tbuckley/cabot-search huggingface dataset:
Effects of soy protein and isoflavones on circulating hormone concentrations in pre- and post-menopausal women: a systematic review and meta-analysis
Authors: L. Hooper, J.J. Ryder, M.S. Kurzer, J.W. Lampe, M.J. Messina, W.R. Phipps, A. Cassidy
Journal: Human Reproduction Update (2009)

Hormonal effects of soy and isoflavones have been investigated in numerous trials with equivocal findings. We aimed to systematically assess the effects of soy and isoflavones on circulating estrogen and other hormones in pre- and post-menopausal women. The Cochrane Library, MEDLINE and EMBASE (plus reviews and experts) were searched to December 2007. Inclusion of randomized or residential crossover trials of soy or isoflavones for 4 or more weeks on estrogens, SHBG, FSH, LH, progesterone and thyroid hormones in women was assessed independently in duplicate. Six percent of papers assessed were included. Data concerning participants, interventions, outcomes, potential effect modifiers and trial quality characteristics were extracted independently in duplicate. Forty-seven studies (11 of pre-, 35 of post- and 1 of perimenopausal women) were included. In premenopausal women, meta-analysis suggested that soy or isoflavone consumption did not affect primary outcomes estradiol, estrone or SHBG concentrations, but significantly reduced secondary outcomes FSH and LH [by ∼20% using standardized mean difference (SMD), P = 0.01 and 0.05, respectively]. Menstrual cycle length was increased by 1.05 days (95% CI 0.13, 1.97, 10 studies). In post-menopausal women, there were no statistically significant effects on estradiol, estrone, SHBG, FSH or LH, although there was a small statistically non-significant increase in total estradiol with soy or isoflavones (∼14%, SMD, P = 0.07, 21 studies). Isoflavone-rich soy products decrease FSH and LH in premenopausal women and may increase estradiol in post-menopausal women. The clinical implications of these modest hormonal changes remain to be determined.
p53 Small-Molecule Inhibitor Enhances Temozolomide Cytotoxic Activity against Intracranial Glioblastoma Xenografts
Authors: Eduard B. Dinca, Kan V. Lu, Jann N. Sarkaria, Russell O. Pieper, Michael D. Prados, Daphne A. Haas-Kogan, Scott R. VandenBerg, Mitchel S. Berger, C. David James
Journal: Cancer Research (2008)

Abstract In this study, we investigated the precursor and active forms of a p53 small-molecule inhibitor for their effects on temozolomide (TMZ) antitumor activity against glioblastoma (GBM), using both in vitro and in vivo experimental approaches. Results from in vitro cell viability analysis showed that the cytotoxic activity of TMZ was substantially increased when p53 wild-type (p53wt) GBMs were cotreated with the active form of p53 inhibitor, and this heightened cytotoxic response was accompanied by increased poly(ADP-ribose) polymerase cleavage as well as elevated cellular phospho-H2AX. Analysis of the same series of GBMs, as intracranial xenografts in athymic mice, and administering corresponding p53 inhibitor precursor, which is converted to the active compound in vivo, yielded results consistent with the in vitro analyses: TMZ + p53 inhibitor precursor cotreatment of three distinct p53wt GBM xenografts resulted in significant enhancement of TMZ antitumor effect relative to treatment with TMZ alone, as indicated by serial bioluminescence monitoring as well as survival analysis (P &amp;lt; 0.001 for cotreatment survival benefit in each case). Mice receiving intracranial injection with p53null GBM showed similar survival benefit from TMZ treatment regardless of the presence or absence of p53 inhibitor precursor. In total, our results indicate that the p53 active and precursor inhibitor pair enhances TMZ cytotoxicity in vitro and in vivo, respectively, and do so in a p53-dependent manner. [Cancer Res 2008;68(24):10034–8]
Measurement of three dimensional shoulder movement patterns with an electromagnetic tracking device in patients with a frozen shoulder
Authors: H M Vermeulen
Journal: Annals of the Rheumatic Diseases (2002)

