tbuckley/cabot-search huggingface dataset:
Abstract 18834: Right Ventricular Fractional Area Change Obtained in Different Echocardiographic Views of Right Heart; Comparison With Right Ventricular Ejection Fraction by Cardiac Magnetic Resonance Imaging
Authors: Rika Takemoto, Hiroki Oe, Satoko Ugawa, Norihisa Toh, Nobuhisa Watanabe, Yasuharu Tanabe, Hiroshi Ito
Journal: Circulation (2013)

Background and Purpose: Fractional area change(FAC) has been shown to correlate well with right ventricular(RV) ejection fraction(EF) by cardiac magnetic resonance(CMR). The guideline recommends that multiple echocardiographic views should be obtained to evaluate RV function. However, there is no clear recommendation which view should be used to evaluate RV FAC. Methods: CMR and transthoracic echocardiography(TTE) were performed in 46 consecutive patients for evaluation of RV function. We measured tricuspid annular plain systolic excursion (TAPSE) , FAC on apical four chamber view (A4CV)(A-FAC) and that of RV focused A4CV (F-FAC) and modified A4CV (M-FAC) and pulsed Doppler peak velocity at the tricuspid annulus (s’) as an assessment of RV systolic function. The association between echocardiography-derived parameters of RV systolic function and CMR-derived measurement of RVEF and RV volume were evaluated. Result: Both A-FAC and F-FAC measurement were fesible in 46 patients (100%) and M-FAC measurement was fesible in 39 patients (85%). End diastolic area (Area ED)(cm2) of A-FAC and F-FAC showed correlation with CMR-derived end diastolic volume, respectively (p&lt;0.0001, r=0.66 vs P=&lt;0.0001,r=0.62 ). End systolic area (Area ES)(cm2) of A-FAC and F-FAC showed correlation with CMR-derived end systolic volume, respectively (p&lt;0.0001, r=0.72 vs p&lt;0.0001, r=0.78) P=&lt;0.0001,r=0.65). A-FAC and F-FAC has good correlation with CMR-derived RVEF(p=0.0003, r=0.50 vs P=&lt;0.0001,r=0.65, respectively). M-FAC has no correlation with CMR-derived RVEF(p=0.065, r=0.30). There were no significant agreement between TAPSE, s’ and CMR-derived RVEF in this study. Conclusion: Both A-FAC and F-FAC had good correlation with CMR-derived RVEF, and M-FAC didn’t show correlation with CMR-derived RVEF.
In vivo proton magnetic resonance spectroscopic (PMRS) evaluation: Emerging tool to solve the diagnostic dilemma in soft tissue sarcoma management
Authors: M. Kar, S. S. Deo, V. Kumar, U. Sharma, N. R. Jagannathan, K. A. Dannishad, V. Deo, N. K. Shukla, S. Datta Gupta, S. Thulkar
Journal: Journal of Clinical Oncology (2007)

10020 Objective: Presently grade is the most important factor used to decide the soft tissue sarcoma management. But it is always very difficult to assign a pathologic grade because of discordance rate is 30–40%, even among experienced sarcoma oncopathologists. Again histopathology has the disadvantages of being invasive, subjective and insensitive to tumour heterogeneity. This emphasizes the need for an objective and accurate assessment of histologic type and grade of sarcoma. The aim of this study is to evaluate the correlation of in vivo proton magnetic resonance spectroscopic findings with histopathological features and validate its diagnostic efficacy in management of different types of soft tissue sarcomas. Methods: PMRS Study was performed at 1.5Tesla MRI machine with a surface coil appropriate for the location of the lesions in 25 patients. Single-voxel (SVS) study has been done in 10 cases and chemical shift imaging (CSI) study characterised the heterogeneity of the tumor in 15 cases by using point - resolved spectroscopic sequence (PRESS) with echo time TR=2,000 / TE = 30, 135 &amp; 270 msec. The choline peak, identified at 3.2 ppm in spectra was considered as significant which shows the activity of the tumour. MRS results and histopathologic findings were correlated and P &lt; 0.001, considered being significant. Results: Choline peak was found in 17 out of 17 patients with malignant soft tissue tumours where as three patient with benign and five treated malignant soft tissue tumour patients with no residual disease did not show any choline. In vivo spectroscopy here shows sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 100% each. Conclusion: Choline peak in MRS study can predict the grade, margin status (especially CSI) and tumour activity in recurrent and / or residual soft tissue sarcoma. Most important findings here was that without using any contrast medium in study the choline peak in CSI spectroscopic evaluation could show the tumor activity at the margin of the tumor which is very important point for evaluation of residual or recurrent or completion of the surgical excision of the tumor A major study should be done to validate its efficacy for routine use in oncology. [Table: see text]
Immunologic targeting of genitourinary malignancies
Authors: J. W. Vieweg
Journal: Journal of Clinical Oncology (2005)

