tbuckley/cabot-search huggingface dataset:
Insulin-Like Growth Factor-I Regulates the Liver Microenvironment in Obese Mice and Promotes Liver Metastasis
Authors: Yingjie Wu, Pnina Brodt, Hui Sun, Wilson Mejia, Ruslan Novosyadlyy, Nomeli Nunez, Xiaoli Chen, Arnulfo Mendoza, Sung-Hyeok Hong, Chand Khanna, Shoshana Yakar
Journal: Cancer Research (2010)

Abstract Among the mechanisms implicated in the tumor-promoting effects of obesity, signaling by insulin-like growth factor-I (IGF-I) and insulin has received considerable attention. However, the emerging realization that obesity is associated with chronic inflammation has prompted other consideration of how the IGF-I axis may participate in cancer progression. In the present study, we used two mouse models of chronic (LID) and inducible (iLID) igf-1 gene deficiency in the liver to investigate the role of IGF-I in regulating the host microenvironment and colorectal carcinoma growth and metastasis in obese mice. Obese mice had a heightened inflammatory response in the liver, which was abolished in mice with chronic IGF-I deficiency (LID). In control animals changes to the hepatic microenvironment associated with obesity sustained the presence of tumor cells in the liver and increased the incidence of hepatic metastases after intrasplenic/portal inoculation of colon carcinoma cells. These changes did not occur in LID mice with chlonic IGF-1 deficiency. In contrast, these changes occured in iLID mice with acute IGF-1 deficiency, in the same manner as the control animals, revealing a fundamental difference in the nature of the requirement for IGF-1 on tumor growth and metastasis. In the setting of obesity, our findings imply that IGF-1 is critical to activate and sustain an inflammatory response in the liver that is needed for hepatic metastasis, not only through direct, paracrine effect on tumor cell growth, but also through indirect effects involving the tumor microenvironment. Cancer Res; 70(1); 57–67
Valvular Aortic Stenosis
Authors: J. TIMOTHY LOMBARD
Journal: Annals of Internal Medicine (1987)

We retrospectively reviewed the clinical and hemodynamic findings in 397 patients with valvular aortic stenosis at their first hemodynamic evaluation. This series is considered representative of aortic stenosis because it is heavily weighted toward older patients (average age, 61.1 years) and severe aortic stenosis (87.3% of patients had aortic valve area less than 1 cm2). We identified two categories of symptoms: angina and syncope, which develop during a fully compensated stage of aortic stenosis ("prefailure symptoms"); and dyspnea or congestive failure, which signifies various degrees of left ventricular malfunction. The preponderance of soft or medium intensity systolic murmur and normal or widened pulse pressure emphasizes the changing clinical picture of aortic stenosis in an aging population. Coexisting coronary artery disease was found in 60% of patients, but those with and without coronary disease did not differ significantly, even in the presence of angina.
Phase II to III Study Comparing Doxorubicin and Docetaxel With Fluorouracil, Doxorubicin, and Cyclophosphamide As First-Line Chemotherapy in Patients With Metastatic Breast Cancer: Results of a Dutch Community Setting Trial for the Clinical Trial Group of the Comprehensive Cancer Centre
Authors: Marijke Bontenbal, Geert-Jan Creemers, Hans J. Braun, Auke C. de Boer, Jos Th. Janssen, Rieneke B. Leys, Jan B. Ruit, Swan Hoo Goey, Paul C. van der Velden, Leon G. Kerkhofs, Kristel L. Schothorst, Paul I. Schmitz, Hansje J. Bokma, Jaap Verweij, Caroline Seynaeve
Journal: Journal of Clinical Oncology (2005)

