tbuckley/cabot-search huggingface dataset:
Multifunctional analysis of cultivated primary adenocarcinoma cells after treatment with different chemotherapeutic drugs
Authors: A. Sprüssel, J. Krüger, J. Hennesen, J. Spangenberg, H. Juhl, K. A. David
Journal: Journal of Clinical Oncology (2008)

22139 Background: The discovery of new anticancer drugs is currently performed by using common cancer cell lines. However, it has been shown that long term cultured cell lines are limited in forecasting in vivo drug sensitivities. Therefore, we developed a standardized procedure to isolate pure epithelial cells directly from gastrointestinal tumor tissues and used them to examine chemotherapeutic effects of various cancer agents. Methods: Primary epithelial cells were freshly derived from adenocarcinoma patients, cultivated for 0, 24, 48 and 72 hours and either treated with various single tumor therapeutics such as Oxaliplatin, Gemcitabine, Iressa and 5-FU or by using drug combinations (Leucovorin/5-FU; FOLFOX; IFOX; and GOLF). Drug responses were analysed by immunofluorescence, ATP measurement and electrochemiluminescence and compared to either similarly treated HT29 cells or short and long term cultivated primary cells. Results: Application of the GOLF regiment showed in all cell cultures the strongest effect on cell proliferation and metabolism. We observed that compared to the single drug treatments, the different drugs composing GOLF were highly synergistic in inducing growth inhibition.The GOLF combination induced apoptosis in all colorectal cancer cells as measured by caspase-3 activation, PARP cleavage, as well as increased levels of total and phosphorylated p53. Since apoptosis onset in eukaryotic cells is substantially regulated by the balance between apoptotic and survival pathways the effects of the different drug treatments on expression and activity of the components of the Erk and Akt dependent pathways were also evaluated. In all cell cultures the induction of apoptosis due to GOLF treatment was paralleled by increased levels of total as well as phosphorylated ERK, whereas the expression and activation of EGFR, MEK, P70s6K, GSK3β and especially AKT were decreased. All these effects were also seen in cells treated with the single drugs or combinations thereof although less pronounced. Conclusions: Primary cells from gastrointestinal patients could provide a cellular platform beyond the common cancer cell lines for in vitro drug screening and might allow individualization of chemotherapies for patient treatments. No significant financial relationships to disclose.
Cyclic Variation of DNA Synthesis in Human Breast Epithelium
Authors: J. R. W. Masters, J. O. Drife, J. J. Scarisbrick
Journal: JNCI Journal of the National Cancer Institute (1977)

DNA synthesis in normal breast epithelium from premenopausal women was assessed by use of autoradiography. In parous women the labeling indexes decreased during the follicular phase of the menstrual cycle and increased to a significantly higher level during the luteal phase.
Semi-quantitative gene expression profiling for therapy prediction in a breast cancer neoadjuvant therapy study applying docetaxel/epirubicin/cyclophosphamide
Authors: U. Vogt, D. Kemming, B. Brandt, U. Bosse, U. Bonk, A. v. d. Assen, H. J. Muhs, C. M. Schlotter
Journal: Journal of Clinical Oncology (2007)

