tbuckley/cabot-search huggingface dataset:
Capecitabine, mitomycin C &amp; radiation for HIV patients with anal squamous cell carcinoma
Authors: W. Adler, F.-C. Lee, G. Wong
Journal: Journal of Clinical Oncology (2004)

4239 Background: With highly active anti-retroviral therapy, HIV-positive patients are living longer. Increased incidence of anal squamous cell carcinoma (ASCC) has been noted in these patients. Optimal therapy for ASCC is yet to be defined. Median time to local failure and to death of 1.7 months and 8 months, respectively, has been reported in HIV-positive patients with ASCC treated with chemoradiation. Mitomycin C and 5-fluorouracil (5-FU) in combination with radiation therapy (XRT) has been advocated as reasonable treatment. We report our growing experience with mitomycin, capecitabine and concurrent XRT. Methods: Seven HIV-positive patients, (CD4 range 7–339, at diagnosis of ASCC) were treated with day 1 mitomycin (dose range 10–12 mg/m2), day 1–7 capecitabine (1.5–2.5 gm/m2 divided b.i.d), and concurrent XRT (30.6 Gy in 17 fractions). Patients were given an additional standard 14-day treatment with capecitabine 3–7 weeks after completion of XRT. Initial tumor grade prior to treatment included 5 patients with T1 lesions and 2 patients with T2 lesions. Results: All patients completed treatment. No grade 3 or 4 hematologic or gastrointestinal toxicities were noted. Grade 2 or 3 skin toxicity from XRT was noted in all patients. No patients died of ASCC. Mean disease free progression is 11 months (range 4–26 months). Four patients remain in remission. Of 3 recurrences, 1 patient has died. This latter patient, at ASCC diagnosis, had poor functional status and a CD4 count of 7, yet lived 11 months after treatment. A second recurrence had bulky disease. Conclusions: This regimen is well-tolerated, with efficacy comparable to previous reports of combination chemoradiation that included infusional 5-FU, and may allow sphincter preservation by sparing abdominoperineal resection in patients without bulky disease. No significant financial relationships to disclose.
Mito-FLAG with Ara-C as bolus versus continuous infusion in recurrent or refractory AML—long-term results of a prospective randomized intergroup study of the East German Study Group Hematology/Oncology (OSHO) and the Study Alliance Leukemia (SAL)
Authors: A. Thiel, J. Schetelig, W. Pönisch, K. Schäfer-Eckart, W. Aulitzky, N. Peter, A. Schulze, G. Maschmeyer, S. Neugebauer, R. Herbst, A. Hänel, A. Morgner, F. Kroschinsky, M. Bornhäuser, T. Lange, M. Wilhelm, D. Niederwieser, G. Ehninger, F. Fiedler, M. Hänel
Journal: Annals of Oncology (2015)
S111 Asthma, puberty and BMI in the 1958 British Birth Cohort
Authors: D. L. Jarvis, L. Gnatiuc, R. B. Newson
Journal: Thorax (2010)

Studies suggest asthma is associated with body mass index (BMI), pubertal development and hormonal status. We used data collected at ages 7, 11, 16 and 33 from the 1958 British Birth Cohort to explore the association of asthma with BMI and pubertal development. Wheeze was considered present at age 7, 11 or 16 if participant9s mothers reported ‘ever attacks of asthma or wheezy bronchitis’ and, at age 33, if participants reported ‘wheezing or whistling in the chest’ in the last year. Age of menarche was reported at age 16. The association at each age of wheeze with BMI (&lt;18.5, 18.5&lt;25, 25+) and with age of menarche (&lt;12, 13–14 years, 16+) was assessed in logistic regression models adjusted for parental asthma, father9s social class, birth order and smoking (age 33 only). At age 7, 11 and 16, being overweight was associated with wheeze, an association that was stronger and more significant in girls than in boys. Wheeze at age 33 was associated with being overweight at age 33 in both men and women, but there was no consistent evidence that being overweight in childhood was associated with wheeze at the age of 33. Among 4524 girls with information 15.4% had reached menarche by age 12, and 2.2% had not reached menarche by age 16. The prevalence of being overweight at age 11 in the early and late menarche groups was 20.6% and 1.25% respectively, and the prevalence of being underweight at the age of 16 was 3.7% and 47.0%. Early menarche was associated with wheeze at age 11 (OR=1.57, 95% CI 1.19 to 2.09) even in 11-year-old girls with normal BMI. Late, but not early menarche was associated with wheeze at age 16 (OR=2.09, 95% CI 1.17 to 3.73). Neither early nor late menarche was associated with wheeze at age 33 years. At each follow-up of the 1958 birth cohort, wheeze was associated with being overweight in females. Although girls with early menarche were more overweight in childhood, and experienced more wheeze at age 11, there was no evidence that early menarche was associated with wheeze at the age of 33 years.
Reticular erythematous mucinosis syndrome and a monoclonal IgG kappa paraprotein-is there an association?
Authors: I. Zaki, L. Shall, L.G. Millard
Journal: British Journal of Dermatology (1993)

