tbuckley/cabot-search huggingface dataset:
A phase I/II study of imatinib and docetaxel as neoadjuvant therapy in locally advanced breast cancer
Authors: B. B. Haley, R. Ashfaq, M. DeHaas, A. Ramaswami, K. Sikder, D. Tripathy
Journal: Journal of Clinical Oncology (2007)

11039 Background: Imatinib mestylate(Gleevec,G) is a tyrosine kinase inhibitor of platelet derived growth factor receptor(PDGFR) and KIT(CD117). In breast cancer(BC),PDGFR signaling regulates tumor interstitial fluid pressure(IFP). PDGFR inhibition lowers IFP enhancing tumor drug delivery and chemo effect. KIT’s role in BC growth is unclear.PDGFR and KIT signal pathways regulate proliferation and cell cycle progression.Receptor blockade may enhance anti-tumor activity combined with chemo.This study evaluated tolerability,toxicity and efficacy of imatinib and docetaxel and treatment changes in biomarker expression and downstream mediators. Methods: Eligibility:Total 12 women, invasive LABC(T2–4,No-2,Mo)IHC + for KIT and/or PDGF, ECOG 0–2,bidimensional disease.Treatment:Assigned to 1of 3 G dose levels(400,600,800mg) taken daily 2 weeks then combined with D30mg/m 2 IV weekly x3 Q28 days. Three completed G(400mg D) and protocol modified to G600 and 800mg dose for 1 week then combined with D30mg/m 2 IV weekly x12. Tumor(T)measured pretreatment and at definitive surgery at conclusion of G+D.T biopsy done preG, postG and at end of G+D for tissue markers. Three treated G400, 5G600 and 4G800mg dose. Results: 12 patients median age 51 (range 39–62), ECOG PS O, 4 pre/8 post menopausal treated. Clinical pretreatment (C-PRx) tumor size (TS)median 6cm (range 3- 12cm).C-PRx node status 7cN 0 and 5cN 1 .PRx x-ray TS median 4.5 cm (range 2.5–8.5cm). Response:OR 25% 1 near CR+2 PR(3/12) at 400 and 600mg dose levels.Two SD(G800mg),3 progressed/off study,2 withdrew/toxicity(G3 rash/edema and G4 N/V), 2 NR.Surgery:5PM and 7MRM. Toxicity:Non- hematologic:nausea(1G4/G400mg),vomiting(1G4/G600mg),diarrhea(1G3/G800mg),fatigue(2G3/G800mg),myalgia(1G3/G800mg),rash(1G3/G600m g) and hypophosphatemia (2G3/G600mg). Hematologic toxicity mild neutropenia/anemia G1/2.One hospitalized for G3 odonophagia/stomatitis,G800mg.Dose Delay:2 missed 1 week of D+G (G600mg),2 missed 2 weeks of D+G (1G600mg and 1G800mg). Conclusion: Imatinib and docetaxel in neoadjuvant LABC is feasible and tolerable with low G3/4 toxicity and acceptable activity.G400mg dose best tolerated. Tissue IHC and molecular profiles to be reported separately.
Postchemotherapy AKR1B10 expression correlates with disease-free survival in muscle-invasive bladder cancer.
Authors: Yasuhiro Hashimoto, Takuya Koie, Hayato Yamamoto, Atsushi Imai, Shingo Hatakeyama, Takahiro Yoneyama, Noritaka Kamimura, Chikara Ohyama
Journal: Journal of Clinical Oncology (2012)

