tbuckley/cabot-search huggingface dataset:
Antibody-Targeted Chemotherapy for the Treatment of Melanoma
Authors: Wendy K. Nevala, Sarah A. Buhrow, Daniel J. Knauer, Joel M. Reid, Elena A. Atanasova, Svetomir N. Markovic
Journal: Cancer Research (2016)

Antibody-directed chemotherapy (ADC) offers an advantage over conventional chemotherapy because it provides antibody-directed targeting, with resultant improvement in therapeutic efficacy and reduced toxicity. Despite extensive research, with notable exceptions, broad clinical application of ADC remains elusive; major hurdles include the instability of antibody-chemotherapy linkers and reduced tumor toxicity of the chemotherapy when bound to the antibody. To address these challenges, we have developed a platform technology that utilizes the nab-paclitaxel formulation of paclitaxel, Abraxane, in which hydrophobic paclitaxel is suspended in 130-nm albumin nanoparticles and thus made water-soluble. We have developed a method to noncovalently coat the Abraxane nanoparticle with recombinant mAbs (anti-VEGF, bevacizumab) and guide Abraxane delivery into tumors in a preclinical model of human A375 melanoma. Here, we define the binding characteristics of bevacizumab and Abraxane, demonstrate that the chemotherapy agent retains its cytotoxic effect, while the antibody maintains the ability to bind its ligand when the two are present in a single nanoparticle (AB160), and show that the nanoparticle yields improved antitumor efficacy in a preclinical human melanoma xenograft model. Further data suggest that numerous therapeutic monoclonal IgG1 antibodies may be utilized in this platform, which has implications for many solid and hematologic malignancies. Cancer Res; 76(13); 3954-64. ©2016 AACR.
P-049 First-line cisplatin plus bolus 5- Fluorouracil combination in patients with locally advanced and metastatic esophageal cancer
Authors: M. Akyol, Y. Kucukzeybek, U. Varol, I. Yildiz, S. Cokmert, I.V. Bayoglu, Y. Yildiz, L. Demir, A. Can, A. Dirican, A. Alacacioglu, M.O. Tarhan
Journal: Annals of Oncology (2015)
A phase II study to assess the efficacy and impact of BIBW 2992 on QTc interval in patients with solid tumors, including brain metastases and recurrent glioblastoma multiforme (GBM).
Authors: L. Trani, S. M. Alam, S. M. Rudman, L. R. Molife, G. W. Middleton, D. Propper, P. Stopfer, M. M. Uttenreuther-Fischer, G. Wallenstein, J. F. Spicer
Journal: Journal of Clinical Oncology (2010)

TPS187 Background: BIBW 2992 is an oral, irreversible inhibitor of EGFR/HER1 and HER2. EGFR and HER2 are amplified and overexpressed in most epithelial cancers as well as 50%–60% of GBMs. In a phase I study, one patient with NSCLC and brain metastases showed a response in both systemic and CNS disease. Preclinical and retrospective ECG analyses did not suggest an effect of BIBW 2992 on QTc, although this has not been prospectively assessed according to ICH E14 Cardiac Assessment of New Drugs Guidelines. The primary objectives of this study are to evaluate the effect of BIBW 2992 on QTc interval and the efficacy in patients with GBM, and patients with eligible tumors with and without brain metastases. Methods: In this phase II open label study, patients ≥18 years, with tumors known to historically overexpress EGFR or HER2, including those with brain metastases, and GBM at 1st recurrence, adequate organ function and ECOG PS 0–2, are eligible for treatment with BIBW 2992 50 mg PO OD q28. Patients with a QTcF-interval >470 ms, a PR-interval >230 ms, a QRS-interval >120 ms and ST-segment and T/U-wave abnormalities at screening, as assessed by central cardiology review, are excluded. All concomitant medications and dose changes within the initial 14 days on BIBW 2992 treatment are recorded. Up to 60 patients are to be recruited and treated until disease progression. Time-matched 24-h electrocardiograms are being performed at baseline, prior to drug exposure, after single dose and at steady state, i.e. Days -1, +1 and +14. PK samples are to be drawn at single dose and at steady state coincident with ECGs The primary endpoints are QTcF interval and objective tumor response according to the Macdonald criteria for GBM patients and for patients with brain metastases, and the RECIST 1.0 for other patients. Secondary endpoints include prolongation of QTcF, PR and QRS interval of ECG, heart rate, T wave and U wave morphology, disease control rate, PFS, molecular determinants of response, adverse events and PK characteristics of BIBW 2992 after single dose and at steady state. To date, 40 patients have been treated and 33 patients have completed ECG assessments on Days -1, +1 and +14. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Boehringer Ingelheim Boehringer Ingelheim Boehringer Ingelheim Boehringer Ingelheim
Nudging the Older Person Into Care: An End to the Dilemma?
Authors: Julian C. Hughes, Marie Poole, Stephen J. Louw
Journal: The American Journal of Bioethics (2013)