Journal Article Reticular erythematous mucinosis syndrome and a monoclonal IgG kappa paraprotein—is there an association? Get access I. Zaki, I. Zaki Department of Dermatology, Queen's Medical Centre, Derby Road, Nottingham NG7 2UH, U.K. Search for other works by this author on: Oxford Academic Google Scholar L. Shall, L. Shall Department of Dermatology, Queen's Medical Centre, Derby Road, Nottingham NG7 2UH, U.K. Search for other works by this author on: Oxford Academic Google Scholar L.G. Millard L.G. Millard Department of Dermatology, Queen's Medical Centre, Derby Road, Nottingham NG7 2UH, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 129, Issue 3, 1 September 1993, Pages 347–348, https://doi.org/10.1111/j.1365-2133.1993.tb11867.x Published: 01 September 1993
Antitumor Activity of NK012 Combined with Cisplatin against Small Cell Lung Cancer and Intestinal Mucosal Changes in Tumor-Bearing Mouse after Treatment
Authors: Tatsuya Nagano, Masahiro Yasunaga, Koichi Goto, Hirotsugu Kenmotsu, Yoshikatsu Koga, Jun-ichiro Kuroda, Yoshihiro Nishimura, Takashi Sugino, Yutaka Nishiwaki, Yasuhiro Matsumura
Journal: Clinical Cancer Research (2009)

To investigate the advantages of treatment with the SN-38-incorporating polymeric micelles NK012 over CPT-11 in combination with cisplatin [cis-dichlorodiammineplatinum (II) (CDDP)] in mice bearing a small cell lung cancer xenograft in terms of antitumor activity and toxicity, particularly intestinal toxicity.Cytotoxic effects were evaluated in human small cell lung cancer cell lines [H69, H82, and vascular endothelial growth factor (VEGF)-secreting cells (SBC-3/VEGF and its mock transfectant SBC-3/Neo)]. In vivo antitumor effects were evaluated in SBC-3/Neo-bearing and SBC-3/VEGF-bearing mice after NK012/CDDP or CPT-11/CDDP administration on days 0, 7, and 14. Drug distribution was analyzed by high-performance liquid chromatography or fluorescence microscopy, and the small intestine was pathologically examined.The in vitro growth-inhibitory effects of NK012 were 198- to 532-fold more potent than those of CPT-11. A significant difference in the relative tumor volume on day 30 was found between NK012/CDDP and CPT-11/CDDP treatments (P = 0.0058). Inflammatory changes in the small intestinal mucosa were rare in all NK012-treated mice but were commonly observed in CPT-11-treated mice. Moreover, a large amount of CPT-11 was excreted into the feces and high CPT-11 concentration was detected in the small intestinal epithelium. On the other hand, a small amount of NK012 was found in the feces and NK012 was weakly and uniformly distributed in the mucosal interstitium.NK012/CDDP combination may be a promising candidate regimen against lung cancer without severe diarrhea toxicity and therefore warrants further clinical evaluation.
Phase 1 trial of a novel anti-CD20 fusion protein in pretargeted radioimmunotherapy for B-cell non-Hodgkin lymphoma
Authors: Andres Forero, Paul L. Weiden, Julie M. Vose, Susan J. Knox, Albert F. LoBuglio, Jordan Hankins, Michael L. Goris, Vincent J. Picozzi, Don B. Axworthy, Hazel B. Breitz, Robert B. Sims, Richard G. Ghalie, Sui Shen, Ruby F. Meredith
Journal: Blood (2004)
Effects of Leisure-Time Physical Activity and Ventilatory Function on Risk for Stroke in Men: The Reykjavík Study
Authors: Uggi Agnarsson
Journal: Annals of Internal Medicine (1999)

