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Sample records for advanced solid tumors

  1. Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors

    Science.gov (United States)

    2016-04-18

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Pheochromocytoma; Pancreatic Polypeptide Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Melanoma; Recurrent Neuroendocrine Carcinoma of the Skin; Recurrent Non-small Cell Lung Cancer; Recurrent Pheochromocytoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Neuroendocrine Carcinoma of the Skin; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Stage IV Renal Cell Cancer; Thyroid Gland Medullary Carcinoma; Unspecified Adult Solid Tumor, Protocol Specific

  2. Temsirolimus, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Tumors

    Science.gov (United States)

    2014-06-18

    Ovarian Sarcoma; Ovarian Stromal Cancer; Recurrent Endometrial Carcinoma; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Stage III Endometrial Carcinoma; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage IV Endometrial Carcinoma; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific

  3. Clinical Analysis of Bisphosphonates Treatment on Bone Metastases and Hypercalcemia of Malignancy in Advanced Solid Tumor

    Institute of Scientific and Technical Information of China (English)

    MING Shu-hong; SUN Tie-ying

    2007-01-01

    Objective: To evaluate the efficacy and toleration of bisphosphonates therapy in patients with bone metastases and hypercalcemia of malignancy in advanced solid tumor. Methods: Patients with histologically or cytologically confirmed cancer and hypercalcemia with bone metastases were designed to open treatment with either 4mg zoledronic acid or 90mg pamidronate. The primary efficacy parameters were pain scores(NRS), Corrected serum calcium(CSC) and CSC effective rate. The vital signs, biochemical and hematological parameters were determined. Results: Twenty patients were enrolled in this study, twelve patients in zoledronic acid group and eight in pamidronate group. Zoledronic acid and pamidronate significantly palliated pain. Pain scores were significantly lower at end-point after Zoledronic acid or pamidronate infusion(5.92 vs 3.25,P<0.01;6.13 vs 4.38, P<0.01, respectively). The mean CSC level decreased significantly after Zoledronic acid or pamidronate infusion from 12.86 to 10.28mg/dl and 13.19 to 10.36mg/dl respectively. The CSC effective rate was about 90% at 14 days after infusion in two groups. There was no statistical significance for all primary efficacy parameters in zoledronic acid group compared with pamidronate group. An adverse reaction was mild fever after pamidronate infusion and then completely reversible. Conclusion: Zoledronic acid and pamidronate disodium were well tolerated and effective for bone metastases and hypercalcemia of malignancy in advanced solid tumor.

  4. Continuation Study of Entinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumors

    Science.gov (United States)

    2016-09-16

    Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Digestive System Neoplasms; Endocrine Gland Neoplasms; Carcinoma, Non-Small-Cell Lung; Lung Diseases; Breast Diseases; Renal Neoplasm; Solid Tumors

  5. Bortezomib in combination with celecoxib in patients with advanced solid tumors: a phase I trial

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    Salzer Shanta

    2007-12-01

    Full Text Available Abstract Background COX-2 inhibitors, such as celecoxib, and ubiquitin-proteasome pathway inhibitors, such as bortezomib, can down-regulate NF-κB, a transcription factor implicated in tumor growth. The objective of this study was to determine the maximum tolerated dose and dose-limiting toxicities of bortezomib in combination with celecoxib in patients with advanced solid tumors. Methods Patients received escalating doses of bortezomib either on a weekly schedule (days 1, 8, 15, 22, and 29 repeated every 42 days or on a twice-weekly administration schedule (days 1, 4, 8, and 11 repeated every 21 days, in combination with escalating doses of celecoxib twice daily throughout the study period from 200 mg to 400 mg twice daily. Results No dose-limiting toxicity was observed during the study period. Two patients had stable disease lasting for four and five months each, and sixteen patients developed progressive disease. Conclusion The combination of bortezomib and celecoxib was well tolerated, without dose limiting toxicities observed throughout the dosing ranges tested, and will be studied further at the highest dose levels investigated. Trial registration number NCT00290680.

  6. Phase I Study of Capecitabine, Oxaliplatin, Bevacizumab, and Everolimus in Advanced Solid Tumors

    Science.gov (United States)

    Rangwala, F.; Bendell, J.; Kozloff, M.; Arrowood, C.; Dellinger, A.; Meadows, J.; Tourt-Uhlig, S.; Murphy, J.; Meadows, K.L.; Starr, A.; Broderick, S.; Brady, J.C.; Cushman, S. M.; Morse, M.; Uronis, H.; Hsu, S.D.; Zafar, S.Y.; Wallace, J.; Starodub, A.; Strickler, J.; Pang, H.; Nixon, A.B.; Hurwitz, H.

    2014-01-01

    Purpose To define maximum tolerated dose (MTD), toxicities, and pharmacodynamics of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumor patients. Design This was a standard “3+3” dose-escalation trial. All subjects received bevacizumab 7.5mg/kg on day one of each cycle. Doses for capecitabine, oxaliplatin and everolimus were modified per dose limiting toxicity (DLT). Baseline and on-treatment plasma biomarkers were analyzed. Archived tumor mRNA levels were evaluated for NRP1, NRP2 and VEGF-A isoforms. Results Twenty-nine patients were evaluable for toxicity and 30 for efficacy. Two DLTs were observed in cohort 1 and one DLT each was observed in cohort -1 and -1b. Grade ≥3 toxicities included neutropenia, hypertension, perforation/fistula/hemorrhage, hypertriglyceridemia, diarrhea, and thromboembolism. Twelve subjects experienced partial response (PR); 12 had stable disease as best response. Three of seven chemorefractory metastatic colorectal cancer (mCRC) subjects experienced PR; eight of 15 chemonaive mCRC subjects experienced PR. Plasma TβRIII and IL-6 increased on treatment but without correlation to outcome. Increased VEGF165 levels significantly correlated with longer progression free survival. Conclusions Everolimus with full dose capecitabine, oxaliplatin, and bevacizumab had unacceptable toxicity. MTD was: everolimus 5mg daily; capecitabine 680mg/m2 BID days 1-14; oxaliplatin 100mg/m2 and bevacizumab 7.5mg/kg, day one. Activity was noted in mCRC. PMID:24711126

  7. Pharmacokinetic characteristics of vincristine sulfate liposomes in patients with advanced solid tumors

    Institute of Scientific and Technical Information of China (English)

    Zhao YAN; Zhong-ling ZHU; Zheng-zi QIAN; Ge HU; Hua-qing WANG; Wan-hui LIU; Guang CHENG

    2012-01-01

    Aim:To evaluate the single- and multiple-dose pharmacokinetics of vincristine sulfate liposomes (VSLI) in patients with advanced solid tumors.Methods:In single-dose pharmacokinetic study,16 patients were administered VSLI (1.5,2.0,or 2.3 mg.m-2) through intravenous infusion.Another 6 patients receiving vincristine sulfate (VCR,2.0 mg) were taken as the control.In multiple-dose pharmacokinetic study,12 patients were administered VSLI (1.5 or 1.8 mg.m-2) through intravenous infusion weekly for 4 consecutive weeks.The plasma concentration of VSLI was determined using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.Results:After intravenous infusion of the single dose of VSLI,the plasma concentrations were characterized by bi-exponential decline curves.No statistically significant differences were observed between the main pharmacokinetic parameters in the 3 dose groups.Compared with the patients receiving VCR,the patients treated with VSLI displayed an increase in the area under the plasma concentration vs time curve (AUC),and a decrease in plasma clearance rates.On the 4th cycle in the multiple-dose study,the plasma concentration of VCR in all subjects prior to the weekly administration was below the lower limit of quantification (LLOQ).The calculated pharmacokinetic parameters from the subjects in the multiple-and single-dose (1.5 mgm-2) groups had no significant differences.Although the administration of liposomal VCR may significantly elevate the plasma concentration of VCR,VSLI-associated adverse events were similar to those associated with conventional VCR.Conclusion:VSLI exhibits a lower clearance and a higher AUC compared with conventional VCR.No accumulation was observed in patients exposed to VSLI for 4 consecutive weeks.VSLI was generally tolerated in the subjects.The phase Ⅱ dose of VSLI may be recommended as 4 doses of 1.5 mg·m-2 for treatment of patients with advanced solid tumors.

  8. Low-Dose Decitabine-Based Chemoimmunotherapy for Patients with Refractory Advanced Solid Tumors: A Phase I/II Report

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    Hui Fan

    2014-01-01

    Full Text Available Aberrant DNA methylation is one of the main drivers of tumor initiation and progression. The reversibility of methylation modulation makes it an attractive target for novel anticancer therapies. Clinical studies have demonstrated that high-dose decitabine, a hypomethylating agent, results in some clinical benefits in patients with refractory advanced tumors; however, they are extremely toxic. Low doses of decitabine minimize toxicity while potentially improving the targeted effects of DNA hypomethylation. Based on these mechanisms, low-dose decitabine combined with chemoimmunotherapy may be a new treatment option for patients with refractory advanced tumors. We proposed the regimen of low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors. A favorable adverse event profile was observed in our trial that was highlighted by the finding that most of these adverse events were grades 1-2. Besides, the activity of our cohort was optimistic and the clinical benefit rate was up to 60%, and the median PFS was prolonged compared with PFS to previous treatment. We also identified a significant correlation between the PFS to previous treatment and clinical response. The low-dose DAC decitabine-based chemoimmunotherapy might be a promising protocol for improving the specificity and efficiency of patients with refractory advanced solid tumors. This trial is registered in the ClinicalTrials.gov database (identifier NCT01799083.

  9. Veliparib, Oxaliplatin, and Capecitabine in Treating Patients With Advanced Solid Tumors

    Science.gov (United States)

    2014-04-01

    Adenocarcinoma of the Pancreas; Adenocarcinoma of the Stomach; BRCA1 Mutation Carrier; BRCA2 Mutation Carrier; Ovarian Mucinous Cystadenocarcinoma; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gastric Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  10. Targeting solid tumors : advances in treatment strategies for glioma and colorectal cancer

    NARCIS (Netherlands)

    van Houdt, W.J.

    2011-01-01

    Curative treatment of most solid tumors includes surgical interference. However, the incidence of local recurrence or distant micrometastases is significantly lower when patients are treated with systemic or locally administered chemo- or targeted therapy. In the last decade, many novel targeting st

  11. Phase I study of olaratumab in Japanese patients with advanced solid tumors.

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    Doi, Toshihiko; Ma, Yan; Dontabhaktuni, Aruna; Nippgen, Cornelia; Nippgen, Johannes; Ohtsu, Atsushi

    2014-07-01

    Olaratumab (IMC-3G3) is a fully human IgG1 monoclonal antibody that selectively binds the external domain of human platelet-derived growth factor receptor-α with high affinity and blocks ligand binding. This was a single-center, dose-escalation, phase I trial of olaratumab in Japanese patients with advanced/refractory solid malignancies. Three to six patients were enrolled into each of three cohorts: Patients received i.v. olaratumab: 10 mg/kg on days 1 and 8 every 3 weeks (cohort 1); 20 mg/kg every 2 weeks (cohort 2); and 15 mg/kg on days 1 and 8 every 3 weeks (cohort 3). Doses were escalated from cohort 1 through cohort 3. The primary objective was to establish the safety and pharmacokinetic profile of olaratumab. Sixteen patients were treated across three cohorts. There were no dose-limiting toxicities, so the maximum tolerated dose was not reached. The most common olaratumab-related treatment-emergent adverse events (TEAEs) were proteinuria (25.0%) and elevated aspartate transaminase (12.5%). One patient (cohort 2) had two olaratumab-related Grade 3 TEAEs (increased aspartate aminotransferase and tumor hemorrhage); otherwise, olaratumab-related TEAEs were Grade 1/2. Seven patients (43.8%) had a best response of stable disease. Based on the pharmacokinetic concentration profile of olaratumab, the trough concentrations following single and multiple doses at 15 mg/kg on days 1 and 8 every 3 weeks (cohort 3) and multiple doses at 20 mg/kg every 2 weeks (cohort 2) were above the 155 μg/mL target. Thus, these two doses could represent an acceptable schedule for future trials in Japanese patients. Olaratumab had an acceptable safety profile and was well tolerated. PMID:24816152

  12. Gamma-Secretase Inhibitor RO4929097 and Cediranib Maleate in Treating Patients With Advanced Solid Tumors

    Science.gov (United States)

    2014-12-22

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Solid Neoplasm; Male Breast Carcinoma; Recurrent Adult Brain Neoplasm; Recurrent Breast Carcinoma; Recurrent Colon Carcinoma; Recurrent Melanoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Carcinoma; Recurrent Rectal Carcinoma; Recurrent Renal Cell Carcinoma; Stage III Pancreatic Cancer; Stage III Renal Cell Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Rectal Cancer; Stage IIIA Skin Melanoma; Stage IIIB Breast Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Rectal Cancer; Stage IIIB Skin Melanoma; Stage IIIC Breast Cancer; Stage IIIC Colon Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Rectal Cancer; Stage IIIC Skin Melanoma; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  13. Phase 1 study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced solid tumors.

    Science.gov (United States)

    Shimizu, Toshio; Seto, Takashi; Hirai, Fumihiko; Takenoyama, Mitsuhiro; Nosaki, Kaname; Tsurutani, Junji; Kaneda, Hiroyasu; Iwasa, Tsutomu; Kawakami, Hisato; Noguchi, Kazuo; Shimamoto, Takashi; Nakagawa, Kazuhiko

    2016-06-01

    Background This phase I study evaluated the safety and tolerability, pharmacokinetics and pharmacodynamics, immunogenicity, and antitumor activity of pembrolizumab in Japanese patients with advanced solid tumors. Methods Following an initial dose and a 28-day rest (cycle 1), pembrolizumab was administered as an intravenous infusion at escalating doses (2 or 10 mg/kg) every 2 weeks (Q2W) until disease progression or unacceptable toxicity. Adverse events (AEs) were assessed using CTCAE v4.0, and tumor response was assessed using both RECIST v1.1 and immune-related response criteria (irRC). Full pharmacokinetic sampling was performed during cycle 1. Results Three patients received pembrolizumab at 2.0 mg/kg and seven at 10 mg/kg. No dose-limiting toxicities were observed during cycle 1. Eighty percent of patients experienced drug-related AEs (mostly grade 1 or 2); the most common drug-related AEs were nausea, malaise, pyrexia, and aspartate aminotransferase/alanine transaminase (AST/ALT) elevations (n = 2 each). No drug-related grade 4 or 5 AEs occurred. Immune-related AEs comprised grade 3 ALT elevation (n = 1), grade 3 AST elevation (n = 1), grade 1 pneumonitis (n = 1), and grade 1 thyroid-stimulating hormone elevation (n = 1). The safety and pharmacokinetic profiles of Japanese patients were similar to those previously reported for Caucasian patients. A partial tumor response was observed in one patient with non-small-cell lung cancer (NSCLC) and in one patient with melanoma. Conclusions Pembrolizumab at both 2 and 10 mg/kg Q2W was well tolerated in Japanese patients with advanced solid tumors and showed encouraging anti-tumor activity against melanoma and NSCLC.

  14. 3-AP and Gemcitabine in Treating Patients With Advanced Solid Tumors or Lymphoma

    Science.gov (United States)

    2013-09-27

    -cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  15. A phase I pharmacokinetic study of ursolic acid nanoliposomes in healthy volunteers and patients with advanced solid tumors

    Directory of Open Access Journals (Sweden)

    Ying G

    2013-01-01

    Full Text Available Zhongling Zhu,1,4 Zhengzi Qian,2,4 Zhao Yan,1,4 Cuicui Zhao,2,4 Huaqing Wang,2,4 Guoguang Ying3,41Department of Clinical Pharmacology, 2Department of Lymphoma, 3Laboratory of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China; 4Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of ChinaBackground: Ursolic acid is a promising anticancer agent. The current study aims to evaluate the single- and multiple-dose pharmacokinetics (PK as well as the safety of ursolic acid nanoliposomes (UANL in healthy volunteers and in patients with advanced solid tumors.Methods: Twenty-four healthy volunteers in the single-dose PK study were divided into three different groups, which received 37, 74, and 98 mg/m2 of UANL. Eight patients in the multiple-dose PK study were administered with 74 mg/m2 of UANL daily for 14 days. The UA plasma concentrations were determined using ultra-performance liquid chromatograph-tandem mass spectrometry.Results: The plasma concentration profiles of all subjects were characterized by a biexponential decline after infusion. The mean peak plasma concentration (Cmax increased linearly as a function of the dose (r = 0.999. The mean area under the plasma concentration-time curve (AUC from 0 to 16 hours also increased proportionally with dose escalation (r = 0.998. However, the clearance was constant over the specific dose interval. In the multiple-dose PK study, the trough and average concentrations remained low. The mean AUC, half-life, Cmax, time to Cmax, and the volume of distribution on the first day were similar to those on the last day. All subjects tolerated the treatments well. Most UANL-associated adverse events varied from mild to moderate.Conclusions: UANL exhibits relatively linear PK behavior with dose levels from 37 mg/m2 to 98 mg/m2. No drug accumulation was observed with repeated doses of UANL. The intravenous infusion of UANL was well

  16. Heterogeneous delivery is a barrier to the translational advancement of oncolytic virotherapy for treating solid tumors

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    Miller AC

    2014-07-01

    Full Text Available Amber C Miller,1,2 Stephen J Russell2,3 1Mayo Graduate School, Mayo Clinic, Rochester, Minnesota, USA; 2Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA; 3Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA Abstract: Oncolytic viruses are a promising experimental anticancer therapy currently undergoing clinical translation. The development of oncolytic virotherapy offers a potential solution to the elusive “one-shot”cancer cure by providing targeted therapy to selectively infect and kill cancer cells while provoking adaptive anticancer immune responses as protection against distant metastasis and recurrent tumor challenge. While this technology has overcome barriers to safety and efficacy through cancer-specific targeting techniques, in order to reach full therapeutic potential, oncolytic therapies must still overcome barriers to intratumoral delivery and spread that result in heterogeneous intratumoral delivery and nonuniform response. This review will discuss barriers to oncolytic virotherapy translation related to mechanisms of delivering virus via tumor vasculature and distributing virus throughout the tumor microenvironment. Barriers include extravasation into the tumor that is dependent on adequate blood flow, tissue perfusion, and tumoral enhanced permeability and retention for transvascular transport. Subsequently, virions must undergo interstitial transport against dense stromal barriers and high interstitial fluid pressure to initiate infection. In order to achieve massive tumor regression, infection must spread to cover large volumes of tumor mass. Furthermore, virus bioavailability is quickly dampened upon systemic administration due to neutralization and sequestration. These barriers to delivery limit the amount of virus that effectively reaches and spreads within the tumor, forcing dose increases that impinge upon limits of production and increase possibility of adverse

  17. Pembrolizumab and Ziv-aflibercept in Treating Patients With Advanced Solid Tumors

    Science.gov (United States)

    2016-09-09

    Adult Solid Neoplasm; Metastatic Melanoma; Metastatic Renal Cell Cancer; Recurrent Colorectal Carcinoma; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Renal Cell Carcinoma; Stage IV Ovarian Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

  18. Novel systemic treatment options for advanced solid tumors with or without central nervous system metastases or malignant glioma

    NARCIS (Netherlands)

    Milojkovic Kerklaan, B.

    2015-01-01

    Chemotherapy is a very frequently used therapy in patients with advanced tumors with or without central nervous system (CNS) metastases or primary brain tumors. Despite the significant progress in drug development, the survival of patients is limited with an unmet need for more effective chemotherap

  19. Bloodstream infections in patients with solid tumors.

    Science.gov (United States)

    Gudiol, Carlota; Aguado, José María; Carratalà, Jordi

    2016-04-01

    Little information is currently available regarding bloodstream infection (BSI) in patients with solid tumors who, for a variety of reasons, are particularly predisposed to develop this condition. In this review we focus on the incidence, epidemiology, clinical features, etiology, antimicrobial resistance, and outcomes of BSI of adult cancer patients with solid tumors. Most episodes of BSI occur in non-neutropenic patients, in whom the site of primary or metastatic tumor often serves as the portal of entry. The urinary tract and the abdomen are the most frequent sources of infection, and cholangitis is the most common recurrent source of BSI. Gram-negative bacilli are becoming the leading cause of BSI in patients with solid tumors, and the rate of multidrug resistance is increasingly being recognized. The case-fatality rate in patients with solid tumors and BSI is high, especially among those with comorbidities, advanced neoplasms, corticosteroid therapy, and shock at presentation.

  20. Imaging Tumor Hypoxia to Advance Radiation Oncology

    OpenAIRE

    Lee, Chen-Ting; Boss, Mary-Keara; Dewhirst, Mark W.

    2014-01-01

    Significance: Most solid tumors contain regions of low oxygenation or hypoxia. Tumor hypoxia has been associated with a poor clinical outcome and plays a critical role in tumor radioresistance. Recent Advances: Two main types of hypoxia exist in the tumor microenvironment: chronic and cycling hypoxia. Chronic hypoxia results from the limited diffusion distance of oxygen, and cycling hypoxia primarily results from the variation in microvessel red blood cell flux and temporary disturbances in p...

  1. A Dose Escalation Study in Adult Patients With Advanced Solid Malignancies

    Science.gov (United States)

    2016-09-19

    Advanced Solid Tumors With Alterations of FGFR1, 2 and/or 3;; Squamous Lung Cancer With FGFR1 Amplification;; Bladder Cancer With FGFR3 Mutation or Fusion; Advanced Solid Tumors With FGFR1 Amplication,; Advanced Solid Tumors With FGFR2 Amplication,; Advanced Solid Tumors With FGFR3 Mutation

  2. Factors affecting the pharmacokinetics and pharmacodynamics of PEGylated liposomal irinotecan (IHL-305) in patients with advanced solid tumors

    Science.gov (United States)

    Wu, Huali; Infante, Jeffrey R; Keedy, Vicki L; Jones, Suzanne F; Chan, Emily; Bendell, Johanna C; Lee, Wooin; Kirschbrown, Whitney P; Zamboni, Beth A; Ikeda, Satoshi; Kodaira, Hiroshi; Rothenberg, Mace L; Burris, Howard A; Zamboni, William C

    2015-01-01

    IHL-305 is a PEGylated liposomal formulation of irinotecan (CPT-11). The objective of this study was to evaluate the factors associated with interpatient variability in the pharmacokinetics and pharmacodynamics of IHL-305 in patients with advanced solid tumors. IHL-305 was administered intravenously once every 4 weeks as part of a Phase I study. Pharmacokinetic studies of the liposomal sum total CPT-11, released CPT-11, SN-38, SN-38G, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin, and 7-ethyl-10-[4-amino-1-piperidino]-carbonyloxycamptothecin in plasma were performed. Noncompartmental and compartmental pharmacokinetic analyses were conducted using pharmacokinetic data for sum total CPT-11. The pharmacokinetic variability of IHL-305 is associated with linear and nonlinear clearance. Patients whose age and body composition (ratio of total body weight to ideal body weight [TBW/IBW]) were greater than the median age and TBW/IBW of the study had a 1.7-fold to 2.6-fold higher ratio of released CPT-11 area under the concentration versus time curve (AUC) to sum total CPT-11 AUC. Patients aged <60 years had a 1.3-fold higher ratio of percent decrease in monocytes at nadir to percent decrease in absolute neutrophil count at nadir as compared with patients aged ≥60 years. There was an inverse relationship between patient age and percent decrease in monocytes at nadir, ie, younger patients have a higher percent decrease in monocytes. Patients with a higher percent decrease in monocytes at nadir have a decreased plasma exposure of sum total CPT-11. The pharmacokinetics and pharmacodynamics of IHL-305 are consistent with those of other PEGylated liposomal carriers. Interpatient variability in the pharmacokinetics and pharmacodynamics of IHL-305 was associated with age, body composition, and monocytes. PMID:25709442

  3. Effect of food on the pharmacokinetics of TAS-102 and its efficacy and safety in patients with advanced solid tumors.

    Science.gov (United States)

    Yoshino, Takayuki; Kojima, Takashi; Bando, Hideaki; Yamazaki, Tomoko; Naito, Yoichi; Mukai, Hirofumi; Fuse, Nozomu; Goto, Koichi; Ito, Yuko; Doi, Toshihiko; Ohtsu, Atsushi

    2016-05-01

    TAS-102, a novel oral antitumor agent, consists of trifluridine and tipiracil hydrochloride (molar ratio, 1:0.5). We investigated the effects of food on trifluridine and tipiracil hydrochloride. The efficacy and safety of TAS-102 were evaluated in patients with advanced solid tumors. We analyzed drug pharmacokinetics using a randomized, single-dose, two-treatment (fed versus fasting), two-period, two-sequence cross-over design, followed by repeated administration. Patients were given single doses of TAS-102 (35 mg/m(2) ) in the pharmacokinetic phase and received twice-daily doses of TAS-102 in 28-day cycles in the repeated administration phase for evaluating efficacy and safety. Food showed no effect on the area under the curve from 0 to 12 h or 0 h-infinity values of trifluridine following administration of TAS-102 under fasting and fed conditions, whereas those of tipiracil hydrochloride decreased by approximately 40%. Maximum concentrations of both drugs decreased by approximately 40%, indicating that food influenced the absorption and bioavailability of trifluridine and tipiracil hydrochloride, respectively. During the repeated administration, stable disease was observed in nine patients with rectal, small-cell lung, breast, thymic, duodenal, and prostate cancers. Major adverse events were neutropenia, leukopenia, anemia, and nausea. Postprandial administration was optimal for TAS-102 because trifluridine's area under the curve was not changed by food, indicating that its clinical efficacy would not be affected. Additionally, postprandial administration was reasonable because the maximum concentration of trifluridine decreased in neutrophils, which correlated with previous studies. These results suggest that TAS-102 would be an effective treatment for small-cell lung, thymic, and colorectal cancers. This trial is registered with the Japan Pharmaceutical Information Center (no. JapicCTI-111482). PMID:26918279

  4. A phase I dose-escalation and pharmacokinetic study of enzastaurin and erlotinib in patients with advanced solid tumors

    OpenAIRE

    Padda, Sukhmani K.; Krupitskaya, Yelena; Chhatwani, Laveena; Fisher, George A; Colevas, Alexander D.; San Pedro-Salcedo, Melanie; Decker, Rodney; Latz, Jane E.; Wakelee, Heather A.

    2011-01-01

    Purpose Enzastaurin, an oral serine/threonine kinase inhibitor, targets the protein kinase C and AKT pathways with anti-tumor and anti-angiogenic effects. Erlotinib, an oral epidermal growth factor receptor (EGFR) inhibitor, has activity in solid tumors. Based on the promising combination of EGFR inhibitors and anti-angiogenic agents, this phase I trial was initiated. Methods This single-institution, open-label, non-randomized trial used a standard 3 + 3 dose-escalation model in patients with...

  5. Phase 1 Study of PLX7486 as Single Agent and With Gemcitabine Plus Nab-Paclitaxel in Patients With Advanced Solid Tumors

    Science.gov (United States)

    2016-06-07

    Solid Tumors; Untreated Pancreatic Adenocarcinoma; Pancreatic Cancer Non-resectable; Metastatic Pancreatic Adenocarcinoma; Tumors of Any Histology With Activating Trk (NTRK) Point or NTRK Fusion Mutations; Tenosynovial Giant Cell Tumor

  6. An Open-Label, Multicenter, Phase 1/2 Study of E7438 (EZH2 Histone Methyl Transferase [HMT] Inhibitor) as a Single Agent in Subjects With Advanced Solid Tumors or With B-cell Lymphomas

    Science.gov (United States)

    2016-09-01

    B-cell Lymphomas (Phase 1); Advanced Solid Tumors (Phase 1); Diffuse Large B-cell Lymphoma (Phase 2); Follicular Lymphoma (Phase 2); Transformed Follicular Lymphoma; Primary Mediastinal Large B-Cell Lymphoma

  7. NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors

    OpenAIRE

    Swain, Sandra M; Brian P. Monahan; Grem, Jean L.; Marc R Blackman; Laura Lee Johnson; Jamie Stagl; Sannes, Timothy S.; Dawn B. Wallerstedt; Mansky, Patrick J.

    2013-01-01

    Purpose. European Mistletoe (Viscum album L.) extracts (mistletoe) are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC) evaluated: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM. Methods. Design: increasing mistlet...

  8. First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors

    DEFF Research Database (Denmark)

    Abdul Razak, Albiruni R; Mau-Soerensen, Morten; Gabrail, Nashat Y;

    2016-01-01

    PURPOSE: This trial evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of selinexor (KPT-330), a novel, oral small-molecule inhibitor of exportin 1 (XPO1/CRM1), and determined the recommended phase II dose. PATIENTS AND METHODS: In total, 189 patients with advanced solid tumors...... complete and six partial responses were observed (n = 7, 4%), with 27 patients (17%) achieving stable disease for ≥ 4 months. CONCLUSION: Selinexor is a novel and safe therapeutic with broad antitumor activity. Further interrogation into this class of therapy is warranted....

  9. Factors affecting the pharmacokinetics and pharmacodynamics of PEGylated liposomal irinotecan (IHL-305 in patients with advanced solid tumors

    Directory of Open Access Journals (Sweden)

    Wu H

    2015-02-01

    Full Text Available Huali Wu,1 Jeffrey R Infante,2 Vicki L Keedy,3 Suzanne F Jones,2 Emily Chan,3 Johanna C Bendell,2 Wooin Lee,4 Whitney P Kirschbrown,1 Beth A Zamboni,5 Satoshi Ikeda,6 Hiroshi Kodaira,6 Mace L Rothenberg,3 Howard A Burris III,2 William C Zamboni1,7–9 1UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 2Sarah Cannon Research Institute/Tennessee Oncology, PLLC, 3Vanderbilt University, Nashville, TN, 4Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 5Department of Mathematics, Carlow University, Pittsburgh, PA, USA; 6Yakult Honsha Co., Ltd., Medical Development Department, Tokyo, Japan; 7UNC Lineberger Comprehensive Cancer Center, 8UNC Institute for Pharmacogenomics and Individualized Therapy, 9Carolina Center for Cancer Nanotechology Excellence, University of North Carolina, Chapel Hill, NC, USA Abstract: IHL-305 is a PEGylated liposomal formulation of irinotecan (CPT-11. The objective of this study was to evaluate the factors associated with interpatient variability in the pharmacokinetics and pharmacodynamics of IHL-305 in patients with advanced solid tumors. IHL-305 was administered intravenously once every 4 weeks as part of a Phase I study. Pharmacokinetic studies of the liposomal sum total CPT-11, released CPT-11, SN-38, SN-38G, 7-ethyl-10-[4-N-(5-aminopentanoic acid-1-piperidino]-carbonyloxycamptothecin, and 7-ethyl-10-[4-amino-1-piperidino]-carbonyloxycamptothecin in plasma were performed. Noncompartmental and compartmental pharmacokinetic analyses were conducted using pharmacokinetic data for sum total CPT-11. The pharmacokinetic variability of IHL-305 is associated with linear and nonlinear clearance. Patients whose age and body composition (ratio of total body weight to ideal body weight [TBW/IBW] were greater than the median age and TBW/IBW of the study had a 1.7-fold to 2.6-fold higher ratio of released CPT-11 area under the concentration versus time

  10. First-in-Man Dose-Escalation Study of the Selective BRAF Inhibitor RG7256 in Patients with BRAF V600-Mutated Advanced Solid Tumors

    DEFF Research Database (Denmark)

    Dienstmann, Rodrigo; Lassen, Ulrik; Cebon, Jonathan;

    2016-01-01

    BACKGROUND: BRAF mutations are a validated target for cancer therapy. A second-generation BRAF inhibitor with an improved preclinical safety profile (RG7256) was evaluated in a first-in-man study in order to determine the safety, efficacy, pharmacokinetics and pharmacodynamics in patients with BRAF...... V600-mutated advanced solid tumors. PATIENTS AND METHODS: Patients received RG7256 orally over 8 dose levels from 200 mg once a day (QD) to 2400 mg twice a day (BID) (50-, 100- and 150-mg tablets) using a classic 3 + 3 dose escalation design. RESULTS: In total, 45 patients were enrolled; most (87...... %) had advanced melanoma (94 % BRAF V600E). RG7256 was rapidly absorbed, with limited accumulation and dose-proportional increase in exposure up to 1950 mg BID. The maximal tolerated dose (MTD) was not reached. The most common drug-related adverse events (AEs) were dyspepsia (20 %), dry skin (18 %), rash...

  11. A phase I study of the human anti-activin receptor-like kinase 1 antibody PF-03446962 in Asian patients with advanced solid tumors.

    Science.gov (United States)

    Doi, Toshihiko; Lee, Kyung-Hun; Kim, Tae-Min; Ohtsu, Atsushi; Kim, Tae Yong; Ikeda, Masafumi; Yoh, Kiyotaka; Gallo Stampino, Corrado; Hirohashi, Tomoko; Suzuki, Akiyuki; Fujii, Yosuke; Andrew Williams, James; Bang, Yung-Jue

    2016-07-01

    Preclinical studies suggest that ALK-1 signaling mediates a complementary angiogenesis pathway activated upon development of resistance to vascular endothelial growth factor (VEGF)-targeted therapies. Inhibition of ALK-1 signaling may lead to disruption of tumor angiogenesis and growth. We report findings from a multicenter, open-label, phase I study of the fully human anti-ALK-1 mAb PF-03446962 conducted in Japan and South Korea, in Asian patients with advanced solid tumors. The dose escalation Part 1 of the study was based on a standard 3 + 3 design (n = 16). In Part 2, patients were treated with PF-03446962 at 7 and 10 mg/kg (10/cohort), including patients with disease progression following prior VEGF receptor (R)-targeted therapy. Primary objectives were determination of the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Secondary objectives included safety, pharmacokinetics, pharmacodynamics, and antitumor activity of PF-03446962. No dose-limiting toxicity (DLT) was noted in the 12 DLT-evaluable patients. Treatment was well tolerated. The MTD for biweekly intravenous administration was estimated to be 10 mg/kg and the RP2D 7 mg/kg. Treatment-related grades 1-3 thrombocytopenia was experienced by 27.8% patients. The most frequent nonhematologic treatment-related AEs were grades 1-2 pyrexia and epistaxis. Four patients (3/4 with hepatocellular carcinoma) developed telangiectasia suggesting vascular targeting and in vivo ALK-1 inhibition by PF-03446962. Stable disease for 12 weeks or more was observed in 25.7% of patients and in 44.4% of those with hepatocellular carcinoma. ALK-1 inhibition by PF-03446962 may represent a novel antiangiogenic strategy for patients with advanced solid malignancies complementary to current treatment with VEGF(R)-targeted inhibitors or chemotherapy. PMID:27075560

  12. NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors

    Directory of Open Access Journals (Sweden)

    Patrick J. Mansky

    2013-01-01

    Full Text Available Purpose. European Mistletoe (Viscum album L. extracts (mistletoe are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM and mistletoe in advanced solid cancers (ASC evaluated: (1 safety, toxicity, and maximum tolerated dose (MTD, (2 absolute neutrophil count (ANC recovery, (3 formation of mistletoe lectin antibodies (ML ab, (4 cytokine plasma concentrations, (5 clinical response, and (6 pharmacokinetics of GEM. Methods. Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT were grade (G 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery. Results. DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380 mg/m2 and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high. Conclusion. GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone.

  13. Advance on Insulin-like Growth Factor Binding Protein 2 in Lung Cancer and Other Solid Tumors

    Institute of Scientific and Technical Information of China (English)

    Wu Weiqin; Lu Kaihua

    2013-01-01

    Increasing evidence has revealed that IGF signalling plays a key role in cellular proliferation, survival, differentiation and senescence. Dysregulation of this signalling pathway is related to the development and progression of many human diseases, including cancer, diabetes and atherosclerosis. Insulin-like growth factor binding protein-2 (IGFBP-2) is reported to be a modulator of the action of insulin-like growth factors (IGFs), whereas IGF-independent effects of IGFBP-2 on cellular proliferation, apoptosis, and mobility have been revealed not only during the embryonic state but also in the pathological state of cancer. IGFBP-2 is involved in the genesis and progress of various malignancies including lung cancer. Recent ifndings show in many pre-clinical trials that IGFBP-2 may contribute to the transformation and progression of lung cancer. These studies suggest that IGFBP-2 may be a potential therapeutic target for lung cancer. In this review, we provide an overview on IGFBP-2, review corresponding studies investigating the role of IGFBP-2 as a cancer target in multiple tumors and discuss its possible mechanism in lung cancer.

  14. ABT-751 in Treating Young Patients With Refractory Solid Tumors

    Science.gov (United States)

    2012-03-14

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Liver Cancer; Neuroblastoma; Ovarian Cancer; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

  15. Advanced mechanics of solids

    CERN Document Server

    Bruhns, Otto T

    2003-01-01

    Mechanics, and in particular, the mechanics of solids, forms the basis of all engi­ neering sciences. It provides the essential foundations for understanding the action of forces on bodies, and the effects of these forces on the straining of the body on the one hand, and on the deformation and motion of the body on the other. Thus, it provides the solutions of many problems with which the would-be engineer is going to be confronted with on a daily basis. In addition, in engineering studies, mechanics has a more vital importance, which many students appreciate only much later. Because of its clear, and analyt­ ical setup, it aids the student to a great extent in acquiring the necessary degree of abstraction ability, and logical thinking, skills without which no engineer in the practice today would succeed. Many graduates have confirmed to me that learning mechanics is generally per­ ceived as difficult. On the other hand, they always also declared that the preoccu­ pation with mechanics made an essential c...

  16. The effect of different dosing regimens of motesanib on the gallbladder: a randomized phase 1b study in patients with advanced solid tumors

    International Nuclear Information System (INIS)

    Gallbladder toxicity, including cholecystitis, has been reported with motesanib, an orally administered small-molecule antagonist of VEGFRs 1, 2 and 3; PDGFR; and Kit. We assessed effects of motesanib on gallbladder size and function. Patients with advanced metastatic solid tumors ineligible for or progressing on standard-of-care therapies with no history of cholecystitis or biliary disease were randomized 2:1:1 to receive motesanib 125 mg once daily (Arm A); 75 mg twice daily (BID), 14-days-on/7-days-off (Arm B); or 75 mg BID, 5-days-on/2-days-off (Arm C). Primary endpoints were mean change from baseline in gallbladder size (volume by ultrasound; independent review) and function (ejection fraction by CCK-HIDA; investigator assessment). Forty-nine patients received ≥1 dose of motesanib (Arms A/B/C, n = 25/12/12). Across all patients, gallbladder volume increased by a mean 22.2 cc (from 38.6 cc at baseline) and ejection fraction decreased by a mean 19.2% (from 61.3% at baseline) during treatment. Changes were similar across arms and appeared reversible after treatment discontinuation. Three patients had cholecystitis (grades 1, 2, 3, n = 1 each) that resolved after treatment discontinuation, one patient developed grade 3 acute cholecystitis requiring cholecystectomy, and two patients had other notable grade 1 gallbladder disorders (gallbladder wall thickening, gallbladder dysfunction) (all in Arm A). Two patients developed de novo gallstones during treatment. Twelve patients had right upper quadrant pain (Arms A/B/C, n = 8/1/3). The incidence of biliary “sludge” in Arms A/B/C was 39%/36%/27%. Motesanib treatment was associated with increased gallbladder volume, decreased ejection fraction, biliary sludge, gallstone formation, and infrequent cholecystitis. ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/NCT00448786?term

  17. Study on changes and clinical significance of coagulation parameters in patients with advanced solid tumors%晚期实体肿瘤患者凝血指标的变化及其临床意义

    Institute of Scientific and Technical Information of China (English)

    李卉惠; 王婧; 车娟娟; 杨薏帆; 刘文婷; 肖婧; 曹邦伟

    2014-01-01

    目的:探讨晚期实体肿瘤患者凝血功能的变化。方法采集71例晚期实体肿瘤患者(晚期肿瘤组)与20例健康人(对照组)的静脉血,检测血小板、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、D -二聚体(D - Di-mer)和纤维蛋白原(Fbg)。结果晚期肿瘤组血小板数值较对照组明显升高,两组比较有显著性差异( P ﹤0.01)。晚期肿瘤组较对照组 Fbg、D - Dimer 显著升高( P ﹤0.01),APTT 显著缩短( P ﹤0.05)。结论晚期实体肿瘤患者存在高凝状态,正确的抗凝治疗是必要的。%Objective To clarify the changes of coagulation function in patients with advanced solid tumors. Methods A total of 71 pa-tients with advanced solid tumors and 20 healthy persons as controls were collected. Platelet count,prothrombin time( PT),activated partial thromboplastin time(APTT),D - Dimer and fibrinogen(Fbg)were detected. Results There was significantly increase of platelets in advanced solid tumors group compared to those of healthy control group;there was significant elevation of Fbg and D - Dimer and significantly shortened APTT in advanced solid tumors group compared to those of healthy control group. Conclusion Patients with advanced solid tumors exist in hyper-coagulable status and appropriate anticoagulation therapy should be applied.

  18. Advances in Solid State Physics

    CERN Document Server

    Haug, Rolf

    2007-01-01

    The present volume 46 of Advances in Solid State Physics contains the written versions of selected invited lectures from the spring meeting of the Arbeitskreis Festkörperphysik of the Deutsche Physikalische Gesellschaft which was held from 27 to 31 March 2006 in Dresden, Germany. Many topical talks given at the numerous symposia are included. Most of these were organized collaboratively by several of the divisions of the Arbeitskreis. The topis range from zero-dimensional physics in quantum dots, molecules and nanoparticles over one-dimensional physics in nanowires and 1d systems to more applied subjects like optoelectronics and materials science in thin films. The contributions span the whole width of solid-state physics from truly basic science to applications.

  19. The Advanced Solid Rocket Motor

    Science.gov (United States)

    Mitchell, Royce E.

    1992-08-01

    The Advanced Solid Rocket Motor will utilize improved design features and automated manufacturing methods to produce an inherently safer propulsive system for the Space Shuttle and future launch systems. This second-generation motor will also provide an additional 12,000 pounds of payload to orbit, enhancing the utility and efficiency of the Shuttle system. The new plant will feature strip-wound, asbestos-free insulation; propellant continuous mixing and casting; and extensive robotic systems. Following a series of static tests at the Stennis Space Center, MS flights are targeted to begin in early 1997.

  20. The Advanced Solid Rocket Motor

    Science.gov (United States)

    Mitchell, Royce E.

    1992-01-01

    The Advanced Solid Rocket Motor will utilize improved design features and automated manufacturing methods to produce an inherently safer propulsive system for the Space Shuttle and future launch systems. This second-generation motor will also provide an additional 12,000 pounds of payload to orbit, enhancing the utility and efficiency of the Shuttle system. The new plant will feature strip-wound, asbestos-free insulation; propellant continuous mixing and casting; and extensive robotic systems. Following a series of static tests at the Stennis Space Center, MS flights are targeted to begin in early 1997.

  1. Solid Tumors of the Mediastinum in Adults.

    Science.gov (United States)

    Azizad, Shameem; Sannananja, Bhagya; Restrepo, Carlos S

    2016-06-01

    A wide spectrum of solid tumors can develop in the mediastinum of adults. Like for any other tumor evaluation, the location and morphology play equally important role for lesion characterization. Compartmentalizing the mediastinal masses greatly narrows the number of possible differential diagnosis. Cross sectional imaging mainly with computed tomography (CT) and magnetic resonance imaging (MRI) are the preferred modalities of choice as they can establish the presence, location and morphology of the lesion allowing to suggest a possible diagnosis.

  2. Advances in Solid State Physics

    CERN Document Server

    Haug, Rolf

    2008-01-01

    The present volume 47 of the Advances in Solid State Physics contains the written version of a large number of the invited talks of the 2007 Spring Meeting of the Arbeitskreis Festkörperphysik which was held in Regensburg, Germany, from March 26 to 30, 2007 in conjunction with the 71st Annual Meeting of the Deutsche Physikalische Gesellschaft.It gives an overview of the present status of solid state physics where low-dimensional systems such as quantum dots and quantum wires are dominating. The importance of magnetic materials is reflected by the large number of contributions in the part dealing with ferromagnetic films and particles. One of the most exciting achievements of the last couple of years is the successful application of electrical contacts to and the investigation of single layers of graphene. This exciting physics is covered in Part IV of this book. Terahertz physics is another rapidly moving field which is presented here by five contributions. Achievements in solid state physics are only rarely...

  3. A phase I and pharmacokinetics study of intravenous calcitriol in combination with oral dexamethasone and gefitinib in patients with advanced solid tumors

    Science.gov (United States)

    Muindi, Josephia R.; Johnson, Candace S.; Trump, Donald L.; Christy, Renee; Engler, Kristie L.

    2009-01-01

    Purpose The primary objective of this study was to determine the maximum tolerated dose (MTD) of intravenously (i.v.) calcitriol administered in combination with a fixed oral dose of dexamethasone and gefitinib in patients with refractory solid tumors. Methods A fixed oral dose of dexamethasone of 4 mg/day was given every 12 h × 3 doses starting 12 h prior to i.v. calcitriol administration. Calcitriol was administered i.v. over 1 h on weeks 1, 3, and weekly thereafter. The starting calcitriol dose level was 57 μg and escalation occurred in cohorts of three patients until the MTD was defined. Gefitinib was given at a fixed oral daily dose of 250 mg starting at week 2 (day 8). Serum calcitriol PK studies were performed on day 1 (calcitriol + dexamethasone) and on day 15 (calcitriol + dexamethasone + gefitinib). Results A total of 20 patients were treated. Dose-limiting hypercalcemia was observed in two out of the four patients receiving 163 mcg/week of calcitriol. Mean (±SE) peak serum calcitriol concentration (Cmax) at the MTD (125 μg/week calcitriol) was 11.17 ± 2.62 ng/ml and the systemic exposure (AUC0–72 h) of 53.30 ± 10.49 ng h/ml. The relationship between calcitriol dose and either Cmax or AUC was linear over the 57–163 μg dose range. Conclusions The addition of a low dose of dexamethasone allowed the safe escalation of calcitriol to the MTD of 125 μg/week. This dose level resulted in serum calcitriol concentrations that are associated with pre-clinical antitumor activity. However, no antitumor activity was noted clinically in patients with solid tumors. PMID:19396601

  4. Advances in Solid State Physics

    CERN Document Server

    Haug, Rolf

    2009-01-01

    The present volume 48 of the Advances in Solid State Physics contains the written version of a large number of the invited talks of the 2008 Spring Meeting of the DPG section Condensed Matter Physics (Sektion kondensierte Materie der DPG) which was held in Berlin, Germany, and gives a nice overview of the present status of condensed matter physics. Low-dimensional systems are dominating the field and especially nanowires and quantum dots. In recent years one learned how to produce nanowires directly during a growth process. Therefore, a number of articles is related to such nanowires. In nanoparticles and quantum dots, the dimensionality is further reduced and we learn more and more how to produce such systems in a defined way and what effects result from the confinement in all three dimensions. Spin effects and magnetism is another important field of present-day research in solid state physics. The third chapter covers this physics. The growing interest into organic materials and biological systems is reflec...

  5. Treatment-related fatigue with sorafenib, sunitinib and pazopanib in patients with advanced solid tumors: an up-to-date review and meta-analysis of clinical trials.

