tbuckley/cabot-search huggingface dataset:
Practice Patterns and Guideline Adherence of Medical Oncologists in Managing Patients with Early Breast Cancer
Authors: Jill A. Foster, Maziar Abdolrasulnia, Hamidreza Doroodchi, Joan McClure, Linda Casebeer
Journal: Journal of the National Comprehensive Cancer Network (2009)

Background Studies of adherence to breast cancer guidelines have often focused on primary therapies, but concordance with other guideline recommendations has not been examined as extensively. This study assesses the knowledge and practice patterns of medical oncologists in the United States to inform education and quality improvement initiatives that can improve breast cancer care. Methods A survey containing case vignettes and related questions was developed to examine oncologists' clinical decision-making in evaluating and treating women with early breast cancer. The instrument was distributed to a random sample of 742 oncologists in the United States and yielded 205 responses (27.6% response rate). Responses from 184 practicing medical oncologists were analyzed relative to the 2007 NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Results Most oncologists made guideline-consistent choices in clarifying indeterminate human epidermal growth factor 2 (HER2) status (85%), initial treatment for early breast cancer (95%), and postsurgical management of locally advanced breast cancer (82%). Guideline-discordant choices were seen in the lack of clip placement before neoadjuvant chemotherapy (36%), unnecessary use of PET scanning for initial assessment (34%), inappropriate assessment of menopausal status (33%), inappropriate use of tumor markers (22%), and use of chest imaging (16%) during posttherapeutic surveillance. Conclusions Oncologists often make guideline-consistent choices, but discordant clinical decisions may occur in important aspects of care for early breast cancer. Broadening the diffusion and adoption of guideline recommendations is an important mechanism for addressing these gaps and may substantially improve the quality of breast cancer care.
Month of Birth and Cancer Mortality&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: John C. Bailar, Joan M. Gurian
Journal: JNCI Journal of the National Cancer Institute (1964)

Journal Article Month of Birth and Cancer Mortality Get access John C. Bailar, III, M.D., John C. Bailar, III, M.D. National Cancer Institute,5Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Joan M. Gurian, B.S. Joan M. Gurian, B.S. National Cancer Institute,5Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 33, Issue 2, August 1964, Pages 237–242, https://doi.org/10.1093/jnci/33.2.237 Published: 01 August 1964 Article history Received: 22 January 1964 Published: 01 August 1964
Effect of nucleated marrow cell dose on relapse and survival in identical twin bone marrow transplants for leukemia.
Authors: A. John Barrett, Olle Ringdén, Mei-Jie Zhang, Asad Bashey, Jean-Yves Cahn, Mitchell S. Cairo, Robert Peter Gale, Alois Gratwohl, Franco Locatelli, Rodrigo Martino, Kirk R. Schultz, Pierre Tiberghien
Journal: Blood (2000)
Chemotherapy for advanced and recurring basal cell carcinoma (BCC) with docetaxel and cisplatin
Authors: E. J. Buarque
Journal: Journal of Clinical Oncology (2007)

16546 Background: Up to 85% of all BCC are localized in head and neck region and can usually be cured by surgery. The recurrent BCC (rBCC) may grow under normal skin and have a more agressive behaviour. Sometimes, when it is discovered could be unresectable or lead to a great deformity if removed. Methods: Between December 2000 and December 2003 we have treated 3 patients (pts), 2 male/1 female with invasive rBCC with osseous involvement in retro-orbital region, invasion of paranasal and ethmoidal sinus, nasal cavity and orbital bone. Medium size 7 cm. Two pts have already received radiotherapy (RXT) one and two years before. Therapy consisted of docetaxel 35 mg/m2 and cisplatin 25 mg/m2 D1,D8 and D15 with one or two weeks interval. Results: They achieved complete response at the 6th cycle and received more 3 cycles- total of nine cycles.The pt that not had RXT before, received 5000 cGy as consolidation. Reconstrutive surgery was not necessary and two pts recovered the vision of the affected eye. Toxicity was mild in all pts with no grade 3 or 4. All pts are in complete remission until now. Conclusions: Contrary to previous reports, advanced BCC is responsive to chemotherapy with a longlasting response even after RXT, improving the quality of life and perhaps survival of pts with rBCC. No significant financial relationships to disclose.
Late-breaking abstract: Influenza A virus infection reduces alveolar fluid clearance by activation of AMPK and subsequent reduction of Na,K-ATPase protein abundance
Authors: Christin Becker, Emilia Lecuona, Thorsten Wolff, Istvan Vadasz, Rory Morty, Jürgen Lohmeyer, Werner Seeger, Iasha Sznajder, Gokhan Mutlu, Scott Budinger, Susanne Herold
Journal: European Respiratory Journal (2014)

