tbuckley/cabot-search huggingface dataset:
LONG-TERM ESTABLISHMENT OF A HUMAN PLASMACYTE CELL LINE DERIVED FROM A PATIENT WITH IgD MULTIPLE MYELOMA
Authors: M. E. Jobin, J. L. Fahey, Z. Price
Journal: The Journal of Experimental Medicine (1974)

Cell line LA-49, derived from pleural fluid cells of a patient with IgD multiple myeloma, was established in culture and maintained for more than 1 yr. The D-myeloma protein produced in culture was similar to the serum D-myeloma protein in electrophoretic mobility and in delta- and lambda-chain antigens. The plasma cell tumor culture, LA-49, differed from numerous immunoglobulin-producing B-lymphoblastoid cell lines established in this laboratory in: (a) Morphology (revealing various stages of maturation); (b) type of immunoglobulin produced (IgD vs. IgM, IgG, and/or, rarely, IgA); (c) growth characteristics (requirement of plasmacyte-stimulating factor); and (d) chromosomal features (polyploid vs. pseudodiploid). A growth factor was needed for cell division and maintenance of culture viability. This factor was supplied readily by irradiated feeder layers of normal human fibroblasts or conditional media from fibroblast cultures. Preliminary characterization of this factor revealed it to be a protein with a mol wt of approximately 150,000 daltons.
Preventing Onset of Anxiety Disorders in Offspring of Anxious Parents: A Randomized Controlled Trial of a Family-Based Intervention
Authors: Golda S. Ginsburg, Kelly L. Drake, Jenn-Yun Tein, Rebekah Teetsel, Mark A. Riddle
Journal: American Journal of Psychiatry (2015)

The authors examined the efficacy of a family-based intervention to prevent the onset of anxiety disorders in offspring of anxious parents.Participants were 136 families with a parent meeting DSM-IV criteria for an anxiety disorder and one child 6-13 years of age without an anxiety disorder. Families were randomly assigned to the family-based intervention (N=70) or to an information-monitoring control condition (N=66). All families were expected to complete assessments, administered by blind interviewers, at baseline, at the end of the intervention (or 8 weeks after randomization) and at 6- and 12-month follow-ups. Onset of any anxiety disorder and anxiety symptom severity (assessed using the Anxiety Disorders Interview Schedule for Children) at 12 months were the primary and secondary outcome measures, respectively.The incidence of child anxiety disorders was 31% in the control group and 5% in the intervention group (odds ratio=8.54, 95% CI=2.27, 32.06). At the 1-year follow-up, youths in the control group also had higher anxiety symptoms ratings than those in the intervention group. Effect sizes were medium to large (0.81 at 6 months and 0.57 at 12 months for anxiety symptoms), and the number needed to treat was 3.9 at 12 months. Significant moderators included baseline levels of child anxiety; significant mediators were parental distress and modeling of anxiety. Child maladaptive cognitions and parental anxiety did not mediate outcomes.A brief psychosocial prevention program holds promise for reducing the 1-year incidence of anxiety disorders among offspring of anxious parents.
A phase I study of a CanAg-targeted immunoconjugate, huC242-DM4, in patients with Can Ag-expressing solid tumors
Authors: M. M. Mita, A. D. Ricart, A. C. Mita, A. Patnaik, J. Sarantopoulos, K. Sankhala, R. J. Fram, A. Qin, J. Watermill, A. W. Tolcher
Journal: Journal of Clinical Oncology (2007)

