tbuckley/cabot-search huggingface dataset:
Effect of Prenatal Supplementation With Vitamin D on Asthma or Recurrent Wheezing in Offspring by Age 3 Years
Authors: Augusto A. Litonjua, Vincent J. Carey, Nancy Laranjo, Benjamin J. Harshfield, Thomas F. McElrath, George T. O’Connor, Megan Sandel, Ronald E. Iverson, Aviva Lee-Paritz, Robert C. Strunk, Leonard B. Bacharier, George A. Macones, Robert S. Zeiger, Michael Schatz, Bruce W. Hollis, Eve Hornsby, Catherine Hawrylowicz, Ann Chen Wu, Scott T. Weiss
Journal: JAMA (2016)

<h3>Importance</h3> Asthma and wheezing begin early in life, and prenatal vitamin D deficiency has been variably associated with these disorders in offspring. <h3>Objective</h3> To determine whether prenatal vitamin D (cholecalciferol) supplementation can prevent asthma or recurrent wheeze in early childhood. <h3>Design, Setting, and Participants</h3> The Vitamin D Antenatal Asthma Reduction Trial was a randomized, double-blind, placebo-controlled trial conducted in 3 centers across the United States. Enrollment began in October 2009 and completed follow-up in January 2015. Eight hundred eighty-one pregnant women between the ages of 18 and 39 years at high risk of having children with asthma were randomized at 10 to 18 weeks' gestation. Five participants were deemed ineligible shortly after randomization and were discontinued. <h3>Interventions</h3> Four hundred forty women were randomized to receive daily 4000 IU vitamin D plus a prenatal vitamin containing 400 IU vitamin D, and 436 women were randomized to receive a placebo plus a prenatal vitamin containing 400 IU vitamin D. <h3>Main Outcomes and Measures</h3> Coprimary outcomes of (1) parental report of physician-diagnosed asthma or recurrent wheezing through 3 years of age and (2) third trimester maternal 25-hydroxyvitamin D levels. <h3>Results</h3> Eight hundred ten infants were born in the study, and 806 were included in the analyses for the 3-year outcomes. Two hundred eighteen children developed asthma or recurrent wheeze: 98 of 405 (24.3%; 95% CI, 18.7%-28.5%) in the 4400-IU group vs 120 of 401 (30.4%, 95% CI, 25.7%-73.1%) in the 400-IU group (hazard ratio, 0.8; 95% CI, 0.6-1.0;<i>P</i> = .051). Of the women in the 4400-IU group whose blood levels were checked, 289 (74.9%) had 25-hydroxyvitamin D levels of 30 ng/mL or higher by the third trimester of pregnancy compared with 133 of 391 (34.0%) in the 400-IU group (difference, 40.9%; 95% CI, 34.2%-47.5%,<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> In pregnant women at risk of having a child with asthma, supplementation with 4400 IU/d of vitamin D compared with 400 IU/d significantly increased vitamin D levels in the women. The incidence of asthma and recurrent wheezing in their children at age 3 years was lower by 6.1%, but this did not meet statistical significance; however, the study may have been underpowered. Longer follow-up of the children is ongoing to determine whether the difference is clinically important. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00920621
Measuring quality of life: Using quality of life measures in the clinical setting
Authors: I. J Higginson
Journal: BMJ (2001)

This is the second in a series of five articles 

In modern medicine the traditional way of assessing change in patients has been to focus on laboratory or clinical tests. At its most simple this involves measuring pulse, blood pressure, and temperature, and carrying out physical examinations. At more complex levels it may include haematological analysis, computed tomography, radiography, organ function tests, genetic analysis, and other investigations. While these give important information about the disease, especially about chronic and progressive diseases, it is impossible to separate disease from an individual's personal and social context. No illness exists in a vacuum.

One way of capturing the personal and social context of patients is to use quality of life measures.1 These are accepted as outcome measures in clinical research but are rarely used in routine clinical practice, despite the fact that Florence Nightingale was one of the first clinicians to insist on measuring the outcome of routine care to evaluate treatment.2 This article reviews the challenges of using quality of life measures in clinical practice including selecting appropriate measures, analysing data, providing feedback, interpreting results, and incorporating these measures into clinical decision making. Practical ways of resolving the tension between the need for approaches suitable in the clinical encounter and the highly individualised nature of quality of life are also examined.

