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Cancer Institute (cancer + institute)
Kinds of Cancer Institute Terms modified by Cancer Institute Selected AbstractsRoutine immunophenotyping in acute leukemia: Role in lineage assignment and reassignmentCYTOMETRY, Issue 5 2006Misbah Qadir Abstract Diagnostic evaluation of acute leukemia at Roswell Park Cancer Institute has routinely included immunophenotyping by multiparameter flow cytometry. In a retrospective analysis of 646 cases, morphology and cytochemistry established lineage in 612, but not in 34 (5%), of which 26, 5, and 3 were myeloid, undifferentiated, and lymphoid, respectively, based on immunophenotyping. In addition, immunophenotyping changed the lineage assigned based on morphology and cytochemistry in 11 cases (2%); 8 changed from lymphoid to myeloid, and 3 from myeloid to lymphoid. The data support routine inclusion of at least limited immunophenotyping in the diagnostic evaluation of acute leukemia. © 2006 International Society for Analytical Cytology [source] Evaluation of agreement between conventional and liquid-based cytology in cervical cancer early detection based on analysis of 2,091 smears: Experience at the Brazilian National Cancer InstituteDIAGNOSTIC CYTOPATHOLOGY, Issue 9 2007Vania Reis Girianelli M.Sc. Abstract The aim of this work was to evaluate the agreement between conventional cytology (CC) and liquid-based cytology (LBC) in cervical cancer early detection. The results of CC and LBC (DNACitoliq®) in 2,059 women aged 25,59 years were compared. The percent agreement, kappa coefficient, prevalence-adjusted bias-adjusted kappa coefficient (PABAK), and Chamberlain's percent positive agreement (PPA) were calculated. The percent agreement between the two methods was very good (80% and 79%, respectively, for normal versus ASCUS+; and normal versus ASCUS, AGUS and LSIL+ vs. HSIL+). The kappa coefficient indicates slight agreement (0.26 and 0.23, respectively), but when PABAK was used the agreement was good (0.61 and 0.68, respectively). PPA was high for normal results (79.2%) and low for the remaining categories. To conclude, in this study, agreement between LBC and CC was only good for normal results, which involves the majority of cases and positively influences the overall agreement rate. Diagn. Cytopathol. 2007;35:545-549. © 2007 Wiley-Liss, Inc. [source] Kernel estimates of hazard functions for carcinoma data setsENVIRONMETRICS, Issue 3 2006Ivana Horová Abstract The present article focuses on kernel estimates of hazard functions and their derivatives. Our approach is based on the model introduced by Müller and Wang (1990). In order to estimate the hazard function in an effective manner an automatic procedure in a paper by Horová et al. (2002) is applied. The procedure chooses a bandwidth, a kernel and an order of a kernel. As a by-product we propose a special procedure for the estimation of the optimal bandwidth. This is applied to the carcinoma data sets kindly provided by the Masaryk Memorial Cancer Institute in Brno. Attention is also paid to the points of the most rapid change of the hazard function. Copyright © 2006 John Wiley & Sons, Ltd. [source] Platinum(IV) Complexes of 3- and 4-Picolinic Acids Containing Ammine or Isopropylamine Ligands , Synthesis, Characterization, X-ray Structures, and Evaluation of Their Cytotoxic Activity against Cancer Cell Lines,EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 30 2008María J. Macazaga Abstract The preparation and characterization of the new complexes trans -[PtCl4(NH3)(3-picolinic acid)] (1), trans -[PtCl4{NH2CH(CH3)2}(3-picolinic acid)] (2), trans -[PtCl4(NH3)(4-picolinic acid)] (3), and trans -[PtCl4{NH2CH(CH3)2}(4-picolinic acid)] (4) are described. The main structural feature of these complexes is the presence of ligands capable of multiple hydrogen-bonding interactions. Crystals of 1, 2, 3, and 4 suitable for single-crystal X-ray diffraction were grown, and the molecular structures of these compounds are discussed. In contrast to the inactive parent PtII complexes, the PtIV complexes displayed cytotoxic activity against various cancer cell lines used at the National Cancer Institute (NCI) for in vitro screens. Once more, the isopropylamine derivatives showed the best cytotoxicity values. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Molecular cytogenetic characterization of non-Hodgkin lymphoma cell linesGENES, CHROMOSOMES AND CANCER, Issue 3 2002Sukvarsha Mehra Spectral karyotyping (SKY) and comparative genomic hybridization (CGH) have greatly enhanced the resolution of cytogenetic analysis, enabling the identification of novel regions of rearrangement and amplification in tumor cells. Here we report the analysis of 10 malignant non-Hodgkin lymphoma (NHL) cell lines derived at the Ontario Cancer Institute (OCI), Toronto, designated as OCI-Ly1, OCI-Ly2, OCI-Ly3, OCI-LY4, OCI-Ly7, OCI-Ly8, OCI-Ly12, OCI-Ly13.2, OCI-Ly17, and OCI-Ly18, by G-banding, SKY, and CGH, and we present their comprehensive cytogenetic profiles. In contrast to the 52 breakpoints identified by G-banding, SKY identified 87 breakpoints, which clustered at 1q21, 7p15, 8p11, 13q21, 13q32, 14q32, 17q11, and 18q21. G-banding identified 10 translocations, including the previously described recurring translocations, t(8;14)(q24;q32) and t(14;18)(q32;q21). In contrast, SKY identified 60 translocations, including five that were recurring, t(8;14)(q24;q32), t(14;18)(q32;q21), t(4;7)(p12;q22), t(11;18)(q22;q21), and t(3;18)(q21;p11). SKY also identified the source of all the marker chromosomes. In addition, 10 chromosomes that were classified as normal by G-banding were found by SKY to be rearranged. CGH identified seven sites of high-level DNA amplification, 1q31-32, 2p12-16, 8q24, 11q23-25, 13q21-22, 13q32-34, and 18q21-23; of these, 1q31-32, 11q23-25, 13q21-22, and 13q32-34 have previously not been described as