    Science.gov (United States)

    Santoni, Matteo; Conti, Alessandro; Massari, Francesco; Arnaldi, Giorgio; Iacovelli, Roberto; Rizzo, Mimma; De Giorgi, Ugo; Trementino, Laura; Procopio, Giuseppe; Tortora, Giampaolo; Cascinu, Stefano

    2015-01-01

    Fatigue is the most common symptom associated with cancer and cancer treatment. We performed an up-to-date meta-analysis to determine the incidence and relative risk (RR) of fatigue in patients (pts) with cancer treated with sorafenib (SO), sunitinib (SU) and pazopanib (PZ). PubMed databases were searched for articles published till August 2013. Eligible studies were selected according to PRISMA statement. Summary incidence, RR and 95% confidence intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. Fifteen studies were included in our analysis. A total of 6,996 pts was enrolled: 2,260 had renal cell carcinomas (RCC), 1,691 non-small cell lung cancers, 1,290 breast cancers, 823 hepatocellular carcinomas, 362 soft tissue sarcomas, 304 gastrointestinal solid tumors, 165 neuroendocrine tumors and 101 melanomas. When stratified by drug, SO registered lower incidence and RR of all and high-grade fatigue when compared to SU, whereas the difference between SO and PZ was significant only for all-grade fatigue (p < 0.001). The difference between SU and PZ was significant for high-grade (p < 0.001) but not for all-grade fatigue (p = 0.52). In RCC pts, PZ showed the lower incidence and RR of all and high-grade fatigue. The differences were significant for SU vs. SO (p < 0.001), SU vs. PZ (p < 0.001) and SO vs. PZ (p < 0.001). Treatment with SO, SU and PZ is associated with an increased incidence of fatigue in pts with cancer. Early and appropriate management is required to avoid unnecessary dose reductions and transitory or definitive treatment discontinuations.

  6. Fanconi's anemia and clinical radiosensitivity. Report on two adult patients with locally advanced solid tumors treated by radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Bremer, M.; Karstens, J.H. [Hannover Medical School, Hannover (Germany). Dept. of Radiation Oncology; Schindler, D.; Gross, M. [Univ. Wuerzburg (Germany). Inst. of Human Genetics; Doerk, T. [Hannover Medical School, Hannover (Germany). Dept. of Obstetrics and Gynecology; Morlot, S. [Hannover Medical School, Hannover (Germany). Inst. of Human Genetics

    2003-11-01

    Background: Patients with Fanconi's anemia (FA) may exhibit an increased clinical radiosensitivity of various degree, although detailed clinical data are scarce. We report on two cases to underline the possible challenges in the radiotherapy of FA patients. Case Report and Results: Two 24- and 32-year-old male patients with FA were treated by definitive radiotherapy for locally advanced squamous cell head and neck cancers. In the first patient, long-term tumor control could be achieved after delivery of 67 Gy with a - in part - hyperfractionated split-course treatment regimen and, concurrently, one course of carboplatin followed by salvage neck dissection. Acute toxicity was marked, but no severe treatment-related late effects occurred. 5 years later, additional radiotherapy was administered due to a second (squamous cell carcinoma of the anus) and third (squamous cell carcinoma of the head and neck) primary, which the patient succumbed to. By contrast, the second patient experienced fatal acute hematologic toxicity after delivery of only 8 Gy of hyperfractionated radiotherapy. While the diagnosis FA could be based on flow cytometric analysis of a lymphocyte culture in the second patient, the diagnosis in the first patient had to be confirmed by hypersensitivity to mitomycin of a fibroblast cell line due to complete somatic lymphohematopoietic mosaicism. In this patient, phenotype complementation and molecular genetic analysis revealed a pathogenic mutation in the FANCA gene. The first patient has not been considered to have FA until he presented with his second tumor. Conclusion: FA has to be considered in patients presenting at young age with squamous cell carcinoma of the head and neck or anus. The diagnosis FA is of immediate importance for guiding the optimal choice of treatment. Radiotherapy or even radiochemotherapy seems to be feasible and effective in individual cases. (orig.)

  7. Animal models of extracranial pediatric solid tumors

    OpenAIRE

    Seitz, Guido; Armeanu-Ebinger, Sorin; WARMANN, STEVEN; Fuchs, Jörg

    2012-01-01

    Animal models, including xenografts, models of metastatic invasion, syngeneic models and transgenic models, are important tools for basic research in solid pediatric tumors, while humanized animal models are useful for novel immunotherapeutical approaches. Optical and molecular imaging techniques are used for in vivo imaging and may be used in conjunction with alternative treatment approaches, including photodynamic therapy. The aim of this review is to highlight the various animal models tha...

  8. NASA's Advanced solid rocket motor

    Science.gov (United States)

    Mitchell, Royce E.

    The Advanced Solid Rocket Motor (ASRM) will not only bring increased safety, reliability and performance for the Space Shuttle Booster, it will enhance overall Shuttle safety by effectively eliminating 174 failure points in the Space Shuttle Main Engine throttling system and by reducing the exposure time to aborts due to main engine loss or shutdown. In some missions, the vulnerability time to Return-to-Launch Site aborts is halved. The ASRM uses case joints which will close or remain static under the effects of motor ignition and pressurization. The case itself is constructed of the weldable steel alloy HP 9-4-0.30, having very high strength and with superior fracture toughness and stress corrosion resistance. The internal insulation is strip-wound and is free of asbestos. The nozzle employs light weight ablative parts and is some 5,000 pounds lighter than the Shuttle motor used to date. The payload performance of the ASRM-powered Shuttle is 12,000 pounds higher than that provided by the present motor. This is of particular benefit for payloads delivered to higher inclinations and/or altitudes. The ASRM facility uses state-of-the-art manufacturing techniques, including continuous propellant mixing and direct casting.

  9. NASA's Advanced solid rocket motor

    Science.gov (United States)

    Mitchell, Royce E.

    1993-01-01

    The Advanced Solid Rocket Motor (ASRM) will not only bring increased safety, reliability and performance for the Space Shuttle Booster, it will enhance overall Shuttle safety by effectively eliminating 174 failure points in the Space Shuttle Main Engine throttling system and by reducing the exposure time to aborts due to main engine loss or shutdown. In some missions, the vulnerability time to Return-to-Launch Site aborts is halved. The ASRM uses case joints which will close or remain static under the effects of motor ignition and pressurization. The case itself is constructed of the weldable steel alloy HP 9-4-0.30, having very high strength and with superior fracture toughness and stress corrosion resistance. The internal insulation is strip-wound and is free of asbestos. The nozzle employs light weight ablative parts and is some 5,000 pounds lighter than the Shuttle motor used to date. The payload performance of the ASRM-powered Shuttle is 12,000 pounds higher than that provided by the present motor. This is of particular benefit for payloads delivered to higher inclinations and/or altitudes. The ASRM facility uses state-of-the-art manufacturing techniques, including continuous propellant mixing and direct casting.

  10. Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

    Science.gov (United States)

    2014-08-26

    ; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  11. Barriers to drug delivery in solid tumors.

    Science.gov (United States)

    Sriraman, Shravan Kumar; Aryasomayajula, Bhawani; Torchilin, Vladimir P

    2014-01-01

    Over the last decade, significant progress has been made in the field of drug delivery. The advent of engineered nanoparticles has allowed us to circumvent the initial limitations to drug delivery such as pharmacokinetics and solubility. However, in spite of significant advances to tumor targeting, an effective treatment strategy for malignant tumors still remains elusive. Tumors possess distinct physiological features which allow them to resist traditional treatment approaches. This combined with the complexity of the biological system presents significant hurdles to the site-specific delivery of therapeutic drugs. One of the key features of engineered nanoparticles is that these can be tailored to execute specific functions. With this review, we hope to provide the reader with a clear understanding and knowledge of biological barriers and the methods to exploit these characteristics to design multifunctional nanocarriers, effect useful dosing regimens and subsequently improve therapeutic outcomes in the clinic. PMID:25068098

  12. Solid Tumor Therapy Using a Cannon and Pawn Combination Strategy.

    Science.gov (United States)

    Song, Wantong; Tang, Zhaohui; Zhang, Dawei; Wen, Xue; Lv, Shixian; Liu, Zhilin; Deng, Mingxiao; Chen, Xuesi

    2016-01-01

    Nanocarrier-based anti-tumor drugs hold great promise for reducing side effects and improving tumor-site drug retention in the treatment of solid tumors. However, therapeutic outcomes are still limited, primarily due to a lack of drug penetration within most tumor tissues. Herein, we propose a strategy using a nanocarrier-based combination of vascular disrupting agents (VDAs) and cytotoxic drugs for solid tumor therapy. Specifically, combretastatin A-4 (CA4) serves as a "cannon" by eradicating tumor cells at a distance from blood vessels; concomitantly, doxorubicin (DOX) serves as a "pawn" by killing tumor cells in close proximity to blood vessels. This "cannon and pawn" combination strategy acts without a need to penetrate every tumor cell and is expected to eliminate all tumor cells in a solid tumor. In a murine C26 colon tumor model, this strategy proved effective in eradicating greater than 94% of tumor cells and efficiently inhibited tumor growth with a weekly injection. In large solid tumor models (C26 and 4T1 tumors with volumes of approximately 250 mm(3)), this strategy also proved effective for inhibiting tumor growth. These results showing remarkable inhibition of tumor growth provide a valuable therapeutic choice for solid tumor therapy. PMID:27217835

  13. A tumor cord model for Doxorubicin delivery and dose optimization in solid tumors

    Directory of Open Access Journals (Sweden)

    Eikenberry Steffen

    2009-08-01

    effect on the spatial profile of cell mortality within tumor cord systems. Therefore, extending infusion times (up to 2 hours and fractionating large doses are two strategies that may preserve or increase anti-tumor activity and reduce cardiotoxicity by decreasing peak plasma concentration. However, even under optimal conditions, doxorubicin may have limited delivery into advanced solid tumors.

  14. Characterization of cell suspensions from solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Pallavicini, M.

    1985-07-10

    The desirable features of cells in suspension will necessarily be dependent upon the use for which the cells were prepared. Adequate cell yield or recovery is defined by the measurement to be performed. Retention of cellular morphology is important for microscopic identification of cell types in a heterogenous cell suspension, and may be used to determine whether the cells in suspension are representative of those in the tumor in situ. Different dispersal protocols may yield cells with different degrees of clonogenicity, as well as altered biochemical features, such as loss of cellular proteins, surface antigens, nucleotide pools, etc. The quality of the cell suspension can be judged by the degree of cell clumping and level of cellular debris, both of which impact on flow cytometric measurements and studies in which the number of cells be known accurately. Finally, if the data measured on the cells in suspension are to be extrapolated to phenomena occurring in the tumor in situ, it is desirable that the cells in suspension are representative of those in the solid tumor in vivo. This report compares characteristics of tumor cell suspensions obtained by different types of selected disaggregation methods. 33 refs., 2 figs., 4 tabs.

  15. Solid Tumors: Facts, Challenges and Solutions

    Directory of Open Access Journals (Sweden)

    Gavhane Y. N.

    2011-01-01

    Full Text Available In 2005, 7.6 million people died of cancer out of 58 million deaths worldwide. Based on projections, cancer deaths will continue to rise with an estimated 9 million people dying from cancer in 2015, and 11.4 million dying in 2030. The increasing trend of cancer incidence has forced the humanity to work more on the cancer prevention and treatments. It is important for the public health professionals to understand the dynamics and kinetics of tumor incidence for future strategies. Over here we have reviewed solid tumor modeling, their detail classification, treatment strategies available along with their merits and demerits. To overcome these limitations, design focus for future studies is suggested.

  16. High-Dose Thiotepa Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory Solid Tumors

    Science.gov (United States)

    2013-03-06

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Ovarian Cancer; Retinoblastoma; Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

  17. Monoclonal antibodies and Fc fragments for treating solid tumors

    Directory of Open Access Journals (Sweden)

    Eisenbeis AM

    2012-01-01

    Full Text Available Andrea M Eisenbeis, Stefan J GrauDepartment of Neurosurgery, University Hospital of Cologne, Cologne, GermanyAbstract: Advances in biotechnology, better understanding of pathophysiological processes, as well as the identification of an increasing number of molecular markers have facilitated the use of monoclonal antibodies and Fc fragments in various fields in medicine. In this context, a rapidly growing number of these substances have also emerged in the field of oncology. This review will summarize the currently approved monoclonal antibodies used for the treatment of solid tumors with a focus on their clinical application, biological background, and currently ongoing trials.Keywords: targeted therapy, monoclonal antibodies, cancer, biological therapy

  18. First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin's lymphomas

    Science.gov (United States)

    Patnaik, A.; Appleman, L. J.; Tolcher, A. W.; Papadopoulos, K. P.; Beeram, M.; Rasco, D. W.; Weiss, G. J.; Sachdev, J. C.; Chadha, M.; Fulk, M.; Ejadi, S.; Mountz, J. M.; Lotze, M. T.; Toledo, F. G. S.; Chu, E.; Jeffers, M.; Peña, C.; Xia, C.; Reif, S.; Genvresse, I.; Ramanathan, R. K.

    2016-01-01

    Background To evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of copanlisib, a phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL). Patients and methods Phase I dose-escalation study including patients with advanced solid tumors or NHL, and a cohort of patients with type 2 diabetes mellitus. Patients received three weekly intravenous infusions of copanlisib per 28-day cycle over the dose range 0.1–1.2 mg/kg. Plasma copanlisib levels were analyzed for pharmacokinetics. Biomarker analysis included PIK3CA, KRAS, BRAF, and PTEN mutational status and PTEN immunohistochemistry. Whole-body [18F]-fluorodeoxyglucose positron emission tomography (18FDG-PET) was carried out at baseline and following the first dose to assess early pharmacodynamic effects. Plasma glucose and insulin levels were evaluated serially. Results Fifty-seven patients received treatment. The MTD was 0.8 mg/kg copanlisib. The most frequent treatment-related adverse events were nausea and transient hyperglycemia. Copanlisib exposure was dose-proportional with no accumulation; peak exposure positively correlated with transient hyperglycemia post-infusion. Sixteen of 20 patients treated at the MTD had reduced 18FDG-PET uptake; 7 (33%) had a reduction >25%. One patient achieved a complete response (CR; endometrial carcinoma exhibiting both PIK3CA and PTEN mutations and complete PTEN loss) and two had a partial response (PR; both metastatic breast cancer). Among the nine NHL patients, all six with follicular lymphoma (FL) responded (one CR and five PRs) and one patient with diffuse large B-cell lymphoma had a PR by investigator assessment; two patients with FL who achieved CR (per post hoc independent radiologic review) were on treatment >3 years. Conclusion Copanlisib, dosed intermittently on days 1, 8, and 15 of a 28-day cycle, was well tolerated and the MTD was determined to be 0.8 mg/kg. Copanlisib

  19. Photodynamic therapy of advanced malignant tumors

    Science.gov (United States)

    Wang, Lian-xing; Dai, Lu-pin; Lu, Wen-qin

    1993-03-01

    Forty patients with advanced tumors were treated by photodynamic therapy (PDT) from May 1991 to August 1991 in our hospital with age ranges from 30 to 81 years old. The pathological diagnosis shows that 13 had tumors in the colon, 3 in the stomach, 2 in the oesophageal, 2 in the palatum, 1 in the cervix, and 19 others with malignant cancers of the skin. The histology was as follows: squamous cell in 20, adenocarcinoma in 19, melanocarcinoma in 1. By TNM classification there were no cases of T1, 5 cases of T2, and 35 cases of T2 - T3. All patients were stage IV. The overall effective rate was 85%, our experience is that the PDT is suitable for the patients with advanced tumor, especially those whose tumor recurrences are hard to treat after conventional treatment (surgery, radiotherapy, chemotherapy). The PDT appears to be a new and promising possibility to treat advanced tumors and to improve the patients' survival rates.

  20. Solid-pseudopapillary tumor of the pancreatic tail

    Institute of Scientific and Technical Information of China (English)

    Frank Eder; Hans-Ulrich Schulz; Christoph R(o)cken; Hans Lippert

    2005-01-01

    We report a case of the rare solid-pseudopapillary tumor of the pancreas. In contrast to other pancreatic tumors,the solid-pseudopapillary tumor has a favorable prognosis.The 60-year-old female patient we report on here was treated by left pancreatic resection combined with splenectomy for a non-metastasizing tumor of the pancreas. A solid-pseudopapillary tumor was found on histology. The patient had no signs of metastases at present.Since a microscopically invasive tumor growth is assumed,oncologically curative resection should be preferred vs the less radical enucleation. The rare solid-pseudopapillary tumor of the pancreas has a good prognosis after successful oncological resection.

  1. Warburg′s effect on solid tumors

    Directory of Open Access Journals (Sweden)

    Talal El Imad

    2014-01-01

    Full Text Available Lactic acidosis is the result of imbalance between the systemic formation of lactate and its hepatic metabolism. In cancer patients, lactic acidosis is mainly associated with hematologic malignancies (leukemia and lymphomas and the mechanism is known as Warburg′s effect. We report a 76-year-old male known to have hypertension and coronary artery disease, who presented with abdominal distension and lactic acidosis. His initial evaluation showed multiple liver masses that were biopsied and the patient was diagnosed with undifferentiated carcinoma of unknown primary, involving the liver. The patient had progression of lactic acidosis leading to his death on day-15. As the lactic acidosis was not in the setting of hypoxia or hemodynamic instability, we made the diagnosis of malignancy-associated type B lactic acidosis, also known as the Warburg′s effect. Warburg′s effect can occur in solid cancer if the tumor involves the liver. It has bad prognostic implications. The use of intravenous bicarbonate as a temporary measure is of controversial benefit, as it can potentially worsen the metabolic acidosis and its use should be limited to patients with very low pH. In cancer patients, the use of lactatebased intravenous fluids can be potentially harmful and can increase the risk of tumor metastasis, at least in animal malignancy models.

  2. MR imaging of solid cerebellar tumors in adult

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Kee Hyun; Han, Moon Hee; Yu, In Kyu [Seoul National University College of Medicine, Seoul (Korea, Republic of); Choo, Sung Wook; Byun, Hong Sik [Samsung Medical Center, Seoul (Korea, Republic of); Choi, Kyu Ho; Kim, Ki Jun [Catholic University Medical College, Seoul (Korea, Republic of)

    1995-07-15

    The solid variety of cerebellar tumors in adult is relatively uncommon. This study is to describe the characteristic MR findings of various solid cerebellar tumors in adult. Twenty three cerebellar solid tumors from 22 consecutive patients over age of 15 with surgical confirmations were retrospectively evaluated with MR findings. Histologic diagnosis included hemangioblastoma (n = 6), metastasis (n = 6), high-grade astrocytoma (n = 3), and medulloblastoma (n = 8). The MR findings were reviewed with attention of the size, the signal intensity of the tumors, pattern of enhancement, tumoral margin, degree of peritumoral edema, signal void vascular structures within and/or around the tumor, and location in relation to attachment to the pial surface of the tumor. Solid hemangioblastomas consistently showed slightly low or iso signal intensity on T1-weighted images and high intensity on T2-weighted images, dense homogeneous enhancement, and signal void vessels within and/or around the mass. Metastatic tumors showed various findings with predominantly low or iso signal intensity on T2-weighted images. Medulloblastomas was midline and/or paramidline in location, and had larger mass formation. High-grade astrocytomas revealed nonspecific MR findings with no signal void vessels. Hemangioblastoma, metastasis, malignant astrocytoma, and medulloblastoma should be included in differential diagnosis of solid cerebellar tumors in adult. Dense homogeneous enhancement and signal void vessels are characteristic of hemangioblastoma. The signal intensity of the tumor, and presence of signal void vessels, location and enhancement pattern can be some value in differential diagnosis of solid cerebellar tumors in adult.

  3. Cancer cell differentiation heterogeneity and aggressive behavior in solid tumors

    OpenAIRE

    Jögi, Annika; Vaapil, Marica; Johansson, Martin; Påhlman, Sven

    2012-01-01

    The differentiation stage of tumors is a central aspect in the histopathological classification of solid malignancies. The differentiation stage is strongly associated with tumor behavior, and generally an immature tumor is more aggressive than the more differentiated counterpart. While this is common knowledge in surgical pathology, the contribution of differentiation-related gene expression and functions to tumor behavior is often overlooked in the experimental, tumor biological setting. Th...

  4. Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors

    Science.gov (United States)

    2015-04-28

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Liver Cancer; Neuroblastoma; Ovarian Cancer; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

  5. Talazoparib in Treating Patients With Advanced or Metastatic Solid Tumors That Cannot Be Removed by Surgery and Liver or Kidney Dysfunction

    Science.gov (United States)

    2016-10-05

    Estrogen Receptor Negative; Head and Neck Squamous Cell Carcinoma; HER2/Neu Negative; Hormone-Resistant Prostate Cancer; Metastatic Pancreatic Adenocarcinoma; Progesterone Receptor Negative; Solid Neoplasm; Stage III Mesothelioma; Stage IIIA Gastric Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Small Cell Lung Carcinoma; Stage IIIB Gastric Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Small Cell Lung Carcinoma; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Cancer; Stage IV Mesothelioma; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Small Cell Lung Carcinoma; Triple-Negative Breast Carcinoma

  6. Measuring Combustion Advance in Solid Propellants

    Science.gov (United States)

    Yang, L. C.

    1986-01-01

    Set of gauges on solid-propellant rocket motor with electrically insulating case measures advance of combustion front and local erosion rates of propellant and insulation. Data furnished by gauges aid in motor design, failure analysis, and performance prediction. Technique useful in determining propellant uniformity and electrical properties of exhaust plum. Gauges used both in flight and on ground. Foilgauge technique also useful in basic research on pulsed plasmas or combustion of solids.

  7. Hypoxic cell turnover in different solid tumor lines.

    NARCIS (Netherlands)

    Ljungkvist, A.; Bussink, J.; Kaanders, J.H.A.M.; Rijken, P.F.J.W.; Begg, A.C.; Raleigh, J.A.; Kogel, A.J. van der

    2005-01-01

    PURPOSE: Most solid tumors contain hypoxic cells, and the amount of tumor hypoxia has been shown to have a negative impact on the outcome of radiotherapy. The efficacy of combined modality treatments depends both on the sequence and timing of the treatments. Hypoxic cell turnover in tumors may be im

  8. Krukenberg tumors diagnosed during pregnancy simultaneously with advanced gastric cancer; A case report

    International Nuclear Information System (INIS)

    Krukenberg tumors recognized during pregnancy are rarely reported. The preoperative diagnosis can be challenging because of the confusing morphological features and symptoms during pregnancy. Here, we report a case of a 29-year-old pregnant woman at 29 weeks gestation presenting with bilateral solid ovarian masses, which were later diagnosed as metastatic ovarian cancer originating from advanced gastric cancer. This case suggests that Krukenberg tumors should be considered when bilateral ovarian solid masses are encountered regardless of pregnancy

  9. Krukenberg tumors diagnosed during pregnancy simultaneously with advanced gastric cancer; A case report

    Energy Technology Data Exchange (ETDEWEB)

    You, Myung Won; Jung, Yoon Young; Shin, Jung Hwan; Hong, Young Ok [Eulji Hospital, Eulji University School of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    Krukenberg tumors recognized during pregnancy are rarely reported. The preoperative diagnosis can be challenging because of the confusing morphological features and symptoms during pregnancy. Here, we report a case of a 29-year-old pregnant woman at 29 weeks gestation presenting with bilateral solid ovarian masses, which were later diagnosed as metastatic ovarian cancer originating from advanced gastric cancer. This case suggests that Krukenberg tumors should be considered when bilateral ovarian solid masses are encountered regardless of pregnancy.

  10. 注射用雷替曲塞在晚期实体瘤患者体内的药动学%Pharmacokinetics of raltitrexed for injection in patients with advanced solid tumors

    Institute of Scientific and Technical Information of China (English)

    李如标; 张为民; 高英

    2011-01-01

    AIM To establish a HPLC method for the determination of raltitrexed in human plasma and to study the pharmacokinetics of raltitrexed for injection in patients with advanced solid tumor. METHODS Theraltitrexed in plasma were extracted by solid phase microextraction (SPME) , and then analyzed by HPLC. Six Chinese patients with advanced solid tumor received intravenously raltitrexed 3 mg-m 2. The plasma concentration of raltitrexed was determined by HPLC, and the pharmacokinetic parameters were calculated by DAS 2.0 software. RESULTS The calibration curve was linear in the range of 2.5 - 2 000 |xg"L~', and the linear equation was Y = 284.79 X+ 853.64, r = 0.996 (n = 3). The extraction recovery of raltitrexed at the concentration of 5, 100 and 1 000 ixg-L"1 were (102.7 ± 2.6) %, (89.7 ± 4.6) % and (99.1 ± 7.5) %, and the RSD were 1.72%, 3.75% and 5.28% respectively. The pharmacokinetic parameters of raltitrexed 3 mg-nT2 were as follows; PU was (839.4 ± 246.2) jjLg-L"1 and AUC^was (719.8 ± 146.7) jig-L^-h. CONCLUSION This HPLC method is simple, accurate, sensitive and reproducible, and suitable for the study of pharmacokinetics of raltitrexed in human plasma.%目的:建立测定人血浆中雷替曲塞浓度的高效液相色谱(HPLC)法,研究国产注射用雷替曲塞在中国晚期实体瘤患者体内的药动学特征.方法:采用固相萃取法提取血浆样品中的雷替曲塞,进行HPLC分析.6名中国晚期实体瘤患者使用雷替曲塞单药3 mg·m(-2)静脉滴注,采用HPLC法测定血浆中雷替曲塞浓度的变化,采用DAS 2.0软件计算药动学参数.结果:雷替曲塞在2.5~2 000μg·L(-1)浓度范围时线性关系良好,回归方程为Y=284.79 X+853.64,r=0.996(n=3).雷替曲塞浓度为5、100和1 000μg·L(-1)的提取回收率分别为(102.7±2.6)%、(89.7±4.6)%和(99.1±7.5)%,RSD分别为1.72%、3.75%和5.28%.雷替曲塞给药剂量3 mg·m(-2)时,ρ(max)为(839.4±246.2)μg·L(-1),AUC(0-t)为(719.8±146.7)μg·L(-1)·h.结论:

  11. Cancer cell differentiation heterogeneity and aggressive behavior in solid tumors.

    Science.gov (United States)

    Jögi, Annika; Vaapil, Marica; Johansson, Martin; Påhlman, Sven

    2012-05-01

    The differentiation stage of tumors is a central aspect in the histopathological classification of solid malignancies. The differentiation stage is strongly associated with tumor behavior, and generally an immature tumor is more aggressive than the more differentiated counterpart. While this is common knowledge in surgical pathology, the contribution of differentiation-related gene expression and functions to tumor behavior is often overlooked in the experimental, tumor biological setting. The mechanisms by which tumor cell differentiation stages are perturbed or affected are poorly explored but have recently come into focus with the introduction.of the tumor stem cell concept. While developmental biologists view the differentiation as a unidirectional event, pathologists and tumor biologists have introduced the concept of dedifferentiation to explain phenotypic changes occurring in solid tumors. In this review we discuss the impact of the tumor cell differentiation stage as used in surgical pathology. We further discuss knowledge gained from exploring the molecular basis of the differentiation and dedifferentiation processes in neuroblastoma and breast cancer, two tumor forms where the tumor cell differentiation concept is used in the clinical diagnostic work and where the tumor stem cell theory has been applied.

  12. Advanced Solid Rocket Launcher and Its Evolution

    Science.gov (United States)

    Morita, Yasuhiro; Imoto, Takayuki; Habu, Hiroto; Ohtsuka, Hirohito; Hori, Keiichi; Koreki, Takemasa; Fukuchi, Apollo; Uekusa, Yasuyuki; Akiba, Ryojiro

    The research on next generation solid propellant rockets is actively underway in various spectra. JAXA is developing the Advanced Solid Rocket (ASR) as a successor to the M-V launch vehicle, which was utilized over past ten years for space science programs including planetary missions. ASR is a result of the development of the next generation technology including a highly intelligent autonomous check-out system, which is connected to not only the solid rocket but also future transportation systems. It is expected to improve the efficiency of the launch system and double the cost performance. Far beyond this effort, the passion of the volunteers among the industry-government-academia cooperation has been united to establish the society of the freewheeling thinking “Next generation Solid Rocket Society (NSRS)”. It aims at a larger revolution than what the ASR provides so that the order of the cost performance is further improved. A study of the Low melting temperature Thermoplastic Propellant (LTP) is now at the experimental stage, which is expected to reform the manufacturing process of the solid rocket propellant and lead to a significant increase in cost performance. This paper indicates the direction of the big flow towards the next generation solid-propellant rockets: the concept of the intelligent ASR under development; and the innovation behind LTP.

  13. Immunotherapeutics for Pediatric Solid Tumors | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The National Cancer Institute’s Pediatric Oncology Branch seeks partners interested in licensing or collaborative research to co-develop new immunotherapeutic agents based on chimeric antigen receptor (CARs) for the treatment of pediatric solid tumors.

  14. Methoxyamine, Cisplatin, and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors or Mesothelioma That Cannot Be Removed by Surgery or Mesothelioma That Is Refractory to Cisplatin and Pemetrexed

    Science.gov (United States)

    2016-07-04

    Advanced Peritoneal Malignant Mesothelioma; Advanced Pleural Malignant Mesothelioma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Solid Neoplasm; Stage III Pleural Mesothelioma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Ovarian Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Pleural Mesothelioma; Thymoma

  15. Diversity of Dynamics and Morphologies of Invasive Solid Tumors

    CERN Document Server

    Jiao, Yang

    2012-01-01

    Complex tumor-host interactions can significantly affect the growth dynamics and morphologies of progressing neoplasms. The growth of a confined solid tumor induces mechanical pressure and deformation of the surrounding microenvironment, which in turn influences tumor growth. In this paper, we generalize a recently developed cellular automaton model for invasive tumor growth in heterogeneous microenvironments by incorporating the effects of pressure. Specifically, we explicitly consider pressure exerted on the growing tumor due to deformation of the microenvironment and model the local tumor-host interface instability. Both noninvasive proliferative growth and invasive growth with individual cells that detach themselves from the primary tumor and migrate into surrounding microenvironment are investigated. We find that while noninvasive tumors growing in "soft" homogeneous microenvironments develop almost isotropic shapes, high pressure and host heterogeneity can strongly enhance malignant behavior, leading to...

  16. Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors

    Science.gov (United States)

    2016-02-10

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Liver Cancer; Lymphoma; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor; Unspecified Childhood Solid Tumor, Protocol Specific

  17. Chromosome aberrations in solid tumors have a stochastic nature

    Energy Technology Data Exchange (ETDEWEB)

    Castro, Mauro A.A. [Departamento de Bioquimica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-anexo, Porto Alegre 90035-003 (Brazil) and Departamento de Medicina Interna, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, Porto Alegre 90035-903 (Brazil) and Instituto de Fisica, Universidade Federal do Rio Grande do Sul, Av. Bento Goncalves 9500, Porto Alegre 91501-970 (Brazil) and Universidade Luterana do Brasil, Rua Miguel Tostes 101, Canoas 92420-280 (Brazil)]. E-mail: mauro@ufrgs.br; Onsten, Tor G.H. [Departamento de Medicina Interna, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, Porto Alegre 90035-903 (Brazil); Universidade Luterana do Brasil, Rua Miguel Tostes 101, Canoas 92420-280 (Brazil); Moreira, Jose C.F. [Departamento de Bioquimica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-anexo, Porto Alegre 90035-003 (Brazil); Almeida, Rita M.C. de [Instituto de Fisica, Universidade Federal do Rio Grande do Sul, Av. Bento Goncalves 9500, Porto Alegre 91501-970 (Brazil)

    2006-08-30

    An important question nowadays is whether chromosome aberrations are random events or arise from an internal deterministic mechanism, which leads to the delicate task of quantifying the degree of randomness. For this purpose, we have defined several Shannon information functions to evaluate disorder inside a tumor and between tumors of the same kind. We have considered 79 different kinds of solid tumors with 30 or more karyotypes retrieved from the Mitelman Database of Chromosome Aberrations in Cancer. The Kaplan-Meier cumulative survival was also obtained for each solid tumor type in order to correlate data with tumor malignance. The results here show that aberration spread is specific for each tumor type, with high degree of diversity for those tumor types with worst survival indices. Those tumor types with preferential variants (e.g. high proportion of a given karyotype) have shown better survival statistics, indicating that aberration recurrence is a good prognosis. Indeed, global spread of both numerical and structural abnormalities demonstrates the stochastic nature of chromosome aberrations by setting a signature of randomness associated to the production of disorder. These results also indicate that tumor malignancy correlates not only with karyotypic diversity taken from different tumor types but also taken from single tumors. Therefore, by quantifying aberration spread, we could confront diverse models and verify which of them points to the most likely outcome. Our results suggest that the generating process of chromosome aberrations is neither deterministic nor totally random, but produces variations that are distributed between these two boundaries.

  18. Tumor lysis syndrome in solid tumors: an up to date review of the literature

    Directory of Open Access Journals (Sweden)

    Aibek E. Mirrakhimov

    2014-06-01

    Full Text Available Tumor lysis syndrome (TLS is a potentially deadly complication of tumors or their treatment. This syndrome consists of a constellation of laboratory findings such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia, known as laboratory TLS. When clinical complications such as seizures, acute renal failure, and cardiac dysrhythmias occur in patients with laboratory TLS, the syndrome is called clinical TLS. TLS is especially common in patients with hematological malignancies with rapid cellular turnover rates such as acute lymphocytic leukemia and Burkitt lymphoma, but is very rare in patients with solid tumors. Nevertheless, there are multiple reports in the literature on the occurrence of TLS in patients with solid tumors. In this review article, we summarize the current data on the occurrence of TLS in patients with solid tumors. We propose an algorithm of risk stratification and prevention of TLS in patients with solid cancers.

  19. Cancer stem cells in solid tumors: elusive or illusive?

    Directory of Open Access Journals (Sweden)

    Lehrach Hans R

    2010-05-01

    Full Text Available Abstract During the past years in vivo transplantation experiments and in vitro colony-forming assays indicated that tumors arise only from rare cells. These cells were shown to bear self-renewal capacities and the ability to recapitulate all cell types within an individual tumor. Due to their phenotypic resemblance to normal stem cells, the term "cancer stem cells" is used. However, some pieces of the puzzle are missing: (a a stringent definition of cancer stem cells in solid tumors (b specific markers that only target cells that meet the criteria for a cancer stem cell in a certain type of tumor. These missing parts started an ongoing debate about which is the best method to identify and characterize cancer stem cells, or even if their mere existence is just an artifact caused by the experimental procedures. Recent findings query the cancer stem cell hypothesis for solid tumors itself since it was shown in xenograft transplantation experiments that under appropriate conditions tumor-initiating cells are not rare. In this review we critically discuss the challenges and prospects of the currently used major methods to identify cancer stem cells. Further on, we reflect the present discussion about the existence of cancer stem cells in solid tumors as well as the amount and characteristics of tumor-initiating cells and finally provide new perspectives like the correlation of cancer stem cells and induced pluripotent cells.

  20. Therapeutic attack of hypoxic cells of solid tumors: presidential address.

    Science.gov (United States)

    Sartorelli, A C

    1988-02-15

    Hypoxic cells of solid tumors are relatively resistant to therapeutic assault. Studies have demonstrated that oxygen-deficient tumor cells exist in an environment conducive to reductive reactions making hypoxic cells particularly sensitive to bioreductive alkylating agents. Mitomycin C, the prototype bioreductive alkylating agent available for clinical use, is capable of preferentially killing oxygen-deficient cells both in vitro and in vivo. This phenomenon is at least in part the result of differences in the uptake and metabolism of mitomycin C by hypoxic and oxygenated tumor cells, with the ultimate critical lesion being the cross-linking of DNA by the mitomycin antibiotic. The combination of mitomycin C with X-irradiation, to attack hypoxic and oxygenated tumor cell populations, respectively, has led to enhanced antitumor effects in mice bearing solid tumor implants and in patients with cancer of the head and neck. More efficacious kill of hypoxic tumor cells may be possible by the use of dicoumarol in combination with mitomycin or by the use of the related antibiotic porfiromycin. The findings support the use of an agent with specificity for hypoxic tumor cells in potentially curative regimens for solid tumors. PMID:3123053

  1. Diversity of dynamics and morphologies of invasive solid tumors

    Science.gov (United States)

    Jiao, Yang; Torquato, Salvatore

    2012-03-01

    Complex tumor-host interactions can significantly affect the growth dynamics and morphologies of progressing neoplasms. The growth of a confined solid tumor induces mechanical pressure and deformation of the surrounding microenvironment, which in turn influences tumor growth. In this paper, we generalize a recently developed cellular automaton model for invasive tumor growth in heterogeneous microenvironments [Y. Jiao and S. Torquato, PLoS Comput. Biol. 7, e1002314 (2011)] by incorporating the effects of pressure. Specifically, we explicitly model the pressure exerted on the growing tumor due to the deformation of the microenvironment and its effect on the local tumor-host interface instability. Both noninvasive-proliferative growth and invasive growth with individual cells that detach themselves from the primary tumor and migrate into the surrounding microenvironment are investigated. We find that while noninvasive tumors growing in "soft" homogeneous microenvironments develop almost isotropic shapes, both high pressure and host heterogeneity can strongly enhance malignant behavior, leading to finger-like protrusions of the tumor surface. Moreover, we show that individual invasive cells of an invasive tumor degrade the local extracellular matrix at the tumor-host interface, which diminishes the fingering growth of the primary tumor. The implications of our results for cancer diagnosis, prognosis and therapy are discussed.

  2. Diversity of dynamics and morphologies of invasive solid tumors

    Directory of Open Access Journals (Sweden)

    Yang Jiao

    2012-03-01

    Full Text Available Complex tumor-host interactions can significantly affect the growth dynamics and morphologies of progressing neoplasms. The growth of a confined solid tumor induces mechanical pressure and deformation of the surrounding microenvironment, which in turn influences tumor growth. In this paper, we generalize a recently developed cellular automaton model for invasive tumor growth in heterogeneous microenvironments [Y. Jiao and S. Torquato, PLoS Comput. Biol. 7, e1002314 (2011] by incorporating the effects of pressure. Specifically, we explicitly model the pressure exerted on the growing tumor due to the deformation of the microenvironment and its effect on the local tumor-host interface instability. Both noninvasive-proliferative growth and invasive growth with individual cells that detach themselves from the primary tumor and migrate into the surrounding microenvironment are investigated. We find that while noninvasive tumors growing in “soft” homogeneous microenvironments develop almost isotropic shapes, both high pressure and host heterogeneity can strongly enhance malignant behavior, leading to finger-like protrusions of the tumor surface. Moreover, we show that individual invasive cells of an invasive tumor degrade the local extracellular matrix at the tumor-host interface, which diminishes the fingering growth of the primary tumor. The implications of our results for cancer diagnosis, prognosis and therapy are discussed.

  3. Irinotecan in Treating Children With Refractory Solid Tumors

    Science.gov (United States)

    2013-06-13

    Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

  4. Effect of tumor shape and size on drug delivery to solid tumors

    Directory of Open Access Journals (Sweden)

    Soltani M

    2012-04-01

    Full Text Available Abstract Tumor shape and size effect on drug delivery to solid tumors are studied, based on the application of the governing equations for fluid flow, i.e., the conservation laws for mass and momentum, to physiological systems containing solid tumors. The discretized form of the governing equations, with appropriate boundary conditions, is developed for predefined tumor geometries. The governing equations are solved using a numerical method, the element-based finite volume method. Interstitial fluid pressure and velocity are used to show the details of drug delivery in a solid tumor, under an assumption that drug particles flow with the interstitial fluid. Drug delivery problems have been most extensively researched in spherical tumors, which have been the simplest to examine with the analytical methods. With our numerical method, however, more complex shapes of the tumor can be studied. The numerical model of fluid flow in solid tumors previously introduced by our group is further developed to incorporate and investigate non-spherical tumors such as prolate and oblate ones. Also the effects of the surface area per unit volume of the tissue, vascular and interstitial hydraulic conductivity on drug delivery are investigated.

  5. The Childhood Solid Tumor Network: A new resource for the developmental biology and oncology research communities.

    Science.gov (United States)

    Stewart, Elizabeth; Federico, Sara; Karlstrom, Asa; Shelat, Anang; Sablauer, Andras; Pappo, Alberto; Dyer, Michael A

    2016-03-15

    Significant advances have been made over the past 25 years in our understanding of the most common adult solid tumors such as breast, colon, lung and prostate cancer. Much less is known about childhood solid tumors because they are rare and because they originate in developing organs during fetal development, childhood and adolescence. It can be very difficult to study the cellular origins of pediatric solid tumors in developing organs characterized by rapid proliferative expansion, growth factor signaling, developmental angiogenesis, programmed cell death, tissue reorganization and cell migration. Not only has the etiology of pediatric cancer remained elusive because of their developmental origins, but it also makes it more difficult to treat. Molecular targeted therapeutics that alter developmental pathway signaling may have devastating effects on normal organ development. Therefore, basic research focused on the mechanisms of development provides an essential foundation for pediatric solid tumor translational research. In this article, we describe new resources available for the developmental biology and oncology research communities. In a companion paper, we present the detailed characterization of an orthotopic xenograft of a pediatric solid tumor derived from sympathoadrenal lineage during development. PMID:26068307

  6. Solid Pseudopapillary Tumor as a Possible Cause of Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Okanoue T

    2004-09-01

    Full Text Available CONTEXT: Acute pancreatitis is not commonly seen in the first presentation of pancreatic neoplasms. Solid pseudopapillary tumor as a cause of acute pancreatitis has not yet been reported. This is the first report of acute pancreatitis resulting from solid pseudopapillary tumor. CASE REPORT: We report the case of a 21-year-old female who presented with a sudden onset of severe abdominal pain associated with elevated serum pancreatic enzyme concentration. The initial diagnosis was acute pancreatitis. However, subsequent ultrasonography and computed tomography showed an abdominal mass in the tail of the pancreas, retroperitoneal fluid and left pleural effusion. There was scarce pain relief even with large doses of analgesics. A distal pancreatectomy was then performed and a final diagnosis of solid pseudopapillary tumor was made histologically. The surrounding pancreatic tissue was characterized as hemorrhagic edematous pancreatitis. CONCLUSIONS: Solid pseudopapillary tumor is generally known as a slow-growing pancreatic neoplasm with few, if any, symptoms. However, solid pseudopapillary tumors should be kept in mind as a possible cause of acute pancreatitis, especially in cases of non-alcoholic young women having an acute pancreatitis attack.

  7. Advances of Tumor Hyperthermia and Tumor Immunology in Translational Medicine

    Institute of Scientific and Technical Information of China (English)

    Hooshang Lahooti

    2015-01-01

    Hyperthermia is another important method in the treatment of tumors, secondary to surgery, radiotherapy, chemotherapy and biotherapy. It has been demonstrated the efifcacy and versatility of hyperthermia in a lot of randomized trials across various primary cancers. Both heat shock proteins (HSPs) and dendritic cells (DCs) are greatly affected by hyperthermia and closely related to the tumor immunology. Nowadays, tumor hyperthermia and tumor immunology have been attached much attention in the field of translational medicine. In this article, the action mechanism and immunological effects of hyperthermia, activation of HSPs and DCs as well as HSP- and DC-based cancer vaccine were reviewed from the perspective of translational medicine.

  8. Pharmacokinetic study of aldoxorubicin in patients with solid tumors.

    Science.gov (United States)

    Mita, Monica M; Natale, Ronald B; Wolin, Edward M; Laabs, Brenda; Dinh, Hillary; Wieland, Scott; Levitt, Daniel J; Mita, Alain C

    2015-04-01

    Introduction Aldoxorubicin, a prodrug of doxorubicin, binds covalently to serum albumin in the bloodstream and accumulates in tumors. Aldoxorubicin can be administered at doses several-fold higher than doxorubicin can, without associated acute cardiotoxicity. Purpose This study fully evaluated the pharmacokinetic profile of aldoxorubicin (serum and urine). Methods Eighteen patients with advanced solid tumors received aldoxorubicin 230 or 350 mg/m(2) (equivalent in drug load to doxorubicin at doses of 170 or 260 mg/m(2), respectively) once every 21 days. Blood samples were taken in cycle 1 before aldoxorubicin infusion, and at 5, 15, 30, and 60 min, and at 2, 4, 8, 12, 16, 24, 48, and 72 h after infusion. Urine samples were taken in cycle 1 at 24, 48, and 72 h after infusion. Limited blood sampling was done in cycle 3, before aldoxorubicin infusion, and at 60 min and at 2, 4, and 8 h after infusion. Results The long mean half-life (20.1-21.1 h), narrow mean volume of distribution (3.96-4.08 L/m(2)), and slow mean clearance rate (0.136-0.152 L/h/m(2)) suggest that aldoxorubicin is stable in circulation and does not accumulate readily in body compartments outside of the bloodstream. Very little doxorubicin and its major metabolite doxorubicinol, which has been implicated in doxorubicin-associated cardiotoxicity, are excreted in urine. This might explain the lack of cardiotoxicity observed thus far with aldoxorubicin. Conclusions Our findings support dosing and administration schemas used in an ongoing phase 3 clinical study of aldoxorubicin in soft tissue sarcoma, and phase 2 clinical studies in small cell lung cancer, glioblastoma, and Kaposi's sarcoma.

  9. Levofloxacin to Prevent Infection Following Chemotherapy in Treating Patients With Solid Tumors or Lymphoma

    Science.gov (United States)

    2013-08-01

    Brain and Central Nervous System Tumors; Breast Cancer; Extragonadal Germ Cell Tumor; Infection; Lung Cancer; Lymphoma; Ovarian Cancer; Small Intestine Cancer; Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific

  10. Development of cell-cycle checkpoint therapy for solid tumors.

    Science.gov (United States)

    Tamura, Kenji

    2015-12-01

    Cellular proliferation is tightly controlled by several cell-cycle checkpoint proteins. In cancer, the genes encoding these proteins are often disrupted and cause unrestrained cancer growth. The proteins are over-expressed in many malignancies; thus, they are potential targets for anti-cancer therapies. These proteins include cyclin-dependent kinase, checkpoint kinase, WEE1 kinase, aurora kinase and polo-like kinase. Cyclin-dependent kinase inhibitors are the most advanced cell-cycle checkpoint therapeutics available. For instance, palbociclib (PD0332991) is a first-in-class, oral, highly selective inhibitor of CDK4/6 and, in combination with letrozole (Phase II; PALOMA-1) or with fulvestrant (Phase III; PALOMA-3), it has significantly prolonged progression-free survival, in patients with metastatic estrogen receptor-positive, HER2-negative breast cancer, in comparison with that observed in patients using letrozole, or fulvestrant alone, respectively. In this review, we provide an overview of the current compounds available for cell-cycle checkpoint protein-directed therapy for solid tumors. PMID:26486823

  11. Solid Tumors: Facts, Challenges and Solutions

    OpenAIRE

    Gavhane Y. N.; Shete A. S; Bhagat A. K.,; Shinde V. R.,; Bhong K. K.; Khairnar G. A.,; Yadav A. V.

    2011-01-01

    In 2005, 7.6 million people died of cancer out of 58 million deaths worldwide. Based on projections, cancer deaths will continue to rise with an estimated 9 million people dying from cancer in 2015, and 11.4 million dying in 2030. The increasing trend of cancer incidence has forced the humanity to work more on the cancer prevention and treatments. It is important for the public health professionals to understand the dynamics and kinetics of tumor incidence for future strategies. Over here we ...