21144 Background: More than 28000 curated human genes can be analyzed semi-quantitatively using a chemiluminescent detection technology and 60mer oligonucleotides on a Human Genome Survey Microarray (HGSM, Applied Biosytems). Methods: HGSM expression profiling was performed on biopsy samplesfrom a setting of patients under neoadjuvant treatment. The protocol for a phase II study was elaborated for the treatment of breast cancer patients suffering from a primary tumor &gt; 1,5 cm or inflammatory breast cancer with Docetaxel / Epirubicin/Cyclophosphamide (TEC) prior to surgical treatment. The study was approved by the local ethical committee and 80 patients will be included into the study after written informed consent. 40 patients have been already included in the ongoing study. In this prospective study a biopsy from the tumor is taken before chemotherapy. Therefore, success of treatment is detectable directly at the operated residual tumor. Our results demonstrate a low rate of false-positives (1.2%), a high specificity and quantification accuracy of HGSM system. Comparison of data from HGSM and RT-PCR obtained on mRNA from fresh frozen tissue resulted a Pearson-correlation of 0.92 to 0.63 for the breast cancer genes. Results: Tumour response (pCR, pPR) of more than 70 % can be achieved using neoadjuvant TEC- regimen. 25 % of pCR in this study is comparable with data of other published neoadjuvant trails. First expression profiling results are obtainable showing that a subset of 148 genes indicates patients with complete remission (pCR, no detectable tumor at end of chemotherapy), partial remission (pPR) and progressive disease (pPD). Remarkable, that the expression profile clearly separated pCR and pPD tumors whereas pPR tumors presented with a closer relationship to pPD tumors than to pCR tumors but displayed small specific subprofiles. A comparable separation of the groups could not achieved by established tumor markers, e.g. ER, PgR, HER2, uPA etc. which are measured simultaneously on the HGSM. Conclusions: HGSM expression profiling is promising to have the potential to figure out genes that are related to cancer progression and chemotherapy resistance, especially in PST. No significant financial relationships to disclose.
Safety and Efficacy of Pacemaker Reuse in Underdeveloped Nations
Authors: Timir S. Baman, Al Romero, James N. Kirkpatrick, Joshua Romero, David C. Lange, Eric O. Sison, Rogelio V. Tangco, Nelson S. Abelardo, George Samson, Rita Grezlik, Edward B. Goldman, Hakan Oral, Kim A. Eagle
Journal: Journal of the American College of Cardiology (2009)
A phase II trial of the Src kinase inhibitor AZD0530 in patients with metastatic or locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: A trial of the PMH phase II consortium.
Authors: H. Mackay, H. Au, E. McWhirter, T. Alcindor, A. Jarvi, K. MacAlpine, L. Wang, J. J. Wright, A. M. Oza
Journal: Journal of Clinical Oncology (2010)

e14544 Background: AZD0530is an oral, anilinoquinazolone, non-receptor tyrosine kinase inhibitor targeting c-SRC, c- Yes, Lck and Bcr-abl. Src family kinases have been implicated in transformation and gastric cancer progression. Methods: The aim of this multi-centre, 2-stage design, phase II study was to assess the activity of AZD0530 in patients (pts) with unresectable or metastatic gastric or GEJ adenocarcinoma. Eligibility criteria included: ECOG PS ≤ 2; prior neoadjuvant or adjuvant chemo radiation and ≤ 1 prior line of chemotherapy for metastatic disease were allowed. Primary endpoint was objective response and/or prolonged stable disease rate (pSD ≥ 16 weeks). Secondary endpoints included time to progression (TTP), overall survival (OS) and tolerability. Pts received AZD0530 175 mg/day of a 28 day cycle. Tumor response was assessed by RECIST criteria every 8 weeks. ≥ 1 pt(s) with response, or ≥ 3 pts with pSD out of the first 18 evaluable pts was required to proceed to second stage accrual. Results: 20 pts with gastric cancer, median age 64 (range 43-83) years received a total of 38 cycles of treatment, median 2 (range 1 to 5) cycles/pt. 7 pts had received prior chemotherapy and 6 prior radiotherapy for advanced disease. Best response was pSD (1 pt). 3 pts had SD, 10 progressive disease and 3 were inevaluable. 3 pts remain on treatment. The most common drug related adverse events any grade (% of patients) were fatigue (40%), elevated phosphate (40%), lymphopenia (35%), anorexia (30%), hypocalcaemia (30%) and elevation of aminotransferases (30%). Grade 3 events possibly related to AZD0530 included: fatigue (2 pts), anemia (2), lymphopenia (2), hyponatraemia (2) and dyspnoea (1). 14 pts have progressed. Median TTP was 1.8 months (95% CI: 1.5-3.5 mos). There have been 6 deaths. Median OS has not been reached. Conclusions: AZD0530 has insufficient activity as a single agent in pts with advanced gastric adenocarcinoma to warrant further investigation. Further development in gastric cancer would require rational drug combinations or identification of a tumor phenotype sensitive to Src inhibiton. The study has closed to accrual. No significant financial relationships to disclose.
Heterogeneity in the specific activity and methotrexate sensitivity of dihydrofolate reductase from blast cells of acute myelogenous leukemia patients.
Authors: S Dedhar, D Hartley, D Fitz-Gibbons, G Phillips, J H Goldie
Journal: Journal of Clinical Oncology (1985)

