tbuckley/cabot-search huggingface dataset:
Cell kinetic-based scheduling of chemotherapy: hypothesis versus reality.
Authors: F A Hayes
Journal: Journal of Clinical Oncology (1987)

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.1987.5.11.1713 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3681366 Cell kinetic-based scheduling of chemotherapy: hypothesis versus reality. F A HayesxF A HayesSearch for articles by this author https://doi.org/10.1200/JCO.1987.5.11.1713 PDF "Cell kinetic-based scheduling of chemotherapy: hypothesis versus reality.." Journal of Clinical Oncology, 5(11), p. 1713© 1987 by American Society of Clinical Oncology
Electronic self-report assessment for cancer (ESRA-C): Results of a randomized clinical trial
Authors: D. L. Berry, B. Halpenny, J. Fann, N. Bush, W. Lober, S. Wolpin, B. T. Karras, M. Austin-Seymour, R. McCorkle
Journal: Journal of Clinical Oncology (2008)

9519 Background: Assessment of common cancer symptoms and quality of life (QOL) during therapy, notably psychosocial concerns, is known to be incomplete at times. Electronic self-report methods for patients are now available, yet evidence that such methods improve patient/clinician communication is lacking. A confidential, electronic self-report method for patients to report symptoms and concerns, ESRA-C, has been created and we report on a randomized clinical trial (RCT) of its effectiveness. Methods: A RCT was conducted at two urban cancer care institutions in adult patients with all types and stages of cancer. Participants completed two assessments, about 6 weeks apart, one prior to treatment and one during treatment, containing validated symptom and QOL measures on touch-screen computers. A graphical, color summary of participant responses was given to clinicians who assessed intervention group patients, versus no summary in the control group. Same-day clinic visits were audio-recorded and then coded by those blind to study group for frequency of symptom/QOL assessment. Generalized estimating equations (GEE) and logistic regression modeled the odds of discussion of 27 symptom and QOL concerns by study arm. Results: 590 participants (294 control & 296 intervention) were assessed by 76 clinicians. The null hypothesis that study arm had no effect was rejected, p=.024. Across all services, topics significantly more likely to be discussed when the ESRA-C summary was provided were: impact of cancer on sexual activities/interest (OR=2.90; CI=1.37–6.16) and perception of change in emotional function (OR=1.73; CI=1.08–2.77). In radiation oncology visits, the odds of discussing appetite were significantly higher (OR=2.51; CI 1.23–5.13) and patient concerns about physical appearance were discussed less often (OR=0.15; CI=0.03–0.68) in transplant when ESRA-C was available. Conclusions: The ESRA-C is the first clinical self-report assessment to be tested in an RCT with directly measured communication outcomes in three cancer care services. In the clinical intervention group, electronic screening and graphical reporting of cancer symptoms and QOL concerns via the ESRA-C summary had a significant, positive effect on communication about patients’ experiences. No significant financial relationships to disclose.
Compliance issues in completion of patient-reported outcomes in a series of NCCTG/Mayo clinical trials
Authors: K. Burger, P. J. Atherton, P. L. Schaefer, M. Y. Halyard, J. A. Sloan
Journal: Journal of Clinical Oncology (2008)

17506 Background: The use of Patient Reported Outcomes (PROs) as measures of primary and secondary endpoints in clinical trials has increased, thus study results rely on patient compliance. This study identifies compliance issues with the purpose of providing clinicians knowledge with which to base monitoring techniques. Methods: Data was compiled from 17 North Central Cancer Treatment Group (NCCTG), 3 Mayo Clinic Cancer Center (MCCC) and 2 Mayo Clinic Cancer Research Consortium (MCCRC) clinical trials where patient compliance in completing PROs was documented. Summary statistics were compiled for non-compliance reasons and appropriate chi- square testing was performed to identify patient characteristics affecting compliance. Results: 85%of 2366 patients provided complete data with no compliance issues. Three trials had 54% of all of the non-compliance instances related to unique protocol characteristics. Of the remaining studies, the non-compliance rate ranged from 1% to 8%. Reasons for non-compliance were patient driven, protocol mandated, or staff driven. Patient reasons for non-compliance included failure to return completed PRO booklet (31%), booklet misplaced (6%), death (2%), not following completion directions (1%) or inavailability to complete the PRO booklet(6%). 7% of PROs were not completed due to protocol treatment issues. PROs not completed due to personnel issues were because staff didn’t give patient the PRO booklet (27%) or staff oversight (6%) or staff unavailable (1%). Patient demographics indicate that more females than males refused to complete PROs and older patients were more likely to not be offered PROs by staff members. Race and country were not indicative of non- compliance reasons. Conclusions: Compliance with PRO completion was remarkedly high in this series of trials. Staff commitment and education regarding PRO completion are vital to successful collection of data. Existing tracking systems used for the other trial outcomes are sufficient to ensure successful compliance with PRO outcomes. No significant financial relationships to disclose.
한국인 윌슨병 유전자의 일배체형 분석과 R778L 돌연변이에서 창시자효과에 대한 연구
Authors: 배선환, 김종원, 서정기
Journal: Clinical and Molecular Hepatology (2009)