  12. Effects of modified fractionated irradiation on the growth of sarcoma 180 solid tumor in mouse

    International Nuclear Information System (INIS)

    The present experimental study has been designed and carried out to investigate the effects of various doses and timings of fractionated irradiation of 6 MV X-rays obtained from a linear accelerator on sarcoma 180 solid tumors produced in DDO/Lee mouse. A total of 2700 to approx. 2800 cGy(or rad) was delivered with daily dose of 250/ cGy, 350cGy, and 450cGy every other day to the inoculated site starting on day 2,4,6, and 8 post-inoculation and the tumor size change was observed by measuring a maximum circumference of tumor bearing region. The dose experimentally established in the mouse for one half of animals to produce a solid tumor (TSD50) from ascitic mouse sarcoma 180 was 10/sup 3.87/ cells/ml. The effect of fractionated irradiation on days 2 and 4 post-inoculation was inhibitory to the growth of solid form tumor of experimentally produced sarcoma 180 (p<0.001). The growth of tumor was also inhibited when irradiated on days 6 and 8 post-inoculation but the grade was less. Histologically tumor cells of mouse sarcoma 180 produced in the experimental animal were shown to be destroyed and eradicated by radiation once they were responsive to X-irradiation. The present study suggests that a small or early tumor is benefitted by a small daily dose(e.g. 250 cGy) irradiation whereas a moderately advanced tumor is beneficially treated with a relatively high dose (e.g. 450 cGy) irradiation. A large tumor responded very poorly to irradiation

  13. Advanced Materials and Solids Analysis Research Core (AMSARC)

    Science.gov (United States)

    The Advanced Materials and Solids Analysis Research Core (AMSARC), centered at the U.S. Environmental Protection Agency's (EPA) Andrew W. Breidenbach Environmental Research Center in Cincinnati, Ohio, is the foundation for the Agency's solids and surfaces analysis capabilities. ...

  14. Solid Tumor Inhibitory and other Constituents of Casimiroa tetrameria

    Institute of Scientific and Technical Information of China (English)

    XU Ya-Ming; Maria del C.Ramirez-Allumada; Frederick A.Valeriote; A.A.Leslie Gunatilaka

    2011-01-01

    AIM:To isolate and characterize solid tumor inhibitory and other constituents from a bioactive extract of Casimiroa tetrameria((Rutaceae).METHODS:A crude extract of C.tetrameria obtained from the US National Cancer Institute Natural Product Repository and found to exhibit selective toxicity to solid tumor cells was subjected bioactivity-guided fractionation involving solvent-solvent partitioning,gel filtration,and chromatography.The structures of all isolated compounds were elucidated by spectroscopic analysis(NMR and MS)and/or by comparison with the reported data.Compounds 1 and 4-9 were evaluated for their solid tumor selective cytotoxicity.RESULTS:Nine metabolites,including a new furenocoumarin,5-methoxy-8-(4'-acetoxy-3'-methylbut-2-enyloxy)-psoralen(1),and the previously known compounds 2-9 were encountered.Of these the flavonoid zapotin(6),and N-benzoyltyramide derivatives 7 and 8 were found to be the active constituents.CONCLUSION:Zapotin(6)is the most potent constituent of C.tetrameria with solid tumor selectivity.

  15. Bioengineered models of solid human tumors for cancer research

    Science.gov (United States)

    Marturano-Kruik, Alessandro; Villasante, Aranzazu; Vunjak-Novakovic, Gordana

    2016-01-01

    Summary The lack of controllable in vitro models that can recapitulate the features of solid tumors such as Ewing’s sarcoma limits our understanding of the tumor initiation and progression and impedes the development of new therapies. Cancer research still relies of the use of simple cell culture, tumor spheroids, and small animals. Tissue-engineered tumor models are now being grown in vitro to mimic the actual tumors in patients. Recently, we have established a new protocol for bioengineering the Ewing’s sarcoma, by infusing tumor cell aggregates into the human bone engineered from the patient’s mesenchymal stem cells. The bone niche allows crosstalk between the tumor cells, osteoblasts and supporting cells of the bone, extracellular matrix and the tissue microenvironment. The bioreactor platform used in these experiments also allows the implementation of physiologically relevant mechanical signals. Here, we describe a method to build an in vitro model of Ewing’s sarcoma that mimics the key properties of the native tumor and provides the tissue context and physical regulatory signals. PMID:27115504

  16. Dextran-doxorubicin/chitosan nanoparticles for solid tumor therapy.

    Science.gov (United States)

    Bisht, Savita; Maitra, Amarnath

    2009-01-01

    Chemotherapy is a major therapeutic approach for the treatment of localized and metastasized cancers. Whereas potent chemotherapeutic agents seem promising in the test tube, clinical trials often fail due to unfavorable pharmacokinetics, poor delivery, low local concentrations, and limited accumulation in the target cell. The pathophysiology of the tumor vasculature and stromal compartment presents a major obstacle to effective delivery of agents to solid tumors. Poor perfusion of the tumor, arterio-venous shunting, necrotic and hypoxic areas, as well as a high interstitial fluid pressure work against favorable drug uptake. Thus, targeted drug delivery using long-circulating particulate drug carriers such as hydrogels of controlled size (EPR) effect] while reducing undesirable side effects. This review focuses on the progress of targeted delivery of nanoparticulated anticancer drug such as doxorubicin chemically conjugated with dextran and encapsulated in chitosan nanoparticles to solid tumor with reduced side effect of drug. Regulated particle size and long circulation of these hydrogel nanoparticles in blood help them accumulate in tumor tissue through EPR effect as evident from the significant regression of the tumor volume. The cardiotoxicity of doxorubicin can be minimized by coupling the drug with dextran and encapsulating it in chitosan nanoparticles. PMID:20049807

  17. Solid Pancreatic Tumors with Unilocular Cyst-Like Appearance on CT: Differentiation from Unilocular Cystic Tumors Using CT

    OpenAIRE

    Lee, Ju Hee; Byun, Jae Ho; Kim, Jin Hee; Lee, Seung Soo; Kim, Hyoung Jung; Lee, Moon-Gyu

    2014-01-01

    Objective To describe the computed tomography (CT) features of neuroendocrine tumors (NETs) and solid pseudopapillary tumors (SPTs) with unilocular cyst-like appearance, and to compare them with those of unilocular cystic tumors of the pancreas. Materials and Methods This retrospective study was approved by our Institutional Review Board, and informed consent was waived. We included 112 pancreatic tumors with unilocular cyst-like appearance on CT (16 solid tumors [nine NETs and seven SPTs] an...

  18. Prospective Clinical Study of Precision Oncology in Solid Tumors.

    Science.gov (United States)

    Sohal, Davendra P S; Rini, Brian I; Khorana, Alok A; Dreicer, Robert; Abraham, Jame; Procop, Gary W; Saunthararajah, Yogen; Pennell, Nathan A; Stevenson, James P; Pelley, Robert; Estfan, Bassam; Shepard, Dale; Funchain, Pauline; Elson, Paul; Adelstein, David J; Bolwell, Brian J

    2016-03-01

    Systematic studies evaluating clinical benefit of tumor genomic profiling are lacking. We conducted a prospective study in 250 patients with select solid tumors at the Cleveland Clinic. Eligibility required histopathologic diagnosis, age of 18 years or older, Eastern Cooperative Oncology Group performance status 0-2, and written informed consent. Tumors were sequenced using FoundationOne (Cambridge, MA). Results were reviewed at the Cleveland Clinic Genomics Tumor Board. Outcomes included feasibility and clinical impact. Colorectal (25%), breast (18%), lung (13%), and pancreatobiliary (13%) cancers were the most common diagnoses. Median time from consent to result was 25 days (range = 3-140). Of 223 evaluable samples, 49% (n = 109) of patients were recommended a specific therapy, but only 11% (n = 24) received such therapy: 12 on clinical trials, nine off-label, three on-label. Lack of clinical trial access (n = 49) and clinical deterioration (n = 29) were the most common reasons for nonrecommendation/nonreceipt of genomics-driven therapy.

  19. Frantz’s Tumor (Solid Pseudopap illary Tumor of the Pancreas. A Case Report

    Directory of Open Access Journals (Sweden)

    Settar Bostanoglu

    2009-03-01

    Full Text Available Context A solid pseudopapillary tumor of the pancreas is a rare neoplasm which, for the most part, affects young women and has a relatively favorable prognosis with a low malignant potential. These tumors usually have unclear clinical features and may form very large masses before being diagnosed. Case report We report the case of a 29-year-old woman who underwent complete resection of the tumor using a distal pancreatectomy and splenectomy procedure. The patient is being followed-up and in good condition. A review of the relevant literature is also presented. Conclusions A solid pseudopapillary tumor of the pancreas is a rare condition with a low potential for malignancy and favorable prognosis; surgical resection is generally curative.

  20. A case of solid pseudopapillary tumor of the pancreas

    Institute of Scientific and Technical Information of China (English)

    Ozan Karatag; Gulden Yenice; Huseyin Ozkurt; Muzaffer Basak; Can Basaran; Banu Yilmaz

    2006-01-01

    We present ultrasound, computed tomography and magnetic resonance imaging findings in a case with pancreatic solid pseudopapillary tumor and their correlations with histopathology. Ultrasound revealed a hypoechogenic mass, and computed tomography revealed a hypodense mass at the pancreatic head minimally enhanced after intravenous contrast agent administration. Magnetic resonance imaging showed a hypointense mass on unenhanced T1-weighted images including a hyperintense focus representing the hemorrhage. The lesion was hyperintense on T2-weighted images. On the postcontrast images the lesion showed peripheral thin contrast enhancement in arterial phase and enhanced slightly diffusely in venous and equilibrium phases. The patient underwent elective resection of the mass and pancreatoduodenectomy with jejunostomy tube placement. A final diagnosis of solid pseudopapillary tumor was made histopathologically.Solid pseudopapillary tumor is a rare pancreatic tumor.It is important to make the diagnosis preoperatively because with an adequate surgical resection the prognosis is good. A multimodalitary approach, especially magnetic resonance imaging can suggest the diagnosis without the need for biopsy.

  1. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma.

    Science.gov (United States)

    Kang, Tae Wook; Rhim, Hyunchul

    2015-09-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID:26674766

  2. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma

    OpenAIRE

    Kang, Tae Wook; Rhim, Hyunchul

    2015-01-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic r...

  3. Solid Pseudopapillary Tumor of the Pancreas: a Case Report

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Case Report Solid pseudopapillary tumors (SPT) of the pancreas are considered to be a rare low-grade malignancy that mainly appears in young women. It accounts for less than 1% of all pancreatic neoplasms and is pathologically distinctive from other types of pancreatic cancers. Curative resection is the optimal choice for SPT and the 5-year survival rate of SPT is about 95%. Here we report a case of a young girl who presented with this rare pancreatic tumor.This case involved a 21-year-old girl with a 3-month history of a slowly growing palpable mass in the right upper abdomen.

  4. Advancement and prospects of tumor gene therapy

    OpenAIRE

    Zhang, Chao; Wang, Qing-Tao; Liu, He; Zhang, Zhen-Zhu; Huang, Wen-Lin

    2011-01-01

    Gene therapy is one of the most attractive fields in tumor therapy. In past decades, significant progress has been achieved. Various approaches, such as viral and non-viral vectors and physical methods, have been developed to make gene delivery safer and more efficient. Several therapeutic strategies have evolved, including gene-based (tumor suppressor genes, suicide genes, antiangiogenic genes, cytokine and oxidative stress-based genes) and RNA-based (antisense oligonucleotides and RNA inter...

  5. The Growth of an Extrapancreatic Solid Pseudopapillary Tumor from the Greater Omentum: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yeum Sik; Lee, Young Hwan; Kang, Eu Gene; Jeon, Se Jeong; Park, Seong Hoon; Yun, Ki Jung [Wonkwang University Hospital, Iksan (Korea, Republic of)

    2010-01-15

    A solid pseudopapillary tumor is an uncommon tumor of the pancreas that rarely metastasizes to other organs and usually shows good prognosis. An extrapancreatic tumor arising from a solid pseudopapillary tumor is very rare. We report a case of an atypical extrapancreatic solid pseudopapillary tumor that arose from the great omentum and disseminated to the peritoneum, and discuss the radiologic findings, including the CT, US, and MRI.

  6. Treatment results in case of advanced tonsillar tumors

    International Nuclear Information System (INIS)

    The authors present 99 patients irradiated for a tonsillar carcinoma. 41 patients were primarily irradiated and 52 patients postoperatively. Radiotherapy was combined with cytostatic chemotherapy in six cases. Most of the cases treated were advanced tumors: 76 patients with T3/T4 tumors. 52% out of the 23 patients with T1/T2 tumors survived five years and 45% ten years; only 26% of the patients with T3 tumors and 15% of those with T4 tumors survived five years. The prognosis was significantly influenced by the lymph node state: whereas 75% of the patients with N0 tumors survived five years, this rate is reduced to 21% in case of lymph node state N3. 22 out of the 34 recurrences were situated in the tumor region, 12 in lymph nodes. 94% of recurrences became evident during the first two years after the end of treatment. (orig.)

  7. Advancement and prospects of tumor gene therapy

    Institute of Scientific and Technical Information of China (English)

    Chao Zhang; Qing-Tao Wang; He Liu; Zhen-Zhu Zhang; Wen-Lin Huang

    2011-01-01

    Gene therapy is one of the most attractive fields in tumor therapy. In past decades, significant progress has been achieved. Various approaches, such as viral and non-viral vectors and physical methods, have been developed to make gene delivery safer and more efficient. Several therapeutic strategies have evolved, including gene-based (tumor suppressor genes, suicide genes, antiangiogenic genes, cytokine and oxidative stress-based genes) and RNA-based (antisense oligonucieotides and RNA interference) approaches. In addition, immune response-based strategies (dendritic cell- and T cell-based therapy) are also under investigation in tumor gene therapy. This review highlights the progress and recent developments in gene delivery systems, therapeutic strategies, and possible clinical directions for gene therapy.

  8. Mathematical Based Calculation of Drug Penetration Depth in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Hamidreza Namazi

    2016-01-01

    Full Text Available Cancer is a class of diseases characterized by out-of-control cells’ growth which affect cells and make them damaged. Many treatment options for cancer exist. Chemotherapy as an important treatment option is the use of drugs to treat cancer. The anticancer drug travels to the tumor and then diffuses in it through capillaries. The diffusion of drugs in the solid tumor is limited by penetration depth which is different in case of different drugs and cancers. The computation of this depth is important as it helps physicians to investigate about treatment of infected tissue. Although many efforts have been made on studying and measuring drug penetration depth, less works have been done on computing this length from a mathematical point of view. In this paper, first we propose phase lagging model for diffusion of drug in the tumor. Then, using this model on one side and considering the classic diffusion on the other side, we compute the drug penetration depth in the solid tumor. This computed value of drug penetration depth is corroborated by comparison with the values measured by experiments.

  9. Decitabine: a promising epi-immunotherapeutic agent in solid tumors.

    Science.gov (United States)

    Li, Xiang; Mei, Qian; Nie, Jing; Fu, Xiaobing; Han, Weidong

    2015-03-01

    The incidence of malignancies is increasing worldwide. Despite early detection, surgical resection, chemotherapy and radiotherapy, numerous patients continue to die from metastasis or recurrence. The immune system has the capacity to eradicate cancer cells; however, many tumors, especially solid tumors, present considerable challenges that render immune cells ineffectual, making cancer cells almost 'invisible' to the immune system. Compelling evidence has demonstrated that DNA methylation is involved in tumor development and progression, leading to the impaired immunogenicity and immune recognition of cancer cells. The hypomethylating agent decitabine has been shown to have therapeutic effects in malignancies and exhibits an effective immune efficacy in eliminating cancer cells. Based on the hypomethylating and immune remodeling effects of decitabine, we propose in this review that decitabine can be considered an epi-immunotherapeutic agent. We summarize the results of recent preclinical studies and clinical trials for decitabine and discuss the connections among its hypomethylating effect, immune-activated mechanisms and clinical activity in solid tumors, keeping in mind the goal of optimizing dosing schedules.

  10. Physiologic upper limit of pore size in the blood-tumor barrier of malignant solid tumors

    Directory of Open Access Journals (Sweden)

    Griffiths Gary L

    2009-06-01

    Full Text Available Abstract Background The existence of large pores in the blood-tumor barrier (BTB of malignant solid tumor microvasculature makes the blood-tumor barrier more permeable to macromolecules than the endothelial barrier of most normal tissue microvasculature. The BTB of malignant solid tumors growing outside the brain, in peripheral tissues, is more permeable than that of similar tumors growing inside the brain. This has been previously attributed to the larger anatomic sizes of the pores within the BTB of peripheral tumors. Since in the physiological state in vivo a fibrous glycocalyx layer coats the pores of the BTB, it is possible that the effective physiologic pore size in the BTB of brain tumors and peripheral tumors is similar. If this were the case, then the higher permeability of the BTB of peripheral tumor would be attributable to the presence of a greater number of pores in the BTB of peripheral tumors. In this study, we probed in vivo the upper limit of pore size in the BTB of rodent malignant gliomas grown inside the brain, the orthotopic site, as well as outside the brain in temporalis skeletal muscle, the ectopic site. Methods Generation 5 (G5 through generation 8 (G8 polyamidoamine dendrimers were labeled with gadolinium (Gd-diethyltriaminepentaacetic acid, an anionic MRI contrast agent. The respective Gd-dendrimer generations were visualized in vitro by scanning transmission electron microscopy. Following intravenous infusion of the respective Gd-dendrimer generations (Gd-G5, N = 6; Gd-G6, N = 6; Gd-G7, N = 5; Gd-G8, N = 5 the blood and tumor tissue pharmacokinetics of the Gd-dendrimer generations were visualized in vivo over 600 to 700 minutes by dynamic contrast-enhanced MRI. One additional animal was imaged in each Gd-dendrimer generation group for 175 minutes under continuous anesthesia for the creation of voxel-by-voxel Gd concentration maps. Results The estimated diameters of Gd-G7 dendrimers were 11 ± 1 nm and those of Gd-G8

  11. A quantitative theory of solid tumor growth, metabolic rate and vascularization.

    Directory of Open Access Journals (Sweden)

    Alexander B Herman

    Full Text Available The relationships between cellular, structural and dynamical properties of tumors have traditionally been studied separately. Here, we construct a quantitative, predictive theory of solid tumor growth, metabolic rate, vascularization and necrosis that integrates the relationships between these properties. To accomplish this, we develop a comprehensive theory that describes the interface and integration of the tumor vascular network and resource supply with the cardiovascular system of the host. Our theory enables a quantitative understanding of how cells, tissues, and vascular networks act together across multiple scales by building on recent theoretical advances in modeling both healthy vasculature and the detailed processes of angiogenesis and tumor growth. The theory explicitly relates tumor vascularization and growth to metabolic rate, and yields extensive predictions for tumor properties, including growth rates, metabolic rates, degree of necrosis, blood flow rates and vessel sizes. Besides these quantitative predictions, we explain how growth rates depend on capillary density and metabolic rate, and why similar tumors grow slower and occur less frequently in larger animals, shedding light on Peto's paradox. Various implications for potential therapeutic strategies and further research are discussed.

  12. Rationally Repurposing Ruxolitinib (Jakafi (®)) as a Solid Tumor Therapeutic.

    Science.gov (United States)

    Tavallai, Mehrad; Booth, Laurence; Roberts, Jane L; Poklepovic, Andrew; Dent, Paul

    2016-01-01

    We determined whether the approved myelofibrosis drug ruxolitinib (Jakafi(®)), an inhibitor of Janus kinases 1/2 (JAK1 and JAK2), could be repurposed as an anti-cancer agent for solid tumors. Ruxolitinib synergistically interacted with dual ERBB1/2/4 inhibitors to kill breast as well as lung, ovarian and brain cancer cells. Knock down of JAK1/2 or of ERBB1/2/3/4 recapitulated on-target drug effects. The combination of (ruxolitinib + ERBB1/2/4 inhibitor) rapidly inactivated AKT, mTORC1, mTORC2, STAT3, and STAT5, and activated eIF2α. In parallel, the drug combination reduced expression of MCL-1, BCL-XL, HSP90, HSP70, and GRP78, and increased expression of Beclin1. Activated forms of STAT3, AKT, or mTOR prevented the drug-induced decline in BCL-XL, MCL-1, HSP90, and HSP70 levels. Over-expression of chaperones maintained AKT/mTOR activity in the presence of drugs and protected tumor cells from the drug combination. Expression of dominant negative eIF2α S51A prevented the increase in Beclin1 expression and protected tumor cells from the drug combination. Loss of mTOR activity was associated with increased ATG13 S318 phosphorylation and with autophagosome formation. Autophagosomes initially co-localized with mitochondria and subsequently with lysosomes. Knock down of Beclin1 suppressed: drug-induced mitophagy; the activation of the toxic BH3 domain proteins BAX and BAK; and tumor cell killing. Knock down of apoptosis-inducing factor (AIF) protected tumor cells from the drug combination, whereas blockade of caspase 9 signaling did not. The drug combination released AIF into the cytosol and increased nuclear AIF: eIF3A co-localization. A 4-day transient exposure of orthotopic tumors to (ruxolitinib + afatinib) profoundly reduced mammary tumor growth over the following 35 days. Re-grown tumors exhibited high levels of BAD S112 phosphorylation and activation of ERK1/2 and NFκB. Our data demonstrate that mitophagy is an essential component of (ruxolitinib

  13. Targeting JAK kinase in solid tumors: emerging opportunities and challenges.

    Science.gov (United States)

    Buchert, M; Burns, C J; Ernst, M

    2016-02-25

    Various human malignancies are characterized by excessive activation of the Janus family of cytoplasmic tyrosine kinases (JAK) and their associated transcription factors STAT3 and STAT5. In the majority of solid tumors, this occurs in response to increased abundance of inflammatory cytokines in the tumor microenvironment prominently produced by infiltrating innate immune cells. Many of these cytokines share common receptor subunits and belong to the interleukin (IL)-6/IL-11, IL-10/IL-22 and IL-12/IL-23 families. Therapeutic inhibition of the JAK/STAT3 pathway potentially offers considerable benefit owing to the capacity of JAK/STAT3 signaling to promote cancer hallmarks in the tumor and its environment, including proliferation, survival, angiogenesis, tumor metabolism while suppressing antitumor immunity. This is further emphasized by the current successful clinical applications of JAK-specific small molecule inhibitors for the treatment of inflammatory disorders and hematopoietic malignancies. Here we review current preclinical applications for JAK inhibitors for the treatment of solid cancers in mice, with a focus on the most common malignancies emanating from oncogenic transformation of the epithelial mucosa in the stomach and colon. Emerging data with small molecule JAK-specific adenosine triphosphate-binding analogs corroborate genetic findings and suggest that interference with the JAK/STAT3 pathway may suppress the growth of the most common forms of sporadic colon cancers that arise from mutations of the APC tumor suppressor gene. Likewise inhibition of cytokine-dependent activation of the JAK/STAT3 pathway may also afford orthogonal treatment opportunities for other oncogene-addicted cancer cells that have gained drug resistance. PMID:25982279

  14. ASAS = NASA's Advanced Solid-state Array Spectroradiometer: 1988 -2000

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — The Advanced Solid-State Array Spectroradiometer (ASAS) data collection contains data collected by the ASAS sensor flown aboard NASA aircraft. A fundamental use of...

  15. Advances in solid dosage form manufacturing technology.

    Science.gov (United States)

    Andrews, Gavin P

    2007-12-15

    Currently, the pharmaceutical and healthcare industries are moving through a period of unparalleled change. Major multinational pharmaceutical companies are restructuring, consolidating, merging and more importantly critically assessing their competitiveness to ensure constant growth in an ever-more demanding market where the cost of developing novel products is continuously increasing. The pharmaceutical manufacturing processes currently in existence for the production of solid oral dosage forms are associated with significant disadvantages and in many instances provide many processing problems. Therefore, it is well accepted that there is an increasing need for alternative processes to dramatically improve powder processing, and more importantly to ensure that acceptable, reproducible solid dosage forms can be manufactured. Consequently, pharmaceutical companies are beginning to invest in innovative processes capable of producing solid dosage forms that better meet the needs of the patient while providing efficient manufacturing operations. This article discusses two emerging solid dosage form manufacturing technologies, namely hot-melt extrusion and fluidized hot-melt granulation. PMID:17855217

  16. Malignant solid pseudopapillary tumor of pancreas causing sinistral portal hypertension

    Directory of Open Access Journals (Sweden)

    Nisar Ahmad Wani

    2011-01-01

    Full Text Available Solid pseudopapillary tumor (SPT of the pancreas is a rare benign or low-grade malignant epithelial tumor that occurs mainly in young females in second to fourth decades of life. Pathologic and imaging findings include a well-defined, encapsulated pancreatic mass with cystic and solid components with evidence of hemorrhage. We report a 23-year-old female who presented with upper abdominal pain of long duration and epigastric mass on palpation. Multidetector-row CT (MDCT demonstrated a large well-defined heterogeneous attenuation mass, containing hyperdense areas of hemorrhage mixed with solid enhancing and cystic non-enhancing areas, arising from the pancreatic body and tail. Splenic vein thrombosis was present with dilated splenoportal collateral vessels between splenic hilum and portal/superior mesenteric veins, with dilated vessels seen in the gastric wall, with patent portal vein, compatible with sinistral portal hypertension. Typical imaging features and age and sex of the patient suggested a diagnosis of SPT of pancreas complicated by segmental portal hypertension due to splenic vein thrombosis. Histopathology of the biopsy material was confirmatory.

  17. Response of quiescent and total tumor cells in solid tumors to neutrons with various cadmium ratios

    International Nuclear Information System (INIS)

    Purpose: Response of quiescent (Q) and total tumor cells in solid tumors to neutron irradiation with three different cadmium (Cd) ratios was examined. The role of Q cells in tumor control was also discussed. Methods and Materials: C3H/He mice bearing SCC VII tumors received continuous administration of 5-bromo-2'-deoxyuridine (BrdU) for 5 days using implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty minutes after intraperitoneal injection of sodium borocaptate-10B (BSH), or 3 h after oral administration of dl-p-boronophenylalanine-10B (BPA), the tumors were irradiated with neutrons, or those without 10B-compounds were irradiated with gamma rays. This neutron irradiation was performed using neutrons with three different cadmium (Cd) ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis-blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in total (P + Q) tumor cells was determined from tumors that were not pretreated with BrdU. The sensitivity to neutrons was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency). Results: Without 10B-compounds, the MN frequency in Q cells was lower than that in the total cell population. The sensitivity difference between total and Q cells was reduced by neutron irradiation. Relative biological effectiveness (RBE) of neutrons compared with gamma rays was larger in Q cells than in total cells, and the RBE values for low-Cd-ratio neutrons tended to be larger than those for high-Cd-ratio neutrons. With 10B-compounds, MN frequency for each cell population was increased, especially for total cells. This increase in MN frequency was marked when high-Cd-ratio neutrons were used. BPA increased the MN frequency for total tumor cells more than BSH. Nevertheless, the sensitivity of Q

  18. Applied solid state science advances in materials and device research

    CERN Document Server

    Wolfe, Raymond

    2013-01-01

    Applied Solid State Science: Advances in Materials and Device Research, Volume 4 covers articles on single crystal compound semiconductors and complex polycrystalline materials. The book discusses narrow gap semiconductors and solid state batteries. The text then describes the advantages of hot-pressed microcrystalline compacts of oxygen-octahedra ferroelectrics over single crystal materials, as well as heterostructure junction lasers. Solid state physicists, materials scientists, electrical engineers, and graduate students studying the subjects being discussed will find the book invaluable.

  19. Thoughts about cancer stem cells in solid tumors.

    Science.gov (United States)

    La Porta, Caterina Am

    2012-03-26

    Cancer chemotherapy efficacy is frequently impaired by either intrinsic or acquired tumor resistance. A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. In recent years, the cancer stem cell (CSC) theory has changed the classical view of tumor growth and therefore the therapeutic perspective. Overcoming intrinsic and acquired resistance of cancer stem/progenitor cells to current clinical treatments represents a major challenge in treating and curing the most aggressive and metastatic cancers. On the other hand, the identification of CSCs in vivo and in vitro relies on specific surface markers that should allow the sorting cancer cells into phenotypically distinct subpopulations. In the present review, recent papers published on CSCs in solid tumors (breast, prostate, brain and melanoma) are discussed, highlighting critical points such as the choice of markers to sort CSCs and mouse models to demonstrate that CSCs are able to replicate the original tumor. A discussion of the possible role of aldehyde dehydrogenase and CXCR6 biomarkers as signaling molecules in CSCs and normal stem cells is also discussed. The author believes that efforts have to be made to investigate the functional and biological properties of putative CSCs in cancer. Developing diagnostic/prognostic tools to follow cancer development is also a challenge. In this connection it would be useful to develop a multidisciplinary approach combining mathematics, physics and biology which merges experimental approaches and theory. Biological models alone are probably unable to resolve the problem completely.

  20. Solid Pancreatic Tumors with Unilocular Cyst-Like Appearance on CT: Differentiation from Unilocular Cystic Tumors Using CT

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ju Hee [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Department of Radiology, National Cancer Center, Goyang 410-769 (Korea, Republic of); Byun, Jae Ho; Kim, Jin Hee; Lee, Seung Soo; Kim, Hyoung Jung; Lee, Moon-Gyu [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of)

    2014-07-01

    To describe the computed tomography (CT) features of neuroendocrine tumors (NETs) and solid pseudopapillary tumors (SPTs) with unilocular cyst-like appearance, and to compare them with those of unilocular cystic tumors of the pancreas. This retrospective study was approved by our Institutional Review Board, and informed consent was waived. We included 112 pancreatic tumors with unilocular cyst-like appearance on CT (16 solid tumors [nine NETs and seven SPTs] and 96 cystic tumors [45 serous cystadenomas, 30 mucinous cystic neoplasms, and 21 branch-duct intraductal papillary mucinous neoplasms]). Two radiologists reviewed the CT images in consensus to determine tumor location, long diameter, morphological features, wall thicknesses, ratio of wall thickness to tumor size, wall enhancement patterns, intratumoral contents, and accompanying findings. Fisher's exact test was used to analyze the results. All 16 solid tumors had perceptible walls (mean thickness, 2.7 mm; mean ratio of wall thickness to tumor size, 7.7%) with variable enhancement. Four NETs and seven SPTs had hemorrhage, calcifications, and/or mural nodules. Six CT findings were specific for solid tumors with unilocular cyst-like appearance: a thick (> 2 mm) wall, uneven thickness of the wall, high ratio of wall thickness to tumor size, hyper- or hypo-attenuation of the wall in the arterial and portal phase, and heterogeneous internal contents. When three or more of the above criteria were used, 100% specificity and 87.5-92% accuracy were obtained for solid tumors with unilocular cyst-like appearance. A combination of CT features was useful for distinguishing solid tumors with unilocular cyst-like appearance from unilocular cystic tumors of the pancreas.

  1. High intensity focused ultrasound ablation: A new therapeutic option for solid tumors

    Directory of Open Access Journals (Sweden)

    Orsi Franco

    2010-01-01

    Full Text Available Surgery has been the standard of care in selected cases with solid tumors. However, a majority of patients are unable to undergo surgical resection because of the tumor sites, advanced stages, or poor general condition. High intensity focused ultrasound (HIFU is a novel non-invasive technique that is capable of producing coagulative necrosis at a precise focal point within the body, without harming overlying and adjacent structures even within the path of the beam. Diagnostic ultrasound was the first imaging modality used for guiding HIFU ablation in the 1990s. Over the last decade, thousands of patients with uterine fibroids, liver cancer, breast cancer, pancreatic cancer, bone tumors, renal cancer have been treated with ultrasound imaging-guided HIFU (USgHIFU worldwide. This USgHIFU system [Chongqing Haifu (HIFU Tech Co., Ltd., Chongqing, China] was first equipped in Asia, now in Europe. Several research groups have demonstrated that HIFU is safe and effective in treating human solid tumors. In 2004, the magnetic resonance guided focused ultrasound surgery (MRgFUS was approved by the United States Food and Drug Administration (FDA for clinical treatments of uterine fibroids. We conclude that HIFU offers patients another choice when no other treatment available or when patients refused surgical operation. This technique may play a key role in future clinical practice.

  2. Hyperuricemic Renal Failure in Nonhematologic Solid Tumors: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Neeraj Saini

    2012-01-01

    Full Text Available Tumor lysis syndrome (TLS is an oncologic emergency that is caused by massive tumor cell lysis. It is commonly associated with hematological cancers like leukemia and lymphoma and uncommonly with solid nonhematologic tumors as well. However, spontaneous tumor lysis syndrome (STLS without any cytotoxic chemotherapy rarely occurs in solid tumors. We describe a case of STLS in a metastatic adenocarcinoma of unknown primary and review the literature of STLS in solid non-hematologic tumors to identify various risk factors for pathogenesis of this entity.

  3. Laser cooling in solids: advances and prospects.

    Science.gov (United States)

    Seletskiy, Denis V; Epstein, Richard; Sheik-Bahae, Mansoor

    2016-09-01

    This review discusses the progress and ongoing efforts in optical refrigeration. Optical refrigeration is a process in which phonons are removed from a solid by anti-Stokes fluorescence. The review first summarizes the history of optical refrigeration, noting the success in cooling rare-earth-doped solids to cryogenic temperatures. It then examines in detail a four-level model of rare-earth-based optical refrigeration. This model elucidates the essential roles that the various material parameters, such as the spacing of the energy levels and the radiative quantum efficiency, play in the process of optical refrigeration. The review then describes the experimental techniques for cryogenic optical refrigeration of rare-earth-doped solids employing non-resonant and resonant optical cavities. It then examines the work on laser cooling of semiconductors, emphasizing the differences between optical refrigeration of semiconductors and rare-earth-doped solids and the new challenges and advantages of semiconductors. It then describes the significant experimental results including the observed optical refrigeration of CdS nanostructures. The review concludes by discussing the engineering challenges to the development of practical optical refrigerators, and the potential advantages and uses of these refrigerators. PMID:27484295

  4. Laser cooling in solids: advances and prospects

    Science.gov (United States)

    Seletskiy, Denis V.; Epstein, Richard; Sheik-Bahae, Mansoor

    2016-09-01

    This review discusses the progress and ongoing efforts in optical refrigeration. Optical refrigeration is a process in which phonons are removed from a solid by anti-Stokes fluorescence. The review first summarizes the history of optical refrigeration, noting the success in cooling rare-earth-doped solids to cryogenic temperatures. It then examines in detail a four-level model of rare-earth-based optical refrigeration. This model elucidates the essential roles that the various material parameters, such as the spacing of the energy levels and the radiative quantum efficiency, play in the process of optical refrigeration. The review then describes the experimental techniques for cryogenic optical refrigeration of rare-earth-doped solids employing non-resonant and resonant optical cavities. It then examines the work on laser cooling of semiconductors, emphasizing the differences between optical refrigeration of semiconductors and rare-earth-doped solids and the new challenges and advantages of semiconductors. It then describes the significant experimental results including the observed optical refrigeration of CdS nanostructures. The review concludes by discussing the engineering challenges to the development of practical optical refrigerators, and the potential advantages and uses of these refrigerators.

  5. Anxiety, depression in patients receiving chemotherapy for solid tumors

    International Nuclear Information System (INIS)

    To determine the frequency of anxiety and depression in patients undergoing chemotherapy for solid tumors using Hospital Anxiety Depression Scale (HADS). Study Design: Cross sectional descriptive study. Place and Duration of Study: Out-patient department of Armed Forces Institute of Mental Health, Rawalpindi from June 2011 to December 2011. Methodology: Consecutive non probability sampling technique was used to select patients of age (25-70 years), male or female, who had received atleast 03 cycles of chemotherapy for solid tumors. Those with history of prior psychiatric illness, current use of psychotropic medication or psychoactive substance use, and any major bereavement in past one year were excluded from the study. After taking informed consent, relevant socio- demographic data was collected and HADS was administered. HADS-A cut off score of 7 was taken as significant anxiety while a HADS-D cut off score of 7 was taken as significant depression. Results: The total number of participants was 209. The mean age of patients was 42.9 years, with 55.5% males and 44.5% females. Overall 33/209 (15.8%) patients had anxiety while 56/209 (26.8%) were found to have depression. There was a higher frequency of anxiety and depression in younger patients (less than age 40 years), females, patients who were single or divorced, and patients receiving chemotherapy for pancreatic carcinoma. Conclusion: Patients undergoing chemotherapy suffer from considerable levels of anxiety and depression, thus highlighting the need for specialized interventions. (author)

  6. Neoadjuvant imatinib in locally advanced gastrointestinal stromal tumors

    Directory of Open Access Journals (Sweden)

    Seshadri Ramakrishnan

    2009-01-01

    Full Text Available Aim : To study the role of neoadjuvant imatinib mesylate in downsizing tumors in patients with locally advanced nonmetastatic gastrointestinal stromal tumors (GISTs, thus improving the possibility of complete resection. Materials and Methods : We used neoadjuvant imatinib in six patients with locally advanced GISTs, at a dose of 400 mg daily, given orally in all patients for a median period of 3.5 months (range 1-20 months. All patients had a computerized tomography scan (CT scan once before starting the treatment and a repeat CT scan 1 month after starting imatinib. Some patients had another CT scan done at 3 months. The tumor volume was calculated using the formula V=4/3 πr 3 . Results : Following imatinib therapy, the median reduction in the tumor volume was 40% (range 20-50%. Four of the six patients underwent successful complete resection of the tumor following neoadjuvant imatinib for a median period of 2 months, and are disease free after a median follow-up of 10.5 months (range 3-20 months. Two patients in whom the tumors were deemed to be operable after downsizing refused surgery and are continuing imatinib. Imatinib did not produce serious toxicity in any patient. Conclusion : Neoadjuvant imatinib can be used successfully in patients with locally advanced nonmetastatic GISTs to improve the rates of complete resection and reduce the chance of tumor spill. The optimal duration of neoadjuvant treatment needs to be tailored based on response assessment at frequent intervals to identify the ideal window period for surgery.

  7. Solid Pseudopapillary Tumor of the Pancreas with Concomitant Pancreas Divisum. A Case Report

    OpenAIRE

    Daisuke Watanabe; Kouichi Miura; Takashi Goto; Hirohide Ohnishi; Hiroshi Nanjo; Yuzo Yamamoto

    2010-01-01

    Context Solid pseudopapillary tumor of the pancreas is a rare neoplasm which affects young women. On the other hand, pancreas divisum is an anomaly which develops at 7 weeks of gestation. Here, we report a case of a solid pseudopapillary tumor of the pancreas with concomitant pancreas divisum. Case report A 26-year-old woman was diagnosed as having a pancreatic tumor with solid and cystic components in the pancreatic head. Pancreatograms obtained by ERCP and MRCP showed no communication betwe...

  8. Magna-field irradiation and autologous marrow rescue in the treatment of pediatric solid tumors

    International Nuclear Information System (INIS)

    Marrow ablative therapy has been given to pediatric patients with a variety of disseminated tumors. Eight patients with advanced neuroblastoma received autologous marrow reinfusion after intensive therapy. Three of eight are in continuous complete remission from 7 to 60 months. An additional four patients received allogeneic marrow transplantation and two remain in continuous complete response at 21 and 39 months. Intensive therapy and autologous marrow reinfusion have been applied to Ewing's sarcoma, but only preliminary results are available. Six patients with disseminated rhabdomyosarcoma and extra-osseous Ewing's sarcoma received conventional chemotherapy followed by sequential hemi-body irradiation. Four of six patients received autologous marrow rescue. Their median disease-free survival is 17 months. This preliminary experience demonstrates the feasibility of using marrow ablative therapy with autologous marrow transplantation in the treatment of pediatric solid tumors. Continuing Phase II studies are required to substantiate its efficacy

  9. Advanced materials for solid oxide fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Armstrong, T.R.; Stevenson, J.

    1995-08-01

    The purpose of this research is to improve the properties of the current state-of-the-art materials used for solid oxide fuel cells (SOFCs). The objectives are to: (1) develop materials based on modifications of the state-of-the-art materials; (2) minimize or eliminate stability problems in the cathode, anode, and interconnect; (3) Electrochemically evaluate (in reproducible and controlled laboratory tests) the current state-of-the-art air electrode materials and cathode/electrolyte interfacial properties; (4) Develop accelerated electrochemical test methods to evaluate the performance of SOFCs under controlled and reproducible conditions; and (5) Develop and test materials for use in low-temperature SOFCs. The goal is to modify and improve the current state-of-the-art materials and minimize the total number of cations in each material to avoid negative effects on the materials properties. Materials to reduce potential deleterious interactions, (3) improve thermal, electrical, and electrochemical properties, (4) develop methods to synthesize both state-of-the-art and alternative materials for the simultaneous fabricatoin and consolidation in air of the interconnections and electrodes with the solid electrolyte, and (5) understand electrochemical reactions at materials interfaces and the effects of component composition and processing on those reactions.

  10. Profile of nintedanib in the treatment of solid tumors: the evidence to date

    Directory of Open Access Journals (Sweden)

    Awasthi N

    2015-12-01

    Full Text Available Niranjan Awasthi,1 Roderich E Schwarz1,2 1Department of Surgery, Indiana University School of Medicine, South Bend, IN, USA; 2Indiana University Health Goshen Center for Cancer Care, Goshen, IN, USA Abstract: Angiogenesis is an essential process for tumor growth and metastasis, and remains a promising therapeutic target process in cancer treatment for several cancer types. Bevacizumab, a monoclonal antibody that targets vascular endothelial growth factor (VEGF, was the first antiangiogenic agent approved for cancer therapy. Novel antiangiogenic agents, such as sunitinib, sorafenib, pazopanib, or vandetanib that target additional proangiogenic signaling pathways beyond VEGF, have also been approved for the treatment of various malignant diseases. While most of these agents are approved in combination with cytotoxic chemotherapy for indications including metastatic colorectal cancer, non-small-cell lung cancer, breast cancer, renal cell carcinoma (RCC, and gastric cancer, some are used as approved monotherapy for advanced RCC, hepatocellular carcinoma and medullary thyroid cancer. Major challenges to the success of antiangiogenic therapy include associated toxicity risks, limitation of efficacy through the possible development of resistance and induction or promotion of metastatic progression. Nintedanib (formally known as BIBF 1120 is a triple angiokinase inhibitor of VEGF, fibroblast growth factor, platelet-derived growth factor signaling with lesser activity against RET, Flt-3, and Src. Through this unique targeting profile nintedanib has demonstrated significant antitumor activity in several tumor types in preclinical studies. Nintedanib has also shown promising clinical efficacy in combination with docetaxel and has been approved for treating patients with locally advanced and metastatic non-small-cell lung cancer in Europe. Nintedanib has also been found to be clinically promising in terms of efficacy and safety in several other solid tumors

  11. [Hormonal therapy of advanced or relapsed ovarian granulosa cell tumor].

    Science.gov (United States)

    Sun, H; Bai, P

    2016-07-01

    Ovarian granulosa cell tumor is a rare gynecologic malignancy with hormonal activity. Surgical excision is the standard treatment for this disease. Most patients present excellent short term prognosis, however, late relapse often occurs, even after many years. Viable treatments of advanced or relapsed granulosa cell tumor are still limited, and the optimal therapy method has not been established. Compared with chemotherapy and radiotherapy, hormonal therapy is a well-tolerated treatment which can be administrated over a long period of time without serious side effects, and the combined application of hormones may achieve a better outcome. Therefore, hormonal therapy has been suggested as a potential treatment option for patients with advanced or relapsed granulosa cell tumor, and to extend the tumor-free interval and attenuate the disease progression. Future researches should be focused on the identification of the hormonal therapy which may provide the greatest clinical benefit, comparing and analyzing the effects of different combined therapeutic regimens of hormone drugs, and on the synthesis of drugs highly activating estrogen receptor β expressed in the granulosa cell tumor cells. PMID:27531259

  12. Applied solid state science advances in materials and device research

    CERN Document Server

    Wolfe, Raymond

    2013-01-01

    Applied Solid State Science: Advances in Materials and Device Research, Volume 1 presents articles about junction electroluminescence; metal-insulator-semiconductor (MIS) physics; ion implantation in semiconductors; and electron transport through insulating thin films. The book describes the basic physics of carrier injection; energy transfer and recombination mechanisms; state of the art efficiencies; and future prospects for light emitting diodes. The text then discusses solid state spectroscopy, which is the pair spectra observed in gallium phosphide photoluminescence. The extensive studies

  13. Ixabepilone in Treating Young Patients With Solid Tumors or Leukemia That Haven't Responded to Therapy

    Science.gov (United States)

    2012-03-14

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Leukemia; Liver Cancer; Neuroblastoma; Ovarian Cancer; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

  14. Advanced methods of solid oxide fuel cell modeling

    CERN Document Server

    Milewski, Jaroslaw; Santarelli, Massimo; Leone, Pierluigi

    2011-01-01

    Fuel cells are widely regarded as the future of the power and transportation industries. Intensive research in this area now requires new methods of fuel cell operation modeling and cell design. Typical mathematical models are based on the physical process description of fuel cells and require a detailed knowledge of the microscopic properties that govern both chemical and electrochemical reactions. ""Advanced Methods of Solid Oxide Fuel Cell Modeling"" proposes the alternative methodology of generalized artificial neural networks (ANN) solid oxide fuel cell (SOFC) modeling. ""Advanced Methods

  15. [Microflora of pharyngeal mucosa in children with solid tumors].

    Science.gov (United States)

    Polishchuk, V B; Baturo, A P; Romanenko, E E; Kostinov, M P; Zaeva, G E; Mikhaĭlova, S N; Leonova, A Iu; Moiseenko, E I

    2008-01-01

    Microbiological study of pharyngeal mucosa in 43 children with solid tumors revealed that 77.2% of isolated microorganisms belonged to Gram-positive flora. It was shown that streptococci and Staphylococcus aureus were the main species. Species composition of streptococci included both pyogenic (S. pyogenes, S. agalactiae, S. dysgalactiae, S. equi) andviridans species (S. acidominimus, S. oralis and "S. milleri" group). Nocardioform actinomycetes, corynebacteria and other staphylococci were referred to additional microflora. Accidental microflora was represented by Neisseria spp., non-fermenting Gram-negative bacteria, enterobacteria and yeast-like fungi. Microbiologic study of pharyngeal mucosa biocenosis showed that monoculture was present only in 2.3% of cases; in other cases microorganisms formed both intra-genus and inter-species associations. 2-6-component associations were revealed with predominance of 3-4-component associations (37.2% and 32.6% respectively). Relationship of distribution of microorganisms belonging to main and additional microflora was revealed. PMID:19186552

  16. 自体DC-CIK细胞回输联合化疗治疗晚期恶性实体瘤疗效观察%The curative effect of autologous DC-CIK cells transfusion combined with chemotherapy in the treatment of advanced malignant solid tumor

    Institute of Scientific and Technical Information of China (English)

    金美四; 朱红梅; 李一辉

    2014-01-01

    目的:观察化疗联合自体DC-CIK细胞回输治疗晚期恶性实体瘤的近期疗效。方法观察单纯化疗(对照组)和化疗联合自体DC-CIK细胞回输(联合组)治疗晚期恶性实体肿瘤疗效,主要观察指标:治疗前后外周血细胞因子、肿瘤标志物、胃肠道反应及骨髓抑制、生活质量、KPS评分。结果对照组20例治疗后CR 0例,PR 1例,MR 2例,SD 7例;PD 10例,缓解率为15%,DCR为50%。联合组治疗后CR 1例,PR 2例,MR 4例,SD 10例,PD 3例,缓解率35%,DCR为85%。两组DCR比较差异有统计学意义(χ2=5.58,P<0.05)。生存质量指标癌性疼痛、精神、睡眠、疲乏无力联合组比对照组改善明显,两组比较差异都有统计学意义(P<0.05);联合组和对照组胃肠道反应比较差异无统计学意义(χ2=1.71,P<0.05);联合组和对照组骨髓抑制情况比较差异有统计学意义(χ2=4.91,P<0.05);联合组治疗前后肿瘤标志物及外周血细胞因子计数变化比较无统计学差异(P>0.05)。结论自体DC-CIK细胞回输联合化疗治疗晚期恶性实体瘤DCR比单纯化疗者高,并且能够改善晚期肿瘤患者生存质量、KPS评分,减轻化疗后骨髓抑制情况,但胃肠道反应无明显差异。肿瘤标志物及细胞因子无明显变化。%Objective To explore the curative effect in the near future that autologous DC-CIK cells transfusion com-bined with chemotherapy in the treatment of advanced malignant solid tumor. Methods Observed the curative effect that au-tologous DC-CIK cells transfusion combined with chemotherapy in the treatment of advanced malignant solid tumor , and the pe-ripheral blood cytokins, tumor markers, gastrointestinal reactions, bone marrow suppression,the quality of life,kamofsky grade. Results There was 0 case completely response (CR) in twenty advanced tumor patients that cured by chemotherapy, part re-sponse(PR) of 1 case

  17. Ultrasonic enhancement of drug penetration in solid tumors

    Directory of Open Access Journals (Sweden)

    Chun-yen eLai

    2013-08-01

    Full Text Available Increasing the penetration of drugs within solid tumors can be accomplished through multiple ultrasound-mediated mechanisms. The application of ultrasound can directly change the structure or physiology of tissues or can induce changes in a drug or vehicle in order to enhance delivery and efficacy. With each ultrasonic pulse, a fraction of the energy in the propagating wave is absorbed by tissue and results in local heating. When ultrasound is applied to achieve mild hyperthermia, the thermal effects are associated with an increase in perfusion or the release of a drug from a temperature-sensitive vehicle. Higher ultrasound intensities locally ablate tissue and result in increased drug accumulation surrounding the ablated region of interest. Further, the mechanical displacement induced by the ultrasound pulse can result in the nucleation, growth and collapse of gas bubbles. As a result of such cavitation, the permeability of a vessel wall or cell membrane can be increased. Finally, the radiation pressure of the propagating pulse can translate particles or tissues. In this perspective, we will review recent progress in ultrasound-mediated tumor delivery and the opportunities for clinical translation.