Purpose To compare the efficacy and safety of doxorubicin and docetaxel (AT) with fluorouracil, doxorubicin, and cyclophosphamide (FAC) as first-line chemotherapy for metastatic breast cancer (MBC). Patients and Methods Patients (n = 216) were randomly assigned to either AT (doxorubicin 50 mg/m 2 and docetaxel 75 mg/m 2 ) or FAC (fluorouracil 500 mg/m 2 , doxorubicin 50 mg/m 2 , and cyclophosphamide 500 mg/m 2 ); both regimens were administered on day 1, every 3 weeks. Results A median number of six cycles was delivered in both arms, with a median relative dose-intensity of more than 98%. Median time to progression (TTP) and median overall survival (OS) were significantly longer for patients on AT compared with FAC (TTP: 8.0 v 6.6 months, respectively; P = .004; and OS: 22.6 v 16.2 months, respectively; P = .019). The overall response rate (ORR) was significantly higher in patients on AT compared with FAC (58% v 37%, respectively; P = .003). The ORR on AT was also higher in patients with visceral disease compared with FAC patients with visceral disease (59% v 36%, respectively; P = .003). There were no differences in grade 3 to 4 neutropenia and infections (AT 89% v FAC 84% and AT 12% v FAC 9%, respectively). Neutropenic fever was more common in AT-treated patients than FAC-treated patients (33% v 9%, respectively; P &lt; .001). Grade 3 to 4 nonhematologic toxicity was infrequent in both arms. Congestive heart failure was observed in 3% and 6% of patients on AT and FAC, respectively. Conclusion In this phase II to III study, AT resulted in a significantly longer TTP and OS and a higher objective ORR than FAC. First-line AT is a valid treatment option for patients with MBC.
Renal Effects of Different Types of Protein in Healthy Volunteer Subjects and Diabetic Patients
Authors: Hiroshi Nakamura, Seiki Ito, Naoko Ebe, Akira Shibata
Journal: Diabetes Care (1993)

To evaluate the effects of acute loading of protein from different sources on the glomerular filtration rate.A total of 6 healthy volunteer subjects and 6 diabetic patients with normoalbuminuria were studied before and after ingestion on separate days of tuna fish containing 0.7 g/kg body wt of protein, boiled egg white containing the same amount of protein as the tuna fish, or boiled egg white containing 1.4 g/kg body wt of protein. Furthermore, to study the possible role of prostaglandins and amino acids in the response of GFR to protein loading, urinary excretion of prostaglandins, and plasma levels of amino acids were measured during these tests.In normal subjects, the GFR rose significantly (P < 0.01) after ingestion of tuna fish. No significant differences were found between GFR before and after ingestion of the different amounts of egg white. The GFRs of the diabetic patients after ingestion of each of the meals were similar to the responses in healthy volunteers. Plasma levels of Gly and Ala (amino acids known to induce glomerular hyperfiltration) were higher after ingestion of tuna fish than after administration of egg white in all subjects. No differences were found in the plasma concentrations of any amino acids except Gly and Ala after loads of tuna fish and egg white containing 1.4 g/kg of protein. Urinary 6-keto-PGF1a excretion increased significantly (P < 0.01) after tuna fish loading, but did not change after egg white challenge.These findings could be explained either by differences in renal vasodilatory prostaglandin secretion or by increased plasma levels of Gly and Ala, which were increased only after ingestion of tuna fish. Thus, egg white has renal effects on GFR different from those of tuna fish, independent of the quantity of protein ingested.
Concerns of poor quality of life should not deprive patients of the opportunity of curative surgery
Authors: K McManus
Journal: Thorax (2003)

Is it worth undergoing lung cancer resection and the resulting poor quality of life when the survival outcomes are not good?

Postoperative pain and breathlessness following lung cancer surgery are important causes of disability. The prospect of such symptoms may influence the decision to proceed with surgery. Incapacitating intercostal neuralgia, unlike other surgical pain, often does not go away. Intolerable breathlessness caused by removing lung tissue from a patient who already has poor lung function can result in severe limitation of exercise tolerance. Is it really worth it when the survival outcomes in lung cancer are so poor anyway?

A surgeon’s main interest is radical clearance of the tumour and long term survival of the patient. Success is judged in terms of operative mortality and 5 year survival. The referring physician, on the other hand, may perceive that the patient will be left physically and emotionally handicapped by surgery and refer him or her for chemotherapy or radiotherapy instead, even though there is little evidence that these treatments are less debilitating and cure rates are known to be lower. What price …
Relationship between conductivity and functional refractoriness of atrioventricular node in man
Authors: D G WYSE
Journal: Cardiovascular Research (1982)

