tbuckley/cabot-search huggingface dataset:
Assessment of Molecular Markers of Clinical Sensitivity to Single-Agent Taxane Therapy for Metastatic Breast Cancer
Authors: Catherine Van Poznak, Lee Tan, Katherine S. Panageas, Crispinita D. Arroyo, Clifford Hudis, Larry Norton, Andrew D. Seidman
Journal: Journal of Clinical Oncology (2002)

PURPOSE: The taxanes affect tubulin polymerization and interfere with mitotic transition. A checkpoint blockade at the G 1 -S boundary would be expected to promote taxane-induced apoptotic cell death through a mechanism that may involve p27. Other proposed determinants of clinical taxane sensitivity/resistance include p53, members of the epidermal growth factor receptor (EGFR) superfamily (eg, HER2, EGFR), and estrogen receptors and progesterone receptors. These molecular markers and their correlation with clinical taxane sensitivity are investigated in this retrospective clinicopathologic study. PATIENTS AND METHODS: We performed immunohistochemistry (IHC) for estrogen receptors, progesterone receptors, HER2, EGFR, p53, and p27 on 144 breast tumor specimens from patients treated for metastatic breast cancer on a series of clinical trials of single-agent taxane chemotherapy for correlation with clinical response (complete or partial response). Patient characteristics that could influence response (ie, performance status, extent of disease, and prior therapy) were also examined. RESULTS: In univariate analysis, Karnofsky performance status ≥ 90% and no prior history of anthracycline therapy correlated with a good clinical response to single-agent taxane (P = .003 and P = .041, respectively). None of the IHC variables tested were predictive of clinical response to taxane therapy, although p27 negativity showed a trend toward significance (P = .075). Concordance between the polyclonal antibody with HercepTest (DAKO, Carpinteria, CA) and the monoclonal antibody CB-11 (BioGenex, San Ramon, CA) was noted (kappa = 0.943); however, neither univariate nor multivariate analysis demonstrated an association between HER2 status and response to taxane chemotherapy. CONCLUSION: The IHC biomarkers studied were not predictive of response to single-agent taxane chemotherapy in patients with metastatic breast cancer. Identification of molecular correlates of taxane response remains an important goal.
Randomized study of vinorelbine (VRB) versus vindesine (VDS) in previously untreated stage IIIB or IV non-small-cell lung cancer (NSCLC)
Authors: K. Furuse, M. Fukuoka, M. Kuba, S. Yamori, Y. Nakai, S. Negoro, N. Katagami, Y. Takada, E. Kinuwaki, M. Kawahara, K. Kubota, A. Sakuma, H. Niitani
Journal: Annals of Oncology (1996)
Familial Gastrointestinal Stromal Tumor Syndrome: Phenotypic and Molecular Features in a Kindred
Authors: Frederick P. Li, Jonathan A. Fletcher, Michael C. Heinrich, Judy E. Garber, Stephen E. Sallan, Clara Curiel-Lewandrowski, Anette Duensing, Matt van de Rijn, Lowell E. Schnipper, George D. Demetri
Journal: Journal of Clinical Oncology (2005)

