tbuckley/cabot-search huggingface dataset:
Erratum: Cage Allocation Designs for Rodent Carcinogenicity Experiments
Authors: Agnes M. Herzberg, Stephen W. Lagakos
Journal: Environmental Health Perspectives (1992)

Cage allocation designs for rodent carcinogenicity experiments are discussed and presented with the goal of avoiding dosage group biases related to cage location.Considerations in selecting a cage design are first discussed in general terms.Specific designs are presented for use in experiments Involving three, four, and five dose groups and with one, four, and five rodents percage.Priorities for ngtreanent groups bwlude horzontal poslton shelf and shelf of rak, nearest neighbor balance, and male-female la It is pposed thatthese baince citeria be conudered tgether with pracical issues, such as the ability to accurately conform to a design and to determine a sensible and efficient design for each experiment.
Abstract 1490: Overexpression of a calcium channel protein TRPM8 in prostate cancer cells enhances their anchorage-independent growth and resistance to paclitaxel-induced apoptosis
Authors: Shan Yu, Zhenyu Xu, Franky L. Chan
Journal: Cancer Research (2010)

Abstract The non-voltaged-gated transient receptor potential protein melastatin member 8 (TRPM8) has been characterized to function as a cold- and menthol-activated calcium-permeable channel protein, which it was originally cloned in a prostate-specific substracted cDNA library and shown to be up-regulated in benign prostatic hyperplasia and prostate cancer as compared to normal prostatic epithelial cells. Recent studies in cultured prostate cancer cells and clinical prostate cancer tissues show that TRPM8 is an androgen receptor-regulated calcium channel which is required for the survival and androgen-dependent growth of prostate cancer cells. Based on this evidence, it is believed that TRPM8 may play an important role in the advanced growth of prostate cancer. However, the prostate-specific function of TRPM8 and the role of TRPM8-regulated calcium-influx in prostate function and its carcinogenesis remain unclear. Our preliminary studies showed that TRPM8 was significantly over-expressed in an androgen-independent and metastatic prostate cancer cell line C4-2B as compared to its parental line LNCaP and also in two animal models of metastatic prostate cancers (a transgenic mouse model of prostate cancer-TGMAP and xenograft model of C4-2B). In order to elucidate the functional significance of TRPM8 in prostate cancer cell growth, we over-expressed TRPM8 in an androgen-sensitive prostate cancer cell line LNCaP by lentiviral transduction and generated stable TRPM8 clones for phenotypic growth studies. Our findings showed that stable ectopic TRPM8 expression induced morphological changes in LNCaP cells with reduction of filopodial processes and also suppressed their in vitro cell proliferation as shown by MTT assay. However, stable LNCaP-TRPM8 clones demonstrated significantly enhanced colony formation efficiencies in soft agar assay. Moreover, stable TRPM8 expression also enhanced the in vivo tumor growth of LNCaP cells in immunodeficient SCID mice and resistance to paclitaxel-induced apoptosis, as compared to their parental line. The results of our present study suggest that altered calcium-homeostasis as disturbed by TRPM8 overexpression in prostate cancer cells could enhance their in vitro anchorage-independent and in vivo tumor growth, and also resistance to paclitaxel-induced apoptosis, while the involved calcium-dependent signaling pathways still remain to be elucidated. (Study supported by a RGC Competitive Earmarked Research Grant project code 461007) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1490.
Does progression-free-survival (PFS) correlate with overall- and cancer-specific survival (OS/CSS) in randomized clinical trials (RCTs) exploring the addition of hormonal therapy (HT) to radiotherapy (RT) for early prostate cancer (EPC)? Analysis of six RCTs
Authors: E. M. Ruggeri, E. Bria, P. Carlini, F. Cuppone, M. Milella, C. Nisticò, I. Sperduti, E. Terzoli, F. Cognetti, D. Giannarelli
Journal: Journal of Clinical Oncology (2007)