amplified in NHL. This comprehensive cytogenetic characterization of 10 NHL cell lines identified novel sites of rearrangement and amplification; it also enhances their value in experimental studies aimed at gene discovery and gene function. © 2002 Wiley-Liss, Inc. [source] Evaluation of newly developed combination therapy of intra-arterial 5-fluorouracil and systemic pegylated interferon ,-2b for advanced hepatocellular carcinoma with portal venous invasion: preliminary resultsHEPATOLOGY RESEARCH, Issue 2 2009Kazuhiro Kasai Aim:, Prognosis is extremely poor for advanced hepatocellular carcinoma (HCC) in patients with portal invasion. The present study evaluated the efficacy of combined intra-arterial 5-fluorouracil (5-FU) and systemic pegylated interferon (PEG-IFN),-2b in patients with advanced HCC. Methods:, The subjects comprised nine HCC patients with portal vein thrombosis treated using subcutaneous administration of PEG-IFN,-2b (50,100 µg on day 1 of every week, for 4 weeks) and intra-arterial infusion of 5-FU (250 mg/day for 5 h on days 1,5 of every week, for 4 weeks). For four patients with hepatitis C virus (HCV) infection, oral administration of ribavirin (400,800 mg/day) was added. At the end of every cycle, response to therapy was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Results:, Partial response (PR) was observed in seven of nine patients, with stable or progressive disease in the remaining two patients. Tumors were resectable in three patients displaying PR after treatment. Tumor markers decreased significantly after therapy. Serum HCV-RNA titers were markedly decreased and became undetectable in all patients with HCV infection. National Cancer Institute,Common Toxicity Criteria: version 3.0 (NCI-CTC) grade 3 thrombocytopenia was seen in one case at the end of treatment, but was resolved with cessation of treatment. Other adverse effects were manageable. Conclusion:, Combination therapy with intra-arterial 5-FU and systemic PEG-IFN,-2b may be useful as a palliative treatment for patients with advanced HCC. A prospective controlled trial using a larger population of patients with advanced HCC is needed to evaluate this new combination therapy. [source] Patterns of Presentation, Diagnosis, and Treatment in Older Patients with Colon Cancer and Comorbid DementiaJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2004Supriya K. Gupta MD Objectives: To estimate patterns of colon cancer presentation, diagnosis, and treatment according to history of dementia using National Cancer Institute (NCI) Surveillance, Epidemiology, and End-Result (SEER) Medicare data. Design: Population-level cohort study. Setting: NCI's SEER-Medicare database. Participants: A total of 17,507 individuals aged 67 and older with invasive colon cancer (Stage I-IV) were identified from the 1993,1996 SEER file. Medicare files were evaluated to determine which patients had an antecedent diagnosis of dementia. Measurements: Parameters relating to the cohort's patterns of presentation and care were estimated using logistic regressions. Results: The prevalence of dementia in the cohort of newly diagnosed colon cancer patients was 6.8% (1,184/17,507). Adjusting for possible confounders, dementia patients were twice as likely to have colon cancer reported after death (i.e., autopsy or death certificate) (adjusted odds ratio (AOR)=2.31, 95% confidence interval (CI)=1.79,3.00). Of those diagnosed before death (n=17,049), dementia patients were twice as likely to be diagnosed noninvasively than with tissue evaluation (i.e., positive histology) (AOR=2.02 95% CI=1.63,2.51). Of patients with Stage I -III disease (n=12,728), patients with dementia were half as likely to receive surgical resection (AOR=0.48, 95% CI=0.33,0.70). Furthermore, of those with resected Stage III colon cancer (n=3,386), dementia patients were 78% less likely to receive adjuvant 5-fluorouracil (AOR=0.22, 95% CI=0.13,0.36). Conclusion: Although the incidences of dementia and cancer rise with age, little is known about the effect of dementia on cancer presentation and treatment. Elderly colon cancer patients are less likely to receive invasive diagnostic methods or curative-intent therapies. The utility of anticancer therapies in patients with dementia merits further study. [source] Identification of genes involved in radiation-induced G1 arrest,JOURNAL OF CHEMOMETRICS, Issue 10-11 2007Giuseppe Musumarra Abstract The advent of microarray gene expression technology permits the simultaneous analysis of the levels of expression of thousands of genes and provides large dataset requiring multivariate analysis tools. Multiple genetic factors may modulate the occurrence and magnitude of the arrest in the G1 phase of the cell cycle following exposure to ionizing radiation in human tumour cell lines. The ability to G1 arrest after exposure to gamma rays and the global gene expression profile, evaluated by cDNA microarray technology, have been reported for the National Cancer Institute (NCI) 60 tumour cell lines panel. The sensitivity of the tumour cell lines to radiations represents an activity fingerprinting that can be correlated by partial least squares (PLS) to the transcriptional profiles of the same cell lines. VIP values obtained by the PLS method are able to detect transcripts relevant to the radiation-induced G1 arrest. High VIP values were obtained for the basal levels of transcripts such as p21/Waf1/Cip1 and MDM2, that are well known for their roles in G1 arrest after irradiation. Novel functional relationships suggested by high VIP values can be investigated experimentally. As an example, in the present study, we report that the transcript for the FLJ11046 protein is induced dose-dependently by gamma-irradiation in a cell line with mutated p53, but not in cell lines with wild-type p53. Moreover specific silencing of FLJ11046 transcript by RNA interference technology results in a block