Influenza A virus (IV) infection can cause primary viral pneumonia resulting in acute respiratory distress syndrome (ARDS) associated with edema formation. As the capability to clear excessive water from the alveolar compartment is of particular importance for the patients9 survival, we aimed to elucidate mechanism that diminish alveolar fluid clearance (AFC) after IV-infection.  The regulation of Na,K-ATPase after IV-infection was determined in primary human or murine alveolar epithelial cells (AEC) in monoculture or coculture with murine alveolar macrophages and in mouse lung homogenates (LH) by Western blot or flow cytometric analysis. AFC was measured 8 hours post infection in vitro or 2 days post infection in vivo.  We found significantly reduced rates of AFC in IV-infected mice as well as a reduction of Na,K-ATPase-dependant fluid clearance after IV-infection in vitro. Na,K-ATPase alpha1 subunit protein levels were significantly reduced in AEC and LH after IV-infection, partly induced by presence of infected macrophages or accordingly by addition of recombinant TRAIL or IP10. Furthermore we could show that the downregulation of Na,K-ATPase was mediated by Ca2+ signalling and subsequent activation of CaMKKbeta and AMPK. Interfering with this pathway in vivo by adenoviral delivery and overexpression of a dominant-negative form of AMPK could restore AFC after IV-infection.  We provide evidence that AFC in IV-infection is impaired by affecting Na,K-ATPase expression levels and that targeting the underlying signalling pathway might provide targets for new treatments increasing edema clearance in IV-induced ARDS.αα
Potential therapeutic significance of CIK cells in gefitinib resistant NSCLC with EGFR mutations
Authors: Chen He, Baodan Yu, Junli Wang, Jun Xu
Journal: European Respiratory Journal (2011)

The gefitinib resistant limits its efficacy in the treatment of non-small cell lung cancer (NSCLC), thus, we tried to evaluate the drug-resistance reversal to gefitinb by the cytokine induced killer (CIK) cells. The gefitinib resistant cell line PC-9/GR was developed from a NSCLC cell line PC-9 harboring EGFR E746-A750 deletion by gefitinib selection. The effect of CIK cells alone or combination with gefitinib on PC-9/GR was determined by the cytotoxicity in vitro as well as growth inhibition of tumors in the nude mice. The immune cell subsets and cytokines expression before and after CIK cells infusion in six patients with tumors were also analyzed. An additional EGFR T790M mutation was obtained in the PC-9/GR with a resistance index of 100.16 to gefitinib. The induction of G0/G1 arrest and apoptosis and inhibition of activation of p-EGFR, p-ERK and p-AKT signaling were significantly attenuated in PC-9/GR following treated with gefitinib. Interestingly, an evident cytolytic activity was presented in the PC-9 and PC-9/GR treated with CIK cells in vitro and vivo, however, there was no significant difference in the cytolytic activity of CIK cells against PC-9 and PC-9/GR targets. In addition, a synergistic cytotoxicity was obtained by the combination CIK cells and geifitinb in PC-9/GR through the inhibition of p-ERK and p-AKT activity by CIK cells. Finally, CIK cells infusion could significantly increase the frequency and function of NK cells and decrease the frequency of Treg cells and level of TGF-β in patients with tumors. In conclusion, CIK cells have a strong cytotoxicity to PC-9/GR and a clinical immune modulation, thus it maybe a favorable treatment of NSCLC with EGFR mutations.
Neuroendocrine Prostate Cancer: Subtypes, Biology, and Clinical Outcomes
Authors: Rahul Aggarwal, Tian Zhang, Eric J. Small, Andrew J. Armstrong
Journal: Journal of the National Comprehensive Cancer Network (2014)