3062 Background: HuC242-DM4 is a novel, targeted anti-cancer agent in development for the treatment of CanAg-expressing tumors such as carcinomas of the colon and pancreas. The compound is formed by the conjugation of the potent cytotoxic maytansinoid drug, DM4, to the humanized monoclonal antibody, huC242. This agent was highly active across a broad spectrum of CanAg-expressing human tumor xenograft models. Methods: Patients were enrolled with metastatic or inoperable colorectal, pancreatic, and other CanAg-expressing tumors who have failed standard therapy (about 95% of pts. had received = 4 prior chemotherapy regimens). Results: Thirty patients were treated with huC242-DM4, receiving a single intravenous (IV) infusion once every three weeks. Cohorts of 3 patients initially were enrolled on each dose level. Patients have received huC242-DM4 at 18, 36, 60, 90, 126, 168, 223, and 297 mg/m 2 . To date, dose limiting toxicity (DLT) was experienced by two of six patients treated at the 223 mg/m 2 dose level during their second cycle of treatment. The patients experienced decreased visual acuity, corneal deposits and keratitis. Both patients were subsequently treated with lubricating eye drops. At present, these adverse events have markedly improved in one patient, while the other patient has completely returned to baseline. Of 10 patients treated at the168 mg/m 2 dose level (including two patients who were dose reduced to 168 mg/m 2 ), seven patients have received at least two cycles of treatment. One patient had grade 3 diarrhea and dehydration during his second cycle at 168 mg/m 2 . The latter improved with intravenous fluids. Preliminary pharmacokinetic data reveal a half-life of huC242-DM4 of about 5 days in patients with low plasma CanAg levels. In patients with high plasma CanAg levels (&gt;900 units/mL), clearance of huC242-DM4 is increased. There has been no clinically significant myelosuppression and no formation of antibody to humanized antibody (HAHA) or drug (HADA). One patient had a 36% decline in CEA (not associated with tumor shrinkage). Conclusions: HuC242-DM4 was well tolerated at the 168 mg/m 2 dose level. The MTD is not yet defined and approaches to prevent /ameliorate ocular toxicity are planned. No significant financial relationships to disclose.
Etiology of Anemia in Patients With Advanced Heart Failure
Authors: John N. Nanas, Charis Matsouka, Drosos Karageorgopoulos, Anastasia Leonti, Elias Tsolakis, Stavros G. Drakos, Eleftheria P. Tsagalou, George D. Maroulidis, George P. Alexopoulos, John E. Kanakakis, Maria I. Anastasiou-Nana
Journal: Journal of the American College of Cardiology (2006)
Tn Antigen Is Expressed on Leukosialin from T-Lymphoid Cells
Authors: Mizue Inoue, Hiroshi Nakada, Nobuhiro Tanaka, Ikuo Yamashina
Journal: Cancer Research (1994)

Various T-lymphoid cells were labeled with [3H] glucosamine and then cell lysates were prepared from them. The Tn antigen was immunoprecipitated and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by fluorography. The Tn antigen was found to be expressed on leukosialin, a major glycoprotein of T-lymphoid cells. The carbohydrate moieties of leukosialin were isolated from Jurkat and Molt 4 cells by alkaline borohydride treatment. The leukosialin in both cases predominantly contained single N -acetylgalactosamine residues, consistent with expression of the Tn antigen. Tryptic glycopeptides containing antigenic sites were isolated using an MLS 128 immunoaffinity column and purified by gel filtration and reverse phase column chromatographies. Sequence analyses revealed that all the glycopeptides obtained contained three consecutive residues of N -acetylgalactosamine-Ser/Thr, supporting the idea that the epitopic structure is a cluster of N -acetylgalactosamineSer/Thr.
Breast Cancer Genomics From Microarrays to Massively Parallel Sequencing: Paradigms and New Insights
Authors: Charlotte K. Y. Ng, Anne M. Schultheis, Francois-Clement Bidard, Britta Weigelt, Jorge S. Reis-Filho
Journal: JNCI Journal of the National Cancer Institute (2015)

Rapid advancements in massively parallel sequencing methods have enabled the analysis of breast cancer genomes at an unprecedented resolution, which have revealed the remarkable heterogeneity of the disease. As a result, we now accept that despite originating in the breast, estrogen receptor (ER)–positive and ER-negative breast cancers are completely different diseases at the molecular level. It has become apparent that there are very few highly recurrently mutated genes such as TP53, PIK3CA, and GATA3, that no two breast cancers display an identical repertoire of somatic genetic alterations at base-pair resolution and that there might not be a single highly recurrently mutated gene that defines each of the “intrinsic” subtypes of breast cancer (ie, basal-like, HER2-enriched, luminal A, and luminal B). Breast cancer heterogeneity, however, extends beyond the diversity between tumors. There is burgeoning evidence to demonstrate that at least some primary breast cancers are composed of multiple, genetically diverse clones at diagnosis and that metastatic lesions may differ in their repertoire of somatic genetic alterations when compared with their respective primary tumors. Several biological phenomena may shape the reported intratumor genetic heterogeneity observed in breast cancers, including the different mutational processes and multiple types of genomic instability. Harnessing the emerging concepts of the diversity of breast cancer genomes and the phenomenon of intratumor genetic heterogeneity will be essential for the development of optimal methods for diagnosis, disease monitoring, and the matching of patients to the drugs that would benefit them the most.
Genomic Imprinting, DNA Methylation, and Cancer
Authors: S. Rainier, A. P. Feinberg
Journal: JNCI Journal of the National Cancer Institute (1994)

