tbuckley/cabot-search huggingface dataset:
Reproducibility of autoantibody measurements in normal individuals using the Early CDT-Lung test.
Authors: A. Murray, C. Chapman, G. Parsons, L. Peek, J. Allen, J. McElveen, J. F. Robertson
Journal: Journal of Clinical Oncology (2010)

e17522 Background: The Early CDT-Lung test is an assay, intended as a tool for risk stratification in a population at high risk for lung cancer. The test measures autoantibodies (AAb) against a panel of six tumor-associated antigens (p53, SOX2, CAGE, NY-ESO-1, GBU4-5 and Annexin 1). The aim of this study was to investigate the variability between repeated samples from the same patient. Methods: Serial serum samples were collected once a week for 4 weeks from premenopausal female smokers (n=46, mean age = 39.9 years) and once every 2 weeks for 4 weeks from post-menopausal female smokers (n=19, mean age = 54.7 years) and male smokers (n=10, mean age=58.4 years). Local ethical approval had been given for the collection. Comparisons between weeks were performed using paired t-tests. Coefficients of variation (CVs) for between-sampling-time (within-patient) reproducibility were compared with historical estimates of between-assay CVs. Results: Paired t-tests showed no significant differences between the paired samples from male smokers. No significant differences were observed between the first sample taken from premenopausal women and any of the subsequent 3 samples. The only significant difference out of 30 t-tests performed was p53 levels in samples from post-menopausal women taken 2 weeks apart (p=0.021). These findings showed that there was no directional trend over time for the patient set while graphics showed constant AAb levels over time within-patient. The comparison of CVs showed that between-sampling-time reproducibility was no higher than that for between-assay CVs for any of the three groups. This confirmed that the within-patient AAb level was not varying over the monthly cycle. Conclusions: The Early CDT-Lung test demonstrates a high degree of reproducibility in measurements of serial samples taken from the same patient. Cyclic hormonal changes do not appear to affect assay results. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Oncimmune Oncimmune Oncimmune, Oncolytics Biotech, Oncommune Oncimmune
Safety, pharmacokinetics, and pharmacodynamics of high-dose etoposide.
Authors: T L Schwinghammer
Journal: Journal of Clinical Oncology (1994)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1994.12.12.2768 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7989956 Safety, pharmacokinetics, and pharmacodynamics of high-dose etoposide. T L SchwinghammerxT L SchwinghammerSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.12.2768 PDF "Safety, pharmacokinetics, and pharmacodynamics of high-dose etoposide.." Journal of Clinical Oncology, 12(12), pp. 2768–2769© 1994 by American Society of Clinical Oncology
Abstract A42: Exogenous normal mammary epithelial mitochondria increase the drug sensitivity of human breast cancer MCF-7 cells
Authors: Xian-Peng Jiang, Jeff Philips, Robert L. Elliott, Jonathan F. Head
Journal: Clinical Cancer Research (2015)

Abstract The mitochondrial dysfunction of cancer cells leads to the suppression of glucose oxidation, increased glycolysis, proliferated advantage, resistance to apoptosis and drug resistance. We hypothesize that the introduction of normal mitochondria into cancer cells will restore the mitochondrial function of cancer cells and increase drug sensitivity. We stained the mitochondria of the normal human mammary epithelial cell line MCF-12A with JC-1 dye, and found orange fluorescence (JC-1 aggregates in mitochondria due to high mitochondrial membrane potential) in the MCF-12A cells. We then isolated the JC-1 stained-mitochondria of the MCF-12A cells and co-cultured them with the cells of human breast cancer MCF-7 cell line. At 30 minutes after co-culture of MCF-7 cells with the isolated JC-1-stained mitochondria, the orange fluorescence was observed in the MCF-7 cells. The fluorescence continued to increase for at least 6 hours and was still detected at 24 hours. This demonstrated that exogenous normal mitochondria of MCF-12A can enter into MCF-7 breast cancer cells. In order to determine whether mitochondria of normal MCF-12A cells improve the sensitivity of breast cancer cells to chemotherapeutic drugs, we co-cultured MCF-7 cells for 24 hours with normal mitochondria of MCF-12A, aspirated off the media and treated the MCF-7 cells with the drugs doxorubicin, abraxane or carboplatin. We found that MCF-7 cells, treated with the normal mitochondria of MCF-12A, were more sensitive to doxorubicin, abraxane and carboplatin than non-treated MCF-7 cells. We also have RT-PCR results demonstrating that uptake of normal mitochondria by cancer cells down-regulates the expression of membrane glucose transporter GLUT3 in MCF-7 cells. In conclusion, we suggest that the introduction of normal cell mitochondria into cancer cells could restore cancer cell mitochondrial function and significantly impact cancer therapy. Citation Format: Xian-Peng Jiang, Jeff Philips, Robert L. Elliott, Jonathan F. Head. Exogenous normal mammary epithelial mitochondria increase the drug sensitivity of human breast cancer MCF-7 cells. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr A42.
KRAS and BRAF mutational status as response biomarkers to cetuximab combination therapy in advanced gastric cancer patients
Authors: G. Stella, F. Rojas Llimpe, C. Barone, A. Falcone, F. Di Fabio, A. Martoni, S. Lamba, C. Ceccarelli, S. Siena, A. Bardelli, C. Pinto
Journal: Journal of Clinical Oncology (2009)

