tbuckley/cabot-search huggingface dataset:
Diagnostic and prognostic value of the new tumour marker CYFRA 21-1 in patients with squamous cell lung cancer
Authors: J Niklinski, M Furman, E Chyczewska, L Chyczewski, F Rogowski, J Laudanski
Journal: European Respiratory Journal (1995)

We wanted to investigate the diagnostic and prognostic significance of serum CYFRA 21-1, especially in predicting the risk of recurrence in patients with operable squamous cell lung cancer. Serum levels of CYFRA 21-1 were measured using an immunoradiometric assay (CIS bio) in 76 patients with squamous cell lung cancer (64 operable and 12 with unresectable tumours), 22 with other non-small-cell type (12 with adenocarcinoma and 10 with large-cell type) and 45 with nonmalignant lung diseases. Elevated preoperative CYFRA 21-1 levels were identified in 63% of patients with squamous cell type (SqCC), 33% with adenocarcinoma, and 30% with large-cell carcinoma type. The diagnostic specificity of the assay was 96%. Positive CYFRA 21-1 levels were observed in 33% of stage I, 52% of stage II, 76% of stage IIIa and 83% of stage IIIb patients with SqCC type. Statistically significant differences were obtained between stages I and II and between II and IIIa, but not between stages IIIa and IIIb. Recurrence-free survival probability for patients with elevated serum CYFRA 21-1 levels before surgery was 63% (24/38) versus 92% (24/26) for patients with normal serum CYFRA 21-1 levels. However, the difference was not statistically significant when adjusted for the TNM stage (primary tumour, regional lymph node involvement, occurrence of distant metastasis). In 9 of the 10 patients with increased trend for CYFRA 21-1 during follow-up, elevated serum CYFRA 21-1 levels preceded (7) or coincided (2) with the clinical detection of tumour recurrence, providing a predictive value of an increased trend of 90%.(ABSTRACT TRUNCATED AT 250 WORDS)
Streptococcal M protein extracted by nonionic detergent. II. Analysis of the antibody response to the multiple antigenic determinants of the M-protein molecule.
Authors: V A Fischetti
Journal: The Journal of Experimental Medicine (1977)

Purified streptococcal M protein extracted by nonionic detergent was used in an RIA and a solid-phase radiocompetitive inhibition assay to determine the nature of the immune response in both human beings and hyperimmunized rabbits to this complex antiphagocytic antigen. Results indicate that a type-specific response to an M antigen with the development of opsonic antibodies is the result of antibodies directed against the majority of the antigenic determinants of the molecule. Cross-reactions between certain M types on the other hand, are represented by antibodies directed against only a small percentage of these antigenic determinants. Results also suggest that avidity may play a role in the action of opsonic antibodies. However, the data indicate that factors besides avidity (i.e. sites bound by the antibodies) also seem essential for opsonization.
Primary cardiac angiosarcoma causing rupture of the heart and spontaneous bilateral pneumothorax.
Authors: A J Lobo, R J Butland, S Stewart, J M Shneerson
Journal: Thorax (1989)

A patient with a primary cardiac angiosarcoma developed two previously unreported manifestations: cardiac rupture, which has not been reported with any primary cardiac tumour; and spontaneous pneumothorax, which is well recognised with other tumours but has not been reported with a cardiac angiosarcoma.
Increased Expression of α6 Integrin in Endothelial Cells Unveils a Proangiogenic Role for Basement Membrane
Authors: Luca Primo, Giorgio Seano, Cristina Roca, Federica Maione, Paolo Armando Gagliardi, Roberto Sessa, Marianna Martinelli, Enrico Giraudo, Laura di Blasio, Federico Bussolino
Journal: Cancer Research (2010)