The authors wish to correct Figs. 1 and 2. Rainier writes, “In Fig. 2, all of the small squares were supposed to be open squares. Minor errors have been corrected in the revised Fig. 1.”
Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy
Authors: J NIU, A AZFER, L ROGERS, X WANG, P KOLATTUKUDY
Journal: Cardiovascular Research (2006)

Cerium oxide (CeO2) nanoparticles have been shown to protect cells in culture from lethal stress, but no protection in vivo has been reported. Cardiac-specific expression of monocyte chemoattractant protein (MCP)-1 in mice causes ischemic cardiomyopathy associated with activation of endoplasmic reticulum (ER) stress. The aim of this study was to assess the effects of CeO2 nanoparticles on cardiac function and remodeling as well as ER stress response in this murine model of cardiomyopathy.MCP-1 transgenic mice (MCP mice) and wild-type controls were administered intravenously 15 nmol of CeO2 nanoparticles or vehicle only twice a week for 2 weeks. Cardiac function, myocardial histology, nitrotyrosine formation, expression of cytokines, and ER stress-associated genes were evaluated.Treatment with CeO2 nanoparticles markedly inhibited progressive left ventricular dysfunction and dilatation in MCP mice and caused a significant decrease in serum levels of MCP-1, C-reactive protein, and total nitrated proteins. The infiltration of monocytes/macrophages, accumulation of 3-nitrotyrosine, apoptotic cell death, and expression of proinflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 in the myocardium were markedly inhibited by CeO2 nanoparticles. Expression of the key ER stress-associated genes, including glucose-regulated protein 78 (Grp78), protein disulfide isomerase (PDI), and heat shock proteins (HSP25, HSP40, HSP70), were also suppressed by CeO2 nanoparticles.CeO2 nanoparticles protect against the progression of cardiac dysfunction and remodeling by attenuation of myocardial oxidative stress, ER stress, and inflammatory processes probably through their autoregenerative antioxidant properties.
Effect of Hypobaric Hypoxia, Simulating Conditions During Long-Haul Air Travel, on Coagulation, Fibrinolysis, Platelet Function, and Endothelial Activation
Authors: William D. Toff, Chris I. Jones, Isobel Ford, Robert J. Pearse, Henry G. Watson, Stephen J. Watt, John A. S. Ross, David P. Gradwell, Anthony J. Batchelor, Keith R. Abrams, Joost C. M. Meijers, Alison H. Goodall, Michael Greaves
Journal: JAMA (2006)

The link between long-haul air travel and venous thromboembolism is the subject of continuing debate. It remains unclear whether the reduced cabin pressure and oxygen tension in the airplane cabin create an increased risk compared with seated immobility at ground level.To determine whether hypobaric hypoxia, which may be encountered during air travel, activates hemostasis.A single-blind, crossover study, performed in a hypobaric chamber, to assess the effect of an 8-hour seated exposure to hypobaric hypoxia on hemostasis in 73 healthy volunteers, which was conducted in the United Kingdom from September 2003 to November 2005. Participants were screened for factor V Leiden G1691A and prothrombin G20210A mutation and were excluded if they tested positive. Blood was drawn before and after exposure to assess activation of hemostasis.Individuals were exposed alternately (> or =1 week apart) to hypobaric hypoxia, similar to the conditions of reduced cabin pressure during commercial air travel (equivalent to atmospheric pressure at an altitude of 2438 m), and normobaric normoxia (control condition; equivalent to atmospheric conditions at ground level, circa 70 m above sea level).Comparative changes in markers of coagulation activation, fibrinolysis, platelet activation, and endothelial cell activation.Changes were observed in some hemostatic markers during the normobaric exposure, attributed to prolonged sitting and circadian variation. However, there were no significant differences between the changes in the hypobaric and the normobaric exposures. For example, the median difference in change between the hypobaric and normobaric exposure was 0 ng/mL for thrombin-antithrombin complex (95% CI, -0.30 to 0.30 ng/mL); -0.02 [corrected] nmol/L for prothrombin fragment 1 + 2 (95% CI, -0.03 to 0.01 nmol/L); 1.38 ng/mL for D-dimer (95% CI, -3.63 to 9.72 ng/mL); and -2.00% for endogenous thrombin potential (95% CI, -4.00% to 1.00%).Our findings do not support the hypothesis that hypobaric hypoxia, of the degree that might be encountered during long-haul air travel, is associated with prothrombotic alterations in the hemostatic system in healthy individuals at low risk of venous thromboembolism.
Metastasis-Suppressing Potential of Ribonucleotide Reductase Small Subunit p53R2 in Human Cancer Cells
Authors: Xiyong Liu, Bingsen Zhou, Lijun Xue, Jennifer Shih, Karen Tye, Wesley Lin, Christina Qi, Peiguo Chu, Frank Un, Wei Wen, Yun Yen
Journal: Clinical Cancer Research (2006)