To compare three dimensional movement patterns of the affected and non-affected shoulder in patients with a frozen shoulder before and after physical therapy.Patients with a unilateral frozen shoulder were assessed before and after three months of treatment. Three dimensional movement analysis was performed with the "Flock of Birds" electromagnetic tracking device while the patient raised their arms in three directions. Slopes of the regression lines of glenohumeral joint rotation versus scapular rotation, reflecting the scapulohumeral rhythm, were calculated. All assessments were made for both the affected and the unaffected side. Additional assessments included conventional range of motion (ROM) measurements and visual analogue scales (VAS) (0-100 mm) for shoulder pain at rest, during movement, and at night.Ten patients with a unilateral frozen shoulder were included. The slopes of the curves of the forward flexion, scapular abduction, and abduction in the frontal plane of the affected and the unaffected side were significantly different in all three movement directions. Mean differences were 0.267, 0.215, and 0.464 (all p values <0.005), respectively. Mean changes of the slopes of the affected side after treatment were 0.063 (p=0.202), 0.048 (p=0.169), and 0.264 (p=0.008) in forward flexion, scapular abduction, and abduction in the frontal plane, respectively. All patients showed significant improvement in active ROM (all p<0.005), and the VAS for pain during movement and pain at night (p<0.05).With a three dimensional electromagnetic tracking system the abnormal movement pattern of a frozen shoulder, characterised by the relatively early laterorotation of the scapula in relation to glenohumeral rotation during shoulder elevation, can be described and quantified. Moreover, the system is sufficiently sensitive to detect clinical improvements. Its value in other shoulder disorders remains to be established.
Randomized Phase II Study of Erlotinib Plus Tivantinib Versus Erlotinib Plus Placebo in Previously Treated Non–Small-Cell Lung Cancer
Authors: Lecia V. Sequist, Joachim von Pawel, Edward G. Garmey, Wallace L. Akerley, Wolfram Brugger, Dora Ferrari, Yinpu Chen, Daniel B. Costa, David E. Gerber, Sergey Orlov, Rodryg Ramlau, Susan Arthur, Igor Gorbachevsky, Brian Schwartz, Joan H. Schiller
Journal: Journal of Clinical Oncology (2011)

c-MET (MET) receptor activation is associated with poor prognosis and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non-small-cell lung cancer (NSCLC). This global, randomized phase II trial examined erlotinib plus tivantinib (ARQ 197; ArQule, Woburn, MA), a novel MET inhibitor.Previously treated patients with EGFR TKI-naive advanced NSCLC were randomly assigned to receive oral erlotinib (150 mg daily) plus oral tivantinib (360 mg twice daily) or erlotinib plus placebo (EP). The primary end point was progression-free survival (PFS). At the time of progression, cross-over from EP to erlotinib plus tivantinib (ET) was permitted. Archival tumor tissue specimens were required.One hundred sixty-seven patients were randomly assigned to ET (n = 84) and to EP (n = 83). Median PFS was 3.8 months for ET and 2.3 months for EP (hazard ratio [HR], 0.81; 95% CI, 0.57 to 1.16; P = .24). Exploratory analysis revealed that the small cohort with KRAS mutations achieved a PFS HR of 0.18 (95% CI, 0.05 to 0.70; interaction P = .006). Objective responses were seen in 10% of patients on ET, 7% of patients on EP, and in two patients who crossed over from EP to ET, including one with EGFR mutation and MET gene copy number greater than 5. There were no significant differences in adverse events between study arms.The combination of the MET inhibitor tivantinib and erlotinib is well-tolerated. Although the study did not meet its primary end point, evidence of activity was demonstrated, especially among patients with KRAS mutations. Additional study of tivantinib and erlotinib in patients with NSCLC is planned.
Psychological and Behavioral Functioning in Adolescent Psychiatric Inpatients Who Report Histories of Childhood Abuse
Authors: Carlos M. Grilo, Charles Sanislow, Dwain C. Fehon, Steve Martino, Thomas H. McGlashan
Journal: American Journal of Psychiatry (1999)

The purpose of this study was to examine psychological and behavioral functioning in psychiatrically hospitalized adolescents who report histories of childhood abuse.Three hundred twenty-two subjects completed an assessment battery of psychometrically well-established instruments. Childhood abuse was assessed by using the childhood abuse scale of the Millon Adolescent Clinical Inventory. Childhood abuse scores of 30 or less and 70 or greater were used to create two study groups--no abuse (N = 93) and high abuse (N = 70), respectively. The two study groups were compared demographically and on the battery of instruments.The two groups differed substantially on most measures of psychological disturbance examined by the assessment battery. When age and depression level were controlled, the high-abuse group was characterized by significantly higher levels of dependency, suicidality, violence, impulsivity, substance use problems, and borderline tendency. Correlational analyses with the entire study group (N = 322) revealed that higher levels of these psychological problems were positively associated with higher levels of childhood abuse.Psychiatrically hospitalized adolescents who report childhood abuse present with a constellation of symptoms that, after removing the effects of depression, are consistent with borderline personality in statu nascendi.
Patients are deceived over benefits and risks of screening, MPs hear
Authors: A. O'Dowd
Journal: BMJ (2014)

Patients are prone to “deception” about the real risks and benefits of national screening in the United Kingdom, MPs have been told.