배경/목적: 윌슨병은 ATP7B 유전자의 돌연변이에 의하여 구리대사에 이상이 발생하는 상염색체열성 질환이다. 윌슨병 유전자의 돌연변이가 300여종이 넘고, 인종별, 지역별 차이가 뚜렷하여, 한국인 윌슨병 유전자 연구는 중요성을 갖는다. 본 연구는 한국인 윌슨병 환자에서 빈발하는 돌연변이를 확인하고, 처음으로 한국인 윌슨병 유전자의 일배체형(haplotype)을 분석하며, 나아가 한국인 윌슨병 유전자에 창시자효과(founder effect)가 존재하는지를 확인하고자 시행되었다. 대상과 방법: 21명의 윌슨병 환아와 환아의 부모 42명, 총 63명을 대상으로 혈액을 채취하여 중합효소연쇄반응(PCR, polymerase chain reaction)을 시행한 후, 직접 염기서열분석방법(direct sequencing method)을 사용하여 돌연변이를 분석하였으며, 발광체가 붙여진 시발체를 사용하여 D13S315, D13S1325 및 D13S316 초위성체(microsatellies)에 대한 분석을 시행하였다. 윌슨병 유전자에 존재하는 창시자효과를 확인하기 위하여, 부모의 정상 DNA 42개를 대조군으로 이용하였다. 연쇄비평형(linkage disequilibrium)을 확인하기 위한 통계적 분석은 Chi-square검사를 이용하였으며, 일배체형 사이의 빈도를 비교한 통계적 분석은 Fisher`s Exact검사를 이용하였고, P 값이 0.05 미만일 때 통계적으로 유의하다고 정의하였다. 결과: 21명의 윌슨병 환아에서 모두 23개의 돌연변이가 발견되었으며, 8번 exon에 존재하는 R778L 돌연변이가 15개(65.2%), 11번 exon에 존재하는 A874V 돌연변이가 6개(26.1%), 18번 exon에 존재하는 N1270S 돌연변이가 2개(8.7%)의 DNA에서 발견되었다. R778L 돌연변이군을 대상으로 초위성체를 분석하였을 때, D13S315좌의 5번 대립유전자의 빈도가 대조군에 비해 통계적으로 유의한 차이를 보여(10/15 대 11/41, P=0.0157) 연쇄비평형을 나타내었으며, D13-S316좌의 4번 대립유전자 또한 대조군에 비해 유의한 차이를 보여(12/15 대 7/42, P=0.0001) 연쇄비평형을 나타내었다. 돌연변이 분석과 초위성체 분석결과를 바탕으로 한국인 윌슨병 유전자의 일배체형을 구성한 결과, 가장 빈발하는 일배체형은 5-3-R778L-4(D13S315-D13S1325-돌연변이-D13S316)로, 대조군과 비교하여 통계적으로 유의한 빈도차를 보였다(P=0.0213). 통계적 의미가 없는 것으로 나타난 D13S1325를 배제하고 구성한 5-R778L-4(D13S315-Mutation-D13S316) 일배체형의 빈도는 대조군과 비교하여 더욱 유의한 차이를 나타내었다(P=0.0018). 결론: D13S315-R778L-13S316(5-돌연변이-4) 일배체형이 한국인 윌슨병 유전자의 원시 일배체형(arche haplotype)으로 추정되며, 한국인 윌슨병은 R778L 돌연변이에 창시자효과가 존재하는 것으로 생각된다.
Intersalt data
Authors: J. Le Fanu, M. Alderman, A. Macnair, N E Day, G. D. Smith, A. N Phillips, G. Watt, J. T. Hart, K. Rennolls, P. Elliott, J. Stamler, A. R Dyer, R. Stamler, H. Kesteloot, M. Marmot, R. H Grimm, B. F Liebman, M. F Jacobson
Journal: BMJ (1997)

Collaborative efforts must be made to reduce sodium in diet
Chemotherapy could make breast cancer patients more vulnerable to common infections
Authors: Jacqui Wise
Journal: BMJ (2016)

Patients with breast cancer who are treated with chemotherapy have depleted immune systems, leaving them vulnerable to common infections, researchers have warned in the journal Breast Cancer Research .1 They said that revaccination against common immunogens may need to be considered in some cases.

