tbuckley/cabot-search huggingface dataset:
Multi-center, phase II study for combination therapy with paclitaxel/doxifluridine to treat advanced/recurrent gastric cancer showing resistance to S-1: Final results (OGSG 0302)
Authors: H. Takiuchi, H. Imamura, M. Imano, Y. Kimura, H. Ishida, Y. Nakane, T. Tsujinaka, H. Narahara, S. Morimoto, H. Furukawa
Journal: Journal of Clinical Oncology (2007)

15025 Background: We report here results of phase II study for a combination therapy with paclitaxel/doxifluridine to treat advanced/recurrent gastric cancer showing resistance to S-1. S-1 is an oral fluoropyrimidine drug that combines tegafur, CDHP, and oxonic acid (Oxo), which has been most frequently used in Japan. Methods: Subject registration was started to employ 35 patients with advanced/recurrent gastric cancer, who were selected among those with measurable lesions fitting to RECIST, and with resistant to S-1 treatment (PS, 0–2; and patient’s ages ranged from over 20 to under 75 years). We employed dosages that Hyodo et. al. used in phase I study and recommended as a standard regimen including paclitaxel, 80 mg/m 2 , i.v. on days 1 and 8; and doxifluridine, 600 mg/m 2 , p.o. on days 1–14.. These were repeated every 3 weeks. Primary endpoint of present phase II study was: RR; and secondary endpoints were OS, PFS, and onset rate of adverse events. Results: From September, 2003 to March, 2005, 35 patients were registered: including 28 men; 7 women; median age of 66 years (range, 49–75 years); and PS levels were, zero with 21 and one with 14 patients. In 33 eligible patients, except 2, clinical usefulness was evaluated resulting in response rate of 18.2% (PR, 6; SD, 15; PD, 10; and NE, 2 patients). OS was 321 days, and PFS was 119 days. Severe adverse events were found in 3 patients to discontinue the present treatment though; other adverse events were relatively mild without no death due to the present therapy. Conclusions: Patients in the present study with advanced/recurrent gastric cancer were those resistant to S-1 treatment. Response rate was 18.2% increasing to 63.6% when SD was added. OS resulted in relatively long period of 321 days, while OS from initial time starting S-1 treatment was 619 days. This suggests that the present treatment is useful as the sequential therapy. Adverse events were controllable suggesting a high reliability of the present therapy. In conclusion, the present therapy with paclitaxel/doxifluridine could be a treatment of choice as an useful second line chemotherapy for patients undergone S-1 treatment. No significant financial relationships to disclose.
Chromosome Damage Induced by 5-Fluoro-2′ -Deoxyuridine in Relation to the Cell Cycle of the Chinese Hamster&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C. H. Ockey, T. C. Hsu, L. Carole Richardson
Journal: JNCI Journal of the National Cancer Institute (1968)

Chromosome damage is induced by 5-fluoro-2′-deoxyuridine (FUDR) in Chinese hamster fibroblast line Don and clone strain Don-C during the DNA synthesis period. The G2 period is insensitive. The characteristic shattering of chromosomes is induced in FUDR-blocked cells at the beginning of the S period with a very narrow time span (3 ± 0.5 hrs after metaphase). Only the early replicating sites or euchromatin of the chromosomes is affected. The Y and the long arm of the × remain unbroken. This period is the most sensitive stage to damage and many cells do not reach metaphase. Cells treated in the later part of the S period are not blocked by FUDR. They show a low frequency of open chromosome breaks in the late or heterochromatic regions. These cells are blocked at the beginning stage of the next S phase. When released by nonradioactive thymidine (TDR), they come to mitosis with one chromatid labeled. The results indicate a large enough TDR pool to permit cells in the mid-S phase to complete DNA synthesis without relying on the endogenous pathway. This TDR pool can be demonstrated by pulse labeling synchronized G1 cells for autoradiography. When such cells are fixed with formaldehyde, the nuclei of the G1 cells are labeled. However, acid fixation removes the label.
Metabolic Imaging as a Biomarker of Early Radiation Response in Tumors
Authors: Stephen Y. Lai, C. David Fuller, Pratip K. Bhattacharya, Steven J. Frank
Journal: Clinical Cancer Research (2015)