319 Background: AKR1B10 is a member of the aldo-keto reductase superfamily of NAD(P)H-dependent oxidoreductases.AKR1B10 is considered to contribute to cell proliferation and chemo-resistance. In the present study, we examined whether AKR1B10 expression correlates with disease free survival in bladder cancer specimens. Methods: The cohort includes consecutive 57 patients with muscle-invasive bladder cancer who received neoadjuvant chemotherapy followed by radical cystectomy. All patients received two cycles of neoadjuvant chemotherapy with gemcitabine plus carboplatin. Bladder cancer specimens were obtained at pre- and post-neoadjuvant chemotherapy, which were subjected to quantitative real-time PCR and immunohistochemistry to evaluate AKR1B10 expression. Intensity scoring for immunohistochemistry was categorized using a 4-graded scoring system according to a previously published method, with positive cells for each specific marker expressed as a percentage of the total number of cells as follows: 0%–10% = 0; 11%–30% = 1; 31%–70% = 2; 71%–100% = 3. Results: AKR1B10 mRNA expression was significantly higher in the post-chemotherapy groups than in the pre-chemotherapy groups (p &lt; 0.001). The average immunohistochemical intensity score in the pre-chemotherapy group was 0.83 ± 1.08, compared to a significantly higher average intensity score of 2.03 ± 1.03 in the post-chemotherapy group (p &lt; 0.001) Disease free survival of the post-chemotherapy AKR1B10(+) patients (61.2%) was significantly lower than that of AKR1B10(−) patients (100%) (log-rank test: p = 0.039). Conclusions: Although the present study is small and preliminary, post-chemotherapy AKR1B10 expression may have a predictive potential for response of chemotherapy and disease recurrence after definitive therapy for muscle-invasive bladder cancer. Further study is warranted to elucidate its clinical significance.
Clinical development of IL13Rα2-targeting CAR T cells for the treatment of glioblastoma
Authors: Christine E Brown, Renate Starr, Brenda Aguilar, Alfonso Brito, Brenda Chang, Aniee Sarkissian, Lihong Weng, Michael Jensen, Michael E Barish, Behnam Badie, Stephen J Forman
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts T cell immunotherapy is emerging as a powerful strategy to treat cancer, and may offer new opportunities to improve outcomes for patients with glioblastoma (GBM). Our group has developed a chimeric antigen receptor (CAR) T cell immunotherapy for GBM targeting IL-13 receptor α2 (
Minimizing leukemia escape: implementing a dual anti-CD20- and CD19-scFv-based chimeric antigen receptor (CAR)
Authors: Dina Schneider, Ying Xiong, Andre Roy, Andrew Kaiser, Boro Dropulic, Rimas Orentas
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Adoptive immunotherapy with chimeric antigen receptor (CAR) transduced T lymphocytes has shown promising results in both pediatric and adult B cell malignancies. Nevertheless, both CAR-based and antibody-based anti-CD19 therapies, e.g. blinatumomab, have seen treatment failures
Confirmation of deficient mismatch repair (dMMR) as a predictive marker for lack of benefit from 5-FU based chemotherapy in stage II and III colon cancer (CC): A pooled molecular reanalysis of randomized chemotherapy trials
Authors: D. J. Sargent, S. Marsoni, S. N. Thibodeau, R. Labianca, S. R. Hamilton, V. Torri, G. Monges, C. Ribic, A. Grothey, S. Gallinger
Journal: Journal of Clinical Oncology (2008)