Members of a family with hereditary gastrointestinal stromal tumors (GISTs) and a germline KIT oncogene mutation were evaluated for other potential syndrome manifestations. A tumor from the proband was analyzed to compare features with sporadic GISTs.Members of a kindred in which six relatives in four consecutive generations comprised an autosomal dominant pattern of documented GISTs and cutaneous lesions underwent physical examination, imaging studies, and germline KIT analysis. A recurrent GIST from the proband was studied using microarray, karyotypic, immunohistochemical, and immunoblotting techniques.In addition to evidence of multiple GISTs, lentigines, malignant melanoma, and an angioleiomyoma were identified in relatives. A previously reported gain-of-function missense mutation in KIT exon 11 (T --> C) that results in a V559A substitution within the juxtamembrane domain was identified in three family members. The proband's recurrent gastric GIST had a 44,XY-14,-22 karyotype and immunohistochemical evidence of strong diffuse cytoplasmic KIT expression without expression of actin, desmin, or S-100. Immunoblotting showed strong expression of phosphorylated KIT and downstream signaling intermediates (AKT and MAPK) at levels comparable with those reported in sporadic GISTs. cDNA array profiling demonstrated clustering with sporadic GISTs, and expression of GIST markers comparable to sporadic GISTs.These studies provide the first evidence that gene expression and mechanisms of cytogenetic progression and cell signaling are indistinguishable in familial and sporadic GISTs. Current investigations of molecularly targeted therapies in GIST patients provide opportunities to increase the understanding of features of the hereditary syndrome, and risk factors and molecular pathways of the neoplastic phenotypes.
Effective Treatment of Advanced Human Melanoma Metastasis in Immunodeficient Mice Using Combination Metronomic Chemotherapy Regimens
Authors: William Cruz-Munoz, Shan Man, Robert S. Kerbel
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The development of effective therapeutic approaches for treatment of metastatic melanoma remains an immense challenge. Present therapies offer minimal benefit. Although dacarbazine chemotherapy remains the standard therapy, it mediates only low response rates, usually of short duration, even when combined with other chemotherapeutic agents. Thus, new therapeutic strategies are urgently needed. Experimental Design: Using a newly developed preclinical model, we evaluated the efficacy of various doublet metronomic combination chemotherapy against established advanced melanoma metastasis and compared these with the standard maximum tolerated dose dacarbazine (alone or in combination with chemotherapeutic agents or vascular endothelial growth factor receptor–blocking antibody). Results: Whereas maximum tolerated dose dacarbazine therapy did not cause significant improvement in median survival, a doublet combination of low-dose metronomic vinblastine and low-dose metronomic cyclophosphamide induced a significant increase in survival with only minimal toxicity. Furthermore, we show that the incorporation of the low-dose metronomic vinblastine/low-dose metronomic cyclophosphamide combination with a low-dose metronomic dacarbazine regimen also results in a significant increase in survival, but not when combined with maximum tolerated dose dacarbazine therapy. We also show that a combination of metronomic vinblastine therapy and a vascular endothelial growth factor receptor 2–blocking antibody (DC101) results in significant control of metastatic disease and that the combination of low-dose metronomic vinblastine/DC101 and low-dose metronomic dacarbazine induced a significant improvement in median survival. Conclusions: The effective control of advanced metastatic melanoma achieved by these metronomic-based chemotherapeutic approaches warrants clinical consideration of this treatment concept, given the recent results of a number of metronomic-based chemotherapy clinical trials.
Fc-receptors, Ia-antigens, and immunoglobulin on normal and activated mouse T lymphocytes.
Authors: P H Krammer, L Hudson, J Sprent
Journal: The Journal of Experimental Medicine (1975)

Using antibody coated bovine erythrocytes we were unable to demonstrate Fc-receptors on either thymus cells or T cells prepared from lymph node cell suspensions by anti-Ig column filtration. However, if parental thymus or lymph node T cells were transferred to X-irradiated F1 hybrids, activated donor T cells recovered from the recipient's spleen (ATC-spleen) were shown to express Fc-receptors. Fc-receptors were also demonstrable on ATC-spleen prepared between strain combinations differing at the M-locus. In marked contrast, Fc-receptors were not detected on ATC recovered from thoracic duct lymph (T.TDL). This applied to (a) H-2-activated T.TDL derived from normal thymus cells, (b) H-2-activated T.TDL derived from thymus cells depleted of B cells, and (c) M-locus-activated T.TDL. Of these three populations, surface Ig (of B cell origin) was detected on a large proportion of the first but not on the second and third populations. Thus, the failure to detect Fc-receptors on any of these populations could not be attributed to blocking by adsorbed surface Ig. In addition, various T-cell populations were examined by a microcytotoxicity assay for the presence of cell surface Ia-antigens. 5--10% of the thymus cells, 20--30% of cortisone-resistant thymus cells, 60--70% of lymph node cells, and 60--80% of ATC-spleen and T.TDL showed Ia.
Phase II Study of Single-Agent Arsenic Trioxide for the Front-Line Therapy of Acute Promyelocytic Leukemia
Authors: Ardeshir Ghavamzadeh, Kamran Alimoghaddam, Shahrbano Rostami, Seyed Hamidolah Ghaffari, Mohamad Jahani, Massoud Iravani, Seyed Asadollah Mousavi, Babak Bahar, Mahdi Jalili
Journal: Journal of Clinical Oncology (2011)