  18. Advanced Solid State Lighting for AES Deep Space Hab Project

    Science.gov (United States)

    Holbert, Eirik

    2015-01-01

    The advanced Solid State Lighting (SSL) assemblies augmented 2nd generation modules under development for the Advanced Exploration Systems Deep Space Habitat in using color therapy to synchronize crew circadian rhythms. Current RGB LED technology does not produce sufficient brightness to adequately address general lighting in addition to color therapy. The intent is to address both through a mix of white and RGB LEDs designing for fully addressable alertness/relaxation levels as well as more dramatic circadian shifts.

  19. Radiation from advanced solid rocket motor plumes

    Science.gov (United States)

    Farmer, Richard C.; Smith, Sheldon D.; Myruski, Brian L.

    1994-01-01

    The overall objective of this study was to develop an understanding of solid rocket motor (SRM) plumes in sufficient detail to accurately explain the majority of plume radiation test data. Improved flowfield and radiation analysis codes were developed to accurately and efficiently account for all the factors which effect radiation heating from rocket plumes. These codes were verified by comparing predicted plume behavior with measured NASA/MSFC ASRM test data. Upon conducting a thorough review of the current state-of-the-art of SRM plume flowfield and radiation prediction methodology and the pertinent data base, the following analyses were developed for future design use. The NOZZRAD code was developed for preliminary base heating design and Al2O3 particle optical property data evaluation using a generalized two-flux solution to the radiative transfer equation. The IDARAD code was developed for rapid evaluation of plume radiation effects using the spherical harmonics method of differential approximation to the radiative transfer equation. The FDNS CFD code with fully coupled Euler-Lagrange particle tracking was validated by comparison to predictions made with the industry standard RAMP code for SRM nozzle flowfield analysis. The FDNS code provides the ability to analyze not only rocket nozzle flow, but also axisymmetric and three-dimensional plume flowfields with state-of-the-art CFD methodology. Procedures for conducting meaningful thermo-vision camera studies were developed.

  20. SOLID CYSTIC PAPILLARY TUMOR OF PANCREAS IN EIGHT CHILDREN

    Institute of Scientific and Technical Information of China (English)

    Ke-ren Zhang; Hui-min Jia; Hong Shu; Xin-yuan Li

    2007-01-01

    Objective To estimate the clinical and pathological features of pancreatic solid cystic papillary tumor (SCPT) in children.Methods From 2000 to 2005 , 8 cases with SCPT of the pancreas were analyzed retrospectively. All cases but one were females. Average age was 12.8 years. By case review, we discussed the clinical and pathological features of SCPT in children.Results The chief complains were abdominal pain and palpable mass. There were 3 cases in the head, 1 case in the body, and 4 cases in the tail of pancreas. The procedures employed included local resection (1 case), distal pancre-atectomy (5 cases) , pancreaticoduodenectomy (1 case) , and biopsy (1 case). Histological examination showed solid with cystic areas and papillary protrusions in the 8 cases; as for immunohistochemical examinations, the positive rate was 100% for ct-antitrypsin (AACT) , 87.5% for vinmentin, and 62.5% for neuron-specific enolase (NSE). The patients were followed up for 2 months to 4 years but one was lost by follow-up and all were alive postoperatively. SCPT in 2 cases relapsed.Conclusion Occurring predominantly in young females, SCPT is usually curable by surgical resection with a favorable prognosis.

  1. Busulfan, Melphalan, Topotecan Hydrochloride, and a Stem Cell Transplant in Treating Patients With Newly Diagnosed or Relapsed Solid Tumor

    Science.gov (United States)

    2016-05-04

    Solid Tumor; Adult Central Nervous System Germ Cell Tumor; Adult Rhabdomyosarcoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Soft Tissue Sarcoma; Ewing Sarcoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Ovarian Mixed Germ Cell Tumor; Previously Untreated Childhood Rhabdomyosarcoma; Recurrent Adult Brain Tumor; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Extragonadal Germ Cell Tumor; Recurrent Extragonadal Non-seminomatous Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Neuroblastoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

  2. Pediatric brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Poussaint, Tina Y. [Department of Radiology, Boston, MA (United States); Panigrahy, Ashok [Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Department of Radiology, Pittsburgh, PA (United States); Huisman, Thierry A.G.M. [Charlotte R. Bloomberg Children' s Center, Johns Hopkins Hospital, Division of Pediatric Radiology and Pediatric Neuroradiology, Baltimore, MD (United States)

    2015-09-15

    Among all causes of death in children from solid tumors, pediatric brain tumors are the most common. This article includes an overview of a subset of infratentorial and supratentorial tumors with a focus on tumor imaging features and molecular advances and treatments of these tumors. Key to understanding the imaging features of brain tumors is a firm grasp of other disease processes that can mimic tumor on imaging. We also review imaging features of a common subset of tumor mimics. (orig.)

  3. Advanced technologies available for future solid propellant grains

    Science.gov (United States)

    Thépénier, Jean; Fonblanc, Gilles

    2001-03-01

    Significant advances have been made during the last decade in several fields of solid propulsion: the advances have enabled new savings in the motor development phase and recurring costs, because they help limit the number of prototypes and tests. The purpose of the paper is to describe the improvements achieved by SNPE in solid grain technologies, making these technologies available for new developments in more efficient and reliable future SRMs: new energetic molecules, new solid propellants, new processes for grain manufacturing, quick response grain design tools associated with advanced models for grain performance predictions. Using its expertise in chemical synthesis, SNPE develops new molecules to fit new energetic material requirements. Tests based on new propellant formulations have produced good results in the propellant performance/safety behavior ratio. New processes have been developed simultaneously to reduce the manufacturing costs of the new propellants. In addition, the grain design has been optimized by using the latest generation of predictive theoretical tools supported by a large data bank of experimental parameters resulting from over 30 years' experience in solid propulsion: Computer-aided method for the preliminary grain design Advanced models for SRM operating and performance predictions

  4. Using a 3-d model system to screen for drugs effective on solid tumors

    OpenAIRE

    Fayad, Walid

    2011-01-01

    There is a large medical need for the development of effective anticancer agents with minimal side effects. The present thesis represents an attempt to identify potent drugs for treatment of solid tumors. We used a strategy where 3-D multicellular tumor spheroids (cancer cells grown in three dimensional culture) were utilized as in vitro models for solid tumors. Drug libraries were screened using spheroids as targets and using apoptosis induction and loss of cell viability as endpoints. The h...

  5. Hypoxia-directed and activated theranostic agent: Imaging and treatment of solid tumor.

    Science.gov (United States)

    Kumar, Rajesh; Kim, Eun-Joong; Han, Jiyou; Lee, Hyunseung; Shin, Weon Sup; Kim, Hyun Min; Bhuniya, Sankarprasad; Kim, Jong Seung; Hong, Kwan Soo

    2016-10-01

    Hypoxia, a distinguished feature of various solid tumors, has been considered as a key marker for tumor progression. Inadequate vasculature and high interstitial pressures result in relatively poor drug delivery to these tumors. Herein, we developed an antitumor theranostic agent, 4, which is activated in hypoxic conditions and can be used for the diagnosis and treatment of solid tumors. Compound 4, bearing biotin, a tumor-targeting unit, and SN38, an anticancer drug, proved to be an effective theranostic agent for solid tumors. SN38 plays a dual role: as an anticancer drug for therapy and as a fluorophore for diagnosis, thus avoids an extra fluorophore and limits cytotoxicity. Compound 4, activated in the hypoxic environment, showed high therapeutic activity in A549 and HeLa cells and spheroids. In vivo imaging of solid tumors confirmed the tumor-specific localization, deep tissue penetration and activation of compound 4, as well as the production of a strong anticancer effect through the inhibition of tumor growth in a xenograft mouse model validating it as a promising strategy for the treatment of solid tumors.

  6. Procalcitonin as diagnostic marker of infection in solid tumors patients with fever.

    Science.gov (United States)

    Vincenzi, B; Fioroni, I; Pantano, F; Angeletti, S; Dicuonzo, G; Zoccoli, A; Santini, D; Tonini, G

    2016-01-01

    In oncologic patients fever is a non-specific clinical marker of different clinical settings. Procalcitonin (PCT) seems to be the most promising infection marker. We aimed to define the potential role of PCT as an earlier diagnostic marker in patients with fever and solid tumor. This retrospective study enrolled 431 patients. All of them performed hemoculture (HE) and basal PCT assessment (reference laboratory cut-off: ≤0.5 or >0.5 ng/dL) before starting antibiotic therapy. Gram positive (G+), negative (G-) or Fungi infection were detected. A statistically significant difference in PCT levels between patients with positive and negative HE was observed (P PCT values in patients with positive and negative HE, we obtain in the positive HE subpopulation an AUC of 0.7 and a cut-off of 1.52 ng/dL reached high sensitivity (61.6%) and specificity (70.1%). Using this last cut-off, instead of the normal reference value, we achieve a risk reduction to overestimate an infection status of 23.4%. We support the clinic usefulness of serum PCT dosage in febrile advanced solid tumor patients. A PCT cut-off of 1.52 ng/dL could be helpful in the management of the antibiotic therapy preventing delays of oncologic treatments. PMID:27312877

  7. Phenylalanine-coupled solid lipid nanoparticles for brain tumor targeting

    Energy Technology Data Exchange (ETDEWEB)

    Kharya, Parul; Jain, Ashish; Gulbake, Arvind; Shilpi, Satish; Jain, Ankit; Hurkat, Pooja [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India); Majumdar, Subrata [Bose Institute, Division of Molecular Medicine (India); Jain, Sanjay K., E-mail: drskjainin@yahoo.com [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India)

    2013-11-15

    The purpose of this study is to investigate the targeting potential of amino acid (phenylalanine)-coupled solid lipid nanoparticles (SLN) loaded with ionically complexed doxorubicin HCl (Dox). Ionic complexation was used to enhance the loading efficiency and release characteristics of water soluble form of Dox. l-Type amino acid transporters (LAT1) are highly expressed on blood brain barrier as well as on many brain cancer cells, thus targeting LAT1 using phenylalanine improved anticancer activity of prepared nanocarrier. The phenylalanine-coupled SLN were characterized by fourier transform infrared spectroscopy, scanning electron microscope, transmission electron microscopy, particle size, zeta potential, entrapment efficiency and in vitro release. The particle size of the resulting SLN was found to be in the range of 163.3 ± 5.2 to 113.0 ± 2.6 nm, with a slightly negative surface charge. In ex vivo study on C6 glioma cell lines, the cellular cytotoxicity of the SLN was highly increased when coupled with phenylalanine. In addition, stealthing sheath of PEG present on the surface of the SLN enhanced the cellular uptake of the SLN on C6 glioma cell line. Results of biodistribution and fluorescence studies clearly revealed that phenylalanine-coupled SLN could deliver high amount of drug into the brain tumor cells and showed the brain-targeting potential.

  8. Phase I studies of porfiromycin (NSC--56410) in solid tumors.

    Science.gov (United States)

    Grage, T B; Weiss, A J; Wilson, W; Reynolds, V

    1975-01-01

    Porfiromycin was given to a group of patients with a variety of solid tumors. Of 114 patients admitted to the study, 103 yielded evaluable data. The following dosage schedules were used to determine the toxicity of porfiromycin when given in multiple doses by intravenous injection: 0.2 mg/kg x 5 days, 0.3 mg/kg x 5 days, 0.35 mg/kg x 5 days, 0.4 mg/kg x 5 days, 0.24 mg/kg x 10 days and 0.6 mg/kg weekly. Toxic effects noted were mainly leukopenia, thrombocytopenia, and, when injected paravenously, local tissue necrosis. Biological effects were noted at all dosage levels and were more severe at the higher dosages. The data suggest that profiromycin administered intravenously at a dose of 0.35 mg/kg daily for 5 days results in moderate hermatological toxicity and clinical evaluation in a Phase II study at this dosage level is indicated. PMID:1177472

  9. Flavopiridol in Treating Children With Relapsed or Refractory Solid Tumors or Lymphomas

    Science.gov (United States)

    2013-07-01

    Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Retinoblastoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  10. Solid rocket technology advancements for space tug and IUS applications

    Science.gov (United States)

    Ascher, W.; Bailey, R. L.; Behm, J. W.; Gin, W.

    1975-01-01

    In order for the shuttle tug or interim upper stage (IUS) to capture all the missions in the current mission model for the tug and the IUS, an auxiliary or kick stage, using a solid propellant rocket motor, is required. Two solid propellant rocket motor technology concepts are described. One concept, called the 'advanced propulsion module' motor, is an 1800-kg, high-mass-fraction motor, which is single-burn and contains Class 2 propellent. The other concept, called the high energy upper stage restartable solid, is a two-burn (stop-restartable on command) motor which at present contains 1400 kg of Class 7 propellant. The details and status of the motor design and component and motor test results to date are presented, along with the schedule for future work.

  11. Recent advances in inorganic solid electrolytes for lithium batteries

    Directory of Open Access Journals (Sweden)

    Can eCao

    2014-06-01

    Full Text Available The review presents an overview of the recent advances in inorganic solid lithium ion conductors, which are of great interest as solid electrolytes in all-solid-state lithium batteries. It is focused on two major categories: crystalline electrolytes and glass-based electrolytes. Important systems such as thio-LISICON Li10SnP2S12, garnet Li7La3Zr2O12, perovskite Li3xLa(2/3-xTiO3, NASICON Li1.3Al0.3Ti1.7(PO43 and glass-ceramic xLi2S•(1-xP2S5 and their progress are described in great detail. Meanwhile, the review discusses different on-going strategies on enhancing conductivity, optimizing electrolyte/electrode interface and improving cell performance.

  12. Craniofacial resection of advanced oral and maxillofacial malignant tumors

    Institute of Scientific and Technical Information of China (English)

    张志愿; 邱蔚六

    2003-01-01

    Objective To evaluate the clinical outcome of craniofacial resection for advanced malignant tumors in oral and maxillofacial regions.Methods Forty-six patients who underwent craniofacial resection for malignancies involving the anterior and middle cranial fossa over a 20-year period between June 1978 and December 1997 at our department were evaluated. Twenty patients received radiation therapy and an adjuvant therapy after the operation. Eleven patients received chemotherapy of various types as an adjuvant therapy.Results The 3- and 5-year survival rates were 48.8% (20/41) and 35.1% (13/37), respectively, while the 10-year survival rate was 20% (4/20).Conclusions Our results revealed good prospects of using craniofacial resection on patients with advanced malignancies in the oral and maxillofacial regions.

  13. New strategies to enhance photodynamic therapy for solid tumors

    OpenAIRE

    Gulik, van der, T.; Heger, M.; Broekgaarden, M.

    2016-01-01

    Photodynamic therapy for cancer uses laser light to specifically activate anti-cancer drugs at the tumor site. However, this potentially effective and patient-friendly therapy has seen limited clinical application due to the inability of these drugs to accumulate at the tumor site and the subsequent survival of the malignancy. The aim of this research was to find out how tumor cells survive this therapy, to develop drug delivery systems that target the anti-cancer drugs towards the tumor site...

  14. Ascitic and solid Ehrlich tumor inhibition by Chenopodium ambrosioides L. treatment.

    Science.gov (United States)

    Nascimento, Flávia R F; Cruz, Gustavo V B; Pereira, Paulo Vitor S; Maciel, Márcia C G; Silva, Lucilene A; Azevedo, Ana Paula S; Barroqueiro, Elizabeth S B; Guerra, Rosane N M

    2006-04-25

    The leaves of Chenopodium ambrosioides L. [Chenopodiaceae] ('mastruz') have been indicated for the treatment of several diseases, among which the cancer. There are no results focusing the effect of C. ambrosioides treatment on tumor development in vivo. The aim of this study was to investigate the effect of treatment with C. ambrosioides on Ehrlich tumor development. Swiss mice were treated by intraperitoneal route (i.p.) with hydroalcoholic extract from leaves of C. ambrosioides (5 mg/kg) or with PBS (control group) 48 h before or 48 h later the Ehrlich tumor implantation. The tumor cells were implanted on the left footpad (solid tumor) or in the peritoneal cavity (ascitic tumor). To determine the solid tumor growth, footpad was measured each 2 days until the fourteenth day, when the feet were weighed. Ascitic tumor development was evaluated after 8 days of tumor implantation by quantification of the ascitic fluid volume and tumor cell number. The i.p. administration of C. ambrosioides extract before or after the tumor implantation significantly inhibited the solid and ascitic Ehrlich tumor forms. This inhibition was observed in ascitic tumor cell number, in the ascitic volume, in the tumor-bearing foot size and foot weight when compared to control mice. The treatments also increased the survival of tumor-bearing mice. In conclusion, C. ambrosioides has a potent anti-tumoral effect which was evident with a small dose and even when the treatment was given two days after the tumor implantation. This effect is probably related with anti-oxidant properties of C. ambrosioides.

  15. Numerical simulation of blood flow and interstitial fluid pressure in solid tumor microcirculation based on tumor-induced angiogenesis

    Institute of Scientific and Technical Information of China (English)

    Gaiping Zhao; Jie Wu; Shixiong Xu; M. W. Collins; Quan Long; Carola S. K(o)nig; Yuping Jiang; Jian Wang; A. R. Padhani

    2007-01-01

    A coupled intravascular-transvascular-interstitial fluid flow model is developed to study the distributions of blood flow and interstitial fluid pressure in solid tumor microcirculation based on a tumor-induced microvascular network.This is generated from a 2D nine-point discrete mathematical model of tumor angiogenesis and contains two parent vessels.Blood flow through the microvascular network and interstitial fluid flow in tumor tissues are performed by the extended Poiseuille's law and Darcy's law, respectively, transvascular flow is described by Starling's law; effects of the vascular permeability and the interstitial hydraulic conductivity are also considered. The simulation results predict the heterogeneous blood supply, interstitial hypertension and low convectionon the inside of the tumor, which are consistent with physiological observed facts. These results may provide beneficial information for anti-angiogenesis treatment of tumor and further clinical research.

  16. Numerical simulation of blood flow and interstitial fluid pressure in solid tumor microcirculation based on tumor-induced angiogenesis

    Science.gov (United States)

    Zhao, Gaiping; Wu, Jie; Xu, Shixiong; Collins, M. W.; Long, Quan; König, Carola S.; Jiang, Yuping; Wang, Jian; Padhani, A. R.

    2007-10-01

    A coupled intravascular transvascular interstitial fluid flow model is developed to study the distributions of blood flow and interstitial fluid pressure in solid tumor microcirculation based on a tumor-induced microvascular network. This is generated from a 2D nine-point discrete mathematical model of tumor angiogenesis and contains two parent vessels. Blood flow through the microvascular network and interstitial fluid flow in tumor tissues are performed by the extended Poiseuille’s law and Darcy’s law, respectively, transvascular flow is described by Starling’s law; effects of the vascular permeability and the interstitial hydraulic conductivity are also considered. The simulation results predict the heterogeneous blood supply, interstitial hypertension and low convection on the inside of the tumor, which are consistent with physiological observed facts. These results may provide beneficial information for anti-angiogenesis treatment of tumor and further clinical research.

  17. Advances in the research of bevacizumab in treating some solid tumors%贝伐单抗在部分实体肿瘤中临床应用的研究进展

    Institute of Scientific and Technical Information of China (English)

    王玉; 方明治

    2011-01-01

    Recently, more and more researchers have focused their interests on the anti-vascular endothelial growth factor (VEGF) antibody-targeted therapy. Bevacizumab (BV) has become one of the most important agents used worldwide, and it was approved for the market as a new targeted agent in May 2010 in China. This review summarizes the clinical advancements in the targeted therapy with BV in metastatic colorectal cancer (mCRC), non-small cell lung cancer (NSCLC), metastatic breast cancer (mBC) and metastatic renal cell carcinoma (mRCC).%随着临床研究的深入,抗血管内皮生长因子(vascular endothelial growth factor,VEGF)抗体的靶向治疗越来越受到重视,其中贝伐单抗( bevacizumab,BV)成为关注的焦点,并于今年2010年5月在中国成功上市.本文就BV在转移性结直肠癌(metastatic colorectal cancer,mCRC)、非小细胞肺癌(non-small cell lung cancer,NSCLC)、转移性乳腺癌(metastatic breast cancer,mBC)及转移性肾细胞癌(metastatic renal cell carcinoma,mRCC)的靶向治疗中的研究进展作一综述.

  18. Recent Advances in the Molecular Characterization of Circulating Tumor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Lowes, Lori E. [London Regional Cancer Program, London Health Sciences Centre, London, ON N6A 4L6 (Canada); Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1 (Canada); Department of Oncology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 4L6 (Canada); Allan, Alison L., E-mail: alison.allan@lhsc.on.ca [London Regional Cancer Program, London Health Sciences Centre, London, ON N6A 4L6 (Canada); Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1 (Canada); Department of Oncology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 4L6 (Canada); Lawson Health Research Institute, London, ON N6C 2R5 (Canada)

    2014-03-13

    Although circulating tumor cells (CTCs) were first observed over a century ago, lack of sensitive methodology precluded detailed study of these cells until recently. However, technological advances have now facilitated the identification, enumeration, and characterization of CTCs using a variety of methods. The majority of evidence supporting the use of CTCs in clinical decision-making has been related to enumeration using the CellSearch{sup ®} system and correlation with prognosis. Growing evidence also suggests that CTC monitoring can provide an early indication of patient treatment response based on comparison of CTC levels before and after therapy. However, perhaps the greatest potential that CTCs hold for oncology lies at the level of molecular characterization. Clinical treatment decisions may be more effective if they are based on molecular characteristics of metastatic cells rather than on those of the primary tumor alone. Molecular characterization of CTCs (which can be repeatedly isolated in a minimally invasive fashion) provides the opportunity for a “real-time liquid biopsy” that allows assessment of genetic drift, investigation of molecular disease evolution, and identification of actionable genomic characteristics. This review focuses on recent advances in this area, including approaches involving immunophenotyping, fluorescence in situ hybridization (FISH), multiplex RT-PCR, microarray, and genomic sequencing.

  19. Tumor

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008479 Preliminary study of MR elastography in brain tumors. XU Lei(徐磊), et al.Neurosci Imaging Center, Beijing Tiantan Hosp, Capital Med Univ, Beijing 100050.Chin J Radiol 2008;42(6):605-608. Objective To investigate the potential values of magnetic resonance elastography (MRE) for evaluating the brain tumor consistency in vivo. Methods Fourteen patients with known solid brain tumor (5 male, 9 female; age range: 16-63 years)

  20. Radiotherapy and high-dose chemotherapy in advanced Ewing's tumors

    International Nuclear Information System (INIS)

    Background: Ewing's tumors are sensitive to radio- and chemotherapy. Patients with multifocal disease suffer a poor prognosis. Patients presenting primary bone marrow involvement or bone metastases at diagnosis herald a 3-year disease-free survival below 15%. The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) has established the following indications for high-dose therapy in advanced Ewing's tumors: Patients with primary multifocal bone disease, patients with early (<2 years after diagnosis) or multifocal relapse. Patients and Method: As of 1987, 83 patients have been treated in the EICESS group, 39 of them at the transplant center in Duesseldorf, who have been analyzed here. All individuals received 4 courses of induction chemotherapy with EVAJA and stem cell collection after course 3 and 4. Consolidation radiotherapy of the involved bone compartments was administered in a hyperfractionated regimen 2 times 1.6 Gy per day, up to 22.4 Gy simultaneously to course 5 and 22.4 Gy to course 6 of chemotherapy. The myeloablative chemotherapy consisted of melphalan and etoposide (ME) in combination with 12 Gy TBI (Hyper-ME) oder Double-ME with whole lung irradiation up to 18 Gy (without TBI). Results: The survival probability at 40 months was 31% (44% DOD; 15% DOC). Pelvic infiltration did not reach prognostic relevance in this cohort. Radiotherapy encompassed 75% of the bone marrow at maximum (average 20%). Engraftment was not affected by radiotherapy. Conclusion: High-dose chemotherapy can improve outcome in poor prognostic advanced Ewing's tumors. The disease itself remains the main problem. The expected engraftment problems after intensive radiotherapy in large volumes of bone marrow can be overcome by stem cell reinfusion. (orig.)

  1. Role of constitutive behavior and tumor-host mechanical interactions in the state of stress and growth of solid tumors.

    Directory of Open Access Journals (Sweden)

    Chrysovalantis Voutouri

    Full Text Available Mechanical forces play a crucial role in tumor patho-physiology. Compression of cancer cells inhibits their proliferation rate, induces apoptosis and enhances their invasive and metastatic potential. Additionally, compression of intratumor blood vessels reduces the supply of oxygen, nutrients and drugs, affecting tumor progression and treatment. Despite the great importance of the mechanical microenvironment to the pathology of cancer, there are limited studies for the constitutive modeling and the mechanical properties of tumors and on how these parameters affect tumor growth. Also, the contribution of the host tissue to the growth and state of stress of the tumor remains unclear. To this end, we performed unconfined compression experiments in two tumor types and found that the experimental stress-strain response is better fitted to an exponential constitutive equation compared to the widely used neo-Hookean and Blatz-Ko models. Subsequently, we incorporated the constitutive equations along with the corresponding values of the mechanical properties - calculated by the fit - to a biomechanical model of tumor growth. Interestingly, we found that the evolution of stress and the growth rate of the tumor are independent from the selection of the constitutive equation, but depend strongly on the mechanical interactions with the surrounding host tissue. Particularly, model predictions - in agreement with experimental studies - suggest that the stiffness of solid tumors should exceed a critical value compared with that of the surrounding tissue in order to be able to displace the tissue and grow in size. With the use of the model, we estimated this critical value to be on the order of 1.5. Our results suggest that the direct effect of solid stress on tumor growth involves not only the inhibitory effect of stress on cancer cell proliferation and the induction of apoptosis, but also the resistance of the surrounding tissue to tumor expansion.

  2. Study of LOXO-101 in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE)

    Science.gov (United States)

    2016-09-16

    Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms; Sarcoma; Colorectal Neoplasms; Salivary Gland Neoplasms; Biliary Tract Neoplasms; Brain Neoplasm, Primary; Carcinoma, Ductal, Breast; Melanoma; Solid Tumors; Glioblastoma; Bile Duct Neoplasms; Astrocytoma; Head and Neck Squamous Cell Carcinoma; Pontine Glioma

  3. Phase I and pharmacologic study of oral ZD9331, a novel nonpolyglutamated thymidylate synthase inhibitor, in adult patients with solid tumors.

    NARCIS (Netherlands)

    Jonge, M.J.A. de; Punt, C.J.A.; Sparreboom, A.; Planting, A.S.T.; Peters, M.E.W.J.; Schraaf, J. van de; Jackman, A.; Smith, R.J.H.; Mulder, P.H.M. de; Verweij, J.

    2002-01-01

    PURPOSE: To assess the toxicity profile and dose-limiting toxicities (DLTs), to determine the maximum-tolerated dose, and to study the pharmacokinetics of ZD9331 when administered orally to patients with advanced solid tumors. PATIENTS AND METHODS: Patients were treated with oral ZD9331 given once d

  4. Liver Metastasis Four Years after Whipple's Resection for Solid-Pseudopapillary Tumor of the Pancreas

    Directory of Open Access Journals (Sweden)

    Srikrishna Nagri

    2007-03-01

    Full Text Available Context Solid-pseudopapillary tumor of the pancreas is a rare tumor which usually affects young females in their second and third decade of life. Metastasis is very rare after a resection of curative intent. Case report We report a case of a 65-yearold white female who presented with metastasis to the liver four years after Whipple’s resection for a solid-pseudopapillary tumor of the pancreas. Conclusions Solid-pseudopapillary tumors of the pancreas can present with metastasis a long time after resection of the primary tumor. Long term close follow up of these patients should be done. The survival rate even after liver metastasis is good.

  5. PD-L1 and Survival in Solid Tumors: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Pin Wu

    Full Text Available Numerous agents targeting PD-L1/PD-1 check-point are in clinical development. However, the correlation between PD-L1 expression and prognosis of solid tumor is still in controversial. Here, we elicit a systematic review and meta-analysis to investigate the potential value of PD-L1 in the prognostic prediction in human solid tumors.Electronic databases were searched for studies evaluating the expression of PD-L1 and overall survival (OS of patients with solid tumors. Odds ratios (ORs from individual studies were calculated and pooled by using a random-effect model, and heterogeneity and publication bias analyses were also performed.A total of 3107 patients with solid tumor from 28 published studies were included in the meta-analysis. The median percentage of solid tumors with PD-L1 overexpression was 52.5%. PD-L1 overexpression was associated with worse OS at both 3 years (OR = 2.43, 95% confidence interval (CI = 1.60 to 3.70, P < 0.0001 and 5 years (OR = 2.23, 95% CI = 1.40 to 3.55, P = 0.0008 of solid tumors. Among the tumor types, PD-L1 was associated with worse 3 year-OS of esophageal cancer, gastric cancer, hepatocellular carcinoma, and urothelial cancer, and 5 year-OS of esophageal cancer, gastric cancer and colorectal cancer.These results suggest that expression of PD-L1 is associated with worse survival in solid tumors. However, the correlations between PD-L1 and prognosis are variant among different tumor types. More studies are needed to investigate the clinical value of PD-L1 expression in prognostic prediction and treatment option.

  6. Clinical observation of intrathecal chemotherapy combined with concurrent radiotherapy for leptomeningeal metastases from malignant solid tumors

    Institute of Scientific and Technical Information of China (English)

    潘振宇

    2014-01-01

    Objective To investigate the efficacy and safety of intrathecal chemotherapy combined with concurrent radiotherapy in patients with leptomeningeal metastases from solid tumors.Methods The clinical and follow-up data of 29 patients with leptomeningeal metastases frommalignant solid tumor who had intrathecal chemotherapy combined with concurrent radiotherapy were retrospectively analyzed.The treatment regimen was that 12.5-15.0 mg of methotrexate intrathecal injection once a week for 8

  7. Ispinesib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Lymphoma

    Science.gov (United States)

    2013-01-15

    Childhood Burkitt Lymphoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Unspecified Childhood Solid Tumor, Protocol Specific

  8. Chimeric Antigen Receptor-Modified T Cells for Solid Tumors: Challenges and Prospects

    Directory of Open Access Journals (Sweden)

    Yelei Guo

    2016-01-01

    Full Text Available Recent studies have highlighted the successes of chimeric antigen receptor-modified T- (CART- cell-based therapy for B-cell malignancies, and early phase clinical trials have been launched in recent years. The few published clinical studies of CART cells in solid tumors have addressed safety and feasibility, but the clinical outcome data are limited. Although antitumor effects were confirmed in vitro and in animal models, CART-cell-based therapy still faces several challenges when directed towards solid tumors, and it has been difficult to achieve the desired outcomes in clinical practice. Many studies have struggled to improve the clinical responses to and benefits of CART-cell treatment of solid tumors. In this review, the status quo of CART cells and their clinical applications for solid tumors will be summarized first. Importantly, we will suggest improvements that could increase the therapeutic effectiveness of CART cells for solid tumors and their future clinical applications. These interventions will make treatment with CART cells an effective and routine therapy for solid tumors.

  9. TCR-engineered T cells meet new challenges to treat solid tumors: choice of antigen, T cell fitness and sensitisation of tumor milieu (review

    Directory of Open Access Journals (Sweden)

    Andre eKunert

    2013-11-01

    Full Text Available Adoptive transfer of T cells gene-engineered with antigen-specific T cell receptors (TCRs has proven its feasibility and therapeutic potential in the treatment of malignant tumors. To ensure further clinical development of TCR gene therapy, it is necessary to target immunogenic epitopes that are related to oncogenesis and selectively expressed by tumor tissue, and implement strategies that result in optimal T cell fitness. In addition, in particular for the treatment of solid tumors, it is equally necessary to include strategies that counteract the immune-suppressive nature of the tumor micro-environment. Here, we will provide an overview of the current status of TCR gene therapy, and redefine the following three challenges of improvement: ‘choice of target antigen’; ‘fitness of T cells’; and ‘sensitisation of tumor milieu’. We will categorize and discuss potential strategies to address each of these challenges, and argue that advancement of clinical TCR gene therapy critically depends on developments towards each of the three challenges.

  10. Increase of the effectiveness in irradiation of solid tumors using free nitroxyl-radical

    International Nuclear Information System (INIS)

    SHK-mice with experimentally induced solid NKLy-tumors were irradiated 15 minutes after injection of 180 mg/kg triacetoneamine-N-oxyl (TAN) when the maximum level of TAN in the tumor cells was reached. Growth dynamics of the tumor and the dose which led to 50% tumor resorption (TLD50) were used as criteria for the effectiveness of the irradiation. It could be shown, that TAN application prior to a single irradiation decreased the TLD50 to 71.4%. Fractionated irradiation after TAN application led also to an increase of irradiation efficiency, but the degree of radiosensitivity of the tumors decreased with increasing numbers of fractions. Free nitroxyl radical-induced increase of efficiency in irradiating solid tumors. (author)

  11. Mitochondrial D310 mutation as clonal marker for solid tumors

    NARCIS (Netherlands)

    W.R.R. Geurts-Giele (Willemina); G.H.G.K. Gathier (Gerard H. G. K.); P.N. Atmodimedjo; H.J. Dubbink (Erik Jan); W.N.M. Dinjens (Winand)

    2015-01-01

    textabstractPatients with multiple tumors, either synchronous or metachronous, can have metastatic disease or suffer from multiple independent primary tumors. While proper diagnosis of these patients is important for prognosis and treatment, this can be challenging using only clinical and histologic

  12. Rare Solid Tumors of the Pancreas as Differential Diagnosis of Pancreatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Sabine Kersting

    2012-05-01

    Full Text Available Context Rare solid tumors of the pancreas can be misinterpreted as primary pancreatic cancer. Objective The aim of this study was to report our experience in the treatment of patients with rare tumor lesions of the pancreas and to discuss clinical and pathological characteristics in the context of the role of surgery. Design Data from patients of our prospective data-base with rare benign and malignant tumors of the pancreas, treated in our division from January 2004 to August 2010, were analyzed retrospectively. Results One-thousand and ninety-eight patients with solid tumors of the pancreas underwent pancreatic surgery. In 19 patients (10 women, 9 men with a mean age of 57 years (range: 20-74 years rare pancreatic tumors (metastasis, solid pseudopapillary tumor, teratoma, hemangioma, accessory spleen, lymphoepithelial cyst, hamartoma, sarcoidosis, yolk sac tumor were the reason for surgical intervention. Conclusion If rare benign and malignant pancreatic tumors, intrapancreatic metastasis, as well as pancreatic malformations or other abnormalities, present themselves as solid masses of the pancreas, they constitute an important differential diagnosis to primary pancreatic neoplasia, e.g. pancreatic ductal adenocarcinoma. Clinical imaging techniques cannot always rule out malignancy, thus operative exploration often remains the treatment of choice to provide the correct diagnosis and initiate adequate surgical therapy.

  13. Neoadjuvant Chemotherapy in Locally Advanced and Borderline Resectable Nonsquamous Sinonasal Tumors (Esthesioneuroblastoma and Sinonasal Tumor with Neuroendocrine Differentiation)

    OpenAIRE

    Patil, Vijay M.; Amit Joshi; Vanita Noronha; Vibhor Sharma; Saurabh Zanwar; Sachin Dhumal; Shubhada Kane; Prathamesh Pai; Anil D’Cruz; Pankaj Chaturvedi; Atanu Bhattacharjee; Kumar Prabhash

    2016-01-01

    Introduction. Sinonasal tumors are chemotherapy responsive which frequently present in advanced stages making NACT a promising option for improving resection and local control in borderline resectable and locally advanced tumours. Here we reviewed the results of 25 such cases treated with NACT. Materials and Methods. Sinonasal tumor patients treated with NACT were selected for this analysis. These patients received NACT with platinum and etoposide for 2 cycles. Patients who responded and were...

  14. Vorinostat and Bortezomib in Treating Young Patients With Refractory or Recurrent Solid Tumors, Including Central Nervous System Tumors and Lymphoma

    Science.gov (United States)

    2013-07-01

    Childhood Burkitt Lymphoma; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Medulloepithelioma; Childhood Meningioma; Childhood Mixed Glioma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Oligodendroglioma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  15. New Strategies for the Treatment of Solid Tumors with CAR-T Cells

    Science.gov (United States)

    Zhang, Hao; Ye, Zhen-long; Yuan, Zhen-gang; Luo, Zheng-qiang; Jin, Hua-jun; qian, Qi-jun

    2016-01-01

    Recent years, we have witnessed significant progresses in both basic and clinical studies regarding novel therapeutic strategies with genetically engineered T cells. Modification with chimeric antigen receptors (CARs) endows T cells with tumor specific cytotoxicity and thus induce anti-tumor immunity against malignancies. However, targeting solid tumors is more challenging than targeting B-cell malignancies with CAR-T cells because of the histopathological structure features, specific antigens shortage and strong immunosuppressive environment of solid tumors. Meanwhile, the on-target/off-tumor toxicity caused by relative expression of target on normal tissues is another issue that should be reckoned. Optimization of the design of CAR vectors, exploration of new targets, addition of safe switches and combination with other treatments bring new vitality to the CAR-T cell based immunotherapy against solid tumors. In this review, we focus on the major obstacles limiting the application of CAR-T cell therapy toward solid tumors and summarize the measures to refine this new cancer therapeutic modality. PMID:27194949

  16. A Phase I Dose Finding Study of 5-Azacytidine in Combination with Sodium Phenylbutyrate in Patients with Refractory Solid Tumors

    Science.gov (United States)

    Lin, Jianqing; Gilbert, Jill; Rudek, Michelle A.; Zwiebel, James A.; Gore, Steve; Jiemjit, Anchalee; Zhao, Ming; Baker, Sharyn D.; Ambinder, Richard F.; Herman, James G.; Donehower, Ross C.; Carducci, Michael A.

    2010-01-01

    Purpose This was a phase I trial to determine the minimal effective dose and optimal dose schedule of 5-AC in combination with sodium phenylbutyrate in patients with refractory solid tumors. The pharmacokinetics, pharmacodynamics, and antineoplastic effects were also studied. Experimental design Three dosing regimens were studied in 27 patients with advanced solid tumors and toxicity was recorded. The pharmacokinetics of the combination of drugs was evaluated. Repeat tumor biopsies and peripheral blood mononuclear cells (PBMC) were analyzed to evaluate epigenetic changes in response to therapy. Epstein Barr Virus (EBV) titers were evaluated as a surrogate measure for gene re-expression of epigenetic modulation in PBMC. Results The three dose regimens of 5-AC and PB were generally well tolerated and safe. A total of 48 cycles was administrated to 27 patients. The most common toxicities were bone marrow suppression related neutropenia and anemia, which were minor. The clinical response rate was disappointing for the combination of agents. One patient demonstrated stable disease for 5 months while 26 patients demonstrated progressive disease as best tumor response. The administration of PB and 5-AC did not appear to alter the pharmacokinetics of either drug. Although there were individual cases of targeted DNMT activity and histone H3/4 acetylation changes from paired biopsy or PBMC, no conclusive statement can be made based on these limited correlative studies. Conclusion The combination of 5-AC and PB across three dose schedules was generally well tolerated and safe, yet lacked any real evidence for clinical benefit. PMID:19789320

  17. Integrin α5β1, the Fibronectin Receptor, as a Pertinent Therapeutic Target in Solid Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Schaffner, Florence; Ray, Anne Marie; Dontenwill, Monique, E-mail: monique.dontenwill@unistra.fr [UMR 7213 CNRS, Laboratoire de Biophotonique et Pharmacologie, Tumoral signaling and therapeutic targets, Université de Strasbourg, Faculté de Pharmacie, 67401 Illkirch (France)

    2013-01-15

    Integrins are transmembrane heterodimeric proteins sensing the cell microenvironment and modulating numerous signalling pathways. Changes in integrin expression between normal and tumoral cells support involvement of specific integrins in tumor progression and aggressiveness. This review highlights the current knowledge about α5β1 integrin, also called the fibronectin receptor, in solid tumors. We summarize data showing that α5β1 integrin is a pertinent therapeutic target expressed by tumoral neovessels and tumoral cells. Although mainly evaluated in preclinical models, α5β1 integrin merits interest in particular in colon, breast, ovarian, lung and brain tumors where its overexpression is associated with a poor prognosis for patients. Specific α5β1 integrin antagonists will be listed that may represent new potential therapeutic agents to fight defined subpopulations of particularly aggressive tumors.

  18. Cytogenetics of solid tumors Revisión de tema Citogenética de tumores sólidos

    Directory of Open Access Journals (Sweden)

    José Luis Ramírez Castro

    2002-02-01

    Full Text Available Cytogenetic analysis of tumors has provided valuable information on the biology of cancer. It has been established that more than half of solid tumors show chromosomal anomalies; therefore, cytogenetic analysis is of great usefulness for diagnostic and prognostic purposes. Identification of recurrent chromosomal anomalies in numerous tumors has been considered as an indicador of clinical importance. Cytogenetic studies in tissue tumors have revealed near 100,000 clonal chromosome abnormalities belonging to more that 30,000 human neoplasms. However, due to technical difficulties in cell cultures, only one third of solid tumors have been cytogenetically characterized. Conventional cytogenetics has been very useful for molecular characterization of new oncogenes and tumor-suppressor genes involved in human tumorigenesis. In this review, some important issues related with tumors of chromosomal etiology, the diverse types of chromosomal anomalies with their frequencies, modern diagnostic techniques as well as their impact on the diagnosis and prognosis of cancer are presented. EL análisis citogenético de tumores ha proporcionado valiosa información sobre la biología del cáncer. Se ha establecido que más de la mitad de los tumores sólidos presentan alteraciones cromosómicas; por lo tanto, el análisis citogenético es de gran utilidad para el diagnóstico y el pronóstico. La identificación de cambios cromosómicos específicos recurrentes en numerosos tumores se considera un indicador de importancia clínica. Los estudios en este campo han revelado cerca de 100.000 alteraciones cromosómicas en más de 30.000 neoplasias humanas. Sin embargo, los tumores sólidos son los menos caracterizados citogenéticamente, sólo una tercera parte del total de ellos, debido a problemas técnicos en los cultivos celulares. La citogenética convencional ha sido muy útil para la posterior caracterización molecular de nuevos oncogenes y genes supresores de

  19. [Research advances of anti-tumor immune response induced by pulse electric field ablation].

    Science.gov (United States)

    Cui, Guang-ying; Diao, Hong-yan

    2015-11-01

    As a novel tumor therapy, pulse electric field has shown a clinical perspective. This paper reviews the characteristics of tumor ablation by microsecond pulse and nanosecond pulse electric field, and the research advances of anti-tumor immune response induced by pulse electric field ablation. Recent researches indicate that the pulse electric field not only leads to a complete ablation of local tumor, but also stimulates a protective immune response, thereby inhibiting tumor recurrence and metastasis. These unique advantages will show an extensive clinical application in the future. However, the mechanism of anti-tumor immune response and the development of related tumor vaccine need further studies.

  20. FR901228 in Treating Children With Refractory or Recurrent Solid Tumors or Leukemia

    Science.gov (United States)

    2013-01-15

    Blastic Phase Chronic Myelogenous Leukemia; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Chronic Myelogenous Leukemia; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  1. Fusion genes in solid tumors:an emerging target for cancer diagnosis and treatment

    Institute of Scientific and Technical Information of China (English)

    Brittany C. Parker; Wei Zhang

    2013-01-01

    Studies over the past decades have uncovered fusion genes, a class of oncogenes that provide immense diagnostic and therapeutic advantages because of their tumor-specific expression. Originally associated with hemotologic cancers, fusion genes have recently been discovered in a wide array of solid tumors, including sarcomas, carcinomas, and tumors of the central nervous system. Fusion genes are attractive as both therapeutic targets and diagnostic tools due to their inherent expression in tumor tissue alone. Therefore, the discovery and elucidation of fusion genes in various cancer types may provide more effective therapies in the future for cancer patients.

  2. [Research advance on clinical blood transfusion and tumor therapy].

    Science.gov (United States)

    Jiang, Xue-Bing; Zhang, Li-Ping; Wang, Yan-Ju; Ma, Cong

    2010-08-01

    Clinical blood transfusion is one of the most important supportive therapy for patients with tumor. The blood transfusion has dual effects for patients with tumor. First, blood transfusion can rectify anemia and improve oxygen saturation, accelerate oxidation and necrosis for tumor cells; the second, blood transfusion can induce immunosuppression, tumor recurrence and postoperative infection for tumor patients. Filtering white blood cells (WBC) before blood transfusion can decrease the incidence of the adverse reactions. The rational perioperative autotransfusion for patients with tumors is focus to which the world medical sciences pay close attention. In this article, the support effect of blood transfusion for treatment of tumor patients, blood transfusion and immunosuppression, blood transfusion and postoperative infection and relapse of tumor patients, depleted leukocyte blood transfusion and autologous transfusion of tumor patients are reviewed.

  3. Bacteria-mediated in vivo delivery of quantum dots into solid tumor

    International Nuclear Information System (INIS)

    Highlights: ► New approach using the probiotic Bifidobacterium bifidum as a vehicle to deliver QDs into the deep tissue of solid tumors in vivo was achieved. ► Bifidobacterium bifidum delivery system has intrinsic biocompatibility. ► The targeting efficacy was improved by folic acids. -- Abstract: Semiconductor nanocrystals, so-called quantum dots (QDs), promise potential application in bioimaging and diagnosis in vitro and in vivo owing to their high-quality photoluminescence and excellent photostability as well as size-tunable spectra. Here, we describe a biocompatible, comparatively safe bacteria-based system that can deliver QDs specifically into solid tumor of living animals. In our strategy, anaerobic bacterium Bifidobacterium bifidum (B. bifidum) that colonizes selectively in hypoxic regions of animal body was successfully used as a vehicle to load with QDs and transported into the deep tissue of solid tumors. The internalization of lipid-encapsuled QDs into B. bifidum was conveniently carried by electroporation. To improve the efficacy and specificity of tumor targeting, the QDs-carrying bacterium surface was further conjugated with folic acids (FAs) that can bind to the folic acid receptor overexpressed tumor cells. This new approach opens a pathway for delivering different types of functional cargos such as nanoparticles and drugs into solid tumor of live animals for imaging, diagnosis and therapy.