Neuroendocrine prostate cancer (NEPC) encompasses various clinical contexts, ranging from the de novo presentation of small cell prostatic carcinoma to a treatment-emergent transformed phenotype that arises from typical adenocarcinoma of the prostate. The development of resistance to potent androgen receptor signaling inhibition may be associated with the emergence of aggressive phenotype, advanced castration-resistant NEPC. Clinically, small cell prostate cancer and NEPC are often manifested by the presence of visceral or large soft tissue metastatic disease, a disproportionately low serum prostate-specific antigen level relative to the overall burden of disease, and a limited response to targeting of the androgen signaling axis. These tumors are often characterized by loss of androgen receptor expression, loss of retinoblastoma tumor suppressor copy number or expression, amplification of Aurora kinase A and N-Myc, and activation of the PI3K pathway. However, a consensus phenotype-genotype definition of NEPC has yet to emerge, and molecularly based biomarkers are needed to expand on traditional morphologic and immunohistochemical markers of NEPC to fully define the spectrum of this aggressive, androgen receptor-independent disease. Emerging studies implicate a shared clonal origin with prostatic adenocarcinoma in many cases, with the adaptive emergence of unique cellular programming and gene expression profiles. Ongoing clinical studies are focused on developing novel targeted therapeutic approaches for this high-risk, lethal subset of disease, to improve on the limited durations of response often observed with traditional platinum-based chemotherapy.
KIAA1324 Suppresses Gastric Cancer Progression by Inhibiting the Oncoprotein GRP78
Authors: Jin Muk Kang, Sujin Park, Staci Jakyong Kim, Hyojung Kim, Bona Lee, Junil Kim, Jinah Park, Shin Tae Kim, Han-Kwang Yang, Woo Ho Kim, Seong-Jin Kim
Journal: Cancer Research (2015)

Recent advances in genome and transcriptome analysis have contributed to the identification of many potential cancer-related genes. Furthermore, biological and clinical investigations of the candidate genes provide us with a better understanding of carcinogenesis and development of cancer treatment. Here, we report a novel role of KIAA1324 as a tumor suppressor in gastric cancer. We observed that KIAA1324 was downregulated in most gastric cancers from transcriptome sequencing data and found that histone deacetylase was involved in the suppression of KIAA1324. Low KIAA1324 levels were associated with poor prognosis in gastric cancer patients. In the xenograft model, KIAA1324 significantly reduced tumor formation of gastric cancer cells and decreased development of preformed tumors. KIAA1324 also suppressed proliferation, invasion, and drug resistance and induced apoptosis in gastric cancer cells. Through protein interaction analysis, we identified GRP78 (glucose-regulated protein 78 kDa) as a KIAA1324-binding partner. KIAA1324 blocked oncogenic activities of GRP78 by inhibiting GRP78-caspase-7 interaction and suppressing GRP78-mediated AKT activation, thereby inducing apoptosis. In conclusion, our study reveals a tumor suppressive role of KIAA1324 via inhibition of GRP78 oncoprotein activities and provides new insight into the diagnosis and treatment of gastric cancer.
Long-term follow-up of patients with Herlitz-type junctional epidermolysis bullosa
Authors: W.Y. Yuen, J.C. Duipmans, B. Molenbuur, I. Herpertz, J.M. Mandema, M.F. Jonkman
Journal: British Journal of Dermatology (2012)

