tbuckley/cabot-search huggingface dataset:
The effect of food on the single dose pharmacokinetics of cediranib
Authors: G. C. Jayson, T. R. Evans, A. Harris, C. L. Mitchell, C. Kelly, M. Middleton, A. Fielding, P. Laud, J. Robertson, T. A. Puchalski
Journal: Journal of Clinical Oncology (2008)

14533 Background: Cediranib (AZD2171) is an oral, highly potent and selective inhibitor of vascular endothelial growth factor (VEGF) signaling, with activity against VEGFR-1, -2 and -3. The effect of food on the pharmacokinetic (PK) profile of cediranib is not known. This study compared the single dose exposure PK parameters of cediranib following single oral doses to patients after a) a standard regulatory meal and b) an overnight fast. Methods: In this randomized, open-label, two-period, crossover study, 34 patients with advanced solid tumors refractory to standard therapies, ECOG PS ≤2, with adequate hematologic, renal and liver function, received two single doses of cediranib 45 mg with ≥8 days washout period. Patients were randomized to receive treatment in either the fed then the fasted state (group 1) or the fasted then the fed state (group 2). In the fed period, patients ate a standard high-fat breakfast (as per FDA guidelines) prior to dosing with cediranib. In both groups, intensive PK sampling occurred over 168 hours post dosing on each occasion. The effect of food on the single dose PK of cediranib was assessed using the criteria for establishing bioequivalence based on the endpoints of AUC and Cmax. Food would be considered to have no effect on the PK of cediranib if confidence intervals (CI) for the food effect ratio for endpoints of AUC and Cmax fell within the acceptance range of 0.8–1.25. CI of 94% were used in order to allow for the 2-group sequential design of the study and obtain an overall 5% significance level. Results: Both the AUC and Cmax of cediranib were lower in the presence of food by a mean of 24% and 33% respectively (94% CI: AUC, 12–34% and Cmax, 20–43%; Table 1). The CI for AUC crossed the lower equivalence boundary of 0.8 but the entirety of the CI was <1. The CI for Cmax was entirely outside the equivalence boundary, indicating a clear food effect. Conclusions: These data indicate that food reduces cediranib plasma exposure in terms of AUC and Cmax. It is recommended that cediranib be administered at least 1 hour before or 2 hours after food. Table 1. 1. Results of primary analysis Fasted GLS mean Fed GLS mean Food effect ratio* 94% CI AUC (ng·h/mL) 2450 1870 0.762 (0.663, 0.876) Cmax (ng/mL) 130 87.3 0.672 (0.567, 0.796) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca Oncology AstraZeneca Oncology AstraZeneca Oncology AstraZeneca Oncology
CXCR4 is involved in multiple functions of cancer cells and is a compelling target for monoclonal antibody-based therapeutics
Authors: A. L. Boynton
Journal: Journal of Clinical Oncology (2006)

20013 Background: CXCR4 is over-expressed on &gt; 75% of cancers and absent on most non-neoplastic cells. It is a G protein coupled receptor spanning the cell membrane with CXCL-12 as its ligand. It is uniquely involved in 3 vital aspects of cancer: 1) proliferation; 2) motility; and 3) metastasis. Our objective was to assess specific Abs as candidates for clinical development in preclinical models. Methods: Several human cancer cell lines were used to study whether either mAbs specific to the CXCR4 receptor or to CXCL12 could inhibit: 1) proliferation; 2) chemotaxis; and 3) invasion through a reconstituted basement membrane. The ability of anti-CXCR4 Ab to inhibit tumor growth in vivo was also tested. Female Nod/Scid mice were injected IP with 2 × 10 5 human Namalwa tumor cells with 10 mice per group. Mice were injected with: Group 1) 100μg irrelevant IgG2b isotype control Ab; Group 2) 100μg CX02 anti-CXCR4 Ab; and Group 3) 100 μg CX05 anti-CXCR4 Ab. All mice in each group received an injection of Ab at day 2, 8, 14 and 20. Mice were observed for tumor growth over the following 4–5 months. Results: We originally found that CXCR4 was over expressed in fresh surgical human Glioblastoma, then showing that it was also over expressed in multiple cancer types. Specific anti-CXCR4 monoclonal Abs, CX02 and CX05 as well as anti-CXCL12 Abs demonstrated the ability to block cell proliferation of a variety of human Glioblastoma tumor cells including GB1690, HTB16, and 5GB, but not the proliferation of cells that do not express CXCR4. CX02 and CX05 Abs bind to live tumor cells with high affinity and have an EC 50 of 3.2 and 2.7 μg/ml respectively (effective concentration required to provide 50% maximal median fluorescence shift). Both Abs (10 μg/ml) also inhibited by over 90% the motility of HS Sultan cells as demonstrated by the standard chemotaxis assays. In addition, both Abs (10–40 μg/ml) also inhibited the ability of HS Sultan cells to penetrate Matrigel, a reconstituted basement membrane assay used to assess malignant potential of cancer cells. Finally, both Abs were successful in extensively prolonging survival of Nod/Scid mice injected with human Namalwa cells. Conclusions: CXCR4 represents a compelling target for mAb therapy; Phase I clinical trails are pending. [Table: see text]
Combination therapy with interferon alfa and ribavirin in interferon alfa relapsers.
Authors: Santino Marchi, A. Ricchiuti, P. Ciccorossi, F. Costa, M. Bellini, E. Tumino, S. Petruccelli, M. R. Romano, F. Maggi, L. Vatteroni, Mauro Pistello, Mauro Bendinelli, S. Milani, C. Surrenti, G. Maltinti
Journal: Hepatology (1996)
Studies on Carcinogenesis by Avian Sarcoma Viruses. III. The Differential Effect of Serum and Polyanions on Multiplication of Uninfected and Converted Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Howard M. Temin
Journal: JNCI Journal of the National Cancer Institute (1966)