2602 Background: Insights into the regulation of immune responses and the malignant process have facilitated the emergence of new immune-based strategies, currently under investigation in clinical trials. Like other forms of targeted therapy, cancer vaccines hold the promise of achieving cancer control without inducing overt toxicity. Results: Our early clinical trials using DC vaccines in patients with advanced genitourinary (GU) malignancies demonstrated low toxicity profiles and have demonstrated bioactivity by stimulating immunological and even clinical responses in selected subjects. In this lecture, I will discuss several novel concepts that have provided new avenues to further enhance the efficacy of DC-based vaccines in GU and other cancer settings. These strategies include: a) Targeting of antigens with critical roles in oncogenesis, b) Selective inhibition of regulatory pathways, c) Enhancing the CD4+ T-cell arm of the immune system, and d) Modulating the DC maturation process. Conclusion: Without question, complex diseases such as cancer will require a combination approach. The concepts described, can be applied simultaneously, sequentially, or in combination with other strategies to generate superior immunization protocols that will have a therapeutic impact. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merix Biosciences
Evidence for rolling-circle replication in a major satellite DNA from the South American rodents of the genus Ctenomys.
Authors: M S Rossi, O A Reig, J Zorzópulos
Journal: Molecular Biology and Evolution (1990)

A major PvuII satellite DNA has been cloned from a South American octodontid rodent of the genus Ctenomys (C. porteousi). The satellite monomer, termed RPCS, is 337 bp in size and 42% G + C. Analysis of the nucleotide sequence demonstrates that RPCS is not composed of a series of shorter repeats. RPCS-related sequences were found in 11 of 12 Ctenomys species analyzed by hybridization under high-stringency conditions. The only negative species, C. opimus, was reactive under low-stringency conditions. RPCS-related sequences were not found under high- or low-stringency conditions in Calomys musculinus and Mus musculus. However, under low-stringency conditions, RPCS-related sequences were found in the octodontid Octodontomys gliroides, which is thought to have diverged from the genus Ctenomys more than 10 Myr ago. The pattern of periodicities observed, by restriction analysis, between Ctenomys species in the satellite array can be mainly accounted for by a rolling-circle amplification mechanism but cannot be solely accounted for by unequal crossing-over.
Low-dose fractionated radiation (LDFRT) plus paclitaxel (P) and carboplatin (CBCDA) as induction therapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN): Two-year follow-up
Authors: S. M. Arnold, M. Kudrimoti, W. Regine, J. Valentino, P. Spring, D. Kenady, M. Ahmed, M. Mohiuddin
Journal: Journal of Clinical Oncology (2004)

5593 Background: LDFRT (< 100cGy) induces cell death through a unique mechanism, hyper-radiosensitivity. Based on demonstrated synergy with chemotherapy, LDFRT was combined with P and C as induction therapy in locally advanced SSCHN. Methods: In this phase II trial, 39 patients with locally advanced SCCHN (77.5% stage IV, 45% T4 and 60% advanced neck disease) received P 225mg/m2 (Day 1), CB AUC 6 (Day 1), and four 80 cGy fractions of radiation (two each on Day 1 & 2) for two cycles. Definitive therapy began 3 weeks after the last dose of induction therapy and was based on response to induction and the decision of a multidisciplinary team. Nineteen patients (49%) received concurrent chemotherapy and radiation, 16 (41%) patients received radiation alone and 4 patients (10%) had surgery. Results: Median follow-up is 26 months. Overall response rate to induction was 82% (90% RR at the primary site). At two years, overall survival was 72%, DFS was 77%. The local control rate was 79% (the majority of failures occurred within the first year) and distant control 88%. Conclusions: Induction LDFRT, P and CB appears to improve distant control rates in patients with locally advanced SCCHN. OS and DFS compare favorably to other aggressive chemoradiotherapy strategies in SCCHN. These results confirm the efficacy of induction LDFRT and chemotherapy followed by aggressive definitive therapy in SCCHN. Supported by a grant from Bristol-Myers Squibb. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Pharmaceuticals Bristol-Myers Squibb
Phase I trial and pharmacokinetic study of two schedules of vincristine, oral irinotecan, and temozolomide (VOIT) for children with refractory solid tumors: A Children's Oncology Group Phase I Consortium study
Authors: L. M. Wagner, J. P. Perentesis, J. M. Reid, M. M. Ames, S. L. Safgren, M. D. Nelson, A. M. Ingle, S. M. Blaney, P. C. Adamson
Journal: Journal of Clinical Oncology (2009)