Junctional epidermolysis bullosa, type Herlitz (JEB-H) is a rare, autosomal recessive disease caused by absence of the epidermal basement membrane adhesion protein laminin-332. It is characterized by extensive and devastating blistering of the skin and mucous membranes, leading to death in early childhood.To present the results of the long-term follow-up of a cohort of patients with JEB-H, and to provide guidelines for prognosis, treatment and care.All patients with JEB-H included in the Dutch Epidermolysis Bullosa (EB) Registry between 1988 and 2011 were followed longitudinally by our EB team. Diagnosis was established using immunofluorescence antigen mapping, electron microscopy and DNA analysis.In total, we included 22 patients with JEB-H over a 23-year period. Their average age at death was 5.8 months (range 0.5-32.6 months). The causes of death were, in order of frequency: failure to thrive, respiratory failure, pneumonia, dehydration, anaemia, sepsis and euthanasia. The pattern of initial weight gain was a predictor of lifespan in these patients. Invasive treatments to extend life did not promote survival in our patients.It is important to diagnose JEB-H as soon as possible after birth so that the management can be shifted from life-saving to comfort care. The palliative end-of-life care can take place in hospital, but is also safe in the home setting. Suffering in patients with JEB-H can become so unbearable that in some patients who do not respond to adequate analgesic and sedative treatment, newborn euthanasia, performed according to the Groningen protocol, is legally permitted in the Netherlands.
Association of "DNA damage signature" with poor outcome in early prostate cancer.
Authors: Mahesh Iddawela, Carmel Pazaro, Mitchell Lawrence, Luc Furic, Renea Taylor, Gail Risbridger
Journal: Journal of Clinical Oncology (2015)

13 Background: Whole genome and matching normal tissue analyses in prostate cancer patients have shown that widespread genomic changes occur in multiple distant regions of the genome simultaneously (Baca et al., Cell. 2013). The inherent genomic instability in prostate cancers causes activation of pathways involved in DNA damage, which could be a prognostic and potentially predictive marker for treatment with agents impacting DNA repair (e.g. PARP inhibitors). Using a published dataset, a “DNA damage signature” was generated to test its role as a potential prognostic marker. Methods: A 10-gene signature was generated, using the top 9 genes (MXD3, ZMYND19, BANF1, TOMM40, UBE2S, SNRPF, RPP21, CDK2AP2 and H2AFX) correlated with H2AFX expression, which is known to be unregulated upon DNA damage. TP53 was added due to its significant role in this pathway. This signature was then assessed in The Cancer Genome Atlas dataset (TCGA, unpublished data at NCI) as a discovery set and then validated in the MSK dataset (Taylor et al., 2010) using mutation, copy number, mRNA and proteomic data. Results: Genes in the signature were altered in 31% (77/246) of patients, by amplification and over expression compared to normal. The most frequent alterations were found in TP53 (15%), MXD3 (7%), BANF1 (7%), UBE28 (7%) and CDK2AF2 (7%). Analysis of protein changes associated with alteration in genomic signature showed upregulation of FOXO3, BCL2L1, BAK1 and PCNA (P&lt;0.05). There were significant correlations between the signature and Gleason score (p=0.0015), PTEN (p=0.003) &amp; RAD51 gene expression (p&lt;0.001), but not with ERG,PSA, PIK3CA or BRCA2. Patients with alterations were associated with poor disease free survival (DFS) (p=0.002). When expression was assessed in the validation set, 73%(62/85) samples showed altered gene signatures and those with alterations also had poor DFS (p=0.003). Conclusions: The DNA damage signature can be used to define a group of patients with poor outcome and has the potential to be used as prognostic marker in treatment decisions in early prostate cancer patients.
Analysis of Surface Antigens on Simian Virus 40-Transformed Cells. I. Unique Antigenicity of Simian Virus 40-Transformed Outbred Hamster Kidney Cell Lines2
Authors: Jeffrey J. Collins, Paul H. Black
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Analysis of Surface Antigens on Simian Virus 40-Transformed Cells. I. Unique Antigenicity of Simian Virus 40-Transformed Outbred Hamster Kidney Cell Lines Get access Jeffrey J. Collins, Jeffrey J. Collins Departments of Microbiology and Molecular Genetics and of Medicine, Harvard Medical School, and the Infectious Disease Unit of the Medical Service, Massachusetts General Hospital, Boston, Massachusetts 02114 Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul H. Black Paul H. Black 6 Departments of Microbiology and Molecular Genetics and of Medicine, Harvard Medical School, and the Infectious Disease Unit of the Medical Service, Massachusetts General Hospital, Boston, Massachusetts 02114 6Address reprint requests to: Dr. Paul H. Black, Infectious Disease Unit, Massachusetts General Hospital, Boston, Mass. 02114. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 1, July 1973, Pages 95–114, https://doi.org/10.1093/jnci/51.1.95 Published: 01 July 1973 Article history Received: 31 July 1972 Revision received: 12 December 1972 Accepted: 02 February 1973 Published: 01 July 1973
Diagnostic yield of specific inhalation challenge in patients with hypersensitivity pneumonitis
Authors: Monica Sanchez, Ana Villar, Maria Jesus Cruz, Ferran Morell, Xavier Muñoz
Journal: European Respiratory Journal (2012)

