tbuckley/cabot-search huggingface dataset:
In vivo and ex vivo ultrasound, fine needle aspiration and molecular biology of sentinel nodes (SN) in melanoma patients
Authors: C. A. Voit, M. Kron, A. Schoengen, H. Audring, A. Lukowsky, W. Sterry, H. Winter, R. Hasert, T. Mayer, G. Schaefer
Journal: Journal of Clinical Oncology (2004)

7522 Background: Final data of a prospective study covering the largest number of SNs examined so far. The recently introduced SN technique allows for detection of micrometastases thus enabling an early staging and characterizing of patients likely to benefit from adjuvant therapies. Method: Over 2 years 136 sentinel nodes of 127 melanoma patients scheduled for sentinel node biopsy (SLND) were examined by in vivo and ex vivo ultrasound (US), fine needle aspiration cytology (FNAC) and tyrosinase RT-PCR. Confirmation by US and measurement of the excised sentinel node. Blood samples of all pts. were tested for tyrosinase by RT-PCR for minimal residual disease. Results: Patients median age 58 yrs., tumor thickness median 3,14mm. 114/127 pts. had 1 SN, 12 pts. 2 SN, 1 patient 3 SN, 1 patient 4 SN. SN size on median 842mm3 in vivo, 714mm3 in vitro. After visualizing and evaluating by US, the SN is punctured and cells are aspirated. FNAC material is partly shock frozen for RT-PCR, partly used for cytology. The excised lymph node was examined by the same procedures. In vivo ultrasound achieved a sensitivity of 78,8% [95% CI.: 61–91] and specificity of 71,6% [95% CI.: 61–81%]. FNAC alone showed a sensitivity of 58,1% [39,1–75,5%] and specificity of 98,7% [92,7–100%]. The in vivo PCR for tyrosinase revealed a sensitivity of 48,5% [30,8–66,5%] and specificity of 97,7% [91,8–99,7%]. By combining all three in vivo methods an overall sensitivity of 81,8% [64,5–93%] and specificity of 71,6% [61–80,7%] was achieved. RT-PCR from peripheral blood reliably depicted pts prior to metastases. Conclusion: US and FNAC is not able to replace SLND with histology, but delivers important additional information prior to SLND since it can identify metastases in all lymph node basins. Patients with positive FNAC may directly undergo elective lymph node dissection, important time is gained. US-FNAC of SN can be performed in all patients refusing operation, in an inoperable status, with a tumor thickness ≤1mm and in departments without know-how of SLND. The method is reproducible, well tolerated, has extremely low risk of spreading tumor cells, infection or other side effects at low cost. No significant financial relationships to disclose.
P-glycoprotein in human sarcoma: evidence for multidrug resistance.
Authors: J H Gerlach, D R Bell, C Karakousis, H K Slocum, N Kartner, Y M Rustum, V Ling, R M Baker
Journal: Journal of Clinical Oncology (1987)

Overexpression of an immunologically conserved, cell-surface glycoprotein (P-glycoprotein) is consistently associated with multidrug resistance in cell lines in vitro. A preliminary survey of specimens from 12 solid tumor types in our laboratories indicates significant overexpression of P-glycoprotein in some sarcomas. When tested by immunoblotting with monoclonal antibodies directed against P-glycoprotein; tumors from six of 25 sarcoma patients displayed elevated levels of P-glycoprotein. Three of the sarcoma patients exhibiting P-glycoprotein had not previously been exposed to chemotherapy, implying that overexpression of this marker and possible concomitant multidrug resistance may not depend only on selection during prior drug treatments. The P-glycoprotein overexpression in the sarcoma specimens is evidence for the presence of multidrug resistant cells in these tumors; thus, our data suggest that this mode of resistance may have clinical significance in sarcoma patients.
ILK Induction in Lymphoid Organs by a TNFα–NF-κB–Regulated Pathway Promotes the Development of Chronic Lymphocytic Leukemia
Authors: Peter W. Krenn, Sebastian W. Hofbauer, Susanne Pucher, Evelyn Hutterer, Elisabeth Hinterseer, Ursula Denk, Daniela Asslaber, Sylvia Ganghammer, Christina Sternberg, Daniel Neureiter, Fritz Aberger, Sara A. Wickström, Alexander Egle, Richard Greil, Tanja N. Hartmann
Journal: Cancer Research (2016)

