tbuckley/cabot-search huggingface dataset:
Use of serum proteins identified by proteomics to predict prognosis in patients with metastatic renal cell cancer (mRCC) and comparison to the currently used MSKCC survival model
Authors: J. Vermaat, I. van der Tweel, N. Mehra, S. Sleijfer, J. Y. Engwegen, C. M. Korse, J. H. Schellens, J. B. Haanen, J. H. Beijnen, E. E. Voest
Journal: Journal of Clinical Oncology (2009)

11078 Background: In mRCC the Memorial Sloan-Kettering Cancer Center (MSKCC) risk model (Motzer et al.,JCO2002) is widely used for clinical trial design and patient management. To improve this model, we searched for serum proteins associated with overall survival (OS) using proteomics and determined their potential contribution to the composition of better prognostic models. Methods: Sera from 125 mRCC patients, mostly interferon-treated, collected between 2001–2006 in three Dutch Cancer Centers, were screened by SELDI-TOF mass spectrometry (MS). Identified proteins were analyzed for their association with OS by Cox regression analysis and Kaplan-Meier curves. Three proteins were subsequently validated with conventional ELISAs and immunoturbidimetry. Computed Cox PH regression models were individually compared with the Akaike's Information Criteria (AIC). The final model was statistically bootstrapped to strengthen its validity. Results: SELDI-TOF MS successfully detected eleven prognostic proteins associated with OS. The strongest prognostic proteins, apolipoprotein A-II (ApoA2), serum amyloid alpha (SAA), and transthyretin were validated by alternative methods and confirmed for their association with OS (p=7.4×10 -9 , p=3.2×10 -8 and p=0.0002, respectively). Stepwise multivariable Cox regression analysis provided an optimal combination of prognostic factors; ApoA2, SAA, LDH, performance status and number of metastasis sites. Subsequent categorization of patients into three risk groups generated a novel survival model that robustly predicts patient prognosis (AIC=684 and p=5.8×10 -15 ) with increased accuracy compared to the MSKCC model (AIC=719, p=2.0×10 -7 ). Bootstrapping our model resulted in an optimism correction of 0.04 (R 2 =0.45). Initiating systemic therapy according to novel proposed model instead of the MSKCC model would result in a change of treatment in 14% of the patients. Conclusions: Using proteomics, serum proteins associated with OS in mRCC patients can be identified. Incorporating some of these factors together with traditional risk factors yields a prognostic model outperforming the MSKCC risk model thereby further improving patients’ management. No significant financial relationships to disclose.
Detection of EGFR mutation in tissue and peripheral blood by denaturing high performance liquid chromatography (DHPLC) for patients with advanced non-small cell lung cancer
Authors: J. Wang, H. Bai, S. Wang, J. Zhao, X. Wang, T. An, L. Yang
Journal: Journal of Clinical Oncology (2008)

11013 Background: Goal of this study is to apply DHPLC as a screening system of detection of EGFR mutation (M) for large scaled population, and to evaluate the correspondence between EGFR M in tissue(T) and in matched serum DNA and their clinical significance in ANSCLC Methods: 230 primary NSCLC T and matched peripheral blood samples(MPBS) were obtained. Special polymerase chain reaction (PCR) of EGFR exon 19 and 21 were performed After DNA extraction. DHPLC was applied to detect the M status in matched samples which were confirmed by standard DNA sequencing. Results: EGFR M was found by DHPLC to be 34.3%(77/230) in T and 34.3%(79/230) in MPBS. 70 pair samples with and without EGFR M were confirmed by sequencing. The sensitivity and specificity of DHPLC of detecting EGFR M were 95% and 93%, respectively, the correlation index(CI) was 0.87 (P<0.001). Among 77 patients who were found to have EGFR M in tissues, 63 was detected to harbour EGFR M in peripheral blood, and high correspondence of EGFR M status in T and in MPBS were confirmed( CI=0.73, P<0.001). EGFR M in both T and B were correlated with histology type, smoking status, and response. The P with EGFR mutations in T and B had longer PFS than the ones without EGFR M (12.8ms Vs 6.4 ms in tissues, p=0.032; 10.2 ms Vs 5.0ms in blood, p=0.04). No significant difference was found for MST of P with and without EGFR M in T and B(P>0.05). Conclusions: The DHPLC may serve as a primary screening method for detecting of EGFR M, EGFR M in plasma DNA was highly consistent with in T and could be a useful marker to predict p response to Gefitinib. Further study to confirm its clinical application is merited. No significant financial relationships to disclose.
India draws a red line under antibiotic misuse
Authors: Cheryl Travasso
Journal: BMJ (2016)

India’s health ministry has launched a campaign aimed at stopping the misuse of antibiotics.