  4. Bacteria-mediated in vivo delivery of quantum dots into solid tumor

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ying [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Zhou, Mei [Dept. of Radiation Medicine, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Luo, Dan; Wang, Lijun; Hong, Yuankai [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Yang, Yepeng, E-mail: yangyepeng@bjmu.edu.cn [Dept. of Radiation Medicine, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Sha, Yinlin, E-mail: shyl@hsc.pku.edu.cn [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Biomed-X Center, Peking University, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer New approach using the probiotic Bifidobacterium bifidum as a vehicle to deliver QDs into the deep tissue of solid tumors in vivo was achieved. Black-Right-Pointing-Pointer Bifidobacterium bifidum delivery system has intrinsic biocompatibility. Black-Right-Pointing-Pointer The targeting efficacy was improved by folic acids. -- Abstract: Semiconductor nanocrystals, so-called quantum dots (QDs), promise potential application in bioimaging and diagnosis in vitro and in vivo owing to their high-quality photoluminescence and excellent photostability as well as size-tunable spectra. Here, we describe a biocompatible, comparatively safe bacteria-based system that can deliver QDs specifically into solid tumor of living animals. In our strategy, anaerobic bacterium Bifidobacterium bifidum (B. bifidum) that colonizes selectively in hypoxic regions of animal body was successfully used as a vehicle to load with QDs and transported into the deep tissue of solid tumors. The internalization of lipid-encapsuled QDs into B. bifidum was conveniently carried by electroporation. To improve the efficacy and specificity of tumor targeting, the QDs-carrying bacterium surface was further conjugated with folic acids (FAs) that can bind to the folic acid receptor overexpressed tumor cells. This new approach opens a pathway for delivering different types of functional cargos such as nanoparticles and drugs into solid tumor of live animals for imaging, diagnosis and therapy.

  5. Nanoparticles carry chemotherapy drug deeper into solid tumors

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ CAS researchers have developed a new drug delivery method using nano-sized molecules to carry the chemotherapy drug doxorubicin to tumors, improving the effectiveness of the drug in mice and increasing their survival time. Their work has been reported online June 26 in the Journal of the National Cancer Institute.

  6. Criteria to define HLA haplotype loss in human solid tumors

    NARCIS (Netherlands)

    Ramal, LM; van der Zwan, AW; Collado, A; Lopez-Nevot, MA; Tilanus, M; Garrido, F

    2000-01-01

    Short tandem repeat (STR) markers are currently used to define loss of heterozygosity (LOH) of genes and chromosomes in tumors. Chromosome 6 and chromosome 15 STR markers are applied to define loss of HLA and related genes (e.g. TAP and beta(2)m) The number of STR identified in the HLA region is sti

  7. An Open-Label Study of a Novel JAK-inhibitor, INCB047986, Given in Patients With Advanced Malignancies

    Science.gov (United States)

    2015-02-03

    Advanced Solid Tumors; Advanced Hodgkin's Lymphoma; Advanced Aggressive Non-Hodgkin's Lymphoma; Advanced Indolent Non-Hodgkin's Lymphoma; Advanced Pancreatic Adenocarcinoma; Advanced Triple-Negative Breast Cancer; Advanced Urothelial Carcinoma

  8. Some epidemiological and clinical characteristics of solid malignant tumors in children from Las Tunas

    Directory of Open Access Journals (Sweden)

    Silvio Laffita Estévez

    2015-11-01

    Full Text Available Background: cancer has kept up as the second cause of death in Las Tunas pediatric population.Objective: to characterize clinical and epidemiological variables of the cases diagnosed with solid malignant tumors in children seen and treated in the onco-pediatric consultation of “Mártires de Las Tunas” Pediatric Hospital from 2010 to 2014.Methods: a descriptive and retrospective study was carried out in 62 patients with solid malignant tumors in the pediatric population of Las Tunas province, from January, 2010 to December, 2014. The variables considered were: presumptive diagnosis, age, family history of tumors, clinical signs of alarm related to the tumor at the moment of diagnosis and investigations to confirm the diagnosis.  Results: non-Hodgkin lymphoma was the most frequently diagnosed tumor, with a 19, 35% of the patients. The most affected age group was between 11 and 14 years old, with a 33, 87%. The 16, 13% of the patients had family history of solid malignant tumors. The most frequent form of presentation was the abdominal tumor, with 29, 03 %. Abdominal ultrasound and computerized axial tomography were the most used complementary diagnostic means, both in the 17, 74% of the patients. Biopsy was used to confirm the 96, 77% of the cases.Conclusions: the clinical and epidemiological variables were characterized in pediatric patients diagnosed with solid malignant tumors in Las Tunas. Children between 11 and 14 years old and family history of malignant tumors were the most significant findings.

  9. Favorable alteration of tumor microenvironment by immunomodulatory cytokines for efficient T-cell therapy in solid tumors.

    Science.gov (United States)

    Tähtinen, Siri; Kaikkonen, Saija; Merisalo-Soikkeli, Maiju; Grönberg-Vähä-Koskela, Susanna; Kanerva, Anna; Parviainen, Suvi; Vähä-Koskela, Markus; Hemminki, Akseli

    2015-01-01

    Unfavorable ratios between the number and activation status of effector and suppressor immune cells infiltrating the tumor contribute to resistance of solid tumors to T-cell based therapies. Here, we studied the capacity of FDA and EMA approved recombinant cytokines to manipulate this balance in favor of efficient anti-tumor responses in B16.OVA melanoma bearing C57BL/6 mice. Intratumoral administration of IFN-α2, IFN-γ, TNF-α, and IL-2 significantly enhanced the anti-tumor effect of ovalbumin-specific CD8+ T-cell (OT-I) therapy, whereas GM-CSF increased tumor growth in association with an increase in immunosuppressive cell populations. None of the cytokines augmented tumor trafficking of OT-I cells significantly, but injections of IFN-α2, IFN-γ and IL-2 increased intratumoral cytokine secretion and recruitment of endogenous immune cells capable of stimulating T-cells, such as natural killer and maturated CD11c+ antigen-presenting cells. Moreover, IFN-α2 and IL-2 increased the levels of activated tumor-infiltrating CD8+ T-cells concomitant with reduction in the CD8+ T-cell expression of anergy markers CTLA-4 and PD-1. In conclusion, intratumoral administration of IFN-α2, IFN-γ and IL-2 can lead to immune sensitization of the established tumor, whereas GM-CSF may contribute to tumor-associated immunosuppression. The results described here provide rationale for including local administration of immunostimulatory cytokines into T-cell therapy regimens. One appealing embodiment of this would be vectored delivery which could be advantageous over direct injection of recombinant molecules with regard to efficacy, cost, persistence and convenience.

  10. Favorable alteration of tumor microenvironment by immunomodulatory cytokines for efficient T-cell therapy in solid tumors.

    Directory of Open Access Journals (Sweden)

    Siri Tähtinen

    Full Text Available Unfavorable ratios between the number and activation status of effector and suppressor immune cells infiltrating the tumor contribute to resistance of solid tumors to T-cell based therapies. Here, we studied the capacity of FDA and EMA approved recombinant cytokines to manipulate this balance in favor of efficient anti-tumor responses in B16.OVA melanoma bearing C57BL/6 mice. Intratumoral administration of IFN-α2, IFN-γ, TNF-α, and IL-2 significantly enhanced the anti-tumor effect of ovalbumin-specific CD8+ T-cell (OT-I therapy, whereas GM-CSF increased tumor growth in association with an increase in immunosuppressive cell populations. None of the cytokines augmented tumor trafficking of OT-I cells significantly, but injections of IFN-α2, IFN-γ and IL-2 increased intratumoral cytokine secretion and recruitment of endogenous immune cells capable of stimulating T-cells, such as natural killer and maturated CD11c+ antigen-presenting cells. Moreover, IFN-α2 and IL-2 increased the levels of activated tumor-infiltrating CD8+ T-cells concomitant with reduction in the CD8+ T-cell expression of anergy markers CTLA-4 and PD-1. In conclusion, intratumoral administration of IFN-α2, IFN-γ and IL-2 can lead to immune sensitization of the established tumor, whereas GM-CSF may contribute to tumor-associated immunosuppression. The results described here provide rationale for including local administration of immunostimulatory cytokines into T-cell therapy regimens. One appealing embodiment of this would be vectored delivery which could be advantageous over direct injection of recombinant molecules with regard to efficacy, cost, persistence and convenience.

  11. Monocyte chemotactic protein-1 expression as a prognosic biomarker in patients with solid tumor: a meta analysis

    OpenAIRE

    Wang, Hong; Zhang, Qiongwen; Kong, Hongyu; Zeng, Yunhui; Hao, Meiqin; Yu, Ting; Peng, Jing; Xu, Zhao; Chen, Jingquan; Shi, Huashan

    2014-01-01

    Purpose: A great deal of studies have been performed on the prognostic value of monocyte chemotactic protein-1 (MCP-1) in solid tumors in recent years. However, no consistent outcomes are reported. Therefore, the prognostic value of MCP-1 still remains controversial in patients with solid tumors. Here we aimed to evaluate the prognostic value of MCP-1 expression for patients with solid tumors. Methods: Comprehensive literature was selected from PUBMED and EMBASE and clinical studies which rep...

  12. Chromosomal aberrations related to metastasis of human solid tumors

    Institute of Scientific and Technical Information of China (English)

    Lun-Xiu Qin

    2002-01-01

    The central role of sequential accumulation of genetic alterations during the development of cancer has been firmly established since the pioneering cytogenetic studies successfully defined recurrent chromosome changes in spedfic types of tumor. In the course of carcinogenesis, cells experience several genetic alterations that are associated with the transition from a preneoplastic lesion to an invasive tumor and finally to the metastatic state. Tumor progression is characterized by stepwise accumulation of genetic alterations.So does the dominant metastatic clone. Modern molecular genetic analyses have clarified that genomic changes accumulate during the development and progression of cancers. In comparison with the corresponding primary tumor,additional events of chromosomal aberrations (including gains or allelic losses) are frequently found in metastases, and the incidence of combined chromosomal alterations in the primary tumor, plus the occurrence of additional aberrations inthe distant metastases, correlated significantly with decreased postmetastatic survival. The deletions at 3p, 4p, 6q, 8p, 10q,11p, 11q, 12p, 13q, 16q, 17p, 18q, 21q, and 22q, as well as the over-representations at 1q, 8q, 9q, 14q and 15q, have been found to associate preferentially with the metastatic phenotype of human cancers. Among of them, the deletions on chromosomes 8p, 17p, 11p and 13p seem to be more significant, and more detail fine regions of them, including 8p11, 8p21-12, 8p22, 8p23, 17p13.3, 11p15.5, and 13q12-13 have been suggested harboring metastasis-suppressor genes.During the past decade, several human chromosomes have been functionally tested through the use of microcell-mediated chromosome transfer (MMCT), and metastasis-suppressor activities have been reported on chromosomes 1, 6, 7, 8, 10,11, 12, 16, and 17. However, it is not actually known at what stage of the metastatic cascade these alterations have occurred.There is still controversial with the association

  13. A review of recent advances in solid film lubrication

    Science.gov (United States)

    Spalvins, T.

    1987-01-01

    Thin, adherent sputtered MoS2 and ion plated metallic (Au, Ag, Pb) lubricating films are primarily used in precision contacting triboelement surfaces where wear debris formation is critical and high reliability requirements have to be satisfied. Detailed structural and compositional characterization of solid film lubricants is of prime importance. It is this information from the nano-micro-macro level which is needed to interpret and improve the frictional behavior and assure long endurance lives. The purpose of this paper is to summarize in a concise review the solid lubricant film structure and morphology and their effects on the tribological properties of the lubricant systems. The tribological performance of thin lubricating films has significantly advanced through progressive understanding of the film parameters such as adhesion, cohesion, interface formation, nucleation and microstructural growth, critical film thickness and substrate finish, and temperature. Sputtered MoS2 and ion plated Au, Ag, and Pb films are separately discussed and evaluated in terms of the above film parameters to establish the most desirable film structures and thicknesses in order to achieve effective lubrication.

  14. Clinical guidance on the perioperative use of targeted agents in solid tumor oncology.

    Science.gov (United States)

    Mellor, James D; Cassumbhoy, Michelle; Jefford, Michael

    2011-06-01

    The use of targeted anti-cancer agents is increasing. It is common to utilize a multi-modal treatment approach towards solid tumors, often including surgical resection, and it has become apparent that some targeted agents can impair wound healing or cause an increased risk of perioperative complications. This article reviews targeted agents used in solid tumor oncology with an emphasis on clinically relevant details. Overall, the evidence of targeted agents causing surgical complications is limited. The greatest amount of evidence exists for bevacizumab causing perioperative complications, possibly due to its extended half-life. There are limited data for cetuximab, sorafenib and sunitinib and very little for other solid tumor targeted agents. Our findings suggest that there should be heightened pharmacovigilence around targeted agents with respect to perioperative complications and increased post-surgical support for patients to aid early detection of postoperative complications until definitive data become available. PMID:21585689

  15. Targeting the epidermal growth factor receptor in solid tumor malignancies

    DEFF Research Database (Denmark)

    Nedergaard, Mette K; Hedegaard, Chris J; Poulsen, Hans S

    2012-01-01

    The epidermal growth factor receptor (EGFR) is over-expressed, as well as mutated, in many types of cancers. In particular, the EGFR variant type III mutant (EGFRvIII) has attracted much attention as it is frequently and exclusively found on many tumor cells, and hence both EGFR and EGFRvIII have...... to the extracellular part of EGFR, blocking the binding sites for the EGFR ligands, and intracellular tyrosine kinase inhibitors (TKIs) that block the ATP binding site of the tyrosine kinase domain. Besides an EGFRvIII-targeted vaccine, conjugated anti-EGFR mAbs have been used in different settings to deliver lethal...... been proposed as valid targets in many cancer therapy settings. Different strategies have been developed in order to either inhibit EGFR/EGFRvIII activity or to ablate EGFR/EGFRvIII-positive tumor cells. Drugs that inhibit these receptors include monoclonal antibodies (mAbs) that bind...

  16. High-intensity focused ultrasound for the treatment of solid tumor: Chinese clinical experience

    Science.gov (United States)

    Takeuchi, Akira; Zhang, Hong; Sun, Kun; Hasumura, Hiromi; Liu, Botao; Fu, Yurui; Yang, Zaocheng

    2006-05-01

    As a non-invasive modality, high-intensity focused ultrasound (HIFU) therapy has been received an interest for the treatment of solid tumor. There are some makers of HIFU for the equipment in China. The Sonic CZ901 is developed from the Mianyang stream that has a great advantage for guiding by color Doppler ultrasound imaging. For the research about possibility of this equipment, we evaluate the clinical usefulness to the solid tumor of HIFU treatment at Wujing general hospital in Beijing. We elucidate the result in 28 cases with benign and malignant tumor (Uterine myoma:16, Benign prostatic hypertrophy:5, Benign breast tumor:2, Breast cancer:1, Retroperitoneal tumor:1, Pheochromocytoma:1, Liver cancer: 2) . After 14˜90days, all cases show the reduction of tumor size (Max.3.2cm, Min.1.6cm, :Mean 2.2cm reduced), and the blood flow of tumor completely reduced in 7/23, partially reduced in16/23. Clinical symptoms disappeared in 7, clearly improved in 14, improved in 7. All treatments had no adverse event except for two cases of liver cancer. They felt an abdominal pain that controllable by medicine and it improved within 6hours. It is concluded that HIFU with guide by ultrasound imaging is very safe, painless and effective as the anti-tumor treatment.

  17. Subcutaneous administration of ketoprofen delays Ehrlich solid tumor growth in mice

    Directory of Open Access Journals (Sweden)

    C.M. Souza

    2014-10-01

    Full Text Available Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID has proven to exert anti-inflammatory, anti-proliferative and anti-angiogenic activities in both neoplastic and non-neoplastic conditions. We investigated the effects of this compound on tumor development in Swiss mice previously inoculated with Ehrlich tumor cells. To carry out this study the solid tumor was obtained from cells of the ascites fluid of Ehrlich tumor re-suspended in physiological saline to give 2.5x106 cells in 0.05mL. After tumor inoculation, the animals were separated into two groups (n = 10. The animals treated with ketoprofen 0.1µg/100µL/animal were injected intraperitoneally at intervals of 24h for 10 consecutive days. Animals from the control group received saline. At the end of the experiment the mice were killed and the tumor removed. We analyzed tumor growth, histomorphological and immunohistochemical characteristics for CDC47 (cellular proliferation marker and for CD31 (blood vessel marker. Animals treated with the ketoprofen 0.1µg/100µL/animal showed lower tumor growth. The treatment did not significantly influence the size of the areas of cancer, inflammation, necrosis and hemorrhage. Moreover, lower rates of tumor cell proliferation were observed in animals treated with ketoprofen compared with the untreated control group. The participation of ketoprofen in controlling tumor malignant cell proliferation would open prospects for its use in clinical and antineoplasic therapy.

  18. Use of Arsenic Trioxide as an Antivascular and Thermosensitizing Agent in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Robert J. Griffin

    2000-01-01

    Full Text Available Arsenic trioxide, As2O3 (ATO, has been found to be an effective chemotherapy drug for acute promyelocytic leukemia but its effect on solid tumors has not been fully explored. In the present report, we describe our observation that ATO is a potent antivascular agent and that it markedly enhances the effect of hyperthermia on tumors. The tumor blood perfusion in SCK tumors of A/J mice and FSall tumors of C3H mice was significantly suppressed for up to 24 hours after an i.p. injection of 8 mg/kg ATO. ATO was also found to be able to increase the thermosensitivity of tumor cells in vitro. As a probable consequence of these effects, ATO treatment markedly increased the tumor growth delay caused by hyperthermia at 41.5-42.5°C. Immunohistochemical staining of tumor tissue revealed that the expression levels of several adhesion molecules and TNFa are noticeably increased in tumors 2–6 hours after systemic ATO treatment. It is concluded that ATO is potentially useful to enhance the effect of hyperthermia on tumors at a clinically relevant temperature.

  19. Solid pseudopapillary tumor of the pancreas and concomitant urogenital malformations in a young woman

    OpenAIRE

    Guan, Zhi-Wei; Lu SUN; Wang, Yan-Qiu; Xu, Bai-Xuan

    2013-01-01

    Abstract Solid pseudopapillary tumor (SPT) of the pancreas is a rare pancreatic tumor with low malignant potential. It occurs characteristically more often in young women. SPT associated with extra- and pancreatic anomalies are occasionally reported. Here we report a case of pancreatic SPT with concomitant urogenital malformations including solitary kidney and uterus didelphys in a 25-year-old woman. The patient underwent central pancreatectomy, and SPT was confirmed with pathological results...

  20. Co-Encapsulation of Doxorubicin With Galactoxyloglucan Nanoparticles for Intracellular Tumor-Targeted Delivery in Murine Ascites and Solid Tumors

    Directory of Open Access Journals (Sweden)

    Manu M. Joseph

    2014-10-01

    Full Text Available Doxorubicin (Dox treatment is limited by severe toxicity and frequent episodes of treatment failure. To minimize adverse events and improve drug delivery efficiently and specifically in cancer cells, encapsulation of Dox with naturally obtained galactoxyloglucan polysaccharide (PST001, isolated from Tamarindus indica was attempted. Thus formed PST-Dox nanoparticles induced apoptosis and exhibited significant cytotoxicity in murine ascites cell lines, Dalton’s lymphoma ascites and Ehrlich’s ascites carcinoma. The mechanism contributing to the augmented cytotoxicity of nanoconjugates at lower doses was validated by measuring the Dox intracellular uptake in human colon, leukemic and breast cancer cell lines. PST-Dox nanoparticles showed rapid internalization of Dox into cancer cells within a short period of incubation. Further, in vivo efficacy was tested in comparison to the parent counterparts - PST001 and Dox, in ascites and solid tumor syngraft mice models. Treatment of ascites tumors with PST-Dox nanoparticles significantly reduced the tumor volume, viable tumor cell count, and increased survival and percentage life span in the early, established and prophylactic phases of the disease. Administration of nanoparticles through intratumoral route delivered more robust antitumor response than the intraperitoneal route in solid malignancies. Thus, the results indicate that PST-Dox nanoparticles have greater potential compared to the Dox as targeted drug delivery nanocarriers for loco regional cancer chemotherapy applications.

  1. Targeting Mitochondrial Function to Treat Quiescent Tumor Cells in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Xiaonan Zhang

    2015-11-01

    Full Text Available The disorganized nature of tumor vasculature results in the generation of microenvironments characterized by nutrient starvation, hypoxia and accumulation of acidic metabolites. Tumor cell populations in such areas are often slowly proliferating and thus refractory to chemotherapeutical drugs that are dependent on an active cell cycle. There is an urgent need for alternative therapeutic interventions that circumvent growth dependency. The screening of drug libraries using multicellular tumor spheroids (MCTS or glucose-starved tumor cells has led to the identification of several compounds with promising therapeutic potential and that display activity on quiescent tumor cells. Interestingly, a common theme of these drug screens is the recurrent identification of agents that affect mitochondrial function. Such data suggest that, contrary to the classical Warburg view, tumor cells in nutritionally-compromised microenvironments are dependent on mitochondrial function for energy metabolism and survival. These findings suggest that mitochondria may represent an “Achilles heel” for the survival of slowly-proliferating tumor cells and suggest strategies for the development of therapy to target these cell populations.

  2. MassARRAY determination of somatic oncogenic mutations in solid tumors: Moving forward to personalized medicine.

    Science.gov (United States)

    Fleitas, Tania; Ibarrola-Villava, Maider; Ribas, Gloria; Cervantes, Andrés

    2016-09-01

    This article will review the impact of the recently developed MassARRAY technology on our understanding of cancer biology and treatment. Analysis of somatic mutations is a useful tool in selecting personalized therapy, and for predicting the outcome of many solid tumors. Here, we review the literature on the application of MassARRAY technology (Sequenom Hamburg, Germany) to determine the mutation profile of solid tumors from patients. We summarize the use of commercially available panels of mutations - such as OncoCarta™ or other combinations - and their concordance with results obtained by using other technologies, such as next generation sequencing. PMID:27501018

  3. High-dose chemotherapy: is it standard management for any common solid tumor?

    Science.gov (United States)

    MacNeil, M; Eisenhauer, E A

    1999-10-01

    High-dose chemotherapy with stem-cell support had as its basis the observation of dose-response relationships for many chemotherapeutic agents in laboratory models. The rationale to explore high-dose treatment in the clinic was further enhanced by several retrospective reviews in the 1980s which suggested delivered dose intensity of treatment was an important determinant of patient outcome. The availability of hematopoietic growth factors and technologic advances in the efficiency of stem-cell collection and administration have made the evaluation of exploring high-dose therapy safe and feasible. However, real questions remain regarding the apparently superior results of this treatment in the management of solid tumors. This paper reviews the results of high-dose chemotherapy in breast, ovarian and small cell lung cancers. Firstly the evidence for a dose-response relationship to chemotherapeutic agents in the 'standard' dosage range is examined. Secondly results of non-randomized and, where available, randomized trials of high-dose chemotherapy (HDCT) with stem-cell support are summarized and finally conclusions regarding the weight of the evidence for use of HDCT as 'standard' treatment are given. In none of these tumors is there sufficient evidence from randomized trials to consider HDCT a standard to be offered to all patients with a given stage of disease. The apparent benefit of HDCT seen in phase II trials could well be explained by such phenomena as stage shifts and patient selection. Many randomized trials in ovary and breast cancer are either ongoing or presented only as abstracts so final results must be awaited to quantify the benefit, if any of HDCT. It is acknowledged, however, that some practitioners already utilize this treatment. We speculate about the differences in philosophical approaches to cancer treatment which might contribute to early acceptance of novel therapies in the absence of adequate randomized data.

  4. Pharmacokinetic strategies to improve drug penetration and entrapment within solid tumors.

    Science.gov (United States)

    Al-Abd, Ahmed M; Aljehani, Zekra K; Gazzaz, Rana W; Fakhri, Sarah H; Jabbad, Aisha H; Alahdal, Abdulrahman M; Torchilin, Vladimir P

    2015-12-10

    Despite the discovery of a large number of anticancer agents, cancer still remains among the leading causes of death since the middle of the twentieth century. Solid tumors possess a high degree of genetic instability and emergence of treatment resistance. Tumor resistance has emerged for almost all approved anticancer drugs and will most probably emerge for newly discovered anticancer agents as well. The use of pharmacokinetic approaches to increase anticancer drug concentrations within the solid tumor compartment and prolong its entrapment might diminish the possibility of resistance emergence at the molecular pharmacodynamic level and might even reverse tumor resistance. Several novel treatment modalities such as metronomic therapy, angiogenesis inhibitors, vascular disrupting agents and tumor priming have been introduced to improve solid tumor treatment outcomes. In the current review we will discuss the pharmacokinetic aspect of these treatment modalities in addition to other older treatment modalities, such as extracellular matrix dissolving agents, extracellular matrix synthesis inhibitors, chemoembolization and cellular efflux pump inhibition. Many of these strategies showed variable degrees of success/failure; however, reallocating these modalities based on their influence on the intratumoral pharmacokinetics might improve their understanding and treatment outcomes. PMID:26342660

  5. Four cases of solid pseudopapillary tumors of pancreas: Imaging findings and pathological correlations

    Energy Technology Data Exchange (ETDEWEB)

    Vargas-Serrano, Blanca [Servicio de Radiologia, Hospitales Universitarios Virgen del Rocio, Avda Manuel Siurot s/n, Sevilla 41013 (Spain); Dominguez-Ferreras, Esther [Servicio de Radiologia, Hospitales Universitarios Virgen del Rocio, Avda Manuel Siurot s/n, Sevilla 41013 (Spain)]. E-mail: blancavargas@terra.es; Chinchon-Espino, David [Servicio de Anatomia Patologica, Hospitales Universitarios Virgen del Rocio, Avda Manuel Siurot s/n, Sevilla 41013 (Spain)

    2006-04-15

    Objective: Solid pseudopapillary tumor of the pancreas (SPTP tumor) is a rare pancreatic neoplasm with low malignant potential, which usually affects female patients in the second or third decades of life. It is a non-functional, slow-growing neoplasm that very often reaches considerable size before the first symptoms appear. Symptomatology is frequently related to tumor size. Surgical excision is usually curative in most cases. Infrequently the tumor can appear in male patients or in aged women, which can make the diagnosis more difficult. Some patients develop liver metastases in the follow-up that can be resected. Our purpose is to review the radiological and pathological findings of SPTP with emphasis on these infrequent cases. Subjects and methods: The medical records and radiological findings of patients who underwent surgery for SPTP between 2000 and 2005 were retrospectively reviewed. Study eligibility required that patients had undergone surgical resection and that a SPTP had been pathologically proved. Results: Four cases of solid pseudopapillary tumor of the pancreas were diagnosed and treated in our institution in the study period. Two of the patients, developed on follow-up liver metastases, and peritoneal, hepatic, and nodal metastases, respectively. Conclusion: Solid pseudopapillary tumors are well-encapsulated neoplasms that usually have a good prognosis after surgical excision. A malignant behavior is uncommon and in this case lymph node involvement, hepatic metastases and occasionally peritoneal invasion may also occur. Resection of liver metastases can prolong the long-term survival of the patients.

  6. Hydrodynamics and convection enhanced macromolecular fluid transport in soft biological tissues: Application to solid tumor.

    Science.gov (United States)

    Dey, Bibaswan; Sekhar, G P Raja

    2016-04-21

    This work addresses a theoretical framework for transvascular exchange and extravascular transport of solute macromolecules through soft interstitial space inside a solid tumor. Most of the soft biological tissues show materialistic properties similar to deformable porous material. They exhibit mechanical behavior towards the fluid motion since the solid phase of the tumor tissue gets compressed by the drag force that is associated with the extracellular fluid flow. This paper presents a general view about the transvascular and interstitial transport of solute nutrients inside a tumor in the macroscopic level. Modified Starling׳s equation is used to describe transvascular nutrient transport. On the macroscopic level, motion of extracellular fluid within the tumor interstitium is modeled with the help of biphasic mixture theory and a spherical symmetry solution is given as a simpler case. This present model describes the average interstitial fluid pressure (IFP), extracellular fluid velocity (EFV) and flow rate of extracellular fluid, as well as the deformation of the solid phase of the tumor tissue as an immediate cause of extracellular fluid flow. When the interstitial transport is diffusion dominated, an analytical treatment of advection-diffusion-reaction equation finds the overall nutrient distribution. We propose suitable criteria for the formation of necrosis within the tumor interstitium. This study introduces some parameters that represent the nutrient supply from tumor blood vessels into the tumor extracellular space. These transport parameters compete with the reversible nutrient metabolism of the tumor cells present in the interstitium. The present study also shows that the effectiveness factor corresponding to a first order nutrient metabolism may reach beyond unity if the strength of the distributive solute source assumes positive non-zero values. PMID:26851443

  7. Clinical Outcomes of Patients with Rare and Heavily Pretreated Solid Tumors Treated according to the Results of Tumor Molecular Profiling

    Science.gov (United States)

    Hayden, Ingrid

    2016-01-01

    Patients with heavily pretreated advanced cancer or with rare tumors are difficult to treat. Molecular profiling (MP) of tumors to identify biomarkers that predict potential outcomes with individual therapies is an emerging strategy to guide treatment decisions. Patients with rare tumors for which standard-of-care therapy was unavailable or more common tumors for which standard-of-care options had been exhausted underwent MP at a single Australian center. Data regarding treating physicians' choice of therapy, MP results and recommendations, and patient outcomes were collected. Seven patients had received prior standard first-line therapy (PST), 16 had rare tumors, and 31 had been heavily pretreated (HPT; ≥2 prior lines). Most treatments suggested by MP (541/594; 91.1%) were common chemotherapy drugs available in generic formulations. MP-guided therapy recommendations differed from physician's recommendations in 48 patients (88.9%). MP-guided therapy produced clinical benefit (improved QOL and/or performance status, symptoms, bodyweight, or RECIST) in 19/31 (61.3%), 11/16 (68.8%), and 3/7 (42.9%) patients with HPTs, rare tumors, and PSTs, respectively, and had a PFS ratio ≥1.3 in 22/37 evaluable patients (59.5%; 95% confidence interval 44–76%). The null hypothesis that ≤15% of these patients would have a PFS ratio ≥1.3 was rejected (one-sided p selection is feasible in clinical practice and may improve patient outcomes. PMID:27525268

  8. Vaccinia Virus-mediated Therapy of Solid Tumor Xenografts: Intra-tumoral Delivery of Therapeutic Antibodies

    OpenAIRE

    Huang, Ting

    2013-01-01

    Over the past 30 years, much effort and financial support have been invested in the fight against cancer, yet cancer still represents the leading cause of death in the world. Conventional therapies for treatment of cancer are predominantly directed against tumor cells. Recently however, new treatments options have paid more attention to exploiting the advantage of targeting the tumor stroma instead. Vaccinia virus (VACV) has played an important role in human medicine since the 18th century...

  9. Strategies for improving chemotherapeutic delivery to solid tumors mediated by vascular permeability modulation

    Science.gov (United States)

    Roy Chaudhuri, Tista

    An essential mode of distribution of blood-borne chemotherapeutic agents within a solid tumor is via the micro-circulation. Poor tumor perfusion, because of a lack of functional vasculature or a lack of microvessels, as well as low tumor vascular permeability, can prevent adequate deposition of even low molecular-weight agents into the tumor. The modulation of tumor vascular function and density can provides numerous strategies for improving intratumor deposition of chemotherapeutic agents. Here we investigated strategies to improve drug delivery to two tumor types that share in common poor drug delivery, but differ in the underlying cause. First, in an angiogenesis-driven brain tumor model of Glioblastoma, the vascular permeability barrier, along with poorly-functional vasculature, hinders drug delivery. A strategy of nanoparticle-based tumor 'priming' to attack the vascular permeability barrier, employing sterically stabilized liposomal doxorubicin (SSL-DXR), was investigated. Functional and histological evaluation of tumor vasculature revealed that after an initial period of depressed vascular permeability and vascular pruning 3--4 days after SSL-DXR administration, vascular permeability and perfusion were restored and then elevated after 5--7 days. As a result of tumor priming, deposition of subsequently-administered nanoparticles was enhanced, and the efficacy of temozolomide (TMZ), if administered during the window of elevated permeability, was increased. The sequenced regimen resulted in a persistent reduction of the tumor proliferative index and a 40% suppression of tumor volume, compared to animals that received both agents simultaneously. Second, in a hypovascular, pancreatic ductal adenocarcinoma model, disruption of tumor-stromal communication via sonic hedgehog (sHH) signaling pathway inhibition mediated an indirect vascular proliferation and a more than 2-fold increase in intratumor nanoparticle deposition. Enhanced delivery of SSL-DXR in tumors pre

  10. Biopsy of solid liver tumors:adverse consequences

    Institute of Scientific and Technical Information of China (English)

    Dhya Al-Leswas; Derek A O'Reilly; Graeme J Poston

    2008-01-01

    BACKGROUND:Percutaneous radiologically-guided liver biopsy is used routinely worldwide in all secondary-level hospital centers. While it has an undoubted role in the investigation and management of acute and chronic inlfammatory conditions of the liver, its role in hepatic oncology is doubtful and probably dangerous. METHOD:We report on two patients who underwent preoperative biopsy of potentially resectable liver tumors. RESULTS:At the time of surgery, there was evidence of seeding at the biopsy site in both cases. In case 1, potentially curative liver resection was rendered incurable because of gross peritoneal carcinomatosis lying adjacent to the site of liver biopsy. In case 2, the patient underwent curative liver resection, but there was histopathological evidence of peritoneal disease beyond the liver capsule along the falciform ligament at the site of the previous biopsy. CONCLUSIONS:No patient with a suspicious liver tumor which is thought to be malignant and has any possibility of being a potential candidate for liver surgery, should be subjected to pre-operative diagnostic biopsy in a non-specialist center.

  11. TAMIS for rectal tumors: advancements of a new approach.

    Science.gov (United States)

    Rega, Daniela; Pace, Ugo; Niglio, Antonello; Scala, Dario; Sassaroli, Cinzia; Delrio, Paolo

    2016-03-01

    TAMIS allows transanal excision of rectal lesions by the means of a single-incision access port and traditional laparoscopic instruments. This technique represents a promising treatment of rectal neoplasms since it guarantees precise dissection and reproducible approaches. From May 2010 to September 2015, we performed excisions of rectal lesions in 55 patients using a SILS port. The pre-operative diagnosis was 26 tumours, 26 low and high grade displasias and 3 other benign neoplasias. 11 patients had a neoadjuvant treatment. Pneumorectum was established at a pressure of 15-20 mmHg CO2 with continuous insufflation, and ordinary laparoscopic instruments were used to perform full thickness resection of rectal neoplasm with a conventional 5-mm 30° laparoscopic camera. The average operative time was 78 min. Postoperative recovery was uneventful in 53 cases: in one case a Hartmann procedure was necessary at two postoperative days due to an intraoperative intraperitoneal perforation; in another case, a diverting colostomy was required at the five postoperative days due to an intraoperative perforation of the vaginal wall. Unclear resection margins were detected in six patients: thereafter five patients underwent radical surgery; the other patient was unfit for radical surgery, but is actually alive and well. Patients were discharged after a median of 3 days. Transanal minimally invasive surgery is an advanced transanal platform that provides a safe and effective method for low rectal tumors. The feasibility of TAMIS also for malignant lesions treated in a neoadjuvant setting could be cautiously evaluated in the future. PMID:27052544

  12. Elucidating the Uptake and Distribution of Nanoparticles in Solid Tumors via a Multilayered Cell Culture Model

    Institute of Scientific and Technical Information of China (English)

    Darren Yohan; Charmainne Cruje; Xiaofeng Lu; Devika Chithrani

    2015-01-01

    Multicellular layers (MCLs) have previously been used to determine the pharmacokinetics of a variety of different cancer drugs including paclitaxel, doxorubicin, methotrexate, and 5-fluorouracil across a number of cell lines. It is not known how nanoparticles (NPs) navigate through the tumor microenvironment once they leave the tumor blood vessel. In this study, we used the MCL model to study the uptake and penetration dynamics of NPs. Gold nanoparticles (GNPs) were used as a model system to map the NP distribution within tissue-like structures. Our results show that NP uptake and transport are dependent on the tumor cell type. MDA-MB-231 tissue showed deeper penetration of GNPs as compared to MCF-7 one. Intracellular and extracellular distributions of NPs were mapped using CytoViva imaging. The ability of MCLs to mimic tumor tissue characteristics makes them a useful tool in assessing the efficacy of particle distribution in solid tumors.

  13. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

    2014-11-04

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

  14. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    International Nuclear Information System (INIS)

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis

  15. Dynamic density functional theory of solid tumor growth: Preliminary models

    Directory of Open Access Journals (Sweden)

    Arnaud Chauviere

    2012-03-01

    Full Text Available Cancer is a disease that can be seen as a complex system whose dynamics and growth result from nonlinear processes coupled across wide ranges of spatio-temporal scales. The current mathematical modeling literature addresses issues at various scales but the development of theoretical methodologies capable of bridging gaps across scales needs further study. We present a new theoretical framework based on Dynamic Density Functional Theory (DDFT extended, for the first time, to the dynamics of living tissues by accounting for cell density correlations, different cell types, phenotypes and cell birth/death processes, in order to provide a biophysically consistent description of processes across the scales. We present an application of this approach to tumor growth.

  16. Dynamic density functional theory of solid tumor growth: Preliminary models.

    Science.gov (United States)

    Chauviere, Arnaud; Hatzikirou, Haralambos; Kevrekidis, Ioannis G; Lowengrub, John S; Cristini, Vittorio

    2012-03-01

    Cancer is a disease that can be seen as a complex system whose dynamics and growth result from nonlinear processes coupled across wide ranges of spatio-temporal scales. The current mathematical modeling literature addresses issues at various scales but the development of theoretical methodologies capable of bridging gaps across scales needs further study. We present a new theoretical framework based on Dynamic Density Functional Theory (DDFT) extended, for the first time, to the dynamics of living tissues by accounting for cell density correlations, different cell types, phenotypes and cell birth/death processes, in order to provide a biophysically consistent description of processes across the scales. We present an application of this approach to tumor growth. PMID:22489279

  17. An unusual presentation of tumor lysis syndrome in a patient with advanced gastric adenocarcinoma: case report and literature review.

    Science.gov (United States)

    Vodopivec, Danica Maria; Rubio, Jose Enrique; Fornoni, Alessia; Lenz, Oliver

    2012-01-01

    Tumor lysis syndrome (TLS) is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, and secondary hypocalcemia in patients with a malignancy. When these laboratory abnormalities develop rapidly, clinical complications such as cardiac arrhythmias, acute renal failure, seizures, or death may occur. TLS is caused by rapid release of intracellular contents by dying tumor cells, a condition that is expected to be common in hematologic malignancies. However, TLS rarely occurs with solid tumors, and here we present the second chemotherapy-induced TLS in a patient with advanced gastric adenocarcinoma to be reported in the literature. We also provide information regarding the total cases of TLS in solid tumors reported from 1977 to present day. Our methodology involved identifying key articles from existing reviews of the literature and then using search terms from these citations in MEDLINE to find additional publications. We relied on a literature review published in 2003 by Baeksgaard et al., where they gathered all total 45 cases reported from 1977 to 2003. Then, we looked for new reported cases from 2004 to present day. All reports (case reports, brief reports, letters to editor, correspondence, reviews, journals, and short communications) identified through these searches were reviewed and included.

  18. An Unusual Presentation of Tumor Lysis Syndrome in a Patient with Advanced Gastric Adenocarcinoma: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Danica Maria Vodopivec

    2012-01-01

    Full Text Available Tumor lysis syndrome (TLS is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, and secondary hypocalcemia in patients with a malignancy. When these laboratory abnormalities develop rapidly, clinical complications such as cardiac arrhythmias, acute renal failure, seizures, or death may occur. TLS is caused by rapid release of intracellular contents by dying tumor cells, a condition that is expected to be common in hematologic malignancies. However, TLS rarely occurs with solid tumors, and here we present the second chemotherapy-induced TLS in a patient with advanced gastric adenocarcinoma to be reported in the literature. We also provide information regarding the total cases of TLS in solid tumors reported from 1977 to present day. Our methodology involved identifying key articles from existing reviews of the literature and then using search terms from these citations in MEDLINE to find additional publications. We relied on a literature review published in 2003 by Baeksgaard et al., where they gathered all total 45 cases reported from 1977 to 2003. Then, we looked for new reported cases from 2004 to present day. All reports (case reports, brief reports, letters to editor, correspondence, reviews, journals, and short communications identified through these searches were reviewed and included.

  19. Secondary solid tumors following radiation in Hodgkin's disease: experience of the Institut Gustave-Roussy

    International Nuclear Information System (INIS)

    From 1961 to 1984, in the Institut Gustave-Roussy, 893 patients have been treated in Hodgkin's disease. The authors study the solid tumors that they have observed after exclusive radiotherapy and chemo-radiotherapy in order to know the radiation effect in the birth of this type of cancer

  20. A Study of CDX-1127 (Varlilumab) in Patients With Select Solid Tumor Types or Hematologic Cancers

    Science.gov (United States)

    2016-04-05

    CD27 Expressing B-cell Malignancies, (for Example: Hodgkin's Lymphoma,; Chronic Lymphocytic Leukemia, Burkett's Lymphoma,; Mantle Cell Lymphoma, Primary Lymphoma of the Central Nervous System,; Marginal Zone B Cell Lymphoma);; Any T-cell Malignancy;; Solid Tumors (Metastatic Melanoma, Renal (Clear) Cell Carcinoma,; Hormone-refractory Prostate Adenocarcinoma, Ovarian Cancer; Colorectal Adenocarcinoma, Non-small Cell Lung Cancer)

  1. Biochemical parameters of bone metabolism in bone metastases of solid tumors (Review)

    NARCIS (Netherlands)

    Meijer, Wilhelmus; van der Veer, E; Willemse, P H

    1998-01-01

    The role of biochemical markers of bone metabolism in the diagnosis and monitoring of bone metastases in solid tumors is reviewed. Emphasis is on the recently developed markers, which may provide a more accurate quantitation of bone metabolism. In metastatic bone disease, bone formation and resorpti

  2. Recent advances in lymphatic targeted drug deliver y system for tumor metastasis

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yu Zhang; Wei-Yue Lu

    2014-01-01

    Te lymphatic system has an important defensive role in the human body. hTe metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors;the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the speciifcity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.

  3. Advanced Research on Circulating Tumor Cells in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Hui LI

    2012-11-01

    Full Text Available Lung cancer is the malignant disease with the highest rate in terms of incidence and mortality in China. Early diagnosis and timely monitoring tumor recurrence and metastasis are extremely important for improving 5-year survival rate of lung cancer patients. Circulating tumor cells (CTCs, as a "liquid biopsy specimens” for the primary tumor, provide the possibility to perform real-time, non-invasive histological identification for lung cancer patients. The detection of CTCs contributes to early diagnosis, surveillance of tumor recurrence and metastasis, and prediction of therapeutic efficacy and prognosis. Furthermore, CTCs-dependent detection emerges as a new approach for molecularly pathologic examination, study of molecular mechanisms involved in drug resistance, and resolution for tumor heterogeneity. This study reviewed the recent progress of CTCs in lung cancer research field.

  4. Three-dimensional conformal radiotherapy for portal vein tumor thrombosis alone in advanced hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ju Hye Kim Dong Hyun; Ki, Yong Kan; Kim, Dong Won; Kim, Won Taek; Heo, Jeong; Woo, Hyun Young [Pusan National University Hospital, Pusan National University School of Medicine, Busan (Korea, Republic of); Nam, Ji Ho [Dept.of Radiation Oncology, Pusan National University Yangsan Hospital, Yangsan (Korea, Republic of)

    2014-09-15

    We sought to evaluate the clinical outcomes of 3-dimensional conformal radiation therapy (3D-CRT) for portal vein tumor thrombosis (PVTT) alone in patients with advanced hepatocellular carcinoma. We retrospectively analyzed data on 46 patients who received 3D-CRT for PVTT alone between June 2002 and December 2011. Response was evaluated following the Response Evaluation Criteria in Solid Tumors. Prognostic factors and 1-year survival rates were compared between responders and non-responders. Thirty-seven patients (80.4%) had category B Child-Pugh scores. The Eastern Cooperative Oncology Group performance status score was 2 in 20 patients. Thirty patients (65.2%) had main or bilateral PVTT. The median irradiation dose was 50 Gy (range, 35 to 60 Gy) and the daily median dose was 2 Gy (range, 2.0 to 2.5 Gy). PVTT response was classified as complete response in 3 patients (6.5%), partial response in 12 (26.1%), stable disease in 19 (41.3%), and progressive disease in 12 (26.1%). There were 2 cases of grade 3 toxicities during or 3 months after radiotherapy. Twelve patients in the responder group (15 patients) received at least 50 Gy irradiation, but about 84% of patients in the non-responder group received less than 50 Gy. The 1-year survival rate was 66.8% in responders and 27.4% in non-responders constituting a statistically significant difference (p = 0.008). Conformal radiotherapy for PVTT alone could be chosen as a palliative treatment modality in patients with unfavorable conditions (liver, patient, or tumor factors). However, more than 50 Gy of radiation may be required.

  5. Environmental impact statement Space Shuttle advanced solid rocket motor program

    Science.gov (United States)

    1989-01-01

    The proposed action is design, development, testing, and evaluation of Advanced Solid Rocket Motors (ASRM) to replace the motors currently used to launch the Space Shuttle. The proposed action includes design, construction, and operation of new government-owned, contractor-operated facilities for manufacturing and testing the ASRM's. The proposed action also includes transport of propellant-filled rocket motor segments from the manufacturing facility to the testing and launch sites and the return of used and/or refurbished segments to the manufacturing site. Sites being considered for the new facilities include John C. Stennis Space Center, Hancock County, Mississippi; the Yellow Creek site in Tishomingo County, Mississippi, which is currently in the custody and control of the Tennessee Valley Authority; and John F. Kennedy Space Center, Brevard County, Florida. TVA proposes to transfer its site to the custody and control of NASA if it is the selected site. All facilities need not be located at the same site. Existing facilities which may provide support for the program include Michoud Assembly Facility, New Orleans Parish, Louisiana; and Slidell Computer Center, St. Tammany Parish, Louisiana. NASA's preferred production location is the Yellow Creek site, and the preferred test location is the Stennis Space Center.

  6. Cytokine and Immuno-Gene Therapy for Solid Tumors

    Institute of Scientific and Technical Information of China (English)

    Chuan-Yuan Li; Qian Huang; Hsiang-Fu Kung

    2005-01-01

    Despite recent progress in our understanding of cancer biology and in many areas of cancer treatment, the success rate for cancer therapy remains dismal. Immunotherapy for cancer has long been an exciting field for many cancer researchers due to the possibility to mobilize the body's own immune system to eradicate cancer not only locally but also systemically. Since its initial discovery, cytokine-based immunotherapy has been vigorously and extensively investigated for cancer treatment due to the perception of it as a relatively easily purifiable, injectable form of cancer treatment agent. However, so far most cytokine-based therapy trials have fallen short of expectations. One of main obstacles is the difficulty to achieve therapeutically relevant dosage in patients without generating excessive normal tissue toxicity. The emergence of novel gene therapy approach to deliver therapeutic cytokine to tumors locally generated great excitement since it has the potential of generating sustained high local concentration of immunostimulatory cytokine without raising the systemic levels of the cytokines, which is responsible for most of the observed toxicity. In this review, we will attempt to provide an overview of the field and discuss some of the problems associated with cytokine-based immuno-gene therapy and potential solutions.Cellular & Molecular Immunology. 2005;2(2):81-91.