Abstract The proliferation of chronic lymphocytic leukemia (CLL) cells requires communication with the lymphoid organ microenvironment. Integrin-linked kinase (ILK) is a multifunctional intracellular adaptor protein that transmits extracellular signals to regulate malignant cell motility, metastasis, and cell-cycle progression, but is poorly characterized in hematologic malignancies. In this study, we investigated the role of ILK in the context of CLL and observed high ILK expression in patient samples, particularly in tumor cells harboring prognostic high-risk markers such as unmutated IGHV genes, high Zap70, or CD38 expression, or a signature of recent proliferation. We also found increased numbers of Ki67 (MKI67)-positive cells in regions of enhanced ILK expression in lymph nodes from CLL patients. Using coculture conditions mimicking the proliferative lymph node microenvironment, we detected a parallel induction of ILK and cyclin D1 (CCND1) expression in CLL cells that was dependent on the activation of NF-κB signaling by soluble TNFα. The newly synthesized ILK protein colocalized to centrosomal structures and was required for correct centrosome clustering and mitotic spindle organization. Furthermore, we established a mouse model of CLL in which B-cell–specific genetic ablation of ILK resulted in decelerated leukemia development due to reduced organ infiltration and proliferation of CLL cells. Collectively, our findings describe a TNFα–NF-κB–mediated mechanism by which ILK expression is induced in the lymph node microenvironment and propose that ILK promotes leukemogenesis by enabling CLL cells to cope with centrosomal defects acquired during malignant transformation. Cancer Res; 76(8); 2186–96. ©2016 AACR.
LP55 : Response guided therapy is not dead: Low Sustained Virologic Response (SVR) rates in patients who have detectable Hepatitis C Virus (HCV) at week 4 of treatment with SOFOSBUVIR (SOF) containing regimens
Authors: K. Thornton, P. Deming, R. Manch, A. Moore, R. Gish, N. Sussman, S. Khaderi, J. Scott, J. Mera, T. Box, C. Qualls, M. Sedillo, S. Arora
Journal: Journal of Hepatology (2015)
Prognostic relevance of alterations in sphingolipid metabolism in breast cancer
Authors: E. Ruckhäberle, A. Rody, K. Engels, R. Gaetje, G. V. Minckwitz, S. Schiffmann, S. Grösch, G. Geisslinger, U. Holtrich, T. Karn, M. Kaufmann
Journal: Journal of Clinical Oncology (2008)

11109 Background: Beside their structural role for the cell membrane sphingolipids act as effector molecules in signal transduction with links to various aspects of cancer initiation, progression and treatment response. The “sphingolipid rheostat” balances between pro-apoptotic ceramid and anti-apoptotic and growth promoting sphingosine-1-phosphate. Knowledge of sphingolipid´s impact on breast cancer and its prognosis is limited. Methods: We analyzed gene expression of 43 proteins from this pathway in different subtypes of breast cancer using microarray data of 1269 tumor samples (test set n=171; validation sets n=1098). Additionally survival analysises were done. Finally immunohistochemistry was done to reveal the source of certain enzymes of the sphingolipid rheostat. Results: Significant differences for several genes of the sphigolipid metabolism were done. Sphingosine kinase 1 (SPHK1), ceramide galactosyltransferase (UGT8), and Ganglioside GD3-Synthase (ST8SIA1) displayed higher expression among ER negative tumors. In contrast, glucosylceramidesynthase (GCS), dihydroceramidesynthases (LASS4, LASS 6) and acid ceramidase (ASAH1) were higher expressed in ER positive samples. Survival analysis revealed a worse outcome of patients with high SPHK1 expression. To avoid a confounding effect of the ER status we also restricted the analysis to 750 patients with ER positive tumors. Again a worse outcome was observed for tumors displaying high SPHK1 expression. While 75.8 ±1.9 % of the patients with tumors low in SPHK1 expression were free of metastasis at 5 years, this was the case for only 64.9 ±3.6 % of patients with tumors displaying high SPHK1 expression (P=0.008). Immunohistochemistry identified the carcinoma cells as the major source of SPHK1 expression in the tumor. Conclusions: Certain enzymes of the sphingolipid metabolism have impact on the prognosis of breast cancer patients.Targeting the sphingolipid rheostat might open new treatment options. No significant financial relationships to disclose.
Immunobiologic factors predictive of clinical outcome in diffuse large-cell lymphoma.
Authors: D J Slymen, T P Miller, S M Lippman, C M Spier, D P Kerrigan, J A Rybski, C S Rangel, L C Richter, T M Grogan
Journal: Journal of Clinical Oncology (1990)