Click to increase image sizeClick to decrease image size Acknowledgments This article includes data from independent research funded by the National Institute for Health Research (NIHR) under the Research for Patient Benefit program (PB-PG-0906-11122). The views expressed in this article are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR, or the Department of Health, UK.
Use of the Antibody-Dependent Cellular Cytotoxicity Test To Detect Antibodies in Sera of Breast Cancer Patients&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: Plain, Meredith J., Whitehead, Robert H., Jose, David G.
Journal: JNCI Journal of the National Cancer Institute (1981)

Sera from 114 breast cancer patients, 53 patients with other tumors, and 29 healthy controls were tested for antibodies reactive in antibody-dependent cellular cytotoxicity tests against a new breast cancer cell line (PMC9), two well-documented cell lines (MCF-7 and BT-20), and two melanoma cell lines. Of the breast cancer sera, 47% reacted with PMC9, whereas 30% reacted with the melanoma cell lines (P less than 0.05). Only 22% of sera from other cancer patients and 21% of sera from healthy controls reacted with PMC9 (P less than 0.05). The reactivity of sera from breast cancer patients was related to clinical stage of disease. Absorption studies on sera showing reactivity to both PMC9 and melanoma cells showed that the antimelanoma reactivity could be removed leaving anti-PMC9 reactivity intact. This study demonstrated the presence of breast cancer-associated antibody to PMC9 but not MCF-7 or BT-20 in the sera of breast cancer patients.
Not using age specific values invalidates study
Authors: K. Spencer
Journal: BMJ (1995)

EDITOR,--J Fletcher and colleagues' paper does little to help purchasing authorities when they have to decide which screening programme and screening policy to choose when introducing screening for Down's syndrome.1 While the methodology used in the paper is valuable when used correctly, the authors were wrong to apply the overall sensitivity and specificity of serum testing obtained from whole population data rather than using age specific values. They argue that “this was done to reduce complexity.” As a consequence of their not making allowance for the fact that in older women (those over …
The prognosis of the patients with gastric cancer intraoperatively detected microscopical free abdominal cancer cells at Douglas cavity
Authors: T. Kishimoto, H. Imamura, H. Furukawa, M. Tatsuta, K. Yamamoto, R. Ohshiro, M. Yonekawa, M. Yamauchi
Journal: Journal of Clinical Oncology (2006)