The integrin alpha6 subunit is part of the alpha6beta1 and alpha6beta4 integrin complexes, which are known to be receptors for laminins and to mediate several biological activities such as embryogenesis, organogenesis, and invasion of carcinoma cells. However, the precise role of alpha6 integrin in angiogenesis has not yet been addressed. We observed that both vascular endothelial growth factor-A and fibroblast growth factor-2 strongly upregulate alpha6 integrin in human endothelial cells. Moreover, alpha6 integrin was positively modulated in angiogenic vessels in pancreatic neuroendocrine carcinoma. In this transgenic mouse model of spontaneous tumorigenesis, alpha6 integrin expression increased in the angiogenic stage, while being expressed at low levels in normal and hyperplastic tissue. We studied the functional role of alpha6 integrin during angiogenesis by lentivirus-mediated gene silencing and blocking antibody. Cell migration and morphogenesis on basement membrane extracts, a laminin-rich matrix, was reduced in endothelial cells expressing low levels of alpha6 integrin. However, we did not observe any differences in collagen matrices. Similar results were obtained in the aortic ring angiogenesis assay. alpha6 integrin was required for vessel sprouting on basement membrane gels but not on collagen gels, as shown by stably silencing this integrin in the murine aorta. Finally, a neutralizing anti-alpha6 integrin antibody inhibited in vivo angiogenesis in chicken chorioallantoic membrane and transgenic tumor mouse model. In summary, we showed that the alpha6 integrin participated in vascular endothelial growth factor-A and fibroblast growth factor-2-driven angiogenesis in vitro and in vivo, suggesting that it might be an attractive target for therapeutic approaches in angiogenesis-dependent diseases such as tumor growth.
Two murine monoclonal antibodies to peripheral blood monocyte differentiation antigens discriminate within M5 acute non-lymphoid leukemia (ANLL) cells
Authors: M. Lopez, G. De Rossi, L. Santoro, F. Mandelli, T. Alescio, L. Annino, D. Pasqualetti, A. G. Siccardi, M. Mottolese, P. G. Natali, M. Cuomo
Journal: American Journal of Hematology (1987)

Abstract Two murine monoclonal antibodies (MoAbs), LAM3 and LAM7 of the IgG 1 isotype, which were produced by immunization with normal peripheral blood monocytes (PBM), were assayed in their specificity by indirect immunofluorescence against a panel of normal as well as leukemic cells. Both LAM3 and LAM7 were reactive with PBM while LAM3 also recognized platelets. Neither MoAb showed reactivity with erythrocytes, granulocytes, or resting and mitogen activated B and T lymphocytes. The reactivity with bone marrow cells correlated with the degree of monocyte contamination. Among the 62 cases of leukemia tested, which included three cases of B‐CLL, 19 cases of ALL, and 40 cases of ANLL, both MoAbs reacted highly homogenously only with M5b ANLL cells. These findings indicate that the two MoAbs, which recognize two distinct epitopes, represent useful markers in the differential diagnosis of M5b ANLL.
Clinical Effectiveness of First and Repeat Influenza Vaccination in Adult and Elderly Diabetic Patients
Authors: Ingrid Looijmans-Van den Akker, Theo J.M. Verheij, Erik Buskens, Kristin L. Nichol, Guy E.H.M. Rutten, Eelko Hak
Journal: Diabetes Care (2006)

OBJECTIVE—Influenza vaccine uptake remains low among the high-risk group of patients with diabetes, partly because of conflicting evidence regarding its potential benefits. We assessed the clinical effectiveness of influenza vaccination in adults with diabetes and specifically examined potential modification of effect by age and prior influenza vaccine uptake. RESEARCH DESIGN AND METHODS—The study was part of the Prevention of Influenza, Surveillance and Management (PRISMA) study, a nested case-control study conducted during the 1999–2000 influenza A epidemic, among 75,235 patients from primary care of any age recommended for vaccination. Among 9,238 adult patients with diabetes, 131 cases arose who were either hospitalized for diabetes dysregulation, acute respiratory disease, or cardiovascular disease and 61 cases who died, and we compared them with 1,561 control subjects. We evaluated the effect of (prior) influenza vaccination by means of logistic regression analysis controlling for age, sex, health insurance coverage, prior health care use, medication use, and comorbid conditions. RESULTS—Vaccination was associated with a 56% reduction in any complication (95% CI 36–70%), a 54% reduction in hospitalizations (26–71%), and 58% reduction in deaths (13–80%). Among study subjects aged 18–64 years, we observed somewhat higher reductions in the occurrence of any complication than among those aged &amp;gt;65 years (72 vs. 39%). In first-time vaccinated subjects, the primary end point was reduced by 47% (0.2–72%), and in those who received vaccination in the year before, the reduction was 58% (4–81%). CONCLUSIONS—Adults with type 2 diabetes, like other individuals from recognized risk groups, benefit considerably from influenza vaccination, and no difference in vaccine effectiveness was observed between first-time and repeat vaccination.
Carcinoid and Neuroendocrine Tumors: Building on Success
Authors: Pamela L. Kunz
Journal: Journal of Clinical Oncology (2015)