Infection of chicken embryo cells with avian sarcoma viruses leads to conversion of many properties of the cell. Further studies of factors affecting cell multiplication are reported here. Secondary cultures of chicken embryo fibroblasts were prepared in a growth medium containing serum. After incubation overnight, the cultures were exposed to medium from cultures of uninfected or virus-infected cells and various media were then added. The uninfected and the infected cells were allowed to multiply until they reached the stationary phase, at which time their number was determined (saturation density). It was found that the saturation density was proportional to the amount of serum in the growth medium. When serum was limiting, cultures of converted cells multiplied to a saturation density 50% higher than parallel cultures of uninfected cells. Agar or other polyanions exerted two effects on the saturation density. One was to bind some substance in serum needed for cell multiplication. This substance was used up in cell multiplication and was needed by normal and converted cells. The other was to stimulate multiplication of both uninfected and converted cells. These results lead to the following hypotheses: 1) Multiplication of uninfected and converted cells requires a substance, bound by polyanions, which is present in serum. However, the converted cells require less of this substance per cell division than uninfected cells. 2) Cells produce a toxin bound by polyanions. Converted cells produce more of this toxin than uninfected cells.
A single institution experience with interstitial brachytherapy for soft tissue sarcoma of the extremities
Authors: C. M. McCluskey, W. L. Barrett, A. Lowy, J. Sussman, J. Sorger
Journal: Journal of Clinical Oncology (2004)

9058 Background: Soft tissue sarcomas (STS) are a rare, histologically diverse group of malignancies which are primarily treated with surgery. Depending on location and grade radiation therapy may be used as adjuvant treatment. In this single institution, retrospective series we examine treatment outcome for STS of the extremity treated with surgery and adjuvant interstitial brachytherapy (BTX). Methods: 21 patients were treated from 9/97 to 5/03 with adjuvant BTX for primary or recurrent STS. 14 patients were treated for primary and 7 for recurrent disease. Histologic subtypes included MFH, liposarcoma, synovial sarcoma, leiomyosarcoma, myxofibrosarcoma, and malignant peripheral nerve sheath sarcoma. 8 patients had low grade and 13 had high grade tumors. The majority of patients had lesions larger than 5 cm. 11 had T2b disease, 6 had T1b disease, 3 had T1a disease and 1 had T2a disease. The median age at presentation for BTX treatment was 45. Patients with low grade tumors received 2500 cGy with BTX, followed by 4500 cGy with external beam radiation therapy (EBRT). High grade tumors were treated with BTX alone to 4500 cGy if they were considered resectable at the time of diagnosis. If there was concern about resectability they received 4500 cGy of EBRT pre-operatively, followed by a 2500 cGy BTX boost. Results: Median follow-up was 21 months. 20 patients were known to be alive at last follow-up. One patient died of a metachronous primary STS. None of the patients with low grade tumors were known to have experienced local recurrence (LR). Of the 13 patients with high grade tumors 11 had no LR and 2 experienced LR. One of these patients had experienced 3 recurrences prior to treatment with BTX and the other recurred after 57 months of follow-up. The freedom from local recurrence rate (FFLR) for low grade disease was 100% and for high grade disease 85%. Overall FFLR was 93%. One patient developed a foot drop post treatment which could possibly have been related to BTX. No other functional deficits have occurred. Conclusions: Interstitial BTX appeared to improve local control in both patients with low grade and high grade STS of the extremity. No significant financial relationships to disclose.
A prospective randomized trial comparing high-dose cisplatin with low-dose cisplatin and chlorambucil in advanced ovarian carcinoma.
Authors: E Wiltshaw, B Evans, G Rustin, E Gilbey, J Baker, G Barker
Journal: Journal of Clinical Oncology (1986)