14090 Background: The free abdominal cancer cells in the patients with gastric cancer probably result in peritoneal dissemination. In Japan, the detection of free abdominal cancer cells at Douglas cavity is usually examined immediately after lapalotomy for advanced gastric cancer, because this procedure is recommended in Japanese Classification of Gastric Carcinoma 1999 provided by Japanese Gastric Cancer Association. The patients detected free abdominal cancer cells are diagnosed as stage IV, even if they undergo the surgical curative operation. However some of them have relatively long survival. We investigated that the amount of free abdominal cancer cells or histological type might affect their prognosis. Methods: Surgeon collected 50ml of saline with which Douglas cavity was irrigated. Pathologist stained cells by Papanicolaou follwed by differential centrifugation (2000G for 5 minutes) of saline. Among all 492 patients who underwent surgery for gastric cancer in our institute between 2000 and 2004, 46 patients underwent the curative surgery except free abdominal cancer cells. We investigated the amount of free abdominal cancer cells and histological type as the factors to affect prognosis of these 46 patients. The log-rank test was used to evaluate the survival curves calculated by Kaplan-Maier method. Results: 5 or less and more than 5 cancer cells per 1 cm 2 were microscopically detected in 22 (Group A) and 24 patients (Group B), respectively. The median survival time (MST) of Group A and B were 877 and 384 days, respectively (P=0.16). The two-year survival rates of Group A and B are 63.7% and 27.2%, respectively. The cancer cells diagnosed histologically as differentiated and undifferentiated type were detected in 13 (Group X) and 33 patients (Group Y), respectively. The MSTs of Group X and Y were 877 and 383 days, respectively (P=0.13). The two-year survival rates of Group X and Y are 82.1% and 28.9%, respectively. Conclusions: In patients who have advanced gastric cancer with free abdominal cancer cells, a larger number or undifferentiated type of cancer cells may reduce the survival periods of patients with curative resection. No significant financial relationships to disclose.
A Randomized Comparison Of Maintenance Therapy With Subcutaneous Rituximab For 2 Years Versus Until Progression In Patients With Indolent Non-Hodgkin’s Lymphoma: Interim Safety Data From The Mabcute Study
Authors: Simon Rule, Javier Briones, Angelo Michele Carella, Olivier Casasnovas, Wolney Gois Barreto, Christopher Pocock, Stuart Osborne, Rodney Smith, Francesco Zaja
Journal: Blood (2013)
Carboplatin combined with the vascular-disrupting agent CYT997 for recurrent glioblastoma multiforme.
Authors: J. Lickliter, R. Fida, H. Wheeler, G. Kichenadasse, Q. Yang, V. Ganju, P. Briggs
Journal: Journal of Clinical Oncology (2010)

e13591 Background: The outcome in recurrent glioblastoma multiforme (GBM) remains poor although recent experience with regimens that include an anti-angiogenesis agent have shown some promise. We initiated a phase Ib trial of an alternative approach to vascular targeting, which evaluates the combination of the vascular-disrupting agent CYT997 with carboplatin. Methods: Patients with recurrent GBM after frontline radiation and temozolomide initially received carboplatin AUC=5 day 1 and etoposide 100 mg/m2 days 1-3, combined with CYT997 by 24-hour continuous IV infusion beginning day 2. Treatment was repeated every 3 weeks. Etoposide was deleted from the regimen after the first 4 patients due to excessive myelotoxicity. MRI scans were repeated every 2 cycles for response assessment and DCE-MRI scans were used to evaluate vascular disruption after the first cycle. Results: Eight patients have received at least one cycle of study therapy. The starting dose of CYT997 was 150 mg/m2. On day 5 of cycle 1, the first patient developed expressive dysphasia due to a left hemisphere infarct (confirmed on MRI with diffusion-weighted images). Subsequent CT angiography revealed a tight stenosis of the left MCA in the region of the previous high-dose radiation field. A protocol amendment then de-escalated the CYT997 dose and mandated screening magnetic resonance angiography and exclusion of patients with hemodynamically-significant cerebrovascular stenoses. Six patients have subsequently received CYT997 at 100 mg/m2 and one patient at 125 mg/m2 without further cerebrovascular toxicities. DCE-MRI showed reduced tumor Ktrans consistent with vascular disruption in 3 out of 6 evaluable patients. One patient had an imaging partial response after 3 cycles, but stopped protocol treatment because of worsening of pre-existing hydrocephalus and neurological deterioration. Another patient remains on study with stable disease after 8 cycles. Conclusions: Treatment with carboplatin and the vascular-disrupting agent CYT997 is feasible in recurrent GBM. Ongoing patient accrual will determine the efficacy of this regimen and the potential role of screening magnetic resonance angiography in avoiding cerebrovascular toxicity. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cytopia Research Pty, Ltd Cytopia Research Pty, Ltd Cytopia Research Pty, Ltd
Hematopoietic and Lymphopoietic Responses in Human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF ) Receptor Transgenic Mice Injected With Human GM-CSF
Authors: I. Nishijima, T. Nakahata, S. Watanabe, K. Tsuji, I. Tanaka, Y. Hirabayashi, T. Inoue, K. Arai
Journal: Blood (1997)
Calreticulin mutants in mice induce an MPL-dependent thrombocytosis with frequent progression to myelofibrosis
Authors: Caroline Marty, Christian Pecquet, Harini Nivarthi, Mira El-Khoury, Ilyas Chachoua, Micheline Tulliez, Jean-Luc Villeval, Hana Raslova, Robert Kralovics, Stefan N. Constantinescu, Isabelle Plo, William Vainchenker
Journal: Blood (2015)
Molecular profiling of neuroendocrine tumors (NETs): The Fox Chase Cancer Center (FCCC) experience.
Authors: Namrata Vijayvergia, Patrick McKay Boland, Steven J. Cohen, Karen S. Gustafson, Harry S. Cooper, Igor A. Astsaturov, Paul F. Engstrom
Journal: Journal of Clinical Oncology (2015)