#### Summary points

Using quality of life measures in clinical practice ensures that treatment and evaluations focus on the patient rather than the disease

The measures are potentially useful in both the clinical encounter and in quality improvement

They are not a substitute for measures of disease outcomes and may not always be the most appropriate patient centred outcome to assess

Measures developed for research often cannot easily be used in clinical practice

Measures that form an integral part of treatment planning …
Co-expression of steroid and HER2 receptors in breast carcinomas in a large (4,493 cases) population-based Polish study
Authors: W. T. Olszewski, A. Mrozkowiak, W. P. Olszewski, M. J. Krzakowski
Journal: Journal of Clinical Oncology (2005)

797 Background: In addition to well-established clinical prognostic and predictive factors (i.e. nodal status), the assessment of parameters such as oestrogen (ER), progesterone (PgR) and HER2 receptor status are needed to make an adequate diagnosis of breast cancer. The study reported here is part of a national HER2 screening project in Poland, which started in 2002 and is still ongoing. By April 2004, 11,557 cases of invasive breast carcinoma had been included. The aim of the study was to investigate the relationship between HER2 and ER/PgR status. Methods: The study was performed in 4,493 non-selected cases of breast cancer. The data originated from 14 oncology centres in Poland and were collected between April 2003 and March 2004. ER, PgR and HER2 receptor status were evaluated by immunohistochemistry (IHC). HER2 IHC results were classed by the DAKO criteria system as: 0, 1+, 2+ or 3+. The cases classed as 0, 1+ and 2+ were considered to have a negative HER2 status. The remaining cases (IHC 3+) were considered HER2 positive. Steroid receptor-positive cases were grouped by the presence of 10% or more positively stained cancer nuclei, regardless of the strength of the stain. A positive ER/PgR status was recorded when ER/PgR receptors were detected. A mixed group consisted of cases in which one steroid hormone was present. Results: The group described by IHC as 0, 1+ and 2+ showed the presence of at least one steroid receptor in more than two-thirds of all cases (71%, 80% and 79%, respectively). Among the tumours exhibiting HER2-receptor overexpression (IHC 3+), 52% were steroid-receptor positive. Conclusion: The results of this large population-based study indicate that there is a relationship between the expression of ER and PgR receptors and HER2 status. The probability of the existence of positive steroid receptor status in the clinically HER2-positive group (3+) was lower than in the clinically HER2-negative group (0, 1+, 2+). However, even so, more than half of the HER2-overexpressing patients were also steroid receptor positive. Taken together, these results emphasise the necessity of independent evaluation of both steroid receptors and HER2 status. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Polska Roche Polska Roche Polska
Schedule of bortezomib administration may be an important determinant of single-agent activity in patients with relapsed or refractory follicular (FL) lymphoma and mantle cell lymphoma (MCL)
Authors: O. O'Connor, P. Hamlin, C. Moskowitz, D. Straus, A. Noy, J. Wright, E. Neylon, B. MacGregor-Cortelli, C. Portlock, A. Zelenetz
Journal: Journal of Clinical Oncology (2007)