Sixty-one patients with FIGO stage III ovarian carcinoma and 30 patients with stage IV ovarian carcinoma were randomized to receive either high-dose cisplatin (100 mg/m2) or low-dose cisplatin (20 mg/m2) and chlorambucil. Overall response rates were similar in both arms, with 68% and 49% of stage III patients and 61% and 72% of stage IV patients responding to high-dose cisplatin and the combination, respectively. There was a strong trend for better survival in stage III (P less than .05) but not in stage IV patients treated with cisplatin alone. The toxicity suffered by patients treated with high-dose cisplatin was severe, and in 15 patients cisplatin therapy was stopped because of unacceptable toxicity.
이번 호의 간 영상 : 혈관육종
Authors: 이원재 ( Won Jae Lee )
Journal: Clinical and Molecular Hepatology (2009)

67세 남자 환자에서 비교적 전형적인 혈관육종의 CT와 MRI 소견을 보이고 조영증강 초음파 소견을 최초로 기술한 사례로 간절제술로 확진하였다. 혈관육종은 매우 드물고 특이적 영상 소견이 없기 때문에 진단이 어렵지만 임상양상과 영상 소견을 잘 이해하고 있으면 진단 및 감별진단에 도움이 된다. 저자는 본 사례를 이용하여 혈관육종의 영상 소견을 조직병리 소견과 연관지어 설명하고자 하였다.
Top US cancer centers push for more use of HPV vaccine
Authors: Michael McCarthy
Journal: BMJ (2016)

Sixty nine of the top cancer centers in the United States have issued a joint letter calling for more widespread use of the vaccines against human papillomavirus (HPV). In the letter, released 28 January, the National Cancer Institute designated cancer centers called the low rate of uptake of HPV vaccines in the US “a serious public health threat.”

The centers noted that …
Expression of critical genes used as prognostic biomarkers and DNA damage in lymphocytes from breast cancer patients
Authors: F. Franke, M. Agnoletto, J. Saffi, T. Guecheva
Journal: Journal of Clinical Oncology (2006)

10641 Breast cancer is the most common malignancy among women and its rate of mortality is still high. The increase knowledge of breast cancer biology is heaving great impact on determining the clinical prognosis and response to treatment. Impaired DNA repair may elevate the risk of malignant transformation of breast cells due to the accumulation of spontaneous mutations in target genes and increasing susceptibility to exogenous carcinogens. The present study was designed to evaluate the relationship between DNA damage and expression of some critical genes including TP53, c-ERBB2, ER (Estrogen Receptor) and PR (Progesterone Receptor) in breast cancer. Blood samples were obtained from female patients with diagnosed breast cancer before chemotherapy as well as from healthy individuals, and were processed in 24 hours. To evaluate the role of DNA repair in breast cancer we determined the level of DNA damage and the capacity to remove DNA damage induced by hydrogen peroxide in the peripheral blood lymphocytes. For this purpose the alkaline version of the comet assay, which provides a sensitive tool to investigate DNA damage and repair, was applied. The level of basal DNA damage was higher in breast cancer patients compared to the control group. Considerable inter-individual variations of DNA damage and repair in breast cancer patients were observed both before and after the treatment. The correlation between DNA damage in peripheral blood and expression of p53, c-erbB-2, PR and ER was analyzed. This preliminary study indicates that the DNA damage accumulation, observed in peripheral blood lymphocytes of breast cancer patients in early stages, could be attributed to impaired DNA repair. Our results suggest that DNA damage, as evaluated by the comet assay, seems to be useful molecular biomarker for monitoring ongoing exposures to DNA damaging agents. Such a research on the mutagen sensitivity and efficacy of DNA repair could impact on the development of new diagnostic and screening strategies. Work Supported by FAPERGS and GENOTOX (UFRGS). No significant financial relationships to disclose.
Characteristics of an Established Cell Line of Retinoblastoma2
Authors: Ted W. Reid, Daniel M. Albert, Alan S. Rabson, Paul Russell, Joseph Craft, Elizabeth W. Chu, Tommie Sue Tralka, Janice L. Wilcox
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Characteristics of an Established Cell Line of Retinoblastoma Get access Ted W. Reid, Ted W. Reid Search for other works by this author on: Oxford Academic PubMed Google Scholar Daniel M. Albert, Daniel M. Albert Search for other works by this author on: Oxford Academic PubMed Google Scholar Alan S. Rabson, Alan S. Rabson Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul Russell, Paul Russell Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph Craft, Joseph Craft Search for other works by this author on: Oxford Academic PubMed Google Scholar Elizabeth W. Chu, Elizabeth W. Chu Search for other works by this author on: Oxford Academic PubMed Google Scholar Tommie Sue Tralka, Tommie Sue Tralka Search for other works by this author on: Oxford Academic PubMed Google Scholar Janice L. Wilcox Janice L. Wilcox Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 2, August 1974, Pages 347–360, https://doi.org/10.1093/jnci/53.2.347 Published: 01 August 1974 Article history Received: 25 January 1974 Accepted: 19 April 1974 Published: 01 August 1974
Five-years experience with high urgency allocation program for lung and heart-lung transplantation in pulmonary hypertension
Authors: Laurent Savale, Jérôme Le Pavec, Olaf Mercier, Sacha Mussot, Dominique Fabre, Xavier Jais, David Montani, Olivier Sitbon, Marc Humbert, Gerald Simonneau, Philippe Dartevelle, Elie Fadel
Journal: European Respiratory Journal (2014)

