survival (since start of Cape treatment) was 7.5 months. Predominant grade 2 and 3 toxicities (per patient analysis) were: hand-foot-syndrome 30%, anemia 24%, diarrhea 14%, nausea/vomiting and leukopenia 11% each. One pt had a grade 3 infection, 1 pt experienced grade 4 cerebral ischemia during treatment with Cape. Conclusion: Single-agent Cape is a safe treatment option for Gem-pretreated pts with advanced PC. The disease control rate of 37% and a median TTP of 2.2 months appear interesting in this patient population. Further evaluation of Cape in controlled clinical trails is recommended in Gem-refractory pts with advanced PC. No significant financial relationships to disclose.
Subcutaneous and Intravenous Bortezomib in Multiple Myeloma Patients Has Similar Response Rates and Toxicity Profile with No Difference in the Incidence of Peripheral Neuropathy: Report of the Czech Myeloma Group
Authors: Jiri Minarik, Petr Pavlicek, Ludek Pour, Tomas Pika, Vladimir Maisnar, Ivan Spicka, Jiri Jarkovsky, Marta Krejci, Jaroslav Bacovsky, Jakub Radocha, Jan Straub, Petr Kessler, Marek Wrobel, Lenka Walterova, Michal Sykora, Jarmila Obernauerova, Evzen Gregora, Dagmar Adamova, Jaromir Gumulec, Zdenek Adam, Vlastimil Scudla, Roman Hajek
Journal: Blood (2014)
Novel Focal Gene Deletions in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia Detected By Array Comparative Genomic Hybridization
Authors: Ingegerd Ivanov Öfverholm, Anh Nhi Tran, Vasilios Zachariadis, Mats Heyman, Eva Rudd, Elisabeth Syk Lundberg, Magnus Nordenskjöld, Ann Nordgren, Gisela Barbany
Journal: Blood (2014)
GW26-e0207 Monocyte activation in atherosclerosis
Authors: Alexander N. Orekhov, Nikita G. Nikiforov, Natalia V. Elizova, Anton V. Kuzmenko, Kirill N. Novikov, Sergey V. Kotelevtsev, Yuri V. Bobryshev, Igor A. Sobenin
Journal: Journal of the American College of Cardiology (2015)