The full pros and cons of screening patients were too often poorly explained, skated over, or presented in a confusing manner, expert witnesses said during an evidence session of the House of Commons science and technology committee’s inquiry into national health screening.

MPs asked whether patients who agreed to participate in screening programmes fully understood the risks and benefits. 

One witness was the former breast cancer surgeon Michael Baum, professor emeritus of surgery and visiting professor of medical humanities at University College London, representing Advocates for Honesty and Transparency in Breast Screening. He said, …
Epigenetic inactivation of the MIR129-2 in hematological malignancies
Authors: Kwan-Yeung Wong, Rita Lok-Hay Yim, Yok-Lam Kwong, Chung-Ying Leung, Pak-Kwan Hui, Florence Cheung, Raymond Liang, Dong-Yan Jin, Chor-Sang Chim
Journal: Journal of Hematology & Oncology (2013)

Abstract Background MIR129-2 has been shown to be a tumor suppressor microRNA hypermethylated in epithelial cancers. Patients and methods Epigenetic inactivation of MIR129-2 was studied by methylation-specific PCR (MSP) in 13 cell lines (eight myeloma and five lymphoma), 15 normal controls and 344 primary samples including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM) at diagnosis, MM at relapse/progression, and monoclonal gammopathy of undetermined significance (MGUS). Expression of MIR129 and its target, SOX4 , in cell lines was measured before and after hypomethylating treatment and MIR129 overexpression. MIR129 expression was correlated with MIR129-2 methylation status in primary lymphoma samples. Tumor suppressor function of MIR129 was demonstrated by MTT and trypan blue exclusion assay after MIR129 overexpression. Results The sensitivity of the methylated-MSP was one in 10 3 . Different MSP statuses, including complete methylation, partial methylation, and complete unmethylation, were verified by quantitative bisulfite pyrosequencing. All five lymphoma and seven of eight myeloma cell lines showed complete and partial MIR129-2 methylation. In primary samples, MIR129-2 methylation was absent in AML and CML, but detected in 5% ALL, 45.9% CLL, 49.5% MM at diagnosis, and 59.1% NHL. In CLL, MIR129-2 methylation adversely impacted on survival (p=0.004). In MM, MIR129-2 methylation increased from 27.5% MGUS to 49.5% MM at diagnosis and 41.5% at relapse/progression (p=0.023). In NHL, MIR129-2 methylation was associated with MIR124-1 and MIR203 methylation (p&lt;0.001), and lower MIR129 expression (p=0.009). Hypomethylation treatment of JEKO-1, homozygously methylated for MIR129-2 , led to MIR129-2 demethylation and MIR129 re-expression, with downregulation of SOX4 mRNA. Moreover, MIR129 overexpression in both mantle cell lines, JEKO-1 and GRANTA-519, inhibited cellular proliferation and enhanced cell death, with concomitant SOX4 mRNA downregulation. Conclusions MIR129-2 is a tumor suppressive microRNA frequently methylated in lymphoid but not myeloid malignancies, leading to reversible MIR129-2 silencing. In CLL, MIR129-2 methylation was associated with an inferior survival. In MM, MIR129-2 methylation might be acquired during progression from MGUS to symptomatic MM. In NHL, MIR129-2 methylation might collaborate with MIR124-1 and MIR203 methylation in lymphomagenesis.
Evaluation of a New Cuvette Densitometer for Determination of Cardiac Output
Authors: OSCAR W. SHADLE, THOMAS B. FERGUSON, DONALD E. GREGG, SAUL R. GILFORD
Journal: Circulation Research (1953)

Quantitation of cardiac output by the Stewart-Hamilton method will have extended usefulness if the accuracy of measuring the concentration of Evans blue dye in whole blood is established. Cardiac outputs by this method have been compared in dogs with outputs by the rotameter and the Fick method. The constant-flow photometer (Friedlich) was used initially, but certain difficulties in its use led to the development of a new cuvette densitometer. Comparisons using both these instruments gave average variations of plus 7.0 per cent and minus 5.4 per cent from the reference methods. With proper caution cardiac outputs in dogs can be accurately obtained from dye dilution curves in whole blood.
Unconventional Role of the Inwardly Rectifying Potassium Channel Kir2.2 as a Constitutive Activator of RelA in Cancer
Authors: Inkyoung Lee, Sook-Ja Lee, Tong Mook Kang, Won Ki Kang, Chaehwa Park
Journal: Cancer Research (2012)

