tbuckley/cabot-search huggingface dataset:
Race and the poor prognosis basal breast tumor (BBT) phenotype in the population-based Carolina Breast Cancer Study (CBCS)
Authors: L. A. Carey, C. M. Perou, L. G. Dressler, C. A. Livasy, J. Geradts, D. Cowan, C.-K. Tse, R. C. Millikan
Journal: Journal of Clinical Oncology (2004)

9510 Background: Gene expression arrays reveal several breast cancer (BrCa) subtypes, with the basal-like subtype (BBT) carrying a poor prognosis (Sorlie T, PNAS 2003). Multiple BrCa microarray datasets (Sorlie et al PNAS 2003; van't Veer et al, Nature 2002; Sotiriou et al, PNAS 2003) suggest that 90% of BBT are ER-negative, PR-negative, and HER-2 nonamplified (Perou C, unpublished). Thus, this “triple negative” phenotype may be used to identify and determine the frequency of BBT. Methods: Data were obtained from the CBCS, a population-based case-control study of BrCa causation among African-American (AA) and non-African American (nonAA) women. The CBCS oversampled AA and women under the age of 50. HER-2 was determined by UNC Lineberger Immunohistochemistry (IHC) Core. We determined the proportion of triple negative BrCa by race (AA vs. non-AA) and by stage, mitotic index (>10 vs. ≤10) nuclear grade and histologic grade (grade 3 vs. 1–2). Results: 657 incident BrCa were evaluated from Phase I of the CBCS, including 260 AA and 397 nonAA women. 26.2% of all BrCa were triple negative, however this phenotype was significantly more frequent in AA (33.9% vs. 21.2%, p=0.0003), premenopausal women (30.3% vs. 21.9%, p=0.02), mitotic index > 10 (45.8% vs. 11.3%, p<0.0001), and nuclear or histologic grade 3 tumors (p=0.0001). The highest prevalence of triple negative BrCa occurred among premenopausal AA women (44.3%) compared with postmenopausal AA women (24.6%) (p=0.0008). In multivariate models combining all factors, the significant predictors of the triple negative phenotype were high mitotic index (p<0.0001), high nuclear or histologic grade (p<0.0001 both), and race (p=0.03). Conclusions: The poor-prognosis BBT subtype is strongly associated with high proliferative capacity (mitotic index > 10) and nuclear pleomorphism. In a large population-based study, the triple negative phenotype characteristic of BBT is markedly more common in AA women, particularly premenopausal AA women. The high proportion of BBT likely plays a role in the poor prognosis experienced by AA women with BrCa. (supported by NCI (SPORE CA58223), NIH (GCRC MO1RR00046). No significant financial relationships to disclose.
Medical training and public health budgets will be cut, Osborne confirms
Authors: Gareth Iacobucci
Journal: BMJ (2015)

The UK chancellor of the exchequer, George Osborne, has confirmed that budgets for medical training and public health will be cut, to help fund increases to the core NHS budget for the next five years.

The Treasury’s spending review outlines that the NHS in England will receive £10bn (€14bn; $15bn) more in real terms by 2020-21 than in 2014-15, with £6bn available by next year.1 This will raise NHS England’s budget to £101bn next year and to £120bn by 2020-21.

But, as experts forecasted ahead of the statement,2 the Department of Health’s wider budget, which pays for areas such as training, public health, and regulation, will be cut by 25%, which would currently amount to a loss of £1.5bn in funding a year.

Although the spending review was short on details of how these cuts would be implemented, it said that funding to local governments for public health would be …
Serum EGFR/HER-2 combination predicts poor survival in metastatic breast cancer
Authors: K. Leitzel, C. Souder, S. M. Ali, L. Demers, D. B. Evans, H. A. Chaudri-Ross, P. Hamer, W. Carney, A. Lipton
Journal: Journal of Clinical Oncology (2005)