We have come a long way in our understanding and treatment of neuroendocrine tumors since the term "karzinoide" was coined in 1907. Neuroendocrine tumors are a group of biologically and clinically heterogeneous neoplasms that most commonly originate in the lungs, GI tract, and pancreas. The selection of initial and subsequent therapies requires careful consideration of both tumor and treatment characteristics. With recent advances, we now have more tools for the diagnosis and treatment of our patients. This comprehensive review article summarizes recent advances in the field of neuroendocrine tumors and places them into context for best management practices.
Influence of paraesophageal venous collaterals on efficacy of endoscopic sclerotherapy for esophageal varices
Authors: Ching-Yih Lin, Pin-Wen Lin, Hong-Ming Tsai, Xi-Zhang Lin, Ting-Tsung Chang, Jeng-Shiann Shin
Journal: Hepatology (1994)

To determine the diagnostic accuracy of computer tomography in the detection of venous collaterals surrounding the esophagus in patients with portal hypertension, preoperative computer tomography interpretations of these veins in 15 patients who were candidates for the Sugiura procedure for treatment of esophageal varices were correlated with those of the intraoperative assessment. Laparotomy revealed severe paraesophageal varices in five patients; four of them were found to have paraesophageal varices in computer tomography films. The sensitivity and specificity of computer tomography in diagnosing severe paraesophageal varices were 80% and 100%, respectively. A second assessment was performed in 59 additional patients with esophageal variceal hemorrhage to investigate the influence of paraesophageal varices on the efficacy of endoscopic sclerotherapy in the treatment of varices. The patients were divided into two groups: Group A included 17 patients with and group B 42 patients without paraesophageal varices on presclerotherapy computer tomography. All patients underwent elective sclerotherapy after being deemed hemodynamically stable. Patients in group A required more treatment sessions, more sclerosant and longer periods to obliterate varices completely than did group B patients. Eight patients in group A and six in group B (57% vs. 16%, p < 0.05) had variceal recurrence after obliteration during mean follow-ups of 20.8 and 19.9 mo, respectively. The mean time elapsed before variceal reappearance was shorter for group A than for group B (4.1 +/- 3.3 vs. 11.8 +/- 2.7 mo, p < 0.05). Among patients who developed new varices, five patients in group A and one in group B experienced repeat bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanisms of Resistance to Histone Deacetylase Inhibitors and Their Therapeutic Implications
Authors: Valeria R. Fantin, Victoria M. Richon
Journal: Clinical Cancer Research (2007)

Histone deacetylase inhibitors (HDI) are a promising new approach to the treatment of cancer. HDIs have been shown to induce differentiation, cell cycle arrest, and apoptosis in a variety of transformed cell lines; inhibit tumor growth in animal models; and show antitumor activity in clinical trials. Vorinostat, which has shown clinical responses in approximately 30% of patients with advanced cutaneous T-cell lymphoma, is the first HDI approved for the treatment of cancer, and it is currently being evaluated in other indications. A better understanding of the molecular determinants of resistance to HDIs may provide the basis for therapeutic combinations with improved clinical efficacy. Poor response to treatment could be linked to systemic factors like pharmacokinetics or to tumor-specific factors both at the level of the malignant cells (tumor intrinsic) or the tumor microenvironment. This review focuses on the tumor intrinsic mechanisms of drug resistance (excluding mechanism of acquired resistance due to chronic exposure). In particular, attention is given to selected mechanisms that are relevant across chemical classes of HDIs and that can aid in the design of rational combination strategies.
Preliminary DNA Identification for the Tsunami Victims in Thailand
Authors: Ya-Jun Deng, Yuan-Zhe Li, Xiao-Guang Yu, Li Li, Dong-Ying Wu, Jun Zhou, Tian-You Man, Guang Yang, Jiang-Wei Yan, Da-Qing Cai, Jian Wang, Huan-Ming Yang, Sheng-Bin Li, Jun Yu
Journal: Genomics Proteomics & Bioinformatics (2005)

The 2004 Southeast Asia Tsunami killed nearly 5,400 people in Southern Thailand, including foreign tourists and local residents. To recover DNA evidence as much as possible from the seriously decomposed bodies, we explored procedures of sample preparation from both bone and tooth samples as well as both mitochondrial and nuclear markers. Despite having failed to recover enough DNA for nuclear marker typing, we succeeded in obtaining fully informative results for mitochondrial markers (HV1 and HV2) from 258 tooth samples with a success rate of 51% (258/507). Using an organic DNA extraction method coupled with an ultrafiltration step, we obtained 16 STR (including 13 CODIS loci, one sex discrimination locus, and two Identifiler loci) profiles for 834 samples with a success rate of 79% (834/1,062). In addition, by comparing the allelic frequencies between the typed samples as a group and other index populations, we conclude that the Thai tsunami victims are a combined group of several populations. Our results provide valuable evidence and protocols for the future forensic practice.
Can the effects of exercise on bone quality be detected using the CUBA clinical ultrasound system?
Authors: N Messenger, S Scott, P McNaught-Davis
Journal: British Journal of Sports Medicine (1998)