The long-term follow-up results of patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid and chemotherapy show high cure rates. Several studies have shown high efficacy of single-agent arsenic trioxide in newly diagnosed APL. However, long-term follow-up results are needed.One hundred ninety-seven patients with newly diagnosed APL were treated with arsenic trioxide 0.15 mg/kg daily intravenous infusion until complete remission (CR). After achieving CR, the patients received one to four more courses of therapy with arsenic trioxide as consolidation and were observed with reverse-transcriptase polymerase chain reaction studies from peripheral blood (to detect of minimal residual disease) every 3 months or until relapse or death.The morphologic CR rate was 85.8%. The most common cause of remission failure was early death owing to APL differentiation syndrome (13.2%). The most important prognostic factor for early mortality was a high WBC count at presentation. The 5-year disease-free survival (DFS) rate was 66.7% ± 4% (SE). Relapse after 5 years in CR was rare. The 5-year overall survival (OS) rate by intention-to-treat analysis was 64.4% ± 4%. In patients who achieved CR, OS and DFS were identical.The long-term follow-up of newly diagnosed patients with APL treated with single-agent arsenic trioxide shows high rates of DFS and OS.
Directed evolution of cellobiose utilization in Escherichia coli K12.
Authors: M Kricker, B G Hall
Journal: Molecular Biology and Evolution (1984)

The cellobiose catabolic system of Escherichia coli K12 is being used to study the role of cryptic genes in evolution of new functions. Escherichia coli does not use beta-glucoside sugars; however, mutations in several loci can activate the cryptic bgl operon and permit growth on the beta-glucoside sugars arbutin and salicin. Such Bgl+ mutants do not use cellobiose, which is the most common beta-glucoside in nature. We have isolated a Cel+ (cellobiose-utilizing) mutant from a Bgl+ mutant of E. coli K12. The Cel+ mutant grows well on cellobiose, arbutin, and salicin. Genes for utilization of these beta-glucosides are located at 37.8 min on the E. coli map. The genes of the bgl operon are not involved in cellobiose utilization. Introduction of a deletion covering bgl does not affect the ability to utilize cellobiose, arbutin, or salicin, indicating that the new Cel+ genes provide all three functions. Spontaneous cellobiose negative mutants also become arbutin and salicin negative. Analysis of beta-glucoside positive revertants of these mutants indicates that there are separate loci for utilization of each of the beta-glucoside sugars. The genes are closely linked and may be activated from a single locus. A fourth gene at an unknown location increases the growth rate on cellobiose. The cel genes constitute a second cryptic system for beta-glucoside utilization in E. coli K12.
Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia/reperfusion injury in mice
Authors: Simon F. De Meyer, Alexander S. Savchenko, Michael S. Haas, Daphne Schatzberg, Michael C. Carroll, Alexandra Schiviz, Barbara Dietrich, Hanspeter Rottensteiner, Friedrich Scheiflinger, Denisa D. Wagner
Journal: Blood (2012)
The Cinderella of Medical Disciplines
Authors: Rebekah Emanuel, Karen Glasser Scandrett, Linda Emanuel
Journal: Journal of Clinical Oncology (2012)

Abdul Rahman Hussein (name and case details changed for confidentiality) was a 60-year-old man with advanced colon cancer who received palliative radiation therapy several years ago in a Jerusalem hospital.APalestinianmanfromtheWestBankcity of Ramallah, Mr. Hussein had been hospitalized for management of a bowel obstruction. Although he had a large family, his visitors were limited to an adult daughter and son, who were the family members best able to navigate the complex system of checkpoints to cross the wall dividing Ramallah from Jerusalem. At the time of Mr. Hussein’s hospitalization, a student chaplain (R.E.) was participating in a new program at the Jerusalem hospital in which all oncology patients were offered chaplaincy visits. She had been assigned to visit another English-speaking patient in the same hospital room as Mr. Hussein, but as she approached the other patient’s bed, Mr. Husseincaughthereyeandsmiled.Shegreetedhim, and he motioned her over to his bedside. When she sat down, he informed her that she, a young American Jew, reminded him of a student from a class in hisyouth.Hebegandescribinghowhespentpartof his childhood in the United States. He talked about how their once-thriving family business had failed and how he had built his own business, and he recounted his family’s journeys back and forth between continents. After a few minutes of conversation, Mr. Hussein’s son, who had been sitting next to him reading abook,rosetogetacupofcoffee.Assoonashisson
Impact of Circulating Vitamin D Binding Protein Levels on the Association between 25-Hydroxyvitamin D and Pancreatic Cancer Risk: A Nested Case–Control Study
Authors: Stephanie J. Weinstein, Rachael Z. Stolzenberg-Solomon, William Kopp, Helen Rager, Jarmo Virtamo, Demetrius Albanes
Journal: Cancer Research (2012)