Introduction: Hypersensitivity pneumonitis (HP) is a potentially serious illness that may progress to pulmonary fibrosis and chronic respiratory insufficiency. Reliable methods are needed to diagnose the condition and, if possible, to identify the causative agent. The aim of the study was to stablish the diagnostic yield of Specific Inhalation Challenge (SIC) in patients with HP.  Material and methods: All patients with suspected HP in whom SIC were performed between June 1995 and December 2010 (n= 113) were included. Diagnosis of HP was established on the basis of internationally accepted criteria ( M.Girard, et al. Allergy 2009; 64:322-334 ). The SIC was considered positive in the case of a decrease >15% in FVC and/or a decrease >20% in TLCO, or a decrease in FVC between 10-15% accompanied by an increase in temperature of 0.5oC within 24h of the inhalation of the antigen ( Morell F, et al. Medicine 2008; 2:110-130 ).  Results: Eighty-eight patients were diagnosed with HP. In 68 the SIC was positive and in 45 negative; four false positives (3.5%) and 24 false negatives (21.2%) were recorded. The sensitivity and specificity of the test were 72.7% and 84% respectively, with a positive predictive value of 94% and a negative predictive value of 47%. Having HP caused by an antigen other than birds or fungi was a predictor of a false negative result (p=0.035).  Conclusions: In HP a positive SIC practically confirms the diagnosis, while a negative result does not rule it out.  Project partially funded by FIS PI 10/01577 (Instituto de Salud Carlos III) and Beca SEPAR 2010.
Beyond Music: Auditory Temporary Threshold Shift in Rock Musicians after a Heavy Metal Concert
Authors: A B Drake-Lee
Journal: Journal of the Royal Society of Medicine (1992)

Audiometry was undertaken before and within half an hour following a heavy metal concert to assess evidence of noise damage. Of the four members tested, one member wore an ear defender in his right ear during the period of noise exposure. All unprotected ears showed a temporary threshold shift which was maximum in the lower frequencies. There was some evidence that early noise damage had occurred with a dip at 6 kHz. The role of music as noise and its potential to damage the cochlea are discussed.
Reduced Inotropic Reserve and Increased Susceptibility to Cardiac Ischemia/Reperfusion Injury in Phosphocreatine-Deficient Guanidinoacetate- <i>N</i> -Methyltransferase–Knockout Mice
Authors: Michiel ten Hove, Craig A. Lygate, Alexandra Fischer, Jürgen E. Schneider, A. Elisabeth Sang, Karen Hulbert, Liam Sebag-Montefiore, Hugh Watkins, Kieran Clarke, Dirk Isbrandt, Julie Wallis, Stefan Neubauer
Journal: Circulation (2005)