Introduced at the inaugural session of a three day international conference on antimicrobial resistance in New Delhi, the campaign highlighted the importance of taking antibiotics only when prescribed by a doctor, and the need to finish the course.

The Medicines with the Red Line public awareness campaign had several key messages: learn how to identify prescription drugs; curb self medication; and become …
Protein phylogeny gives a robust estimation for early divergences of eukaryotes: phylogenetic place of a mitochondria-lacking protozoan, Giardia lamblia.
Authors: T Hashimoto, Y Nakamura, F Nakamura, T Shirakura, J Adachi, N Goto, K Okamoto, M Hasegawa
Journal: Molecular Biology and Evolution (1994)

A partial nucleotide sequence of the mRNA encoding a major part of elongation factor 1 alpha (EF1 alpha) from a mitochondria-lacking protozoan, Giardia lamblia, was reported, and the phylogenetic relationship among lower eukaryotes was inferred by the maximum-likelihood and maximum-parsimony methods of protein phylogeny. Both the methods consistently demonstrated that, G. lamblia among the four protozoan species being analyzed, is the earliest offshoot of the eukaryotic tree. Although the Giardia EF1 alpha gene showed an extremely high G+C content as compared with those of other protozoa, it was concentrated only at the third codon positions, resulting in no remarkable differences of amino acid frequencies vis-à-vis those of other species. This clearly suggests (a) that the amino acid frequencies of conservative proteins are free from the drastic bias of genome G+C content, which is a serious problem in the widely used tree of ribosomal RNA, and (b) that protein phylogeny gives a robust estimation for the early divergences in the evolution of eukaryotes.
Frequency, indications, outcomes, and factors associated with successful opioid rotation in cancer patients presenting to an outpatient supportive care center.
Authors: Akhila Sunkepally Reddy, Sriram Yennurajalingam, Kalyan Pulivarthi, Jung Hye Kwon, Susan Frisbee-Hume, Eduardo Bruera
Journal: Journal of Clinical Oncology (2012)

e19599 Background: Opioids are first line medications for cancer pain. Opioid rotation (OR) is recommended for uncontrolled cancer pain (UCP) and opioid induced neurotoxicity (OIN). Limited data exist on frequency, indications and outcomes of OR in ambulatory cancer patients in outpatient setting. Methods: We reviewed consecutive outpatient visits to the Supportive Care Center in 2008 for OR. Data regarding demographics, Edmonton Symptom Assessment Scale (ESAS), Memorial Delirium Assessment Scale, pain characteristics, opioid use, indication for OR, outcomes, morphine equivalent daily dose (MEDD) and supportive counseling was collected in all patient visits who followed up within 5 weeks of OR. Successful OR was defined as a 2 point or 30% reduction in ESAS symptom score, resolved symptoms of OIN and continuation of new opioid at follow up. Stepwise logistic regression analysis was performed to determine factors associated with successful OR. Results: 244/2471(10%) patient visits had OR and 142 (58%) were followed up within 5 weeks. 40% (57/142) were consult visits. 74% (105/142) were white, 60% (85/142) male. Median age and performance status were 55 and 1. GI (24%) and lung (22%) were the most common cancer types with 77% (110/142) advanced cancer. Median time (Q1-Q3) between OR and follow up was 14 (7-21) days. Most common indications for OR were UCP 82% and OIN 13%. 34% had partial OR and 16% had more than one reason for OR. Pain characteristics were 49% nociceptive, 21% mixed and 11% neuropathic. Median (Q1-Q3) pain and symptom distress score improved: -2 (-4-0, P=.003) and -5 (-14-7, P=.004). Median MEDD (Q1-Q3) decreased from 162 (90-287) to 156 (90-280, P=.82). 66% (94/142) had successful OR. Fentanyl (34%) before and Methadone (55%) after OR were most common opioids. 17% (24/142) had another OR at follow up visit. High MEDD (P=.05) prior to OR was associated with successful OR. Conclusions: 10% of outpatient visits had OR with a 66% success rate in treating UCP and OIN. Further research is needed to determine predictors of successful OR.
The Surgery of the Sympathetic Nervous System
Authors: H J ATKINS
Journal: JAMA (1934)