High concentrations of circulating 25-hydroxyvitamin D [25(OH)D] have been associated with elevated pancreatic cancer risk. As this is contrary to an expected inverse association between vitamin D status and cancer, we examined whether vitamin D binding protein (DBP), the primary carrier of vitamin D compounds in circulation, plays a role in this relationship. Prediagnostic serum DBP and 25(OH)D were studied in relation to risk of pancreatic cancer in a nested case-control study of 234 cases and 234 controls in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. ORs and 95% CIs were estimated using logistic regression, and statistical tests were two-sided. We found that DBP and 25(OH)D were correlated (r = 0.27, P < 0.0001), and DBP was inversely associated with pancreatic cancer risk (OR = 0.66, 95% CI = 0.39-1.12, for the highest vs. lowest quartile; P(trend) = 0.02). Importantly, this association seemed to have a threshold between quartiles 2 to 4 and quartile 1, and was primarily evident among men with concurrent high 25(OH)D concentrations (OR = 0.33, 95% CI = 0.16-0.70 for highest vs. lowest quartile; P(trend) = 0.002), with no association in men with lower serum 25(OH)D (OR = 1.28, 95% CI = 0.62-2.61 for highest vs. lowest quartile, P(trend) 0.63, P(interaction) = 0.01). Men with higher 25(OH)D concentrations and serum DBP below the median showed greatly elevated risk of pancreatic cancer (OR = 5.01, 95% CI 2.33-10.78, for highest vs. lowest quartile; P(trend) < 0.0001), while risk was weakly inversely associated with serum 25(OH)D when DBP concentrations were higher (P(interaction) = 0.001). Taken together, our findings indicate that higher DBP concentrations may sequester more 25(OH)D and reduce free 25(OH)D bioavailability. Simultaneous examination of DBP and 25(OH)D may be important in determining the association of vitamin D with cancer risk.
Comment on ‘Associations between statin use and changes in pain, function and structural progression: a longitudinal study of persons with knee osteoarthritis’
Authors: Stefan Clockaerts, G J V M Van Osch, Sita M Bierma-Zeinstra
Journal: Annals of the Rheumatic Diseases (2013)

We read with interest the article by Riddle et al 1 entitled ‘Associations between Statin use and changes in pain, function and structural progression: a longitudinal study of persons with knee osteoarthritis’, where the authors used data on a subset of 2207 subjects included in the Osteoarthritis Initiative with radiological suspected or confirmed knee osteoarthritis (OA). Their article was partly based on the article by Clockaerts et al ,2 where we report an association between statin use, and incidence and progression of radiological knee OA in the Ommoord cohort of the Rotterdam study. Riddle et al also investigated the association between pain and function scores, progression of radiological knee OA and statin use, and found no associations.

Their data may indicate that there is indeed no association between statin use and knee OA, and that our results were due to an unexpected bias or …
Performance of Diagnostic Mammography for Women With Signs or Symptoms of Breast Cancer
Authors: W. E. Barlow
Journal: JNCI Journal of the National Cancer Institute (2002)

The performance of diagnostic mammography for women with signs or symptoms of breast cancer has not been well studied. We evaluated whether age, breast density, self-reported breast lump, and previous mammography influence the performance of diagnostic mammography.From January 1996 through March 1998, prospective diagnostic mammography data from women aged 25-89 years with no previous breast cancer were linked to cancer outcomes data in six mammography registries participating in the Breast Cancer Surveillance Consortium. We used the final mammographic assessment at the end of the imaging work-up to determine abnormal mammographic examination rate, positive predictive value (PPV), sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve. We used age, breast density, prior mammogram, and self-reported breast lump jointly as predictors of performance. All statistical tests were two-sided.Of 41 427 diagnostic mammograms, 6279 (15.2%) were judged abnormal. The overall PPV was 21.8%, sensitivity was 85.8%, and specificity was 87.7%. Multivariate analysis showed that sensitivity and specificity generally declined as breast density increased (P =.007 and P<.001, respectively), that previous mammography decreased sensitivity (odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.36 to 0.74; P<.001) but increased specificity (OR = 1.43, 95% CI = 1.31 to 1.57; P<.001), and that a self-reported breast lump increased sensitivity (OR = 1.64, 95% CI = 1.13 to 2.38; P =.013) but decreased specificity (OR = 0.54, 95% CI = 0.49 to 0.59; P<.001). ROC analysis showed that higher breast density and previous mammography were negatively related to accuracy (P<.001 for both).Diagnostic mammography in women with signs or symptoms of breast cancer shows higher sensitivity and lower specificity than screening mammography does. Higher breast density and previous mammographic examination appear to impair performance.
Preventing progression of cardiac hypertrophy and development of heart failure by paricalcitol therapy in rats
Authors: Soochan Bae, Bhargavi Yalamarti, Qingen Ke, Sangita Choudhury, Hyeon Yu, S. Ananth Karumanchi, Paul Kroeger, Ravi Thadhani, Peter M. Kang
Journal: Cardiovascular Research (2011)