10017 Background: In preclinical models, temozolomide (TMZ) and vincristine (VCR) are synergistic with irinotecan (IRN). We sought to determine the dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of orally administered IRN given on two different schedules together with TMZ and VCR in children with refractory solid tumors, using cefixime to reduce IRN-associated diarrhea. Methods: Schedule A: Oral IRN daily for 5 days for 2 weeks (dx5x2), with VCR 1.5 mg/m 2 on days 1 and 8 and TMZ 100 mg/m 2 on days 1 - 5. Schedule B: Oral IRN daily for 5 days for 1 week (dx5x1) with VCR 1.5 mg/m 2 on day 1 and TMZ 100 - 150 mg/m 2 on days 1 - 5. Courses were repeated every 3 weeks. A standard cohorts of 3 + 3 design was used. Results: On Schedule A, 18 evaluable patients (median age 15 yrs, range 3 - 21) received 55 courses. At IRN 50 mg/m 2 /day, 4/12 pts had DLT (hepatotoxicity, abdominal pain, anorexia, hypokalemia, and thrombocytopenia). The oral IRN MTD on this dx5x2 schedule was 35 mg/m 2 /d (1/6 pts with DLT of hypoalbuminemia). On Schedule B, 18 evaluable patients (median age 9 yrs, range 3–21) received 71 courses of oral IRN 70 - 90 mg/m 2 /d x 5 with TMZ 100 - 150 mg/m 2 /d x 5. At oral IRN 90 mg/m 2 /d with TMZ 150 mg/m 2 /d, 0/6 pts had DLT, and no Grade 4 toxicities were seen. No further doses were explored. First-course and cumulative toxicity appeared worse with Schedule A, including 3 patients with responding or stable tumors who withdrew due to fatigue, nausea, and weight loss. UGT1A1*28genotype did not correlate with DLT. At the oral IRN MTD of 90 mg/m 2 /d, the median SN-38 AUC inf was 72 ng/ml*h. One patient with osteosarcoma had a confirmed partial response. Unconfirmed complete and partial responses were seen in 2 Ewing sarcoma patients. Eight additional patients received &gt; 6 courses, including 2 each with neuroblastoma and medulloblastoma. Conclusions: The dx5x1 schedule of VOIT was well tolerated, with SN-38 exposures similar to those achieved with intravenous IRN. Activity on this and prior studies suggests a potential role for VOIT in sarcoma patients. No significant financial relationships to disclose.
CISCA (cisplatin vs. carboplatin) meta-analysis: An individual patient data meta-analysis comparing cisplatin versus carboplatin-based chemotherapy in first-line treatment of advanced non-small cell lung cancer (NSCLC)
Authors: A. Ardizzoni, M. Tiseo, L. Boni, R. Rosell, F. V. Fossella, J. H. Schiller, M. Paesmans, D. Radosavljevic, A. Paccagnella, P. Mazzanti, D. Bisset
Journal: Journal of Clinical Oncology (2006)