Background.  French patients with severe pulmonary hypertension (PH) and imminent risk of death can access to heart-lung transplantation (HLT) or lung transplantation (LT) according to a high urgency allocation program (HUAP) since September 2006 and July 2007 respectively.   Objective and methods.  To report results of HLT and LT in PH patients listed on HUAP from 2007 to 2012. Characteristics and outcome of these patients were retrospectively analyzed and compared to the cohort of PH patients receiving non-urgent (NU) HLT or LT.   Results . During the study period, 28/42 (67%) HLT and 24/53 (45%) LT were performed according to the HUAP. Based on the clinical classification of PH 64% of patients were group 1 (pulmonary arterial hypertension), 18% group 19 (veno-occlusive disease), 2% group 3, 8% group 4 and 7% group 5. Total median time on waiting list was 0.3 months (IQR 25-75%, 0.1-2.7) and 3.6 months (IQR 25-75%, 2-12) in HUAP and NU groups respectively (p   Conclusion.  This study suggests that HUAP for HLT or LT may improve survival of PH patients on waiting list with respect to similar morbidity and mortality after transplantation.
Phase I trial of carboplatin, irinotecan and etoposide in advanced solid tumors
Authors: A. Chiappori, G. R. Simon, L. Kvols, L. Tetteh, J. J. Mahany, R. Lush, D. M. Sullivan
Journal: Journal of Clinical Oncology (2004)

2132 Background. Carboplatin(C), Irinotecan(T) and Etoposide (E) are drugs with a broad spectrum of activity. Synergism has been demonstrated between a platinum compound and a top I inhibitor. Additionally synergism has also been documented with the sequential use of top I ->top II inhibitor. We designed a phase I trial to take advantage of these pharmacodynamic interactions. Methods. Four previously treated patients with advanced malignancies were enrolled in the first dose level of C at AUC of 2.5 on days 1 & 8; T at 60mg/m2 on days 1 & 8 and E at 60 mg/m2 on days 2 & 3. Cycles were repeated Q 21 days. Two deaths occurred in this cohort. Dose was then deescalated to the dose –1 tier where the dose of C and T were the same but the dose of E was reduced to 50mg/m2 of days 2 & 3. Six additional patients were enrolled on this cohort. Results. A total of 10 patients were enrolled from April 2002 to October 2002.Patient characteristics were M/F 5/5; age range 24 to 65, ECOG PS 0/1=1/9; number of prior treatments 0/1/2/3= 4/2/3/1; median number of cycles given=3 (range 1 - 8). Tumor types enrolled were NSCLC = 3, Carcinoid = 3, and 1 each of Head and Neck Cancer, Mesothelioma, Sarcoma and Islet Cell Cancer of the pancreas. A total of 30 cycles were delivered. In the first cohort of 4 patients, 2 second-cycle grade IV non-febrile neutropenia was observed. Two deaths occurred in previously treated advanced stage NSCLC patients. One patient died from massive pulmonary hemorrhage secondary to progressive disease in the presence of normal platelet count. The second patient died at home of gastrointestinal hemorrhage secondary to NSAID use. The subsequent cohort of 6 patients tolerated chemotherapy well with no first-cycle or second-cycle grade III or IV neutropenia or thrombocytopenia. Five of the 8 evluable patients had SD, 2 of whom had MR. Further dose escalation was not attempted owing to 2/2 patients experiencing Grade IV neutropenia in the first cohort. Conclusions. The recommended phase II dose for this regimen is C at AUC of 2.5 on days 1 & 8, T at 60mg/m2 on days 1 & 8 and E at 50mg/m2 on days 2 & 3. A phase II trial of extensive stage SCLC is planned with this regimen with correlative intra-tumoral top I and II estimations. No significant financial relationships to disclose.
Complications of acute leukemia. Case two: epidural chloroma of the lower spinal canal.
Authors: G M Proulx, P McCarthy
Journal: Journal of Clinical Oncology (1998)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1998.16.9.3201 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9738593 Complications of acute leukemia. Case two: epidural chloroma of the lower spinal canal. G M ProulxxG M ProulxSearch for articles by this author , P McCarthyxP McCarthySearch for articles by this author Show More Roswell Park Cancer Institute, Buffalo, NY, USA. https://doi.org/10.1200/JCO.1998.16.9.3201 First Page PDF © 1998 by American Society of Clinical Oncology
A randomized clinical trial of phenelzine and imipramine for posttraumatic stress disorder
Authors: J B Frank, T R Kosten, E L Giller, E Dan
Journal: American Journal of Psychiatry (1988)