8051 Background: We previously demonstrated the significant activity of bortezomib for the treatment of FL and MCL. The activity in MCL has been confirmed in a multi-center study leading to the recent approval by the FDA. The demonstrated activity was observed on the twice weekly schedule. Recent data using bortezomib in combination with rituximab suggested that weekly bortezomib was less toxic and possibly equally as efficacious as twice weekly bortezomib. This study does not allow a determination of weekly single agent activity alone. We sought to evaluate the single agent activity of bortezomb in FL and MCL administered on a weekly schedule. Methods: Pts with FL and MCL were treated with bortezomib at a dose of 1.8 mg/m 2 weekly for 4 of 6 consecutive weeks. To date, 20 pts (12 FL, 8 MCL) have been treated on this schedule, of which 18 are assessable for response. Two pts were inevaluable: 1 pt received steroids for bronchitis (MCL); and 1 pt (FL) with grade 2 diarrhea withdraw consent making her data inaccessible. Results: The range of cycles administered was 1 to 8, with a median of 2. The weekly dosing schedule was well tolerated with 1 pt. developing neuropathy (grade 3). Fourteen pts completed at least two cycles of therapy and underwent restaging. Two pts had a PR (both FL), 8 had SD (5 FL, 3 MCL) and 4 had POD (2 FL, 2 MCL). The other 4 evaluable patients are now being restaged. Conclusions: These data suggest weekly dosing with bortezomib may not be as effective as twice weekly. Typically, bortezomib administered on the twice weekly schedule has an ORR of 30% in MCL and 50% in FL. Additionally, the frequency of pts. experiencing POD appears to be less common on the twice weekly schedule. One difference in the schedules is the dose intensity and dose density. A cycle of twice weekly bortezomib administers 1.7 mg/m 2 /week, while a weekly schedule administers only 1.2 mg/m 2 /week, a 30% difference in dose intensity and a 100% difference in dose density (1.33 × per week vs. .67 × per week). What remains unclear from a pharmacologic perspective is the relative importance of high Cmax vs high AUC exposures, and their impact on both toxicity and efficacy. These data suggest that schedule is critical in the activity of bortezomib. No significant financial relationships to disclose.
Atopy, rhinitis, lung function and inflammation in asthmatic preschoolers and healthy controls
Authors: E Roumpedaki, P Xepapadaki, P Taprantzi, Tineke Dutre, Claus Bachert, H Lukkarinen, T Jartti, A Graser, T Zimmermann, S Finotto, A Sobanska, ML Kowalski, NG Papadopoulos
Journal: Allergy (2014)
Granulopoiesis Longevity in Continuous Bone Marrow Cultures and Factor-Dependent Cell Line Generation: Significant Variation Among 28 Inbred Mouse Strains and Outbred Stocks&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: M A Sakakeeny, J S Greenberger
Journal: JNCI Journal of the National Cancer Institute (1982)

Longevity of granulopoiesis in corticosteroid-supplemented continuous bone marrow cultures and generation of permanent WEHI-3 dialyzed conditioned medium (DCM)-dependent hematopoietic progenitor cell lines were evaluated for 28 inbred mouse strains and outbred stocks. Cultures from AKR/J, NZW, C58/J, DBA/2J, and C57BL/KsJ mice generated granulocytes for 45-58 weeks and released more than 10(5) murine sarcoma virus (MuSV) rescue units of endogenous retrovirus; nonadherent (NA) cells from 50% or more cultures produced permanent WEHI-3 DCM-dependent cell lines. Cultures from 129/J, BALB/cJ, SJL/J, RF/J, CD-1 Swiss, C57BR/cdJ, C57BL/Ka, CBA/J, RFM/Sn, NZB, C3H/HeJ, NIH Swiss [N:NIH(S)], C57BL/10J, C57L/J, SWR/J, HRS/J, and C57BL/6J mice generated granulocytes for 12-38 weeks; some released 10(1)-10(2) MuSV rescue units of retrovirus, and NA cells from less than 50% of cultures from all but SWR/J and C57L/J mice produced WEHI-3 DCM-dependent cell lines. Thus longevity of granulopoiesis in mouse continuous bone marrow cultures varies significantly among strains.
Abstract 1549: Development and validation of a biomarker for prospective selection of Notch1 activation in patients with certain advanced solid tumors in a first-in-human phase1 study of the cancer stem cell targeting antibody OMP-52M51 (anti-Notch1)
Authors: Belinda Cancilla, Raymond Tam, Chun Zhang, Steve Anderson, John Lewicki, Tim Hoey, Bryan McCune, Lori Johnson, Esohe Idusogie, Ann M. Kapoun
Journal: Cancer Research (2015)