4008 Background: Patients (pts) with CC demonstrating high-frequency MSI (MSI-H) have a stage-independent improved survival compared to pts with microsatellite- stable (MSS) tumors. We have previously published that MSI status is a predictive marker for lack of response to 5-FU-based chemotherapy (rx) (Ribic, NEJM 2003). dMMR by immunohistochemisty for MMR proteins is an almost perfect predictor for MSI status. We sought to confirm the value of dMMR as a predictor of survival benefit from adjuvant rx in stage II & III CC pts in an independent dataset drawn from randomized clinical trials. Methods: MSI or IHC analyses were performed on tumors from pts enrolled in trials conducted by the NCCTG (N=135), GIVIO (N=183), and ECOG (N=23) that have not been used in previous MSI or dMMR analyses. All trials randomized pts with stage II and III CC to either 5-FU based rx (either 5-FU + levamisole or 5-FU + leucovorin, n=166)) or no post-surgical rx (n=175). XX microsatellite loci from the National Cancer Institute panel were used to amplify genomic DNA and determine MSI status (GIVIO); IHC testing for hMLH1 and hMSH2 was used for the NCCTG and ECOG trials. Patients with MSI-H tumors or negative IHC staining were classified as dMMR;, the remainder were considered to have proficient MMR (pMMR). Median follow-up on living pts was 6.4 years with a primary outcome of overall survival (OS). Results: 341 tissue specimens were examined, of which 47 (13.8%, 20 treated, 27 untreated) exhibited dMMR. Adjuvant rx had a significant beneficial effect on OS (HR = 0.69, p= 0.047) and DFS (HR = 0.59, p = 0.004) in pts with pMMR tumors. However, pts with dMMR tumors receiving 5-FU rx had no trend toward improved OS (HR = 1.26, p = 0.68) or DFS (HR=1.41, p = 0.53) compared to those randomized to no rx. Results were maintained in multivariate models adjusted for stage and age. Conclusions: Stratification of pts according to MMR status provides a more tailored approach to the use of adjuvant rx in CC. Our data suggest that in a patient being considered for 5-FU alone rx (i.e a stage II pt), MMR status should be assessed and considered in rx decision making. No significant financial relationships to disclose.
Randomized Controlled Trial Investigating the Effects of a Low–Glycemic Index Diet on Pregnancy Outcomes in Women at High Risk of Gestational Diabetes Mellitus: The GI Baby 3 Study
Authors: Tania P. Markovic, Ros Muirhead, Shannon Overs, Glynis P. Ross, Jimmy Chun Yu Louie, Nathalie Kizirian, Gareth Denyer, Peter Petocz, Jon Hyett, Jennie C. Brand-Miller
Journal: Diabetes Care (2015)

OBJECTIVE Dietary interventions can improve pregnancy outcomes in women with gestational diabetes mellitus (GDM). We compared the effect of a low–glycemic index (GI) versus a conventional high-fiber (HF) diet on pregnancy outcomes, birth weight z score, and maternal metabolic profile in women at high risk of GDM. RESEARCH DESIGN AND METHODS One hundred thirty-nine women [mean (SD) age 34.7 (0.4) years and prepregnancy BMI 25.2 (0.5) kg/m2] were randomly assigned to a low-GI (LGI) diet (n = 72; target GI ∼50) or a high-fiber, moderate-GI (HF) diet (n = 67; target GI ∼60) at 14–20 weeks’ gestation. Diet was assessed by 3-day food records and infant body composition by air-displacement plethysmography, and pregnancy outcomes were assessed from medical records. RESULTS The LGI group achieved a lower GI than the HF group [mean (SD) 50 (5) vs. 58 (5); P &amp;lt; 0.001]. There were no differences in glycosylated hemoglobin, fructosamine, or lipids at 36 weeks or differences in birth weight [LGI 3.4 (0.4) kg vs. HF 3.4 (0.5) kg; P = 0.514], birth weight z score [LGI 0.31 (0.90) vs. HF 0.24 (1.07); P = 0.697], ponderal index [LGI 2.71 (0.22) vs. HF 2.69 (0.23) kg/m3; P = 0.672], birth weight centile [LGI 46.2 (25.4) vs. HF 41.8 (25.6); P = 0.330], % fat mass [LGI 10 (4) vs. HF 10 (4); P = 0.789], or incidence of GDM. CONCLUSIONS In intensively monitored women at risk for GDM, a low-GI diet and a healthy diet produce similar pregnancy outcomes.
Nutritional Support on the Medical Wards—Thought for Food
Authors: Jonathan P. Kushner, Joseph A. Lacy, Steven R Gay
Journal: JAMA Internal Medicine (2015)

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Non-invasive topical delivery of plasmid DNA to the skin using a peptide carrier
Authors: Manika Vij, Poornemaa Natarajan, Bijay Ranjan Pattnaik, Shamshad Alam, Nidhi Gupta, Deenan Santhiya, Rajpal Sharma, Archana Singh, Kausar M. Ansari, Rajesh S. Gokhale, Vivek T. Natarajan, Munia Ganguli
Journal: Journal of Controlled Release (2015)
Ubiquitin in the activation and attenuation of innate antiviral immunity
Authors: Steven M. Heaton, Natalie A. Borg, Vishva M. Dixit
Journal: The Journal of Experimental Medicine (2015)