Researchers from the University of Leeds measured the levels of lymphocytes and antibodies in 88 women with breast cancer, before chemotherapy and at intervals for nine months after completing chemotherapy. No …
Abstract 3705: Pioglitazone Augments Niacin-Induced Increases in Adiponectin in Non-Diabetics with Metabolic Syndrome and Low HDL
Authors: Richard L Dunbar, Ramprasad Gadi, LeAnne T Bloedon, Sushma Ramprasad, Megan Wolfe, Amanda Baer, Daniel J Rader, Frederick F Samaha
Journal: Circulation (2008)

Background Niacin and pioglitazone (PIO) increase HDL by uncertain mechanisms. Both increase adiponectin, whose effects on carbohydrate and fatty acid metabolism may benefit HDL indirectly. Little is known of the combined effects of the drugs on adiponectin and other adipokines. We hypothesized that PIO would complement changes in adipokines from niacin, and in turn, augment HDL. Methods In an open-label run-in, non-diabetics with low HDL titrated from 0 to 2 g extended-release niacin over 4 weeks, and were randomized to add PIO 30 mg or placebo in a double-blind manner. After 6 weeks, PIO was increased to 45 mg for another 6 weeks. We assessed changes in fasting adiponectin, resistin, complement C3 (the serum-detectable precursor of acylation stimulating protein), free fatty acids (FFA), hydroxy-butyrate (HBA), and triglycerides (TG), and their relationship to changes in HDL. Results Of 72 completers, 34 took niacin and placebo and 38 took niacin and PIO. The table shows absolute and relative change of each analyte from baseline to 16 weeks. Relative change in adiponectin was strongly correlated with change in HDL (Spearman’s rho +0.49, p&lt;0.0001), as was change in TG (rho −0.50, p&lt;0.0001); the other analytes had little influence. On multivariable regression, change in HDL was predicted by change in adiponectin (p=0.0001) and TG (p&lt;0.0001), which remained significant on adjustment for changes in glucose and insulin. Conclusion Pioglitazone augments niacin-induced changes in adiponectin and complement C3 thought to be favorable, and neutralizes niacin’s unfavorable increase in FFA. Adiponectin strongly predicted HDL after adjustment for TG. Since PIO had no independent effect on TG, we speculate that additional HDL-raising from PIO is mediated by the large increase in adiponectin. In summary, PIO enhances HDL-raising from niacin in proportion to increased adiponectin.
The use of adjuvant chemotherapy in the ATAC trial: Nationality correlates with the use of chemotherapy
Authors: R. Sainsbury, G. Locker, J. Cuzick
Journal: Journal of Clinical Oncology (2004)

597 Background: The ATAC trial in 1996–2000, randomized 9366 postmenopausal women, from 21 countries, with early stage breast cancer, to adjuvant therapy with anastrozole, tamoxifen or the combination after primary surgery +/- radiotherapy +/- chemotherapy. Although there was an equal distribution of prognostic and therapeutic factors across treatment arms, there were marked differences in the use of adjuvant chemotherapy between participating countries (2–65%). Methods: A retrospective analysis was done looking for features which predicted for receiving chemotherapy in addition to the protocol-determined hormonal therapy to see if national differences could be explained. Results: In a univariate analysis (p<.05) node positivity (particularly>4), tumor size>2 cm, poorly differentiated tumors, ER negative receptor status, and use of mastectomy predicted for receiving chemotherapy. Older age predicted for not receiving chemo. Using the United States (n=2222, 33% chemotherapy rate) as a standard, in a multivariate analysis including all potential predictive factors, nationality remained predictive for the use of chemotherapy. All countries except three had a significantly (p<.05) lower usage of chemotherapy than the US. Three groups were identified: those with a with an odds ratio of less than 0.1 versus the US (8 of 21 nations including the United Kingdom & Germany, adjusted chemo usage rate <5%) those with an odds ratio of 0.1- 0.5 (n=9 including France, Canada, Sweden, adjusted chemo rate 5–19%), those with an odds ratio similar to or greater than that of the US (Portugal, Italy and Spain, adjusted chemo rate 23–41%). Conclusions: In a retrospective analysis of a selected patient population, enrollees in ATAC, nationality was a statistically significant independent predictor for the use of adjuvant chemotherapy. Chemotherapy usage in the US was among the highest of any nation participating in ATAC. We thank Chris Wale for statistical support No significant financial relationships to disclose.
Exploratory data analysis and the use of the hazard function for interpreting survival data: an investigator's primer.
Authors: R J Simes, M Zelen
Journal: Journal of Clinical Oncology (1985)