(13)C-pyruvate hyperpolarized magnetic resonance imaging (HP-MRI) is emerging as a viable quantitative biomarker for solid tumor response and normal tissue toxicity after radiotherapy. This technology effectively predicts response related to metabolic agents or alterations in the tumor microenvironment, but challenges remain to be addressed to ensure successful translational implementation. See related article by Saito et al., p. 5073.
Adrenocortical carcinoma: The University of Texas M. D. Anderson Cancer Center experience update.
Authors: S. Ejaz, S. Jamal, N. Busaidy, C. Jimenez, R. Vassilopoulou-Sellin, M. A. Habra
Journal: Journal of Clinical Oncology (2010)

e15075 Background: Adrenocortical carcinoma is a rare aggressive malignancy. Advances in treatment and supportive care improved the outcome in patients with cancer including patients with adrenocortical carcinoma. In the past decade, there have been efforts to improve the outcome of these patients through molecular profiling to identify potential therapeutic targets. This move resulted in ongoing clinical trials to explore the efficacy of new therapeutic agents. Methods: Retrospective analysis of the clinical outcomes of patients with adrenocortical carcinoma registered at the University of Texas M. D. Anderson Cancer Center from 1998-2009 and comparison with earlier reports from our institution. Institutional review board approval was granted for this review. We summarized the patients' characteristics, survival curves, and changes in clinical management of patients seen at our institution in the past 12 years. We also reviewed treatment regimens utilized in these patients. Results: At the University of Texas M. D. Anderson Cancer Center, 287 patients have registered with adrenocortical carcinoma compared with 139 patients who were seen from 1980-1997 and reported in an earlier series. The increase in number of patients is attributed to changes in referral pattern, increased identification through increasing use of cross sectional imaging; or possibly a true increased in incidence. The 5-year survival rate was 50% (Kaplan-Meier analysis) in this series compared with 60% in the 1980-1997 series. There has been a progressive increase in the use of positron emission tomography for staging and treatment planning. Compared to earlier report, more patients were enrolled in research protocols mostly using targeted therapy in phase I trials. Detailed data about treatment will be presented in the full report. Conclusions: Adrenocortical carcinoma is a rare malignancy with high mortality rate. The recent use of targeted therapy and advanced surveillance methods have not translated yet into a major breakthrough in the management of these patients. Further concerted efforts are needed to prospectively evaluate and treat these patients through research based programs. No significant financial relationships to disclose.
Pharmacology and phase I/II study of continuous intravenous infusions of iododeoxyuridine and hyperfractionated radiotherapy in patients with glioblastoma multiforme.
Authors: T J Kinsella, J Collins, J Rowland, R Klecker, D Wright, D Katz, S M Steinberg, E Glastein
Journal: Journal of Clinical Oncology (1988)

Forty-seven adult patients with glioblastoma multiforme (GBM) were treated in a phase I/II study combining continuous intravenous (IV) infusions of iododeoxyuridine (IdUrd) and hyperfractionated radiation therapy. IdUrd was administered as a continuous infusion (24 h/d) for two separate 14-day infusion periods. The dose of IdUrd was escalated from 500 to 1,200 mg/m2/d. The initial wide-field tumor volume was treated to 45 Gy at 1.5 Gy fractions twice daily over 3 weeks. Following a planned 2-week break, a reduced-field boost of 25 Gy was delivered using 1.25 Gy fractions twice daily over 2 weeks (total dose, 70 Gy over 9 weeks). The IdUrd infusion preceded both the wide-field and reduced-field irradiation by 1 week. All treatment was performed on an outpatient basis. Dose-limiting systemic toxicity to the bone marrow (primarily thrombocytopenia) and gastrointestinal (GI) tract (both stomatitis and diarrhea) established the maximum tolerable dose (MTD) at 1,000 mg/m2/d for a 14-day infusion. Significant local toxicity (within the radiation field) was not seen. The kinetics of IdUrd were linear with dose escalation and reached steady-state plasma concentrations of 1.3 to 3.4 mumol/L. The total body clearance of IdUrd was .82 L/min/m2. The primary metabolite, 5-iodouracil (IUra) approached steady state by day 6 of the infusion when plasma levels were 60 times higher than IdUrd. Plasma levels of uracil and thymine, but not thymidine, were elevated throughout the infusion. With a minimum follow-up of 1 year, ten patients remain alive, while 33 patients died of progressive disease, and four patients died of other causes (including one treatment-related death). The median survival for all 47 patient and for the 40 patients receiving the MTD was 45 and 47 weeks, respectively, with 12% and 14% survivals at 24 months. Using a Cox regression analysis, age (less than or equal to 50 years v greater than 50 years) and pretreatment performance status (PS) (Eastern Cooperative Oncology Group [ECOG]-PS 0 to 1 v PS 2 to 3) were independent, statistically significant (P2 less than .05) predictors of survival, with the ECOG status being a better predictor. Patients with a PS 0 to 1 (28 patients) had a median survival of 64 weeks with 21% survival at 24 months, compared with a median survival of 29 weeks and 0% survival at 12 months in the 19 patients with PS 2 to 3. The overall and subgroup survival data are at least comparable to other combined modality treatment approaches in patients with GBM.
To analyze the efficacy, tolerability, toxicity profile, quality of life and pharmaco-economics of adjuvant TAC compared to FAC regimen in hormone receptor-positive breast cancer with more than four involved lymph nodes
Authors: U. Batra, P. P. Bapsy, K. V. Saini, A. K. Jain, A. V. Atilli, D. Lokanatha, K. S. Babu, K. S. Sanjeevan, C. J. Devaraju, G. Anupama
Journal: Journal of Clinical Oncology (2007)