AimsVitamin D deficiency is associated with cardiac hypertrophy and heart failure, and vitamin D therapy prevents the progression of cardiac hypertrophy in animal models. Here, we examine whether vitamin D therapy prevents progression of pre-existing cardiac hypertrophy and development of heart failure.
Fertility Drugs and Young-Onset Breast Cancer: Results From the Two Sister Study
Authors: Chunyuan Fei, Lisa A. DeRoo, Dale P. Sandler, Clarice R. Weinberg
Journal: JNCI Journal of the National Cancer Institute (2012)

Background Fertility drugs stimulate hyperovulation, which may have implications for breast cancer. We examined the association between use of fertility drugs (clomiphene citrate [CC] and follicle-stimulating hormone [FSH]) and subsequent risk of young-onset (<50 years at diagnosis) breast cancer.
Preventive Psychiatry for the Family: Theory, Approaches, and Programs
Authors: WILLIAM M. BOLMAN
Journal: American Journal of Psychiatry (1968)

In this paper the author attempts to connect theory, general programmatic approaches, and specific programs related to family-oriented preventive programs in a systematic and meaningful way. His theoretical framework views the family as a flexible social organization—an open system subject to stress from its environment, which includes biologic, intrapsychic, and interpersonal forces as well as sociologic and community levels.
Bleomycin-Induced Chronic Lung Damage Does Not Resemble Human Idiopathic Pulmonary Fibrosis
Authors: GISELLA BORZONE, RODRIGO MORENO, RODRIGO URREA, MANUEL MENESES, MANUEL OYARZÚN, CARMEN LISBOA
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Administration of bleomycin into the lungs of experimental animals has been utilized as a model to understand human pulmonary fibrosis. Most of the studies, however, have focused on early stages of the lung reaction. We hypothesized that chronic stages of the model may not mimic idiopathic pulmonary fibrosis, since in preliminary studies, lung volume and compliance were not decreased. Eight male Sprague-Dawley rats receiving intratracheal bleomycin (0.5 U/100 g body weight) underwent measurement of FRC, inspiratory capacity, and lung compliance 120 d later. Lung histologic changes were evaluated using light microscopy. Eight rats without intervention served as controls. Results show that our model, in early stages, has histologic changes no different from those previously described elsewhere. In chronic stages, however, the model does not behave as a restrictive syndrome: FRC is normal or increased, whereas lung compliance is normal. Focal peribronchiolar inflammation and fibrosis associated with paracicatricial emphysematous changes are the main histologic features of long-term lung remodeling after bleomycin. We conclude that while the chronic stages of the model may be informative in understanding mechanisms of fibrosis, care should be taken not to extrapolate to human idiopathic pulmonary fibrosis. We speculate that the model might resemble a particular subgroup of human interstitial lung disease, namely, those involving peribronchiolar structures.
Right-Sided Congestive Heart Failure in Dogs Produced by Controlled Progressive Constriction of the Pulmonary Artery
Authors: JAMES O. DAVIS, ROBERT E. HYATT, DAVID S. HOWELL, ALFRED CASPER
Journal: Circulation Research (1955)

Right heart failure was produced in dogs by controlled progressive stenosis of the pulmonary artery. Cardiac enlargement, systemic venous engorgement, tachycardia, hepatomegaly and ascites were consistent findings. The course of cardiac failure was characterized by continual changes in cardiovascular hemodynamics; either cardiac decompensation became progressively severe or circulatory function improved and diuresis resulted. Sodium (Na) retention was always associated with high central venous pressure. Cardiac output was reduced during Na retention except during spontaneous anemia superimposed on cardiac failure. Glomerular filtration rate was frequently normal at the onset of cardiac failure.