Dihydrofolate reductase activity was found to be highly heterogeneous in terms of its specific activity and methotrexate sensitivity in the blast cells of patients with acute myelogenous leukemia. None of the patients had previously been treated with methotrexate (MTX). The blast cells of four of 12 patients studied contained methotrexate-insensitive forms of dihydrofolate reductase, and the blast cells of three (distinct from the four mentioned previously) of the 12 had significantly higher dihydrofolate reductase activities than the rest. The presence of MTX-insensitive dihydrofolate reductases and high levels of enzyme activity represent intrinsic mechanisms of resistance and may explain the apparent clinical resistance of acute myelogenous leukemia to methotrexate.
Survival after resection of perihilar cholangiocarcinoma—development and external validation of a prognostic nomogram
Authors: B. Groot Koerkamp, J.K. Wiggers, M. Gonen, A. Doussot, P.J. Allen, M.G.H. Besselink, L.H. Blumgart, O.R.C. Busch, M.I. D'Angelica, R.P. DeMatteo, D.J. Gouma, T.P. Kingham, T.M. van Gulik, W.R. Jarnagin
Journal: Annals of Oncology (2015)
Unusual Pulmonary Lesions
Authors: Henk Codrington, Tom Sutedja, Richard Golding, Johan van Mourik, Elle Risse, Pieter E. Postmus
Journal: Journal of Clinical Oncology (2002)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.11.2747 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12039938 Unusual Pulmonary Lesions Case 2. Endobronchial Carcinoid of the Lung Henk CodringtonxHenk CodringtonSearch for articles by this author , Tom SutedjaxTom SutedjaSearch for articles by this author , Richard GoldingxRichard GoldingSearch for articles by this author , Johan van MourikxJohan van MourikSearch for articles by this author , Elle RissexElle RisseSearch for articles by this author , Pieter E. PostmusxPieter E. PostmusSearch for articles by this author Show More Vrije Universiteit Medical Centre, Amsterdam, the Netherlands https://doi.org/10.1200/JCO.2002.20.11.2747 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Single-step nanoparticle antigen presentation system for tumor immunotherapy
Authors: Frederick Kohlhapp, Erica Huelsmann, Jai Rudra, Arman Nabatiyan, Andrew Zloza
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts While only 10-30% of patients treated with currently approved single immunotherapies demonstrate long-term benefit, treatment efficacy in responders correlates with increased CD8+ T cell responses to neoantigens (tumor antigens hidden from the immune system). Thus, to improve
Laboratory-acquired vaccinia virus infection - Virginia, 2008.
Authors: E. Davies, L. Peake, D. Woolard, C. Novak, K. Hall, R. T. Leonard, R. Allen, V. Reynolds, M. Davidson, C. Hughes, V. Olson, S. Smith, H. Zhao, Y. Li, K. Karem, I. Damon, A. Macneil, A. Roess
Journal: MMWR Morbidity and Mortality Weekly Report (2009)
The American founder mutation for Lynch syndrome: Prevalence and cancer control implications
Authors: H. T. Lynch, A. de la Chapelle, H. Hampel, A. Wagner, R. Fodde, R. Okimoto, M. B. Clark, S. Coronel, A. Trowonou, G. R. Haynatzki, G. Gong
Journal: Journal of Clinical Oncology (2005)