Previous gene transfection studies have shown that the accumulation of human ribonucleotide reductase small subunit M2 (hRRM2) enhances cellular transformation, tumorigenesis, and malignancy potential. The latest identified small subunit p53R2 has 80% homology to hRRM2. Here, we investigate the role of p53R2 in cancer invasion and metastasis.The immunohistochemistry was conducted on a tissue array including 49 primary and 59 metastatic colon adenocarcinoma samples to determine the relationship between p53R2 expression and metastasis. A Matrigel invasive chamber was used to sort the highly invasive cells and to evaluate the invasion potential of p53R2.Univariate and multivariate analyses revealed that p53R2 is negatively related to the metastasis of colon adenocarcinoma samples (odds ratio, 0.23; P<0.05). The decrease of p53R2 is associated with cell invasion potential, which was observed in both p53 wild-type (KB) and mutant (PC-3 and Mia PaCa-2) cell lines. An increase in p53R2 expression by gene transfection significantly reduced the cellular invasion potential to 54% and 30% in KB and PC-3 cells, respectively, whereas inhibition of p53R2 by short interfering RNA resulted in a 3-fold increase in cell migration.Opposite regulation of hRRM2 and p53R2 in invasion potential might play a critical role in determining the invasion and metastasis phenotype in cancer cells. The expression level of ribonucleotide reductase small subunits may serve as a biomarker to predict the malignancy potential of human cancers in the future.
Relationship of CDX2 Loss with Molecular Features and Prognosis in Colorectal Cancer
Authors: Yoshifumi Baba, Katsuhiko Nosho, Kaori Shima, Ellen Freed, Natsumi Irahara, Juliet Philips, Jeffrey A. Meyerhardt, Jason L. Hornick, Ramesh A. Shivdasani, Charles S. Fuchs, Shuji Ogino
Journal: Clinical Cancer Research (2009)

The homeodomain transcription factor CDX2 is a relatively specific immunohistochemical marker for gastrointestinal carcinoma. However, no study has comprehensively examined the relationship between CDX2 expression in colon cancer and clinical, pathologic, prognostic, and molecular features, including microsatellite instability and CpG island methylator phenotype (CIMP).Utilizing 621 colorectal cancers with clinical outcome and molecular data, CDX2 loss was detected in 183 (29%) tumors by immunohistochemistry.In multivariate logistic regression analysis, CDX2 loss was associated with female gender [odds ratio (OR), 3.32; P < 0.0001], CIMP-high (OR, 4.42; P = 0.0003), high tumor grade (OR, 2.69; P = 0.0085), stage IV disease (OR, 2.03; P = 0.019), and inversely with LINE-1 hypomethylation (for a 30% decline; OR, 0.33; P = 0.0031), p53 expression (OR, 0.55; P = 0.011), and beta-catenin activation (OR, 0.60; P = 0.037), but not with body mass index, tumor location, microsatellite instability, BRAF, KRAS, PIK3CA, p21, or cyclooxygenase-2. CDX2 loss was not independently associated with patient survival. However, the prognostic effect of CDX2 loss seemed to differ according to family history of colorectal cancer (P(interaction) = 0.0094). CDX2 loss was associated with high overall mortality (multivariate hazard ratio, 2.40; 95% CI, 1.28-4.51) among patients with a family history of colorectal cancer; no such association was present (multivariate hazard ratio, 0.97; 95% CI, 0.66-1.41) among patients without a family history of colorectal cancer.CDX2 loss in colorectal cancer is independently associated with female gender, CIMP-high, high-level LINE-1 methylation, high tumor grade, and advanced stage. CDX2 loss may be associated with poor prognosis among patients with a family history of colorectal cancer.
Integrating Tobacco Cessation Into Mental Health Care for Posttraumatic Stress Disorder&lt;subtitle&gt;A Randomized Controlled Trial&lt;/subtitle&gt;
Authors: Miles McFall, Andrew J. Saxon, Carol A. Malte, Bruce Chow, Sara Bailey, Dewleen G. Baker, Jean C. Beckham, Kathy D. Boardman, Timothy P. Carmody, Anne M. Joseph, Mark W. Smith, Mei Chiung Shih, Ying Lu, Mark Holodniy, Philip W. Lavori
Journal: JAMA (2010)