of cell growth. Copyright © 2007 John Wiley & Sons, Ltd. [source] Akt expression may predict favorable prognosis in cholangiocarcinomaJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2006Milind M Javle Abstract Background:, Overexpression of signaling proteins including epidermal growth factor receptor (EGFR), Akt, mitogen activated protein kinase (MAPK) and cyclooxygenase-2 (COX-2) occurs in cholangiocarcinoma cell lines. However, the prognostic value of these markers is unknown. No prior study correlated the expression of these signaling proteins with clinical outcome. Further, co-expression of these proteins has not been reported. Co-expression may reflect cross-talk between signaling pathways. The aim of this clinicopathological study was to investigate the overexpression and co-expression of EGFR and related signaling proteins in cholangiocarcinoma and explore their relationship to clinical outcome. Methods:, Twenty-four consecutive cases of cholangiocarcinoma treated from 1996 to 2002 at Roswell Park Cancer Institute were included. Immunohistochemical staining of paraffin-embedded tissue sections was performed using antibodies against Akt, p-Akt, MAPK, p-MAPK, COX-2, EGFR and p-EGFR. Two pathologists independently scored the protein expression. Results:, Cyclooxygenase-2, Akt, and p-MAPK were commonly expressed in biliary cancers (100%, 96% and 87% of malignant cells, respectively). EGFR (60%) and p-EGFR (22%) overexpression was also detected. There was a significant association between EGFR and p-EGFR (P = 0.027) and between Akt and p-Akt (P = 0.017) expression in tumor tissue. A noteworthy association was shown between MAPK and p-Akt (P = 0.054). Multivariate analysis using the Cox proportional hazard model identified the use of chemotherapy (hazard ratio [HR] = 0.039, P = 0.0002), radiation (HR = 0.176, P = 0.0441) and Akt expression (HR = 0.139, P = 0.006) as the best predictors of overall prognosis. Conclusion:, Epidermal growth factor receptor signaling intermediates are commonly expressed in cholangiocarcinoma. Expression of Akt and use of systemic chemotherapy or radiation may correlate with improved survival. [source] Application of 3-methylthiopyrido[4,3- e]-1,4,2-dithiazine 1,1-dioxide to the synthesis of novel series of 4H -pyrido[4,3- e]-1,2,4-thiadiazine derivatives with potential biological activityJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 6 2009Zdzis, aw Brzozowski Two series of 4H -pyrido[4,3- e]-1,2,4-thiadiazine derivatives 3,5 and 7,12 were synthesized by the reactions of 3-methylthiopyrido[4,3- e]-1,4,2-dithiazine 1,1-dioxide 1 with 2-or 6-hydrazinoazines and 2-aminophenols or 2-aminothiophenol, respectively. Aminolysis of 8 (R = Me, Y = O) afforded the corresponding 3-(R-amino)-4-(2-hydroxy-5-methylphenyl)-4H -pyrido[4,3- e]-1,2,4-thiadiazine 1,1-dioxides 13,18. The structures of these compounds were confirmed on the basis of elemental analysis, spectral data, and X-ray crystallography. Compounds 3,5, 7,10, 12,15, and 17,18 were screened in vitro for antibacterial activity. Moreover, preliminary in vitro anticancer assay was performed for compounds 3, 7, 10, 11,13, and 17,18 at the National Cancer Institute (Bethesda, MD) at a single dose (10 ,M) in the full NCI 60 cell panel. J. Heterocyclic Chem., (2009). [source] Novel derivatives of the benzo[b][1,6]naphthyridine systemJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 2 2006Leslie W. Deady An efficient synthesis of 2-hydroxy-6-methylbenzo[b][1,6]naphthyridin-1(2H)-one was devised. The hydroxy group was alkylated, acylated and replaced by hydrogen. Electrophilic nitration, bromination and chlorosulfonation occurred readily in the 4-position. From the last, various sulfonamide derivatives were prepared. A selection of the products was screened by the National Cancer Institute. Cytotoxicities were generally low. [source] Progress in the development of immunotherapy for the treatment of patients with cancerJOURNAL OF INTERNAL MEDICINE, Issue 6 2001S. A. Rosenberg Abstract.,Rosenberg SA (National Cancer Institute, Institutes of Health, Bethesda, MD, USA). Progress in the development of immunotherapy for the treatment of patients with cancer (Review). J Intern Med 2001; 250: 462,475. Several recent developments have hallmarked progress in tumour immunology and immunotherapy. The use of interleukin-2 (IL-2) in cancer patients demonstrated that an immunological manipulation was capable of mediating the regression of established growing cancers in humans. The identification of the genes encoding cancer antigens and the development of means for effectively immunizing patients against these antigens has opened important new avenues of exploration for the development of effective active and cell-transfer immunotherapies for patients with cancer. [source] Scoring ligand similarity in structure-based virtual screeningJOURNAL OF MOLECULAR RECOGNITION, Issue 4 2009Maria I. Zavodszky Abstract Scoring to identify high-affinity compounds remains a challenge in virtual screening. On one hand, protein,ligand scoring focuses on weighting favorable and unfavorable interactions between the two molecules. Ligand-based scoring, on the other hand, focuses on how well the shape and chemistry of each ligand candidate overlay on a three-dimensional reference ligand. Our hypothesis is that a hybrid approach, using ligand-based scoring to rank dockings selected by protein,ligand scoring, can ensure that high-ranking molecules mimic the shape and chemistry of a known ligand while also complementing the binding site. Results from applying this approach to screen nearly 70,000 National Cancer Institute (NCI) compounds for thrombin inhibitors tend to support the hypothesis. EON ligand-based ranking of docked molecules yielded the majority (4/5) of newly discovered, low to mid-micromolar inhibitors from a panel of 27 assayed compounds, whereas ranking docked