The constitutive activation of NF-κB is a major event leading to the initiation, development, and progression of cancer. Recently, we showed that the size of preestablished tumors was reduced after the depletion of Kir2.2, an inwardly rectifying potassium channel. To determine the precise mechanism of action of Kir2.2 in the control of tumor growth, we searched for interacting proteins. Notably, NF-κB p65/RelA was identified as a binding partner of Kir2.2 in a yeast two-hybrid analysis. Further analyses revealed that Kir2.2 directly interacted with RelA in vitro and coimmunoprecipitated with RelA from cell lysates. Kir2.2 increased RelA phosphorylation at S536 and facilitated its translocation from the cytoplasm to the nucleus, thereby activating the transcription factor and increasing the expression level of NF-κB targets, including cyclin D1, matrix metalloproteinase (MMP)9, and VEGF. Kir2.2 was overexpressed in human cancer and the expression level was correlated with increased colony formation and tumor growth in mouse tumor models. On the basis of these findings, we propose an unconventional role for Kir2.2 as a constitutive RelA-activating protein, which is likely to contribute to tumor progression in vivo.
Toward a Better Understanding of Race and Cancer
Authors: Otis W. Brawley
Journal: Clinical Cancer Research (2010)

Abstract A better understanding of breast cancer subtypes is allowing their use as prognostic markers. For some time, it has been documented that black women with breast cancer have a poorer prognosis than white women of the same stage. Advances in immunohistochemistry and the appreciation of breast cancer subtypes are enabling investigators to study the distribution of these subtypes among populations. Clin Cancer Res; 16(24); 5920–2. ©2010 AACR.
The long term outcome of gastric non-invasive neoplasia
Authors: M Rugge
Journal: Gut (2003)

<b>Background:</b> The cancer risk associated with gastric non-invasive neoplasia (formerly dysplasia) is debated. This prospective long term follow up study investigates the clinicopathological behaviour of non-invasive gastric neoplasia (and related lesions), focusing on the cancer risk associated with each different histological phenotype. <b>Patients and methods:</b> A total of 118 consecutive cases (nine indefinite for non- invasive neoplasia; 90 low grade non-invasive neoplasia; 16 high grade non- invasive neoplasia; and three suspicious for invasive adenocarcinoma) with a histological follow up of more than 12 months (average 52 months; range 12–206) were prospectively followed up with a standardised protocol. Patients in whom gastric cancer was detected within 12 months from the initial diagnosis of non-invasive neoplasia were excluded, assuming that invasive carcinoma had been missed at the initial endoscopy procedure. <b>Results:</b> Non-invasive neoplasia was no longer detectable in 57/118 cases (48%), was unchanged in 32 (30%), and evolved into gastric cancer in 20 patients (17%). Evolution to invasive adenocarcinoma was documented in both low and high grade non-invasive neoplastic lesions (8/90 low grade; 11/16 high grade) and correlated with histological severity (low versus high grade) at baseline (p&lt;0.001). Seventy five per cent of cancers occurring during the long term follow up were stage I. <b>Conclusions:</b> The risk of invasive gastric cancer increases with the histological grade of the non-invasive neoplasia. Following up non-invasive gastric neoplasia increases the likelihood of gastric cancer being detected in its early stages.
Electrostatic potential on human leukocyte antigen: implications for putative mechanism of chronic beryllium disease.
Authors: James A Snyder, Ainsley Weston, Sally S Tinkle, Eugene Demchuk
Journal: Environmental Health Perspectives (2003)