The prognostic importance of immunobiologic factors in diffuse large-cell lymphoma (DLCL) is studied in 105 consecutive DLCL patients. Multivariate results using the Cox proportional hazards model clearly indicate that the Ki-67 index (P = .002), a marker of cell proliferation activity, and the presence or absence of human leukocyte antigen-DR (HLA-DR) (P = .007) are strong predictors of survival even in the presence of established clinical factors of stage (P = .015) and symptoms (P = .050). Using these four variables, prognostic groups were formed identifying patient groups with varying degrees of risk. The group of patients with three or four risk factors present at the time of diagnosis had a median survival of 4 months compared with a median survival of 59 months for the group with no risk factors. Similarly, prognostic groups for disease-free survival (DFS) were constructed based on the proportional hazards model that involved B versus T phenotype (P = .035) and HLA-DR (P = .054). Median DFS for the patient group with one or two risk factors present was 11 months compared with 43 months with no risk factors present. This study suggests immunobiologic parameters are important predictors of clinical outcome in DLCL patients and are of value in identifying subgroups of patients who have not responded to currently available therapy. The practical significance of this study is to identify parameters that may suggest specific changes in therapy of patient subgroups.
Combination of the PAM4 and CA19-9 biomarkers to improve the detection of pancreatic adenocarcinoma.
Authors: David V. Gold, Jochen Gaedcke, B. Michael Ghadimi, Michael Goggins, Ralph H. Hruban, Mengling Liu, Guy Newsome, David M. Goldenberg
Journal: Journal of Clinical Oncology (2012)