9613 Background: Epidermal growth factor receptor (EGFR, erbB1) is overexpressed in primary breast cancer and in some reports is a poor prognostic factor. We previously reported that metastatic breast cancer patients with elevated pretreatment serum HER-2/neu have decreased response and survival. (JCO 21: 1967, 2003). Methods: Pretreatment serum EGFR was quantified in the 1st line phase III letrozole-tamoxifen trial and in controls using the Oncogene Science/Bayer Diagnostics EGFR ELISA. Results: Serum EGFR from 117 healthy post-menopausal female controls measured 64.1 ± 13.3 ng/ml (mean ± SD) (Range 39.5–117.1 ng/ml). Using a cutpoint of 44.1 ng/ml from the control group (5% non-parametric method), 62/542 patients (11%) had decreased serum EGFR. Patients with decreased serum EGFR had no significant difference in objective response rate (ORR), clinical benefit rate (CBR), time to progression (TTP), or time to treatment failure (TTF) to 1st line hormone therapy, but did have significantly reduced survival compared to patients with normal serum EGFR levels (median survival 22.8 vs. 30.4 mos.) (P= .006). Combined analysis of pretreatment serum EGFR and HER-2 yielded no additional predictive information for ORR, CBR, TTP, and TTF compared to serum HER-2 alone. However, combined serum EGFR and HER-2 analysis identified a subgroup of patients with decreased serum EGFR and normal serum HER-2 (n = 43/542, 8%) that had significantly reduced survival compared to patients with normal serum levels of both EGFR and HER-2 (median survival 23.5 vs. 37.1 mos.) (P= .007). In multivariate analysis, decreased serum EGFR level remained a significant independent prognostic factor for decreased survival (hazard ratio HR = 1.59, P= .005). Other significant variables for decreased survival included the presence of liver metastasis (HR = 2.31, P <.0001) and elevated serum HER-2 (HR = 1.80, P= <.0001), while positive hormone receptor status lowered the risk of mortality (HR = .78, P= .03). Conclusions: In metastatic breast cancer patients, decreased serum EGFR/normal serum HER-2 predicted for a shorter survival - similar to elevated serum HER-2. This patient subgroup deserves further study to assess response to anti-EGFR-directed therapies. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Oncogene Science/Bayer Diagnostics Bayer Bayer, Novartis Bayer, OSI/Bayer Diagnostics
Abstract 1903: Corticosteroids Are Associated With Increased Morbidity in Children Undergoing Congenital Heart Surgery
Authors: Sara K Pasquali, Matthew Hall, Jennifer S Li, Eric D Peterson, James Jaggers, Andrew J Lodge, Bradley S Marino, Denise M Goodman, Samir S Shah
Journal: Circulation (2009)

Background: Children undergoing congenital heart surgery often receive corticosteroids (CS) with the aim of reducing post-operative inflammation and capillary leak following cardiopulmonary bypass;...
Not all teenagers are sexually active [letter]
Authors: Duffield K, Josen Pk, Low E, Teare K, Wray E
Journal: BMJ (2001)

Churchill et al. in their study dispel the myth that teenagers do not consult their general practitioners about contraception.  They also conclude however that teenagers who become pregnant have higher consultation rates than their age matched peers most of the difference owing to consultation for contraception.  We do not believe that this claim is justified as the potential confounder of sexual activity was not controlled for.  While the case group (pregnant teenagers) must be sexually active the same cannot be said of the age matched controls.  It is probable that rates of sexual activity were lower among controls especially at the lower end of the age range used (13-19 years).  In a recent survey only 20% of 13-year-olds reported having had full or oral sexual intercourse.  Abstinent controls would not be expected to consult about contraception.  This would lower the average contraceptive consultation rate per individual within the control group potentially masking higher consultation rates for sexually active controls.  Therefore teenagers who become pregnant could be underconsulting for contraception compared with their sexually active peers.  On the basis of this paper it cannot be assumed that teenagers who become pregnant make greater use of general practitioners contraceptive services.  Churchill et al acknowledge in discussion that sexual activity is a confounding variable but proceed to draw an unjustified conclusion because of their use of inappropriate controls.  (full text)
Nomogram to predict risk of 30-day mortality for patients with disseminated malignancy undergoing surgical intervention.
Authors: W. H. Tseng, N. H. Willits, S. L. Chen, S. R. Martinez, F. J. Meyers, R. J. Bold, J. E. Goodnight, R. J. Canter
Journal: Journal of Clinical Oncology (2010)