Viral infection activates danger signals that are transmitted via the retinoic acid-inducible gene 1-like receptor (RLR), nucleotide-binding oligomerization domain-like receptor (NLR), and Toll-like receptor (TLR) protein signaling cascades. This places host cells in an antiviral posture by up-regulating antiviral cytokines including type-I interferon (IFN-I). Ubiquitin modifications and cross-talk between proteins within these signaling cascades potentiate IFN-I expression, and inversely, a growing number of viruses are found to weaponize the ubiquitin modification system to suppress IFN-I. Here we review how host- and virus-directed ubiquitin modification of proteins in the RLR, NLR, and TLR antiviral signaling cascades modulate IFN-I expression.
Childhood physical abuse and combat-related posttraumatic stress disorder in Vietnam veterans
Authors: J D Bremner, S M Southwick, D R Johnson, R Yehuda, D S Charney
Journal: American Journal of Psychiatry (1993)

Early trauma in the form of childhood physical or sexual abuse has been associated with adult psychopathology. The purpose of this study was to compare rates of childhood abuse in Vietnam veterans with and without combat-related posttraumatic stress disorder (PTSD).Premilitary stressful and traumatic events including childhood abuse and other potential predisposing factors were assessed in Vietnam combat veterans who sought treatment for PTSD (N = 38) and Vietnam combat veterans without PTSD who sought treatment for medical disorders (N = 28). Stressful and traumatic events including childhood physical abuse were assessed with the Checklist of Stressful and Traumatic Events and a clinician-administered interview for the assessment of childhood abuse. Level of combat exposure was measured with the Combat Exposure Scale.Vietnam veterans with PTSD had higher rates of childhood physical abuse than Vietnam veterans without PTSD (26% versus 7%). The association between childhood abuse and PTSD persisted after controlling for the difference in level of combat exposure between the two groups. Patients with PTSD also had a significantly higher rate of total traumatic events before joining the military than patients without PTSD (mean = 4.6, SD = 4.5, versus mean = 2.8, SD = 2.9).These findings suggest that patients seeking treatment for combat-related PTSD have higher rates of childhood physical abuse than combat veterans without PTSD. Childhood physical abuse may be an antecedent to the development of combat-related PTSD in Vietnam combat veterans.
A phase I pharmacokinetic and pharmacodynamic study of AMG 479, a fully human monoclonal antibody against insulin-like growth factor type 1 receptor (IGF-1R), in advanced solid tumors
Authors: A. W. Tolcher, M. L. Rothenberg, J. Rodon, D. Delbeke, A. Patnaik, L. Nguyen, F. Young, Y. Hwang, C. Haqq, I. Puzanov
Journal: Journal of Clinical Oncology (2007)