9505 Background: We have recently reported a new founder mutation, namely, an exon 1–6 deletion in the MSH2 gene detectable by a recently designed single PCR reaction in 9 kindreds with Lynch Syndrome. In 3 of the kindreds this mutation has been traced through genealogy 12 to 13 generations back to a common founder and thus termed the American Founder Mutation (AFM). We have since identified 11 additional apparently unrelated kindreds with AFM. The new PCR test might serve as first-line screening for Lynch syndrome provided the mutation were prevalent and widespread, which we assess in this study. Methods: With the genealogy data, the expected number of AFM carriers at generation k is E(mk)= mk-1sk/2, where k is number of generations that had passed since the founder had settled in the US, and skis the number of reproductive offspring per mutation carrier at generation k-1. The 95% C.I. was computed based on the probability distribution of mk with simulation of 1 million replicates. From E(mk) we estimated the recent annual incidence of Lynch syndrome caused by AFM. The incidence was also estimated based on published proportion of mismatch repair gene mutation-negative (MMR-MN) cases with Lynch syndrome among all colorectal cancer cases, and the recently reported proportion of AFM carriers among MMR-MN cases with Lynch syndrome (13%). Results: There are 1595 members from 256 nuclear families over 12 to 13 generations with relatively reliable data concerning the number of reproductive offspring per individual in the initial 9 pedigrees. Based on genealogy data, there are 15460 (95% C.I, 5670, 25270) current AFM carriers, or 156 (95% C.I., 58, 258) Lynch syndrome cases/y due to AFM, assuming the last two generations (median age 17 and 41 yrs) and half of the earlier generation are alive. Based on data of the random sample, the incidence of Lynch syndrome caused by AFM is 113 to 396 cases/y. Conclusions: A large number of AFM carriers exist in the US. Further studies will define the proportion and geographic distribution of Lynch syndrome cases due to AFM. Testing for AFM may become the first choice in mutation screening of Lynch syndrome. Expanding the 9 original and 11 “new” AFM pedigrees for AFM carriers should be extremely effective for cancer control. No significant financial relationships to disclose.
Out-of-pocket costs (OPC) and time costs (TC) for patients with stage IV non-small cell lung cancer (NSCLC) and their caregivers
Authors: D. Romanus, P. Neumann, C. Earle, M. Weinstein, J. Tsai, B. Neville, J. Weeks
Journal: Journal of Clinical Oncology (2004)

6021 Background: Despite the high incidence of NSCLC, little is known about the associated economic burdens experienced by patients and caregivers. Methods: Patients participating in a multicenter cohort study of outcomes of newly diagnosed stage IV NSCLC and their surrogates were asked to report OPC and TC in monthly diaries and surveys. Time was valued at the median age- and gender-specific income reported by the U.S. Census Bureau in 2001. We report on the first submitted monthly survey; no temporal trends were observed over 6 months of follow-up. Results: Among 181 respondents, mean age was 59 years and median income was $60,000. 33% and 11% worked full- and part-time, respectively;11% were on paid medical leave, and 39% were retired, unemployed or working as a homemaker. Monthly OPCs for patients are shown in the table. Monthly mean (range) wage losses reported by patients and caregivers were $1,697 ($126–3,371) and $564 ($0–644), respectively; the mean value for leisure time lost by the primary caregiver for provision of care to the patient was $1,393 (range: $110–1,718). 48% reported costs associated with complementary and alternative medicine (CAM), defined as visits to alternative or holistic practitioners, homeopathic or herbal remedies, vitamins, or nutritional supplements. At a mean cost of $128 (range: $0–3045), CAM accounted for 40% of overall monthly OPC. Conclusions: OPC and costs related to wages and leisure time lost represent a substantial burden on patients and caregivers. Transportation and OPC for prescription medication account for over half of total OPC. A large proportion of patients report expenditures on CAM, totaling over a third of all OPC. Given the significant monthly cost estimates of TC and OPC, the incorporation of these costs should be considered in future economic analyses of stage IV NSCLC. No significant financial relationships to disclose.
The Initial Detection and Partial Characterization of Circulating Tumor Cells in Neuroendocrine Prostate Cancer
Authors: Himisha Beltran, Adam Jendrisak, Mark Landers, Juan Miguel Mosquera, Myriam Kossai, Jessica Louw, Rachel Krupa, Ryon P. Graf, Nicole A. Schreiber, David M. Nanus, Scott T. Tagawa, Dena Marrinucci, Ryan Dittamore, Howard I. Scher
Journal: Clinical Cancer Research (2015)

Abstract Purpose: The transition of prostate adenocarcinoma to a predominantly androgen receptor (AR) signaling independent phenotype can occur in the later stages of the disease and is associated with low AR expression +/− the development of small-cell or neuroendocrine tumor characteristics. As metastatic tumor biopsies are not always feasible and are difficult to repeat, we sought to evaluate noninvasive methods to identify patients transitioning toward a neuroendocrine phenotype (NEPC). Experimental Design: We prospectively studied a metastatic tumor biopsy, serum biomarkers, and circulating tumor cells (CTC, Epic Sciences) from patients with castration-resistant prostate cancer (CRPC) including those with pure or mixed NEPC histology present on biopsy. CTCs labeled with the patient's clinical status were used to learn features that discriminate NEPC patients, which was then applied to an independent cohort. Results: Twenty-seven patients with CRPC including 12 NEPC and 5 with atypical clinical features suggestive of NEPC transition were studied. CTCs from NEPC patients demonstrated frequent clusters, low or absent AR expression, lower cytokeratin expression, and smaller morphology relative to typical CRPC. A multivariate analysis of protein and morphologic variables enabled distinguishing CTCs of NEPC from CRPC. This CTC classifier was applied to an independent prospective cohort of 159 metastatic CRPC patients and identified in 17/159 (10.7%) of cases, enriched in patients with high CTC burden (P &amp;lt; 0.01) and visceral metastases (P = 0.04). Conclusions: CTCs from patients with NEPC have unique morphologic characteristics, which were also identified in a subset of CRPC patients with aggressive clinical features potentially undergoing NEPC transition. Clin Cancer Res; 22(6); 1510–9. ©2015 AACR.
Idiotype (Id) immunotherapy (IT) following high dose therapy and autologous stem cell transplant (HDT/ASCT) in mantle cell (MC) and indolent lymphoma (IL): Cellular, humoral and clinical responses
Authors: P. R. Holman, M. Demagalhaes-Silverman, B. M. Medina, S. Corringham, A. Bashey, J. E. Castro, E. Carrier, T. Lane, D. P. Gold, E. D. Ball
Journal: Journal of Clinical Oncology (2005)

2546 Background: ASCT can induce and prolong remissions in MCL and follicular lymphoma (FL) but patients uniformly progress. IT may prolong remissions. Rituximab is frequently used but has unclear benefit. Reports of GVL in allo-transplants provide a rationale for exploring other IT approaches post-ASCT. Id immunization, a potential option for many patients with MCL and FL has demonstrated efficacy in FL, even inducing molecular remissions. Therefore, we designed a trial to evaluate the ability of Id-KLH + GM-CSF to induce Id specific responses in MCL and IL when administered at least 3 months post-ASCT. Methods: 13 patients (8 MCL, 5 IL including 1 transformed) received Id-KLH + GM-CSF following HDT/ASCT. Biopsy tissue was used to prepare Id. Chemotherapy was then given prior to HDT/ASCT. At ≥ 3 months following ASCT, 5 Id-KLH treatments were administered over 6 months. 6 MCL patients have completed the immunization protocol, 2 continue receiving immunizations. 3 IL patients have completed the immunization protocol, 2 continue on protocol. Results: Cellular (CD4+ T cell) and humoral responses against Id and KLH were seen in most patients. In all but one, the appearance of anti-Id or KLH T cell responses preceded the corresponding antibody response, possibly reflecting earlier repopulation of T cells compared to B cells. T cell responses were often detectable after a single vaccination. Regarding clinical response, post ASCT and prior to the first vaccine, 6 MCL patients were in CR, 1 had CRu and 1 had a PR. For the IL patients, 2 were in CR, 1 had PR and 2 had SD. 4 MCL patients are in CCR between 14 and 38 months post-SCT. 2 MCL patients progressed at 9 and 14 months. Of the 3 IL patients who have completed all protocol treatment, one with PR post SCT converted to CR after 5 Id-KLH treatments and remained in a CR until MDS developed at 27 months. Another also converted to CR after all treatment and remains in CR at 36 months. Another remains with SD at 14 months. Conclusions: Id-KLH post-SCT results in a high frequency of rapid immune responses in patients with MCL and IL. Anti-lymphoma activity is suggested by the late and durable clinical responses. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Favrille
Differences between patient and family assessments of depression in Alzheimer's disease
Authors: T B Mackenzie, W N Robiner, D S Knopman
Journal: American Journal of Psychiatry (1989)

A structured interview covering the DSM-III criteria for major depression was adapted for separate use with Alzheimer's disease patients and with their families. Data from 36 patients yielded a depression rate of 13.9%, whereas information from their families indicated that the rate was 50.0%. This disagreement reflected greater family endorsement of patients' loss of interest or pleasure, irritability, fatigue, and feelings of worthlessness. Use of DSM-III-R criteria narrowed but did not eliminate the discrepancy between patients' and families' assessments of the patients' depression. Uniform procedures for gathering and integrating data from the family that are relevant to diagnosis in this group are indicated.