jANUARY 19, 1935 (of the Siedentopf type) acts.Although a good plate (XIII, facing page 154) is given of spectra photographed by Gerlach and Schweitzer for deducing the composition of a mixture of tin and a small percentage of cadmium, no reference is made in the text to the diagram or to the fundamental principle underlying photographic spectrophotometry.There is a good section on autochrome photography but no account of ordinary photographic processes, or of the d ensity curves of photographic plates.There is an interesting laboratory experiment devised by Dr. Grimsehl himself to explain the formation of rainbows.
Identification of a Tumor-Associated Antigen in Cervical Carcinoma by Two-Dimensional (Crossed) Immunoelectrophoresis2
Authors: Wen-Tsuo Chiang, E. Russell Alexander, George E. Kenny
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Identification of a Tumor-Associated Antigen in Cervical Carcinoma by Two-Dimensional (Crossed) Immunoelectrophoresis Get access Wen-Tsuo Chiang, M.D., Wen-Tsuo Chiang, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Russell Alexander, M.D., E. Russell Alexander, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar George E. Kenny, Ph.D. George E. Kenny, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 1, January 1977, Pages 43–48, https://doi.org/10.1093/jnci/58.1.43 Published: 01 January 1977 Article history Received: 01 March 1976 Accepted: 14 June 1976 Published: 01 January 1977
Association between activation of ErbB pathway genes and survival following gefitinib treatment in advanced BAC (SWOG 0126)
Authors: W. A. Franklin, K. Chansky, P. H. Gumerlock, F. R. Hirsch, H. West, J. J. Crowley, D. R. Gandara
Journal: Journal of Clinical Oncology (2004)

7015 Background: Bronchioloalveolar carcinoma (BAC) and its variants are subtypes of pulmonary adenocarcinoma characterized by in situ growth along alveolar septae. We have previously shown (Franklin: ASCO, 2003) that BAC expresses both ErbB1 (EGFR) and ErbB2 (HER2) and exhibits activation of downstream signaling pathways reflected in phosphorylation of Akt and MAPK (Erk1/2). We hypothesized that biologic correlates of ErbB pathways in patient tumor tissue would predict benefit from Gefitinib in patients with BAC treated on S0126. Methods: Paraffin sections from 68 chemo-naïve and 31 previously treated patients were evaluated for the presence of tumor, cell type, grade, stromal invasion, mucin production, ErbB1, ErbB2, Ki-67, as well as pMAPK and pAKT, nuclear (N) and cytoplasmic (C). Each cell compartment was scored by two observers using the formula: % tumor cells positive (in 10% increments) X intensity of staining (0–4+ scale) = labeling score. Ki-67 was reported as percentage of tumor cells positive. Results: Pearson correlations (table) and survival analysis by Kaplan Meyer analysis in chemo-naïve patients are summarized below. There were significant correlations (**p<0.001) between ErbB2 and pMAPK (N and C), but not for ErbB1. There was a significant survival advantage for low (<=100) pMAPk N score (p=.02). A combination index of low ErbB2 (<=150) and low pMAPK(N) (<=100) also predicted better survival (p<0.01). ErbB1, pAKT and Ki-67 levels were not associated with outcome. Conclusions: 1) Low pMAPK(N) and combined low ErbB2 and pMAPK(N) predict increased survival with Gefitinib therapy in patients with advanced BAC. 2) These data suggest that dual inhibition of ErbB1 and ErbB2 may lead to improved therapeutic efficacy. 3) Correlations with histologic subtypes are ongoing. (CA32102, CA38926, CA58187) Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca SWOG
An open-label positron emission tomography (PET) study to investigate and quantify brain and tumor penetration of carbon-11 labeled lapatinib in patients with HER2-overexpressing (HER2+) advanced or metastatic breast cancer (MBC).
Authors: R. C. Coombes, J. A. Reise, M. Lau, S. C. Carme, G. E. Searle, M. Huiban, P. Burgess, K. Koch, A. Das-Gupta, A. Saleem
Journal: Journal of Clinical Oncology (2011)