compounds by protein,ligand scoring alone resulted in one new inhibitor. Since the results depend on the choice of scoring function, an analysis of properties was performed on the top-scoring docked compounds according to five different protein,ligand scoring functions, plus EON scoring using three different reference compounds. The results indicate that the choice of scoring function, even among scoring functions measuring the same types of interactions, can have an unexpectedly large effect on which compounds are chosen from screening. Furthermore, there was almost no overlap between the top-scoring compounds from protein,ligand versus ligand-based scoring, indicating the two approaches provide complementary information. Matchprint analysis, a new addition to the SLIDE (Screening Ligands by Induced-fit Docking, Efficiently) screening toolset, facilitated comparison of docked molecules' interactions with those of known inhibitors. The majority of interactions conserved among top-scoring compounds for a given scoring function, and from the different scoring functions, proved to be conserved interactions in known inhibitors. This was particularly true in the S1 pocket, which was occupied by all the docked compounds. Copyright © 2009 John Wiley & Sons, Ltd. [source] Effect of berberine on proliferation, cell cycle and apoptosis in HeLa and L1210 cellsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2003a Jantová Previous studies on the anticancer activity of protoberberine alkaloids against a variety of cancer cell lines were extended to human tumour HeLa and murine leukemia L1210 cell lines. An attempt was also made to investigate the relationship between the cytotoxic activity of berberine and its molecular mechanism of action. Cytotoxicity was measured in-vitro using a primary biochemical screening according to Oyama and Eagle, and the growth inhibition assay. The in-vitro cytotoxic techniques were complemented by cell cycle analysis and determination of apoptotic DNA fragmentation in L1210 cells. Berberine acted cytotoxically on both tumour cell lines. The sensitivity of leukemia L1210 cells to the berberine was higher than that of HeLa cells. The IC100 was below 100 ,g mL,1 for HeLa cells and approached a 10 , mL,1 limit for the leukemia L1210 cells. For both cell lines the IC50 was found to be less than 4 ,g mL,1, a limit put forward by the National Cancer Institute (NCI) for classification of the compound as a potential anticancer drug. In L1210 cells treated with 10,50 , mL,1 berberine, G0/G1 cell cycle arrest was observed. Futhermore, a concentration-dependent decrease of cells in S phase and increase in G2/M phase was detected. In addition, apoptosis detected as sub-G0 cell population in cell cycle measurement was proved in 25,100 ,g mL,1 berberine-treated cells by monitoring the apoptotic DNA fragmentation (DNA ladder) using agarose gel electrophoresis. [source] Adjuvant radiation therapy is associated with improved survival for gallbladder carcinoma with regional metastatic diseaseJOURNAL OF SURGICAL ONCOLOGY, Issue 1 2007Pablo Mojica MD Abstract Background Gallbladder carcinoma is a rare malignancy and is associated with dismal outcomes. The aim of this study was to better define the role of adjuvant radiation therapy in the management of gallbladder carcinoma. Methods The Surveillance, Epidemiological, and End Results (SEER) survey from the National Cancer Institute was queried from 1992 to 2002. Retrospective analysis was done. The end-point of the study was overall survival. Results There were a total of 3,187 cases of gallbladder carcinoma in the registry from 1992 to 2002. Of the surgical group, 35% were stage I, 36% were stage II, 6% were stage III, and 21% were stage IV. Adjuvant radiation was used in 17% of the cases. The median survival for those patients receiving adjuvant radiation therapy was 14 months compared to an 8 months median survival for those treated without adjuvant radiation therapy (P,,,0.001). The survival benefit associated with radiation use was only presenting those patients with regional spread (P,=,0.0001) and tumors infiltrating the liver (P,=,0.011). Conclusion The use of adjuvant radiation therapy is associated with improved survival in patients with locally advanced gallbladder cancer or gallbladder cancer with regional disease. J. Surg. Oncol. 2007;96:8,13 © 2007 Wiley-Liss, Inc. [source] Barriers to the optimal rehabilitation of surgical cancer patients in the managed care environment: An administrator's perspectiveJOURNAL OF SURGICAL ONCOLOGY, Issue 5 2007Pamela Germain MBA Abstract Ensuring that surgical cancer patients obtain optimal rehabilitation care (defined here as all care provided post-operatively following cancer surgery) can be challenging because of the fragmented nature of the U.S. healthcare delivery and payment systems. In the managed care environment, surgical cancer patients' access to rehabilitation care is likely to vary by type of health insurance plan, by setting, by type of provider, and by whether care is provided in-network or out-of-network. The author of this article, who negotiates managed care contracts for the Roswell Park Cancer Institute (RPCI), gives examples of strategies used with some success by RPCI to collaborate with local payers to ensure that surgical cancer patients get optimal rehabilitation care, especially as they make the transition from hospital to outpatient care. She suggests that further collaborations of healthcare providers, payers, consumers, and policymakers are needed to help ensure optimal rehabilitation care for surgical cancer patients. J. Surg. Oncol. 