3002 Background: Increased IGF-1 signaling mediates tumor proliferation, reduces apoptosis, and correlates with higher incidence and progression of common cancers. AMG 479, a fully human monoclonal antibody against IGF-1R, exhibited broad antitumor activity in xenograft models, both as a monotherapy and with chemotherapy. Methods: Patients (pts) entered escalating dose cohorts of AMG 479 (from 1 to 20 mg/kg administered intravenously [IV] every two weeks [Q2W]). Study objectives were to determine safety, maximum tolerated dose (MTD), pharmacokinetic (PK) parameters, pharmacodynamic (PD) parameters of tumor glucose metabolism (FDG PET/CT), human anti- AMG 479 antibody formation, IGF-1R occupancy in neutrophils, and tumor response (CT RECIST, and PET/CT criteria). Results: Sixteen pts with advanced malignancies were treated with doses from 1 to 20 mg/kg. The median number of cycles was 3 (range 1 to 16). Grade 3 thrombocytopenia was considered dose limiting in 1 pt at 20 mg/kg. Other grade 3/4 non-hematologic toxicities were observed in 2 pts; no hyperglycemia greater than grade 2 was observed. Anti-AMG 479 antibodies, but not neutralizing antibodies, were detected in 1 pt. One pt had an infusion reaction (grade 2 chills/rigors resolving in 15 minutes) but could be retreated following premedication. AMG 479 exhibited dose-linear PK in the dose range from 1 to 20 mg/kg, reaching steady state after 3 doses; mean terminal t 1/2 ranged from 7 to 11 days; mean serum clearance ranged from 9 to 14 mL/day/kg; C ss exceeded IC 90 measured in preclinical models. PD results indicated a trend to dose-proportional occupancy of IGF-1R in neutrophils and increased levels of serum IGF-1 and IGF-BP3 (40% and 20% on day 3, respectively). By CT RECIST criteria, 1 pt with a neuroendocrine tumor had a confirmed partial response and 5 pts had durable stable disease. By FDG-PET/CT criteria, 1 pt with breast cancer had a mixed response. Conclusions: AMG 479 appears to be well tolerated at doses up to 20 mg/kg IV Q2W; dose escalation is complete. AMG 479 administration resulted in PK values adequate for activity in preclinical models, saturable binding of IGF-1R in neutrophils, and preliminary anti-tumor activity. [Table: see text]
Capecitabine (X) as single agent in elderly patients (p) with metastatic breast cancer (MBC)
Authors: P. Zamora, M. Álvarez de Mon, L. Calvo, C. Jara, J. A. Virizuela, A. Yubero, J. I. Chacón, J. Mira, M. González Barón
Journal: Journal of Clinical Oncology (2005)

843
Assessment of Liver Fibrosis With Acoustic Radiation Force Imaging (Arfi) Versus Liver Histology in Patients With Chronic Hepatitis C: A Pilot Study
Authors: M. Kohla, O. El-Abd, S. Ezzat, E. Tharwa, S. Kohla, M. Abdel-Rahman
Journal: Clinical Gastroenterology and Hepatology (2015)
Abstract P201: Cardiovascular Risk Factor Patterns And Their Associations With Total And Abdominal Obesity In Children Referred To A Cardiology Clinic
Authors: Lawrence de Koning, Erica Denhoff, Mark D Kellogg, Sarah D de Ferranti
Journal: Circulation (2014)

Background: Excess adipose tissue is associated with abnormal lipids, glucose, blood pressure, and inflammatory factors. In children, body mass index percentiles (BMI%) are commonly used to define adiposity. Although waist circumference percentiles (WC%) have not been universally accepted, they may better reflect visceral fat. The objective of this study was to determine the relationship between BMI% and WC% in identifying risk factor patterns in children at risk for developing cardiovascular disease. Methods: Children (8-19y free of major disorders and medications) with obesity, hypertension, lipid disorders, and/or a family history of premature cardiovascular disease (&lt; 55 years in male and &lt;65 years in female first-degree relatives) were recruited from the Preventive Cardiology clinic at Boston Children’s Hospital (n=150). Lifestyle (physical activity, screen time, tobacco exposure), anthropomorphic (height, weight, WC) and blood pressure (SBP, DBP) measures were made, as well as fasting lipids (total cholesterol, HDL, triglycerides (TG), LDL, VLDL) and inflammatory markers (hs-CRP, ICAM-1, P-selectin, and TNFαR2) from a serum sample. Principal component analysis (PCA) with varimax rotation was used to identify independent patterns explaining risk factor variance. Quintiles of pattern scores were associated with BMI% and WC% using multiple linear regression. Results: PCA identified 4 patterns: lipid (low HDL, high TG and LDL), inflammatory (high ICAM and TNFαR2), blood pressure (high SBP and DBP) and Lp(a) [high Lp(a)]. BMI% was significantly associated with higher levels of the lipid and blood pressure patterns (p&lt;0.03), explaining 15.8% and 4.7% of variance (partial r2) respectively. A higher WC% was associated with significantly higher levels of the lipid pattern (p&lt;0.001), explaining 16.2% of variance. When both BMI% and WC% were used together, neither BMI% nor WC% remained associated with the lipid pattern;, however, BMI% was inversely associated (p=0.02) and WC% positively associated (p=0.01) with the inflammatory pattern. The combined use of BMI and WC explained 12.2% of variance in the inflammatory pattern. Conclusion: In a sample of high-risk children, BMI% or WC% explained similar variance in lipid levels; however, the combined use of BMI% (representing lean body mass) and WC% (representing abdominal fat) together explained greater variance in elevated inflammatory factors than either alone. This suggests that using WC% along with BMI% may contribute to cardiovascular risk assessments of high-risk children.
Preliminary activity of XL880, a dual MET/VEGFR2 inhibitor, in MET amplified poorly differentiated gastric cancer (PDGC): Interim results of a multicenter phase II study
Authors: M. P. Jhawer, H. L. Kindler, Z. A. Wainberg, J. R. Hecht, R. O. Kerr, J. M. Ford, C. Henderson, T. Mueller, H. N. Keer, M. A. Shah
Journal: Journal of Clinical Oncology (2008)