TPS107 Background: Patients with HER2+ breast cancer tend to develop visceral metastases. Several anti-cancer agents including trastuzumab are not believed to readily cross the blood-brain barrier (BBB); hence, central nervous system (CNS) disease progression is emerging as an important clinical problem in this patient population. Although preclinical data suggest that lapatinib brain concentrations are low in healthy animals, probably due to the BBB efflux transporters, observations from clinical studies suggest lapatinib treatment might be associated with reduced CNS tumor growth. One hypothesis is that disruption of the BBB by tumors circumvents the usual protective function of transporters or that inhibition of efflux transporters by lapatinib enhances accumulation upon repeat dosing. The role of lapatinib in prevention of brain metastases is currently explored in a Phase III trial, EGF 111438 (CEREBREL). Methods: In order to directly assess if lapatinib penetrates into the brain and brain metastases, an open-label, non-randomized study using carbon-11 labeled [11C] lapatinib is performed in patients with HER2+ MBC. A minimum of 10 patients with an ECOG of < 3 into two cohorts: (a) with at least one 1 cm diameter brain metastasis or (b) without brain metastases. Two PET scans are performed in each pt following intravenous administration of a microdose of [11C] lapatinib – (1) in lapatinib -naïve patients and (2) at steady state lapatinib, after treatment with unlabelled oral lapatinib 1500mg OD for 8 days. [11C] lapatinib time-activity curves are generated for normal brain and brain metastases, the PET volume of distribution in brain calculated and penetration of [11C] lapatinib into brain quantified. Analysis of brain PET data is explorative as [11C] lapatinib is a new tracer. Therefore, this study investigates both the difference in lapatinib brain penetration between patients with and without brain metastases, as well as the effect of low and high concentrations of lapatinib on the BBB efflux system.
Long-term survival of ipilimumab-naive patients (pts) with advanced melanoma (MEL) treated with nivolumab (anti-PD-1, BMS-936558, ONO-4538) in a phase I trial.
Authors: F. Stephen Hodi, Mario Sznol, Harriet M. Kluger, David F. McDermott, Richard D. Carvajal, Donald P. Lawrence, Suzanne Louise Topalian, Michael B. Atkins, John D. Powderly, William Howard Sharfman, Igor Puzanov, David C. Smith, Philip D. Leming, Evan J. Lipson, Janis M. Taube, Robert Anders, Christine E. Horak, Georgia Kollia, Ashok Kumar Gupta, Jeffrey Alan Sosman
Journal: Journal of Clinical Oncology (2014)

9002 Background: We have shown that nivolumab, a fully human IgG4 PD-1 immune-checkpoint inhibitor antibody, is tolerable and active in pts with advanced solid tumors in a large phase I trial (Topalian et al. N Eng J Med 366:2443-54, 2012). For the MEL pts in this trial, we report long-term clinical activity, pts' response off therapy, tumor PD-1 ligand (PD-L1) expression associated with survival endpoints, and for the first time, 3-y overall survival (OS). Methods: Previously treated advanced MEL pts with no prior ipilimumab therapy received nivolumab (0.1, 0.3, 1, 3, or 10 mg/kg IV) Q2Wk for ≤96 wk and were evaluated for OS and progression-free survival (PFS). PD-L1 tumor cell membrane expression was retrospectively assessed in archival specimens by a Dako immunohistochemistry assay with ≥5% tumor cells designated as PD-L1(+). Results: From 2008-2012, 107 MEL pts initiated treatment with nivolumab; 25% had ≥3 prior therapies. Across doses, the 2- and 3-y OS rates were 48 and 41%, respectively (Table). For the 34/107 (32%) pts with objective responses (OR; RECIST), median response duration was 22.9 mo. Twenty-four OR pts stopped nivolumab for reasons other than disease progression; 11 (46%) maintained responses for ≥24 wk off drug (range: 24, 56+ wk). Four (4%) pts had unconventional "immune-related" responses. In a subset of pts with evaluable tumor samples (41/107), pts with PD-L1(+) and (–) tumors (n=18 and 23, respectively) had median OS of not reached and 12.5 mo; median PFS was 9.1 mo and 1.9 mo. Safety has been previously reported (Sznol et al. J Clin Oncol 31:abs CRA9006, 2013). Conclusions: In advanced MEL pts, nivolumab demonstrated favorable 2- and 3-y OS rates, durable responses with a number persisting off therapy, and an acceptable safety profile. Additional analyses will be presented by pts' characteristics across the full population, the long-term survival subgroup, and the PD-L1(+/–) tumor subgroups. Ongoing phase III trials are further evaluating nivolumab for MEL pts and PD-L1 as a potential predictive biomarker for response to nivolumab. Clinical trial information: NCT00730639. OS rate* n=107 % (95% CI) Pts at risk 1 y 63 (53, 71) 63 2 y 48 (38, 57) 44 3 y 41 (31, 51) 22 *September 2013 analysis.
Pulmonary Function in Patients With Germ Cell Cancer Treated With Bleomycin, Etoposide, and Cisplatin
Authors: Jakob Lauritsen, Maria Gry Gundgaard Kier, Mikkel Bandak, Mette Saksø Mortensen, Frederik Birkebæk Thomsen, Jann Mortensen, Gedske Daugaard
Journal: Journal of Clinical Oncology (2016)