7011 Background: The issue of the equivalence between carboplatin and cisplatin in the treatment of advanced NSCLC is still controversial. To answer this question, we conducted an individual patient (pt) data meta-analysis of randomized trials comparing cisplatin- and carboplatin-based chemotherapy (CT) in first-line treatment of advanced NSCLC. Methods: A literature search was performed to identify randomized trials investigating the substitution of carboplatin for cisplatin, combined with the same agent/s, in the first-line CT of advanced NSCLC. The primary end-point was overall survival (OS) and the secondary end-points were response rate (RR) and toxicity. For each end-point the analysis was based on a fixed-effects model. For the study of the effect on OS, Cox proportional hazards model was used. The probability to have an objective response or an adverse event was studied using a logistic regression model. Results: Nine trials were identified and the relative databases obtained. In total, 2,968 pts were randomized to receive CT with cisplatin (1,489) or with carboplatin (1,479), respectively. The RR was 30% and 24% for cisplatin- and carboplatin-based CT, respectively, with an OR of 1.37 (95% C.I.: 1.16–1.62; p &lt; 0.001). Concerning the OS, carboplatin was associated with a relative risk of death 7% higher compared with cisplatin, even if this difference was not statistically significant (HR = 1.07; 95% C.I.: 0.99–1.15; p = 0.101). Patients on cisplatin-based CT had more nausea-vomiting and nephro-toxicity while thrombocytopenia was more frequent during carboplatin-based CT. Subgroup analyses revealed that cisplatin-based CT led to statistically significant advantage in survival in the subgroups of pts with non-squamous tumours and in those treated with third generation CT. Conclusions: CISCA is the first individual pt data meta-analysis on this subject. We found that cisplatin-based is superior to carboplatin-based CT in terms of RR; however, the increased RR does not translate into an OS benefit. Nevertheless, selected pts with advanced NSCLC may obtain slightly more benefit from cisplatin-based third generation CT. No significant financial relationships to disclose.
ERCC1 protein, mRNA expression, and T19007C polymorphism as prognostic markers in head and neck squamous cell carcinoma (HNSCC) patients treated with surgery and adjuvant cisplatin-based chemoradiation (CRT).
Authors: G. Castro, F. S. Pasini, S. A. Siqueira, A. R. Ferraz, R. C. Villar, I. M. Snitcovsky, M. H. Federico
Journal: Journal of Clinical Oncology (2010)

5540 Background: Adjuvant cisplatin-based CRT improves overall survival (OS) in some HNSCC patients (pts) presenting with risk features, but toxicity is not negligible. ERCC1 is involved in NER pathway and is associated with resistance to chemo- and RT. We studied ERCC1 expression and the SNP T19007C in these pts. Methods: It is a retrospective study in HNSCC pts submitted to surgery and presenting with pathologic risk features. They were treated with 60-70 Gy and concurrent cisplatin 100 mg/m2d1, 22, 43. ERCC1 protein, mRNA expression and the SNP were studied in archived tissue blocks. ERCC1 expression was evaluated by immunohistochemistry, using a semi-quantitative H- score, and its mRNA expression was determined by quantitative RT-PCR. T19007C genotypes were detected using PCR-RFLP carried out in genomic DNA extracted from normal lymph nodes. Results: 69 pts (median age 56 y, 81% male) were studied. Primary sites: oral cavity 41%, larynx 32%, hypopharynx 16%, oropharynx 12%; stage IV 86%, pT3-pT4 78% and pN2-pN3 58%. 43 pts presented with ≥2 +ve lymph nodes, 27 with extracapsular spread and 18 with +ve margins. High-risk features were diagnosed in 40 pts (58%). During the median follow-up of 47 mo., we observed 30 deaths (22 disease-related). The 5-y OS was 40% and the 5-y disease-free survival was 31%. High H-score (>1.5) was seen in 32 pts (54%), who presented better 5-y OS (50% vs. 18%, HR 0.43, 95%CI 0.20-0.90, p=0.026). 15 out of 45 pts (33%), whose tumors had high ERCC1 mRNA expression (>3.1), presented better 5-y OS (86% vs. 30%, HR 0.26, 95%CI 0.14-1.01, p=0.052). Genotype distribution in 49 pts was 39% C/T, 37% C/C, and 24% T/T. No difference was detected among genotypes in terms of 5-y OS (45%, 46%, 46%; p=0.808). High H-score and ERCC1 mRNA expression remained significant as favorable prognostic factors in a multivariate analysis. Conclusions: High ERCC1 expression was associated with better prognosis in HNSCC pts submitted to adjuvant cisplatin-based CRT. It may be useful to better stratify these pts, however a prospective validation is needed. No significant financial relationships to disclose.
Polymorphism and evolution of influenza A virus genes.
Authors: N Saitou, M Nei
Journal: Molecular Biology and Evolution (1986)