11043 Aim: To analyze the efficacy, tolerability, toxicity profile, quality of life, survival rates and pharmaco-economics of TAC vs. FAC in women with ER/PR positive breast cancer and &gt;4 involved lymph nodes. Methods: 100 patients with &gt;4 node-positive breast cancer were randomly assigned to receive either 6 cycles of taxane-based (TAC) or anthracycline-based (FAC) adjuvant chemotherapy. All the patients received adjuvant radiotherapy and hormonal therapy after completion of chemotherapy. The primary end point was to assess disease-free survival (2 years), toxicity profile, QOL and to analyze the pharmaco-economics of both therapies. All patients completed EORTC QLQ 30, BR 23 questionnaire before randomization and before every cycle of chemotherapy. Pharmaco-economic feasibility was determined using cost of drugs, duration of hospital stay, laboratory investigations, management of complications and loss of wages. Treatment: The treatment (dose in mg/m 2 ) was as follows: TAC: docetaxel 75, doxorubicin 50, cyclophosphamide 500; CAF: 5 flourouracil 500, doxorubicin 50, cyclophosphamide 500. Results: The patient demographics and primary tumor characteristics were comparable in both the arms. Taxane- based regimen was associated with decreased global QOL and physical function. The cost of TAC regimen was 25 times more than FAC regimen. Conclusion: Although TAC regimen had longer DFS as compared to FAC, it was associated with a higher incidence of side effects and increased duration of hospital stay. Further, high cost precludes its wide-spread use, and FAC regimen still continues to be the first choice treatment of high-risk node and receptor-positive breast cancer in a third world country like India. [Table: see text] No significant financial relationships to disclose.
Prevalence of metabolic syndrome (MS) in a population of apneic patients:A prospective study with cardiovascular risk estimation
Authors: Rahma Ben Jazia, Halima Ben Salem, Imen Gargouri, Sana Aissa, Abdelhamid Garrouche, Abdelaziz Hayouni, Mohamed Benzarti, Mohamed Boussarsar, Ahmed Abdelghani
Journal: European Respiratory Journal (2014)

Background. Obstructive sleep apnea (OSA) is a highly prevalent condition. Literature has suggested the independent contribution of OSA in the pathogenesis of metabolic disturbances. Metabolic syndrome (MS), a cardiovascular risk, was frequently associated with OSA.

Aims and Objectives .

Evaluate the prevalence of MS in a sample of OSA patients.

Identify risk factors independently associated with the presence of MS in patients with OSA.

Assess compared cardiovascular risks according to the presence of MS by validated scores to demonstrate the impact of MS in these patients.

Methods. Prospective study. Were included patients referred to the Pulmonology department for suspected OSA confirmed by respiratory polygraphy. All parameters needed to define the MS were collected. MS was defined according to the IDF 2005. Assessment of cardiovascular risk related to MS was performed by validated scores.

Results. We recruited 50 patients with OSA. They were 53.9±11.7yr aged; 38%, males ; BMI,38.3±5.7Kg/m²; waist circumference, 117.38±12.27cm. Sixty eight per cent had comorbidities.The AHIwas49±21/h. In our study sample, the prevalence of MS demonstrated high, 60%. Logistic regression analysis identifiedBMI and AHI as only factors independently associated with MS in OSA patients. The study of scores, D'Agostino and SCORE, (respectively 21.52±17.4 (>20) and 5.54±3.49 (<5)) showed no significant difference between OSA/SM+ and OSA/SM- subgroups.