For patients with germ cell cancer, various pulmonary toxicity risk factors have been hypothesized for treatment with bleomycin, etoposide, and cisplatin (BEP). Because existing studies have shortcomings, we present a large, unselected cohort of patients who have undergone close monitoring of lung function before, during, and after treatment with BEP to disclose valid pulmonary toxicity risk factors.All patients who were treated with BEP at Rigshospitalet, Copenhagen, Denmark, from 1984 to 2007, were included. Pulmonary function tests (PFTs) that measured the diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in 1 second, and forced vital capacity were performed systematically before, during, and after treatment with BEP for 5 years of follow-up. According to local protocol, bleomycin was discontinued if hemoglobin-corrected DLCO (DLCOc) decreased ≥ 25% compared with pretreatment value. Covariates of possible importance were evaluated with a multiple regression analysis for pretreatment PFTs and with a mixed model for follow-up PFTs. Bleomycin was adjusted on the basis of PFT results and was thus omitted as covariate.Overall, 565 patients were evaluated with a PFT before or after treatment with BEP. During BEP, 15 patients died of progressive disease or toxicity, including one patient from bleomycin-induced pneumonitis. Post-treatment DLCOc decreased significantly, with a rebound during follow-up. Forced expiratory volume in 1 second and forced vital capacity remained unchanged after BEP but increased significantly to levels above pretreatment during follow-up. International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic group, mediastinal primary, pulmonary metastases, and smoking all significantly influenced baseline PFT results. Pulmonary surgery, pulmonary embolism, IGCCCG poor prognosis, and smoking influenced PFT during follow-up. Mediastinal primary, pulmonary metastases, age, or doses of cisplatin and etoposide had no influence on follow-up PFT, and renal function did not influence PFT.After 5 years of follow-up, pulmonary impairment in patients with germ cell cancer who were treated with BEP was limited. Exceptions were patients treated with pulmonary surgery, those who suffered pulmonary embolism, and those in the IGCCCG poor prognostic group.
AXIN2 and prostate cancer recurrence after radical prostatectomy.
Authors: Brian Robin Hu, Adrian Stuart Fairey, Dongyun Yang, Meng Li, Susan G. Groshen, Craig Stephens, David I. Quinn, Philip Kim, Navneet Virk, Lina Wang, Sue Ellen Martin, Inderbir S Gill, Amir Goldkorn
Journal: Journal of Clinical Oncology (2014)

145 Background: Sub-populations of cancer stem cells (CSC) present in prostate cancer (PCa) and other malignancies have been associated with more aggressive characteristics. We investigated whether tumor expression of genes putatively linked to the CSC phenotype is associated with PCa recurrence. Methods: Expression of mRNA from radical prostatectomy specimens in 241 patients (cases 147, control 94) was analyzed by RT-PCR. Univariate analysis and recursive partitioning measured associations between expression of 12 CSC genes and PCa recurrence. Bootstrap internal validation was used to confirm associations. External validation was performed in-silico using the Oncomine microarray data compendium, analyzing differential gene expression in relevant studies. Results: Four genes (AXIN2, p&lt;0.001; CD44A, p=0.036; OCT 4, p=0.017; TACSTD2, p=0.008) were differentially expressed in PCa recurrence. Recursive partitioning analysis identified three genes jointly predictive of disease recurrence (AXIN2, NANOG, CTNNB1; OR 5.1 to 8.5). Bootstrap internal validation identified low AXIN2 expression as the CSC gene most predictive of PCa recurrence. In-silico external validation was performed for AXIN2, identifying one closely-matched cohort. Primary data analysis confirmed the association between low AXIN2 expression with PCa recurrence after prostatectomy (p=0.003). Additional queries of the Oncomine platform correlated low AXIN2 expression to worse disease in PCa: metastatic versus primary (six of seven studies, p=2.6x10 -9 to 0.07) and locally-advanced versus low grade (four of seven studies, p= 0.007 to 0.037). Lastly, low AXIN2 expression was associated with worse disease in multiple other cancers (10 of 10 studies, p=7.7x10 - 6 to 0.007). Conclusions: Low AXIN2 expression was internally and externally validated as predictive of PCa recurrence after radical prostatectomy. In-silico analysis demonstrates low AXIN2 expression is associated with more aggressive disease and worse clinical outcomes in prostate and other cancer cohorts. This novel finding delineates a link between the CSC phenotype and disease prognosis, suggesting AXIN2’s role as a potential biomarker.
An open-label phase II study of the Hsp90 inhibitor ganetespib (STA-9090) in patients (pts) with metastatic and/or unresectable GIST.
Authors: G. D. Demetri, M. C. Heinrich, B. Chmielowski, J. A. Morgan, S. George, R. Bradley, R. K. Blackman, F. Teofilovici, J. A. Fletcher, W. D. Tap, M. von Mehren
Journal: Journal of Clinical Oncology (2011)

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