OBJECTIVES: To determine whether the CUBA clinical quantitative ultrasound bone analyser was able to distinguish variations in bone quality between groups categorised according to activity level. METHOD: Eighty one white women aged 32 to 89 completed a confidential questionnaire on general health, diet, and exercise participation and underwent ultrasound testing at the right calcaneus utilising a CUBA clinical ultrasound system. RESULTS: The results confirmed the inverse relationship between age and the ultrasound indicators of bone quality: broadband ultrasound attenuation (BUA) (r = -0.52) and velocity of sound (VOS) (r = -0.68). Subject height weakly but significantly correlated with BUA (r = 0.39) and VOS (r = 0.35), and subject weight only correlated significantly with BUA (r = 0.37). Activity level was significantly associated (p &lt; 0.05) with the changes in ultrasound attenuation (BUA). The use of hormone replacement therapy or the contraceptive pill, a family history of osteoporosis, and gross indicators of calcium consumption did not yield significant results. CONCLUSION: Data obtained from the CUBA clinical system were sensitive enough to allow women to be classified into groups according to activity level. These data were within the range of "normal" ultrasound data and hence it is suggested that the machine has research as well as clinical value.
Identification of an Aurora Kinase Inhibitor Specific for the Aurora B Isoform
Authors: Hua Xie, Mee-Hyun Lee, Feng Zhu, Kanamata Reddy, Cong Peng, Yan Li, Do Young Lim, Dong Joon Kim, Xiang Li, Soouk Kang, Haitao Li, Weiya Ma, Ronald A. Lubet, Jian Ding, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2012)

Abstract Aurora kinases play an important role in chromosome alignment, segregation, and cytokinesis during mitosis. In the present study, we used a ligand docking method to explore the novel scaffold of potential Aurora B inhibitors. One thousand compounds from our in-house compound library were screened against the Aurora B structure and one compound, (E)-3-((E)-4-(benzo[d][1,3]dioxol-5-yl)-2-oxobut-3-en-1-ylidene)indolin-2-one (designated herein as HOI-07) was selected for further study. HOI-07 potently inhibited in vitro Aurora B kinase activity in a dose-dependent manner, without obvious inhibition of another 49 kinases, including Aurora A. This compound suppressed Aurora B kinase activity in lung cancer cells, evidenced by the inhibition of the phosphorylation of histone H3 on Ser10 in a dose- and time-dependent manner. This inhibition resulted in apoptosis induction, G2–M arrest, polyploidy cells, and attenuation of cancer cell anchorage-independent growth. Moreover, knocking down the expression of Aurora B effectively reduced the sensitivity of cancer cells to HOI-07. Results of an in vivo xenograft mouse study showed that HOI-07 treatment effectively suppressed the growth of A549 xenografts, without affecting the body weight of mice. The expression of phospho-histone H3, phospho-Aurora B, and Ki-67 was also suppressed in the HOI-07 treatment group. Taken together, we identified HOI-07 as a specific Aurora B inhibitor, which deserves further investigation. Cancer Res; 73(2); 716–24. ©2012 AACR.
Mixed Lineage Kinase MLK4 Is Activated in Colorectal Cancers Where It Synergistically Cooperates with Activated RAS Signaling in Driving Tumorigenesis
Authors: Miriam Martini, Mariangela Russo, Simona Lamba, Elisa Vitiello, Emily Hannah Crowley, Francesco Sassi, Davide Romanelli, Milo Frattini, Antonio Marchetti, Alberto Bardelli
Journal: Cancer Research (2013)