Abstract The Notch pathway plays a key role in embryonic development, the regulation of stem and progenitor cells, and is implicated centrally in many forms of human cancer. Notch1 is known to be frequently activated in certain solid tumor types. OMP-52M51 is a humanized IgG2 antibody that inhibits the signaling function of the Notch1 receptor. Mouse xenograft studies using minimally-passaged, patient-derived xenografts have shown that OMP-52M51 impedes tumor growth and selectively eliminates CSCs in a range of tumor types particularly in tumors with activated Notch1 signaling. We previously reported the frequency of Notch pathway activation across a large panel of human tumors (n&amp;gt;600) by an Immunohistochemistry (IHC) assay that detects the activated form of Notch1 using an antibody that specifically recognizes the Notch1 intracellular domain (ICD). Using this test and a rigorous H-score cut-off, we found elevated Notch1 ICD in 7-53% of the following cancers: chemo-resistant breast (29%), gastric (13%), cholangiocarcinoma (20%), esophageal (27%), hepatacellular carcinoma (HCC, 7%), small cell lung cancer (SCLC, 12%), pancreatic (12%) and colorectal cancer (53%). Here we developed a specific CLIA-validated IHC assay capable of identifying patients with Notch1 activation. The assay has a rapid turn-around time and shows robust precision, reproducibility and accuracy. The sensitivity of the method was confirmed by comparing results obtained on xenograft tumor tissue samples with known levels of Notch1 expression and response to anti-Notch1 therapy. From these results, the cut-off of the assay was set. This predictive biomarker was specifically designed to screen patients for prospective selection in the first-in-human Phase1 study of OMP-52M51 (anti-Notch1) in certain advanced solid tumors (NCT01778439). Detailed assay validation data and its application to the analysis of clinical trial samples will be highlighted. Citation Format: Belinda Cancilla, Raymond Tam, Chun Zhang, Steve Anderson, John Lewicki, Tim Hoey, Bryan McCune, Lori Johnson, Esohe Idusogie, Ann M. Kapoun. Development and validation of a biomarker for prospective selection of Notch1 activation in patients with certain advanced solid tumors in a first-in-human phase1 study of the cancer stem cell targeting antibody OMP-52M51 (anti-Notch1). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1549. doi:10.1158/1538-7445.AM2015-1549
간과 관련된 한국의 민간요법 비평 / 인진쑥(茵蔯蒿)이란 무엇인가? 사철쑥(Artemisia capillaris), 더위지기(Artemisia iwayomogi)와 개똥쑥(Artemisia annua)
Authors: 안병민(Byung Min An)
Journal: Clinical and Molecular Hepatology (2000)
A phase 2 clinical trial of pemetrexed plus gemcitabine as front-line chemotherapy for patients with malignant pleural mesothelioma (MPM)
Authors: P. A. Janne, C. Obasaju, G. Simon, R. Taub, K. Kelly, P. Fidias, L. P. Bloss, H. L. Kindler
Journal: Journal of Clinical Oncology (2004)

7053 Background: Pemetrexed and gemcitabine are synergistic in preclinical models. Each agent is active in MPM, but the combination has not been studied in this disease in the phase 2 setting. Methods: From 12/02 to 06/03, 53 chemo-naive patients with unresectable MPM were enrolled from 12 sites in the US. Treatment consisted of gemcitabine 1250 mg/m2 on days 1 and 8, with pemetrexed 500mg/m2 on day 8, followed by gemcitabine, every 21 days for a total of 6 cycles or until progressive disease. All patients received folic acid, vitamin B12 and steroid prophylaxis. Pathologic diagnosis included epithelial 68.3%, mixed 12.2%, sarcomatoid 7.3%, and unclassified/other 12.2%. Enrolled patients had a median age of 69.5 years (range: 36 - 88), PS 0:1:2 = 20%:61%:9.8%, and 90% were males. Results: Toxicity information is currently available on 41 patients. Cycle specific Grade 3/4 hematologic toxicities consisted of neutropenia 33.1%, anemia 1.7%, thrombocytopenia 1.7%, and febrile neutropenia 1.7%. Non-hematologic Grade 3/4 events (% of cycles) were fatigue (5%), neurotoxicity (3.3%), nausea (2.5%), asthenia (1.7%) with the following occurring in < 1% of cycles: vomiting, renal insufficiency, alopecia (grade 1), diarrhea, and rash. Of the 121 cycles administered, 15.7% (n=19) required dose reductions, resulting in a median dose intensity for gemcitabine and pemetrexed of 91.95% and 99.61%. Median number of doses/patient: gemcitabine = 4, pemetrexed = 3. Preliminary response rate=20% out of 34 evaluable patients; CR=0, PR=7 (20%-CI 9–38%), SD=18 (52.9%-CI 35–70%), PD=9 (26.5% CI 13–44%). To date, the clinical benefit rate = 72.9%. Conclusions: Pemetrexed plus gemcitabine in MPM has an encouraging toxicity profile which is manageable and comparable to other doublet combinations. Especially for the elderly patient with MPM (50% of trial population = 69.5 yrs), this combination of gemcitabine plus pemetrexed may prove a better-tolerated, viable alternative to cisplatin –pemetrexed. Early response data is promising and time-to-event, updated response, and survival information on all 53 patients will be forthcoming. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly & Co. Eli Lilly & Co. Eli Lilly & Co. Eli Lilly & Co. Eli Lilly & Co.
The mTOR inhibitor CCI-779 (temsirolimus) downregulates p21 and induces cell cycle arrest and autophagy in mantle cell lymphoma (MCL)
Authors: V. Y. Yazbeck, G. V. Georgakis, Y. Li, A. Younes
Journal: Journal of Clinical Oncology (2006)