  7. Cytokine and Immuno-Gene Therapy for Solid Tumors

    Institute of Scientific and Technical Information of China (English)

    Chuan-YuanLi; QianHuang; Hsiang-FuKung

    2005-01-01

    Despite recent progress in our understanding of cancer biology and in many areas of cancer treatment, the success rate for cancer therapy remains dismal. Immunotherapy for cancer has long been an exciting field for many cancer researchers due to the possibility to mobilize the body's own immune system to eradicate cancer not only locally but also systemically. Since its initial discovery, cytokine-based immunotherapy has been vigorously and extensively investigated for cancer treatment due to the perception of it as a relatively easily purifiable, injectable form of cancer treatment agent. However, so far most cytokine-based therapy trials have fallen short ofexpectations. One of main obstacles is the difficulty to achieve therapeutically relevant dosage in patients without generating excessive normal tissue toxicity. The emergence of novel gene therapy approach to deliver therapeutic cytokine to tumors locally generated great excitement since it has the potential of generating sustained high local concentration of immunostimulatory cytokine without raising the systemic levels of the cytokines, which is responsible for most of the observed toxicity. In this review, we will attempt to provide an overview of the field and discuss some of the problems associated with cytokine-based immuno-gene therapy and potential solutions. Cellular & Molecular Immunology. 2005;2(2):81-91.

  8. Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors

    Science.gov (United States)

    Moeendarbari, Sina; Tekade, Rakesh; Mulgaonkar, Aditi; Christensen, Preston; Ramezani, Saleh; Hassan, Gedaa; Jiang, Ruiqian; Öz, Orhan K.; Hao, Yaowu; Sun, Xiankai

    2016-02-01

    Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form 103Pd@Au nanoseeds. The therapeutic efficacy of 103Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of 103Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.

  9. Modulation of macrophage cytokine profiles during solid tumor progression: susceptibility to Candida albicans infection

    Directory of Open Access Journals (Sweden)

    Venturini James

    2009-06-01

    Full Text Available Abstract Background In order to attain a better understanding of the interactions between opportunist fungi and their hosts, we investigated the cytokine profile associated with the inflammatory response to Candida albicans infection in mice with solid Ehrlich tumors of different degrees. Methods Groups of eight animals were inoculated intraperitoneally with 5 × 106 C. albicans 7, 14 or 21 days after tumor implantation. After 24 or 72 hours, the animals were euthanized and intraperitoneal lavage fluid was collected. Peritoneal macrophages were cultivated and the levels of IFN-γ, TNF-α, IL-12, IL-10 and IL-4 released into the supernatants were measured by ELISA. Kidney, liver and spleen samples were evaluated for fungal dissemination. Tumor-free animals and animals that had only been subjected to C. albicans infection were used as control groups. Results Our results demonstrated that the mice produced more IFN-γ and TNF-α and less IL-10, and also exhibited fungal clearance, at the beginning of tumor evolution. With the tumor progression, this picture changed: IL-10 production increased and IFN-γ and TNF-α release decreased; furthermore, there was extensive fungal dissemination. Conclusion Our results indicate that solid tumors can affect the production of macrophage cytokines and, in consequence, affect host resistance to opportunistic infections.

  10. An overview of viral oncology in Italy - report from the Pavia meeting on solid tumors

    Directory of Open Access Journals (Sweden)

    Perfetti Vittorio

    2012-09-01

    Full Text Available Abstract This is a report on some of the research activities currently ongoing in Italy as outlined at the “Viruses and solid tumors” meeting jointly organized by the Oncology Sections of IRCCS Policlinico “San Matteo” (Pavia and IRCCS National Cancer Institute (Aviano, held in Pavia, Italy, on October 2011. Experts from the various disciplines involved in the study of the complex relationships between solid tumors and viruses met to discuss recent developments in the field and to report their personal contributions to the specified topics. Secondary end point was to establish a multidisciplinary work group specifically devoted to solid tumors and infectious agents, aimed to identify areas of common interest, promoting and establishing collaborative projects and programs, and to coordinate clinical and research activities. The group, which will be named IVOG (Italian Viral Oncology Group, will operate under the patronage of the various scientific societies of interest.

  11. Research Advances on Th17 Cells in Tumor

    Directory of Open Access Journals (Sweden)

    Jiansheng WANG

    2011-11-01

    Full Text Available The Th17 cells, identified recently as a novel CD4+ T cell lineage, are characteristic of their production of IL-17 and distinct from Th1 and Th2 lineages. Their involvement in autoimmune and chronic inflammation diseases has been well observed. Recent evidence suggests that Th17 cells are also involved in tumor immunology. However, it remains unclear that how these cells regulate immune responses to tumor growth. In this review, we summarize the most recent findings about the biologics of the Th17 cells in tumor development with a hope of providing new insights into future development of effective new cancer immunotherapies.

  12. Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival

    OpenAIRE

    Mathiesen, Randi R.; Borgen, Elin; Renolen, Anne; Løkkevik, Erik; Nesland, Jahn M; Anker, Gun; Østenstad, Bjørn; Lundgren, Steinar; Risberg, Terje; Mjaaland, Ingvil; Kvalheim, Gunnar; Lønning, Per E.; Naume, Bjørn

    2012-01-01

    Introduction Presence of disseminated tumor cells (DTCs) in bone marrow (BM) and circulating tumor cells (CTC) in peripheral blood (PB) predicts reduced survival in early breast cancer. The aim of this study was to determine the presence of and alterations in DTC- and CTC-status in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy (NACT) and to evaluate their prognostic impact. Methods ...

  13. Multifrequency solid state YAG:Nd laser for diagnosis of malignant tumors

    Science.gov (United States)

    Lalayan, Asatur A.; Aidinian, Lusine E.; Galstian, Hayro M.

    1998-09-01

    The possibility of laser fluorescence diagnosis of malignant tumors with the aid of multifrequency (355, 440, 446, 532, 660, 670 nm) solid state YAG:Nd laser and the rise in accuracy of this method were discussed. Permitted for clinical employment sodium fluorescein has been used as human tumor-localizing dye. The fluorescence spectra of sodium fluorescein containing human normal tissue and breast, stomach, intestine, skin cancer during excitation with the third harmonics of YAG:Nd and with help of multichannel fiber-optic spectrofluorometer were studied. The contrast accumulation of the dye in tumors of different localization was investigated. The fluorescence spectra of chlorine e6, containing animal tissues at different excitation wavelength (355, 532 and 660 nm) were obtained. The pharmacokinetic behavior of chlorine e6, containing different organs and tumor tissues of rats, infected with Sarcoma-45 has been investigated.

  14. Clinical Outcomes of Patients with Rare and Heavily Pretreated Solid Tumors Treated according to the Results of Tumor Molecular Profiling.

    Science.gov (United States)

    Dean, Andrew; Byrne, Aisling; Marinova, Mira; Hayden, Ingrid

    2016-01-01

    Patients with heavily pretreated advanced cancer or with rare tumors are difficult to treat. Molecular profiling (MP) of tumors to identify biomarkers that predict potential outcomes with individual therapies is an emerging strategy to guide treatment decisions. Patients with rare tumors for which standard-of-care therapy was unavailable or more common tumors for which standard-of-care options had been exhausted underwent MP at a single Australian center. Data regarding treating physicians' choice of therapy, MP results and recommendations, and patient outcomes were collected. Seven patients had received prior standard first-line therapy (PST), 16 had rare tumors, and 31 had been heavily pretreated (HPT; ≥2 prior lines). Most treatments suggested by MP (541/594; 91.1%) were common chemotherapy drugs available in generic formulations. MP-guided therapy recommendations differed from physician's recommendations in 48 patients (88.9%). MP-guided therapy produced clinical benefit (improved QOL and/or performance status, symptoms, bodyweight, or RECIST) in 19/31 (61.3%), 11/16 (68.8%), and 3/7 (42.9%) patients with HPTs, rare tumors, and PSTs, respectively, and had a PFS ratio ≥1.3 in 22/37 evaluable patients (59.5%; 95% confidence interval 44-76%). The null hypothesis that ≤15% of these patients would have a PFS ratio ≥1.3 was rejected (one-sided p < 0.0001). In conclusion, using MP to guide therapy selection is feasible in clinical practice and may improve patient outcomes. PMID:27525268

  15. Development and Validation of a Scalable Next-Generation Sequencing System for Assessing Relevant Somatic Variants in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Daniel H. Hovelson

    2015-04-01

    Full Text Available Next-generation sequencing (NGS has enabled genome-wide personalized oncology efforts at centers and companies with the specialty expertise and infrastructure required to identify and prioritize actionable variants. Such approaches are not scalable, preventing widespread adoption. Likewise, most targeted NGS approaches fail to assess key relevant genomic alteration classes. To address these challenges, we predefined the catalog of relevant solid tumor somatic genome variants (gain-of-function or loss-of-function mutations, high-level copy number alterations, and gene fusions through comprehensive bioinformatics analysis of >700,000 samples. To detect these variants, we developed the Oncomine Comprehensive Panel (OCP, an integrative NGS-based assay [compatible with 95% accuracy for KRAS, epidermal growth factor receptor, and BRAF mutation detection as well as for ALK and TMPRSS2:ERG gene fusions. Associating positive variants with potential targeted treatments demonstrated that 6% to 42% of profiled samples (depending on cancer type harbored alterations beyond routine molecular testing that were associated with approved or guideline-referenced therapies. As a translational research tool, OCP identified adaptive CTNNB1 amplifications/mutations in treated prostate cancers. Through predefining somatic variants in solid tumors and compiling associated potential treatment strategies, OCP represents a simplified, broadly applicable targeted NGS system with the potential to advance precision oncology efforts.

  16. Combined radioimmunotherapy and external irradiation for solid tumors in the mouse

    International Nuclear Information System (INIS)

    Objective: To evaluate the optimal external irradiation dose and potential benefits with different treatment timing strategies and sequence of combined external irradiation and radioimmunotherapy for solid tumors in the mouse. Methods: TS1, a monoclonal antibody directed against anticytokeratin 8, can specifically combined with anticytokeratin in the necrotic parts of tumors. Mab TS1 was iodinated with 131I. Among sixty nude mice with tumor cells xenografts (human cervical squamous carcinoma) used in this study, twenty-four were used in a pilot experiment to determine the appropriate level of external irradiation dose by observing the tumor growth inhibition while thirty-six were used in the experiment proper which were divided into 6 groups and given different treatment protocols. Total accumulated dose, percentage of injected activity per gram of tumor tissue and accumulated dose per injected activity were compared between these different groups. Results: In the pilot experiment, the tumor growth was inhibited markedly by 20 Gy of external irradiation, but the response did not significantly increase when the dose was increased to 26 Gy. In the experiment proper, the highest yields in terms of total accumulated dose, percentage of injected activity per gram of tumor tissue and accumulated dose per injected activity were seen in the group which received external irradiation prior to Mab injection. Conclusions: Enhanced effects can be achieved by combined external irradiation with radioimmunotherapy using the monoclonal anticytokeratin antibody 131I-TS1. 20 Gy of external irradiation should be given prior to Mab injection

  17. Distribution of porfiromycin in EMT6 solid tumors and normal tissues of BALB/c mice.

    Science.gov (United States)

    Keyes, S R; Rockwell, S; Kennedy, K A; Sartorelli, A C

    1991-05-01

    The distribution of porfiromycin was studied in BALB/c mice bearing EMT6 mammary tumors. The levels of 3H in blood and most tissues peaked approximately 15 minutes after intraperitoneal injection of [3H]porfiromycin. The levels of radioactivity present in most of the tissues and in the tumors were similar at 4 hours and 24 hours after administration. Most of the normal tissues showed uniform, low grain densities when analyzed by autoradiography; the liver and the small intestine had the highest labeling densities. Only kidney, bladder, and tumor showed differential distributions of grains from [3H]porfiromycin. In the kidney, higher grain counts were found in cortex than in medullary regions; grains were uniformly distributed within each region. In the bladder, the highest labeling densities were found in regions near the lumen. Tumor regions that had some necrotic features or regions of necrosis that included some viable cells showed higher labeling intensities than healthy-looking tumor regions, probably because the abnormal microenvironments in these regions led to increased rates of activation of porfiromycin to electrophilic species. These findings show that porfiromycin can reach and be activated in tumor regions containing cells resistant to many chemotherapeutic agents and to x rays. The results also support the concept that agents such as porfiromycin can target cells in specific microenvironmental subpopulations of solid tumors. PMID:2023281

  18. Field study of disposed solid wastes from advanced coal processes

    International Nuclear Information System (INIS)

    Radian Corporation and the North Dakota Energy and Environmental Research Center (EERC) are funded to develop information to be used by private industry and government agencies for managing solid wastes produced by advanced coal combustion processes. This information will be developed by conducting several field studies on disposed wastes from these processes. Data will be collected to characterize these wastes and their interactions with the environments in which they are disposed. Three sites were selected for the field studies: Colorado Ute's fluidized bed combustion (FBC) unit in Nucla, Colorado; Ohio Edison's limestone injection multistage burner (LIMB) retrofit in Lorain, Ohio; and Freeman United's mine site in central Illinois with wastes supplied by the nearby Midwest Grain FBC unit. During the past year, field monitoring and sampling of the four landfill test cases constructed in 1989 and 1991 has continued. Option 1 of the contract was approved last year to add financing for the fifth test case at the Freeman United site. The construction of the Test Case 5 cells is scheduled to begin in November, 1992. Work during this past year has focused on obtaining data on the physical and chemical properties of the landfilled wastes, and on developing a conceptual framework for interpreting this information. Results to date indicate that hydration reactions within the landfilled wastes have had a major impact on the physical and chemical properties of the materials but these reactions largely ceased after the first year, and physical properties have changed little since then. Conditions in Colorado remained dry and no porewater samples were collected. In Ohio, hydration reactions and increases in the moisture content of the waste tied up much of the water initially infiltrating the test cells

  19. Solid and Cystic Tumor (SCT of the Pancreas in an Adult Man

    Directory of Open Access Journals (Sweden)

    K. Ohiwa

    1997-01-01

    Full Text Available Solid and cystic tumor (SCT of the pancreas predominantly Occurs in women, and the occurrence in men is extremely rare. We experienced a male case of SCT. A 38-year-old man was admitted with the complaint of upper abdominal pain. CT scan showed the presence of a mass in the head of the pancreas. The mass was composed of high density areas and low density areas. Ultrasonograms revealed the mass being composed of high echoic areas and low echoic areas. The mass .was hypovascular on angiography. SCT was suspected and pancreaticoduodenectomy was performed. The cut surface of the tumor showed mainly cystic degenerative areas containing dark red hemorrhagic materials. Microscopically, there were solid areas in the periphery and pseudopapillary areas in the center. No metastasis was found in the removed lymph nodes. The tumor cells were not stained by Grimelius' silver stain. The tumor cells were positive for alpha-l-antitrypsin (AAT and neuron-specific enolase (NSE. Pancreatic hormones such as insulin, glucagon, and somatostatin were all negative. Electron micrograph showed that tumor cells were rich in mitochondria. Zymogen granules and neurosecretory granules were not detected. Estrogen receptor (ER and progesterone receptor (PR were both negative.

  20. Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors.

    Science.gov (United States)

    Fox, Alan J; Hiemenz, Matthew C; Lieberman, David B; Sukhadia, Shrey; Li, Barnett; Grubb, Joseph; Candrea, Patrick; Ganapathy, Karthik; Zhao, Jianhua; Roth, David; Alley, Evan; Loren, Alison; Morrissette, Jennifer J D

    2016-01-01

    As our understanding of the driver mutations necessary for initiation and progression of cancers improves, we gain critical information on how specific molecular profiles of a tumor may predict responsiveness to therapeutic agents or provide knowledge about prognosis. At our institution a tumor genotyping program was established as part of routine clinical care, screening both hematologic and solid tumors for a wide spectrum of mutations using two next-generation sequencing (NGS) panels: a custom, 33 gene hematological malignancies panel for use with peripheral blood and bone marrow, and a commercially produced solid tumor panel for use with formalin-fixed paraffin-embedded tissue that targets 47 genes commonly mutated in cancer. Our workflow includes a pathologist review of the biopsy to ensure there is adequate amount of tumor for the assay followed by customized DNA extraction is performed on the specimen. Quality control of the specimen includes steps for quantity, quality and integrity and only after the extracted DNA passes these metrics an amplicon library is generated and sequenced. The resulting data is analyzed through an in-house bioinformatics pipeline and the variants are reviewed and interpreted for pathogenicity. Here we provide a snapshot of the utility of each panel using two clinical cases to provide insight into how a well-designed NGS workflow can contribute to optimizing clinical outcomes. PMID:27684276

  1. Predictive Factors of Tumor Response After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

    International Nuclear Information System (INIS)

    Purpose: Neoadjuvant chemoradiation followed by surgery is the standard of care for locally advanced rectal cancer. The aim of this study was to correlate tumor response to survival and to identify predictive factors for tumor response after chemoradiation. Methods and Materials: From 1998 to 2008, 168 patients with histologically proven locally advanced adenocarcinoma treated by preoperative chemoradiation before total mesorectal excision were retrospectively studied. They received a radiation dose of 45 Gy with a concomitant 5-fluorouracil (5-FU)-based chemotherapy. Analysis of tumor response was based on lowering of the T stage between pretreatment endorectal ultrasound and pathologic specimens. Overall and progression-free survival rates were correlated with tumor response. Tumor response was analyzed with predictive factors. Results: The median follow-up was 34 months. Five-year disease-free survival and overall survival rates were, of 44.4% and 74.5% in the whole population, 83.4% and 83.4%, respectively, in patients with pathological complete response, 38.6% and 71.9%, respectively, in patients with tumor downstaging, and 29.1and 58.9% respectively, in patients with absence of response. A pretreatment carcinoembryonic antigen (CEA) level of <5 ng/ml was significantly independently associated with pathologic complete tumor response (p = 0.019). Pretreatment small tumor size (p = 0.04), pretreatment CEA level of <5 ng/ml (p = 0.008), and chemotherapy with capecitabine (vs. 5-FU) (p = 0.04) were significantly associated with tumor downstaging. Conclusions: Downstaging and complete response after CRT improved progression-free survival and overall survival of locally advanced rectal adenocarcinoma. In multivariate analysis, a pretreatment CEA level of <5 ng/ml was associated with complete tumor response. Thus, small tumor size, a pretreatment CEA level of < 5ng/ml, and use of capecitabine were associated with tumor downstaging.

  2. Intrathecal dexamethasone and methotrexate treatment of neoplastic meningitis from solid tumors

    Directory of Open Access Journals (Sweden)

    Wen-Jing Lv

    2015-01-01

    Full Text Available Aim: Neoplastic meningitis (NM from solid tumors is an advanced malignancy with poor prognosis. Intrathecal chemotherapy is a reliable treatment, and we have obtained some experiences in the treatment of NM with intrathecal dexamethasone and methotrexate (IT DXM and MTX. Methods: Retrospective study of 23 patients with NM from lung cancer (n = 11, breast cancer (n = 3, gastric cancer (n = 1, malignant melanoma (n = 1, unknown cancer (n = 7 was conducted. Among these patients, eight received IT DXM and MTX treatment, and 15 patients were placed into a palliative care group. Overall survival (OS was compared, and the patients′ characteristics, symptoms, and some laboratory examinations were analyzed to find the risk factors affecting OS. Results: OS of IT DXM and MTX group was significantly longer than that of the palliative care group (P = 0.01. The median survival (MS of palliative care group was 7.53 weeks (5.50-9.57; n = 15, and of the IT DXM and MTX group, 28.63 weeks (12.50-44.75; n = 8; IT DXM and MTX prolonged the OS of NM patients (regression coefficient = −2.923, with odds ratio (OR being 0.054 (0.09-0.323. Spinal nerves damage decreased the OS (regression coefficient = 1.595, with OR being 4.928 (1.382-17.579. Conclusion: IT DXM and MTX have prolonged the patients′ MS, which could be used as a fundamental treatment of NM. Time of induction treatment should be flexible and individualized, and induction treatment could restart when central nervous system relapse. Patients with spinal nerves damage are apt to live shorter.

  3. Eosinophilia in routine blood samples as a biomarker for solid tumor development

    DEFF Research Database (Denmark)

    Andersen, Christen Bertel L; Siersma, V.D.; Hasselbalch, H.C.;

    2014-01-01

    eosinophilia in routine blood samples as a potential biomarker of solid tumor development in a prospective design. MATERIAL AND METHODS: From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356 196 individuals with at least one differential cell count (DIFF) encompassing the...... tumors within the first three years following the DIFF. Using multivariable logistic regression, odds ratios (OR) were calculated and adjusted for previous eosinophilia, sex, age, year, month, C-reactive protein, previous cancer and Charlson's Comorbidity Index. RESULTS: The risk of bladder cancer was...

  4. Solid-Pseudopapillary Tumor of the Pancreas: One Case Report and Literatures Review

    Institute of Scientific and Technical Information of China (English)

    Shifu Hu; Naiqiang Cui; Erpeng Zhao

    2009-01-01

    @@ Introduction Solid-pseudopapillary tumor(SPT)is a very mre primary neoplasm of the pancreas.Franz first described it in 1959.It iS usually seen in young females.In spite of possible histological findings of malignancy,SPPT typically shows a benign clinical course and a low malignant potential.The pathogenesis of these tumors iS still controversial.It has been suggested that it might originate from ductal and acinar pancreatic cells,endocrine cells or pluripotential stem cells.

  5. Solid pseudopapillary tumor of the pancreas and concomitant urogenital malformations in a young woman.

    Science.gov (United States)

    Guan, Zhi-Wei; Sun, Lu; Wang, Yan-Qiu; Xu, Bai-Xuan

    2013-01-01

    Solid pseudopapillary tumor (SPT) of the pancreas is a rare pancreatic tumor with low malignant potential. It occurs characteristically more often in young women. SPT associated with extra- and pancreatic anomalies are occasionally reported. Here we report a case of pancreatic SPT with concomitant urogenital malformations including solitary kidney and uterus didelphys in a 25-year-old woman. The patient underwent central pancreatectomy, and SPT was confirmed with pathological results. Recurrence or metastasis was not found after 14 months of follow-up. PMID:23445554

  6. Neuroimaging of pediatric brain tumors: from basic to advanced magnetic resonance imaging (MRI).

    Science.gov (United States)

    Panigrahy, Ashok; Blüml, Stefan

    2009-11-01

    In this review, the basic magnetic resonance concepts used in the imaging approach of a pediatric brain tumor are described with respect to different factors including understanding the significance of the patient's age. Also discussed are other factors directly related to the magnetic resonance scan itself including evaluating the location of the tumor, determining if the lesion is extra-axial or intra-axial, and evaluating the contrast characteristics of the lesion. Of note, there are key imaging features of pediatric brain tumors, which can give information about the cellularity of the lesion, which can then be confirmed with advanced magnetic resonance imaging (MRI) techniques. The second part of this review will provide an overview of the major advanced MRI techniques used in pediatric imaging, particularly, magnetic resonance diffusion, magnetic resonance spectroscopy, and magnetic resonance perfusion. The last part of the review will provide more specific information about the use of advanced magnetic resonance techniques in the evaluation of pediatric brain tumors.

  7. Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis.

    Science.gov (United States)

    Blakeley, Jaishri O; Plotkin, Scott R

    2016-05-01

    Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are tumor-suppressor syndromes. Each syndrome is an orphan disease; however, the tumors that arise within them represent the most common tumors of the nervous system worldwide. Systematic investigation of the pathways impacted by the loss of function of neurofibromin (encoded byNF1) and merlin (encoded byNF2) have led to therapeutic advances for patients with NF1 and NF2. In the syndrome of SWN, the genetic landscape is more complex, with 2 known causative genes (SMARCB1andLZTR1) accounting for up to 50% of familial SWN patients. The understanding of the molecular underpinnings of these syndromes is developing rapidly and offers more therapeutic options for the patients. In addition, common sporadic cancers harbor somatic alterations inNF1(ie, glioblastoma, breast cancer, melanoma),NF2(ie, meningioma, mesothelioma) andSMARCB1(ie, atypical teratoid/rhabdoid tumors) such that advances in management of syndromic tumors may benefit patients both with and without germline mutations. In this review, we discuss the clinical and genetic features of NF1, NF2 and SWN, the therapeutic advances for the tumors that arise within these syndromes and the interaction between these rare tumor syndromes and the common tumors that share these mutations. PMID:26851632

  8. C-Reactive Protein Is an Important Biomarker for Prognosis Tumor Recurrence and Treatment Response in Adult Solid Tumors: A Systematic Review.

    LENUS (Irish Health Repository)

    Shrotriya, Shiva

    2015-01-01

    A systematic literature review was done to determine the relationship between elevated CRP and prognosis in people with solid tumors. C-reactive protein (CRP) is a serum acute phase reactant and a well-established inflammatory marker. We also examined the role of CRP to predict treatment response and tumor recurrence.

  9. Research Advances on Th17 Cells in Tumor

    OpenAIRE

    Wang, Jiansheng; Yuan, Baozhu

    2011-01-01

    The Th17 cells, identified recently as a novel CD4+ T cell lineage, are characteristic of their production of IL-17 and distinct from Th1 and Th2 lineages. Their involvement in autoimmune and chronic inflammation diseases has been well observed. Recent evidence suggests that Th17 cells are also involved in tumor immunology. However, it remains unclear that how these cells regulate immune responses to tumor growth. In this review, we summarize the most recent findings about the biologics of th...

  10. Gallium Chloride Potentiate the Radiation Effects on Solid Tumor in Ehrlich Carcinoma Bearing Mice

    International Nuclear Information System (INIS)

    The objective of this study is to evaluate the effect of co-administration of Gallium Chloride ( GaCl3 ) with gamma irradiation (R) on solid tumor in Ehrlich Carcinoma (EC) bearing mice. Animals were divided into 5 groups. 1-Control: normal healthy mice. 2-Tumour: EC bearing mice. 3- Tumor + GaCl3 : EC bearing mice receiving orally GaCl3 (300 mg/ Kg body weight) for 5 consecutive days/week during 3 weeks. 4- Tumor + R: EC bearing mice whole body gamma irradiated with 2 Gy/week for 3 weeks. 5- Tumor + GaCl3 + R: EC bearing mice receiving orally GaCl3 (300 mg/ Kg body weight) for 5 consecutive days/week and whole body gamma irradiated with 2 Gy/week for 3 weeks. Biochemical analysis in tumor and liver tissues of EC bearing mice revealed a significant increase of malondialdehyde (MDA) level parallel to a significant decrease of glutathione (GSH) content, compared to their respective levels in control rats, indicating oxidative stress. In addition, tumor necrosis factor-alpha (TNF-α) level showed a significant increase. Biochemical analysis in the serum of EC bearing mice showed a significant increase of serum alanine amino transferase (ALT) activity, and bilirubin content and a significant decrease of albumin, compared to their re - spective levels in control rats, indicating alteration of liver function. The results showed also a significant decrease in serum iron level. The co-administration of GaCl3 with R to EC bearing mice potentiate the radiation-induced increase of MDA and TNF-α levels in tumor tissues which was associated to a higher reduction of tumor volume. On the other side, the co-administration of GaCl3 and R had no effect on radiation-induced oxidative stress in liver tissues, but increased TNF-α. Moreover, the co-administration of GaCl3 and R has not intensified radiation-induced alteration of liver function while intensified the decrease of iron. It can be concluded that the effect of radiation on tumor tissue can be potentiated by using GaCl3 , in

  11. Chromosomal mapping of specific DNA gains and losses in solid tumors using comparative genomic hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Schrock, E.; Manoir, S. du; Speicher, M. [National Center for Human Genome Research, Bethesda, MD (United States)] [and others

    1994-09-01

    Comparative genomic hybridization (CGH) is a new molecular cytogenetic technique that is based on two color FISH and quantitative digital imaging microscopy. CGH is used to comprehensively survey tumor genomes for copy number changes and to determine the map position of amplification sites on normal reference chromosomes. CGH was used to analyze 107 different solid tumors, including 16 low grade astrocytomas, 15 recurrent astrocytic tumors, 13 high grade astrocytomas, 13 small cell lung cancers (SCLC), 14 breast cancer samples (7 diploid and 7 aneupoid tumors), 18 chromophobe renal cell carcinomas and 5 seminomas. Tumor DNA was extracted from frozen tissue, autopic material and formalin fixed, paraffin-embedded tissue samples. Our results revealed tumor specific gains and losses of certain chromosomes or chromosomal subregions (e.g., chromosomes 7 and 10 in glioblastomas, chromosomes 3 and 5 in SCLC). Numerous DNA-amplifications were mapped on reference metaphase and prometaphase chromosomes. The frequent amplification of the EGFR gene (malignant gliomas), protooncogenes of the myc family (SCLC) and of c-myc, int-2 and c-erbB2 (breast cancer) was confirmed. Many additional amplification sites, however, were mapped that were not described before. The results of CGH analysis were independently confirmed by means of cytogenetic banding analysis, interphase cytogenetics with region specific DNA-clones, Southern-Blot analysis, DNA-cytometry and studies of loss of heterozygosity.

  12. The Way that PEGyl-DSPC Liposomal Doxorubicin Particles Penetrate into Solid Tumor Tissue

    Directory of Open Access Journals (Sweden)

    Xing Qing Pan

    2006-01-01

    Full Text Available Background: For enhancement of drug effectiveness and reduction of drug toxicity, liposomal drugs have been studied in laboratories and clinics for decades. Although the results obtained from in vitro are encouraging, but the results from in vivo tests were not satisfactory. The main reasons for this situation were that we do not have enough information about the way how liposomal particles penetrating into solid tumor tissue, and what happening to the liposome particles after they got into the tumor tissue. In this paper, we are going to report the results from our observations on the way folic acid targeted and non-targeted PEGyl-DSPC liposomal doxorubicin particles penetrate into solid tumor tissue.Methods: Subcutaneous transplanted murine L1210JF solid tumors in mice were used as a model. PEGyl liposomal doxorubicins were injected through tail venue, and tumor tissue samples were collected at special time points. Cryosections were cut and dried by a fl owing of air after mounted on the slides right away. Then the dried cryosections were stained in water systems; the blood vessel cells were stained with green fluorescent FITC labeled antibody against CD31 antigen; the nuclei of the living cells were stained with a blue fluorescent dye DAPI. Since the whole procedure was carried out in aquatic system, the red color fluorescent liposomal doxorubicin particles remain visible under fl uorescence microscope.Results: Both folate conjugated and non-conjugated PEGyl-DSPC liposomal doxorubicin particles were only leaking out from the broken holes of blood vessels with a special direction and spread out for a limited distance, which was similar to the results showed before, in that observation a latex microsphere sample was used as a model.

  13. Experience of implanting fiducial markers for 504 cases with body malignant solid tumors

    Institute of Scientific and Technical Information of China (English)

    Sujing Zhang; Yu Li; Huijun Xu; Xiao Yang; Liyan Song; Xiaoliang Liu; Hao Wu

    2014-01-01

    Objective:The purpose of the study is to investigate the technical points, ef ects and complications of fiducial marker implantation within target areas before the CyberKnife treatment on body malignant solid tumors. Methods:Five hundred and four cases of patients with body malignant solid tumors accepted fiducial implantation within target areas under CT guidance before the treatment of CyberKnife. Observe the complications and ef ect. Results:Among the 504 cases, 500 cases successful y accepted the implantation (a success rate of 99.2%). 158 patients felt pain at the punctured sites and 3 patients had tachycardia. 33 patients had abdominal pain after the surgery due to a smal amount of bleeding in the needle passage during liver puncturing process. Among the 19 lung cancer patients who accepted lung paracentesis, 1 case had light pneumothorax and 1 case got light haemothorax. Among the 453 patients who accepted liver paracentesis, 6 had fiducial migration. Conclusion:The method of fiducial implantation within target areas before treating body malignant solid tumor with CyberKnife is minimal y invasive and comparatively secure.

  14. The ubiquitin–proteasome system as a molecular target in solid tumors: an update on bortezomib

    Directory of Open Access Journals (Sweden)

    A Milano

    2009-06-01

    Full Text Available A Milano,1 F Perri,2 F Caponigro21Sandro Pitigliani Medical Oncology Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Prato, Italy; 2Head and Neck Medical Oncology Unit, National Tumour institute of Naples, Naples, ItalyAbstract: The ubiquitin–proteasome system has become a promising molecular target in cancer therapy due to its critical role in cellular protein degradation, interaction with cell cycle and apoptosis regulation, and unique mechanism of action. Bortezomib (PS-341 is a potent and specific reversible proteasome inhibitor, which has shown strong in vitro antitumor activity as single agent and in combination with other cytotoxic drugs in a broad spectrum of hematological and solid malignancies. In preclinical studies, bortezomib induced apoptosis of malignant cells through the inhibition of NF-κB and stabilization of pro-apoptotic proteins. Bortezomib also promotes chemo- and radiosensitization of malignant cells in vitro and inhibits tumor growth in murine xenograft models. The proteasome has been established as a relevant target in hematologic malignancies and bortezomib has been approved for the treatment of multiple myeloma. This review summarizes recent data from clinical trials in solid tumors. Keywords: proteasome, bortezomib, NF-κB, clinical studies, solid tumors

  15. Treatment of advanced pancreatic neuroendocrine tumors: potential role of everolimus

    OpenAIRE

    Cen P; Amato RJ

    2012-01-01

    Putao Cen, Robert J AmatoDivision of Oncology, Department of Internal Medicine, University of Texas Health Science Center at Houston (Medical School), Houston, TXAbstract: Pancreatic neuroendocrine tumors (PanNETs) are frequently diagnosed at unresectable stage and remain a medical challenge. Everolimus (RAD001, Afinitor®, Novartis, Basel, Switzerland), an orally administered inhibitor of mammalian target of rapamycin (mTOR), was recently approved by the Food and Drug Administration t...

  16. Advances in the research on the solid propellant properties abroad

    Science.gov (United States)

    Du, Lei; Jiang, Zhirong

    1994-06-01

    The recent research on the mechanical properties, burning behavior and processing technology of solid propellants abroad was reviewed. There are some available results in predicting theoretically the mechanical and rheological properties of solid propellants. In order to reduce the cost and increase the reliability in propellants processing, there is great demand on the design and manufacture of continuous mixer of high efficiency and safety. The research on the thermoplastic elastomers used as a kind of future binder of solid propellants has attracted more and more attention of many relevant experts.

  17. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

    oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer......oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer...

  18. Rationally Repurposing Ruxolitinib (Jakafi®) as a Solid Tumor Therapeutic

    Science.gov (United States)

    Tavallai, Mehrad; Booth, Laurence; Roberts, Jane L.; Poklepovic, Andrew; Dent, Paul

    2016-01-01

    We determined whether the approved myelofibrosis drug ruxolitinib (Jakafi®), an inhibitor of Janus kinases 1/2 (JAK1 and JAK2), could be repurposed as an anti-cancer agent for solid tumors. Ruxolitinib synergistically interacted with dual ERBB1/2/4 inhibitors to kill breast as well as lung, ovarian and brain cancer cells. Knock down of JAK1/2 or of ERBB1/2/3/4 recapitulated on-target drug effects. The combination of (ruxolitinib + ERBB1/2/4 inhibitor) rapidly inactivated AKT, mTORC1, mTORC2, STAT3, and STAT5, and activated eIF2α. In parallel, the drug combination reduced expression of MCL-1, BCL-XL, HSP90, HSP70, and GRP78, and increased expression of Beclin1. Activated forms of STAT3, AKT, or mTOR prevented the drug-induced decline in BCL-XL, MCL-1, HSP90, and HSP70 levels. Over-expression of chaperones maintained AKT/mTOR activity in the presence of drugs and protected tumor cells from the drug combination. Expression of dominant negative eIF2α S51A prevented the increase in Beclin1 expression and protected tumor cells from the drug combination. Loss of mTOR activity was associated with increased ATG13 S318 phosphorylation and with autophagosome formation. Autophagosomes initially co-localized with mitochondria and subsequently with lysosomes. Knock down of Beclin1 suppressed: drug-induced mitophagy; the activation of the toxic BH3 domain proteins BAX and BAK; and tumor cell killing. Knock down of apoptosis-inducing factor (AIF) protected tumor cells from the drug combination, whereas blockade of caspase 9 signaling did not. The drug combination released AIF into the cytosol and increased nuclear AIF: eIF3A co-localization. A 4-day transient exposure of orthotopic tumors to (ruxolitinib + afatinib) profoundly reduced mammary tumor growth over the following 35 days. Re-grown tumors exhibited high levels of BAD S112 phosphorylation and activation of ERK1/2 and NFκB. Our data demonstrate that mitophagy is an essential component of (ruxolitinib

  19. Overview of the manufacturing sequence of the Advanced Solid Rocket Motor

    Science.gov (United States)

    Chapman, John S.; Nix, Michael B.

    1992-01-01

    The manufacturing sequence of NASA's new Advanced Solid Rocket Motor, developed as a replacement of the Space Shuttle's existing Redesigned Solid Rocket Motor, is overviewed. Special attention is given to the case preparation, the propellant mix/cast, the nondestructuve evaluation, the motor finishing, and the refurbishment. The fabrication sequences of the case, the nozzle, and the igniter are described.

  20. Clinicopathologic features and surgical outcome of solid pseudopapillary tumor of the pancreas: analysis of 17 cases

    Directory of Open Access Journals (Sweden)

    Wang Xiao-Guang

    2013-02-01

    Full Text Available Abstract Background We summarize our experience of the diagnosis, surgical treatment, and prognosis of solid pseudopapillary tumors (SPTs. Methods We carried out a retrospective study of clinical data from a series of 17 patients with SPT managed in two hospitals between October 2001 and November 2011. Results All of the 17 patients were female and the average age at diagnosis was 26.6 years (range 11 years to 55 years. The tumor was located in the body or tail in ten patients, the head in five patients, and the neck in two patients. The median tumor size was 5.5 cm (range 2 cm to 10 cm. All 17 patients had curative resections, including seven distal pancreatectomies, five local resections, four pancreaticoduodenectomies, and one central pancreatectomy. Two patients required concomitant splenic vein resection due to local tumor invasion. All patients were alive and disease-free at a median follow-up of 48.2 months (range 2 to 90 months. There were no significant associations between clinicopathologic factors and malignant potential of SPT. Ki-67 was detected in three patients with pancreatic parenchyma invasion. Conclusions The SPT is an infrequent tumor, typically affecting young women without notable symptoms. Surgical resection is justified even in the presence of local invasion or metastases, as patients demonstrate excellent long-term survival. Positive immunoreactivity for Ki-67 may predict the malignant potential of SPTs.

  1. Leveraging Hypoxia-Activated Prodrugs to Prevent Drug Resistance in Solid Tumors

    Science.gov (United States)

    Lindsay, Danika; Garvey, Colleen M.; Mumenthaler, Shannon M.; Foo, Jasmine

    2016-01-01

    Experimental studies have shown that one key factor in driving the emergence of drug resistance in solid tumors is tumor hypoxia, which leads to the formation of localized environmental niches where drug-resistant cell populations can evolve and survive. Hypoxia-activated prodrugs (HAPs) are compounds designed to penetrate to hypoxic regions of a tumor and release cytotoxic or cytostatic agents; several of these HAPs are currently in clinical trial. However, preliminary results have not shown a survival benefit in several of these trials. We hypothesize that the efficacy of treatments involving these prodrugs depends heavily on identifying the correct treatment schedule, and that mathematical modeling can be used to help design potential therapeutic strategies combining HAPs with standard therapies to achieve long-term tumor control or eradication. We develop this framework in the specific context of EGFR-driven non-small cell lung cancer, which is commonly treated with the tyrosine kinase inhibitor erlotinib. We develop a stochastic mathematical model, parametrized using clinical and experimental data, to explore a spectrum of treatment regimens combining a HAP, evofosfamide, with erlotinib. We design combination toxicity constraint models and optimize treatment strategies over the space of tolerated schedules to identify specific combination schedules that lead to optimal tumor control. We find that (i) combining these therapies delays resistance longer than any monotherapy schedule with either evofosfamide or erlotinib alone, (ii) sequentially alternating single doses of each drug leads to minimal tumor burden and maximal reduction in probability of developing resistance, and (iii) strategies minimizing the length of time after an evofosfamide dose and before erlotinib confer further benefits in reduction of tumor burden. These results provide insights into how hypoxia-activated prodrugs may be used to enhance therapeutic effectiveness in the clinic. PMID

  2. Pattern of malignant solid tumors and lymphomas in children in the east delta of Egypt: A five-year study

    OpenAIRE

    HESHAM, MERVAT; ATFY, MERVAT; HASSAN, TAMER; ABDO, MOHAMED; MORSY, SAED; EL MALKY, MOHAMED; LATIF, DALIA ABDEL

    2014-01-01

    Worldwide, the incidence and mortality rates of childhood cancers differ. The study of incidence patterns and survival rates in childhood malignancies is important in aiding in the planning of treatment centers and in obtaining further information with regard to the etiology. Few studies have investigated the survival in cases of childhood solid tumors in Egypt. The aim of the current study was to evaluate the patterns, frequency and outcome of solid tumors and lymphomas in children admitted ...

  3. Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10−9), but was less obvious in other types of solid tumors except for prostate and Epstein–Barr virus (EBV)-positive gastric cancer (FDR<10−3). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection

  4. Outcome for children with metastatic solid tumors over the last four decades.

    Directory of Open Access Journals (Sweden)

    Stephanie M Perkins

    Full Text Available Outcomes for pediatric solid tumors have significantly improved over the last 30 years. However, much of this improvement is due to improved outcome for patients with localized disease. Here we evaluate overall survival (OS for pediatric patients with metastatic disease over the last 40 years.The United States Surveillance, Epidemiology, and End Results (SEER database was used to conduct this study. Patients diagnosed between 0 and 18 years of age with metastatic Ewings sarcoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma or Wilms tumor were included in the analysis.3,009 patients diagnosed between 1973-2010 met inclusion criteria for analysis. OS at 10 years for patients diagnosed between 1973-1979, 1980-1989, 1990-1999 and 2000-2010 was 28.3%, 37.2%, 44.7% and 49.3%, respectively (p<0.001. For patients diagnosed between 2000-2010, 10-year OS for patients with Ewing sarcoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma and Wilms tumor was 30.6%, 54.4%, 29.3%, 27.5%, and 76.6%, respectively, as compared to 13.8%, 25.1%, 13.6%, 17.9% and 57.1%, respectively, for patients diagnosed between 1973-1979. OS for neuroblastoma significantly increased with each decade. For patients with osteosarcoma and Ewing sarcoma, there was no improvement in OS over the last two decades. There was no improvement in outcome for patients with rhabdomyosarcoma or Wilms tumor over the last 30 years.OS for pediatric patients with metastatic solid tumors has significantly improved since the 1970s. However, outcome has changed little for some malignancies in the last 20-30 years. These data underscore the importance of continued collaboration and studies to improve outcome for these patients.

  5. Auto Transplant for High Risk or Relapsed Solid or CNS Tumors

    Science.gov (United States)

    2016-01-22

    Ewing's Family Tumors; Renal Tumors; Hepatoblastoma; Rhabdomyosarcoma; Soft Tissue Sarcoma; Primary Malignant Brain Neoplasms; Retinoblastoma; Medulloblastoma; Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET); Atypical Teratoid/Rhabdoid Tumor (AT/RT); CNS Tumors; Germ Cell Tumors

  6. Comparison of Suspended Solid Separation in Advanced Storm Overflow Structures

    DEFF Research Database (Denmark)

    Larsen, Torben; Sørensen, Morten Steen

    1990-01-01

    This paper describes a laboratory investigation of the separation of suspended solids in a circular weir overflow and a vortex separator. The basic idea is to evaluate the efficiency of a vortical flow in the overflow chamber, and to compare these results with other overflow structures.......This paper describes a laboratory investigation of the separation of suspended solids in a circular weir overflow and a vortex separator. The basic idea is to evaluate the efficiency of a vortical flow in the overflow chamber, and to compare these results with other overflow structures....

  7. INVESTIGATION ON EFFECT OF DRUG DOSING REGIMENTS ON DRUG DELIVERY IN SOLID TUMOR VIA LUMPED PARAMETER MODELING AND ANIMAL EXPERIMENTS

    Institute of Scientific and Technical Information of China (English)

    GAO Ci-xiu; XU Shi-xiong; JIANG Yu-ping; TU Jiang-long

    2009-01-01

    This work aims to investigate the effects of dosing regiments on drug delivery in solid tumors and to validate them with experiments on rats.The lumped parameter models of pharmacokinetics and of drug delivery in tumor were developed to simulate time courses of average drug concentration(Ct)of tumor interstitium in two types of dosing regiments(i.e.,single-shot and triple-shot ones).The two regiments were performed via antitumor drug,hydroxycamptothecin(HCPT),on rats,to measure the drug concentration in the tumor.The simulations of the drug concentration in the tumor of the two dosing regiments were conducted and compared with the experimental data on rats.The coefficients in the models were investigated.It is concluded that the triple-shot method is more effective than that of single-shot injection.The present lumped-parameter model is quantitatively competent for drug delivery in solid tumor.

  8. Preface: Special Topic Section on Advanced Electronic Structure Methods for Solids and Surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Michaelides, Angelos, E-mail: angelos.michaelides@ucl.ac.uk [London Centre for Nanotechnology and Department of Chemistry, University College London, London (United Kingdom); Martinez, Todd J. [Department of Chemistry and the PULSE Institute, Stanford University, Stanford, California 94305, USA and SLAC National Accelerator Laboratory, Menlo Park, California 94025 (United States); Alavi, Ali [Max Planck Institute for Solid State Research, Heisenbergstr. 1, 70569 Stuttgart, Germany and Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW (United Kingdom); Kresse, Georg [Faculty of Physics and Center for Computational Materials Science, Department of Physics, University of Vienna, Sensengasse 8/12, A-1090 Vienna (Austria); Manby, Frederick R. [Centre for Computational Chemistry, School of Chemistry, University of Bristol, Bristol BS8 1TS (United Kingdom)

    2015-09-14

    This Special Topic section on Advanced Electronic Structure Methods for Solids and Surfaces contains a collection of research papers that showcase recent advances in the high accuracy prediction of materials and surface properties. It provides a timely snapshot of a growing field that is of broad importance to chemistry, physics, and materials science.

  9. Preface: Special Topic Section on Advanced Electronic Structure Methods for Solids and Surfaces

    International Nuclear Information System (INIS)

    This Special Topic section on Advanced Electronic Structure Methods for Solids and Surfaces contains a collection of research papers that showcase recent advances in the high accuracy prediction of materials and surface properties. It provides a timely snapshot of a growing field that is of broad importance to chemistry, physics, and materials science

  10. Solid state physics advances in research and applications

    CERN Document Server

    Ehrenreich, Henry

    1994-01-01

    The latest volume in the world renowned Solid State Physics series marks the fruition of Founding Editor David Turnbull''s outstanding tenure as series editor. Volume 47 presents five articles written by leadingexperts on areas including crystal-melt interfacial tension, order-disorder transformation in alloys, brittle matrix composites, surfaces and interfaces, and magnetoresistance.

  11. Electrochemical impedance spectroscopy in solid state ionics: recent advances

    NARCIS (Netherlands)

    Boukamp, Bernard A.

    2004-01-01

    Electrochemical Impedance Spectroscopy (EIS) has become an important research tool in Solid State Ionics. Some new developments are highlighted: new methods of automatic parameter extraction from impedance measurements are briefly discussed. The Kramers–Kronig data validation test presents another p

  12. Therapeutic ureteral occlusion in advanced pelvic malignant tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kinn, A.C.; Ohlsen, H.; Brehmer-Andersson, E.; Brundin, J.

    1986-01-01

    A technique for ureteral occlusion, combining insertion of nylon plugs with injection of polidocanol, is described. The method was used in 15 patients with vesicovaginal fistulas after operation and irradiation for advanced gynecological malignancy, or with severe malfunction and fibrosis of the bladder after radiotherapy for bladder carcinoma. The urinary leakage ceased in 11 patients, was greatly diminished in 2 and was unchanged in 2. Migration of plugs to the renal pelvis was the most serious complication and may have been the cause of pyelonephritis in 1 case. The technique is recommended for patients with a short life expectancy and uncontrolled, distressing leakage of urine.