Eighty-one consecutive patients representing a wide clinical spectrum were studied to assess the degree of limitation of the atrial extrastimulus technique for measurement of atrioventricular node refractoriness; and, to determine the relationship between conductivity and functional refractoriness of the atrioventricular node (AVN). Four patients developed sustained atrial fibrillation and a total of 277 basic cycle lengths (BCLs) were evaluated in the remaining 77. Four different patterns of AVN conduction were defined on the basis of plots of H1H2 versus A2A2 and discontinuity in the plot was observed for some of each of the three major patterns. No functional refractory period (FRP) of AVN could be determined in 10/77 patients (13%) and in 127/277 BCLs (46%). A mathematical formula relating measurements of conductivity (A2H2 interval) to FRP which was derived from the canine heart was applied to the data for those BCLs where FRP was known. Optimal agreement between measured and calculated FRP (y = x + 3, r = 0.97, n = 38) was obtained when subsets of data were selected according to an algorithm derived from repetetive computer analysis of the parent data base. The calculation is independent of patient variables (medication, impaired AVN conduction, pattern of AVN conduction). These results demonstrate that the atrial extrastimulus technique often will not permit measurement of AVN refractoriness in the human heart but conductivity and FRP are related in a fashion similar to that determined for the canine heart. This relationship permits calculation of FRP from measurements of conductivity. Calculation of FRP is recommended for brevity and greater yield of data.
Prevalences of sexually transmitted infections in young adults and female sex workers in Peru: a national population-based survey
Authors: César P Cárcamo, Pablo E Campos, Patricia J García, James P Hughes, Geoff P Garnett, King K Holmes
Journal: The Lancet Infectious Diseases (2012)

BackgroundWe assessed prevalences of seven sexually transmitted infections (STIs) in Peru, stratified by risk behaviours, to help to define care and prevention priorities.MethodsIn a 2002 household-based survey of the general population, we enrolled randomly selected 18–29-year-old residents of 24 cities with populations greater than 50 000 people. We then surveyed female sex workers (FSWs) in these cities. We gathered data for sexual behaviour; vaginal specimens or urine for nucleic acid amplification tests for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis; and blood for serological tests for syphilis, HIV, and (in subsamples) herpes simplex virus 2 (HSV2) and human T-lymphotropic virus. This study is a registered component of the PREVEN trial, number ISRCTN43722548.Findings15 261 individuals from the general population and 4485 FSWs agreed to participate in our survey. Overall prevalence of infection with HSV2, weighted for city size, was 13·5% in men, 13·6% in women, and 60·6% in FSWs (all values in FSWs standardised to age composition of women in the general population). The prevalence of C trachomatis infection was 4·2% in men, 6·5% in women, and 16·4% in FSWs; of T vaginalis infection was 0·3% in men, 4·9% in women, and 7·9% in FSWs; and of syphilis was 0·5% in men, 0·4% in women, and 0·8% in FSWs. N gonorrhoeae infection had a prevalence of 0·1% in men and women, and of 1·6% in FSWs. Prevalence of HIV infection was 0·5% in men and FSWs, and 0·1% in women. Four (0·3%) of 1535 specimens were positive for human T-lymphotropic virus 1. In men, 65·0% of infections with HIV, 71·5% of N gonorrhoeae, and 41·4% of HSV2 and 60·9% of cases of syphilis were in the 13·3% who had sex with men or unprotected sex with FSWs in the past year. In women from the general population, 66·7% of infections with HIV and 16·7% of cases of syphilis were accounted for by the 4·4% who had been paid for sex by any of their past three partners.InterpretationDefining of high-risk groups could guide targeting of interventions for communicable diseases—including STIs—in the general Peruvian population.FundingWellcome Trust-Burroughs Wellcome Fund Infectious Disease Initiative and US National Institutes of Health.
Neurocognitive outcome 12 months following cerebellar mutism syndrome in pediatric patients with medulloblastoma
Authors: S. L. Palmer, T. Hassall, K. Evankovich, D. J. Mabbott, M. Bonner, C. Deluca, R. Cohn, M. J. Fisher, E. B. Morris, A. Broniscer, A. Gajjar
Journal: Neuro-Oncology (2010)

The aim is to prospectively assess early neurocognitive outcome of children who developed cerebellar mutism syndrome (CMS) following surgical resection of a posterior fossa embryonal tumor, compared with carefully matched control patients. Children who were enrolled on an ongoing IRB-approved protocol for treatment of embryonal tumors, were diagnosed with postoperative CMS, and had completed prospectively planned neuropsychological evaluation at 12 months postdiagnosis were considered eligible. The cognitive outcomes of these patients were examined in comparison to patients without CMS from the same treatment protocol and matched with regard to primary diagnosis, age at diagnosis, and risk/corresponding treatment (n = 22 pairs). Seventeen were also matched according to gender, and 14 were also matched according to race. High-risk patients received 36–39.6 Gy CSI and 3D conformal boost to the primary site to 55.8–59.4 Gy. Average-risk patients received 23.4 Gy CSI and 3D conformal boost to the primary site to 55.8 Gy. Significant group differences were found on multiple cognitive outcomes. While the matched control patients exhibited performance in the average range, patients who developed CMS postsurgery were found to have significantly lower performance in processing speed, attention, working memory, executive processes, cognitive efficiency, reading, spelling, and math. Patients treated for medulloblastoma who experience postoperative CMS show an increased risk for neurocognitive impairment, evident as early as 12 months following diagnosis. This study highlights the need for careful follow-up with neuropsychological evaluation and for obtaining critical support for patients and their families.
P243 Anxiety and depression in adolescents and adults with cystic fibrosis
Authors: V. Fainardi, E. Iacinti, F. Longo, M. C. Tripodi, G. Pisi
Journal: Thorax (2011)