5056 Background: Although PFS is considered the standard primary end-point in EPC, the correlation with OS has never been explored in RCTs randomizing patients (pts) to HT plus radiotherapy (RT) versus RT. Given the relatively long prognosis in this disease setting, the correlation between PFS and CSS should be investigated as well. Methods: All phase III trials reporting all outcome’ data were considered eligible. The correlation has been explored according to a linear regression model considering both each single outcome pair (PFS, OS and CSS rates) for all arms, and each reported Hazard Ratio (HRs). The correlation was estimated according to both the Pearson- (r) and R 2 -coefficient (parametric) and the Spearman coefficient (Rho, non-parametric). A sensitivity analysis in 2 subgroups (long- and short-term HT) to test for effect robustness has been accomplished as well. A model to determine the target sample size to determine CSS benefit of 3%, 4%, 6% and 7% months, respectively, was calculated as well. Results: Six RCTs (4,212 pts) were collected (follow-up range: 4.5–7.6 years). In the overall population, when considering the crude rates, a linear stronger correlation was found between PFS and CSS (r=0.71, R 2 =0.51, p=0.003; Rho=0.75, p=0.005), rather than with OS (r=0.55, R 2 =0.30, p=0.06; Rho=0.78, p=0.11). Again, when considering HRs, a linear stronger correlation was found between PFS and CSS (r=0.87, R 2 =0.76, p=0.02; Rho=0.94, p=0.005), rather than with OS (r=0.75, R 2 =0.56, p=0.08; Rho=0.77, p=0.07). Similar correlations were found whatever subgroups was explored. The sample size model (on the basis of the beta-coefficient=0.71), calculate 4,575, 2,006, 1,115 and 700 pts to improve PFS of 4%, 6%, 8%, and 10% months, which means to improve CSS of 2.8%, 4.3%, 5.7% and 7.1%, respectively. Conclusions: The correlation between PFS and CSS in RCTs exploring the benefit of adding HT to RT for EPC is significant, and suggests its further investigation as surrogate end-point. The natural history of the disease clearly explains the stronger correlation of PFS with CSS rather than with OS. No significant financial relationships to disclose.
Endoscopic ultrasound diagnosis of pneumatosis cystoides coli initially misdiagnosed as colonic polyps
Authors: Khaled Bamakhrama, Luka Abdulhady, Peter Vilmann
Journal: Endoscopy (2014)