  13. Amifostine - a radioprotector in locally advanced head and neck tumors

    Energy Technology Data Exchange (ETDEWEB)

    Schoenekaes, K.G.; Wagner, W. [Paracelsus-Strahlenklinik, Osnabrueck (Germany); Prott, F.J. [Muenster Univ. (Germany). Inst. fuer Strahlenonkologie

    1999-11-01

    Purpose: There are some preliminary informations about the beneficial use of amifostine in avoiding side effects in patients with head and neck tumors who underwent radiotherapy. Patients and method: Amifostine was given as daily intravenous application (500 mg) 10 to 15 minutes prior to radiotherapy in 20 patients. The results were compared with another collective of patients which was similar. Results: According to the WHO score mucositis became manifest in 10 patients (Grade I) and 4 patients (Grade II) in the amifostine group vs 9 patients (Grade II), 6 patients (Grade III) and 1 patient (Grade IV) in the control group. Xerostomia has been seen in 15 patients (Grade I) and 5 patients (Grade II) after administration of amifostine. Without the drug 2 patients suffered from xerostomia (Grade I), 8 patients (Grade II) and 8 patients (Grade III), respectively. Administering amifostine had been feasible and non problematic. Only a small rate of toxic side effects like nausea (11%) or emesis (4%) was documented. Conclusions: Amifostine is an effective radioprotector decreasing acute and late side effects in patients with head and neck tumors. (orig.) [German] Zielsetzung: Bisher gibt es nur wenige Informationen ueber den Nutzen von Amifostin bezueglich der Verminderung oder Vermeidung von Nebenwirkungen einer Radiatio bei Patienten mit Tumoren im HNO-Trakt. Patienten und Methode: Amifostin wurde als intravenoese Kurzinfusion mit einer Dosis von 500 mg zehn bis 15 Minuten vor der Bestrahlung bei 20 Patienten appliziert. Die unter Radiatio aufgetretenen Nebenwirkungen wurden nach WHO bzw. nach dem Oral Assessment Guide nach Eilers ausgewertet und mit einem entsprechenden historischen Kollektiv der Klinik verglichen. Ergebnisse: In der Amifostin-Gruppe wurde bei zehn Patienten eine Mukositis Grad I und bei vier Patienten eine Mukositis Grad II nach WHO beobachtet. Grad-III- und Grad-IV-Nebenwirkungen traten nicht auf. In der Kontrollgruppe waren dagegen bei neun

  14. A methodological study on modified comet assay in predicting solid tumor radiosensitivity

    International Nuclear Information System (INIS)

    Objective: To improve the method of 'modified comet assay' in predicting the radiosensitivity of solid tumor. Methods: A single cell suspension from biopsy sample was irradiated on ice with a dose of 5 Gy. The microscope slide was spread with agarose, lysed for 50 minutes, rinsed 3 times in rinse solution, and given electrophoresis for 20 minutes. After being stained with PI, cell images were collected through the microscope and analyzed with Lucia G software (Version 4.6). In order to check system/background errors, every sample was made into control slide and irradiation slide. The end-points were cell DNA contents and tail moment. Results: The factors influencing the results included: (1) Sample was faulty for the biopsy taken from mucosa and no tumor cells were contained. (2) The slides with a high background (induced by necrosis) disturbed the measurement of comet assay. (3) Setting lymphocytes as control to check system errors was very important. (4) To separately collect images of the normal tissue cells and tumor cells from the biopsy sample improved the conformity between the clinical observation and the lab resuit. Conclusions: To increase the correlation between comet assay and clinical response, it is very helpful to set double control for checking system/background errors and to collect images of the normal tissue cells and tumor cells through the microscope, respectively. (authors)

  15. Recognizing and managing the expanded risk of tumor lysis syndrome in hematologic and solid malignancies

    Directory of Open Access Journals (Sweden)

    McBride Ali

    2012-12-01

    Full Text Available Abstract Tumor lysis syndrome (TLS is widely recognized as a serious adverse event associated with the cytotoxic therapies primarily used in hematologic cancers, such as Burkitt lymphoma and acute lymphoblastic leukemia. In recent years, TLS has been more widely observed, due at least in part to the availability of more effective cancer treatments. Moreover, TLS is seen with greater frequency in solid tumors, and particularly in bulky tumors with extensive metastases and tumors with organ or bone marrow involvement. The consequences of TLS include the serious morbidity and high risk of mortality associated with the condition itself. Additionally, TLS may delay or force an alteration in the patient’s chemotherapy regimen. The changing patterns of TLS, as well as its frequency, in the clinical setting, result in unnecessarily high rates of illness and/or fatality. Prophylactic measures are widely available for patients at risk of TLS, and are considered highly effective. The present article discusses the various manifestations of TLS, its risk factors and management options to prevent TLS from occurring.

  16. Therapeutic potential and challenges of Natural killer cells in treatment of solid tumors

    Directory of Open Access Journals (Sweden)

    Andrea eGras Navarro

    2015-04-01

    Full Text Available Natural killer (NK cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for a broad range of cancers. Due to the mode of NK cell killing requiring one–to-one target engagement and site directed release of cytolytic granules, the therapeutic potential of NK cells has been most extensively explored in hematological malignancies. However, their ability to precisely kill antibody coated cells, cancer stem cells (CSCs and genotoxically altered cells, while maintaining tolerance to healthy cells makes them appealing therapeutic effectors for all cancer forms, including metastases. Due to their release of pro-inflammatory cytokines, NK cells may potently reverse the anti-inflammatory tumor microenvironment (TME and augment adaptive immune responses by promoting differentiation, activation and/ or recruitment of accessory immune cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms of subversion of NK cell activity against the tumor and its microenvironment exist. Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the diversity of ligands and receptors is complex, as is their mechanistic foundations in regulating NK cell function. In this article, we review the literature and highlight how the TME manipulates the NK cell phenotypes, genotypes and tropism to evade tumor recognition and elimination. We discuss counter strategies that may be adopted to augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that have been undertaken so far in solid malignancies, critically weighing the challenges and opportunities with this approach.

  17. Advanced solid elements for sheet metal forming simulation

    Science.gov (United States)

    Mataix, Vicente; Rossi, Riccardo; Oñate, Eugenio; Flores, Fernando G.

    2016-08-01

    The solid-shells are an attractive kind of element for the simulation of forming processes, due to the fact that any kind of generic 3D constitutive law can be employed without any additional hypothesis. The present work consists in the improvement of a triangular prism solid-shell originally developed by Flores[2, 3]. The solid-shell can be used in the analysis of thin/thick shell, undergoing large deformations. The element is formulated in total Lagrangian formulation, and employs the neighbour (adjacent) elements to perform a local patch to enrich the displacement field. In the original formulation a modified right Cauchy-Green deformation tensor (C) is obtained; in the present work a modified deformation gradient (F) is obtained, which allows to generalise the methodology and allows to employ the Pull-Back and Push-Forwards operations. The element is based in three modifications: (a) a classical assumed strain approach for transverse shear strains (b) an assumed strain approach for the in-plane components using information from neighbour elements and (c) an averaging of the volumetric strain over the element. The objective is to use this type of elements for the simulation of shells avoiding transverse shear locking, improving the membrane behaviour of the in-plane triangle and to handle quasi-incompressible materials or materials with isochoric plastic flow.

  18. Procalcitonin as diagnostic marker of infection in solid tumors patients with fever

    OpenAIRE

    Vincenzi, B; I. Fioroni; Pantano, F; Angeletti, S; G. Dicuonzo; Zoccoli, A.; Santini, D; Tonini, G

    2016-01-01

    In oncologic patients fever is a non-specific clinical marker of different clinical settings. Procalcitonin (PCT) seems to be the most promising infection marker. We aimed to define the potential role of PCT as an earlier diagnostic marker in patients with fever and solid tumor. This retrospective study enrolled 431 patients. All of them performed hemoculture (HE) and basal PCT assessment (reference laboratory cut-off: ≤0.5 or >0.5 ng/dL) before starting antibiotic therapy. Gram positive (G+)...

  19. Solid pseudopapillary tumor of the pancreas:A review of 553 cases in Chinese literature

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To sum up the clinical and pathological characte- ristics of solid pseudopapillary tumor (SPT) and the experience with it.METHODS: A total of 553 SPT patients reported in Chinese literature between January 1996 and January 2009 were retrospectively reviewed and analyzed. RESULTS: The mean age of the 553 SPT patients included in this review was 27.2 years, and the male to female ratio was 1:8.37. Their symptoms were non-specific, and nearly one third of the patients were asymptomatic. Computed tomography...

  20. Tumor phosphatidylinositol-3-kinase signaling and development of metastatic disease in locally advanced rectal cancer.

    Directory of Open Access Journals (Sweden)

    Anne Hansen Ree

    Full Text Available BACKGROUND: Recognizing EGFR as key orchestrator of the metastatic process in colorectal cancer, but also the substantial heterogeneity of responses to anti-EGFR therapy, we examined the pattern of composite tumor kinase activities governed by EGFR-mediated signaling that might be implicated in development of metastatic disease. PATIENTS AND METHODS: Point mutations in KRAS, BRAF, and PIK3CA and ERBB2 amplification were determined in primary tumors from 63 patients with locally advanced rectal cancer scheduled for radical treatment. Using peptide arrays with tyrosine kinase substrates, ex vivo phosphopeptide profiles were generated from the same baseline tumor samples and correlated to metastasis-free survival. RESULTS: Unsupervised clustering analysis of the resulting phosphorylation of 102 array substrates defined two tumor classes, both consisting of cases with and without KRAS/BRAF mutations. The smaller cluster group of patients, with tumors generating high ex vivo phosphorylation of phosphatidylinositol-3-kinase-related substrates, had a particularly aggressive disease course, with almost a half of patients developing metastatic disease within one year of follow-up. CONCLUSION: High phosphatidylinositol-3-kinase-mediated signaling activity of the primary tumor, rather than KRAS/BRAF mutation status, was identified as a hallmark of poor metastasis-free survival in patients with locally advanced rectal cancer undergoing radical treatment of the pelvic cavity.

  1. Extended postinterventional tumor necrosis-implication for outcome in liver transplant patients with advanced HCC.

    Directory of Open Access Journals (Sweden)

    Arno Kornberg

    Full Text Available BACKGROUND: Locoregional interventional bridging therapy (IBT is an accepted neoadjuvant approach in liver transplant candidates with hepatocellular carcinoma (HCC. However, the prognostic value of IBT in patients with advanced HCC is still undefined. AIM: The aim of this trial was to evaluate the impact of postinterventional tumor necrosis on recurrence-free long-term survival after liver transplantation (LT in patients with HCC, especially focusing on those exceeding the Milan criteria on pretransplant radiographic imaging. PATIENTS AND METHODS: A total of 93 consecutive liver transplant candidates with HCC were included in this trial. In 36 patients, tumors were clinically staged beyond Milan criteria prior LT. Fifty-nine patients underwent IBT by transarterial chemoembolization or radiofrequency ablation pretransplantation. Postinterventional tumor necrosis rate as assessed at liver explant pathology was correlated with outcome post-LT. RESULTS: There was no significant difference in 5-year tumor-free survival rate between the IBT- and the non-IBT subpopulation (78% versus 68%, P=0.25. However, tumor response following IBT (≥ 50% tumor necrosis rate at explant pathology resulted in a significantly better outcome 5 years post-LT (96% than tumor non-response to IBT (<50% tumor necrosis rate at explant pathology; 21%; P<0.001. Five-year recurrence-free survival rate was 80% in Milan Out patients with extended post-IBT tumor necrosis versus 0% in Milan Out patients without tumor response to IBT (P<0.001. None of macromorphological HCC features, but only the absence of increased (18F-fluoro-deoxy-glucose ((18FDG uptake on pretransplant positron emission tomography (PET was identified as independent predictor of postinterventional tumor response (P<0.001. CONCLUSION: Our results implicate that extended postinterventional tumor necrosis promotes recurrence-free long-term survival in patients with HCC beyond standard criteria. Pretransplant PET

  2. The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors.

    Science.gov (United States)

    Willingham, Stephen B; Volkmer, Jens-Peter; Gentles, Andrew J; Sahoo, Debashis; Dalerba, Piero; Mitra, Siddhartha S; Wang, Jian; Contreras-Trujillo, Humberto; Martin, Robin; Cohen, Justin D; Lovelace, Patricia; Scheeren, Ferenc A; Chao, Mark P; Weiskopf, Kipp; Tang, Chad; Volkmer, Anne Kathrin; Naik, Tejaswitha J; Storm, Theresa A; Mosley, Adriane R; Edris, Badreddin; Schmid, Seraina M; Sun, Chris K; Chua, Mei-Sze; Murillo, Oihana; Rajendran, Pradeep; Cha, Adriel C; Chin, Robert K; Kim, Dongkyoon; Adorno, Maddalena; Raveh, Tal; Tseng, Diane; Jaiswal, Siddhartha; Enger, Per Øyvind; Steinberg, Gary K; Li, Gordon; So, Samuel K; Majeti, Ravindra; Harsh, Griffith R; van de Rijn, Matt; Teng, Nelson N H; Sunwoo, John B; Alizadeh, Ash A; Clarke, Michael F; Weissman, Irving L

    2012-04-24

    CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.

  3. The Influence of Frontal Lobe Tumors and Surgical Treatment on Advanced Cognitive Functions.

    Science.gov (United States)

    Fang, Shengyu; Wang, Yinyan; Jiang, Tao

    2016-07-01

    Brain cognitive functions affect patient quality of life. The frontal lobe plays a crucial role in advanced cognitive functions, including executive function, meta-cognition, decision-making, memory, emotion, and language. Therefore, frontal tumors can lead to serious cognitive impairments. Currently, neurosurgical treatment is the primary method to treat brain tumors; however, the effects of the surgical treatments are difficult to predict or control. The treatment may both resolve the effects of the tumor to improve cognitive function or cause permanent disabilities resulting from damage to healthy functional brain tissue. Previous studies have focused on the influence of frontal lesions and surgical treatments on patient cognitive function. Here, we review cognitive impairment caused by frontal lobe brain tumors. PMID:27072331

  4. Advances in sputtered and ion plated solid film lubrication

    Science.gov (United States)

    Spalvins, T.

    1985-01-01

    The glow discharge or ion assisted vacuum deposition techniques, primarily sputtering and ion plating, have rapidly emerged and offer great potential to deposit solid lubricants. The increased energizing of these deposition processes lead to improved adherence and coherence, favorable morphological growth, higher density, and reduced residual stresses in the film. These techniques are of invaluable importance where high precision machines tribo-components require very thin, uniform lubricating films (0.2 m), which do not interface with component tolerances. The performance of sputtered MoS2 films and ion plated Au and Pb films are described in terms of film thickness, coefficient of friction, and wear lives.

  5. Tumor Volume Reduction Rate After Preoperative Chemoradiotherapy as a Prognostic Factor in Locally Advanced Rectal Cancer

    International Nuclear Information System (INIS)

    Purpose: To investigate the prognostic significance of tumor volume reduction rate (TVRR) after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods and Materials: In total, 430 primary LARC (cT3–4) patients who were treated with preoperative CRT and curative radical surgery between May 2002 and March 2008 were analyzed retrospectively. Pre- and post-CRT tumor volumes were measured using three-dimensional region-of-interest MR volumetry. Tumor volume reduction rate was determined using the equation TVRR (%) = (pre-CRT tumor volume − post-CRT tumor volume) × 100/pre-CRT tumor volume. The median follow-up period was 64 months (range, 27–99 months) for survivors. Endpoints were disease-free survival (DFS) and overall survival (OS). Results: The median TVRR was 70.2% (mean, 64.7% ± 22.6%; range, 0–100%). Downstaging (ypT0–2N0M0) occurred in 183 patients (42.6%). The 5-year DFS and OS rates were 77.7% and 86.3%, respectively. In the analysis that included pre-CRT and post-CRT tumor volumes and TVRR as continuous variables, only TVRR was an independent prognostic factor. Tumor volume reduction rate was categorized according to a cutoff value of 45% and included with clinicopathologic factors in the multivariate analysis; ypN status, circumferential resection margin, and TVRR were significant prognostic factors for both DFS and OS. Conclusions: Tumor volume reduction rate was a significant prognostic factor in LARC patients receiving preoperative CRT. Tumor volume reduction rate data may be useful for tailoring surgery and postoperative adjuvant therapy after preoperative CRT.

  6. Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature.

    Directory of Open Access Journals (Sweden)

    Qiong-wen Zhang

    Full Text Available PURPOSE: Tumor associated macrophages (TAMs are considered with the capacity to have both negative and positive effects on tumor growth. The prognostic value of TAM for survival in patients with solid tumor remains controversial. EXPERIMENTAL DESIGN: We conducted a meta-analysis of 55 studies (n = 8,692 patients that evaluated the correlation between TAM (detected by immunohistochemistry and clinical staging, overall survival (OS and disease free survival (DFS. The impact of M1 and M2 type TAM (n = 5 on survival was also examined. RESULTS: High density of TAM was significantly associated with late clinical staging in patients with breast cancer [risk ratio (RR  = 1.20 (95% confidence interval (CI, 1.14-1.28] and bladder cancer [RR = 3.30 (95%CI, 1.56-6.96] and with early clinical staging in patients with ovarian cancer [RR = 0.52 (95%CI, 0.35-0.77]. Negative effects of TAM on OS was shown in patients with gastric cancer [RR = 1.64 (95%CI, 1.24-2.16], breast cancer [RR = 8.62 (95%CI, 3.10-23.95], bladder cancer [RR = 5.00 (95%CI, 1.98-12.63], ovarian cancer [RR = 2.55 (95%CI, 1.60-4.06], oral cancer [RR = 2.03 (95%CI, 1.47-2.80] and thyroid cancer [RR = 2.72 (95%CI, 1.26-5.86],and positive effects was displayed in patients with colorectal cancer [RR = 0.64 (95%CI, 0.43-0.96]. No significant effect was showed between TAM and DFS. There was also no significant effect of two phenotypes of TAM on survival. CONCLUSIONS: Although some modest bias cannot be excluded, high density of TAM seems to be associated with worse OS in patients with gastric cancer, urogenital cancer and head and neck cancer, with better OS in patients with colorectal cancer.

  7. Correlation of primary tumor FDG uptake with histopathologic features of advanced gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hae Won; Won, Kyoung Sook; Song, Bong Il; Kang, Yu Na [Keimyung University Dongsan Medical Center, Daegu (Korea, Republic of)

    2015-06-15

    Histopathologic features could affect the FDG uptake of primary gastric cancer and detection rate on FDG PET/CT. The aim of this study was to evaluate the FDG uptake of primary gastric cancer by correlating it with the histopathologic features of the tumors. Fifty patients with locally advanced gastric adenocarcinoma who were referred for preoperative FDG-PET/CT scans were enrolled in this study. The detection rate of PET/CT and maximum standardized uptake values (SUV{sub max}) of the primary tumor were compared using the WHO, Lauren, Ming and Borrmann classifications and tumor size and location. In 45 of the 50 patients (90 %), the primary gastric tumors were detected by FDG PET/CT. On comparison using the WHO classification, the detection rate and SUV{sub max} of the tubular type were significantly higher than those of the poorly cohesive type. On comparison using the Lauren and Ming classifications, the SUV{sub maxs} of the intestinal type and expanding type were significantly higher than those of the diffuse and infiltrative type, respectively. On comparison using the Borrmann classification and tumor size and location, there was no significant difference in the detection rate and SUV{sub max} of primary gastric tumors. This study demonstrates that the poorly cohesive type according to the WHO classification, diffuse type according to the Lauren classification and infiltrative type according to the Ming classification have low FDG uptake in patients with locally advanced gastric carcinoma. Understanding the relationship between primary tumor FDG uptake and histopathologic features would be helpful in detecting the primary tumor by FDG PET/CT in patients with gastric cancer.

  8. Solid State Ionics Advanced Materials for Emerging Technologies

    Science.gov (United States)

    Chowdari, B. V. R.; Careem, M. A.; Dissanayake, M. A. K. L.; Rajapakse, R. M. G.; Seneviratne, V. A.

    2006-06-01

    Keynote lecture. Challenges and opportunities of solid state ionic devices / W. Weppner -- pt. I. Ionically conducting inorganic solids. Invited papers. Multinuclear NMR studies of mass transport of phosphoric acid in water / J. R. P. Jayakody ... [et al.]. Crystalline glassy and polymeric electrolytes: similarities and differences in ionic transport mechanisms / J.-L. Souquet. 30 years of NMR/NQR experiments in solid electrolytes / D. Brinkmann. Analysis of conductivity and NMR measurements in Li[symbol]La[symbol]TiO[symbol] fast Li[symbol] ionic conductor: evidence for correlated Li[symbol] motion / O. Bohnké ... [et al.]. Transport pathways for ions in disordered solids from bond valence mismatch landscapes / S. Adams. Proton conductivity in condensed phases of water: implications on linear and ball lightning / K. Tennakone -- Contributed papers. Proton transport in nanocrystalline bioceramic materials: an investigative study of synthetic bone with that of natural bone / H. Jena, B. Rambabu. Synthesis and properties of the nanostructured fast ionic conductor Li[symbol]La[symbol]TiO[symbol] / Q. N. Pham ... [et al.]. Hydrogen production: ceramic materials for high temperature water electrolysis / A. Hammou. Influence of the sintering temperature on pH sensor ability of Li[symbol]La[symbol]TiO[symbol]. Relationship between potentiometric and impedance spectroscopy measurements / Q. N. Pham ... [et al.]. Microstructure chracterization and ionic conductivity of nano-sized CeO[symbol]-Sm[symbol]O[symbol] system (x=0.05 - 0.2) prepared by combustion route / K. Singh, S. A. Acharya, S. S. Bhoga. Red soil in Northern Sri Lanka is a natural magnetic ceramic / K. Ahilan ... [et al.]. Neutron scattering of LiNiO[symbol] / K. Basar ... [et al.]. Preparation and properties of LiFePO[symbol] nanorods / L. Q. Mai ... [et al.]. Structural and electrochemical properties of monoclinic and othorhombic MoO[symbol] phases / O. M. Hussain ... [et al.]. Preparation of Zircon (Zr

  9. Expansion Cohorts in First-in-Human Solid Tumor Oncology Trials.

    Science.gov (United States)

    Theoret, Marc R; Pai-Scherf, Lee H; Chuk, Meredith K; Prowell, Tatiana M; Balasubramaniam, Sanjeeve; Kim, Tamy; Kim, Geoffrey; Kluetz, Paul G; Keegan, Patricia; Pazdur, Richard

    2015-10-15

    In 1962, the passage of the Kefauver-Harris Amendment to the 1938 Food, Drug, and Cosmetic Act required that sponsors seeking approval of new drugs demonstrate the drug's efficacy, in addition to its safety, through a formal process that includes "adequate and well-controlled" clinical trials as the basis to support claims of effectiveness. As a result of this amendment, FDA formalized in regulation the definitions of various phases of clinical investigations (i.e., phase I, phase II, and phase III). The clinical drug development paradigm for anticancer drugs intended to support marketing approval has historically followed this "phased" approach with sequential, stand-alone trials, with an increasing number of patients exposed to an investigational drug with each trial in order to fulfill the objectives of that particular stage in development. Increasingly, it is the Office of Hematology and Oncology Products' experience that commercial sponsors of solid tumor oncology drug development programs are amending ongoing phase I trials to add expansion cohorts designed to evaluate study objectives typical of later-phase trials. For investigational anticancer drugs that demonstrate preliminary clinical evidence of substantial antitumor activity early in clinical testing, use of expansion cohorts as a component of the solid tumor oncology drug development pathway, with appropriate measures to mitigate the risks of this approach, may fit in well with the goals and concepts described by FDA's expedited programs for serious conditions. PMID:26473190

  10. Expansion Cohorts in First-in-Human Solid Tumor Oncology Trials.

    Science.gov (United States)

    Theoret, Marc R; Pai-Scherf, Lee H; Chuk, Meredith K; Prowell, Tatiana M; Balasubramaniam, Sanjeeve; Kim, Tamy; Kim, Geoffrey; Kluetz, Paul G; Keegan, Patricia; Pazdur, Richard

    2015-10-15

    In 1962, the passage of the Kefauver-Harris Amendment to the 1938 Food, Drug, and Cosmetic Act required that sponsors seeking approval of new drugs demonstrate the drug's efficacy, in addition to its safety, through a formal process that includes "adequate and well-controlled" clinical trials as the basis to support claims of effectiveness. As a result of this amendment, FDA formalized in regulation the definitions of various phases of clinical investigations (i.e., phase I, phase II, and phase III). The clinical drug development paradigm for anticancer drugs intended to support marketing approval has historically followed this "phased" approach with sequential, stand-alone trials, with an increasing number of patients exposed to an investigational drug with each trial in order to fulfill the objectives of that particular stage in development. Increasingly, it is the Office of Hematology and Oncology Products' experience that commercial sponsors of solid tumor oncology drug development programs are amending ongoing phase I trials to add expansion cohorts designed to evaluate study objectives typical of later-phase trials. For investigational anticancer drugs that demonstrate preliminary clinical evidence of substantial antitumor activity early in clinical testing, use of expansion cohorts as a component of the solid tumor oncology drug development pathway, with appropriate measures to mitigate the risks of this approach, may fit in well with the goals and concepts described by FDA's expedited programs for serious conditions.

  11. MORAb-004 in Treating Young Patients With Recurrent or Refractory Solid Tumors or Lymphoma

    Science.gov (United States)

    2016-01-07

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  12. Engineering phosphopeptide-decorated magnetic nanoparticles as efficient photothermal agents for solid tumor therapy.

    Science.gov (United States)

    Wu, Man; Guo, Qiaoyan; Xu, Feng; Liu, Shujun; Lu, Xuehong; Wang, Jing; Gao, Hongwen; Luo, Ping

    2016-08-15

    Due to the high therapeutic efficiency and minimum damage towards normal tissues, phototherapy has drawn a great deal of attention in recent decades. Herein, we reported the synthesis of novel phosphopeptide-decorated magnetic nanoparticles (peptide-Fe3O4 nanoparticles), and their usages in photothermal therapy against solid tumor. By using a classical coprecipitation method and a facile ligand exchange route, these peptide-Fe3O4 nanoparticles were prepared with inexpensive inhesion. Upon the irradiation of a near-infrared (NIR) light, these nanoagents exhibited great photothermal effect with high photo-stability. In vitro biocompatibility studies of these peptide-Fe3O4 nanoparticles indicated their low cytotoxicity, negligible hemolysis, and no effect on blood coagulation. As expected, 4T1 murine breast cancer cells could be effectively damaged by these light-mediated nanoagents. Significantly, animal experiments demonstrated that these nanoagents held great solid tumor ablation effect with the assistance of a NIR laser irradiation. Additional studies focused on the long-term toxicity of these nanoagents indicated their high bio-compatibility. Thus, these peptide-Fe3O4 nanoparticles could bring more opportunities to a new generation of photothermal agents in the field of biomedicine. PMID:27214146

  13. Neoadjuvant Chemotherapy in Locally Advanced and Borderline Resectable Nonsquamous Sinonasal Tumors (Esthesioneuroblastoma and Sinonasal Tumor with Neuroendocrine Differentiation

    Directory of Open Access Journals (Sweden)

    Vijay M. Patil

    2016-01-01

    Full Text Available Introduction. Sinonasal tumors are chemotherapy responsive which frequently present in advanced stages making NACT a promising option for improving resection and local control in borderline resectable and locally advanced tumours. Here we reviewed the results of 25 such cases treated with NACT. Materials and Methods. Sinonasal tumor patients treated with NACT were selected for this analysis. These patients received NACT with platinum and etoposide for 2 cycles. Patients who responded and were amenable for gross total resection underwent surgical resection and adjuvant CTRT. Those who responded but were not amenable for resection received radical CTRT. Patients who progressed on NACT received either radical CTRT or palliative radiotherapy. Results. The median age of the cohort was 42 years (IQR 37–47 years. Grades 3-4 toxicity with NACT were seen in 19 patients (76%. The response rate to NACT was 80%. Post-NACT surgery was done in 12 (48% patients and radical chemoradiation in 9 (36% patients. The 2-year progression free survival and overall survival were 75% and 78.5%, respectively. Conclusion. NACT in sinonasal tumours has a response rate of 80%. The protocol of NACT followed by local treatment is associated with improvement in outcomes as compared to our historical cohort.

  14. Advanced impedance modeling of solid oxide electrochemical cells

    DEFF Research Database (Denmark)

    Graves, Christopher R.; Hjelm, Johan

    2014-01-01

    Impedance spectroscopy is a powerful technique for detailed study of the electrochemical and transport processes that take place in fuel cells and electrolysis cells, including solid oxide cells (SOCs). Meaningful analysis of impedance measurements is nontrivial, however, because a large number of...... modeling parameters are fit to the many processes which often overlap in the same frequency ranges. Also, commonly used equivalent circuit (EC) models only provide zero-dimensional (0-D) approximations of the processes of the two electrodes, electrolyte and gas transport. Employing improved analytical...... electrode and 2-D gas transport models which have fewer unknown parameters for the same number of processes, (ii) use of a new model fitting algorithm, “multi-fitting”, in which multiple impedance spectra are fit simultaneously with parameters linked based on the variation of measurement conditions, (iii...

  15. Solid state physics advances in research and applications

    CERN Document Server

    Turnbull, David

    1991-01-01

    The explosion of the science of mesoscopic structures is having a great impact on physics and electrical engineering because of the possible applications of these structures in microelectronic and optoelectronic devices of the future. This volume of Solid State Physics consists of two comprehensive and authoritative articles that discuss most of the physical problems that have so far been identified as being of importance in semiconductor nanostructures. Much of the volume is tutorial in characture--while at the same time time presenting current and vital theoretical and experimental results and a copious reference list--so it will be essential reading to all those taking a part in the research and development of this emerging technology.

  16. Advanced impedance modeling of solid oxide electrochemical cells

    DEFF Research Database (Denmark)

    Graves, Christopher R.; Hjelm, Johan

    2014-01-01

    Impedance spectroscopy is a powerful technique for detailed study of the electrochemical and transport processes that take place in fuel cells and electrolysis cells, including solid oxide cells (SOCs). Meaningful analysis of impedance measurements is nontrivial, however, because a large number...... techniques to provide good guesses for the modeling parameters, like transforming the impedance data to the distribution of relaxation times (DRT), together with experimental parameter sensitivity studies, is the state-of-the-art approach to achieve good EC model fits. Here we present new impedance modeling...... electrode and 2-D gas transport models which have fewer unknown parameters for the same number of processes, (ii) use of a new model fitting algorithm, “multi-fitting”, in which multiple impedance spectra are fit simultaneously with parameters linked based on the variation of measurement conditions, (iii...

  17. Fate of orally administered {sup 15}N-labeled polyamines in rats bearing solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Masaki; Samejima, Keijiro; Goda, Hitomi; Niitsu, Masaru [Josai Univ., Sakado, Saitama (Japan). Faculty of Pharmaceutical Sciences; Xu Yongji [Qingdao Univ. of Science and Technology (China). Inst. of Chemical and Molecular Technology; Takahashi, Masakazu [Sasaki Inst., Tokyo (Japan); Hashimoto, Yoshiyuki [Kyoritsu Coll. of Pharmacy, Tokyo (Japan)

    2003-03-01

    We studied absorption, distribution, metabolism, and excretion of polyamines (putrescine, spermidine, and spermine) in the gastrointestinal tract using {sup 15}N-labeled polyamines as tracers and ionspray ionization mass spectrometry (IS-MS). The relatively simple protocol using rats bearing solid tumors provided useful information. Three {sup 15}N-labeled polyamines that were simultaneously administered were absorbed equally from gastrointestinal tract, and distributed within tissues at various concentrations. The uptake of {sup 15}N-spermidine seemed preferential to that of {sup 15}N-spermine since the concentrations of {sup 15}N-spermidine in the liver and tumors were higher, whereas those of {sup 15}N-spermine were higher in the kidney, probably due to the excretion of excess extracellular spermine. Most of the absorbed {sup 15}N-putrescine seemed to be lost, suggesting blood and tissue diamine oxidase degradation. Concentrations of {sup 15}N-spermidine and {sup 15}N-spermine in the tumor were low. We also describe the findings from two rats that were administered with {sup 15}N-spermine. The tissue concentrations of {sup 15}N-spermine were unusually high, and significant levels of {sup 15}N-spermidine were derived from {sup 15}N-spermine in these animals. (author)

  18. A Pancreatic Solid Pseudo-Papillary Tumor Detected After Abdominal Injury

    Science.gov (United States)

    Ishii, Atsushi; Yoshimura, Kazuko; Ideguchi, Hiroshi; Hirose, Shinichi

    2013-01-01

    Solid pseudo-papillary tumor (SPT) of the pancreas is a relatively benign tumor that is more frequently reported in females. Most patients usually present with abdominal pain or mass. We experienced the girl who identified SPT with the injury. We diagnosed SPT in a previously healthy 14-year-old Asian girl after abdominal injury. She experienced upper abdominal pain and vomiting after being hit by a basketball. Blood examination revealed a high serum amylase level. Abdominal radiography indicated abnormal bowel gases. Contrast-enhanced computed tomography revealed a smooth, peripheral and unilocular mass approximately 55 mm in diameter in the pancreatic tail. Based on these observations, acute pancreatitis complicated by a pancreatic mass was initially diagnosed. Therapy for acute pancreatitis was instituted, while we simultaneously investigated the mass. Levels of tumor markers were not profoundly elevated in serum. Dynamic contrast-enhanced magnetic resonance imaging (MRI) revealed moderate and gradual increase in contrast-enhanced imaging, consistent with findings of SPT of the pancreas. We thus elected surgical resection for her. Pathological examination of the surgical specimen confirmed our diagnosis of SPT. SPT of the pancreas should be considered as a differential diagnosis of acute abdomen disorders, especially in instances after minor abdominal injuries in young women, and diagnoses must be confirmed with MRIs.

  19. Circulating lymphangiogenic growth factors in gastrointestinal solid tumors, could they be of any clinical significance?

    Institute of Scientific and Technical Information of China (English)

    Theodore D Tsirlis; George Papastratis; Kyriaki Masselou; Christos Tsigris; Antonis Papachristodoulou; Alkiviadis Kostakis; Nikolaos I Nikiteas

    2008-01-01

    Metastasis is the principal cause of cancer mortality,with the lymphatic system being the first route of tumor dissemination.The glycoproteins VEGF-C and VEGF-D are members of the vascular endothelial growth factor (VEGF)family,whose role has been recently recognized as lymphatic system regulators during embryogenesis and in pathological processes such as inflammation,lymphatic system disorders and malignant tumor metastasis.They are ligands for the VEGFR-3 receptor on the membrane of the lymphatic endothelial cell,resulting in dilatation of existing lymphatic vessels as well as in vegetation of new ones (lymphangiogenesis).Their determination is feasible in the circulating blood by immunoabsorption and in the tissue specimen by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR).Experimental and clinicopathological studies have linked the VEGF-C,VEGF-D/VEGFR3 axis to lymphatic spread as well as to the clinical outcome in several human solid tumors.The majority of these data are derived from surgical specimens and malignant cell series,rendering their clinical application questionable,due to subjectivity factors and post-treatment quantification.In an effort to overcome these drawbacks,an alternative method of immunodetection of the circulating levels of these molecules has been used in studies on gastric,esophageal and colorectal cancer.Their results denote that quantification of VEGF-C and VEGF-D in blood samples could serve as lymph node metastasis predictive biomarkers and contribute to preoperative staging of gastrointestinal malignancies.

  20. Emergency surgery due to complications during molecular targeted therapy in advanced gastrointestinal stromal tumors (GIST)

    International Nuclear Information System (INIS)

    Aim. The aim of the study was to assess the frequency and results of disease/treatment-related emergency operations during molecular targeted therapy of advanced gastrointestinal stromal tumors (GISTs). Methods. We analyzed emergency operations in patients with metastatic/inoperable GISTs treated with 1st-line imatinib - IM (group I: 232 patients; median follow-up time 31 months) and 2nd-line sunitinib - SU (group II: 43 patients; median follow-up 13 months; 35 patients in trial A6181036) enrolled into the Polish Clinical GIST Registry. Results. In group I 3 patients (1.3%) underwent emergency surgery due to disease/treatment related complications: one due to bleeding from a ruptured liver tumor (1 month after IM onset) and two due to bowel perforation on the tumor with subsequent intraperitoneal abscess (both 2 months after IM onset). IM was restarted 5-8 days after surgery and no complications in wound healing were observed. In group II 4 patients (9.5%) underwent emergency operations due to disease/treatment related complications: three due to bowel perforations on the tumor (2 days, 20 days and 10 months after SU onset; 1 subsequent death) and one due to intraperitoneal bleeding from ruptured, necrotic tumor (3.5 months after SU start). SU was restarted 12-18 days after surgery and no complications in wound healing were observed. Conclusions. Emergency operations associated with disease or therapy during imatinib treatment of advanced GISTs are rare. The frequency of emergency operations during sunitinib therapy is considered to be higher than during first line therapy with imatinib which may be associated with more advanced and more resistant disease or to the direct mechanism of sunitinib action, i.e. combining cytotoxic and antiangiogenic activity and thus leading to dramatic tumor response. Molecular targeted therapy in GISTs should always be conducted in cooperation with an experienced surgeon. (authors)

  1. Cancer incidence in atomic bomb survivors. Part II: Solid tumors, 1958-1987

    International Nuclear Information System (INIS)

    This report presents, for the first time, comprehensive data on the incidence of solid cancer and risk estimates for A-bomb survivors in the extended Life Span Study (LSS-E85) cohort. Among 79,972 individuals, 8613 first primary solid cancers were diagnosed between 1958 and 1987. As part of the standard registration process of the Hiroshima and Nagasaki tumor registries, cancer cases occurring among members of the LSS-E85 cohort were identified using a computer linkage system supplemented by manual searches. Special efforts were made to ensure complete case ascertainment, data quality and data consistency in the two cities. For all sites combined, 75% of the cancers were verified histologically, 6% were diagnosed by direct observation, 8% were based on a clinical diagnosis, and 12.6% were ascertained by death certificate only. A standard set of analyses was carried out for each of the organs and organ systems considered. Depending on the cancer site, Dosimetry System 1986 (DS86) organ or kerma doses were used for computing risk estimates. Analyses were based on a general excess relative risk model (the background rate times one plus the excess relative risk). Analyses carried out for each site involved fitting the background model with no dose effect, a linear dose-response model with no effect modifiers, a linear-quadratic dose-response model with no effect modifiers, and a series of linear dose-response models that included each of the covariates (sex, age at exposure, time since exposure, attained age and city) individually as effect modifiers. Because the tumor registries ascertain cancers in the registry catchment areas only, an adjustment was made for the effects of migration. In agreement with prior LSS findings, a statistically significant excess risk for all solid cancers was demonstrated. 116 refs., 8 figs., 78 tabs

  2. Simvastatin With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors

    Science.gov (United States)

    2016-04-11

    Retinoblastoma; Clear Cell Sarcoma; Renal Cell Carcinoma; Rhabdoid Tumor; Wilms Tumor; Hepatoblastoma; Neuroblastoma; Germ Cell Tumors; Ewings Sarcoma; Non-rhabdomyosarcoma Soft Tissue Sarcoma; Osteosarcoma; Rhabdomyosarcoma

  3. Tenascin-W is a better cancer biomarker than tenascin-C for most human solid tumors

    Directory of Open Access Journals (Sweden)

    Brellier Florence

    2012-09-01

    Full Text Available Abstract Background Tenascins are large glycoproteins found in the extracellular matrix of many embryonic and adult tissues. Tenascin-C is a well-studied biomarker known for its high overexpression in the stroma of most solid cancers. Tenascin-W, the least studied member of the family, is highly expressed in the stroma of colon and breast tumors and in gliomas, but not in the corresponding normal tissues. Other solid tumors have not been analyzed. The present study was undertaken to determine whether tenascin-W could serve as a cancer-specific extracellular matrix protein in a broad range of solid tumors. Methods We analyzed the expression of tenascin-W and tenascin-C by immunoblotting and by immunohistochemistry on multiple frozen tissue microarrays of carcinomas of the pancreas, kidney and lung as well as melanomas and compared them to healthy tissues. Results From all healthy adult organs tested, only liver and spleen showed detectable levels of tenascin-W, suggesting that tenascin-W is absent from most human adult organs under normal, non-pathological conditions. In contrast, tenascin-W was detectable in the majority of melanomas and their metastases, as well as in pancreas, kidney, and lung carcinomas. Comparing lung tumor samples and matching control tissues for each patient revealed a clear overexpression of tenascin-W in tumor tissues. Although the number of samples examined is too small to draw statistically significant conclusions, there seems to be a tendency for increased tenascin-W expression in higher grade tumors. Interestingly, in most tumor types, tenascin-W is also expressed in close proximity to blood vessels, as shown by CD31 co-staining of the samples. Conclusions The present study extends the tumor biomarker potential of tenascin-W to a broad range of solid tumors and shows its accessibility from the blood stream for potential therapeutic strategies.

  4. Applied solid state science advances in materials and device research 3

    CERN Document Server

    Wolfe, Raymond

    2013-01-01

    Applied Solid State Science: Advances in Materials and Device Research, Volume 3 covers reviews that are directly related to the two devices which are the epitome of applied solid state science - the transistor and the laser. The book discusses the physics of multilayer-gate IGFET memories; the application of the transient charge technique in drift velocity; and trapping in semiconductors and in materials used in xerography, nuclear particle detectors, and space-charge-limited devices; as well as thin film transistors. The text describes the manipulation of laser beams in solids and discusses

  5. Advances in Fmoc solid-phase peptide synthesis.

    Science.gov (United States)

    Behrendt, Raymond; White, Peter; Offer, John

    2016-01-01

    Today, Fmoc SPPS is the method of choice for peptide synthesis. Very-high-quality Fmoc building blocks are available at low cost because of the economies of scale arising from current multiton production of therapeutic peptides by Fmoc SPPS. Many modified derivatives are commercially available as Fmoc building blocks, making synthetic access to a broad range of peptide derivatives straightforward. The number of synthetic peptides entering clinical trials has grown continuously over the last decade, and recent advances in the Fmoc SPPS technology are a response to the growing demand from medicinal chemistry and pharmacology. Improvements are being continually reported for peptide quality, synthesis time and novel synthetic targets. Topical peptide research has contributed to a continuous improvement and expansion of Fmoc SPPS applications. PMID:26785684

  6. Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia

    Science.gov (United States)

    2014-11-04

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Gonadotroph Adenoma; Pituitary Basophilic Adenoma; Pituitary Chromophobe Adenoma; Pituitary Eosinophilic Adenoma; Prolactin Secreting Adenoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Pituitary Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; TSH Secreting Adenoma; Unspecified Childhood Solid Tumor, Protocol Specific

  7. Imaging features of solid pseudopapillary tumor of the pancreas on multi-detector row computed tomography

    Institute of Scientific and Technical Information of China (English)

    Deng-Bin Wang; Qing-Bing Wang; Wei-Min Chai; Ke-Min Chen; Xia-Xing Deng

    2009-01-01

    AIM:To retrospectively analyze the imaging features of solid-pseudopapillary tumors (SPTs) of the pancreas on multi-detector row computed tomography (MDCT) and define the imaging findings suggestive of malignant potential.METHODS: A total of 24 consecutive cases with surgically and pathologically confirmed SPTs of the pancreas underwent preoperative abdominal MDCT studies in our hospital. All axial CT images, CT angiographic images, and coronally and sagittally reformed images were obtained. The images were retrospectively reviewed at interactive picture archiving and communication system workstations. RESULTS: Of the 24 cases of SPTs, 11 cases (45.8%) occurred in the pancreatic head and seven (29.1%) in the tail. Eighteen were pathologically diagnosed as benign and six as malignant. MDCT diagnosis of SPTs was well correlated with the surgical and pathological results (Kappa = 0.6, P < 0.05). The size of SPTs ranged from 3 to 15 cm (mean, 5.8 cm). When the size of the tumor was greater than 6 cm (including 6cm), the possibilities of vascular (8 vs 1) and capsular invasion (9 vs 0) increased significantly ( P < 0.05). Two pathologically benign cases with vascular invasion and disrupted capsule on MDCT presented with local recurrence and hepatic metastases during follow-up about 1 year after the resection of the primary tumors.CONCLUSION: Vascular and capsular invasion with superimposed spread into the adjacent pancreatic parenchyma and nearby structures in SPTs of the pancreas can be accurately revealed by MDCTpreoperatively. These imaging findings are predictive of the malignant potential associated with the aggressive behavior of the tumor, even in the pathologically benign cases.

  8. SU-E-QI-20: A Review of Advanced PET and CT Image Features for the Evaluation of Tumor Response

    Energy Technology Data Exchange (ETDEWEB)

    Lu, W [University of Maryland School of Medicine, Baltimore, MD (United States)

    2014-06-15

    Purpose: To review the literature in using quantitative PET and CT image features for the evaluation of tumor response. Methods: We reviewed and summarized more than fifty papers that use advanced, quantitative PET/CT image features for the evaluation of tumor response. We also discussed future works on extracting disease-specific features, combining multiple and complementary features in response modeling, delineating tumor in multimodality images, and exploring biological explanations of these advanced features. Results: Advanced PET image features considering spatial information, such as tumor volume, tumor shape, total glycolytic volume, histogram distance, and texture features (characterizing spatial distribution of FDG uptake) have been found more informative than the traditional SUVmax for the prediction of tumor response. Advanced CT features, including volumetric, attenuation, morphologic, structure, and texture descriptors, have also been found advantage over the traditional RECIST and WHO criteria in certain tumor types. Conclusions: Advanced, quantitative FDG PET/CT image features have been shown promising for the evaluation of tumor response. With the emerging multi-modality imaging performed at multiple time points for each patient, it becomes more important to analyze the serial images quantitatively, select and combine both complementary and contradictory information from various sources, for accurate and personalized evaluation of tumor response to therapy.

  9. Incidence of anemia in patients diagnosed with solid tumors receiving chemotherapy, 2010–2013

    Directory of Open Access Journals (Sweden)

    Xu H

    2016-04-01

    Full Text Available Hairong Xu,1 Lanfang Xu,2 John H Page,1 Kim Cannavale,2 Olivia Sattayapiwat,2 Roberto Rodriguez,3 Chun Chao2 1Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA; 2Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA; 3Department of Hematology Oncology, Los Angeles Medical Center, Kaiser Permanente Southern California, Psadena, CA, USA Purpose: The purpose of this study was to evaluate and characterize the risk of anemia during the course of chemotherapy among patients with five common types of solid tumors. Patients and methods: Patients diagnosed with incident cancers of breast, lung, colon/rectum, stomach, and ovary who received chemotherapy were identified from Kaiser Permanente Southern California Health Plan (2010–2012. All clinical data were collected from the health plan’s electronic medical records. Incidence proportions of patients developing anemia and 95% confidence intervals were calculated overall and by anemia severity and type, as well as by stage at cancer diagnosis, and by chemotherapy regimen and cycle. Results: A total of 4,426 patients who received chemotherapy were included. Across cancers, 3,962 (89.5% patients developed anemia during the course of chemotherapy (normocytic 85%, macrocytic 10%, microcytic 5%; normochromic 47%, hyperchromic 44%, hypochromic 9%. The anemia grades were distributed as follows: 58% were grade 1, 34% grade 2, 8% grade 3, and <1% grade 4. The incidence of grade 2+ anemia ranged from 26.3% in colorectal cancer patients to 59.2% in ovarian cancer patients. Incidence of grade 2+ anemia increased from 29% in stage I to 49% in stage IV. Incidence of grade 2+ anemia varied from 18.2% in breast cancer patients treated with cyclophosphamide + docetaxel regimen to 59.7% in patients with ovarian cancer receiving carboplatin + paclitaxel regimen. Conclusion: The incidence of moderate-to-severe anemia (hemoglobin <10 g/dL remained considerably

  10. Risk of solid tumors and hematological malignancy in persons with Turner and Klinefelter syndromes: A national cohort study.