e15503 Background: The prognosis of advanced gastric cancer (GC) patients (pt) is still poor despite the introduction of new chemotherapy regimens. In colorectal cancer (CRC) it has been demonstrated that KRAS or BRAF mutations are associated with resistance to treatment with the anti-EGFR mAbs. We have assessed whether, and to what extent, the mutational profile of KRAS and BRAF genes affects the response to cetuximab combination therapy in GC. Methods: We have collected 44 tumor samples from pts affected by locally advanced or metastatic GC undergoing cetuximab combination therapy as first-line treatment in two consecutive phase II studies. Thirteen pts received cetuximab plus FOLFIRI (FOLCETUX Study) and 31 pts cetuximab plus cisplatin and docetaxel (DOCETUX Study). Genomic DNA was extracted from paraffin-embedded tumor specimens from all cases. The mutational status of KRAS (exon 2) and BRAF (exon 15) was ascertained by PCR amplification followed by direct sequencing. The objective response was evaluated every 6 weeks by CT according to RECIST criteria. Results: KRAS and BRAF mutations were detected in 5 (11.4%) and 1 (2.3%), respectively, of the 44 tumors analyzed. These frequencies are consistent with those previously reported in GC. In the case of KRAS, 3 cases displayed amino acid substitutions of codon 12 and 1 of codon 13. One case had the A11V variant that had been reported in hematopoietic and lymphoid tissue of the stomach. The only BRAF mutation found in 1 sample was the classic V600E substitution. As a whole, 13.6 % of the analyzed tumors carried a mutation in either KRAS or BRAF genes. K-RAS and BRAF mutations were, as expected, mutually exclusive. In this pt cohort oncogenic activation of KRAS/BRAF-signaling pathways was not significantly associated to objective response (p= 0.757). Also, we found no correlation between KRAS/BRAF mutations and clinical outcome measured as overall survival. Conclusions: In advanced GC the frequency of mutations in KRAS and BRAF is lower as compared with CRC cancer. In our cases, the mutational status of KRAS and BRAF genes does not correlate with the response to cetuximab-based therapy in advanced gastric cancer patients. No significant financial relationships to disclose.
Abstract 13396: Downregulation of the Angiomir-126 Contributes to the Failing Right Ventricle in Pulmonary Arterial Hypertension
Authors: Francois Potus, Augan Camille, sandra Breuils Bonnet, Roxane Paulin, Evangelos Michelakis, Provencher Steeve, Sebastien Bonnet
Journal: Circulation (2013)

INTRODUCTION: Right Ventricular Failure (RVF) is the most important predictor of both morbidity and mortality in pulmonary arterial hypertension (PAH). Nonetheless, RVF remained understudied compar...
Response to Letters Regarding Article, “Clinical Management of Catecholaminergic Polymorphic Ventricular Tachycardia: The Role of Left Cardiac Sympathetic Denervation”
Authors: Gaetano M. De Ferrari, Veronica Dusi, Carla Spazzolini, J. Martijn Bos, Dominic J. Abrams, Charles I. Berul, Lia Crotti, Michael Eldar, Maria Kharlap, Asaad Khoury, Andrew D. Krahn, Antoine Leenhardt, Christopher R. Moir, Attilio Odero, Louise Olde Nordkamp, Thomas Paul, Ferran Rosés i Noguer, Maria Shkolnikova, Jan Till, Arthur A.M. Wilde, Michael J. Ackerman, Peter J. Schwartz
Journal: Circulation (2016)
Prescribing and safety issues of oral molecular therapies and chemotherapies in Australian haematology oncology practice.
Authors: M. J. Dooley, M. A. Larizza, S. G. Poole, C. Carrington
Journal: Journal of Clinical Oncology (2010)

6149 Background: There is increasing use of oral therapies for the treatment of cancer, and although oral treatments have many benefits, the extent to which safe prescribing practices are employed is unknown. The aim was to determine the prescribing practices of oncologists and haematologists regarding oral molecular and chemotherapy medications across various practice settings in Australia. Methods: Ethics approval was obtained. A 19-question survey was developed, based, with permission, on that of Weingart et al (BMJ 2007); examining aspects of prescribing and supply of oral chemotherapy and molecular therapies. The survey was distributed electronically to all 203 medical oncologist and haematologist members of Medical Oncology Group of Australia (MOGA) and/or Clinical Oncology Society of Australia (COSA) in April 2008. Results: 84 surveys were returned (41% response rate). Ninety percent of respondents agreed that oral molecular medications should be prescribed and supplied using the same procedures as oral chemotherapy. 21%-45% of prescribers state that they prescribe the exact number of tablets/capsules required for each cycle for commonly used oral chemotherapies (capecitabine, temozolomide, vinorelbine, etoposide) and molecular therapies (gefitinib, imatinib, sunitinib, erlotinib). One third of respondents stated that they always assess a patient's adherence to oral chemotherapy and molecular therapies. In the past year, 43% of prescribers reported at least one medication error relating to oral chemotherapy and 15% relating to oral molecular therapies in the ambulatory setting. The vast majority of prescribers treating patients in the public setting have oral chemotherapy and molecular therapy prescriptions checked by an oncology pharmacist. Significantly fewer of these prescriptions are checked by an oncology pharmacist in private practice. Conclusions: There is significant variability in the prescribing of oral chemotherapy and molecular therapies among oncologist/haematologists which could contribute to potential for error. No significant financial relationships to disclose.
Morphological Transformation of Rat Embryo Cells Induced by Diethylnitrosamine and Murine Leukemia Viruses&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A E Freeman, P J Price, H J Igel, J C Young, J M Maryak, R J Huebner
Journal: JNCI Journal of the National Cancer Institute (1970)
Drug resistance among new TB cases and relapses
Authors: Punga Victor, Larisa Rusakova, Yakimova Marina, Kapkov Lev, Elvira Putova
Journal: European Respiratory Journal (2011)

Purpose of the study:  To study prevalence and range of drug resistance (DR) of TB mycobacteria (MbT) among 41,574 new TB cases and 5,890 relapses in 14 RF territories over the period of 2007-2009.   Materials and methods:  Analysis of MbT DR was performed based on the official and applied statistical data quarterly received at the Center of Monitoring, CTRI RAMS.   Results:  Over the period of 2007-2009, the proportion of new cases with DR MbT increased from 30.9% to 40.1%, and with MDR TB - from 10.8% to 13.2%. In the group of relapses the incidence of DR (48.4% and 55.4%) and MDR (26.7% and 33.0%) was much higher than among new TB patients. One third of new TB cases had resistance to isoniazid and streptomycin and 15.0-20.0%% of new TB cases were resistant to rifampicin and ethambutol. Among TB relapses DR TB, MDR TB and any other resistance to isoniazid, streptomycin, rifampicin and ethambutol was reported 2-3 times more often than among new TB cases. Over the period of 2007-2009, the rage of drug resistance was increasing in all TB patients; cases of XDR TB were reported regularly.   Conclusion:  Over the period of 2007-2009, an annual increase in proportion and number of DR cases was reported. Therefore, it is necessary to perform monitoring of quality of the laboratory tests, data collection and follow up of TB patients9 groups. Knowledge of DR MbT range of patients allows performance of the adequate chemotherapy, its adjustment, evaluation of the epidemiological situation on TB and timely managerial solutions. Increase in prevalence of DR MbT is the result of the previous failed courses of chemotherapy.
Phase I trial of dacarbazine and bortezomib in melanoma and soft tissue sarcoma
Authors: J. D. Roberts, M. S. Ernstoff, C. Birdsell
Journal: Journal of Clinical Oncology (2006)

18008 Background: Dacarbazine (D) has modest single agent activity against melanoma and soft tissue sarcomas. NFκB is a transcription factor that in general promotes cell survival and antagonizes apoptosis. In melanoma NFκB is constitutively activated and increases further in response to D. Bortezomib (B) is a prosteasome inhibitor that down-regulates NFκB. In tissue culture and xenograft melanoma models B potentiates anticancer effects of D and the related agent temozolomide. Methods: The primary objective is to identify recommended phase II doses for D+B administered weekly. Patients with advanced melanoma or sarcoma are enrolled in a traditional ‘3+3‘ dose escalation format. Results: Recommended phase II doses will be at least D 250 mg/m 2 and B 1.6 mg/m 2 , and dose escalation continues. Treatment has been generally well tolerated with known D and B toxicities. Among 8 melanoma patients there is 1 partial response (PR), 1 with stable disease on treatment 15 weeks, 6 with progressive disease (PD) 6, 7, 8, 8, 13, and 13 weeks. Among 5 sarcoma patients there is 1 PR and 4 with PD 4, 8, 16, and 24 wks. Conclusions: At full dose B and moderate dose D for this schedule, D+B is feasible and generally well-tolerated. Activity beyond that of D alone is not apparent to date, but several or all patients have been treated at less than maximum tolerated doses. [Table: see text]
INCIDENCE AND CLINICAL IMPACT OF STENT FRACTURE AFTER EVEROLIMUS-ELUTING STENT IMPLANTATION
Authors: Shoichi Kuramitsu, Masashi Iwabuchi, Takenori Domei, Takuya Haraguchi, Ayumu Nagae, Yoshio Kazuno, Soichiro Enomoto, Toru Mazaki, Makoto Hyodo, Yoshimitsu Soga, Katsuhiro Kondo, Shinichi Shirai, Kenji Ando, Koyu Sakai, Yoshitaka Takabatake, Hiroyoshi Yokoi, Fumitoshi Toyota, Masakiyo Nobuyoshi
Journal: Journal of the American College of Cardiology (2012)
An analysis of 539 palliative interventional radiology procedures for advanced cancer
Authors: G. B. Melton, T. J. Miner, L. K. Temple, A. M. Covey, D. P. Jaques
Journal: Journal of Clinical Oncology (2005)

8055 Background: The comprehensive management of advanced cancer requires an understanding of the value of interventional radiology (IR) in palliation of symptoms. Methods: All patients undergoing an IR procedure to palliate symptoms for advanced cancer over a one-year period were identified, and outcomes at 30 and 100 days were analyzed. Results: Between July 2002 and June 2003, 234 patients underwent 539 IR palliative procedures (median 2 per patient, range 1–9 procedures). At 30 days, 98% of patients still alive had improvement or resolution of their targeted symptom. At 100 days after initial palliative intervention, 92% of patients still alive remained symptom free, though 37% (n=49) of these required additional procedures to maintain this state. The median durability of palliation was 104 days and was adversely associated with morbidity at the initial procedure, type of procedure, poor nutrition (albumin<3.5), and no post-procedure cancer treatment. Procedures to palliate jaundice were more durable (median 172 days) and abdominal distension less (median 33 days), most commonly due to progression of disease. The median survival following IR palliation was 134 days. The 30 day post-procedure morbidity was 13% (n=30) and mortality 28% (n=65). Conclusions: Symptom relief following palliative IR procedures can be expected though it will commonly require additional procedures to maintain. Disease progression limits the durability of this palliation and is indicative of the common use of these procedures near the end of life when associated morbidity must be limited. No significant financial relationships to disclose.
Trisomy 13 in patients with hematological malignancies
Authors: R. Santana-Davila, M. Ellliott, C. Hook, S. Kaufmann, L. Letendre, R. Pruthi, A. Tefferi, D. Van Dyke, A. Wiktor, M. R. Litzow
Journal: Journal of Clinical Oncology (2007)