<h3>Background</h3> Little is currently known about the anxiety and depression co-morbidities and Cystic Fibrosis (CF). <h3>Aim</h3> To evaluate the association between anxiety and depression and long-term treatment burden in CF patients. <h3>Subjects and Methods</h3> In 82 CF patients (36 males, age range 12–44 years, BMI range 15–29 kg/m<sup>2</sup>), anxiety and depression were assessed by the Hospital Anxiety Depression Scale (HADS). In all patients, spirometry and current therapy, such as scheduled intravenous antibiotics, chronic use of aerosolized antibiotics, insulin therapy, pancreatic enzymes and long-term oxygen therapy, were recorded. <h3>Results</h3> A wide range of airflow obstruction was found (FEV<sub>1</sub> range 26–129% pred). 54, 68, 12, 85, and 11 patients underwent intravenous antibiotics, aerosolized antibiotics, insulin therapy, pancreatic enzymes and long-term oxygen therapy, respectively. 33 (40%) and 15 (18%) out of 82 patients were respectively anxious and depressive. Depression was significantly associated with intravenous antibiotics (p&lt;0.01, OR 6.0, CI 0.9 to 41) and with long-term oxygen therapy (p&lt;0.01, OR 1.4, CI 0.9 to 1.9). <h3>Conclusions</h3> The present study shows that use of scheduled intravenous antibiotics and long-term oxygen therapy significantly affect psychological functioning profile in adolescents and adults with CF. Our results further suggest the value of psychological support in CF patients with advanced lung disease.
Association of Age With Survival in Patients With Metastatic Colorectal Cancer: Analysis From the ARCAD Clinical Trials Program
Authors: Christopher H. Lieu, Lindsay A. Renfro, Aimery de Gramont, Jeffrey P. Meyers, Timothy S. Maughan, Matthew T. Seymour, Leonard Saltz, Richard M. Goldberg, Daniel J. Sargent, S. Gail Eckhardt, Cathy Eng
Journal: Journal of Clinical Oncology (2014)

Purpose This study addressed whether age is prognostic for overall survival (OS) or progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC). Patients and Methods A total of 20,023 patients from 24 first-line clinical trials in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analyzed. Primary age effects and interactions with age, sex, performance status (PS), and metastatic site were modeled using Cox proportional hazards stratified by treatment arm within study. Results Of total patients, 3,051 (15%) were age ≤ 50 years. Age was prognostic for both OS (P &lt; .001) and PFS (P &lt; .001), with U-shaped risk (ie, highest risk was evident in youngest and oldest patients). Relative to patients of middle age, the youngest patients experienced 19% (95% CI, 7% to 33%) increased risk of death and 22% (95% CI, 10% to 35%) increased risk of progression. The oldest patients experienced 42% (95% CI, 31% to 54%) increased risk of death and 15% (95% CI, 7% to 24%) increased risk of progression or death. This relationship was more pronounced in the first year of follow-up. Age remained marginally significant for OS (P = .08) when adjusted for PS, sex, and presence of liver, lung, or peritoneal metastases, and age was significant in an adjusted model for PFS (P = .005). The age effect did not differ by site of metastatic disease, year of enrollment, type of therapy received, or biomarker mutational status. Conclusion Younger and older age are associated with poorer OS and PFS among treated patients with mCRC. Younger and older patients may represent higher-risk populations, and additional studies are warranted.
Forced expiratory indices in normal Libyan children aged 6-19 years.
Authors: M H Shamssain, J Thompson, S A Ogston
Journal: Thorax (1988)

Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured in 796 Libyan children (386 boys and 410 girls) with ages ranging from 6 to 19 years. Values in girls were significantly less than those in boys after allowance had been made for age and height. FVC and FEV1 correlated best with standing height but were also correlated with body weight. These results may be used as a source of standard values for Libyan children.
Reversal of Italian Reimbursement Restriction on Antihistamines is Associated with Better Clinical Outcomes among Children with Allergy-Induced Asthma
Authors: D.S. Battleman, C. Burudtakdee, J. Tierce, M. Sturkenboom, C. Giaquinto, G. Picelli, L. Cantarutti, P. Berto, G. Canonica
Journal: Journal of Allergy and Clinical Immunology (2006)
Activation of Akt as a Mechanism for Tumor Immune Evasion
Authors: Kyung Hee Noh, Tae Heung Kang, Jin Hee Kim, Sara I Pai, Ken Y Lin, Chien-Fu Hung, T-C Wu, Tae Woo Kim
Journal: Molecular Therapy (2008)

Immune evasion is an important reason why the immune system cannot control tumor growth. To elucidate the mechanism for tumor immune evasion, we generated an immune-resistant human papillomavirus type 16 (HPV-16) E7-expressing tumor cell line by subjecting a susceptible tumor cell line to multiple rounds of in vivo immune selection with an E7-specific vaccine. Comparison of parental and immune-resistant tumors revealed that Akt is highly activated in the immune-resistant tumors. Retroviral transfer of a constitutively active form of Akt into the parental tumor significantly increased its resistance against E7-specific CD8(+) T-cell mediated apoptosis. The observed resistance against apoptosis was found to be associated with the upregulation of antiapoptotic molecules. We also observed that intratumoral injection of an Akt inhibitor enhanced the therapeutic efficacy of E7-specific vaccine or E7-specific CD8(+) T-cell adoptive transfer against the immune-resistant tumors. Thus, our data indicate that the activation of PI3K/Akt pathway represents a new mechanism of immune escape and has important implications for the development of a novel strategy in cancer immunotherapy against immune-resistant tumor cells.
Identification and Validation of an Anthracycline/Cyclophosphamide–Based Chemotherapy Response Assay in Breast Cancer
Authors: Jude M. Mulligan, Laura A. Hill, Steve Deharo, Gareth Irwin, David Boyle, Katherine E. Keating, Olaide Y. Raji, Fionnuala A. McDyer, Eamonn O’Brien, Max Bylesjo, Jennifer E. Quinn, Noralane M. Lindor, Paul B. Mullan, Colin R. James, Steven M. Walker, Peter Kerr, Jacqueline James, Timothy S. Davison, Vitali Proutski, Manuel Salto-Tellez, Patrick G. Johnston, Fergus J. Couch, D. Paul Harkin, Richard D. Kennedy
Journal: JNCI Journal of the National Cancer Institute (2014)

There is no method routinely used to predict response to anthracycline and cyclophosphamide–based chemotherapy in the clinic; therefore patients often receive treatment for breast cancer with no benefit. Loss of the Fanconi anemia/BRCA (FA/BRCA) DNA damage response (DDR) pathway occurs in approximately 25% of breast cancer patients through several mechanisms and results in sensitization to DNA-damaging agents. The aim of this study was to develop an assay to detect DDR-deficient tumors associated with loss of the FA/BRCA pathway, for the purpose of treatment selection. DNA microarray data from 21 FA patients and 11 control subjects were analyzed to identify genetic processes associated with a deficiency in DDR. Unsupervised hierarchical clustering was then performed using 60 BRCA1/2 mutant and 47 sporadic tumor samples, and a molecular subgroup was identified that was defined by the molecular processes represented within FA patients. A 44-gene microarray-based assay (the DDR deficiency assay) was developed to prospectively identify this subgroup from formalin-fixed, paraffin-embedded samples. All statistical tests were two-sided. In a publicly available independent cohort of 203 patients, the assay predicted complete pathologic response vs residual disease after neoadjuvant DNA-damaging chemotherapy (5-fluorouracil, anthracycline, and cyclophosphamide) with an odds ratio of 3.96 (95% confidence interval [Cl] =1.67 to 9.41; P = .002). In a new independent cohort of 191 breast cancer patients treated with adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, a positive assay result predicted 5-year relapse-free survival with a hazard ratio of 0.37 (95% Cl = 0.15 to 0.88; P = .03) compared with the assay negative population. A formalin-fixed, paraffin-embedded tissue-based assay has been developed and independently validated as a predictor of response and prognosis after anthracycline/cyclophosphamide–based chemotherapy in the neoadjuvant and adjuvant settings. These findings warrant further validation in a prospective clinical study.