Colorectal cancers (CRC) are commonly classified into those with microsatellite instability and those that are microsatellite stable (MSS) but chromosomally unstable. The latter are characterized by poor prognosis and remain largely intractable at the metastatic stage. Comprehensive mutational analyses have revealed that the mixed lineage kinase 4 (MLK4) protein kinase is frequently mutated in MSS CRC with approximately 50% of the mutations occurring in KRAS- or BRAF-mutant tumors. This kinase has not been characterized previously and the relevance of MLK4 somatic mutations in oncogenesis has not been established. We report that MLK4-mutated alleles in CRC are constitutively active and increase the transformation and tumorigenic capacity of RAS-mutated cell lines. Gene expression silencing or targeted knockout of MLK4 impairs the oncogenic properties of KRAS- and BRAF-mutant cancer cells both in vitro and in xenograft models. In establishing the role of MLK4 in intracellular signaling, we show it directly phosphorylates MEK1 (MAP2K1) and that MEK/ERK (MAPK1) signaling is impaired in MLK4 knockout cells. These findings suggest that MLK4 inhibitors may be efficacious in KRAS- and BRAF-mutated CRCs and may provide a new opportunity for targeting such recalcitrant tumors.
ASSESSMENT OF OCCUPATIONAL EXPOSURES IN COMMUNITY-BASED CASE-CONTROL STUDIES
Authors: Valerie McGuire, Lorene M. Nelson, Thomas D. Koepsell, Harvey Checkoway, W. T. Longstreth
Journal: Annual Review of Public Health (1998)

▪ Abstract Assessing occupational exposures in community-based studies is a challenge for investigators because there are no standardized or validated approaches for collecting information regarding occupational history. The strengths and limitations of the methods available for assessing occupational exposures are reviewed. In community-based case-control studies, the prevalence of most chemical agents is low. The common sources of misclassification in these studies are addressed, as are strategies for dealing with misclassification bias. Methods to assess the presence and magnitude of differential reporting by cases and controls are outlined, together with analytic strategies to improve the classification of occupational exposures.
Lower extremity osteoarthritis management needs a paradigm shift
Authors: David J Hunter
Journal: British Journal of Sports Medicine (2011)

The current pre-eminent focus in osteoarthritis research and clinical practice is on persons with established radiographic disease. This is the very end-stage of disease genesis and modern therapies are thus largely palliative. A major shift in the focus of osteoarthritis research and clinical practice is critically needed if an impact is to be made for the millions living with the chronic pain and disability of osteoarthritis. The disease management paradigm needs to be revolutionised to focus on persons at high risk of developing or with early disease in which structural changes may be preventable or reversible. Similarly, current palliation should shift towards coordinated conservative management with reorganisation of the delivery of health services.
The clonogenic assay as a reproducible in vitro system to study predictive parameters of treatment outcome in acute nonlymphoblastic leukemia
Authors: George Browman, Jack Goldberg, Arlan J. Gottlieb, Harvey D. Preisler, Nozar Azarnia, Roger L. Priore, James K. Brennan, William R. Vogler, Elliott F. Winton, Kenneth B. Miller, Hans Grunwald
Journal: American Journal of Hematology (1983)

Abstract Seven institutions studied the cloning pattern of leukemic cells from pretherapy bone marrows of 273 patients with newly presenting and relapsed acute nonlymphoblastic leukemia. The cloning assay was done in all centers using an identical double‐layer agar method with a common source of colony‐stimulating factor. Cells were incubated for seven days, and clones were identified visually with an inverted microscope. All centers were able to obtain clonal growth in a substantial proportion of patients. Differences in growth pattern were observed between the major contributing center and the pooled results for all other centers. However, an analysis of clinical results suggested that in vitro differences were more likely related to differences in the patient populations than to variability in laboratory technique. The proportion of marrows in which leukemic cells formed colonies (&gt;40 cells) and large clusters (20‐40 cells) was greater in relapsed patients than in newly presenting patients (P &lt; .06). A progressive improvement in induction treatment outcome was seen with decreasing clonal growth. Patients whose marrows did not produce clones had a complete remission (CR) rate of 83% versus 50% for those patients whose marrow leukemic cells formed colonies and/or large clusters (P=.05). In vitro drug sensitivity studies with cytosine arabinoside and adriamycin were performed on bone marrow cells of patients treated with this combination clinically. The percent killing of clonogenic cells in this assay correlated with remission induction outcome. Complete remission was obtained in 73% of 15 patients whose bone marrow leukemic cells showed &gt;30% killing by in vitro drug exposure, and CR was obtained in only 30% of 23 patients whose marrows showed &lt; 30% killing (P&lt; .01). The results indicate that the clonogenic assay correlates with treatment outcome and can be used for drug sensitivity testing in patients with acute nonlymphoblastic leukemia. The limitations of the assay are discussed.