95:386,392. © 2007 Wiley-Liss, Inc. [source] An overview of ethnicity and assessment of family history in primary care settingsJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 10 2006Ann Maradiegue PhD(c), FNP-C (Instructor, Family Nurse Practitioner Program) Abstract Purpose: To discuss the importance of and the nurse practitioner's (NP's) role in the assessment of ethnicity/family of origin in conducting a multigenerational family history in primary care settings. Data sources: A review of the literature on past research results addressing racial and ethnic disparities and current articles from scientific journals exploring the relationship between race and genetics. Web sites were from the National Institutes of Health, the Human Genome Research Institute, the National Cancer Institute, and the Health and Human Services Minority Health and Disparities report. Conclusions: The family history has received renewed interest due to the sequencing of the human genome. A multigenerational family history is an important first step in screening for a multitude of disorders impacted by genetic susceptibility, shared environments, and common behaviors. Assessment of the patient's ethnicity/family of origin is an integral part of the multigenerational family history, particularly in the diagnosis of chronic diseases and the assessment of risks for genetic disorders. The multigenerational family history is important in diagnosis, predictive genetic testing, disease prevention, and health promotion. Challenges facing NPs and the utilization of a multigenerational family history in the current U.S. health system include (a) training clinicians on the correct assessment and utilization of a multigenerational family history, (b) assessment of the subtleties of ethnicity and identifying multiple ethnic groups within a family, (c) collection of the family history in a manner that is sensitive to the cultural beliefs of individuals, and (d) avoidance of stereotyping Implications for practice: Significant advances in genetics and genetic testing requires that NPs be well versed in collecting and interpreting a multigenerational family history to include assessment of the patient/family's ethnicity/family of origin. The ability to effectively conduct and evaluate the individual's and family's health risk through a multigenerational family history will be important in diagnosis, health promotion, disease prevention, and the determination for genetic counseling referral and predictive testing when appropriate. Assessment of risk and prevention of disease is also important in reducing health disparities. [source] Clinical Pharmacokinetics of the PDT Photosensitizers Porfimer Sodium (Photofrin), 2-[1-Hexyloxyethyl]-2-Devinyl Pyropheophorbide-a (Photochlor) and 5-ALA-Induced Protoporphyrin IXLASERS IN SURGERY AND MEDICINE, Issue 5 2006David A. Bellnier PhD Abstract Background and Objectives Photodynamic therapy (PDT) uses a photosensitizer activated by light, in an oxygen-rich environment, to destroy malignant tumors. Clinical trials of PDT at Roswell Park Cancer Institute (RPCI) use the photosensitizers Photofrin, Photochlor, and 5-ALA-induced protoporphyrin IX (PpIX). In some studies the concentrations of photosensitizer in blood, and occasionally in tumor tissue, were obtained. Pharmacokinetic (PK) data from these individual studies were pooled and analyzed. This is the first published review to compare head-to-head the PK of Photofrin and Photochlor. Study Design/Materials and Methods Blood and tissue specimens were obtained from patients undergoing PDT at RPCI. Concentrations of Photofrin, Photochlor, and PpIX were measured using fluorescence analysis. A non-linear mixed effects modeling approach was used to analyze the PK data for Photochlor (up to 4 days post-infusion; two-compartment model) and a simpler multipatient-data-pooling approach was used to model PK data for both Photofrin and Photochlor (at least 150 days post-infusion; three-compartment models). Physiological parameters were standardized to correspond to a standard (70 kg; 1.818 m2 surface area) man to facilitate comparisons between Photofrin and Photochlor. Results Serum concentration-time profiles obtained for Photofrin and Photochlor showed long circulating half-lives, where both sensitizers could be found more than 3 months after intravenous infusion; however, estimated plasma clearances (standard man) were markedly smaller for Photofrin (25.8 ml/hour) than for Photochlor (84.2 ml/hour). Volumes of distribution of the central compartment (standard man) for both Photofrin and Photochlor were about the size (3.14 L, 4.29 L, respectively) of plasma volume, implying that both photosensitizers are almost 100% bound to serum components. Circulating levels of PpIX were generally quite low, falling below the level of instrument sensitivity within a few days after topical application of 5-ALA. Conclusion We have modeled the PK of Photochlor and Photofrin. PK parameter estimates may, in part, explain the relatively long skin photosensitivity attributed to Photofrin but not Photochlor. Due to the potential impact and limited experimental PK data in the PDT field further clinical studies of photosensitizer kinetics in tumor and normal tissues are warranted. Lasers Surg. Med. © 2006 Wiley-Liss, Inc. [source] Combined Use of PCA and QSAR/QSPR to Predict the Drugs Mechanism of Action.MOLECULAR INFORMATICS, Issue 4 2009An Application to the NCI ACAM Database Abstract During the years the National Cancer Institute (NCI) accumulated an enormous amount of information through the application of a complex protocol of drugs screening involving several tumor cell lines, grouped into panels according to the disease class. The Anti-cancer Agent Mechanism (ACAM) database is a set of 122 compounds with anti-cancer activity and a reasonably well known mechanism of action, for which are available drug screening data that measure their ability to inhibit growth of a panel of 60 human tumor lines, explicitly designed as a training set for neural network and multivariate analysis. The aim of this work is to adapt a methodology (previously developed for the analysis of DNA