245 Background: The rarity of NETs can limit clinical trial accrual to develop new therapies. Given fewer approved treatments, a better understanding of underlying biology is critical to development of and assignment of patients (pts) to clinical trials. Methods: Pts with NETs (excluding small/large cell lung cancer) of all grades at FCCC were enrolled onto a prospective IRB approved protocol that utilized an NGS platform to detect somatic mutations (SM) in 50 cancer-related genes (Cancer Code) on archived tissue from primary or metastatic sites. Genes tested included ABL1, AKT1, ALK, APC, ATM, BRAF, CDH1, CDKN2A, CSF1R, CTNNB1, EGFR, ERBB2, ERBB4, EZH2, FBXW7, FGFR1, FGFR2, FGFR3, FLT3, GNA11, GNAQ, GNAS, HNF1A, HRAS, IDH1, IDH2, JAK2, JAK3, KDR, KIT, KRAS, MET, MLH1, MPL, NOTCH1, NPM1, NRAS, PDGFRA, PIK3CA, PTEN, PTPN11, RB1, RET, SMAD4, SMARCB1, SMO,SRC, STK11, TP53 and VHL. Review of pathology specimens for grade and Ki -67 was also performed. Results: Thirty-nine pts (median age 59 y, males 46%) were enrolled from October 2013 to July 2014. Gene profiling results are available on thirty-five pts. Ki-67 score was reviewed for 31/35 tumors. 6 (20%) pts had high grade (HG) tumors (Ki-67 &gt; 20%) and 25 (80%) had low/intermediate grade (LIG) tumors (Ki-67 ≤20%). Thirteen (37%) pts were found to have SMs and 22 (63%) did not, with 4 (12%) pts’ tumors having &gt;1 SMs (2 HG and 2 LIG tumors). Incidence of SM was 41% (12/29) in Caucasians, 16% (1/6) in other races, 46% (6/13) in smokers and 30% (6/20) in non-smokers. Incidence of SM was 24% (6/25) in LIG NETs and 84% (5/6) in the HG NETs. Among HG tumors, 66% (4/6) harbored TP53 gene mutation and 33% (2/6) were BRAF mutation positive. Conclusions: Tumor-specific mutations are seen in a minority of low grade NETs but are common in high grade tumors. Interestingly, no mutations were identified in pts with unknown primary. Analysis of clinical outcomes based on treatment received is ongoing to assess for possible prognostic/therapeutic implications of these mutations. [Table: see text]
Exercise and pregnancy in recreational and elite athletes: 2016 evidence summary from the IOC expert group meeting, Lausanne. Part 1—exercise in women planning pregnancy and those who are pregnant
Authors: Kari Bø, Raul Artal, Ruben Barakat, Wendy Brown, Gregory A L Davies, Michael Dooley, Kelly R Evenson, Lene A H Haakstad, Karin Henriksson-Larsen, Bengt Kayser, Tarja I Kinnunen, Michelle F Mottola, Ingrid Nygaard, Mireille van Poppel, Britt Stuge, Karim M Khan
Journal: British Journal of Sports Medicine (2016)

Guidelines on physical activity or exercise and pregnancy encourage pregnant women to continue or adopt an active lifestyle during and following pregnancy.1–3 Two systematic reviews of pregnancy-related guidelines on physical activity found similarities between recommendations from different countries, but noted that the guidelines differed in focus.4 ,5 The guidelines provided variable guidance on prenatal exercise, or on how pregnant women might approach continuing or adopting sport activities.6 However, most guidelines did not include important topics such as prevalence and known risk factors for common pregnancy-related diseases and complaints, and the role of exercise in preventing and treating them.