164 Background: Pancreatic ductal adenocarcinoma (PDAC) is almost universally lethal, due mainly to the inability to detect early-stage disease. Thus, identification of biomarkers that can identify patients with early-stage PDAC may improve overall survival. Methods: In a blinded study, PAM4 and CA19-9 immunoassays were performed on sera from 480 patients, including those with confirmed PDAC (N=234), other cancers (N=84), benign diseases of the pancreas (N=89), and healthy adults (N=50). Results: Overall sensitivity for PDAC was similar, 74% and 77% for PAM4 and CA19-9, respectively. Sensitivity for detection of early, stage-1 disease (N=26), although somewhat higher for the PAM4-antigen, was also statistically similar, 65% and 58% for PAM4 and CA19-9, respectively (P = 0.5775). However, specificity was significantly lower for CA19-9, particularly with respect to chronic pancreatitis (CP): 68% vs.86% for the PAM4 assay (P = 0.014). Furthermore, CA19-9 results showed considerably higher detection rates for non-PDAC neoplasia, including patients with other cancers that metastasized to the pancreas. Thus, positive likelihood ratios (+LR) were lower for CA19-9 (+LR = 2.41) than for the PAM4 assay (+LR = 5.29). PAM4 and CA19-9 antigen levels in PDAC were independent of each other (r 2 = 0.003, P=0.410); however, the positive and negative interpretations were concordant in 68% of the cases. Thus, we used a combined biomarker analysis that ultimately improved the overall PDAC detection rate (84%), without a significant decrease in specificity (83%). Comparison of the ROC curves for PDAC vs. CP and PDAC vs. benign disease demonstrated a statistically significant improvement for the combined immunoassay, as compared to either assay alone (P &lt; 0.0001 in both comparisons), to detect and discriminate PDAC from benign disease. Conclusions: While the PAM4-immunoassay provides high sensitivity and specificity for detection and diagnosis of PDAC, inclusion of the CA19-9 biomarker significantly enhanced positive identification of PDAC patients, from 74% to 84%. Further studies are needed to confirm these results. (Supported in part by NIH grants CA096924, CA120432 and CA62924, and the Turpin Foundation.)
Nonsyndromic Thoracic Aortic Aneurysm and Dissection
Authors: Andrew G. Sherrah, Sarah Andvik, Denise van der Linde, Lucy Davies, Paul G. Bannon, Ratnasari Padang, Michael P. Vallely, Michael K. Wilson, Anthony C. Keech, Richmond W. Jeremy
Journal: Journal of the American College of Cardiology (2016)
Role of -511C>T and +3953C>T SNPs of IL1B gene as risk factors of COPD and bronchial asthma in Bulgarian population
Authors: Dimo Dimov, Tatyana Vlaykova, Mateusz Kurzawski, Joanna Lapczuk, Anna Wajda, Vanya Ilieva, Atanas Koychev, Gospodinka Prakova, Vasil Dimitrov, Marek Drozdzik
Journal: European Respiratory Journal (2011)

A common characteristic of COPD and bronchial asthma is the chronic inflammation in the airways. In the current case-control study we investigated -511C>T promoter polymorphism and +3953C>T silent polymorphism of  IL1B  and their haplotypes as candidate risk factors of COPD and Bronchial asthma. We genotyped 163 patients with COPD, 47 with Bronchial asthma and 174 control individuals using Taqman genotyping assay for  IL1B  -511C>T and PCR-RFLP-based method for +3953C>T.  We did no observed significant differences in genotype frequencies of studied SNPs between controls and patients both with COPD and asthma, however the minor T allele of  IL1B  -511C>T was less frequently found in controls (0.305) than the patients with COPD (0.377, p=0.046) and especially with asthma (0.415, p=0.0002). The carriers of  IL1B  -511T allele (TT and TC genotypes) had 1.56-fold higher risk for development of COPD (p=0.045) and 2.25-fold higher risk of Bronchial asthma (p=0.019). The performed estimations of  IL1B  haplotypes showed that T_C haplotype (alleles found to determine enhanced expression of IL-1b), appeared to be associated with higher risk of COPD (OR=1.25, p=0.231) and asthma (OR=1.78, p=0.035) compared to the most common C_C haplotype and with 1.70-fold higher risk of COPD (p=0.018) and 1.37-fold higher risk of asthma (p=0.313) compared to the C_T haplotype, associated with lower  IL1B  expression.  We suggest that the -511C>T promoter SNP and +3953C>T silent polymorphisms in exon 5 of  IL1B  may influence the genetic predisposition of COPD and Bronchial asthma: the carriers of alleles and haplotypes supposed to define higher IL-1b levels are more susceptible for these diseases.
Abstract 14075: Comparative Effectiveness of Dabigatran versus Warfarin in Patients With Non-Valvular Atrial Fibrillation
Authors: Alvaro Alonso, Lin Y Chen, Richard F MacLehose, Pamela L Lutsey
Journal: Circulation (2013)