An 85-year-old lady with chronic abdominal pain underwent a colonoscopy, which showed flat, spreading polypoidal lesions in the descending colon, and she was consequently referred for endoscopic mucosal resection (EMR). A repeat colonoscopy (Pentax EC 38-i10 L) demonstrated multiple polypoidal lesions of varying sizes (3 mm – 3 cm), which were apparently interconnected, in the descending colon ([Fig. 1]; [Video 1]). The mucosa was of normal appearance on white-light endoscopy and also on i-scan with a Kudo's pit pattern type I. These features raised the suspicion of pneumatosis cystoides coli (PCC) and a radial endoscopic ultrasound (EUS; Pentax EG 3670 URK) confirmed this by showing multiple hyperechoic air pockets in the third wall layer of the descending colon ([Fig. 2]; [Video 2]). A computed tomography (CT) scan performed to rule out other malignant disease subsequently also demonstrated air-filled cysts in the wall of the colon ([Fig. 3]).
SAT0045 Serum Vegf Level and ANG2/ANG1 Ratio Measured at Baseline are Correlated with the Synovial Blood Flow Measured One Month Later in Rheumatoid Arthritis
Authors: S. Machaly, M. K. Senna
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Synovial angiogenesis is considered to be an important early step in the pathogenesis of rheumatoid arthritis (RA) and in the perpetuation of disease.<sup>1</sup> Because angiogenesis and formation of new blood vessels is a component of pannus in RA, we hypothesized that the balance between angiopoietin-1(Ang1) and angiopoietin-2 (Ang2) is in favor of Ang2 (represented by Ang2/Ang1 ratio) in RA pannus. <h3>Objectives</h3> To evaluate the serum levels of Ang1, Ang2 as well as the significance of Ang2/Ang1 ratio in RA in relation to blood flow signals in total of 10 joints and RA activity parameters. In addition, we studied their relevance to predict the state of angiogenesis. <h3>Methods</h3> This study was conducted on 65 consecutive very early RA patients. Power Doppler ultrasonography (PDUS) was performed in a total of 10 joints: the bilateral elbows, wrists, metacarpophalangeal, knees, and ankles. The blood flow signals at various sites of the synovial membrane of each joint were scored on a 3- grade scaling system. The score at the site with the strongest finding in each joint was adopted as the score of the joint, and the total of the scores of the 10 joints was defined as the total signal score (TSS). On the same day, Serum variables including serum VEGF, Ang1, and Ang2 levels as well as clinical disease activity were evaluated. All measured parameters were reassessed after one month. <h3>Results</h3> Serum VEGF and serum Ang2 levels as well as Ang2/Ang1 ratio were significantly correlated with CRP and DAS28-CRP at baseline and one month after. While, serum Ang1 level did not correlate with the indices of disease activity. Additionally, serum VEGF and Ang2 levels and Ang2/Ang1 ratio were significantly correlated with TSS at baseline and after one month. Moreover, significant correlations were noted between serum VEGF and level of Ang2 and Ang2/Ang1 ratio both at baseline and one month later. Serum Ang1 level was significantly inversely correlated with Ang2/Ang1 ratio in contrast to serum Ang2 level which correlated significantly with Ang2/Ang1 ratio at baseline and after one month. Interestingly baseline serum VEGF level was significantly correlated with TSS after one month. Also, baseline Ang2/Ang1 ratio was significantly correlated with TSS after one month. <h3>Conclusions</h3> Serum concentrations of VEGF and Ang2 as well as Ang2/Ang1 ratio were correlated with parameters of inflammation in early RA. Our results demonstrate that the elevated serum VEGF and Ang2/Ang1 ratio (in favor of Ang2) reflect a phase of vigorous angiogenesis. <h3>References</h3> Taylor PC. Serum vascular markers and vascular imaging in assessment of rheumatoid arthritis disease activity and response to therapy. Rheumatology 2005;44:721–728 <h3>Disclosure of Interest</h3> None Declared
Abstract P4-14-11: Risk reducing mastectomy for women with high personal breast cancer risk
Authors: O Onyekwelu, G Shetty, A Baildam
Journal: Cancer Research (2012)

Abstract Introduction: For high-risk familial history of breast cancer, risk reducing mastectomy (RRM) is now regarded as one of the management options. The aim of this study is to analyse the outcome of women undergoing RRM from 1994 to 2010 during which surgical techniques evolved and were refined. Methods: A cohort of women undergoing RRM was followed from this single centre. Surgical and further details about demographics, comorbidities, and follow-up were retrieved form medical records. Analysis was carried out using the IBM®-SPSS®-Statistics-19system. Results: Of 154 women 139 had bilateral RRM and 15 had unilateral surgery after earlier contralateral breast cancer. Median age at operation was 39.4 years (22–63years). 54 (45.5%) women were BRCA1/2 gene mutation carriers. Most women had nipple sacrificing (86) skin-sparing mastectomy with immediate reconstruction. 132 (85.7%) had submuscular expander/implant reconstruction, whilst 9 had either LD flap reconstruction or TRAM flap reconstruction. 31 (20.1%) women had some complication including haematoma requiring evacuation, minor skin/nipple necrosis, but implant loss was rare (2). 52 (33.8%) women had revisional surgeries in 5 years post RRM of whom 29 had one unanticipated secondary operation. Complications were more common in the early years of the cohort. On histology, 3 women were identified with lobular carcinoma in-situ and one was associated with 1mm of microinvasion. 4 had ductal carcinoma in-situ and 2 of them were BRCA carriers. Two (1.2%) primary breast cancers were subsequently identified during a mean follow-up period of 9.82 years (2–18 years) but this was substantially less than prediction modelling. Both were BRCA gene mutation carriers - one had nipple sparing RRM and the other did not. Conclusions: In asymptomatic high-risk women, RRM is safe and efficacious in reducing medium term future breast cancer incidence. Surgery carries the risk of complications and cosmetic revisions can be anticipated. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-11.
Plague or pure hype?
Authors: F. Godlee
Journal: BMJ (1997)