Conclusion. This study demonstrate a high prevalence of MS, it would be associated with the most obese patients and severe OSA. Cardiovascular risk scores used, seem here inappropriate for the assessment of MS-releated cardiovascular risk.
Long-term glycemic control using polymer-encapsulated human stem cell–derived beta cells in immune-competent mice
Authors: Arturo J Vegas, Omid Veiseh, Mads Gürtler, Jeffrey R Millman, Felicia W Pagliuca, Andrew R Bader, Joshua C Doloff, Jie Li, Michael Chen, Karsten Olejnik, Hok Hei Tam, Siddharth Jhunjhunwala, Erin Langan, Stephanie Aresta-Dasilva, Srujan Gandham, James J McGarrigle, Matthew A Bochenek, Jennifer Hollister-Lock, Jose Oberholzer, Dale L Greiner, Gordon C Weir, Douglas A Melton, Robert Langer, Daniel G Anderson
Journal: Nature Medicine (2016)
Intermedin1–53 attenuates vascular calcification in rats with chronic kidney disease by upregulation of α-Klotho
Authors: Jin Rui Chang, Jun Guo, Yue Wang, Yue Long Hou, Wei Wei Lu, Jin Sheng Zhang, Yan Rong Yu, Ming Jiang Xu, Xiu Ying Liu, Xiu Jie Wang, You Fei Guan, Yi Zhu, Jie Du, Chao Shu Tang, Yong Fen Qi
Journal: Kidney International (2016)
Considerations for Epidemiologic Studies To Test the Hypothesis of Viral Causation of Human Breast Cancer&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: K V Shah, F B Bang, H Abbey
Journal: JNCI Journal of the National Cancer Institute (1972)

Epidemiologic studies, designed to determine if there is a correlation between the presence of type-B particles in milk and a high incidence of breast cancer, would be most meaningful if they were done uniformly in several populations selected to cover a wide range of breast cancer incidence, e.g., Parsi and U.S. white women For high-incidence and Hindu and Japanese women for low-incidence populations; and if frequencies and numbers of B particles in milk were compared in high-risk and control women in the same population. A history of breast cancer in a close blood relative may identify the high-risk woman in each of these populations, although the evidence for a familial aggregation of breast cancer is not unequivocal. Each lactating high-risk woman (with a family history of breast cancer) should be paired with one without such a history but matching with respect to other characteristics which influence breast cancer risk, e.g., ethnic group and religion, age, parity, and socioeconomic status. If the prevalence or numbers of B particles in the milk of high-risk women were higher as compared to that in control women in each population studied, such a finding would strengthen the hypothesis of B-type virus etiology. Much more definitive information would be obtained if normal lactating women were first studied for B particles in their milk and then followed for the occurrence of breast cancer.
iGenomicViewer, a Gynecologic Oncology Group software library for the creation of highly customizable, portable, interactive, and linked visualizations of high throughput genomic data
Authors: D. P. Gaile, L. Shepherd, S. Liu, K. Darcy, M. Brady, C. Morrison
Journal: Journal of Clinical Oncology (2009)

e16544 Background: An R software library was created with the goal of creating customizable, platform independent, and portable visualization tools for the annotation, dissemination and interrogation of high dimensioned genomic data. Methods: A set of R functions were created to extend the functionality of the sendplot R library. The functions were applied to BAC aCGH data generated for several GOG studies. Results: The iGenomicViewer function calls created and populated a directory structure which was then ported to a password protected server for interrogation by research team members. The linked html and image output allows users to examine genome wide plots of aberration frequencies and p-values and then drill down to visualizations of regions of interest. Users can interrogate a panel of plots which includes: 1) a heat map of the aCGH data for with tool-tip display of sample and assay specific data (e.g., assay values, sample IDs, and hyperlinks to UCSC browser and sample specific images); 2) a set of interactive annotation tracks which display location of cancer, disease and DNA repair genes; and 3) a plot which displays -log10 p-values and/or aberration frequencies for the BAC assays depicted in the heatmap. For the smallest regions of interest, the panel of plots contains a tiled heatmap which depicts the overlap and gaps in BAC coverage and their alignment with the gene locations represented in the adjacent annotation track. Conclusions: The iGenomicViewer library provides open source software for creation of customizable visualization tools for collaborative research projects involving high dimensioned genomic data. No significant financial relationships to disclose.
Adjuvant chemotherapy for muscle invasive bladder cancer: A systematic review and meta-analysis
Authors: M. R. S. Cruz, E. Sasse, A. Sasse, L. Clark, O. Clark
Journal: Journal of Clinical Oncology (2005)