Stroke is a major cause of illness, death, and health expenditures. Leisure-time physical activity may reduce the risk for stroke.To examine the association of leisure-time physical activity and pulmonary function with risk for stroke.Prospective cohort study.Reykjavík, Iceland.4484 men 45 to 80 years of age followed for a mean (+/-SD) of 10.6 +/- 3.6 years.Patients underwent physical examination, blood sampling, and spirometry and completed a questionnaire about health and exercise. Computerized hospital records were used to identify strokes, and the Icelandic National Registry was used to identify deaths.New stroke developed in 249 men (5.6%) (hemorrhagic stroke in 44 [18%] and ischemic stroke in 205 [82%]). In a multivariable hazard analysis that controlled for known risk factors for cerebrovascular disease, leisure-time physical activity maintained after 40 years of age was associated with a reduced risk for stroke (relative risk, 0.69 [CI, 0.47 to 1.01] for total stroke and 0.62 [CI, 0.40 to 0.97] for ischemic stroke). Risk for stroke increased with diminished ventilatory function (FVC or FEV1) (relative risk, 1.9 [CI, 1.06 to 3.25] for the lowest compared with the highest quintile).Middle-aged men who participate in leisure-time physical activity and have good pulmonary function seem to have a lower risk for stroke than men who are not active or have diminished pulmonary function.
Both TEAD-Binding and WW Domains Are Required for the Growth Stimulation and Oncogenic Transformation Activity of Yes-Associated Protein
Authors: Bin Zhao, Joungmok Kim, Xin Ye, Zhi-Chun Lai, Kun-Liang Guan
Journal: Cancer Research (2009)

The Yes-associated protein (YAP) transcription coactivator is a candidate human oncogene and a key regulator of organ size. It is phosphorylated and inhibited by the Hippo tumor suppressor pathway. TEAD family transcription factors were recently shown to play a key role in mediating the biological functions of YAP. Here, we show that the WW domain of YAP has a critical role in inducing a subset of YAP target genes independent of or in cooperation with TEAD. Mutation of the WW domains diminishes the ability of YAP to stimulate cell proliferation and oncogenic transformation. Inhibition of YAP oncogenic-transforming activity depends on intact serine residues 127 and 381, two sites that could be phosphorylated by the Hippo pathway. Furthermore, genetic experiments in Drosophila support that WW domains of YAP and Yki, the fly YAP homologue, have an important role in stimulating tissue growth. Our data suggest a model in which YAP induces gene expression and exerts its biological functions by interacting with transcription factors through both the TEAD-binding and WW domains.
Riedel's thyroiditis, retroperitoneal fibrosis, and sclerosing cholangitis: diseases with one pathogenesis?
Authors: W A De Boer
Journal: Gut (1993)

Letters the appreciable differences seen in the results.The studies of Lauritsen et al, with faecal dialysates reflect only the intraluminal concen- trations but provide no information about the intramucosal concentrations.The information that results from both types of studies, how- ever, can be complementary.Finally, we totally agree that the very low mucosal concentrations of 5-ASA after Salazopyrin supports the hypothesis that Salazopyrin has pharmocological properties that are different from those of 5-ASA and contribute to its therapeutic efficacy.
Predictors of Occult Metastasis in Clinical Stage I Nonseminoma: A Systematic Review
Authors: Yvonne Vergouwe, Ewout W. Steyerberg, Marinus J.C. Eijkemans, Peter Albers, J. Dik F. Habbema
Journal: Journal of Clinical Oncology (2003)

Patients with clinical stage I nonseminomatous testicular germ cell tumor should ideally receive adjuvant therapy only when they are at high risk for occult metastasis. We aimed to quantify the importance of predictors for occult metastasis by performing a systematic review of the relevant literature. In addition, we reviewed published multivariable models and risk-adapted treatment policies.We identified 23 publications between 1979 and 2001, reporting a total of 2,587 patients. Twenty-nine percent of the patients (759 of 2,587 patients) had occult metastases, which was diagnosed either at retroperitoneal lymph node dissection (n = 193) or during follow-up (n = 566). Odds ratios (OR) were pooled using meta-analysis techniques.The presence of vascular invasion of the primary tumor cells had the strongest effect (OR, 5.2; 95% CI, 4.0 to 6.8). Immunohistochemical staining of the primary tumor cells with the MIB-1 monoclonal antibody showing proliferative activity was a promising predictor (OR, 4.7; 95% CI, 2.0 to 11). Intermediate effects were found for embryonal carcinoma in the primary tumor (OR, 2.9; 95% CI, 2.0 to 4.4) and a high pathologic stage of the tumor (OR, 2.6; 95% CI, 1.8 to 3.8). Size of the primary tumor and age of the patient had weaker though also statistically significant associations with occult metastasis. Until now, multivariable models often included vascular invasion and embryonal carcinoma with one or two weaker predictors. None of the published risk-adapted treatment policies included MIB-1 staining.Several strong predictors for occult metastasis were identified. A risk-adapted treatment policy should be developed that incorporates all relevant predictors so that adjuvant therapy is targeted better to those with occult metastases.
Reduction of Regulatory T Cells by Mogamulizumab, a Defucosylated Anti-CC Chemokine Receptor 4 Antibody, in Patients with Aggressive/Refractory Mycosis Fungoides and Sézary Syndrome
Authors: Xiao Ni, Jeffrey L. Jorgensen, Meghali Goswami, Pramoda Challagundla, William K. Decker, Youn H. Kim, Madeleine A. Duvic
Journal: Clinical Cancer Research (2014)