Newspapers recently gave great prominence to a story that a “ME plague” was sweeping through Britain's schools, Fiona Godlee looks behind the hype 

Of the many words–such as “breakthrough” and “cure”–that should alert newspaper readers to a science story being hyped, “plague” must be high on the list. The word suggests a deadly contagious epidemic. So, when the Guardian 's front page on 22 May carried the headline “Schools swept by ME plague,” readers may well have been sceptical. The first sentence of the story should have made them more so: according to the Guardian , “The largest study ever made of … ME … shows it is responsible for 51% of long term sickness absence among schoolchildren.” To “show” anything with certainty requires a study of exceptional rigour. And though the study was large, rigorous it was not.

The authors of the study, Jane Colby, a former headmistress, herself recovering from myalgic encephalomyelitis …
ED-39 * GANGLIOGLIOMA IN CHILDREN; IDENTIFICATION OF CASES AT RISK OF DEATH DUE TO PROGRESSION FOLLOWING INITIAL SURGERY
Authors: G. Zieman, C. Dardis, A. Gomes, A. Scheck, J. Eschbacher, S. Coons, L. Ashby
Journal: Neuro-Oncology (2014)

Gangliogliomas have traditionally been considered benign tumors, particularly in children. Following resection, the prognosis is thought to be excellent. We reviewed all cases of ganglioglioma at our institution over the preceding 10 years. Cases were identified by a review of the Neuro-Pathology records. Clinical and radiographic information was generated by a retrospective review of charts by the Dept. of Neuro-Oncology. 40 cases occurred in those age <18. Of these 48% were male. Age of onset peaked age 10-15. Similarly to adults, the majority of these were in the temporal lobe (or another cortical lobe). Pre-operative imaging showed the following characteristics: enhancing (70%), cystic (48%), calcification (30%). Gross total resection was achieved in 44%. Histology showed co-occurrence of cortical dysplasia in 7.5%. Survival information was available in 36 cases, out of which there were 3 deaths. These occurred at 1.3, 2.6 and 44.7 months following initial surgery. The only two cases where biopsy alone was performed died. In one, this appears to be due to location in the sella turcica; in the other due to the young age (age <1 year at diagnosis). No patients with gross total resection died. Two of the three also had features of juvenile pilocytic astrocytoma (JPA); only one other in the group had these features (chi-squared test p < 0.001). The one which was did not have features of JPA had features of anaplasia; only one other such case was present in the group (p = 0.03). All had a high p53 labeling index of >25% by immunohistochemistry (IHC); this was present in 3/9 cases checked in those who did not die (p < 0.05). Conclusion: While generally benign tumors, we suggest close surveillance in children with the following characteristics: biopsy alone undertaken, histological features of JPA or anaplasia and a high p53 by IHC.
RECORD-4: A multicenter, phase II trial of second-line everolimus (EVE) in patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Robert Motzer, Anna Alyasova, Dingwei Ye, Andrey Karpenko, Hanzhong Li, Boris Y. Alekseev, Liping Xie, Galina Petrova Kurteva, Ruben Dario Kowalyszyn, Yeni Neron, Thomas Cosgriff, LaTonya Collins, Thomas Brechenmacher, Scott Segal, Liza M. Morgan, Lin Yang
Journal: Journal of Clinical Oncology (2015)

4518 Background: In the pivotal RECORD-1 trial, EVE was superior to placebo in pts with mRCC previously treated with sunitinib, sorafenib, or both; prior treatment with cytokines, bevacizumab, and chemotherapy was permitted (Cancer 2010;116:4256). The RECORD-4 study assessed EVE in pts with mRCC who progressed after 1 prior anti-VEGF or cytokine. Methods: RECORD-4 enrolled pts with clear cell mRCC into 3 cohorts based on prior first-line therapy: sunitinib, other anti-VEGF, or cytokines. Pts received EVE 10 mg/d until progression of disease (PD; RECIST, v1.0) or intolerance. Primary endpoint was PFS per investigator review. Data cutoff was Sept 1, 2014. Results: Enrolled pts (N = 134) previously received sunitinib (n = 58), other anti-VEGF therapy (n = 62: 23 sorafenib, 16 bevacizumab, 13 pazopanib, 10 other), or cytokines (n = 14). Demographics were balanced among cohorts; overall 90% of pts had good/intermediate MSKCC prognosis; most were white (56%) or Asian (41%). At data cutoff, 88% of pts had discontinued, mainly due to PD (54%). Median duration of exposure was 5.8 mo. Median overall PFS (95% CI) was 7.8 (5.7-11.0) mo, 5.7 (3.7-11.3) mo with prior sunitinib, and 7.8 (5.7-11.0) mo with prior other anti-VEGFs (Table). Overall response rate (ORR) was 7.5% (95% CI, 3.6-13.3%); most pts achieved stable disease (67%) as best overall response. Overall rate of grade 3 or 4 adverse events (AEs) was 56%. Conclusions: RECORD-4 results reinforce the clinical benefit of EVE in the second line setting after sunitinib and other first-line therapies. EVE safety profile was consistent with previous experience. (ClinicalTrials.gov ID, NCT01491672). Clinical trial information: NCT01491672.Key efficacy and safety results. Prior therapy CytokinesN=14 Overall population N=134 Sunitinib N=58 Other anti-VEGF N=62 Median PFS (95% CI), mo 7.8 (5.7-11.0) 5.7 (3.7-11.3) 7.8 (5.7-11.0) 12.9 (2.6-NE) ORR, % (95% CI) 7.5 (3.6-13.3) 6.9 (1.9-16.7) 4.8 (1.0-13.5) 21.4 (4.7-50.8) Safety set N=133 N=58 N=61 N=14 Grade 3/4 AEsa, n (%) Anemia 17 (13) 6 (10) 7 (11) 4 (29) Stomatitis/mouth ulceration 10 (8) 4 (7) 4 (7) 2 (14) Hyperglycemia 6 (5) 2 (3) 4 (7) 0 (0) Hypertriglyceridemia 6 (5) 3 (5) 3 (5) 0 (0) NE, not evaluable. aCommonly reported (incidence ≥ 4%).
THU0018 Discrimination Analysis of Multiple Genetic Risk Markers Associated with Rheumatoid Arthritis in Slovakia
Authors: L. Chovanova, M. Vlcek, K. Krskova, F. Spoutil, A. Penesova, B. Vohnout, K. Raslova, J. Rovensky, I. Jochmanova, I. Lazurova, Z. Killinger, H. Radner, G. Steiner, J. Smolen, R. Imrich
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Several genes have been identified so far in the pathogenesis of rheumatoid arthritis (RA). The most important region is the Human Leukocyte Antigen (HLA) that contributes to approximately half of the genetic susceptibility for RA. The association seems to be stronger or specific for anti-citrullinated protein antibodies (ACPA) positive disease. More than 30 other variants in potentially pathogenic genes located in non-MHC regions have been identified by recently performed genome wide analysis studies among individuals of European ancestry. These alleles explain about 23% of the RA genetic burden. <h3>Objectives</h3> The aim of our study was to analyze the association of previously confirmed RA risk alleles in Slovak population and to determine their relationship and involvement in the increase of disease risk. <h3>Methods</h3> Genetic analysis was conducted in 1224 samples (494 RA patients, 728 controls; 83% females, 17% males) with balanced geographic distribution. The presence of HLA-DRB1 alleles (DRB1*04:01, 04:04, 04:05, 04:08, 04:10, 01:01, 01:02, 10:01) considered as shared epitope (SE) was analysed by ELPHA (Enzyme Linked Probe Hybridization Assay). Eight non-MHC single nucleotide polymorphysms (SNPs): PTPN22 (rs2476601), STAT4 (rs75744865), CTLA4 (rs3087243), PADI4 (rs2240340), AFF3 (rs11676922), IRF5 (rs10488631), TNFAIP3 (rs5029937) and TRAF1/C5 (rs3761847) were genotyped by real-time PCR using the TaqMan 5′-allele discrimination assay. Principal component analysis (PCA) followed by discrimination analysis were applied to reveal the relations between these genetic factors and disease. <h3>Results</h3> Our results show that of all genes analysed, the distribution of PTPN22, STAT4, IRF5 and PADI4 risk alleles and genotypes was significantly different between RA patients and healthy subjects in Slovak population (<i>P</i>&lt; 0.05, chi-square test). The principal component analysis showed that the most important variables for sample discrimination are SE followed by STAT4, PADI4 and CTLA4. The discrimination analysis with forward selection have chosen SE as the most important variable for RA presence and showed that non-risk genotypes in STAT4, PTPN22, IRF5, PADI4, respectively are predictors for classifying subjects into healthy controls (F = 127.373; p = 0.0002). <h3>Conclusions</h3> Genetic factors explain 11.1% of data variability in our cohort. The RA diagnose is significantly affected by presence of SE risk allele and RA associated alleles in genes STAT4, PTPN22, IRF5 and PADI4 with emphasis on heterozygozyty being sufficient to increase the risk of disease. <h3>Acknowledgements</h3> Study was supported by grants: ATMOS N00024, VEGA 2/0018/12, ITMS 26240220058 <h3>Disclosure of Interest</h3> None Declared
Nonosseous Uptake on Bone Scan in Adenocarcinoma of Unknown Primary Origin
Authors: XIAOMING CHEN, ARNOLD F. JACOBSON
Journal: Clinical Nuclear Medicine (2000)