4733 Background: Some studies have evaluated the role of adjuvant chemotherapy (CT) for muscle-invasive bladder cancer (BC), with conflicting results. In order to offer the totality of evidence available for clinical decision, we performed a systematic review and meta-analysis of randomized controlled trials (RCT) that compared surgery versus surgery plus adjuvant CT in the treatment of muscle-invasive BC. Methods: The main electronic databases (CENTRAL Cochrane, MEDLINE, LILACS) were scanned. We also searched trials register databases and hand searched meeting proceedings (ASCO, ESMO). The objective of this study was to investigate whether CT administered after surgery improves the survival and reduces recurrence rates of patients with muscle invasive BC. The data extracted from individual studies were pooled in a meta-analysis and the results are expressed as Peto’s Odds Ratio (OR) and the correspondent 95% confidence interval (95% CI). Heterogeneity was calculated according to the I index, based on the chi-square statistics. Subgroup analysis according to prognostic and methodological features was also performed. Results: Of 140 reports identified in the search, four trials with 272 participants (CT arm= 134; observation arm= 138) meet the inclusion criteria. A meta-analysis of four trials revealed that adjuvant CT was effective in reducing the recurrence rate (OR= 0.40; 95% CI 0.24 to 0.66) without evidence of heterogeneity (I2=57,9%). The difference in overall survival rate for adjuvant CT was not significant (OR=0.70; 95% CI 0.41 to 1.20) and no significant difference in treatment-related mortality was observed. Subgroup analysis according to node status was also performed: node positive patients had recurrence rate reduction (OR= 0,28; 95% CI 0.10 to 0.82); node negative patients had a similar recurrence rate reduction (OR=0.32; 95% CI 0.11 to 0.88). Conclusions: Adjuvant chemotherapy for muscle-invasive bladder cancer improves disease free survival, but has no effect on overall survival. Future RCTs should focus on long term follow up and determination of the ideal scheme of adjuvant chemotherapy in order to evaluate its real role in patients with bladder cancer. No significant financial relationships to disclose.
Prognostic Significance of Magnetic Resonance Imaging of Femoral Marrow in Patients With Myelodysplastic Syndromes
Authors: Shojiro Takagi, Osamu Tanaka, Hideki Origasa, Yasusada Miura
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To investigate whether the abnormalities observed on femoral marrow magnetic resonance images are related to the development of leukemia and survival of patients with myelodysplastic syndromes (MDS). PATIENTS AND METHODS: The findings on magnetic resonance images of the femoral marrow were evaluated over periods of 1 to 92 months (median, 18 months) in 42 consecutive adult patients with newly diagnosed MDS. Magnetic resonance images were obtained by the T1-weighted spin echo method and the short TI inversion recovery technique. RESULTS: Magnetic resonance images showed that the femoral marrow patterns changed from fatty, faint, or nodular to scattered or uniform as the disease progressed. Development of acute myeloid leukemia was observed in only 13 patients whose marrow exhibited a scattered or uniform pattern. The overall survival of the 29 patients with a scattered or uniform marrow pattern was significantly shorter than that of the 13 patients with a fatty, faint, or nodular marrow pattern (10.7% v 73.3% at 7 years; P &lt; .01). The period of leukemia-free survival was also significantly shorter in the patients with a scattered or uniform marrow pattern versus a fatty, faint, or nodular pattern (37.7% v 100% at 7 years; P &lt; .01). CONCLUSION: Magnetic resonance images of the femoral marrow can provide valuable information for assessing the prognosis and determining the most appropriate management of patients with MDS.
A Breakthrough: Macrophage-Directed Cancer Immunotherapy
Authors: Charles D. Mills, Laurel L. Lenz, Robert A. Harris
Journal: Cancer Research (2016)

Abstract Successful immunotherapy of cancer is becoming a reality aided by the realization that macrophages play an important role in the growth or regression of tumors. Specifically, M2/repair-type macrophages predominate in human cancers and produce growth-promoting molecules that actively stimulate tumor growth in much the same way they help wounds heal. However, modulating M2/repair-type macrophages to M1/kill-type can slow or stop cancer growth. The effects involve direct activity of M1 kill-type as well as the ability of M1-type macrophages to stimulate Th1-type cytotoxic T cells and other effector cells. Macrophage responses can also predict cancer susceptibility; individuals with a high M1/kill to M2/repair ratio are less prone. That macrophages/innate immunity can be modulated to play a central role in directly or indirectly combating cancer is a breakthrough that seems likely to finally make successful immunotherapy of cancer a reality. Cancer Res; 76(3); 513–6. ©2016 AACR.