6105 Background: Limited data exist regarding the perioperative outcomes and risk of surgical intervention among patients with disseminated malignancy (DMa). We examined the 30-day morbidity and mortality for this group of patients and developed a risk assessment tool to enhance surgical decision- making. Methods: TheAmerican College of Surgeons National Surgical Quality Improvement Program (NSQIP) prospectively captures risk-adjusted, audited data from 248 US hospitals on patients undergoing general and vascular operations. Data from 2005-07 (n = 363,897) were used to identify 7,447 patients with DMa. Univariate analyses were performed using all 53 preoperative NSQIP variables to assess risk of morbidity and mortality. Logistic regression models were developed using stepwise model selection and generalized additive models. Covariates were evaluated for non-linearity and interactions among variables. A nomogram was constructed utilizing covariates significant at p ≤ 0.001 on multivariate analysis. Results: Overall 30-day morbidity and mortality rates were 28% and 8.9%, respectively. Mortality rates reached 18.4% for vascular procedures and 27.9% for emergent operations (14.1% of total). Increasing age, impaired functional status, DNR status, impaired respiratory function, ascites, hypoalbuminema, elevated creatinine, and abnormal WBC were all significant predictors (p < 0.0001) on multivariate analysis of increased morbidity and mortality. Preoperative sepsis, radiotherapy, steroid use, and diabetes showed a strong trend but did not meet our cutoff for significance (0.02 < 0.04). A nomogram to predict individual 30-day risk of death based on preoperative factors was developed and validated, with a Kendall's tau value of 0.722. Conclusions: Surgical intervention among patients with DMa is associated with substantial morbidity and mortality. A nomogram to predict operative risk has been constructed. This has considerable implications for surgical decision-making in this group of patients. No significant financial relationships to disclose.
Nuclear Spin Relaxation in Solutions Prepared from Normal and Tumor Hepatic Tissues: Brief Communication 2
Authors: Ronald E. Block, Gayle P. Maxwell, Donna L. Branam
Journal: JNCI Journal of the National Cancer Institute (1977)

Water proton nuclear spin relaxation times were investigated at two frequencies (10.7 and 100 MHz) in solutions prepared from Dunning hepatomas (LC-18) and normal Iivers of F344 rats. The solutions (saps) were prepared by homogenization of the tissue without the addition of water or chemieals, followed by two centrifugations. The water proton spin-lattice and spin-spin relaxation times (T1 and T2, respectively) were longer in the tumor sap than in the Iiver sap. The T1/T2 ratio was higher than that for pure water, and the T1 values were higher at the higher frequency. A rough correlation with significant scatter was found between T1−1 and F/(1−F), where F is grams protein/grams solution. Precipitation of protein with trichloroacetic acid yielded solutions that showed higher T1 values when prepared from tumor sap than from Iiver sap. Glycogen concentrations were much higher in the deproteinated liver saps than in deproteinated hepatoma saps. Dialysis of fresh sap against butter for 4 hours produced no change in T1. Addition of the reducing agent sodium dithionite produced no change in T1. It was concluded that water-protein and water-glycogen interactions are the predominant mechanism for the shortening of sap relaxation times relative to that of distilled water. The higher concentrations of protein and glycogen in liver sap compared to hepatoma sap were the likely cause of the liver sap T1 values being shorter than those of hepatoma sap. No evidence of a significant paramagnetic speeies ettect on sap T1 was found.
Etiology of Cancer of the Renal Pelvis
Authors: J K McLaughlin, W J Blot, J S Mandel, L M Schuman, E S Mehl, J F Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1983)

A population-based case--control interview study of cancer of the renal pelvis (74 cases and 697 controls) conducted in the Minneapolis--St. Paul metropolitan area showed cigarette smoking to be the major cause of this cancer. The odds ratio (OR) for cigarette smoking was 7.6 among males [95% confidence interval (CI): 2.2-31.5] and 5.8 among females (95% CI: 2.0-17.3), with the OR exceeding 10 for heavy smokers of both sexes. Long-term use of analgesics and several occupational exposures were also found to be risk factors. In addition, there were unexpected positive associations among females for heavy tea consumption and for use of estrogen medications, although the significance of these relationships remains to be clarified.
Abstract 16670: Insulin Resistance is Associated With Impaired Cardiac Sympathetic Innervation in Patients Affected by Heart Failure
Authors: Stefania Paolillo, Giuseppe Rengo, Teresa Pellegrino, Gianluigi Savarese, Gennaro Pagano, Roberto Formisano, Laura Petraglia, Raffaella Carotenuto, Dario Leosco, Bruno Trimarco, Alberto Cuocolo, Pasquale Perrone-Filardi
Journal: Circulation (2013)
A comparative analysis of angiogenesis between male and female breast cancers
Authors: R. Bakkar, Z. Nahleh, H. Bui, S. Samaan, J. Sanders, A. Namakydoust, R. Komrokji
Journal: Journal of Clinical Oncology (2007)