The nucleotide sequences of four genes of the influenza A virus (nonstructural protein, matrix protein, and a few subtypes of hemagglutinin and neuraminidase) are compiled for a large number of strains isolated from various locations and years, and the evolutionary relationship of the sequences is investigated. It is shown that all of these genes or subtypes are highly polymorphic and that the polymorphic sequences (alleles) are subject to rapid turnover in the population, their average age being much less than that of higher organisms. Phylogenetic analysis suggests that most polymorphic sequences within a subtype or a gene appeared during the last 80 years and that the divergence among the subtypes of hemagglutinin genes might have occurred during the last 300 years. The high degree of polymorphism in this RNA virus is caused by an extremely high rate of mutation, estimated to be 0.01/nucleotide site/year. Despite the high rate of mutation, most influenza virus genes are apparently subject to purifying selection, and the rate of nucleotide substitution is substantially lower than the mutation rate. There is considerable variation in the substitution rate among different genes, and the rate seems to be lower in nonhuman viral strains than in human strains. The difference might be responsible for the so-called freezing effect in some viral strains.
Gossypol — Proposed Contraceptive for Men Passes the Ames Test
Authors: A de Peyster, Y Y Wang
Journal: New England Journal of Medicine (1979)

Scientists from China recently reported that the administration of gossypol acetate or gossypol formate to men by mouth at a daily dosage of 20 mg caused sperm counts to drop to contraceptive levels.  Monthly maintenance dosages of 150 to 220 mg were sufficient for contraceptive effectiveness in 99.89% of the 4000 men tested.  If approved for general use in China the proposed contraceptive dosage would be about 3 g per man per year.  The mode of action of gossypol a phenol extracted from the roots stems and seeds of the cotton plant is still under investigation.  It is apparent however that gossypol does not act by alteration of serum hormone levels and its contraceptive effect is reversible.  Side effects for some men were transient nausea reduced levels of potassium and inability to perspire but the relation of these symptoms to gossypol intake has not yet been firmly established.  Although much information is available on the acute toxicity of gossypol systematic screening for possible mutagenic carcinogenic or teratogenic effects in standard bioassays has not yet been reported.  However the authors have tested gossypol in the Ames salmonella-microsome test in 2 separate assays which have indicated that gossypol is not mutagenic to the 5 standard tester strains of S. typhimurium either with or without inclusion of a rat-liver metabolic-enzyme fraction.  Nevertheless other tests on the chronic effects of gossypol may be warranted in view of the fact that it is a lipid-soluble compound and its retention time in the body is prolonged.  High tissue concentrations may be reached.
Association of persistence of isolated tumor cells (ITC) in bone marrow (BM) of breast cancer patients with risk for relapse
Authors: W. Janni, B. Rack, C. Schindlbeck, B. Strobl, D. Rjosk, S. Braun, H. Sommer, K. Pantel, B. Gerber, K. Friese
Journal: Journal of Clinical Oncology (2004)

579 Background: The prognostic significance of ITC in the BM of breast cancer patients at the time of primary diagnosis has recently been confirmed by a large pooled analysis (Braun S, SABCS 2003). If the persistence of ITC after adjuvant therapy confers a similar risk for relapse, there would be an indication to consider secondary adjuvant therapy. Methods: We analyzed BM aspirates of 228 patients during recurrence-free follow-up at a median interval of 21.3 months (standard deviation [std] 29.1 mon) after primary diagnosis of breast cancer pT1–2 pN0–3 pM0. Carcinoma cells were detected using a standardized immunoassay with monoclonal antibody A45-B/B3, directed against cytokeratin (CK). Patients were followed for a median of 49.8 months (std 32.1 mon) after primary diagnosis. Results: Persistent ITC in the BM were detected in 12.7% of the patients (n=29). Positive BM status was more frequent (15.7%) within the first 21 months after primary diagnosis, than after a follow-up longer than 21 mon (9.7%). The Kaplan-Meier estimate for mean relapse-free survival was 149.7 mon (139.6 –159.8 95%CI) in patients with negative and 86.5 mon (65.7 –107.4 95% CI, p= .0003, log rank test) in patients with positive BM status Patients without evidence of persistent ITC had a significantly longer overall survival (162.1 mon, [152.1 –172.0]), than patients with positive BM status (98.7 mon, [79.7 –117.9], p= .0008). In multivariate Cox regression analysis, allowing for bone marrow status, tumor size, nodal status, and histopathological grading, evidence for ITC was an independent significant predictor for reduced survival (RR 5.57, p= .002). Persistent ITC had the greatest prognostic relevance when detected between 25 and 42 months after primary diagnosis (RR 7.68). Conclusion: Evidence of persistent ITC in the bone marrow of breast cancer patients indicates an increased risk for subsequent relapse, and may serve as follow-up tool in future. Prospective trials should investigate the benefit of secondary adjuvant treatment on the basis of the bone marrow status. No significant financial relationships to disclose.