7573 Background: Mantle cell lymphoma (MCL) is a distinct type of B-cell lymphoma associated with transient response to conventional chemotherapy, continuous relapses and median survival of only 3–4 years. The mammalian target of rapamycin (mTOR) pathway is activated in many human malignancies where it regulates cyclin D1 translation. In a phase II trial, temsirolimus (CCI-779), an inhibitor of mTOR kinase used as single agent achieved an overall response rate of 38% in relapsed MCL patients. Our goal was to determine the activity and the mechanism of action of CCI-779 in MCL cell lines and to examine whether CCI-779 may synergizes with proteasome inhibitors. Methods: The activity of CCI-779 was determined in 3 mantle cell lymphoma cell lines (Jeko 1, Mino, Sp 53). Cell viability was determined by MTS assay, and autophagy by Acridine orange. Analysis of cell cycle was performed by flow cytometry and apoptosis by Annexin-V binding. Molecular changes were determined by western blot . Results: CCI-779 induced cell growth arrest in all cell lines in a time and dose dependent manner. The antiproliferative activity was due to cell cycle arrest in the G0/G1 phase followed by autophagy. CCI-779 decreased S6 phosphorylation in Jeko 1,Sp 53 indicative of mTOR inhibition. Furthermore, CCI-779 downregulated p21 expression in all three cell lines, without altering p 27 expression. Moreover, CCI-779 decreased the expression of the antiapoptotic protein cFLIP and ERK in both Jeko1 and Sp 53, but had no effect on cyclin D1 expression. The proteasome inhibitor bortezomib was also effective in all MCL cell lines, but failed to demonstrate significant synergy with CCI-779. Conclusions: The antiproliferative activity of CCI-779 in MCL is mediated by p21 downregulation and autophagy, without significant effect on cyclin D1 expression. The lack of synergy between bortezomib and CCI-779 should be confirmed using fresh MCL tumor cells. No significant financial relationships to disclose.
Loosening the grip
Authors: Kamran Abbasi
Journal: BMJ (2015)

When cautious, evidence informed writers such as Christiane Muth and Paul Glasziou describe a research paper as “pioneering work,” it is sensible to pay attention (doi:10.1136/bmj.h5145). The world’s health systems are besieged by ageing populations and multimorbidity. We struggle to find effective and affordable solutions. Research evidence, in its artificial bubble, may be limited by the age range of the study population and generally focuses on single therapies. The reality of medical care is different: older patients with complex chronic diseases, taking many drugs. Our evidence base and guidelines, the tools of best practice, tend not to cater for the messiness of clinical problems. …
Changing pattern of pulmonary metastases with adjuvant chemotherapy in patients with osteosarcoma: results from the multiinstitutional osteosarcoma study.
Authors: A M Goorin, J J Shuster, A Baker, M E Horowitz, W H Meyer, M P Link
Journal: Journal of Clinical Oncology (1991)

The multiinstitutional osteosarcoma study (MIOS), a randomized trial of adjuvant therapy for osteosarcoma with a concurrent control group, registered 113 patients from June 1982 to August 1984. Preliminary analysis of the study indicated a significant event-free survival advantage favoring immediate adjuvant chemotherapy, (P less than .001). For patients treated with surgery alone or with surgery and adjuvant chemotherapy, the lungs were involved in more than 80% of the relapses. Patients relapsing after surgery alone tended to relapse earlier (P less than .01), had more pulmonary nodules (P less than .01), and had more frequent bilateral pulmonary involvement (P less than .01) than those treated with immediate postsurgical adjuvant chemotherapy. However, patients relapsing after treatment with surgery alone experienced a significantly longer interval to further disease progression (P less than .01) and improved survival after relapse (P = .01) when compared with patients who relapsed after treatment with immediate adjuvant chemotherapy. The only factor predictive of survival after relapse was if the patient could be made surgically disease-free after initial relapse (P = .03).