21101 Background: Tumor angiogenesis and vascularization are essential for the growth and metastasis of tumors. VEGF-C expression and peritumoral lymphocyte density (PLD) are markers of angiogenesis. They have been correlated with poor prognosis in female breast cancer (FBC). The purpose of this study is to characterize VEGF-C expression and PLD in MBC and correlate with FBC specimens. Method: We reviewed records of patients diagnosed with MBC and FBC at the Cincinnati VAMC, from 1989 to 2006. Pathology slides were retrieved. We used VEGF-C (Host Rabbit, PAD: Z-CVC7) . Imunohistochemical stains of VEGF-C were given scores of 0 to 3+ based on nuclear stains. PLD was analyzed based on the number of lymphocyte cells surrounding the tumor; score of 0 to 3+. Slides were reviewed independently by two pathologists. Results: We found nine MBC cases and selected 9 FBC cases. Mean age was 72 in the male patients and 62 in the females. Stages of disease were distributed as follows in MBC versus FBC, 11% versus 22% stage 0, 23% versus 23% stage I, 44% versus 44% stage II, and 22% versus 11% stage IV. Ductal carcinoma was the predominant histology in 88% of FBC and 88% MBC. Other histological types included papillary (1 MBC) and lobular (1 FBC). Among the invasive MBC tumors , 75 % were ER+/PR +, 13% ER+/PR-, and 12% ER -/PR- , compared to 72 % ER+/PR+, 14% ER+/PR-, and 14% ER-/PR- in FBC. Eight out of the 9 MBC cases (89%) stained positive for VEGF-C expression, compared to one FBC case (11%). The 1 male breast intraductal carcinoma was positive for VEGF-C expression, compared to none of the two intraductal FBC. PLD was more intense in male than female tumors : score 0 or 1+: 44% in MBC versus 67% in FBC , score 2+: 22% in MBC Versus 22% in FBC, and score 3+: 22% in MBC versus 11% in FBC. VEGF-C expression did not seem to correlate with ER/PR status. The median survival for patients with MBC was 4.5 years and for patients with FBC 6.9 years. Conclusion: VEGF-C expression and PLD were more pronounced in MBC versus FBC. This finding may correlate with more aggressive behavior of breast tumor cells in male patients, more intense angiogenic reaction and lower median survival. Further studies are warranted to further elucidate the role of angiogenesis in male breast cancer and explore potential antiangiogenic therapeutic modalities. No significant financial relationships to disclose.
Increased mean corpuscular volume of erythrocytes with capecitabine treatment in metastatic breast cancer patients: A marker of clinical benefit?
Authors: S. Aksoy, C. Arslan, M. Kurt, O. Dizdar, D. Sener Dede, E. Dogan, I. H. Gullu, Y. Y. Ozisik, M. K. Altundag, N. Guler
Journal: Journal of Clinical Oncology (2010)

1147 Background: We aimed to investigate the mean corpuscular volume (MCV) changes of red blood cells (RBC), and the possible association of clinical response in metastatic breast cancer patients (MBCP) under capecitabine treatment retrospectively. Methods: The data of 75 MBCP receiving capecitabine treatment between years of 2001 and 2005 were evaluated retrospectively. Capecitabine was used 2,500 mg2 daily for 14 days every 3 weeks. The complete blood count (CBC) including MCV (fl) was controlled at the beginning of capecitabine treatment, and periodically thereafter. ΔMCV was calculated by subtraction of MCV at the beginning from control date. Results: Forty-six of MBCP were premenopausal (61.3%). Mean age was 51.5 ± 10.8 years. Sixty-seven patients had invasive ductal carcinoma (89.4%). Estrogen and progesterone receptors were positive at 56% and 49% of the patients, respectively. Forty-eight patients (64%) had visceral, 11 had (14.7%) bone, 16 had soft tissue (21.3%) metastases. Capecitabine was administered as the median third line treatment for metastatic disease (range, 1-9 lines). There were 4 CR (5.3%), 35 PR (46.7%), 21 SD (28%), and 15 PD (20%) under capecitabine treatment. Mean hemoglobin level was 12.5 gr/dl at the beginning and 12.2 gr/dl at ninth week (p>0.05). Median ΔMCV level was 9.32 (±5.64) for patients having clinical benefit (CR+PR+SD), and 5.71 ± 3.74 for the nonresponders (p=0.005). Mean ΔMCV level was 9.85 ± 6.15 for the patients having PR and CR and 7.24 ± 4.35 for the patients with SD and PD (p > 0.037). However, there was not a significant correlation between PFS and ΔMCV. Conclusions: Capecitabine increases the MCV levels of RBCs in MBCP. Early increment of MCV levels might predict the clinical benefit from treatment. No significant financial relationships to disclose.
Lithium vs. valproate vs. olanzapine vs. quetiapine as maintenance monotherapy for bipolar disorder: a population‐based UK cohort study using electronic health records
Authors: Joseph F. Hayes, Louise Marston, Kate Walters, John R. Geddes, Michael King, David P.J. Osborn
Journal: World Psychiatry (2016)