Abstract Purpose: The CC chemokine receptor 4 (CCR4) is expressed on malignant T cells in cutaneous T-cell lymphoma (CTCL) as well as on regulatory T cells (Treg). When mogamulizumab, a defucosylated monoclonal antibody, binds to CCR4, it induces antibody-dependent cellular cytotoxicity against CCR4+ malignant T cells. The goal of this study was to determine the effect of mogamulizumab on CCR4+ Tregs in patients with CTCL. Experimental Design: Peripheral blood of 24 patients with CTCL participating in a phase I/II trial was analyzed for CCR4 expression on different T-cell subsets by flow cytometry, before and after one course of mogamulizumab. The number and function of natural killer (NK) cells were also analyzed. Lesional biopsies were examined for CCR4, Foxp3, and CD16 expression by immunohistochemistry. Results: Malignant T cells in peripheral blood were 20.8%–100% positive for CCR4 at baseline. Fourteen patients who achieved a response in blood had high baseline CCR4 expression on malignant T cells. Tregs in blood were 58.6% to 100% positive for CCR4 at baseline and showed decreased numbers and CCR4 expression after treatment. CD8+ T cells in blood were 3.2% to 23.2% positive for CCR4 at baseline and showed limited reduction of CCR4 expression with increased percentages of CD8+ T cells after treatment. Of 14 patients tested for NK cells in blood, 10 showed increased percentages after treatment. Four of 6 patients tested showed increased NK cell cytotoxicity. Sixteen of 18 patients who had CCR4+ lymphocytes in baseline lesions showed decreased numbers after treatment. Conclusions: Mogamulizumab reduces levels of CCR4+ malignant T cells and also CCR4+ Tregs in patients with CTCL, which may in turn improve immune profiles. Clin Cancer Res; 21(2); 274–85. ©2014 AACR.
A Large Palindrome With Interchromosomal Gene Duplications in the Pericentromeric Region of the D. melanogaster Y Chromosome
Authors: M. Mendez-Lago, C. M. Bergman, B. de Pablos, A. Tracey, S. L. Whitehead, A. Villasante
Journal: Molecular Biology and Evolution (2011)

The non-recombining Y chromosome is expected to degenerate over evolutionary time, however, gene gain is a common feature of Y chromosomes of mammals and Drosophila. Here, we report that a large palindrome containing interchromosomal segmental duplications is located in the vicinity of the first amplicon detected in the Y chromosome of D. melanogaster. The recent appearance of such amplicons suggests that duplications to the Y chromosome, followed by the amplification of the segmental duplications, are a mechanism for the continuing evolution of Drosophila Y chromosomes.
Macrophages Generate Reactive Oxygen Species in Response to Minimally Oxidized Low-Density Lipoprotein
Authors: Yun Soo Bae, Jee Hyun Lee, Soo Ho Choi, Sunah Kim, Felicidad Almazan, Joseph L. Witztum, Yury I. Miller
Journal: Circulation Research (2008)

Oxidative modification of low-density lipoprotein (LDL) plays a causative role in the development of atherosclerosis. In this study, we demonstrate that minimally oxidized LDL (mmLDL) stimulates intracellular reactive oxygen species (ROS) generation in macrophages through NADPH oxidase 2 (gp91phox/Nox2), which, in turn, induces production of RANTES and migration of smooth muscle cells. Peritoneal macrophages from gp91phox/Nox2 −/− mice or J774 macrophages in which Nox2 was knocked down by small interfering RNA failed to generate ROS in response to mmLDL. Because mmLDL-induced cytoskeletal changes were dependent on Toll-like receptor (TLR)4, we analyzed ROS generation in peritoneal macrophages from wild-type, TLR4 −/− , or MyD88 −/− mice and found that mmLDL-mediated ROS was generated in a TLR4-dependent, but MyD88-independent, manner. Furthermore, we found that ROS generation required the recruitment and activation of spleen tyrosine kinase (Syk) and that mmLDL also induced phospholipase PLCγ1 phosphorylation and protein kinase C membrane translocation. Importantly, the phospholipase Cγ1 phosphorylation was reduced in J774 cells expressing Syk-specific short hairpin RNA. Nox2 modulated mmLDL activation of macrophages by regulating the expression of proinflammatory cytokines interleukin-1β, interleukin-6, and RANTES. We showed that purified RANTES was able to stimulate migration of mouse aortic smooth muscle cells and addition of neutralizing antibody against RANTES abolished the migration of mouse aortic smooth muscle cells stimulated by mmLDL-stimulated macrophages. These results suggest that mmLDL induces generation of ROS through sequential activation of TLR4, Syk, phospholipase Cγ1, protein kinase C, and gp91phox/Nox2 and thereby stimulates expression of proinflammatory cytokines. These data help explain mechanisms by which endogenous ligands, such as mmLDL, can induce TLR4-dependent, proatherogenic activation of macrophages.
Patterns of nuclear fluorescence and DNA-binding activity.
Authors: A Luciano, N.F Rothfield
Journal: Annals of the Rheumatic Diseases (1973)

