tbuckley/cabot-search huggingface dataset:
A phase I-II study of cyclophosphamide, thiotepa, and carboplatin with autologous bone marrow transplantation in solid tumor patients.
Authors: J P Eder, A Elias, T C Shea, S M Schryber, B A Teicher, M Hunt, J Burke, R Siegel, L E Schnipper, E Frei
Journal: Journal of Clinical Oncology (1990)

The principles of dose-response and combination chemotherapy were basic to the design of the initial curative standard-dose treatment regimens for leukemias, lymphomas, and testis cancer. Agents were selected with different dose-limiting toxicities, resulting in subadditive toxicity in combination. A fourth principle in the design of curative regimens was to combine agents with different mechanisms of action to avoid cross-resistance. Based on these principles, combinations of the highest tolerated doses of active noncross-resistant agents are required to decrease the emergence of drug resistance and achieve optimum cytotoxicity. Hematopoietic stem-cell support provides a mechanism for significantly increasing the doses of active agents, a strategy that has resulted in the cure of 10% to 50% of selected patients with lymphoma who could not be cured with standard-dose therapy. The lack of sufficiently effective cytoreductive conditioning regimens remains the major impediment to improving the high-dose therapy of patients with solid tumors. In this study, 27 patients with solid tumors were treated with a combination of cyclophosphamide, thiotepa, and carboplatin (CTCb) in a phase I-II study. Severe mucositis and neurotoxicity were dose-limiting. The maximum-tolerated dose (MTD) of the combination was 6.0 g/m2 of cyclophosphamide, 500 mg/m2 of thiotepa, and 800 mg/m2 of carboplatin. There were two deaths (7%) of sepsis, and an overall response rate of 72% in refractory tumors (81% in breast cancer). CTCb is a combination with low morbidity and high cytoreductive efficacy designed to exploit the principles of curative cancer chemotherapy.
Beyond the Bench: Hunting Down Fugitive Literature
Authors: Karalyn R. Colopy
Journal: Environmental Health Perspectives (2004)

The first step to becoming a successful fugitive is to abandon all forms of conventional identification—driver’s license, passport, checking account. People who stay out of the commercial realm are extremely hard to find. The same is true of literature. Libraries, with their online catalogs and helpful reference librarians, make it easy to find just about any piece of commercially published material. But lurking beyond the reach of the card catalog are thousands of materials such as reports, fact-sheets, newsletters, meeting transcripts, lesson plans, presentations, manuals, and interactive websites—so-called “fugitive literature”—that have never darkened the library’s door. Today, some of those fugitives have been found: the COEP Resource Center website (http://www-apps.niehs.nih.gov/coeprc/) offers visitors a bibliographic database for searching and reading about more than 600 environmental health materials developed by the Community Outreach and Education Programs, or COEPs, associated with each of the 25 NIEHS centers.

Since 1996, when the NIEHS established COEPs as an essential component of its Core Center Program, NIEHS grantees have been generating large volumes of fugitive literature. Charged with increasing public understanding of environmental health science research, the 25 COEPs carry out diverse projects. They host public forums and town meetings, offer professional development opportunities to teachers and health care providers, bring students to their laboratories for tours and summer science camps, and arrange for scientists to give presentations at local schools. They also develop curricula on environmental health for students in kindergarten through twelfth grade. These curricula are based on the latest research and are designed to meet state and national education standards.

The documents created during the course of the COEPs’ activities represent a wealth of environmental health information, innovative ideas, creative teaching approaches, lesson plans, videos, posters, brochures, training manuals, and successful outreach strategies. These materials are usually free and ready to use in a variety of education and outreach settings. However, until recently the people who could most use them—teachers, parents, nurses, community groups—were unlikely to find them.

That changed in 2000, when the NIEHS developed the COEP Resource Center to collect and catalog the products of the COEPs’ projects. Today, most printed resources are available for download in PDF format, and the database provides an abstract and ordering information for nonprint materials such as videos and CD-ROMs. The site also posts information about upcoming events, news, related links, and contact information for each COEP grantee.

The COEP Resource Center is now expanding its scope by incorporating materials produced by grantees in several other NIEHS programs besides the Core Center Program. Additions are planned over the next few months.
The Global Cancer Genomics Consortium: Interfacing Genomics and Cancer Medicine
Authors: Jeyanthy Eswaran, Sudeep Gupta, Amit Dutt, Masakazu Toi, M. Radhakrishna Pillai, Luis Costa, Stefan Knapp, Rajandra A Badwe, Rakesh Kumar
Journal: Cancer Research (2012)

The Global Cancer Genomics Consortium (GCGC) is an international collaborative platform that amalgamates cancer biologists, cutting-edge genomics, and high-throughput expertise with medical oncologists and surgical oncologists; they address the most important translational questions that are central to cancer research and treatment. The annual GCGC symposium was held at the Advanced Centre for Treatment Research and Education in Cancer, Mumbai, India, from November 9 to 11, 2011. The symposium showcased international next-generation sequencing efforts that explore cancer-specific transcriptomic changes, single-nucleotide polymorphism, and copy number variations in various types of cancers, as well as the structural genomics approach to develop new therapeutic targets and chemical probes. From the spectrum of studies presented at the symposium, it is evident that the translation of emerging cancer genomics knowledge into clinical applications can only be achieved through the integration of multidisciplinary expertise. In summary, the GCGC symposium provided practical knowledge on structural and cancer genomics approaches, as well as an exclusive platform for focused cancer genomics endeavors.
Reduced risk of bone metastases in breast cancer patients treated with Cox-2 inhibitors
Authors: W. J. Tester, M. Valsecchi, S. Pomerantz, R. Jaslow
Journal: Journal of Clinical Oncology (2008)

526 Background: Approximately 40–70% of women diagnosed with breast cancer will develop bone metastases. The level of cyclooxygenase-2 (Cox-2) is overexpressed in human bone metastases and correlates with the occurrence of bone metastases in animal models. We hypothesize that the use of Cox-2 inhibitors in early phases of breast cancer could protect against the development of bone metastases. Methods: The medical charts of all patients treated for stage II and III breast cancer between 1999–2005 were reviewed. Patients were subsequently subdivided into those who took Cox-2 inhibitors (celecoxib, rofecoxib or valdecoxib) for at least 6 months following the diagnosis of breast cancer and those who did not. The diagnosis of bone metastases required conclusive radiologic imaging. Fisher's exact test and a multivariate logistic regression were used to analyze the data. Results: A total of 692 patients were included in this analysis. The patients’ mean age was 59 and the mean follow up was 3.9 years. Eleven percent (74/644) of patients who did not take Cox-2 inhibitors developed bone metastasis compared to two percent (1/48) of those who did (Fisher's exact test p = 0.05). Significant predictors for developing bone metastases using a multivariate logistic regression model were: 3 or more positive nodes (p<0.001; Odds Ratio = 3.19, 95% CI = 1.79 - 5.70), stage IIb-IIIc (p = 0.001; OR = 4.61, 95% CI = 2.19–9.72) and use of Cox-2 inhibitors (p = 0.025; OR = 0.10, 95% CI = 0.013–0.75). Adjusting for TNM stage, of the 327 patients in stages IIb-IIIc, 21.5% (63/293) had bone metastasis in the non-Cox-2 group vs. 3% (1/34) in the Cox-2 group (p = 0.006). In this high-risk group of patients, the calculated odds ratio for development of bone metastases associated with the use of Cox-2 inhibitors was 0.10 (95% CI = 0.014–0.78). There was no significant difference between the groups in the number of patients that received adjuvant radiotherapy, chemotherapy, or hormone therapy. Conclusions: This retrospective study suggests that the use of Cox-2 inhibitors can reduce the risk of bone metastases in patients with stage II and III breast cancer. Prospective randomized trials of adjuvant Cox-2 inhibitors in patients with high-risk breast cancer are needed to validate this conclusion. No significant financial relationships to disclose.
Evaluation of HER-2 in serum and tissue: correlation with clinical-pathological parameters and outcome in early stage breast cancer (BC) patients (pts)
Authors: V. Ludovini, S. Gori, A. Mosconi, L. Pistola, E. Rulli, A. Rulli, P. Anastasi, E. Pacifico, A. Sidoni, F. R. Tofanetti, M. Colozza
Journal: Journal of Clinical Oncology (2006)

20066 Background: HER2 is amplified and/or overexpressed in approximately 20–30% of invasive BC and is associated with poor prognosis. It is also a predictive marker of response to trastuzumab. The extracellular domain of the HER2 protein (sHER2) is frequently cleaved and released into the circulation where it can be detected by ELISA in up to 45% of advanced BC. We evaluated HER2 expression in paired serum and tissue samples of operable BC pts to analyze 1) the correlation between sHER2 and HER2 tumor status 2) their relationship with clinical-pathological parameters and 3) their impact on the outcome. Methods: 188 consecutive stage I-III BC pts were included in this study from May 2000 to July 2005. sHER2 was measured by ELISA (manual Kit “Oncogene Science Diagnostics” and automated version “ADVIA Centaur”) before the local treatment. Tumor tissue was analyzed by IHC with CB11 antibody and scored with Dako Hercept-test. HER2 amplification was determined using the Ventana FISH assay in patients with 2+ by IHC. Chi-squared test was used to evaluate the association between HER2 and patients’ clinical-pathological features. Survival outcomes were analyzed using Cox’s model. Results: Median age was 56.6 years; 122 pts received adjuvant chemotherapy, 54 endocrine therapy and 83 both. Forty-three pts (23%) had HER2 overexpression/amplification in tumor tissue and 25 pts (13%) had sHER2 levels ≥15 ng/ml (cut-off level) with a concordance of 85%. Both high sHER2 levels and HER2 tumor expression were associated with high histological grade (p = .02 and p &lt; .0001 respectively) and negativity of ER (p = .0035 and p &lt; .0001) and PgR (p = .0056 and p =. 002). At a median follow-up of 2.4 years we observed 8 deaths and 19 relapses. At univariate analysis high sHER2 levels (evaluated as continuous variable) were significantly correlated with shorter DFS (p = 0.0002) even if at multivariate analysis high sHER2 levels, after adjustment for stage and ER status, were associated with a shorter DFS with borderline significance (p = 0.06). Conclusion: Our preliminary data indicate that the evaluation of sHER2 at diagnosis defines a small subgroup of early BC pts with a poor prognosis even if it needs to be confirmed in a longer follow up. No significant financial relationships to disclose.
Thoracic-Outlet Syndrome
Authors: W W Woods
Journal: New England Journal of Medicine (1972)

Soft tissue cervical injuries are among the most common posttrauma problems faced by general practitioners, orthopedists and neurosurgeons. The development of the thoracic outlet syndrome (TOS) following such injuries is more frequent than is generally recognized. Conservative treatment with physiotherapy, muscle relaxants, anti-inflammatory drugs and percutaneous electrostimulation usually proves effective in relieving TOS. In this series of 1,958 soft tissue cervical injuries, 459 patients (23 percent) were diagnosed as having TOS. Of these patients, 185 (41 percent) failed to respond to all conservative measures and consequently surgical operation in the form of a supraclavicular neurovascular decompression became necessary to relieve not only the symptoms of the neck-shoulder-arm syndrome but also to relieve a frequently unrecognized (72 percent) vertebrobasilar artery syndrome. The latter is most definitely an integral part of TOS. The most common misdiagnoses were cervical disc syndrome (42 percent) and cervical strain (42 percent). A long-term follow-up (average of seven years) of 90 patients showed that the results were judged good in 75 percent, fair in 11 percent and poor in 14 percent.
Pulmonary gene expression of tenascin-C and fibronectin in chronic obtructive pulmonary disease (COPD)
Authors: Mariana Munoz-Esquerre, Susanna Estany, Marta López, Maria Molina-Molina, Ignacio Escobar, Rosa M. Penin, Victor Peinado, Joan A. Barberà, Jordi Dorca, Salud Santos
Journal: European Respiratory Journal (2012)

BACKGROUND   COPD is characterized by pulmonary vascular remodeling and is associated with high prevalence of cardiovascular events regardless of other risk factors. Tenascin-C (TNC) and fibronectin (EDA-FN) are extracellular matrix proteins involved in cardiovascular pathology and in lung fibroproliferative diseases. Our principal aim was to elucidate whether this lung gene expression is different between COPD and smokers patients.   METHODS   Specimens of lung tissue from two groups, COPD and smokers without COPD, both who required surgery for lung cancer were studied. Clinical and spirometric data were collected. Gene expression was measured by quantitative polymerase chain reaction (Real time PCR) using comparative method (Ct) and RQ (fold change ratio) as a unit of measure.   RESULTS   Ten of the 28 patientes had COPD (FEV 1 , 69±3% ref.; DLCO, 67±5% ref.) and 18 were only smokers (FEV 1 , 92±3% ref.; DLCO, 86±4% ref.). There was no difference in the prevalence of cardiovascular risk factors between groups. The expression of TNC and EDA-FN (mean±SEM) in COPD group was 17,6±6 and 5,1±1 respectively, versus 15,5±5 and 3,9±1 in the control group (p NS). In multivariate analysis, only the active smoking was associated with higher expression of TNC (s= 24,588; p=0,002) but not with the COPD condition.   CONCLUSIONS   In our study, there were no differences in the gene expression of TNC and EDA-FN in lung tissue of COPD patients compared to smokers without COPD. However, we found an increased expression of TNC in relation to active smoking, so it might have a role in the pathogenesis of COPD, although the mechanisms involved in cardiovascular disease require other specific studies.  Funded by FUCAP 2011.
Patient's view
Authors: Mahon William, Saroj Kumar Das
Journal: BMJ (2006)

I first visited my general practitioner with a urine infection. This had been a reoccurring symptom for several months and I was referred for a scan on my kidneys. The technician started the scan and said that he had seen something he was not happy with and called for a colleague. I was then told that I would not have to worry about my …
Incidence of bone metastases in GIST: A single center analysis of 307 patients with metastatic disease
Authors: M. Schuler, M. Zeile, D. Pink, P. Tunn, A. Kretzschmar, B. Rau, P. Reichardt
Journal: Journal of Clinical Oncology (2008)

10565 Background: Gastrointestinal stromal tumors (GISTs) are rare tumors and account for 0.1–0.3% of all gastrointestinal cancers and 5% of all soft tissue sarcomas. The most common sites are stomach (60%) and small intestine (20–30%), but they can also arise from colon and rectum (10%). The most frequent metastatic sites are liver (65%) and peritoneum (21%). Lymph node (6%), bone (6%) and lung metastases (2%) are uncommon. Methods: In a single center retrospective analysis we evaluated patients (pts.) between Jan. 2000 and Oct. 2007 with the diagnosis of metastatic GIST. Patient, tumor and metastatic variables were analyzed for their relation to outcome. No routine bone scans were applied. All times were calculated until the last day of follow-up or death. Results: Out of the 309 consecutive patients with metastatic GIST 17 (5.5%) were identified to have bone metastases. Those were either found due to symptomatic disease (7/19 pts.) or in the course of routine diagnostic procedures (12/19 pts.). Median age was 54.5 years and 5/17 pts. Had synchronous metastatic disease. In one case bone metastases were the first manifestation of a late relapse eight years after primary curative resection. 6 of 17 pts. Had unilocular and 11/17 pts. Multilocular disease with a focus on spine bone lesions (10/17 pts.) with multilocular metastases (7/10 pts.). All patients also had other typical manifestations (17/17 hepatic, 10/17 peritoneal), but we also observed a coincidence with other rare manifestations (pulmonary/pleural [4], epidural [2], retroorbital [1]) in 7/17 pts. Palliative treatment consisted of bisphophonates, radiation and orthopedic surgery. In this group of pts. With bone metastases median survival was 325 weeks (w) (SD 59) from time of diagnosis, 252 w (SD 22) from diagnosis of distant metastases and 135 w (SD 24) from the time of occurrence of bone metastases. Conclusions: In a large series of unselected, consecutive pts. With metastatic GIST 5.5% were found to have bone metastases. Commonly those pts. Suffered from other rare metastatic localizations. The incidence of bone metastases may be underestimated due to the fact that especially bone lesions of the extremities were mainly found due to clinical symptoms. We should be aware of this in the long term follow-up. No significant financial relationships to disclose.
Asthma and vitamin D
Authors: Ismail Hanta, Oya Baydar, Ezgi Özyilmaz, Sedat Kuleci
Journal: European Respiratory Journal (2012)

