tbuckley/cabot-search huggingface dataset:
Dose-Dense Sequential Chemotherapy With Epirubicin and Paclitaxel Versus the Combination, as First-Line Chemotherapy, in Advanced Breast Cancer: A Randomized Study Conducted by the Hellenic Cooperative Oncology Group
Authors: George Fountzilas, Christos Papadimitriou, Urania Dafni, Dimitrios Bafaloukos, Dimosthenis Skarlos, Lia A. Moulopoulos, Evangelia Razis, Haralambos P. Kalofonos, Gerassimos Aravantinos, Evangelos Briassoulis, Pavlos Papakostas, Konstantina Abela, Eleni Gogas, Paris Kosmidis, Nicholas Pavlidis, Meletios A. Dimopoulos
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To compare the efficacy of two different schedules of epirubicin and paclitaxel, as first-line chemotherapy, in patients with advanced breast cancer (ABC). PATIENTS AND METHODS: From October 1997 until May 1999, 183 eligible patients with ABC entered the study. Chemotherapy in group A (93 patients) consisted of four cycles of epirubicin at a dose of 110 mg/m 2 followed by four cycles of paclitaxel at a dose of 225 mg/m 2 in a 3-hour infusion. All cycles were repeated every 2 weeks with granulocyte colony-stimulating factor support. The therapeutic regimen in group B (90 patients) consisted of epirubicin (80 mg/m 2 ) immediately followed by paclitaxel (175 mg/m 2 in a 3-hour infusion) every 3 weeks for six cycles. RESULTS: In total, 79 patients (85%) in group A and 72 patients (80%) in group B completed treatment. The median relative dose-intensity of epirubicin was 0.96 in both groups, and that of paclitaxel was 0.96 and 0.97 in groups A and B, respectively. The complete response rate was higher in group A (21.5% v 9% P = .02). Nevertheless, there was no significant difference in the overall response rate between the two groups (55% v 42%, P = .10). Severe neutropenia was more frequently observed with concurrent treatment. After a median follow-up of 16.5 months, median time to progression was 10 months in group A and 8.5 months in group B (P = .27), and median survival was 21.5 and 20 months, respectively (P = .17). CONCLUSION: The present study failed to demonstrate a significant difference in overall response rate between dose-dense sequential administration of epirubicin and paclitaxel compared with the combination of the two drugs given on the same day, even though the sequential treatment resulted in a significantly higher complete response rate.
Lynch syndrome <i>TACSTD1</i> family with predominant colorectal cancer.
Authors: H. T. Lynch, S. N. Thibodeau, C. Snyder, J. F. Lynch, J. M. Davies, C. R. Boland, P. M. Lynch, D. Riegert-Johnson
Journal: Journal of Clinical Oncology (2010)

1500 Background: Germline mutations in the mismatch repair (MMR) genes MLH1 and MSH2 cannot be identified in about 30% of families fulfilling Amsterdam I criteria for Lynch syndrome (LS). Recently, deletions in the TACSTD1 gene have also been identified as a cause of LS. Kovacs et al. (Hum Mutat 2009;30:197-203) identified large germline deletions of TACSTD1 upstream of MSH2 among 19% (5/27) of LS families lacking evidence of a mutation in MSH2 or MLH1. TACSTD1 deletions result in hypermethylation and incomplete silencing of MSH2 suggesting that some TACSTD1 mutation carriers may have a different phenotype than carriers of MSH2 or MLH1 mutations, namely an almost exclusive expression of colorectal cancer (CRC) without extracolonic cancers. We evaluated for TACSTD1 mutations in this large LS kindred that was critical in our original description of LS; we initiated study of this family in 1970. Methods: TACSTD1 analysis was performed using a commercially available MLPA kit (P072 version 6, MRC Holland) on patients' DNA. Extensive genealogy, cancer pathology verification, and genetic counseling has been a constant process among consenting family members. We identified a TACSTD1 mutation in this highly extended LS family which had served as LS's phenotypic template since we initiated its study. Results: Family characteristics comprised 605 bloodline relatives, 73% of whom are over the age of 25, living, and eligible for DNA testing. In 2009, a Family Information Service (FIS) was held to educate, counsel, and collect DNA samples on high-risk family members for TACSTD1 testing. Over 70 family members attended this FIS with 45 of them providing DNA samples wherein 14 were confirmed to be TACSTD1 mutation carriers. Affected family members had primarily CRC, and only a few had extracolonic cancers. Conclusions: Identification of TACSTD1 mutations as a cause of LS has important cancer control implications for this and other LS families thereby enabling family members to identify their cancer risk, receive genetic counseling, and enroll in an appropriate cancer surveillance/management program. Extracolonic cancer risk may be decreased in TACSTD1 mutation carriers but this will require further confirmation. No significant financial relationships to disclose.
A requirement for the immediate early gene Zif268 in the expression of late LTP and long-term memories
Authors: M. W. Jones, M. L. Errington, P. J. French, A. Fine, T. V. P. Bliss, S. Garel, P. Charnay, B. Bozon, S. Laroche, S. Davis
Journal: Nature Neuroscience (2001)
Paraneoplastic syndromes of gynecologic neoplasms.
Authors: A A Ashour, C F Verschraegen, A P Kudelka, J J Kavanagh
Journal: Journal of Clinical Oncology (1997)

PURPOSE AND DESIGN The purpose of this review is to define and describe the paraneoplastic syndromes associated with gynecologic neoplasms. A comprehensive search of MEDLINE from 1966 to January 1996 and Cancerlit was performed. One hundred twenty-two reports were reviewed. RESULTS Twenty-four paraneoplastic syndromes have been associated with gynecologic malignancies. Six anatomic systems are affected by these syndromes. However, except for disseminated intravascular coagulation and hypercalcemia, these syndromes are rare. CONCLUSION Paraneoplastic syndromes are not frequently associated with gynecologic malignancies. The diagnosis of these syndromes is essential, as they can be occasionally life-threatening. Some paraneoplastic syndromes can be used as marker of progression or regression of the underlying malignancy.
Clinical and dermoscopic features of combined cutaneous squamous cell carcinoma (SCC)/neuroendocrine [Merkel cell] carcinoma (MCC)
Authors: Andrea Luísa Suárez, Peter Louis, Jasmine Kitts, Klaus Busam, Patricia L. Myskowski, Richard J. Wong, Chih-Shan Jason Chen, Philip Spencer, Mario Lacouture, Melissa P. Pulitzer
Journal: Journal of the American Academy of Dermatology (2015)
Lymphokine-Activated Killer Activity of Tumor-Associated and Peripheral Blood Lymphocytes Isolated From Patients With Ascites Ovarian Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Paola Allavena, Flavia Zanaboni, Silvano Rossini, Anna Merendino, Cristina Bonazzi, Laura Vassena, Costantino Mangioni, Alberto Mantovani
Journal: JNCI Journal of the National Cancer Institute (1986)

Peripheral blood lymphocytes (PBLs) and tumor-associated lymphocytes (TALs) were isolated from 36 patients with advanced ovarian adenocarcinoma and peritoneal effusions for study of lymphokine-activated killer activity. PBLs and TALs cultured in vitro for 3-5 days in the presence of interleukin-2 (IL-2, supernatant of the MLA 144 gibbon cell line, or human recombinant IL-2) expressed higher levels of cytotoxicity as compared to cells cultured in medium alone, against natural killer (NK)-susceptible (K562) or NK-resistant targets (Daudi and the human ovarian carcinoma cell line SW626). When ovarian tumor cells, freshly isolated from carcinomatous ascites or surgical specimens, were used as target cells in the cytotoxicity assay, 8 of 14 PBLs and 5 of 7 TAL preparations lysed the autologous tumor after treatment with IL-2, while no spontaneous reactivity was observed in any of the 14 patients tested. Although levels of lysis were usually relatively low, these data demonstrate that PBLs and TALs from ovarian cancer patients (TALs usually exhibiting low NK activity) when stimulated in vitro by IL-2 acquire some cytotoxic potential against the autologous tumor.
End-of-Life Care in the Intensive Care Unit
Authors: J. Randall Curtis, Ruth A. Engelberg, Mark E. Bensink, Scott D. Ramsey
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

The incidence and costs of critical illness are increasing in the United States at a time when there is a focus both on limiting the rising costs of healthcare and improving the quality of end-of-life care. More than 25% of healthcare costs are spent in the last year of life, and approximately 20% of deaths occur in the intensive care unit (ICU). Consequently, there has been speculation that end-of-life care in the ICU represents an important target for cost savings. It is unclear whether efforts to improve end-of-life care in the ICU could significantly reduce healthcare costs. Here, we summarize recent studies suggesting that important opportunities may exist to improve quality and reduce costs through two mechanisms: advance care planning for patients with life-limiting illness and use of time-limited trials of ICU care for critically ill patients. The goal of these approaches is to ensure patients receive the intensity of care that they would choose at the end of life, given the opportunity to make an informed decision. Although these mechanisms hold promise for increasing quality and reducing costs, there are few clearly described, effective methods to implement these mechanisms in routine clinical practice. We believe basic science in communication and decision making, implementation research, and demonstration projects are critically important if we are to translate these approaches into practice and, in so doing, provide high-quality and patient-centered care while limiting rising healthcare costs.
Loss of estrogen receptor in recurrent breast cancer is associated with poor response to endocrine therapy.
Authors: T Kuukasjärvi, J Kononen, H Helin, K Holli, J Isola
Journal: Journal of Clinical Oncology (1996)

PURPOSE Up to 30% to 40% of metastases from hormone receptor-positive primary breast cancer do not respond to endocrine therapy. We studied how often hormone receptor status changes between primary and recurrent tumors and whether such a change might explain unresponsiveness to endocrine therapy. PATIENTS AND METHODS Primary breast cancer samples and matched asynchronous recurrences were studied from 50 patients who had not received any adjuvant therapy. Estrogen receptor (ER) and progesterone receptor (PR) status was determined immunohistochemically from histologically representative formalin-fixed paraffin-embedded tumor samples. ER status was ascertained by mRNA in situ hybridization. RESULTS Thirty-five (70%) of 50 primary tumors were positive for ER and 30 (60%) for PR. Hormone receptor status of the recurrent tumor differed from that of the primary tumor in 18 cases (36%). Discordant cases were due to the loss of ER (n = 6), loss of PR (n = 6), or loss of both receptors (n = 6). Receptor-negative primary tumors were always accompanied by receptor-negative recurrences. Among 27 patients with ER-positive primary tumors, loss of ER was a significant predictor (P = .0085) of poor response to subsequent endocrine therapy. Only one of eight patients (12.5%) with lost ER expression responded to tamoxifen therapy, whereas the response rate was 74% (14 of 19) for patients whose recurrent tumors retained ER expression. CONCLUSION Loss of ER expression in recurrent breast cancer should be considered as a cause for poor response to endocrine therapy in primarily ER-positive patients. We conclude that analysis of recurrent tumor samples may improve the predictive value of ER and PR assays.
Airway and lung elastic fibre is not reduced in asthma nor in asthmatics following corticosteroid treatment
Authors: RW Godfrey, S Lorimer, S Majumdar, E Adelroth, PW Johnston, AV Rogers, SA Johansson, PK Jeffery
Journal: European Respiratory Journal (1995)

By morphometric investigation of the relative content of elastic and collagen fibres, we have tested the hypothesis that loss of elastic fibres in the conducting airways and lung parenchyma may reduce tissue elastic recoil, resulting in increased airway maximal closure and apparent increased responsiveness. The study groups comprised: Group A (n = 11) with relatively mild atopic asthma using inhaled bronchodilators prn (i.e. short-term corticosteroids users); Group B (n = 9) with more severe asthma requiring inhaled bronchodilators regularly, and daily inhaled glucocorticosteroids (i.e. longterm corticosteroid users); Group C (n = 12) normal healthy workers. Bronchial biopsy samples were taken from three sites from the left lung. Group A biopsy samples were taken before and after a 4 wk treatment period with inhaled corticosteroids (200 micrograms b.i.d.) and the relative elastic and collagen fibre content of a subepithelial zone was determined from electron micrographs. In a parallel study, the relative proportion of elastic fibre in post mortem lung tissue samples (inner aspect of the bronchial wall, alveolar wall, and points of attachment of surrounding alveoli to intrapulmonary bronchi) from subjects suffering a fatal asthma attack (n = 11), and non-asthmatic suffering sudden death (n = 9), were determined using Miller's elastic and eosin counterstain for light microscopy. In bronchial biopsies of normal subjects, 4.6 (SEM 1.1)% of subepithelial connective tissue was elastic fibre, similar to mild asthmatic subjects, 1.9 (SEM 0.48)%. Neither short-term (4 weeks) inhaled corticosteroid (200 micrograms b.i.d.) nor long-term (&lt; 6 months) treatment with variable doses of inhaled steroids (100-1000 micrograms b.i.d.) significantly altered the elastic or collagen content of the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in right ventricular mass are unrelated to changes in pulmonary pressures in pulmonary arterial hypertension
Authors: Marielle van de Veerdonk, Sophie Dusoswa, Taco Kind, Johannes Marcus, Nico Westerhof, Anton Vonk-Noordegraaf
Journal: European Respiratory Journal (2011)

Background: In pulmonary arterial hypertension (PAH), chronic pressure overload leads to right ventricular (RV) dilatation, hypertrophy and ultimately RV failure and death. Yet, the relevance of changes in RV mass and the interaction with changes in pulmonary pressure have never been investigated.

Objectives: To assess the relationship between changes in pulmonary pressure, changes in RV mass and survival in PAH patients under PAH targeted therapies.

Methods: 45 patients underwent right heart catheterization to measure mean pulmonary artery pressure (mPAP) and cardiac magnetic resonance to assess RV mass before and after 12 months of therapy. RV mass was indexed for body surface area. During long-term follow-up of 59±27 months, 11 patients died.

Results: At baseline, survivors and non-survivors showed a similar mPAP (p=0.43) and RV mass index (p=0.06). RV mass index correlated to mPAP (R=0.51, p<0.01). During 1-year follow-up, changes in mPAP did not differ between survivors (-8±28%) and non-survivors (3±30%) (p=0.86). Overall, RV mass increased by 11±26% (p=0.03). Survivors showed an increased RV mass (17±25%; p<0.01), non-survivors showed an unchanged RV mass (-7±11%; p=0.16). Changes in RV mass were unrelated to age (p=0.50) or gender (p=0.44). Changes in RV mass were unrelated to changes in mPAP (R=0.14; p=0.37).

A decreased RV mass was associated with mortality (HR: 0.95; 95%-CI 0.91-0.99; p=0.02) whereas changes in mPAP did not relate to mortality (HR: 1.01; 95%-CI 0.98–1.02; p=0.25).

Conclusions: In PAH, changes in mPAP were not followed by changes in RV mass. An increased RV mass during follow-up was associated with a favorable prognosis.
A phase 3, multicenter, double-blind, placebo-controlled trial of lenvatinib (E7080) in patients with <sup>131</sup>I-refractory differentiated thyroid cancer (SELECT).
Authors: Martin Schlumberger, Makoto Tahara, Lori J. Wirth, Bruce Robinson, Marcia S. Brose, Rossella Elisei, Corina E. Dutcus, Begoña de las Heras, Junming Zhu, Mouhammed Amir Habra, Kate Newbold, Manisha H. Shah, Ana O. Hoff, Andrew G Gianoukakis, Naomi Kiyota, Matthew Hiram Taylor, Sung-Bae Kim, Monika K Krzyzanowska, Steven I. Sherman
Journal: Journal of Clinical Oncology (2014)

LBA6008 Background: Lenvatinib (LEN) is an oral tyrosine kinase inhibitor of the VEGFR1-3, FGFR1-4, PDGFRβ, RET, and KIT signaling networks. Based on efficacy results of the phase 2 study of patients (pts) with 131 I-refractory differentiated thyroid cancer (RR-DTC), this phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) was developed. Methods: This randomized, double-blind, placebo (PBO)-controlled study enrolled pts with RR-DTC with documented disease progression within 13 months (mo). Pts were stratified by age (≤65, &gt;65 years), region and ≤1 prior VEGFR-targeted therapies and randomized 2:1 to LEN or PBO (24mg/d, 28-d cycle). Upon progression, pts receiving PBO could crossover to open-label LEN. The primary endpoint was PFS assessed by Independent Radiologic Review; secondary endpoints included overall response rate (ORR; complete response [CR] + PR), overall survival (OS) and safety. Results: 392 pts (63.0 years median age; 51.0% male) were randomized. Pts on LEN had a significantly prolonged PFS vs PBO (hazard ratio 0.21, 95% confidence interval [CI] 0.14–0.31; P &lt;.0001); median PFS was LEN: 18.3 mo (95% CI 15.1–not evaluable), PBO: 3.6 mo (95% CI 2.2–3.7). A LEN PFS benefit was observed in all predefined subgroups; median LEN PFS for pts with prior vs no prior VEGF-therapy was 15.1 mo (n=66) and 18.7 mo (n=195), respectively. Rates (n) of CRs were LEN: 1.5% (4), PBO: 0; PRs were LEN: 63.2% (165), PBO: 1.5% (2).Median exposure duration was LEN: 13.8 mo, PBO: 3.9 mo; median time to LEN response was 2.0 mo. Median OS has not been reached; deaths per arm were LEN: 71 (27.2%), PBO: 47 (35.9%). The 5 most common LEN treatment-related adverse events (TRAEs; any grade) were hypertension (68%), diarrhea (59%), appetite decreased (50%), weight loss (46%), nausea (41%). LEN grade ≥3 TRAEs (≥5%) were hypertension (42%), proteinuria (10%), weight loss (10%), diarrhea (8%), appetite decreased (5%). The dose was reduced in 78.5% of pts and discontinued due to adverse events (AEs) in 14.2% of pts. Conclusions: LEN significantly improved PFS compared with PBO in pts with progressive RR-DTC. There were no unexpected toxicities and AEs were manageable. Clinical trial information: NCT01321554.
Impact of therapy with epoetin alfa on clinical outcomes in patients with nonmyeloid malignancies during cancer chemotherapy in community oncology practice. Procrit Study Group.
Authors: J Glaspy, R Bukowski, D Steinberg, C Taylor, S Tchekmedyian, S Vadhan-Raj
Journal: Journal of Clinical Oncology (1997)

To study the impact of Procrit (epoetin alfa; Amgen Inc, Thousand Oaks, CA) on quality of life, transfusion requirements, and hemoglobin in anemic cancer patients receiving chemotherapy.More than 500 community-based oncologists enrolled 2,342 patients with malignancies undergoing cytotoxic chemotherapy in an open-label study. Patients were treated with epoetin alfa 150 U/kg three times weekly, which could be doubled if the therapuetic response was judged inadequate. Total treatment was up to 4 months.Of the 2,342 patients enrolled, data were available for 2,030 patients. Of the 2,030, 1,047 patients completed all 4 months of epoetin alfa therapy. Epoetin alfa was associated with significant increases in mean self-rated scores for energy level, activity level, and overall quality of life; these improvements correlated with the magnitude of the hemoglobin increase and were independent of tumor response. In addition, epoetin alfa was associated with a significant increase in mean hemoglobin and with a significant decrease in the proportion of patients requiring transfusions (baseline to final value, P < .001). Epoetin alfa was well tolerated.Epoetin alfa is effective in improving the functional status and quality of life in anemic cancer patients receiving chemotherapy, as well as increasing hemoglobin level and decreasing transfusion requirements. Improvement in functional status can be attributed to an increase in hemoglobin level, demonstrating that quality of life in this group of patients can be improved by aggressively treating anemia. Further studies will be required to define the optimal doses and schedules for epoetin alfa.
5-HT1A receptors on mature dentate gyrus granule cells are critical for the antidepressant response
Authors: Benjamin Adam Samuels, Christoph Anacker, Alice Hu, Marjorie R Levinstein, Anouchka Pickenhagen, Theodore Tsetsenis, Noelia Madroñal, Zoe R Donaldson, Liam John Drew, Alex Dranovsky, Cornelius T Gross, Kenji F Tanaka, René Hen
Journal: Nature Neuroscience (2015)
"Trial-skilled" patients: How big the improvement in cooperation?
Authors: Andrii Sidorov, Yuriy Mostovoy, Nataliia Slepchenko
Journal: European Respiratory Journal (2013)