Background:  In clinical trials, dabigatran has been shown to be efficacious for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. However, the ‘real-world’ effectiveness and risks of dabigatran compared to warfarin in these patients have not been well described.   Methods:  We used data from the US MarketScan Commercial and Medicare Supplemental databases in 2010-2011, which include claims information on >45 million individuals. We selected patients with NVAF initiating oral anticoagulants after their diagnosis, and with at least 6 months of enrollment before first anticoagulant use. Patients initiating dabigatran were matched with up to 5 warfarin users by age, sex, and time since database enrollment. Outcomes of interest (ischemic stroke, intracranial bleeding, and myocardial infarction (MI)) were defined according to validated algorithms. Information on other comorbidities and medication use was obtained from inpatient, outpatient, and pharmacy claims. Propensity score-adjusted Cox proportional hazards regression was used to estimate the association of dabigatran use vs warfarin with each outcome of interest.   Results:  The analysis included 28,151 dabigatran and 92,633 warfarin users with NVAF. During an average 7-month follow-up, 368 ischemic strokes, 101 intracranial bleeds, and 381 MIs were identified. Rate of ischemic stroke and MI was similar in patients initiating dabigatran compared to those on warfarin. However, rate of intracranial bleeding was 61% lower in patients using dabigatran compared to warfarin users (Table).   Conclusion:  In this large patient population, compared to warfarin, dabigatran was associated with lower risk of intracranial bleeding and similar risk of ischemic stroke and MI. These results are comparable to those reported in the RE-LY trial, suggesting that effectiveness of dabigatran in the ‘real-world’ is similar to that described in RE-LY.
The rate and pattern of nucleotide substitution in Drosophila mitochondrial DNA.
Authors: K Tamura
Journal: Molecular Biology and Evolution (1992)

The nucleotide sequences of a segment of mitochondrial DNA (mtDNA) have been determined for nine species or subspecies of the subgenus Drosophila of the genus Drosophila. This segment contains two complete protein-coding genes (i.e., NADH dehydrogenase subunit 1 and cytochrome b) and a transfer RNA gene (tRNA(ser)). The G+C content at third-codon positions for the two protein-coding genes was 1.5 times higher than that in the D. melanogaster species group, which belongs to the subgenus Sophophora. However, there was a substantial difference between the nucleotide frequencies of G and C. The number of nucleotide substitutions per silent site was more than three times higher than that for nuclear DNA, although it was only 60% of that for mammalian mtDNA. Both parametric and nonparametric analyses revealed a strong transition-transversion bias in nucleotide substitution, as was observed in mammalian mtDNA. Moreover, the rate of substitution of A and T for G and C is higher than that for the opposite direction. This bias seems to be responsible for the extremely A+T-rich base composition of Drosophila mtDNA. It is also noted that the rate of transitional change between A and G is higher than that between T and C.
Gastric submucosal tumors: Lessons learned from 10-year follow-up
Authors: A. Sawaki, N. Mizuno, T. Takagi, K. Hara, T. Nakamura, M. Tajika, H. Kawai, K. Matsumoto, Y. Kobayashi, K. Yamao
Journal: Journal of Clinical Oncology (2009)