Objectives: Recent studies indicate a relationship between low vitamin D level and asthma pathogenesis. The aim of this prospective study is to evaluate vitamin D levels in asthmatic patients and investigate the relationship between vitamin D and asthma pathogenesis.  Material and method: 112 asthmatic patients and 94 healthy people who admitted to Cukurova University Chest Diseases Department were included. The age and gender of asthmatics and control group were similar. The demographic data were recorded. Both asthmatics and control group had detailed pulmonary function tests and their serum vitamin D levels are studied with liquid chromotography.  Results: 86 (76.8%) of asthmatics were female, 26 (23.2%) were male. Mean age of asthmatics were 43.6± 14.1. Sixty two (66%) of control group were female and 32 (34%) were male. The age and gender were similar between asthmatics and control group. No statistically significant difference was determined between vitamin D levels of asthmatics and control group (p=0.27). The mean vitamin D level of asthmatics was 25.19±12.01, of control group was 27.09± 12.9 ng/ml. When the mean Vitamin D levels were compared in asthmatics according to gender, the mean vitamin D level of female patients was significantly lower than the male patients (23.88± 11.92 ng/ml in females and 29.52± 11.48 ng/ml in males) (p=0.03). Again in asthmatic patients, a significant positive correlation is determined between the forced expiratory volume in first second and serum vitamin D level (p=0.004).  Conclusion: With these results, it is thought that vitamin D levels could be associated with asthma pathogenesis especially in females and poor lung functions.
Abstract 4864: Electrocardiographic and Angiographic Correlations in Patients With Left Bundle Branch Block With Suspected Myocardial Infarction Undergoing Urgent Coronary Angiography
Authors: Madhab Ray, Dzanan Ramic, J P Kleaveland, Larry E Jacobs
Journal: Circulation (2009)

Background: The purpose of this study is to determine the accuracy of the Sgarbosa criteria to identify the presence of acute Myocardial Infarction (MI) diagnosed by biomarkers and to predict coronary occlusions in patients with new or presumed new Left Bundle Branch Block (LBBB) and suspected acute MI. Methods: We retrospectively reviewed the records of 1322 consecutive patients presenting to our institution with suspected acute transmural MI who underwent urgent coronary angiography between 2004 and 2008. Results: Thirty four patients (2.6%) had LBBB. Results of Sgarbosa criteria versus presence of an occluded coronary artery and troponin status are shown in the table below. Conclusions: In our cohort of patients 26 out of 34 (76%) patients had MI as determined by elevated tropnin levels. Sgarbosa criteria, when applied with the weighted score of &gt;/=2, could detect patients of myocardial infarction with a sensitivity of 62%, specificity of 63%, positive predictive value of 76% and negative predictive value of 23%. When the same criteria were applied to detect occlusion of any coronary artery the sensitivity was found to be 50% with a specificity of 32%, positive predictive value of 29% and negative predictive value of 54%. In conclusion, the incidence of MI among the patients of new or presumed new LBBB is high at 76%. The overall usefulness of Sgarbosa criteria to diagnose MI and occluded coronaries (which are most likely to benefit from early revascularization) in patients with LBBB is moderate but the negative predictive value is very low. Hence patients with new or presumed new LBBB with suspected myocardial infarction should get the benefit of early catheterization if clinically justified. Occluded Coronary Artery and Troponin Status
Ocular surface changes after excimer laser phototherapeutic keratectomy11The authors have no proprietary interest in any of the products mentioned in this paper.
Authors: Murat Dogru, Chikako Katakami, Masato Miyashita, Etsuko Hida, Mamoru Uenishi, Kazuaki Tetsumoto, Sanae Kanno, Teruo Nishida, Akio Yamanaka
Journal: Ophthalmology (2000)