4572 Background: XL880 is a potent, orally available small molecule inhibitor of MET and VEGFR2/KDR. Gastric cancer cell lines with MET amplification at 7q31 are sensitive to MET inhibition. Since, in retrospective clinical series, 7q31 amplification has been associated with PDGC, this phase II study examines the safety and efficacy of XL880 in pts with metastatic PDGC. Methods: The primary endpoint is response rate (RR), with 30 pts required to test the hypothesis that the RECIST confirmed RR with XL880 is 29% with 81% power and type I error of.041, versus Ho RR 11%. Eligibility requirements include: 0–2 prior chemotherapy regimens, adequate organ function, measurable disease, and ECOG 0–2. Pts receive XL880 240 mg/day on d1–5 of 14 day treatment cycles, and response is assessed every 8 weeks. MET amplification, determined by FISH of archival tissue, is defined as > 3 copies of 7q31. Optional pre- and on-treatment tumor biopsies are analyzed by immunohistochemistry for XL880 effects on direct and downstream drug targets. Plasma markers are analyzed for effects of anti-angiogenic therapy including VEGF-A and sVEGFR2. XL880 pharmacokinetics are evaluated as well. Results: As of 12/28/07, 18 pts have enrolled, 16 with tumor available for FISH. XL880 was well tolerated: all AEs were grade 1 or 2, most commonly hypertension, nausea, anorexia, fatigue, and asymptomatic liver function abnormalities. No related grade 4 or 5 AEs have been observed. Four of 16 pts had MET amplification by FISH: 2 evaluable pts demonstrated 20% decrease in tumor size, one progressed prior to XL880 treatment initiation, and one has not yet had the first efficacy evaluation. Overall, of 12 evaluable pts 2 patients had 20% decrease in tumor size at the first 8-week evaluation. Of these 12 pts, 6 remain on study (2 for > 12 wks, 4 for 8+ wks) and 6 had disease progression at <8 wks. Conclusions: XL880 as a single agent demonstrates preliminary anti-tumor activity in pts with previously treated PDGC. Approximately 25% of pts had MET amplification. Preliminary analysis suggests that pts with MET amplification may be sensitive to inhibition of MET with XL880. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Exelixis
Diagnostic Dilemmas in Oncology
Authors: Ian E. Krop, Tad J. Wieczorek, Robert J. Mayer
Journal: Journal of Clinical Oncology (2000)

Article Tools Diagnostic Dilemmas in Oncology Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.17.3189 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10963649 Diagnostic Dilemmas in Oncology Ian E. KropxIan E. KropSearch for articles by this author , Tad J. WieczorekxTad J. WieczorekSearch for articles by this author , Robert J. MayerxRobert J. MayerSearch for articles by this author Show More Dana-Farber Cancer Institute, Boston, MA https://doi.org/10.1200/JCO.2000.18.17.3189 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology