tbuckley/cabot-search huggingface dataset:
Bendamustine, lenalidomide, and dexamethasone (BRD) is highly effective with durable responses in relapsed multiple myeloma
Authors: Shaji K Kumar, Amrita Krishnan, Betsy LaPlant, Kristina Laumann, Vivek Roy, Todd Zimmerman, Morie A Gertz, Francis K Buadi, Keith Stockerl Goldstein, Ann Birgin, Mark Fiala, Lupe Duarte, Michelle Maharaj, Joan Levy, Ravi Vij
Journal: American Journal of Hematology (2015)

Bendamustine is a multifunctional alkylating agent with single agent activity in myeloma. We designed the current phase 1/2 trial to determine the maximum tolerated doses (MTD) of bendamustine that can be safely combined with lenalidomide and dexamethasone and to assess the safety and efficacy of the combination. Patients with relapsed MM following at least 1 prior therapy, but no more than four lines of prior therapy and with measurable disease were enrolled. Bendamustine 75 mg/m(2) given on days 1 and 2, lenalidomide 25 mg given days 1-21 and dexamethasone 40 mg on days 1, 8, 15, and 22, was the recommended Phase 2 dose. Seventy-one patients were accrued: 21 on Phase 1 and 50 on Phase 2. The median age was 62.3 years; patients had a median of three prior lines of therapy (range 1-4), with over 70% of the patients having received prior lenalidomide, bortezomib, and/or peripheral blood stem cell transplant. Thirty-four of 70 (49%) patients had a confirmed partial response or better, including 20 patients (29%) with a very good partial response or better. An additional 4 patients had a minor response, translating to an overall 55% clinical benefit rate. Grade 3 or higher toxicity was seen in 96% of patients, with ≥grade 3 hematologic in 94% and nonhematologic in 50%. The median progression free survival was 11.8 months and the median duration of response was 23 months. The combination of bendamustine, lenalidomide, and dexamethasone is very effective in relapsed multiple myeloma with high response rates and durable responses
In Situ Fc Receptor-Bearing Cells in Two Murine Tumors. I. Isolation and Identificationo 2 o 3
Authors: J. H. Korn, J. S. Haskill, H. T. Holden, L. A. Radov, F. L. Ritter
Journal: JNCI Journal of the National Cancer Institute (1978)

The in situ inflammatory response was studied in 2 different tumors, the T1699 mammary adenocarcinoma in inbred DBA/2 mice and a sarcoma induced in inbred C57BL/6 mice by murine sarcoma virus. The presence of Fc receptors (FcR's) on infiltrating host cells was determined by rosette formation with antibody-coated sheep red blood cells (EA). Differences in FcR-binding activity among various cells were detected with the use of EA prepared with a range of antibody concentrations. Cells bearing FcR represented one-third or more of the inflammatory cell population in both tumors. The FcR-positive cells were heterogeneous in regard to both cell type and FcR activity. Monocytes and macrophages had greater FcR activity than did lymphocytes. Different populations of FcR-positive cells could be isolated by their EA-binding characteristics.
Antisense Oligonucleotides: Promise and Reality
Authors: Irina Lebedeva, CA Stein
Journal: The Annual Review of Pharmacology and Toxicology (2001)

Antisense oligonucleotides have been used for more than a decade to downregulate gene expression. Phosphodiester oligonucleotides are nuclease sensitive, and the more nuclease-resistant phosphorothioate oligonucleotides are now in common use in the laboratory and have entered clinical trials. However, these molecules are highly bioactive and may inhibit gene expression by more than one mechanism. Although some dramatic successes have been demonstrated, it can still be difficult to properly interpret experimental data derived from the use of this class of oligonucleotide. This review discusses some of these issues with particular reference to a major area of current interest—inhibition of bcl-2 expression in tumor cells.
Amphiregulin Is a Critical Downstream Effector of Estrogen Signaling in ERα-Positive Breast Cancer
Authors: Esther A. Peterson, Edmund C. Jenkins, Kristopher A. Lofgren, Natasha Chandiramani, Hui Liu, Evelyn Aranda, Maryia Barnett, Paraic A. Kenny
Journal: Cancer Research (2015)

Estrogen stimulation promotes epithelial cell proliferation in estrogen receptor (ERα)-positive breast cancer. Many ERα target genes have been enumerated, but the identities of the key effectors mediating the estrogen signal remain obscure. During mouse mammary gland development, the estrogen growth factor receptor (EGFR) ligand amphiregulin acts as an important stage-specific effector of estrogen signaling. In this study, we investigated the role of amphiregulin in breast cancer cell proliferation using human tissue samples and tumor xenografts in mice. Amphiregulin was enriched in ERα-positive human breast tumor cells and required for estrogen-dependent growth of MCF7 tumor xenografts. Furthermore, amphiregulin levels were suppressed in patients treated with endocrine therapy. Suppression of EGF receptor signaling appeared necessary for the therapeutic response in this setting. Our findings implicate amphiregulin as a critical mediator of the estrogen response in ERα-positive breast cancer, emphasizing the importance of EGF receptor signaling in breast tumor pathogenesis and therapeutic response.
Do We Need Yet Another Blocker of the Renin-Angiotensin System?⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Franz H. Messerli, Richard N. Re
Journal: Journal of the American College of Cardiology (2007)
PALETTE: A randomized, double-blind, phase III trial of pazopanib versus placebo in patients (pts) with soft-tissue sarcoma (STS) whose disease has progressed during or following prior chemotherapy—An EORTC STBSG Global Network Study (EORTC 62072).
Authors: W. T. Van Der Graaf, J. Blay, S. P. Chawla, D. Kim, B. Bui Nguyen, P. G. Casali, P. Schöffski, M. Aglietta, A. P. Staddon, Y. Beppu, A. Le Cesne, H. Gelderblom, I. R. Judson, N. Araki, M. Ouali, S. Marreaud, R. Hodge, M. Dewji, A. P. Dei Tos, P. Hohenberger
Journal: Journal of Clinical Oncology (2011)

LBA10002 Background: Pazopanib, a multi targeted angiogenesis inhibitor, has demonstrated single-agent activity in pts with advanced STS. The efficacy and safety of pazopanib versus placebo as second or later line treatment were evaluated in pts with metastatic STS in a multi-center, international, double-blind, placebo-controlled phase III trial. Methods: Pts ≥18 years of age with angiogenesis inhibitor-naïve, histologically proven, metastatic STS, who failed at least one anthracycline containing regimen, could enter the study. They should have ≥1 measurable baseline lesion (per RECIST v1.0), WHO PS 0-1, adequate bone marrow, coagulation, hepatic and renal function, no poorly controlled hypertension, no bleeding diathesis, and no CNS involvement. The study has been conducted by EORTC and GSK in collaboration with 72 sarcoma centers worldwide. Pts were randomized 2:1 to receive either pazopanib 800 mg once daily or placebo until tumor progression, unacceptable toxicity, death, or pt’s request. Results: A total of 369 randomized pts (246 pazopanib, 123 placebo), median age of 56 years, participated in the study (EORTC 45 %, other 55%). Median duration of follow-up at clinical cut-off date is 15 months. The primary endpoint of progression-free survival (PFS) per independent review is significantly prolonged with pazopanib (median: 20 vs 7 weeks; HR=0.31, 95% CI 0.24-0.40 ; P&lt;0.0001). The interim analysis for overall survival shows a statistically non-significant improvement of pazopanib vs placebo (median: 11.9 vs 10.4 months, HR=0.83, 95% CI 0.62-1.09). Main on-therapy grade 3-4 toxicities in the pazopanib vs placebo arm respectively: fatigue (13%, 6%), hypertension (7%, nil), anorexia (6%, nil), and diarrhea (5%, 1%). Similarly, thromboembolic events (grade 3-5 ) (3%, 2%), LVEF drop of &gt;15% (8%, 3%). Median relative dose intensity of pazopanib was 768 mg daily. Conclusions: Pazopanib is an active drug in anthracycline pretreated metastatic STS pts with an increase in median PFS of 13 weeks.
Ventilation-perfusion inequality in patients with non-alcoholic liver cirrhosis
Authors: G Hedenstierna, C Soderman, LS Eriksson, J Wahren
Journal: European Respiratory Journal (1991)

Ventilation-perfusion relationships were studied in patients with non-alcoholic liver cirrhosis. Spirometry was essentially normal but the transfer factor of the lung (DLCO) was reduced by an average 34% of predicted. Arterial oxygen tension (PaO2) ranged from normal down to 6.9 kPa. Varying degrees of ventilation-perfusion (VA/Q) abnormalities (multiple inert gas elimination technique) were observed with increased dispersion of the perfusion distribution (log SDQ, 0.90; range 0.32-1.71; upper normal limit, 0.60) and the presence of both regions of low VA/Q ratios (between 0.1 and 0.005) (mean 4.1%; range 0-18.8%) and shunt (VA/Q ratios below 0.005) (mean 3.9%; range 0.19.8%). There was a close similarity between measured and calculated PaO2 in normoxaemic patients, but calculated values exceeded measured PaO2 in hypoxaemic patients. The difference between calculated and measured PaO2 correlated inversely to DLCO (r = 0.65, p less than 0.05). An inverse correlation was also noted between DLCO and the sum of shunt and low VA/Q regions (r = 0.87, p less than 0.001). It is concluded that hypoxaemia in non-alcoholic liver cirrhosis patients can be accounted for by intrapulmonary shunting and VA/Q mismatch, and possibly a "diffusion-perfusion" defect in patients with more severe gas exchange impairment.
Chromosomes of Primary Granulocytic Leukemia (Chloroleukemia) in the Rat
Authors: Peter C. Nowell, Sandra Ferry, David A. Hungerford
Journal: JNCI Journal of the National Cancer Institute (1963)

Chromosome studies were done on 9 rats with primary granulocytic leukemia (chloroleukemia) induced by gastric instillation of methylcholanthrene. Significant deviation from the normal diploid number (2n = 42) or from normal chromosome morphology was observed in only 1 rat whose leukemic cells showed at least 2 abnormal stemlines with 43 and 44 chromosomes. The other 8 rats with chloroleukemia and 3 with primary lymphocytic leukemia, similarly induced, did not show chromosome changes. A transplantable chloroleukemia, carried for 10 years, showed an apparently stable abnormal stemline with 43 chromosomes. It is concluded that there is no consistent or specific chromosome change associated with the primary methylcholanthrene-induced leukemias investigated.—J Nat Cancer Inst 30: 687–703, 1963.
Adherence and tolerance of an auto-CPAP (APAP) device specially designed for occidental way of life and bedroom: Beyond technology, medical appearance is obsolete
Authors: Eric Hazouard, Jean-Philippe Maffre, Violaine Kubiszewski
Journal: European Respiratory Journal (2012)

Observance up than 3 hr/night, only is required in France to allocate reimbursement of CPAP treatment for Sleep Apnoeas Syndrome. But control of hypertension requires up than 4hr /night. Breas i-Sleep, or Fisher&Pakell ICON are clearly designed to look as a clock or a radio-alarm-clock without external electric tranformer.

Aim: Definite if such CPAP device is associated with a mean sleep use up than 4hr30, achieving 3 sleep's cycles. Data collection [confort, residual AHI, therapeutic Pressure, etc.]

Methods: two HomeCare HealthCare Providers (no financial or material conflict of interest), Non6comparative observational study. We collect use's duration of a non-randomized cohort of consecutive OSA patients, all ventilated by ICON, APAP mode, 4/16 cmH20, no ramp with optimal subjective comfort humidification setting.

Results: 108 consecutive symptomatic OSA patients (IAH > 30/hr), evaluation time: 5 months delay treatment, [male] 61%, 65 +/- 16 y/o; residual AHI = 4,8 +/- 3,8/hr and P95% = 9,3 +/- 3,76 cmH2O.

Observance 342 +/- 42 min; confort's evaluation through a modified Analogic Visual Scale (AVS) 7,4 +/- 1,2; Design's evaluation through a modified AVS 8,7 +/- 4,3.

Conclusions : 

A pretty bedroom designed CPAP device is associated with a therapeutic duration up than 5hr30. An affective-based customer societal approach of such treatment seems relevant to enhance patient adherence. Comparative studies are required to comfort this monocentric and limited non comparative descriptive study

Acknowledgements, Mrs Baucher M, Mbar®, Safond M, SOS-Oxygene®; Hesbert R, Fisher&Paykell,France.
Responsiveness and Progression of Mammary Tumors in High-Cancer-Strain Mice<xref ref-type="fn" rid="fn1">2</xref>
Authors: Francesco Squartini
Journal: JNCI Journal of the National Cancer Institute (1962)

The growth curves of 176 mammary tumors in 94 BALB/cf and RIII female mice that delivered litters while bearing tumors were checked for the occurrence of responsiveness to pregnancy. Responsiveness, in the form of a total or partial dependence of growth on the stimuli of pregnancy, was observed in many tumors. However, strain differences have been found. In BALB/cf mice, 19 percent of the tumors was responsive to pregnancy, with a clear prevalence of the partially responsive tumors (12.7%). In RIII mice, 80.3 percent of the tumors was responsive to pregnancies, either totally (39.4%) or partially (40.9%). Usually in BALB/cf tumors, responsiveness was rapidly lost by progression, whereas in RIII tumors it was often maintained for long periods. These data lead to the conclusion that responsiveness is a rule with few exceptions in tumors of the RIII strain, whereas it is apparently an exception to the rule in the BALB/cf strain. Other differences in the growth characteristics of mammary tumors of the same strains were shown in a previous investigation. Possible causes for these strain differences are suggested.
Phase III trial of gemcitabine plus docetaxel (GD) compared to capecitabine plus docetaxel (CD) with planned crossover to the alternate single agent in metastatic breast cancer (MBC)
Authors: A. D. Seidman, A. Brufsky, R. H. Ansari, J. R. Rubinsak, R. S. Stein, L. S. Schwartzberg, J. F. Stewart, L. Zhao, J. Gill, D. Tai
Journal: Journal of Clinical Oncology (2009)

1000 Background: GD and CD are efficacious in patients (pts) with MBC. This study compared safety and efficacy of GD and CD induction regimens, where the alternate, single-agent, crossover therapy (GD to C or CD to G) was predetermined. Primary endpoint was time to progressive disease (TTP). Secondary endpoints included toxicities, overall response (ORR), and overall survival (OS). Methods: This multicenter, open-label, phase III study enrolled MBC pts with possible prior anthracycline therapy, adjuvant or neoadjuvant taxane therapy, but no taxane therapy for MBC ≤6 months prior to entry. Enrollment of 442 pts (221 per arm) was planned with 385 progressions required to achieve 80% power for a 2-month observed difference in median TTP between arms. Pts were randomized to: GD: G 1,000mg/m 2 Days 1, 8 plus D 75 mg/m 2 Day 1, q21 days; or CD: C 1,000 mg/m 2 BID, Days 1–14 plus D 75 mg/m 2 Day 1, q 21 days. Upon disease progression, pts were given crossover C or G at doses and schedules identical to induction. ORR was assessed by RECIST. Results: Demographics of 472 enrolled pts were balanced between arms; 57% had prior anthracycline. GD caused greater myelosuppression than CD, but without greater febrile neutropenia. Gastrointestinal toxicities, mucositis, and hand-foot syndrome were greater with CD. More pts in the CD arm (n=61, 26.2%) versus the GD arm (n=41, 17.2%) discontinued due to toxicity (p=0.023). ORR, TTP, and OS were not significantly different comparing GD and CD. However, ORR and TTP were significantly greater for the GD to C crossover monotherapy compared to CD to G. Post-hoc analysis of crossover pts showed that the TTP sum from induction through crossover was 6.1 months greater for GD to C. Conclusions: GD and CD had similar efficacy with toxicity profiles consistent with prior clinical experience. Results suggest that the GD to C crossover sequence may provide a clinical benefit over CD to G. [Table: see text] [Table: see text]
Clinical and laboratory predictors of survival in patients with severe community-acquired pneumonia (CAP)
Authors: Tetyana Kireeva, Tetyana Pertseva, Kseniia Bielosludtseva, Svitlana Volkova
Journal: European Respiratory Journal (2014)

Objectives: to determine the significance of different clinical, inflammatory (procalcitonin (PCT) and C-reactive protein (CRP)), immunological (CD4, CD8) markers as predictors of survival in patients with severe CAP.

Methods: 51 patients with verified severe CAP without HIV (age – 57,50±4,31 years, men – 37 (72,5%),women – 14 (27,5%)). General analysis, SMRT-CO count, determination of serum PCT and CRP, blood CD4, CD8 prior antibacterial therapy (ABT) (visit 1), on 8–10 day of ABT (visit 2) with count of delta (v 2-1), statistic including factor loading.

Results: in 6 (11,7%) patients with severe CAP, despite adequate ABT, lethal end of disease was determined. Statistical value on survival of different parameters is present in table (maximum is 1)

View this table:

Factor loading of different parameters in patients with severe CAP





.

Conclusions: 1) initial SMRT-CO count cannot serve as a predictor of survival in patients with severe CAP; 2) feature of survival predicting in patients with severe CAP is the complex account of immune and inflammatory markers; 3) the most significant laboratory predictors of outcome in patients with severe CAP is individual dynamic of CD4 and PCT.
Dry Eye Syndrome in Subjects With Diabetes and Association With Neuropathy
Authors: Vasilis Achtsidis, Ioanna Eleftheriadou, Eleftheria Kozanidou, Konstantine I. Voumvourakis, Eleftherios Stamboulis, Panos G. Theodosiadis, Nicholas Tentolouris
Journal: Diabetes Care (2014)

Diabetes mellitus has been identified as a risk factor for dry eye syndrome (DES). The prevalence of DES in diabetes has been reported to be up to 54.3% (1). DES compromises quality of life because it induces ocular discomfort and visual disturbance and may be complicated by corneal epithelial defects, erosions, or ulcers. Therefore, it is recognized as a growing public health problem that should be diagnosed and treated (1).

Among the various forms of diabetic neuropathies, chronic sensorimotor distal symmetric polyneuropathy (PN) is the most common form and may manifest with symptoms while sensory and motor deficits are detected (2). The cornea is one of the most densely innervated parts of the human body containing myelinated A-δ and unmyelinated C fibers, deriving its innervation from the ophthalmic division …
Dietary Recommendations for Children and Adolescents
Authors: Samuel S. Gidding, Barbara A. Dennison, Leann L. Birch, Stephen R. Daniels, Matthew W. Gilman, Alice H. Lichtenstein, Karyl Thomas Rattay, Julia Steinberger, Nicolas Stettler, Linda Van Horn
Journal: Circulation (2005)

Since the American Heart Association last presented nutrition guidelines for children, significant changes have occurred in the prevalence of cardiovascular risk factors and nutrition behaviors in children. Overweight has increased, whereas saturated fat and cholesterol intake have decreased, at least as percentage of total caloric intake. Better understanding of children's cardiovascular risk status and current diet is available from national survey data. New research on the efficacy of diet intervention in children has been published. Also, increasing attention has been paid to the importance of nutrition early in life, including the fetal milieu. This scientific statement summarizes current available information on cardiovascular nutrition in children and makes recommendations for both primordial and primary prevention of cardiovascular disease beginning at a young age.
Genetic Modification of the Association between Peripubertal Dioxin Exposure and Pubertal Onset in a Cohort of Russian Boys
Authors: Olivier Humblet, Susan A. Korrick, Paige L. Williams, Oleg Sergeyev, Claude Emond, Linda S. Birnbaum, Jane S. Burns, Larisa M. Altshul, Donald G. Patterson, Wayman E. Turner, Mary M. Lee, Boris Revich, Russ Hauser
Journal: Environmental Health Perspectives (2012)

Background: Exposure to dioxins has been associated with delayed pubertal onset in both epidemiologic and animal studies. Whether genetic polymorphisms may modify this association is currently unknown. Identifying such genes could provide insight into mechanistic pathways. This is one of the first studies to assess genetic susceptibility to dioxins.Objectives: We evaluated whether common polymorphisms in genes affecting either molecular responses to dioxin exposure or pubertal onset influence the association between peripubertal serum dioxin concentration and male pubertal onset.Methods: In this prospective cohort of Russian adolescent boys (n = 392), we assessed gene–environment interactions for 337 tagging single-nucleotide polymorphisms (SNPs) from 46 candidate genes and two intergenic regions. Dioxins were measured in the boys' serum at age 8–9 years. Pubertal onset was based on testicular volume and on genitalia staging. Statistical approaches for controlling for multiple testing were used, both with and without prescreening for marginal genetic associations.Results: After accounting for multiple testing, two tag SNPs in the glucocorticoid receptor (GR/NR3C1) gene and one in the estrogen receptor-α (ESR1) gene were significant (q < 0.2) modifiers of the association between peripubertal serum dioxin concentration and male pubertal onset defined by genitalia staging, although not by testicular volume. The results were sensitive to whether multiple comparison adjustment was applied to all gene–environment tests or only to those with marginal genetic associations.Conclusions: Common genetic polymorphisms in the glucocorticoid receptor and estrogen receptor-α genes may modify the association between peripubertal serum dioxin concentration and pubertal onset. Further studies are warranted to confirm these findings.
Tumor localization of adoptively transferred indium-111 labeled tumor infiltrating lymphocytes in patients with metastatic melanoma.
Authors: B Fisher, B S Packard, E J Read, J A Carrasquillo, C S Carter, S L Topalian, J C Yang, P Yolles, S M Larson, S A Rosenberg
Journal: Journal of Clinical Oncology (1989)

Lymphoid cells infiltrating into human tumors can be expanded in vitro in medium containing interleukin-2 (IL-2). Adoptive transfer of these tumor-infiltrating lymphocytes (TIL) mediates potent antitumor effects in murine tumor models. Clinical trials to evaluate the efficacy of these cells in patients with advanced cancer are underway. We have investigated whether infused TIL labeled with indium 111 (111In) oxine can traffic and localize to metastatic deposits of tumor. Six patients with metastatic malignant melanoma who had multiple sites of subcutaneous, nodal, and/or visceral disease were the subjects of the study. The patients received cyclophosphamide 36 hours before receiving the intravenous (IV) infusion of TIL followed by IL-2 IV every eight hours. The distribution and localization of the TIL were evaluated using serial whole body gamma camera imaging, serial blood and urine samplings, and serial biopsies of tumor and normal tissue. 111In-labeled TIL localized to lung, liver, and spleen within two hours after the infusion of activity. Activity in the lung diminished within 24 hours. As early as 24 hours after injection of 111In-labeled TIL, localization of TIL to sites of metastatic deposits was demonstrated in all six patients using either imaging studies or biopsy specimens or both. 111In activity in tumor tissue biopsies ranged from three to 40 times greater than activity in normal tissue. A progressive increase in the radioactive counts at sites of tumor deposit was seen. This study shows that labeled TIL can localize preferentially to tumor, and provides information concerning the possible mechanism of the therapeutic effects of TIL.