7055 Introduction: Cytogenetic abnormalities have been shown to be the most important determinant of prognosis in patients with acute myeloid leukemia (AML). In AML, trisomy 13 has been placed in the intermediate prognostic category although recent reports associate it with a more dismal outcome. The number of cases reported in the literature are relatively few, we reviewed our experience with trisomy 13 in hematologic malignancies to determine its significance and prognosis. Methods: We conducted a clinicopathological review of cases seen in our institution from January of 1990 to October of 2006. Our cytogenetic records were searched for patients, who had a hematological disorder whose non-stimulated bone marrow karyotype was found to have trisomy 13 as a sole abnormality. In men the absence of the Y chromosome was not regarded as a separate abnormality. Results: A total of 27 patients were identified. The median age was 76 years (range 25–87), 22/27 were male. The number of cases and diseases identified were 15 with AML, 5 with a myelodysplastic syndrome, 4 with an uncategorized myelodysplastic/myeloproliferative disorder, 2 with acute lymphoblastic leukemia and 1 with a chronic myeloproliferative disorder. Of the AML group 7 were M0 according to the FAB classification, 2 patients were identified to have M4 and another two M2. A single case each of M1 and M6 was also identified. In these 15 patients, 9 underwent induction chemotherapy, which consisted of intermediate dose Ara-C in 3 cases, anthracycline plus Ara-C in 5 patients, and daunorubicin, vincristine and prednisone in 1. Another 3 patients were given palliative treatment. For the rest of the subjects the type of treatment was unknown. A CR was obtained in 6 patients, 1 patient underwent a myeloablative stem cell transplant. Death has occurred in 24 patients, the median survival of the entire group was 5.4 months. In the patients with AML the median survival was 4.7 months, of the patients who achieved a CR the median survival was 9.5 months. Conclusions: We describe one of the largest series reported to date of trisomy 13 in hematologic malignancies and found that trisomy 13 is associated with male gender and an older age at presentation, as well as a poor prognosis. In AML its presence is associated with an FAB-M0 phenotype and its occurrence should be regarded as a high-risk feature. No significant financial relationships to disclose.
Policy layers delay funding of innovative care deal for elderly people, conference hears
Authors: Nigel Hawkes
Journal: BMJ (2016)

Devolution of health and social care spending to Manchester—known as “Devo Manc”—has created a new obstacle to creating new care models, a seminar in London heard on 10 February.

Terry Dafter, director of adult social care in Stockport, Greater Manchester, described how social care, community health services, and primary care were being combined under pooled funding from the borough council and the Stockport clinical commissioning group. The care model being developed is a multispecialty community provider (MCP), as described in NHS England’s Five Year Forward View.

Dafter told a Westminster Health Forum on mental health services that getting all services to agree to the plan was tortuous. “You have to be dogged, and it’s hard going,” he said. “But the final outcome is worth it.”

The arrival of Devo Manc, another policy backed by NHS …
A pilot study with correlation of pre-therapy serum retinol levels to response to chemo-radiotherapy and quality of life parameters in advanced head and neck cancers
Authors: K. Gupta, A. Bhiman
Journal: Journal of Clinical Oncology (2005)

5583 Background: Lower intake of vitamin A increases risk of certain cancers. We correlated pre therapy serum retinol levels with response to therapy and quality of life parameters in head & neck cancers. This is a pioneer study of its kind. Methods: 153 patients, matched for age, histology, stage, socioeconomic status, pretreatment performance status, method of retinol level assessment, clinicoradiologically measurable disease, cardiorespiratory status & chemo-radiotherapy; with advanced (Stage III/IV) squamous cell cancer were recruited after informed consent. 6 cycles of neoadjuvant chemotherapy of Cyclophosphamide [500mg/m2, i.v.]+Adriamycin [50 mg/m2,i.v.]+cisplatin[70mg/m2, i.v.] at 21 day intercycle gaps for followed by 54–60 Gy external beam irradiation was given. Serum retinol was assayed by High performance liquid chromatography. Standard methods for response rate (RR), complete response (CR) and partial response (PR) were used. Functional Assessment of Cancer therapy-General tool was used for QOL assessment. Log rank test, Cox’s proportional hazard method, Student’s t test, Fischer’s exact test and chi2test was used for statistical analysis. Correlation coefficients were determined by linear regression analysis. Results: Till date, 135 out of 153 patients were evaluable for response. 21% CR and 58% PR was noted. QOL improvement was statistically significant (p<.001) at 6 and 12 month. Major gain was noted in physical & emotional well being followed by functional & social well being. Patients with lower retinol levels had poor response to therapy (p<.001). Progression of the cancer was 4 times higher in women with lower retinol levels (p=0.08). Also, lower retinol levels corresponded to inferior QOL parameters (p<.01). Conclusions: This pioneer study indicates that besides causing higher incidence of malignancy, lower retinol also leads to poor outcome in terms of therapeutic response and QOL. Further larger multicentre studies might substantiate our results. No significant financial relationships to disclose.