The pathobiology of chronic beryllium disease (CBD) involves the major histocompatibility complex class II human leukocyte antigen (HLA). Although occupational exposure to beryllium is the cause of CBD, molecular epidemiologic studies suggest that specific (Italic)HLA-DPB1(/Italic) alleles may be genetic susceptibility factors. We have studied three-dimensional structural models of HLA-DP proteins encoded by these genes. The extracellular domains of HLA-DPA1*0103/B1*1701, *1901, *0201, and *0401, and HLA-DPA1*0201/B1*1701, *1901, *0201, and *0401 were modeled from the X-ray coordinates of an HLA-DR template. Using these models, the electrostatic potential at the molecular surface of each HLA-DP was calculated and compared. These comparisons identify specific characteristics in the vicinity of the antigen-binding pocket that distinguish the different HLA-DP allotypes. Differences in electrostatics originate from the shape, specific disposition, and variation in the negatively charged groups around the pocket. The more negative the pocket potential, the greater the odds of developing CBD estimated from reported epidemiologic studies. Adverse impact is caused by charged substitutions in positions 55, 56, 69, 84, and 85, namely, the exact same loci identified as genetic markers of CBD susceptibility as well as cobalt-lung hard metal disease. These findings suggest that certain substitutions may promote an involuntary cation-binding site within a putatively metal-free peptide-binding pocket and therefore change the innate specificity of antigen recognition.
Physical activity and risk of gastric cancer: a meta-analysis of observational studies
Authors: Ajibola Ibraheem Abioye, Majeed Olaniyi Odesanya, Asanat Iyabode Abioye, Nasiru Akanmu Ibrahim
Journal: British Journal of Sports Medicine (2014)

Studies evaluating the relationship of physical activity and stomach cancer risk have yielded inconsistent and largely inconclusive results. We therefore conducted a systematic review and meta-analysis of observational studies that assessed the relationship between physical activity and risk of gastric cancer.Following a standard protocol, we searched medical literature databases (PubMed, EMBASE, CINAHL, PsycINFO and Google Scholar) from inception to July 2012, and conducted a random effects meta-analysis.Seven prospective cohorts and four case-control studies of physical activity and gastric cancer risk, with 1,535,006 people and 7944 cases of gastric cancer were included. We found a modest protective association between sufficient physical activity and gastric cancer risk (relative risk: 0.81 (95% CI 0.69 to 0.96); I(2)=68.5%) in the prospective studies and (relative risk: 0.78 (95% CI 0.66 to 0.91); I(2)=0%) in case-control studies. The association appeared weaker in smokers than in non-smokers (p heterogeneity=0.035). The association may also be weaker for gastric cardia cancer relative to the distal non-cardia subtypes. Physical activity type (recreational or occupational), intake of alcohol, total energy intake, consumption of fruits and vegetables and infection with Helicobacter pylori had no influence on the association. The effect measure from cohort studies (relative risk: 0.82 (95% CI 0.70 to 0.97); I(2)=61.7%) and case-control studies (relative risk: 0.83 (95% CI 0.66 to 1.04); I(2)=49.8%) did not differ materially at higher physical activity levels.We conclude that a regular physical activity may be protective against stomach cancer risk.
Emergence of Sentinel Node Biopsy in Breast Cancer as Standard-of-Care in Academic Comprehensive Cancer Centers
Authors: S. B. Edge, J. C. Niland, M. A. Bookman, R. L. Theriault, R. Ottesen, E. Lepisto, J. C. Weeks
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Ongoing clinical trials are addressing the accuracy and safety of sentinel node biopsy (SNB) in the treatment of breast cancer; however, SNB is already increasingly being used in clinical practice. This study examined the extent and time trends of the use of SNB in stage I and II breast cancer patients. Methods: Clinical data were collected from stage I and II (tumor size ⩽5.0 cm) breast cancer patients (n = 3003) who were treated at five comprehensive cancer centers between July 1, 1997, and December 31, 2000. Axillary surgery was classified as SNB alone, SNB + axillary node dissection (AND), AND alone, or none. Patterns of use of axillary surgery were summarized as the percentage of patients receiving each surgery type. The statistical significance of time trends for the use of SNB alone was analyzed by logistic regression models. All statistical tests were two-sided. Results: Overall, SNB alone was used in 13% of patients, SNB + AND in 22%, AND alone in 59%, and no axillary surgery in 6%. Use of SNB alone was statistically significantly associated with breast-conserving surgery of both smaller (⩽2 cm) and larger tumors (2–5 cm) (P<.001 for both associations). For stage I cancer patients treated with breast-conserving surgery (n = 1763), use of SNB increased statistically significantly over the study period, from 8% in 1997 to 9%, 14%, 15%, 22%, 42%, and 58% for the next six consecutive 6-month time intervals, respectively. After controlling for center, age, and comorbidity, the odds ratio for the use of SNB alone was 2.30 (95% confidence interval = 1.88 to 2.82) for each 6-month interval (P<.001). Conclusions: Widespread use of SNB outside the clinical trial setting suggests that oncologists at cancer centers in our study have accepted SNB as standard-of-care for the treatment of breast cancer. This acceptance, if it occurs in other cancer centers and community practice, may affect accrual and generalizability of ongoing clinical trials of SNB.