e15631 Background: Gastric Submucosal tumors (SMTs) were incidentally discovered esophagogastroduodenoscopy (EGD). However, they have not been studied in detail of epidemiology. Furthermore, no treatment strategy for SMTs has been established with few studies looking into long-term outcomes. The aim of this study is to clarify the clinical features and long-term outcomes of gastric SMT at a single institute for 10-year period. Methods: We performed a total of 5307 EGDs and detected 188 gastric SMTs during 1998. All clinical data including incidence, size and location in stomach were analyzed for the medical records. A retrospective review was conducted for 10-year period for 109 patients and 79 patients were excluded because of simultaneous surgery (3), disappear in follow- up EGD (27), lost of follow-up (49). Results: Gastric SMTs were detected 188 (81 males, 107 females) of 5307 patients (3.5%). Majority size of SMTs was less than 1cm (64%) and SMTs&lt;2cm were 91%. 56% of SMTs located middle one third of stomach, and half (22%) of the remaining SMTs were detected at upper and lower one third, respectively. In 10-year follow-up, 83 of 109 patients were alive at December 2008. One patient was dead of SMT and the remaining 25 patients were dead of other disease till December 2008. Enlargement of SMT was observed in 2 of 109 SMTs (1.8%). Both of them underwent surgical resection and diagnosed as gastrointestinal stromal tumors (GIST). One patient was annually monitored by endoscopy, from 0.6cm to 1.5cm during 4 years, without recurrence for 6 years after surgical intervention. Another didn't undergo regular endoscopy, from 1.8cm to 8cm during 2 years, with recurrence, and consequently died of SMT. Conclusions: The incidence of SMTs is 3.5%, majority (91%) is small (&lt;2cm), and frequent location is middle one third of stomach. Most of SMTs might be managed conservatively, but regular endoscopy is required. No significant financial relationships to disclose.
Adjuvant chemotherapy in osteogenic sarcoma.
Authors: N Jaffe
Journal: Journal of Clinical Oncology (1984)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1984.2.10.1179 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 6593436 Adjuvant chemotherapy in osteogenic sarcoma. N JaffexN JaffeSearch for articles by this author https://doi.org/10.1200/JCO.1984.2.10.1179 First Page PDF © 1984 by American Society of Clinical Oncology
Phase II study of docetaxel (T), carboplatin (C), and gemcitabine (G), in advanced tumors of unknown primary site
Authors: J. R. Mel Sr., M. Provencio, C. Balañá, J. M. López-Vega, A. Casado, A. Segura, J. M. Cervera, J. L. Martí, J. Munárriz, F. Arranz
Journal: Journal of Clinical Oncology (2006)

12028 Background: Treatment of tumors of unknown primary site is still a challenge nowadays. D, C and G have shown high activity in solid tumors. We designed this study to evaluate activity and toxicity profile of a combination of these three drugs, according a protocol previously tested in lung cancer (Pectasides D, et al. J Clin Oncol 1999). Methods: Patients with histological diagnosis of solid tumor of unknown primary site, age ≥ 18 years old, ECOG PS ≤ 2 and adequate bone marrow, renal, hepatic and cardiac functions, were included. Treatment consisted in (d1): C AUC = 5 and G 800 mg/m 2 IV; and d8): D 75 mg/m 2 and G 800 mg/m 2 IV, with G-CSF support. Courses were repeated every 28d for a maximum of 8 cycles, unless progression, unacceptable toxicity or consent withdrawal, whichever comes first. Results: Sixty-three patients have been included: median age was 66 years old (28–90), 89.6% of patients had ECOG PS 0–1. Tumor histology included adenocarcinoma (65.1%), undifferentiated (17.5%) and carcinoma (7.9%) or large-cell carcinoma (1.6%). Main metastatic sites were lung (49%), liver (44%), lymph nodes (41%) and bone (25%). Previous treatments included surgery (20.6%), chemotherapy (1.6%) and radiotherapy (12.7%). Treatment: 296 cycles (median 6, range 1–11) were administered. Median relative dose intensity was 96% for D, C and G. Efficacy: 8 patients achieved CR and 15 PR, resulting in an overall response rate of 36.5% (95% CI: 24.6–48.4%). Main grade III/IV toxicity per patient were asthenia (19%), diarrhea (18%), mucositis (11%), vomiting (10%), nausea (6%), thrombocytopenia (38%), neutropenia (24%), leucopenia (19%) and anemia (13%). Febrile neutropenia was observed in 2 patients (3%). Fourteen patients (22.2%) experienced severe toxicity: 9 of them were dropped out and 5 were toxic deaths (2 sepses, 2 pancytopenia and 1 pulmonary thromboembolism). Median time to treatment failure was 6.0 months (95% CI: 4.8–7.1), median TTP was 10.8 months (95% CI: 8.6–13.0) and median OS was 11.8 months (95% CI: 9.4–12.3), with a median follow up of 10.8 months. Conclusions: Despite the combination of D, C and G shows high activity in tumors of unknown primary site, its toxic death rate is &gt; 5%. Thus, our group is working no longer with such a triplet combination. No significant financial relationships to disclose.