Importantly, the focus of most previous guidelines has been on healthy pregnant women in the general population, in whom there is almost always a decline in physical activity during pregnancy.7 ,8 Indeed, a high proportion of pregnant women follow neither physical activity nor exercise guidelines,9 putting them at increased risk of obesity, gestational diabetes mellitus (GDM), and other pregnancy-related diseases and complaints.1

On the other hand, there are enthusiastic exercisers and elite athletes who often meet and exceed general exercise recommendations for pregnant women, but there are no exercise guidelines specifically for these women. Important questions for such women are unanswered in current guidelines: Which activities, exercises and sports can they perform, for how long and at what intensity, without risking their own health and the health of the fetus? How soon can they return to high-intensity training and competition after childbirth?

The IOC and most National Sports Federations encourage women to participate in all Olympic sport disciplines. The IOC promotes high-level performance, and it is also strongly committed to promoting lifelong health among athletes10—not just during their competitive sporting careers. With an increasing number of elite female athletes competing well into …
Effect of Normal Cells on Viscosity of Sickle-Cell Blood
Journal: JAMA (1963)

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Optimal dose of cetuximab (C) given every 2 weeks (q2w): A phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of weekly (q1w) and q2w schedules in patients (pts) with metastatic colorectal cancer (mCRC)
Authors: J. Tabernero, A. Cervantes, E. Martinelli, E. Vega-Villegas, F. Rojo, A. Pérez-Fidalgo, E. Casado, F. Ciardiello, A. Zubel, J. Baselga
Journal: Journal of Clinical Oncology (2006)

3085 Background: The anti-EGFR Mab C is active in mCRC. Since C has a long terminal half-life and it is frequently given in combination with q2w chemotherapy, we decided to compare the safety and PK/PD of a more convenient q2w schedule with the currently approved q1w schedule in pts with EGFR-expressing mCRC. Methods: In this study C was given q2w at the standard q1w regimen (400 mg/m 2 initial dose and 250 mg/m 2 weekly) to 10 pts as a comparator. In the experimental arm, C was given q2w with a dose escalation in sequential steps for cohorts of 10 pts each (400, 500, 600 &amp; 700 mg/m 2 ). Dose levels were escalated if no dose-limiting toxicities (DLTs) were observed. DLTs were defined as grade 3–4 toxicities (except for hypersensitivity reactions and grade 3 skin toxicity), and/or administration of less than 66% of the assigned dose due to toxicity. In order to conduct the PK/PD studies, all treatment groups were given C alone for 6 weeks and subsequently, the FOLFIRI regimen was added. Complete PK profile was obtained during the initial 6 weeks of treatment. Skin and tumor biopsies for PD profiling were obtained prior to therapy and on day 28 (steady state) and have been analyzed by IHC for total (t) and phospho (p)-EGFR, p-MAPK, p-Akt, proliferation (Ki67) &amp; p27 expression. Results: 29 pts have been included so far: 9 in the q1w group and 20 in the q2w group (10 pts each at 400 and 500 mg/m 2 ). To date there have been no DLTs. PK data are predictable (C min , AUC) and comparable (t 1/2 , CL ss ) between both regimens (see table below). Preliminary skin PD studies show no major difference in the EGFR-signaling inhibition by C in the q1w and q2w regimens. Conclusions: C can be safely administered in a q2w regimen at 400 and 500 mg/m 2 . The MTD of q2w C has not yet been reached and dose escalation is ongoing. Our findings show no major difference in PK and PD profiles with the q1w and q2w schedules. C given q2w may be an alternative and convenient schedule of administration. [Table: see text] [Table: see text]
Establishment and Characterization of a Panel of Patient-Derived Soft Tissue Sarcoma (Sts) Xenograft Models for in Vivo Testing of Novel Therapeutic Approaches
Authors: H. Li, J. Cornillie, A. Wozniak, J. Wellens, T. Van Looy, U. Vanleeuw, I. Samson, D. Hompes, M. Stas, F. Sinnaeve, M. Debiec-Rychter, R. Sciot, P. Schöffski
Journal: Annals of Oncology (2014)