minor groove binders) for the analysis of NCI ACAM database, using Principal Component Analysis (PCA) and QSAR/QSPR for the prediction of the mechanism of action of anti-cancer drugs. The entire database was splitted in a training set of 60 structures and a test set of 48 ones, and each set was expressed in form of a matrix on which further procedures were performed. Three statistical parameters were calculated: First Attempt of Prediction (FAP) expresses the percentage of correct predictions at first attempt, Total Attempt of Prediction (TAP) expresses the total percentage of correct predictions across all the three attempts, Non-Classified (NC) expresses the percentage of compounds whose mechanism of action has failed to be predicted. The predictive ability of this approach is variable, but the results obtained are generally good; using 50% Growth Inhibiting concentration (GI50) values as training data, we were able to assign a correct mechanism of action with a good degree of reliability (more than 79%). [source] Training program in cancer and blood diseases: Pediatric Hematology/Oncology Fellowship Program, Children's Hospital Boston/Dana-Farber Cancer Institute,AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2010David A. Williams No abstract is available for this article. [source] The pediatric preclinical testing program: Description of models and early testing results,PEDIATRIC BLOOD & CANCER, Issue 7 2007Peter J. Houghton PhD Abstract Background The Pediatric Preclinical Testing Program (PPTP) is an initiative supported by the National Cancer Institute (NCI) to identify novel therapeutic agents that may have significant activity against childhood cancers. The PPTP has established panels of childhood cancer xenografts and cell lines to be used for in vivo and in vitro testing. These include panels for Wilms tumor, sarcomas (rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma), neuroblastoma, brain tumors (glioblastoma, ependymoma, and medulloblastoma), rhabdoid tumors (CNS and renal), and acute lymphoblastic leukemia (ALL). Here, we describe the characteristics of the in vivo tumor panels and report results for the in vivo evaluation of two standard agents, vincristine and cyclophosphamide. Procedures Solid tumors were grown subcutaneously in immune-deficient mice and tumor dimensions were measured weekly. ALL xenografts were inoculated intravenously and human CD45-positive cells were enumerated weekly. Results Vincristine-induced objective responses in 6 of 24 (25%) and cyclophosphamide-induced objective responses in 18 of 28 (64%) solid tumor models. Comparable assessments of high levels of activity for these two agents were obtained using a tumor growth delay (TGD) measure. Both agents induced regressions in each of the ALL models evaluated. Conclusions We have established 51 solid tumor and 10 ALL in vivo models. The models identify vincristine and cyclophosphamide as having broad-spectrum activity. The PPTP tumor panels appear to generally recapitulate the activity of these agents against specific childhood cancers and to have the potential for identifying novel agents having significant clinical activity. Pediatr Blood Cancer 2007;49:928,940. Published 2006 Wiley-Liss, Inc. [source] Screening for Wilms tumor and hepatoblastoma in children with Beckwith-Wiedemann syndromes: A cost-effective model,PEDIATRIC BLOOD & CANCER, Issue 4 2001D. Elizabeth McNeil MD Abstract Background We undertook a cost-benefit analysis of screening for Wilms tumor and hepatoblastoma in children with Beckwith-Wiedemann syndrome (BWS), a known cancer predisposition syndrome. The purpose of this analysis was twofold: first, to assess whether screening in children with BWS has the potential to be cost-effective; second, if screening appears to be cost-effective, to determine which parameters would be most important to assess if a screening trial were initiated. Procedures We used data from the BWS registry at the National Cancer Institute, the National Wilms Tumor Study (NWTS), and large published series to model events for two hypothetical cohorts of 1,000 infants born with BWS. One hypothetical cohort was screened for cancer until a predetermined age, representing the base case. The other cohort was unscreened. For our base case, we assumed: (a) sonography examinations three times yearly (triannually) from birth until 7 years of age; (b) screening would result in one stage shift downward at diagnosis for Wilms tumor and hepatoblastoma; (c) 100% sensitivity and 95% specificity for detecting clinical stage I Wilms tumor and hepatoblastoma; (d) a 3% discount rate; (e) a false positive result cost of $402. We estimated mortality rates based on published Wilms tumor and hepatoblastoma stage specific survival. Results Using the base case, screening a child with BWS from birth until 4 years of age results in a cost per life year saved of $9,642 while continuing until 7 years of age results in a cost per life-year saved of $14,740. When variables such as cost of screening examination, discount rate, and effectiveness of screening were varied based on high and low estimates, the incremental cost per life-year saved for screening up until age four remained comparable to acceptable population based cancer screening ranges (<,$50,000 per life year saved). Conclusions Under our model's assumptions, abdominal sonography examinations in children with BWS represent a reasonable strategy for a cancer screening program. A cancer screening trial is warranted to determine if, when, and how often children with BWS should be screened and to determine cost-effectiveness in clinical practice. Med Pediatr Oncol 2001;37:349,356. Published 2001 Wiley-Liss, Inc. [source] Latitude and Incidence of Ocular MelanomaPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2006Guo-Pei Yu We investigated the associations between latitude and the incidence of two different