This report discusses how one can use the hazard function to gain important insights on the patterns of failure in clinical studies when the principal endpoint is a time metric. These new insights may help gain increased understanding into the pathogenesis of a chronic disease and how it is affected by treatment intervention. The qualitative behavior of the hazard function can reveal whether mortality is increasing, decreasing, or is constant over time. Simple graphic plots are all that is necessary to show characteristic failure patterns. These informal procedures are in the spirit of carrying out exploratory analyses on the data. This report discusses the organization of clinical data using a "branch and leaf" plot, outlines the calculation of the hazard function and life table, and uses examples from lung cancer and uveal melanoma to illustrate calculations and ways of interpreting hazard functions.
Toll-like Receptor 7 Is Reduced in Severe Asthma and Linked to an Altered MicroRNA Profile
Authors: Hitasha Rupani, Rocio T. Martinez-Nunez, Patrick Dennison, Laurie C. K. Lau, Nivenka Jayasekera, Tom Havelock, Ana S. Francisco-Garcia, Christopher Grainge, Peter H. Howarth, Tilman Sanchez-Elsner
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Asthma is one of the most common chronic diseases worldwide, and individuals with severe asthma experience recurrent exacerbations. Exacerbations are predominantly viral associated and have been linked to defective airway IFN responses. Ascertaining the molecular mechanisms underlying this deficiency is a major research goal to identify new therapeutic targets.We investigated the hypothesis that reduced Toll-like receptor 7 (TLR7)-derived signaling drove the impaired IFN responses to rhinovirus by asthmatic alveolar macrophages (AMs); the molecular mechanisms underlying this deficiency were explored.AMs were recovered from bronchoalveolar lavage from healthy subjects and patients with severe asthma. Expression of pattern-recognition receptors and microRNAs was evaluated by quantitative polymerase chain reaction and Western blotting. A TLR7-luciferase reporter construct was created to evaluate binding of microRNAs to the 3' untranslated region of TLR7. IFN production was measured by quantitative polymerase chain reaction and ELISA.The expression of TLR7 was significantly reduced in severe asthma AMs and was associated with reduced rhinovirus and imiquimod-induced IFN responses by these cells compared with healthy AMs. Severe asthma AMs also expressed increased levels of three microRNAs, which we showed were able to directly reduce TLR7 expression. Ex vivo knockdown of these microRNAs restored TLR7 expression with concomitant augmentation of virus-induced IFN production.In severe asthma, TLR7 deficiency drives impaired innate immune responses to virus by AMs. Blocking a group of microRNAs that are up-regulated in these cells can restore antiviral innate responses, providing a novel approach for therapy in asthma.
A phase I study of the chimeric monoclonal anti-epidermal growth factor receptor (EGFR) antibody cetuximab as a single agent in subjects from Japan with advanced solid tumors: Safety, pharmacokinetics (PK)
Authors: H. Yasui, K. Shirao, N. Yamamoto, Y. Shimada, Y. Yamada, K. Muro, T. Hamaguchi, N. Boku, T. Yoshino, N. Saijo
Journal: Journal of Clinical Oncology (2005)

3209 Background: Cetuximab is a monoclonal antibody that selectively binds to the Epidermal Growth Factor Receptor (EGFR). Cetuximab as a single agent is effective in patients with colorectal cancer refractory to irinotecan and oxaliplatin (Lenz ASCO 2004). This phase I study assessed the safety and PK profile of cetuximab as a single agent in Japanese patients with solid tumors. Methods: Monotherapy with cetuximab was examined across a 100–500mg/m2 dose range. Thirty patients with chemotherapy refractory, EGFR -expressing solid tumors were enrolled in cohorts of five to receive weekly IV infusions of 100 mg/m2 cetuximab following an initial dose of 100mg/m2 (cohort 1), or weekly IV infusions of 250mg/m2 following initial doses of 250 (cohort 2), 400 (cohort 3) or 500 mg/m2 (cohort 4). To investigate the PK profile, cetuximab infusion was skipped on day 8 in the 1st to 4th cohort. Following an initial dose of 400mg/m2, cetuximab was administered weekly IV infusion of 250mg/m2 in the last cohort (cohort 5). Blood samples for PK analysis were collected for up to eight weeks after the initial dose. Results: Thirty pts were enrolled in total (CRC 29 pts, NSCLC 1 pt), median age 54 (range: 37-73) with a median of 3 prior chemotherapy regimens (range: 1–5). Twenty-four pts (up to cohort 4) were evaluable, and no DLT has been observed to date. The most frequent adverse events were rash (71%), acne (58%), anorexia (50%), diarrhea (46%), fatigue (46%) and fever (38%), which were of Grade 1–2 in severity. The preliminary PK results in the first cohort were virtually identical to those observed in Caucasians. In preliminary efficacy results of 18 evaluable pts, 2 CRC pts had PR, 10 pts SD. Conclusions: Preliminary results suggest that Cetuximab is well tolerated as a single agent in Japanese patients with solid tumors at the cohort 1–4. An updated analysis will be provided. No significant financial relationships to disclose.
Alternating versus hybrid MOPP and ABVD combinations in advanced Hodgkin's disease: ten-year results.
Authors: S Viviani, G Bonadonna, A Santoro, V Bonfante, M Zanini, L Devizzi, F Soncini, P Valagussa
Journal: Journal of Clinical Oncology (1996)