Two patients without histories of cancer underwent Tc-99m MDP bone scans as part of evaluations of pain and abnormal laboratory and radiologic findings. Both scans showed abnormal soft tissue uptake in tumor deposits and in visceral organs associated with hypercalcemia and metastatic calcification. One scan showed diffuse increased bone uptake (superscan pattern), and the other revealed focal metastatic bone uptake. Adenocarcinoma of unknown primary (AUP) origin was subsequently identified in both patients. AUP occurs in multiple organs more than 50% of the time, with bone involvement in 4% to 31% of cases. The patients described here reflect the variety of patterns of osseous and nonosseous uptake of diphosphonate bone agents in patients with AUP.
Obesity Associated with a Mutation in a Genetic Regulator of Adipocyte Differentiation
Authors: Michael Ristow, Dirk Müller-Wieland, Andreas Pfeiffer, Wilhelm Krone, C. Ronald Kahn
Journal: New England Journal of Medicine (1998)

There is increasing evidence of genetic factors leading to obesity, but the exact genes involved have not been defined. Peroxisome-proliferator–activated receptor γ2 (PPARγ2) is a transcription factor that has a key role in adipocyte differentiation, and therefore mutations of the gene for this factor might predispose people to obesity.
INTENSIVE MEDICAL MANAGEMENT AND OUTCOMES FOLLOWING MYOCARDIAL INFARCTION
Authors: Paul Muntner, Keri Monda, Maria Corina Serban, Mark Woodward, Lisandro Colantonio, Ben Taylor, Michael Farkouh, Vera Bittner, Todd Brown, Luqin Deng, Ransi Somaratne, Robert Rosenson
Journal: Journal of the American College of Cardiology (2016)