Background— The role of the creatine kinase (CK)/phosphocreatine (PCr) energy buffer and transport system in heart remains unclear. Guanidinoacetate- N -methyltransferase–knockout (GAMT −/− ) mice represent a new model of profoundly altered cardiac energetics, showing undetectable levels of PCr and creatine and accumulation of the precursor (phospho-)guanidinoacetate (P-GA). To characterize the role of a substantially impaired CK/PCr system in heart, we studied the cardiac phenotype of wild-type (WT) and GAMT −/− mice. Methods and Results— GAMT −/− mice did not show cardiac hypertrophy (myocyte cross-sectional areas, hypertrophy markers atrial natriuretic factor and β-myosin heavy chain). Systolic and diastolic function, measured invasively (left ventricular conductance catheter) and noninvasively (MRI), were similar for WT and GAMT −/− mice. However, during inotropic stimulation with dobutamine, preload-recruitable stroke work failed to reach maximal levels of performance in GAMT −/− hearts (101±8 mm Hg in WT versus 59±7 mm Hg in GAMT −/− ; P &lt;0.05). 31 P-MR spectroscopy experiments showed that during inotropic stimulation, isolated WT hearts utilized PCr, whereas isolated GAMT −/− hearts utilized P-GA. During ischemia/reperfusion, GAMT −/− hearts showed markedly impaired recovery of systolic (24% versus 53% rate pressure product recovery; P &lt;0.05) and diastolic function (eg, left ventricular end-diastolic pressure 23±9 in WT and 51±5 mm Hg in GAMT −/− during reperfusion; P &lt;0.05) and incomplete resynthesis of P-GA. Conclusions— GAMT −/− mice do not develop hypertrophy and show normal cardiac function at low workload, suggesting that a fully functional CK/PCr system is not essential under resting conditions. However, when acutely stressed by inotropic stimulation or ischemia/reperfusion, GAMT −/− mice exhibit a markedly abnormal phenotype, demonstrating that an intact, high-capacity CK/PCr system is required for situations of increased cardiac work or acute stress.
The preliminary proteomics analysis of bone marrow eosinophil progenitors in allergic asthmatic mice
Authors: Tao Fan, Gang Wang, Deyun Cheng, Bing Mao
Journal: European Respiratory Journal (2012)

Introduction:  The early-stage airway inflammation of allergic asthma is associated with bone marrow (BM) progenitor cell commitment towards eosinophilic differentiation after allergen challenge. We sought to identify the differently expressed proteins by novel proteomic technology from the BM CD 34  +  progenitor cells of asthmatic mice and analyzed their bioinformatics.   Methods:  The magnetic activated cell sorting separation coupled to fluorescence activated cell sorting separation strategy was used to harvest BM CD34 +  progenitor cells from naive and ovalbumin-challenged asthmatic mice. Isobaric tags for relative and absolute quantitation combined with 2D nano LC-MS/MS technology was employed to profile proteome alterations in CD 34  +  progenitor cells. The analysis of bioinformatics was performed finally.   Results:  Twenty-five proteins with 18 up-regulated and 7 down-regulated ones were identified. In the dysregulated proteins, 4 clusters of proteins were observed around collagen groups, ACTN1/Myosin groups, Mdh2 and Serpinh1, predominantly participating in pathways of focal adhesion, ECM-receptor interaction, tight junction and regulation of actin cytoskeleton.   Conclusions:  Collagen group and ACTN1 related focal adhesion, ECM-receptor interaction and regulation of actin cytoskeleton could be the key pathway in bone marrow response of asthma.