Serafrompatients withsystemic lupus erythematosus (SLE) andother connective tissue diseases havebeen demonstrated tocontain avariety ofantinuclear antibodies. Antibodies tonative DNA appear tobepresentonlyinserafrompatients withclinically active SLE.These antibodies havebeendetected byavariety of techniques, suchas precipitation in agar (Seligmann, 1957), complement fixation (Ceppellini, Polli, andCelada, 1957; Robbins, Holman,Deicher andKunkel, 1957), immunofluorescence (Friou,
Performance pay remuneration for consultants in the NHS: is the current system fair and fit for purpose?
Authors: P. Abel, A. Esmail
Journal: Journal of the Royal Society of Medicine (2006)

Despite reforms to the performance pay review system for NHS consultants, little has changed since the original Distinction Awards Scheme was conceived in 1948.Inherent weaknesses and biases in the scheme persist and result in discrimination against women and ethnic minority consultants in the allocation of awards.The literature on performance-related pay suggests that such schemes can be inappropriate in a public sector health service.The continued focus on rewarding individuals in performancerelated pay schemes can seem out of place in the modern era where there is an increasing focus on the performance of teams.
CD2 engagement induces dendritic cell activation: implications for immune surveillance and T-cell activation
Authors: Keith Crawford, Aleksandra Stark, Betsy Kitchens, Kerry Sternheim, Vassilios Pantazopoulos, Ellen Triantafellow, Zhigang Wang, Baldev Vasir, Charles E. Larsen, Dana Gabuzda, Ellis Reinherz, Chester A. Alper
Journal: Blood (2003)
Oral Nutritional Interventions in Malnourished Patients With Cancer: A Systematic Review and Meta-Analysis
Authors: Christine Baldwin, Ayelet Spiro, Roger Ahern, Peter W. Emery
Journal: JNCI Journal of the National Cancer Institute (2012)

International guidelines on the nutritional management of patients with cancer recommend intervention with dietary advice and/or oral nutritional supplements in patients who are malnourished or those judged to be at nutritional risk, but the evidence base for these recommendations is lacking. We examined the effect of oral nutritional interventions in this population on nutritional and clinical outcomes and quality of life (QOL). Electronic searches of several databases including MEDLINE, EMBASE, and CINAHL (from the first record to February 2010) were searched to identify randomized controlled trials of patients with cancer who were malnourished or considered to be at risk of malnutrition and receiving oral nutritional support compared with routine care. We performed a meta-analysis using a fixed effect model, or random effects models when statistically significant heterogeneity was present, to calculate relative risk (mortality) or mean difference (weight, energy intake, and QOL) with 95% confidence intervals (CIs). Heterogeneity was determined by using the χ 2 test and the I2 statistic. All statistical tests were two-sided. Thirteen studies were identified and included 1414 participants. The quality of the studies varied, and there was considerable clinical and statistical heterogeneity. Nutritional intervention was associated with statistically significant improvements in weight and energy intake compared with routine care (mean difference in weight = 1.86 kg, 95% CI = 0.25 to 3.47, P = .02; and mean difference in energy intake = 432 kcal/d, 95% CI = 172 to 693, P = .001). However, after removing the main sources of heterogeneity, there was no statistically significant difference in weight gain or energy intake. Nutritional intervention had a beneficial effect on some aspects of QOL (emotional functioning, dyspnea, loss of appetite, and global QOL) but had no effect on mortality (relative risk = 1.06, 95% CI = 0.92 to 1.22, P = .43; I2 = 0%; Pheterogeneity = .56). Oral nutritional interventions are effective at increasing nutritional intake and improving some aspects of QOL in patients with cancer who are malnourished or are at nutritional risk but do not appear to improve mortality.