types of ocular melanoma, external ocular melanoma (exposed to sunlight) and internal melanoma (not exposed to sunlight), separately. Using 1992,2002 data from the Surveillance, Epidemiology, and End Results (SEER) Program of National Cancer Institute, we identified 2142 ocular melanoma cases in non-Hispanic whites, and then regressed the incidences of various types of ocular melanomas with latitude. Our analysis indicated that the higher the latitude (away from the equator, the less sun exposure), the lower the risk of external ocular melanoma (eyelid and conjunctival melanomas) among non-Hispanic whites (P for trend = 0.018). The incidence increased 2.48 fold from 47,48° to 20,22°. This trend is very similar to that of skin melanoma. The incidence of internal ocular melanoma (uveal melanoma) increased significantly with increasing latitudes (the less sun exposure, P for trend < 0.0001), it increased 4.91 fold from 20,22° to 47,48°. The latitudinal patterns of ocular melanomas may reflect the dual effects of sunlight exposure, i.e. a mutagenic effect of direct solar radiation on external ocular melanomas and a protective effect for internal uveal melanoma, which is similar to the sun radiation protective effects for various internal malignant tumors that are not exposed to the sunlight. [source] Gail Model Risk Factors: Impact of Adding an Extended Family History for Breast CancerTHE BREAST JOURNAL, Issue 3 2008Anna Crispo ScD Abstract:, An approach commonly used in estimating breast cancer risk is the Gail model. The objective of this study was to evaluate the feasibility and impact of adding extended family history as a new breast cancer risk factor into the Gail model. The data of the present study include cases with breast cancer and hospitalized controls recruited in the National Cancer Institute of Naples (southern Italy) between 1997 and 2000. We compared the first-degree relative (FDR) risk factor (standard Gail model) with the second-degree relative (SDR) information; and the FDR risk factor (standard Gail model) with the combination of FDR and SDR. We computed the c-statistic by comparing the risks found in our population to those in Gail-US population. The concordance for the model with FDR was 0.55 (95% CI 0.53,0.58), the model with SDR shows a modest but significant discriminatory accuracy (0.56, 95% CI 0.53,0.59), and the combination of FDR+SDR gave the concordance statistic of 0.57 (95% CI 0.54,0.60), indicating a good comparison between the two models. The results of our study show that extended family history information could be useful to improve the discriminatory power of the Gail model risk factors. [source] Local institutional review board (IRB) review of a multicenter trial: Local costs without local contextANNALS OF NEUROLOGY, Issue 2 2010Bernard Ravina MD, MSCE Multicenter clinical research involves parallel Institutional Review Board (IRB) reviews based on the premise that local review reflects aspects of the research environment. We examined the costs and effects of local IRB review of the consent and protocol in a multicenter clinical trial in Parkinson disease. Seventy-six percent of changes to the consent reflected standard institutional language, with no substantive changes to the protocol. The costs of this process exceeded $100,000. These findings support initiatives by the Office of Human Research Protections (OHRP) and the National Cancer Institute (NCI) to facilitate centralized reviews. This may be an opportune time for the National Institute of Neurological Disorders and Stroke (NINDS) to adopt a central review model. ANN NEUROL 2010;67:258,260 [source] SQUAMOUS CELL CARCINOMA OF THE LIP: A RETROSPECTIVE REVIEW OF THE PETER M ACCALLUM CANCER INSTITUTE EXPERIENCE 1979,88ANZ JOURNAL OF SURGERY, Issue 5 2000D. Mccombe Background: Squamous cell carcinoma (SCC) of the lower lip is a common malignancy in Australia. Surgical excision and/or radiotherapy are used in treatment, and are regarded as equally effective. Methods: A retrospective review of 323 patients treated at the Peter MacCallum Cancer Institute with either surgical excision and/or radiotherapy, evaluated disease recurrence, cause-specific mortality, and the incidence of metachronous lesions. Results: Recurrence-free survival at 10 years was estimated to be 92.5%, and cause-specific survival at 10 years was estimated to be 98.0%. Equivalent rates of local control were obtained with surgery and radiotherapy. Recurrence was related to tumour stage and differentiation. A high incidence of metachronous lesions was noted, 25 patients had a lesion prior to presentation and 33 patients developed second lip lesions during the study period. Conclusions: Squamous cell carcinoma of the lower lip is well treated with surgery or radiotherapy. The preferred treatment for most patients with SCC of the lower lip in the Australian population is surgical excision. This study has shown a significant incidence of metachronous lip neoplasia, except in those patients whose whole lip had been resurfaced. [source] Synthesis of 2-Fluoro N10 -Substituted Acridones and Their Cytotoxicity Studies in Sensitive and Resistant Cancer Cell Lines and Their DNA Intercalation StudiesARCHIV DER PHARMAZIE, Issue 11 2009Yergeri C. Mayur Abstract A series of 2-fluoro N10 -substituted acridone derivatives with varying alkyl side chain length with propyl, butyl substitution, and a tertiary amine group at the terminal end of the alkyl side chain were synthesized and screened against cancer cell lines SW 1573, SW 1573 2R 160 (P-gp substrate) which are non-small lung cancer cell lines, MCF-7, MCF-7/MR (BCRP substrate) are breast cancer cell lines, 2008 WT, 2008MRP1, 2008MRP2, 2008MRP3 are ovarian cancer cell lines, and human embryo kidney cell lines like HEK293, HEK293 MRP4, and HEK293 MRP5i. The propyl-series compounds showed lipophilicity in the range of 1.93 to 4.40 and the