PURPOSE To compare, in a prospective randomized trial, the efficacy of two different sequences of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy in untreated advanced Hodgkin's disease. PATIENTS AND METHODS From June 1982 to September 1990, 427 consecutive previously untreated patients with pathologic stage IB, IIA bulky, IIB, III (A and B), and IV (A and B) disease were prospectively randomized to receive two different sequences of MOPP and ABVD for a minimum of six cycles followed by radiotherapy (median dose, 30 Gy) to the nodal site(s) of pretreatment bulky disease. Of 415 assessable patients, 211 received one cycle of MOPP monthly, alternated with one cycle of ABVD (alternating regimen), and 204 patients received one-half cycle of MOPP alternated with one-half cycle of ABVD within a 1-month period (hybrid regimen). RESULTS The complete remission (CR) rate was 91% with the alternating regimen and 89% with the hybrid regimen. At 10 years, the freedom-from-progression (FFP) rate was 67% versus 69% and the overall survival (OS) rate was 74% versus 72%, respectively. After attainment of CR, 85 patients relapsed in nodal (n = 60) versus extranodal with or without nodal (n = 25) sites. In patients given consolidative radiation because of bulky lymphoma, the true recurrence rate was 13%. A total of 23 second malignancies (6%) were documented, including 11 cases of acute nonlymphocytic leukemia. No cases of congestive heart failure attributable to doxorubicin or pulmonary toxicity related to bleomycin were documented. CONCLUSION By delivering MOPP and ABVD, it is possible to cure approximately 70% of patients with advanced Hodgkin's disease. The two different drug sequences yielded superimposable results.
Increased sputum inflammatory cell count of PMA subjects during luteal phase of the cycle
Authors: Szymon Skoczynski, Aleksandra Semik-Orzech, Ewa Sozanska, Wojciech Szanecki, Michal Majewski, Krzysztof Kolodziejczyk, Andrzej Witek, Wladyslaw Pierzchala
Journal: European Respiratory Journal (2013)

Background : Although up to 40% of asthmatic women report significant perimenstrual exacerbations of asthma (PMA), the actual triggers of this phenomenon and the influence of changes in hormone concentrations remain unclear.   Objective : The aim of the study was to assess the impact of changes in blood hormone concentrations on the markers of inflammation in lower airways of PMA subjects.   Method s: Premenopausal women with regular menstrual cycles diagnosed as: PMA (n= 10), non-PMA asthmatics (n=8), and healthy controls (n=5) were prospectively followed for 10 weeks over 2 consecutive menstrual cycles. Asthma symptoms, medicine use and peak expiratory flow twice daily were recorded. Sputum induction and blood progesterone, estradiol, prolactin, TSH and cortisole levels were determined in the 10th and 26th day of each of the two cycles. Differential cell counts in sputum were determined and concentration of eotaxin, IL-5 and IL-10 were measured by ELISA.   Results:  Increased prolactin serum concentrations in luteal (compared to follicular) phase were detected only in PMA patients (p=0,01), but not in non-PMA asthmatics and healthy controls. Compared to follicular phase, induced sputum of PMA patients obtained in luteal phase contained increased eosinophil (p=0,03) and neutrophil (p=0,04) counts. No follicular-to-luteal phase changes of induced sputum cytokine concentrations were observed in all patients.   Conclusions : The obtained results indicate for the first time the important role of prolactin in the development of PMA symptoms. The study also shows that mechanisms underlying PMA include increased eosinophil and neutrophil count in lower airways during late luteal phase of menstrual cycle.