It is unclear which maintenance treatment for bipolar disorder is superior in clinical practice. Randomized controlled head-to-head trials of available drugs either do not exist or are inconclusive. We aimed to compare rates of monotherapy treatment failure in individuals prescribed lithium, valproate, olanzapine or quetiapine by a population-based cohort study using electronic health records. 5,089 patients with bipolar disorder were prescribed lithium (N=1,505), valproate (N=1,173) olanzapine (N=1,366) or quetiapine (N=1,075) as monotherapy. Treatment failure was defined as time to stopping medication or add-on of another mood stabilizer, antipsychotic, antidepressant or benzodiazepine. In unadjusted analyses, the duration of successful monotherapy was longest in individuals treated with lithium. Treatment failure had occurred in 75% of those prescribed lithium by 2.05 years (95% CI: 1.63-2.51), compared to 0.76 years (95% CI: 0.64-0.84) for those prescribed quetiapine, 0.98 years (95% CI: 0.84-1.18) for those prescribed valproate, and 1.13 years for those prescribed olanzapine (95% CI: 1.00-1.31). Lithium's superiority remained in a propensity score matched analysis; when treatment failure was defined as stopping medication or add-on of a mood stabilizer or antipsychotic; and when treatment failure was restricted to more than three months after commencing the study drug. Lithium appears to be more successful as monotherapy maintenance treatment than valproate, olanzapine or quetiapine. Lithium is often avoided because of its side effect profile, but alternative treatments may reduce the time to being prescribed more than one drug, with potential additive side effects of these treatments.
Antimelanogenic effects of luteolin 7-sulfate isolated from<i>Phyllospadix iwatensis</i>Makino
Authors: J.Y. Kwak, J.K. Seok, H.-J. Suh, Y.-H. Choi, S.S. Hong, D.S. Kim, Y.C. Boo
Journal: British Journal of Dermatology (2016)

Abnormal deposition of melanin may cause an aesthetic skin problem; therefore, the control of unwanted excessive melanin synthesis is the major goal of cosmetic research.To identify novel tyrosinase (TYR) inhibitors from marine plants and examine their cellular antimelanogenic effects.The extracts of 50 marine plants endemic to Korea were screened against human TYR. Active constituents were then isolated from the selected plant extracts that showed potential and their chemical structures elucidated. Furthermore, their antimelanogenic effects were examined using murine melanoma B16/F10 cells and human epidermal melanocytes (HEM).Among the tested extracts, that of Phyllospadix iwatensis Makino exhibited the strongest human TYR inhibitory activity. The active constituents were purified from the butanol fraction of the P. iwatensis extract and identified as hispidulin 7-sulfate and luteolin 7-sulfate. Luteolin 7-sulfate inhibited human TYR more strongly than hispidulin 7-sulfate, luteolin, hispidulin and arbutin. Furthermore, luteolin 7-sulfate showed lower cytotoxicity than luteolin in both B16/F10 cells and HEM. Luteolin 7-sulfate attenuated cellular melanin synthesis more effectively in B16/F10 cells and HEM stimulated by α-melanocyte-stimulating hormone and l-tyrosine than arbutin.This study demonstrates that luteolin 7-sulfate isolated from P. iwatensis is a human TYR inhibitor with advantageous antimelanogenic properties, and would be useful for development as a therapeutic agent for the control of unwanted skin pigmentation.