Most smokers with mental illness do not receive tobacco cessation treatment.To determine whether integrating smoking cessation treatment into mental health care for veterans with posttraumatic stress disorder (PTSD) improves long-term smoking abstinence rates.A randomized controlled trial of 943 smokers with military-related PTSD who were recruited from outpatient PTSD clinics at 10 Veterans Affairs medical centers and followed up for 18 to 48 months between November 2004 and July 2009.Smoking cessation treatment integrated within mental health care for PTSD delivered by mental health clinicians (integrated care [IC]) vs referral to Veterans Affairs smoking cessation clinics (SCC). Patients received smoking cessation treatment within 3 months of study enrollment.Smoking outcomes included 12-month bioverified prolonged abstinence (primary outcome) and 7- and 30-day point prevalence abstinence assessed at 3-month intervals. Amount of smoking cessation medications and counseling sessions delivered were tested as mediators of outcome. Posttraumatic stress disorder and depression were repeatedly assessed using the PTSD Checklist and Patient Health Questionnaire 9, respectively, to determine if IC participation or quitting smoking worsened psychiatric status.Integrated care was better than SCC on prolonged abstinence (8.9% vs 4.5%; adjusted odds ratio, 2.26; 95% confidence interval [CI], 1.30-3.91; P = .004). Differences between IC vs SCC were largest at 6 months for 7-day point prevalence abstinence (78/472 [16.5%] vs 34/471 [7.2%], P < .001) and remained significant at 18 months (86/472 [18.2%] vs 51/471 [10.8%], P < .001). Number of counseling sessions received and days of cessation medication used explained 39.1% of the treatment effect. Between baseline and 18 months, psychiatric status did not differ between treatment conditions. Posttraumatic stress disorder symptoms for quitters and nonquitters improved. Nonquitters worsened slightly on the Patient Health Questionnaire 9 relative to quitters (differences ranged between 0.4 and 2.1, P = .03), whose scores did not change over time.Among smokers with military-related PTSD, integrating smoking cessation treatment into mental health care compared with referral to specialized cessation treatment resulted in greater prolonged abstinence.clinicaltrials.gov Identifier: NCT00118534.
Molecular Pathways: Old Drugs Define New Pathways: Non-Histone Acetylation at the Crossroads of the DNA Damage Response and Autophagy
Authors: Oronza Antonietta Botrugno, Thomas Robert, Fabio Vanoli, Marco Foiani, Saverio Minucci
Journal: Clinical Cancer Research (2012)

Histone deacetylases (HDAC) modulate acetylation and the function of histone and non-histone proteins. HDAC inhibitors have been developed to block the aberrant action of HDACs in cancer, and several are in clinical use (vorinostat, romidepsin, and valproic acid). Detailed understanding of their action is lacking, however, and their clinical activity is limited in most cases. Recently, HDACs have been involved in the control of the DNA damage response (DDR) at several levels and in directly regulating the acetylation of a number of DDR proteins (including CtIP and Exo1). Mechanistically, acetylation leads to the degradation of double-strand break repair enzymes through autophagy, providing a novel, direct link between DDR and autophagy. These observations, obtained in yeast cells, should now be translated to mammalian model systems and cancer cells to reveal whether this acetylation link is maintained in mammals, and if and how it is deregulated in cancer. In addition to HDACs, DDR and autophagy have been addressed pharmacologically, suggesting that the acetylation link, if involved in cancer, can be exploited for the design of new anticancer treatments.
Progressive Leg Pain and Weakness
Authors: Digvijaya D. Navalkele, Maria-Magdalena Georgescu, Dennis K. Burns, Tasha Greenberg, Steven Vernino
Journal: JAMA Neurology (2013)

A 54-year-old man presented with progressive asymmetric leg pain and weakness. He had a history of invasive squamous cell carcinoma that was fully treated 2 years earlier. His leg symptoms progressed relentlessly during several months. Imaging studies demonstrated enhancement of the cauda equina and leptomeninges of the lower spinal cord. Initial cerebrospinal fluid examination showed an elevated protein concentration and lymphocytic pleocytosis with no malignant cells on cytological analysis. There was short-term improvement in symptoms and cerebrospinal fluid abnormalities with intravenous steroids. Two additional cerebrospinal fluid studies showed normal cytological findings, elevated IgG synthesis, and elevated antibody titers to varicella-zoster virus. Over time, the patient worsened, developed cranial neuropathies, and ultimately died. The pathological diagnosis and the approach to the clinical data are discussed.