The aim of the study was to evaluate how the participation in trial in the past may improve the level of cooperation between the patient and investigator in the next trial.  Methods. The 30 patients with severe persistent bronchial asthma (BA) took part in 2 trials. The indication in both trials was BA. The trials had similar design in features concerning the cooperation of the patient and investigator: using of inhalers, completion of electronic diaries, performing of home peak flowmetry, performing of spirometry in clinic. These parameters were compared in the same patients in the first and in the second trial. The duration of each trial was 1 year. The duration of the period between the trials was 2,1±0,3 months. Data were summarized, using mean, median and standard deviation and range for continuous parameters and using counts and percentages for categorical parameters.  Results. In the second trial delay for the visits decreases from 7,7±1,2% to 6,9±1,3% (p>0,05). The returning of the used inhalers became 98,2±4,3% instead of 91,1±5,9% (p=0,04). The compliance for using electronic diaries and performing of the home spirometry increased from 84,2±7,3% to 93,5±6,4% (p=0,034). The persent of unacceptable spirometries during the clinic visits decreases from 5,5±0,9% to 3,6±0,5% (p=0,041).  Conclusions. It was demonstrated statistically significant improvement in performing of the trial procedures. But initial data were also good and improvement was not so clinically significant in order to choose trial-skilled patient instead of trial-naive one for enrollment in future trials. In case of worse initial data or bigger experience of the patients in trials this difference may become clinically significant.
Latent tuberculosis infection among close contacts of multidrugs-resistant tuberculosis patients in eastern Taiwan
Authors: Chih-Bin Lin, Jen-Jyh Lee, Hsu-Wen Chou
Journal: European Respiratory Journal (2012)

Tuberculin skin test (TST) and QuantiFERON-TB Gold in Tube test (QFT-GIT) are diagnostic tools for detection of  Mycobacterium tuberculosis  infection. These tests can be used to study the rate of infection in contacts of multidrug-resistance tuberculosis (MDR-TB) patients.  We performed TST and QFT-GIT to close contacts of MDR-TB patient in eastern Taiwan to evaluate the transmission and the efficiency of such tests.  A total of 592 close contacts of 112 confirmed MDR-TB patients were included in the study. TST-positive subjects were 310 (52.4%) and QFT-GIT-positive contacts were 326 (55.1%). Both tests are positive in 217 patients (37%), TST-positive and QFT-GIT-negative in 93 (16%), TST-negative and QFT-GIT-positive in 109 (18%), and both negative in 173 (29%). People older than 50 and aborigines showed higher rates of QFT-GIT-positive than people younger than 30 (69.9% vs.39.2%) and non-aborigines (60.5% vs. 30.6%).  Both TST and QFT-GIT can be used to detect latent tuberculosis infection, and both tests should be used in conjunction with risk assessment, radiography and other diagnostic tools. High incidence of latent tuberculosis infection among close contacts of MDR-TB patients in eastern Taiwan were detected and close follow up and monitoring are mandatory for early detection of possible active MDR-TB cases.