In a double-blind, randomized clinical trial, the efficacy of imipramine and of phenelzine was compared with that of placebo in 34 male veterans with posttraumatic stress disorder (PTSD). Both medications reduced PTSD symptoms.
6 Juvenile dermatomyositis
Authors: C PILKINGTON, NJ OWEN, S BOSE, C MACHADO, CM OWENS, K MURRAY
Journal: Annals of the Rheumatic Diseases (2000)

the subgroups of patients with JIA.The mean (SD) antibody levels in the children with JIA were significantly lower (175.5 (118.4)mIU/ ml) than those of the healthy subjects (317.08 (180.5)mIU/ml) There was no diVerence between the sexes in vaccine responsiveness.When the antibody levels between the two vaccination schedules were compared in healthy children, there was no statistical diVerence.However, there was a slightly higher, but statistically insignificant, response in JIA subjects vaccinated in group II than in those in group I.The vaccine responsiveness was not influenced either by methotrexate or prednisolone treatment.However, there was a negative correlation between prednisolone dose and anti-HBs titre (r=-0.23).Conclusion-Children with JIA responded adequately to hepatitis B vaccination, and this response was not negatively influenced by immunosuppressive treatment.The more appropriate vaccination schedule for children with JIA is the schedule given at 0, 1, and 6 months.
Randomized, placebo-controlled, multicenter trial of granulocyte-macrophage colony-stimulating factor as infection prophylaxis in oncologic surgery. Leukine Surgical Prophylaxis Research Group.
Authors: N J Meropol, D E Wood, J Nemunaitis, N J Petrelli, B J Lipman, J M Agosti, J B Whitmore
Journal: Journal of Clinical Oncology (1998)

PURPOSE Postoperative infections are a frequent source of preventable morbidity and mortality in the oncologic population. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent modulator of immune effector cells in vitro and in vivo. This study was conducted to determine whether GM-CSF, when administered perioperatively, could reduce the incidence of surgical infections in cancer patients. METHODS This was a prospective, randomized, placebo-controlled, multicenter study. Cancer patients at high risk of infectious surgical morbidity were randomized to receive GM-CSF 125 microg/m2 per day or placebo subcutaneously for 8 days beginning 3 days preoperatively. Routine antibiotic prophylaxis was administered to all patients. RESULTS Three hundred ninety-nine patients were enrolled, with 198 randomized to receive GM-CSF. Twenty-one percent of patients experienced infections during the first 2 weeks postoperatively, and there was no difference in infection rate between the study groups. The most common sites of infection were respiratory tract (53%) and surgical wound (25%). The duration of operation and American Society of Anesthesiology (ASA) physical status classification were the most significant predictors of infection in multivariate analysis. GM-CSF was well tolerated and was not associated with fever. CONCLUSION The eligibility criteria for this study were successful at defining a patient subgroup at high risk for postoperative infections. At an immunomodulatory dose of 125 microg/m2 per day, GM-CSF was safe and well tolerated, but did not reduce the incidence of postoperative infections in this high-risk oncologic population. Infectious morbidity in surgical oncology remains an important subject for continued clinical investigation.