butyl series in the range of 2.37 to 4.78. The compounds 4, 7, and 8 showed good cytotoxicity against the 60 human cancer cell line panel of the National Cancer Institute, USA. The compounds 14 and 15 showed a better cytotoxicity in most of the cancer cell lines compared to other compounds tested. The DNA-binding properties of the compounds were evaluated based on their affinity or intercalation with CT-DNA measured with absorption titration. The compound 11 bearing planar tricyclic ring linked with a butyl methylpiperazino side chain showed the highest binding affinity with a binding constant (Ki) of 10.38×10 M,1. Evaluation of the compounds in cell lines with an overexpression of various multidrug resistance-related protein (MRP), P-glycoprotein (P-gp), or Breast Cancer Resistance Protein (BCRP) showed that all compounds are not substrates for any of these transporters. [source] Synthesis and Biological Evaluation of Some Polymethoxylated Fused Pyridine Ring Systems as Antitumor AgentsARCHIV DER PHARMAZIE, Issue 10 2009Sherif A. F. Rostom Abstract A series of 3,5- bis(arylidene)-4-piperidones like chalcone analogues carrying variety of methoxylated aryl groups, pyrazolo[4,3- c]pyridines, pyrido[4,3- d]pyrimidines, and pyrido[3,2- c]pyridines, carrying an arylidene moiety, and some pyrano[3,2- c]pyridines, like flavone and coumarin isosteres, were synthesized and screened for their in-vitro antitumor activity at the National Cancer Institute (NCI, USA). The tested compounds 7, 9, 10, 12, 13, 15, 17, and 19 exhibited a broad spectrum of antitumor activity. Compounds belonging to the pyrazolo[4,3- c]pyridine series proved to be more active than those of the pyrido[3,2- c]pyridine and pyrano[3,2- c]pyridine analogues, in which the monomethoxylated derivatives showed better antitumor activity when compared with their corresponding dimethoxylated congeners. Compound 7 is considered to be the most active member identified in this study with a broad spectrum of activity against 22 different tumor cell lines belonging to the nine subpanels employed, and a particular effectiveness against the breast cancer T-47D cell line (GI 54.7%). The pyrano[3,2- c]pyridine heterocyclic system 19 proved to be the most active antitumor agent among the six-membered fused pyridines, with variable activity against 18 different tumor cell lines, and special activity against the non-small cell lung cancer Hop-92 and ovarian cancer OVCAR-4 cell lines (GI values 63.9 and 48.5%, respectively). [source] Colposcopic and histologic findings in women with a cytologic diagnosis of atypical squamous cells of undetermined significanceAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 6 2004Fariba YARANDI Abstract Background: The optimal method for managing a patient diagnosed with atypical squamous cells of undetermined significance (ASCUS) has not yet been established. The interim guidelines published by the National Cancer Institute suggest that a patient should be referred for colposcopy after the second ASCUS diagnosis within 2 years. Aim: To assess the significance of ASCUS in predicting the presence of underlying squamous intraepithelial lesion (SIL) of the uterine cervix. Study population: Women undergoing colposcopy for ASCUS cytology at a teaching hospital in Tehran University, in the years 1998,2001, considered eligible to enter this retrospective study. Results: Of the 266 patients who underwent colposcopy, 28 (11%) had low-grade squamous intraepithelial lesion (LSIL), 16 (6.3%) had high-grade squamous intraepithelial lesion (HSIL) two (0.8%) had squamous cell carcinoma (SCC), and 48 (18.8%) had flat condyloma. Conclusion: Atypical squamous cells of undetermined significance (ASCUS) on a cervical smear is a good marker for detecting underlying SIL and condyloma. Thus, immediate colposcopy and directed biopsy are appropriate follow-up procedures. [source] An Age-Stratified Poisson Model for Comparing Trends in Cancer Rates Across Overlapping RegionsBIOMETRICAL JOURNAL, Issue 4 2008Yi Li Abstract The annual percent change (APC) has been used as a measure to describe the trend in the age-adjusted cancer incidence or mortality rate over relatively short time intervals. The yearly data on these age-adjusted rates are available from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. The traditional methods to estimate the APC is to fit a linear regression of logarithm of age-adjusted rates on time using the least squares method or the weighted least squares method, and use the estimate of the slope parameter to define the APC as the percent change in the rates between two consecutive years. For comparing the APC for two regions, one uses a t-test which assumes that the two datasets on the logarithm of the age-adjusted rates are independent and normally distributed with a common variance. Two modifications of this test, when there is an overlap between the two regions or between the time intervals for the two datasets have been recently developed. The first modification relaxes the assumption of the independence of the two datasets but still assumes the common variance. The second modification relaxes the assumption of the common variance also, but assumes that the variances of the age-adjusted rates are obtained using Poisson distributions for the mortality or incidence counts. In this paper, a unified approach to the problem of estimating the APC is undertaken by modeling the counts to follow an age-stratified Poisson regression model, and by deriving a corrected Z -test for testing the equality of two APCs. A simulation study is carried out to assess the performance of the test and an application of the test to compare the trends, for a selected number of cancer sites, for two overlapping regions and with varied degree of overlapping time intervals is presented. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] | |||||||||||||||||||||||||||||||||||||