    Science.gov (United States)

    Ji, Jianguang; Zöller, Bengt; Sundquist, Jan; Sundquist, Kristina

    2016-08-15

    The risk of solid and hematological malignancy in patients with Turner syndrome, characterized by X chromosome monosomy in women, and Klinefelter syndrome, characterized with two and more X chromosomes in men, is not well established, but such evidence may have etiological implications on cancer development. We identified a total of 1,409 women with Turner syndrome and 1,085 men with Klinefelter syndrome from the Swedish Hospital Discharge and Outpatient Register. These individuals were further linked to the Swedish Cancer Register to examine the standardized incidence ratios (SIRs) of cancer using the general population without Turner and Klinefelter syndromes as reference. The overall risk of cancer was 1.34 for women with Turner syndrome; it was increased only for solid tumors. For a specific type of tumor, the risk of melanoma and central nervous system tumor was significantly increased. For persons with Klinefelter syndrome, the risk of solid tumors was decreased (SIR = 0.66), whereas the risk of hematological malignancy was increased (SIR = 2.72). Non-Hodgkin lymphoma and leukemia showed an increased SIR of 3.02 and 3.62, respectively. Our study supported the hypothesis that X chromosome plays an important role in the etiology of solid tumors. The underlying mechanisms for the increased incidence of non-Hodgkin lymphoma and leukemia in persons with Klinefelter syndrome need to be investigated further.

  11. Risk of solid tumors and hematological malignancy in persons with Turner and Klinefelter syndromes: A national cohort study.

    Science.gov (United States)

    Ji, Jianguang; Zöller, Bengt; Sundquist, Jan; Sundquist, Kristina

    2016-08-15

    The risk of solid and hematological malignancy in patients with Turner syndrome, characterized by X chromosome monosomy in women, and Klinefelter syndrome, characterized with two and more X chromosomes in men, is not well established, but such evidence may have etiological implications on cancer development. We identified a total of 1,409 women with Turner syndrome and 1,085 men with Klinefelter syndrome from the Swedish Hospital Discharge and Outpatient Register. These individuals were further linked to the Swedish Cancer Register to examine the standardized incidence ratios (SIRs) of cancer using the general population without Turner and Klinefelter syndromes as reference. The overall risk of cancer was 1.34 for women with Turner syndrome; it was increased only for solid tumors. For a specific type of tumor, the risk of melanoma and central nervous system tumor was significantly increased. For persons with Klinefelter syndrome, the risk of solid tumors was decreased (SIR = 0.66), whereas the risk of hematological malignancy was increased (SIR = 2.72). Non-Hodgkin lymphoma and leukemia showed an increased SIR of 3.02 and 3.62, respectively. Our study supported the hypothesis that X chromosome plays an important role in the etiology of solid tumors. The underlying mechanisms for the increased incidence of non-Hodgkin lymphoma and leukemia in persons with Klinefelter syndrome need to be investigated further. PMID:27061708

  12. Recent advances in secondary ion mass spectrometry of solid acid catalysts : Large zeolite crystals under bombardment

    NARCIS (Netherlands)

    Hofmann, Jan P.; Rohnke, Marcus; Weckhuysen, Bert M.

    2014-01-01

    This Perspective aims to inform the heterogeneous catalysis and materials science community about the recent advances in Time-of-Flight-Secondary Ion Mass Spectrometry (ToF-SIMS) to characterize catalytic solids by taking large model H-ZSM-5 zeolite crystals as a showcase system. SIMS-based techniqu

  13. Advances in the Treatment of Pancreatic Neuroendocrine Tumors (pNETs)

    OpenAIRE

    Strosberg, Jonathan

    2013-01-01

    Recent clinical trials have led to significant advancements in treatment options for metastatic neuroendocrine tumors of the pancreas. Sunitinib and everolimus have been approved by the Food and Drug Administration for treatment of progressive pancreatic NETs based on phase III trial data demonstrating improvements in progression-free survival. Cytotoxic drugs such as temozolomide and capecitabine have been associated with high radiographic response rates; however data derives primarily from ...

  14. Development of solid phase immunoradiometric assay for determination of carcinoembryonic antigen as a tumor marker

    International Nuclear Information System (INIS)

    Development of solid phase coated tube immunoradiometric assay for estimation of carcinoembryonic antigen (CEA) was the aim of the present study. Labeling of CEA was carried out using Ch-T and iodogen as oxidizing agents and 125I. The tracers were used to test the presence of antibodies produced by immunization. Production of polyclonal antibody was carried out through immunization of four mice. After purification step, the tubes were coated by purified polyclonal antibodies. Immunoradiometric that system was performed using the commercial IZOTOP 125I-anti hCEA tracer then the validity studies were carried out. The results show that the local coated tubes made the assay is more than sufficient to fulfill the clinical requirement of CEA as a tumor marker. (author)

  15. Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia

    Science.gov (United States)

    2014-06-16

    Childhood Acute Promyelocytic Leukemia (M3); Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Juvenile Myelomonocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  16. Pancreatic neuroendocrine tumor and solid-pseudopapillary neoplasm: Key immunohistochemical profiles for differential diagnosis

    Science.gov (United States)

    Ohara, Yusuke; Oda, Tatsuya; Hashimoto, Shinji; Akashi, Yoshimasa; Miyamoto, Ryoichi; Enomoto, Tsuyoshi; Satomi, Kaishi; Morishita, Yukio; Ohkohchi, Nobuhiro

    2016-01-01

    AIM To reveal better diagnostic markers for differentiating neuroendocrine tumor (NET) from solid-pseudopapillary neoplasm (SPN), focusing primarily on immunohistochemical analysis. METHODS We reviewed 30 pancreatic surgical specimens of NET (24 cases) and SPN (6 cases). We carried out comprehensive immunohistochemical profiling using 9 markers: Synaptophysin, chromogranin A, pan-cytokeratin, E-cadherin, progesterone receptor, vimentin, α-1-antitrypsin, CD10, and β-catenin. RESULTS E-cadherin staining in NETs, and nuclear labeling of β-catenin in SPNs were the most sensitive and specific markers. Dot-like staining of chromogranin A might indicate the possibility of SPNs rather than NETs. The other six markers were not useful because their expression overlapped widely between NETs and SPNs. Moreover, two cases that had been initially diagnosed as NETs on the basis of their morphological features, demonstrated SPN-like immunohistochemical profiles. Careful diagnosis is crucial as we actually found two confusing cases showing disagreement between the tumor morphology and immunohistochemical profiles. CONCLUSION E-cadherin, chromogranin A, and β-catenin were the most useful markers which should be employed for differentiating between NET and SPN.

  17. Investigation of the effects of long-term infusion of 125I-iododeoxyuridine on tumor growth in mice (solid mouse tumor sarcoma-180)

    International Nuclear Information System (INIS)

    The present experiments were designed to test the therapeutic qualification of 125I incorporated in DNA of tumor cells. The tumor-host system used was the solid mouse tumor sarcoma-180 growing on female albino mice (NMRI). A device was built which makes it possible to intravenously infuse tumor bearing mice with solutions of 125IUdR for several weeks. Three or, respectively, 5 days before the onset of the infusions the mice were inocculated into the right hind leg with 3x105 tumor cells in 0.1 ml physiological salt solution. The total activity administered per mouse was 100 μCi infused during a period of 10 days. After termination of the infusions tumor sizes and retained radioactivities were measured every 5 days until death of the animals occured. In comparison with tumors of control animals tumors of mice infused with 125IUdR showed a mean retardation in growth of about 27% of the volumes of control tumors during the total period of post-infusion observation (25 days). Extension of life expectancy and an increase of the rate of final tumor regression did not occur. Likewise, no significant differences were observed between tumors which were 3 or 5 days old on the first day of infusion. After termination of the infusions the residual whole-body radioactivity per mouse was about 1% of the total activity infused per animal. This was in good agreement with calculations considering rates of incorporation and excretion and confirmed earlier assumptions that only about 5% of the administered IUdR is incorporated initially. The number further confirmed that, during the first 10 days after incorporation, the daily loss of activity - due to cell death - is about 30%. Control animals without tumors showed a faster decrease of incorporated activity or, respectively, loss of cells than tumor bearing mice. This difference could in part be explained by an exhaution of the short-lived cell populations of the reticulo-endothelial system of tumor bearing animals. (orig./MG)

  18. Immunogenicity of murine solid tumor models as a defining feature of in vivo behavior and response to immunotherapy.

    Science.gov (United States)

    Lechner, Melissa G; Karimi, Saman S; Barry-Holson, Keegan; Angell, Trevor E; Murphy, Katherine A; Church, Connor H; Ohlfest, John R; Hu, Peisheng; Epstein, Alan L

    2013-01-01

    Immune profiling has been widely used to probe mechanisms of immune escape in cancer and identify novel targets for therapy. Two emerging uses of immune signatures are to identify likely responders to immunotherapy regimens among individuals with cancer and to understand the variable responses seen among subjects with cancer in immunotherapy trials. Here, the immune profiles of 6 murine solid tumor models (CT26, 4T1, MAD109, RENCA, LLC, and B16) were correlated to tumor regression and survival in response to 2 immunotherapy regimens. Comprehensive profiles for each model were generated using quantitative reverse transcriptase polymerase chain reaction, immunohistochemistry, and flow cytometry techniques, as well as functional studies of suppressor cell populations (regulatory T cells and myeloid-derived suppressor cells), to analyze intratumoral and draining lymphoid tissues. Tumors were stratified as highly or poorly immunogenic, with highly immunogenic tumors showing a significantly greater presence of T-cell costimulatory molecules and immune suppression in the tumor microenvironment. An absence of tumor-infiltrating cytotoxic T lymphocytes and mature dendritic cells was seen across all models. Delayed tumor growth and increased survival with suppressor cell inhibition and tumor-targeted chemokine+/-dendritic cells vaccine immunotherapy were associated with high tumor immunogenicity in these models. Tumor MHC class I expression correlated with the overall tumor immunogenicity level and was a singular marker to predict immunotherapy response with these regimens. By using experimental tumor models as surrogates for human cancers, these studies demonstrate how select features of an immune profile may be utilized to identify patients most likely to respond to immunotherapy regimens. PMID:24145359

  19. AFP464 in Treating Patients With Metastatic or Refractory Solid Tumors That Cannot Be Removed By Surgery

    Science.gov (United States)

    2014-02-21

    Male Breast Cancer; Recurrent Breast Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Recurrent Renal Cell Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer; Stage IV Renal Cell Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  20. PNU-145156E, a novel angiogenesis inhibitor, in patients with solid tumors : A phase I and pharmacokinetic study

    NARCIS (Netherlands)

    Groen, HJM; de Vries, EGE; Wynendaele, W; van der Graaf, WTA; Lechuga, EFMJ; Poggesi, [No Value; Dirix, LY; van Oosterom, AT

    2001-01-01

    Our aim was to establish, in patients with solid tumors, the dose-limiting toxicity, maximum tolerated dose (MTD), and pharmacology of PNU-145156E, a new sulfonated distamycin A derivative that blocked circulating angiogenesis-promoting growth factors in animal studies and exhibited an antitumor eff

  1. Impact of TROP2 expression on prognosis in solid tumors: A Systematic Review and Meta-analysis

    Science.gov (United States)

    Zeng, Ping; Chen, Min-Bin; Zhou, Li-Na; Tang, Min; Liu, Chao-Ying; Lu, Pei-Hua

    2016-01-01

    Over-expression of TROP2 (the trophoblast cell surface antigen 2) was reported to predict poor prognosis in various solid tumors in number of studies. However, the results remained not comprehensive. Therefore, we here carried out this meta-analysis of relevant studies published on this topic to quantitatively evaluate the clinicopathological significance of TROP2 in solid tumors. Relevant articles were identified through searching the PubMed, Web of Science and Embase database. The primary outcomes were overall survival (OS) and disease-free survival (DFS). In this meta-analysis, 16 studies involving 2,569 participants were included, and we drew the conclusion that TROP2 overexpression was significantly associated with poor OS (pooled HR = 1.896, 95% CI = 1.599–2.247, P genital system neoplasms, as well in gastrointestine neoplasms. In addition, subgroup analysis found no difference HR across populations of different descent.Taken together, TROP2 overexpression was associated with poor survival in human solid tumors. TROP2 may be a valuable prognosis predictive biomarker and a potential therapeutic target in human solid tumors. PMID:27645103

  2. The clinicopathological and immuohistochemical analysis of solid-pseudopapillary tumor of the pancreas: report of 9 cases

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To investigate the clinical features,pathological characteristics and immunophenotype of solid-pseudopapillary tumor of the pancreas(SPTP).Methods:Nine surgically treated cases of SPTP were retrospectively reviewed.Hematoxylin and Eosin(HE)staining and immunohistochemical staining were used to analyze all cases,and the general clinical data was collected.Results:Six patients were asymptomatic except for a palpable mass.Two patients complained of vague-epigastric pain.One patient appeared jaundice.The tumor was encapsulated and solid tissues alternately with cystic tissues.Histologically,the histological structure of solid portion was pseudopapillary with a fibrovascular core.Tumor cells were uniform and medium-sized which were arranged in sheets ets or nests or pseudopapillary patterns.Immunohistochemical studies demonstrated that SPTP proved positive in vimenfin(9/9 cases),AAT(9/9 cases),,NSE(9/9 cases),ACT(7/9 cases),CK20(2/9 cases),CgA(1/9 cases),S-100(3/9cases),PR(4/9cases),Syn(3/9 cases)and CD56(5/9cases),negative in CEA and ER.Conclusion:SPTP is a tumor predominantly occurring in young women frequently without special symptoms.This tumor has various characteristical histological patterns with different immunophenotype.

  3. Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors

    Directory of Open Access Journals (Sweden)

    Li W

    2012-08-01

    Full Text Available Wei Li,1,2,* Huafei Li,1,* Jinfeng Li,1,* Huajing Wang,1,* He Zhao,1 Li Zhang,1 Yu Xia,1 Zengwei Ye,1 Jie Gao,1,2 Jianxin Dai,1–3 Hao Wang,1–3 Yajun Guo1–31International Joint Cancer Institute, The Second Military Medical University, Shanghai, 2National Engineering Research Center for Antibody Medicine, State Key Laboratory of Antibody Medicine and Targeting Therapy and Shanghai Key Laboratory of Cell Engineering, Shanghai, 3PLA General Hospital Cancer Center, PLA Graduate School of Medicine, Beijing, People's Republic of China*These authors contributed equally to this workAbstract: The main obstacles for cationic polyplexes in gene delivery are in vivo instability and low solid-tumor accumulation. Safe vectors with high transfection efficiency and in vivo tumor accumulation are therefore highly desirable. In this study, the amphiphilic block copolymer poly(n-butyl methacrylate-b-poly(N-acryloylmorpholine was synthesized by reversible addition–fragmentation chain-transfer (RAFT radical polymerization. The corresponding well-defined vesicles with narrow size distribution were tailored by finely regulating the packing parameter (β of copolymer (1/2 < β < 1. Compared with traditional "gold-standard" polycation (polyethylenimine, 25 kDa, plasmid DNA condensing efficiency, DNase I degradation protection, and cellular uptake were improved by the supramolecular nano vesicles. In addition, the plasmid DNA transferring efficiency in 10% fetal bovine serum medium was enlarged five times to that of polyethylenimine in renal tubular epithelial and human hepatocellular carcinoma cell lines. This improved in vitro transfection was mainly attributed to the densely packed bilayer. This stealth polyplex showed high serum stability via entropic repulsion, which further protected the polyplex from being destroyed during sterilization. As indicated by the IVIS® Lumina II Imaging System (Caliper Life Sciences, Hopkinton, MA 24 hours post

  4. Reproducibility of Digital PCR Assays for Circulating Tumor DNA Analysis in Advanced Breast Cancer

    Science.gov (United States)

    Hrebien, Sarah; O’Leary, Ben; Beaney, Matthew; Schiavon, Gaia; Fribbens, Charlotte; Bhambra, Amarjit; Johnson, Richard; Turner, Nicholas

    2016-01-01

    Circulating tumor DNA (ctDNA) analysis has the potential to allow non-invasive analysis of tumor mutations in advanced cancer. In this study we assessed the reproducibility of digital PCR (dPCR) assays of circulating tumor DNA in a cohort of patients with advanced breast cancer and assessed delayed plasma processing using cell free DNA preservative tubes. We recruited a cohort of 96 paired samples from 71 women with advanced breast cancer who had paired blood samples processed either immediately or delayed in preservative tubes with processing 48–72 hours after collection. Plasma DNA was analysed with multiplex digital PCR (mdPCR) assays for hotspot mutations in PIK3CA, ESR1 and ERBB2, and for AKT1 E17K. There was 94.8% (91/96) agreement in mutation calling between immediate and delayed processed tubes, kappa 0.88 95% CI 0.77–0.98). Discordance in mutation calling resulted from low allele frequency and likely stochastic effects. In concordant samples there was high correlation in mutant copies per ml plasma (r2 = 0.98; pprocessed tubes, although overall quantification of total cell free plasma DNA had similar prognostic effects in immediate (HR 3.6) and delayed (HR 3.0) tubes. There was moderate agreement in changes in allele fraction between sequential samples in quantitative mutation tracking (r = 0.84, p = 0.0002). Delayed processing of samples using preservative tubes allows for centralized ctDNA digital PCR mutation screening in advanced breast cancer. The potential of preservative tubes in quantitative mutation tracking requires further research. PMID:27760227

  5. Changes in hemoglobin concentration during chemoradiation of locally advanced head and neck tumors

    International Nuclear Information System (INIS)

    Background: Despite multimodality treatment strategies of locally advanced head and neck cancers long-term results leave much to be desired. There is evidence that oxygenation status of head and neck tumors is directly influenced by the hemoglobin concentration. The aim of this study was to verify changes in the hemoglobin level during combined radio-chemotherapy of locally advanced head and neck tumors. Patients and methods: Sixty-eight patients with locally advanced head and neck cancer had primary or adjuvant radiotherapy with doses of 60 to 74 Gy in combination with cisplatin (±5-FU) or carboplatin chemotherapy in the first and fifth week of treatment. Hemoglobin levels were analyzed before and at the end of radiotherapy. Results: In 41% of all patients the initial hemoglobin concentration was below normal levels. The mean hemoglobin values in all patients dropped significantly from 12.9±1.7 g/dl before to 11.6±1.6 g/dl at the end of treatment. In 12 cases (18%) allogeneic erythrocytes had to be transfused during treatment. At the end of treatment 76% of all patients had anemic hemoglobin levels. In the groups of patients with cisplatin and carboplatin chemotherapy a significant decrease in hemoglobin levels was seen without meaningful statistical difference between these 2 groups. Conclusions: In patients with locally advanced head and neck cancer a high initial rate of anemia was registered (41%): This rate was nearly doubled during chemoradiation (76%). Since several studies have shown a correlation between hemoglobin levels and local tumor control, there is evidence, that this group might benefit from correcting anemia before combined radio-chemotherapy. (orig.)

  6. A facile route to core-shell nanoparticulate formation of arsenic trioxide for effective solid tumor treatment

    Science.gov (United States)

    Zhang, Zongjun; Liu, Hanyu; Zhou, Hualu; Zhu, Xianglong; Zhao, Zhenghuan; Chi, Xiaoqin; Shan, Hong; Gao, Jinhao

    2016-02-01

    Arsenic trioxide has achieved great clinical success in the treatment of acute promyelocytic leukemia (APL). However, it is difficult to replicate the success in other cancers, such as solid tumors, in part because of the rapid renal clearance and dose-limiting toxicity. Nanotechnology is expected to overcome these disadvantages through altering its pharmacokinetics and concentrating the drug at the desired sites. Herein, we report a ``one-pot'' method to develop arsenic-based nanodrugs by in situ coating the as-prepared arsenic nanocomplexes with porous silica shells. This process can be easily reproduced and scaled up because no complicated synthesis and purification steps are involved. This core-shell embedding method endows nanodrugs with high loading capacity (57.9 wt%) and a prolonged pH-responsive releasing profile, which is crucial to increase the drug concentration at tumor sites and improve the drug efficacy. Based on these unique features, the nanodrugs significantly inhibit the growth of solid tumors without adverse side effects. Therefore, we anticipate that the arsenic-based nanodrugs generated by this facile synthetic route may be a powerful and alternative strategy for solid tumor therapy.Arsenic trioxide has achieved great clinical success in the treatment of acute promyelocytic leukemia (APL). However, it is difficult to replicate the success in other cancers, such as solid tumors, in part because of the rapid renal clearance and dose-limiting toxicity. Nanotechnology is expected to overcome these disadvantages through altering its pharmacokinetics and concentrating the drug at the desired sites. Herein, we report a ``one-pot'' method to develop arsenic-based nanodrugs by in situ coating the as-prepared arsenic nanocomplexes with porous silica shells. This process can be easily reproduced and scaled up because no complicated synthesis and purification steps are involved. This core-shell embedding method endows nanodrugs with high loading capacity

  7. Recombination Mutant Human Tumor Necrosis Factor Combined with Chemotherapy in the Treatment of Advanced Cancer

    Institute of Scientific and Technical Information of China (English)

    LIUXing; ZHANGXiangfu; ZHENGZhiweng; LUHuishan; WUXinyuan; HUANGChangmin; WANGChuan; GUANGuoxian

    2005-01-01

    Objective: Past studies showed that tumor necrosis factor (TNF) assisted anti-tumor treatment and intensified the sensitivity of chemotherapy. However its clinical application has been curbed because of its low purity, high dosage, and strong toxicity. The objective of present study is to evaluate the therapeutic effects and adverse reactions of recombinant mutant human tumor necrosis factor (rmhTNF) combined with chemotherapy in patients with advanced malignant tumor. Methods: 105 patients with advanced malignant tumor were randomly divided into trial group, 69 patients, and control group, 36 patients.rm hTNF was injected intramuscularly to the trial group at a dose of 4×106 U/m2, from the 1st to 7th days, the llth to 17th days combined with chemotherapy course. The chemotherapy plan was as follows:CAP for patients with the NSCLC; FAM for patients with gastric cancer; FC for patients with colorectal cancer. One treatment cycle lasted for 21 days and two cycles were scheduled. The control group was given only the same chemotherapy as the trial group. Results: In the trial group there was 1 CR case and 12 PR cases, and the response rate was 13/69 (18.84%); in the control group 1 PR case, the response rate 1/36 (2.78%). The response rate in the trial group was significantly higher than that in the control group (P=0.022). The response rate for NSCLC in the trial group was 8/17 (47.06%), and 1/6 (16.67%) in the control group. The response rates for gastric cancer and colorectal cancer in the trial groups also were higher than those in the control groups. After the treatment the KPS was 89.00+9.92 in the trial group,and 84.17±8.84 in the control group, with a significant difference between the two groups (P=0.028). The adverse reactions of rmhTNF injection included: pain in the injection area, chill, hardening and swelling and redness in the injection area, fever, ostealgia and myosalgia, and cold-like symptoms. All these adverse reactions were mild and bearable

  8. Advances in managing medulloblastoma and intracranial primitive neuro-ectodermal tumors.

    Science.gov (United States)

    Adamski, Jenny; Ramaswamy, Vijay; Huang, Annie; Bouffet, Eric

    2014-01-01

    Medulloblastoma and central nervous system (CNS)-primitive neuro-ectodermal tumors (PNETs) are a diverse group of entities which encompasses different pathological and clinical pictures. Initially divided based on histology and location, molecular insight is leading to new definitions and a change in the borders delineating these diseases, such that they become more divergent. Current treatment approaches consist of surgical resection, radiotherapy and intensive chemotherapy, dependent on age. Stratification is one risk factor shown to be prognostic and is divided into high- and average-risks. Outcomes with modern treatment regimens are good, particularly in average-risk medulloblastoma patients, but the cost of cure is high, with high rates of neurocognitive, endocrine and social dysfunction. The changing biological landscape, however, may allow for clearer prediction of tumor behavior, to better identify "good" and "bad" players within these groups. Discovery of subgroups with changes in dependent molecular pathways will also lead to the development of new specific targeted therapies. Presenting exciting opportunities, these advances may transform the treatment for some patients, revolutionizing therapy in the future. Several challenges, however, are yet to be faced and caution is needed not to abandon previously defined prognostic factors on the strength of thus far retrospective evidence. We are witnessing a new era of trials with biological stratification involving multiple subgroups and treatment arms, based on specific tumor-related targets. This review discusses the changing face of medulloblastoma and CNS-PNETs and how we move molecular advances into clinical trials that benefit patients. PMID:25184046

  9. Interleukin-12 in Treating Patients With Hematologic Cancers or Solid Tumors

    Science.gov (United States)

    2014-09-09

    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

  10. Advances of wogonin, an extract from Scutellaria baicalensis, for the treatment of multiple tumors

    Directory of Open Access Journals (Sweden)

    Wu X

    2016-05-01

    Full Text Available Xue Wu,1 Haijun Zhang,2 Jumah Masoud Mohammad Salmani,1 Rong Fu,3 Baoan Chen1 1Department of Hematology, 2Department of Oncology, The Affiliated Zhongda Hospital, School of Medicine, Southeast University, 3Department of Physiology, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: As the major bioactive compound of Scutellaria baicalensis that has been approved to be effective as an anti-inflammatory and antiviral inhibitor in cardiovascular diseases, wogonin (WG showed potent and promising antitumor effects both in vitro and in vivo. It has been proved that WG has the ability to inhibit the growth of tumor cells, induce apoptosis, and suppress angiogenesis. The molecular mechanisms involve reactive oxygen species, Ca2+, NF-κB, tumor necrosis factor-related apoptosis-inducing ligand, and tumor necrosis factor-alpha. Furthermore, the synergistic effect of WG with 5-fluorouracil, etoposide, and adriamycin to enhance chemotherapy and reverse drug resistance has also been confirmed. In this review, we summarize the advances in recent years on the antitumor effect of WG on multiple tumors; in addition, we also present information regarding the synergistic and chemosensitizing effects of WG with other drugs to illustrate its potential use in the clinic. Keywords: antitumor effect, drug resistance, mechanisms, synergistic effect

  11. Cancer incidence in atomic bomb survivors. Part II: Solid tumors, 1958-1987.

    Science.gov (United States)

    Thompson, D E; Mabuchi, K; Ron, E; Soda, M; Tokunaga, M; Ochikubo, S; Sugimoto, S; Ikeda, T; Terasaki, M; Izumi, S

    1994-02-01

    This report presents, for the first time, comprehensive data on the incidence of solid cancer and risk estimates for A-bomb survivors in the extended Life Span Study (LSS-E85) cohort. Among 79,972 individuals, 8613 first primary solid cancers were diagnosed between 1958 and 1987. As part of the standard registration process of the Hiroshima and Nagasaki tumor registries, cancer cases occurring among members of the LSS-E85 cohort were identified using a computer linkage system supplemented by manual searches. Special efforts were made to ensure complete case ascertainment, data quality and data consistency in the two cities. For all sites combined, 75% of the cancers were verified histologically, 6% were diagnosed by direct observation, 8% were based on a clinical diagnosis, and 12.6% were ascertained by death certificate only. A standard set of analyses was carried out for each of the organs and organ systems considered. Depending on the cancer site, Dosimetry System 1986 (DS86) organ or kerma doses were used for computing risk estimates. Analyses were based on a general excess relative risk model (the background rate times one plus the excess relative risk). Analyses carried out for each site involved fitting the background model with no dose effect, a linear dose-response model with no effect modifiers, a linear-quadratic dose-response model with no effect modifiers, and a series of linear dose-response models that included each of the covariates (sex, age at exposure, time since exposure, attained age and city) individually as effect modifiers. Because the tumor registries ascertain cancers in the registry catchment areas only, an adjustment was made for the effects of migration. In agreement with prior LSS findings, a statistically significant excess risk for all solid cancers was demonstrated [excess relative risk at 1 Sv (ERR1Sv) = 0.63; excess absolute risk (EAR) per 10(4) person-year sievert (PY Sv) = 29.7]. For cancers of the stomach (ERR1SV = 0.32), colon

  12. Humanized mouse model of ovarian cancer recapitulates patient solid tumor progression, ascites formation, and metastasis.

    Directory of Open Access Journals (Sweden)

    Richard B Bankert

    Full Text Available Ovarian cancer is the most common cause of death from gynecological cancer. Understanding the biology of this disease, particularly how tumor-associated lymphocytes and fibroblasts contribute to the progression and metastasis of the tumor, has been impeded by the lack of a suitable tumor xenograft model. We report a simple and reproducible system in which the tumor and tumor stroma are successfully engrafted into NOD-scid IL2Rγ(null (NSG mice. This is achieved by injecting tumor cell aggregates derived from fresh ovarian tumor biopsy tissues (including tumor cells, and tumor-associated lymphocytes and fibroblasts i.p. into NSG mice. Tumor progression in these mice closely parallels many of the events that are observed in ovarian cancer patients. Tumors establish in the omentum, ovaries, liver, spleen, uterus, and pancreas. Tumor growth is initially very slow and progressive within the peritoneal cavity with an ultimate development of tumor ascites, spontaneous metastasis to the lung, increasing serum and ascites levels of CA125, and the retention of tumor-associated human fibroblasts and lymphocytes that remain functional and responsive to cytokines for prolonged periods. With this model one will be able to determine how fibroblasts and lymphocytes within the tumor microenvironment may contribute to tumor growth and metastasis, and will make it possible to evaluate the efficacy of therapies that are designed to target these cells in the tumor stroma.

  13. Molecular cytogenetic analysis of formalin-fixed, paraffin-embedded solid tumors by comparative genomic hybridization after universal DNA-amplification.

    Science.gov (United States)

    Speicher, M R; du Manoir, S; Schröck, E; Holtgreve-Grez, H; Schoell, B; Lengauer, C; Cremer, T; Ried, T

    1993-11-01

    We present a technique which allows the detection and chromosomal localization of DNA sequence copy number changes in solid tumor genomes from frozen sections and paraffin embedded, formalin fixed specimens. Based on comparative genomic hybridization and on universal DNA amplification procedures this technique is possible even if only a few tumor cells are available. We demonstrate the feasibility of this method to visualize complete and partial chromosome gains and losses and gene amplifications in archived solid tumor samples. PMID:8281155

  14. Re-irradiation in the treatment of patients with cerebral metastases of solid tumors: retrospective analysis

    International Nuclear Information System (INIS)

    Goal of this retrospective analysis was to evaluate the role of repeat whole brain radiotherapy in the palliative care of patients with brain metastases due to solid tumors. Data regarding demographic data, primary tumor, metastasis, radiotherapy and symptoms were compiled on 134 patients with cerebral metastases that received repeat whole brain radiotherapy (WBRT) in our clinic between 2002 and 2011. The analyzed group consisted of 63 (47%) women and 71 (53%) men with a median age of 57 at the start of re-irradiation. Most frequent primary site was the lung (87%). Sixty patients with lung cancer received the first WBRT prophylactically. At the time of re-WBRT 81% of all patients suffered from additional extracerebral metastases. Time between first and second WBRT was a median of 13.4 months. Full dose for the first WBRT was 30 Gy in 2.0 Gy single dose, for the second 20 Gy in 2.0 Gy single dose. At the start of the Re-WBRT 81 patients (60.4%) had mild, 32 (23.9%) severe neurological symptoms, 21 patients (15.7%) were asymptomatic. The median Karnofsky performance status was 70%. Overall, re-WBRT was tolerated satisfactorily. Main side effects were fatigue, erythema and focal alopecia, 10% of patients discontinued treatment before reaching the planned dose. Median survival was 2.8 months since the end of the re-WBRT with good performance status at the start of the re-irradiation being a key indicator for longer survival. Fifty-two patients (39%) showed a clinical improvement of neurological symptoms after the therapy, 59 patients (44%) remained stable, 23 patients (17%) showed worse symptoms. From this large patient collective we were able to show that re-WBRT can be an important therapeutic option with low rate of acute side effects for patients in adequate general condition

  15. Solid pseudopapillary tumors of the pancreas. Case report and review of the literature.

    Science.gov (United States)

    Leggio, Samuele; Orofino, Antonio; Anzillotto, Maria Paola L; Zullino, Francesca; Di Napoli, Geremia; Paradies, Guglielmo

    2014-07-21

    I Tumori solidi pseudopapillari del pancreas rappresentano una rara forma di tumori pancreatici: caratterizzati da un basso grado di malignità ed una lenta crescita, essi colpiscono più frequentemente donne giovani adulte ma anche, in circa il 20% dei casi descritti in letteratura, bambini ed adolescenti, epoca in cui viene riferita una minore aggressività biologica rispetto all’adulto. Nella maggior parte dei casi pediatrici la neoplasia è asintomatica e viene scoperta solo occasionalmente; diversamente, in altri casi, si manifesta come una massa addominale palpabile, talora dolente, oppure esordisce con dolore improvviso e con i segni ed i sintomi dovuti alla compressione degli organi vicini. Riportiamo il recente caso di una ragazza di 15 anni, giunta alla nostra osservazione per il riscontro di una massa interessante il corpo e la coda del pancreas, scoperta incidentalmente nel corso di un esame ecografico Published online (EP) 18 July 2014 - Ann. Ital. Chir 5 Solid pseudopapillary tumors of the pancreas. Case report and review of the literature dell’addome eseguito dopo un lieve trauma.Gli ulteriori successivi esami diagnostici cui veniva sottoposta la ragazza, confermavano la presenza della lesione pancreatica che appariva ben delimitata, apparentemente capsulata, a struttura disomogenea ,strettamente aderente alla vena splenica. Posto il sospetto diagnostico di un tumore solido pseudo-papillare del pancreas, si procedeva chirurgicamente alla sua enucleazione. L’esame istolopatologico della massa confermava la diagnosi preoperatoria. Il caso ,che viene presentato nei suoi aspetti clinico-diagnostici e terapeutici, offre l’occasione per ricercare e discutere alcuni interessanti aspetti di questa rara patologia, ancora ampiamente dibattuti in Letteratura.

  16. Synchronous intraoperative radiofrequency ablation for multiple liver metastasis and resection of giant solid pseudopapillary tumors of the pancreas

    Institute of Scientific and Technical Information of China (English)

    LI Jia-xin; WU Hong; HUANG Ji-wei; Pankaj Prasoon; ZENG Yong

    2012-01-01

    The solid pseudopapillary tumors of the pancreas (SPTP) are rare tumors,which are commonly found in adolescent women.Radical surgical resection of the primary tumor or metastases is the standard treatment for SPTP and could achieve long-term survival.We reported a case of a 20-year-old female with multiple liver metastases of SPTP,and performed surgical resection for primary tumor 14 cm in diameter and 2 major liver metastases (both 5 cm in diameter),radiofrequency ablation (RFA) for small lesions and one major liver metastase 6 cm in diameter successfully.No evidence of recurrence in situ or in the liver was found by computed tomography (CT) scan 3 months after the operation.RFA is a safe and effective treatment for unresectable multiple liver metastases of SPTP.

  17. Prognostic Value of Fluoro-D-glucose Uptake of Primary Tumor and Metastatic Lesions in Advanced Nonsmall Cell Lung Cancer

    OpenAIRE

    Nguyen, Xuan Canh; Nguyen, Khoi; Tran, Minh Thong; Maurea, Simone; Salvatore, Marco

    2014-01-01

    To assess the prognostic value of maximum standardized uptake value (maxSUV) of the primary tumor (maxSUVpt), maxSUV of whole-body tumors (maxSUVwb) and sum of maximum standardized uptake value (sumaxSUV) measured by the sum of maxSUVs of the primary tumor, metastatic lymph nodes, and metastatic lesions per each organ on fluoro-D-glucose-positron emission tomography/computed tomography in advanced non-small cell lung cancer (NSCLC). Eighty-three patients (49 male, 34 female) with advanced NSC...

  18. Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours

    OpenAIRE

    Bahleda, Rastislav; Hollebecque, Antoine; Varga, Andrea; Gazzah, Anas; Massard, Christophe; Deutsch, Eric; Amellal, Nadia; Farace, Françoise; Ould-Kaci, Mahmoud; Roux, Flavien; Marzin, Kristell; Soria, Jean-Charles

    2015-01-01

    Background: This Phase I study evaluated continuous- and intermittent-dosing (every other week) of afatinib plus nintedanib in patients with advanced solid tumours. Methods: In the dose-escalation phase (n=45), maximum tolerated doses (MTDs) were determined for continuous/intermittent afatinib 10, 20, 30 or 40 mg once daily plus continuous nintedanib 150 or 200 mg twice daily. Secondary objectives included safety and efficacy. Clinical activity of continuous afatinib plus nintedanib at the MT...

  19. The effect of chemotherapy combined with recombination mutant human tumor necrosis factor on advanced cancer

    Directory of Open Access Journals (Sweden)

    Huang Changmin

    2004-10-01

    Full Text Available Abstract Background Past studies suggested that tumor necrosis factor (TNF assisted anti-tumor treatment and intensified the sensitivity of chemotherapy. However its clinical application has been curbed because of its low purity, high dosage, and strong toxicity. This research, through perspective random clinical control experiment, observed the therapeutic effect of the treatment of late malignant tumor through the injection of recombinant mutant human tumor necrosis factor (rmhTNF combined with general chemotherapy and its adverse reactions. Methods 105 patients with advanced malignant tumor were randomly divided into trial group, 69 patients, and control group, 36 patients. Injection of rmhTNF 4 × 106u/m2 was given to the trial group, from the 1st to 7th days, the 11th to 17th days combined with chemotherapy course. The chemotherapy plan was as follows: CAP for patients with the NSCLC; FAM for patients with gastric cancer; FC for patients with colorectal cancer. One treatment cycle lasted for 21 days and two cycles were scheduled. The control group was given only the same chemotherapy as the trial group. Results In the trial group there was 1 CR case and 12 PR cases, and the response rate is 13/69 (18.84%; in the control group 1 PR case, the response rate 1/36 (2.78%. The response rate of the trial group was significantly higher than that of the control group (P = 0.022. The response rate for NSCLC in the trial group was 8/17 (47.06%, and 1/6 (16.67% in the control group. The response rates for gastric cancer and colorectal cancer in the trial groups also were higher than those of the control groups. After the treatment the KPS is 89.00 ± 9.92 in the trial group, and 84.17 ± 8.84 in the control group, with a significant difference between the two groups (P = 0.028. The adverse reactions of rmhTNF injection included: pain in the injection area, chill, hardening and swelling and redness in the injection area, fever, ostealgia and myosalgia

  20. Sorafenib induced tumor lysis syndrome in an advanced hepatocellular carcinoma patient

    Institute of Scientific and Technical Information of China (English)

    Wu-Shiung Huang; Chang-Hsu Yang

    2009-01-01

    A 55-year-old male patient with hepatitis B-related liver cirrhosis was found to have advanced hepatocellular carcinoma. His AFP was initially 9828 mg/L and rapidly dropped to 5597 mg/L in ten days after oral sorafenib treatment. However, he developed acute renal failure, hyperkalemia, and hyperuricemia 30 d after receiving the sorafenib treatment. Tumor lysis syndrome was suspected and intensive hemodialysis was performed. Despite intensive hemodialysis and other supportive therapy, he developed multiple organ failure (liver, renal, and respiratory failure) and metabolic acidosis. The patient expired 13 d after admission.

  1. Interactions of BMS-181174 and radiation: studies with EMT6 cells in vitro and in solid tumors.

    Science.gov (United States)

    Rockwell, S; Kelley, M

    1996-04-01

    N-7[2-(4-nitrophenyldithio)-ethyl] mitomycin C, (BMS-181174; previously designated as BMY25067) is a mitomycin C analog now in initial clinical trials. The experiments described in this report were performed to assess whether BMS-181174, like mitomycin C and porfiromycin, was selectively toxic to the hypoxic cells in solid tumors and might therefore prove valuable in combination with radiotherapy. In contrast to mitomycin C and porfiromycin, BMS-181174 was more toxic to aerobic EMT6 cells in vitro than to cells made acutely hypoxic. In vitro, BMS-181174 and radiation produced cytotoxicity compatible with either additive or slightly supra-additive cytotoxicity. In vivo, BMS-181174 was effective in killing cells in solid EMT6 tumors. The effects of regimens combining BMS-181174 and radiation in vivo were complex. Combinations of low doses of BMS-181174 plus a large dose of radiation were very effective in killing cells in solid tumors. However, the survival curve plateaued at high doses of BMS-181174, providing evidence for a subpopulation of tumor cells which were resistant to both BMS-181174 and radiation; this was hypothesized to be a hypoxic cell population. PMID:8735495

  2. Phase I trial of a monoclonal antibody specific for alphavbeta3 integrin (MEDI-522) in patients with advanced malignancies, including an assessment of effect on tumor perfusion.

    Science.gov (United States)

    McNeel, Douglas G; Eickhoff, Jens; Lee, Fred T; King, David M; Alberti, Dona; Thomas, James P; Friedl, Andreas; Kolesar, Jill; Marnocha, Rebecca; Volkman, Jennifer; Zhang, Jianliang; Hammershaimb, Luz; Zwiebel, James A; Wilding, George

    2005-11-01

    At present, a variety of agents targeting tumor angiogenesis are under clinical investigation as new therapies for patients with cancer. Overexpression of the alpha(v)beta(3) integrin on tumor vasculature has been associated with an aggressive phenotype of several solid tumor types. Murine models have shown that antibodies targeting the alpha(v)beta(3) integrin can affect tumor vasculature and block tumor formation and metastasis. These findings suggest that antibodies directed at alpha(v)beta(3) could be investigated in the treatment of human malignancies. The current phase I dose escalation study evaluated the safety of MEDI-522, a monoclonal antibody specific for the alpha(v)beta(3) integrin, in patients with advanced malignancies. Twenty-five patients with a variety of metastatic solid tumors were treated with MEDI-522 on a weekly basis with doses ranging from 2 to 10 mg/kg/wk. Adverse events were assessed weekly; pharmacokinetic studies were done; and radiographic staging was done every 8 weeks. In addition, dynamic computed tomography imaging was done at baseline and at 8 weeks in patients with suitable target lesions amenable to analysis, to potentially identify the effect of MEDI-522 on tumor perfusion. Treatment was well tolerated, and a maximum tolerated dose was not identified by traditional dose-limiting toxicities. The major adverse events observed were grade 1 and 2 infusion-related reactions (fever, rigors, flushing, injection site reactions, and tachycardia), low-grade constitutional and gastrointestinal symptoms (fatigue, myalgias, and nausea), and asymptomatic hypophosphatemia. Dynamic computed tomography imaging suggested a possible effect on tumor perfusion with an increase in contrast mean transit time from baseline to the 8-week evaluation with increasing doses of MEDI-522. No complete or partial responses were observed. Three patients with metastatic renal cell cancer experienced prolonged stable disease (34 weeks, >1 and >2 years) on

  3. Prospects in cancer immunotherapy: treating advanced stage disease or preventing tumor recurrence?

    Science.gov (United States)

    Manjili, Masoud H; Payne, Kyle K

    2015-06-01

    Human vaccines against infectious agents are often effective in a prophylactic setting. However, they are usually not effective when used post-exposure. Rabies vaccine is one of the exceptions, which can be used post-exposure, but is effective only when used in combination with other treatments. Similar results have been obtained with cancer vaccines and immunotherapies. Cancer immunotherapies generally prolong patients' survival when they are used during advanced stage disease. The potential of immunotherapy to cure cancer could be revealed when it is applied in a prophylactic setting. This article provides a brief overview of cancer immunotherapeutics and suggests that immunotherapy can cure cancer if used at the right time against the right target; we suggest that targeting cancer during dormancy in order to prevent tumor recurrence as advanced stage disease is potentially curative.

  4. Recent advances in nanotechnology-based detection and separation of circulating tumor cells.

    Science.gov (United States)

    Myung, Ja Hye; Tam, Kevin A; Park, Sin-jung; Cha, Ashley; Hong, Seungpyo

    2016-01-01

    Although circulating tumor cells (CTCs) in blood have been widely investigated as a potential biomarker for diagnosis and prognosis of metastatic cancer, their inherent rarity and heterogeneity bring tremendous challenges to develop a CTC detection method with clinically significant specificity and sensitivity. With advances in nanotechnology, a series of new methods that are highly promising have emerged to enable or enhance detection and separation of CTCs from blood. In this review, we systematically categorize nanomaterials, such as gold nanoparticles, magnetic nanoparticles, quantum dots, graphenes/graphene oxides, and dendrimers and stimuli-responsive polymers, used in the newly developed CTC detection methods. This will provide a comprehensive overview of recent advances in the CTC detection achieved through application of nanotechnology as well as the challenges that these existing technologies must overcome to be directly impactful on human health. PMID:26296639

  5. Direct solid-phase synthesis of octreotide conjugates: precursors for use as tumor-targeted radiopharmaceuticals.

    Science.gov (United States)

    Hsieh, H P; Wu, Y T; Chen, S T; Wang, K T

    1999-09-01

    Somatostatin analogues, such as octreotide, are useful for the visualization and treatment of tumors. Unfortunately, these compounds were produced synthetically using complex and inefficient procedures. Here, we describe a novel approach for the synthesis of octreotide and its analogues using p-carboxybenzaldehyde to anchor Fmoc-threoninol to solid phase resins. The reaction of the two hydroxyl groups of Fmoc-threoninol with p-carboxybenzaldehyde was catalyzed with p-toluenesulphonic acid in chloroform using a Dean-Stark apparatus to form Fmoc-threoninol p-carboxybenzacetal in 91% yield. The Fmoc-threoninol p-carboxybenzacetal acted as an Fmoc-amino acid derivative and the carboxyl group of Fmoc-threoninol p-carboxybenzacetal was coupled to an amine-resin via a DCC coupling reaction. The synthesis of protected octreotide and its conjugates were carried out in their entirety using a conventional Fmoc protocol and an autosynthesizer. The acetal was stable during the stepwise elongation of each Fmoc-amino acid as shown by the averaged coupling yield (> 95%). Octreotide (74 to 78% yield) and five conjugated derivatives were synthesized with high yields using this procedure, including three radiotherapy octreotides (62 to 75% yield) and two cellular markers (72 to 76% yield). This novel approach provides a strategy for the rapid and efficient large-scale synthesis of octreotide and its analogues for radiopharmaceutical and tagged conjugates.

  6. Prevalence of Café-au-Lait Spots in children with solid tumors.

    Science.gov (United States)

    Santos, Anna Claudia Evangelista Dos; Heck, Benjamin; Camargo, Beatriz De; Vargas, Fernando Regla

    2016-05-24

    Cafe-au-lait maculae (CALM) are frequently observed in humans, and usually are present as a solitary spot. Multiple CALMs are present in a smaller fraction of the population and are usually associated with other congenital anomalies as part of many syndromes. Most of these syndromes carry an increased risk of cancer development. Previous studies have indicated that minor congenital anomalies may be more prevalent in children with cancer. We investigated the prevalence of CALMs in two samples of Brazilian patients with childhood solid tumors, totaling 307 individuals. Additionally, 176 school children without diagnosis of cancer, or of a cancer predisposing syndrome, were investigated for the presence of CALMs. The prevalence of solitary CALM was similar in both study groups (18% and 19%) and also in the group of children without cancer. Multiple CALMs were more frequently observed in one of the study groups (Z = 2.1). However, when both groups were analyzed together, the significance disappeared (Z = 1.5). The additional morphological abnormalities in children with multiple CALMs were analyzed and compared to the findings observed in the literature. The nosologic entities associated with CALMs are reviewed. PMID:27223488

  7. Could tumor characteristics identified by colonoscopy predict the locally advanced rectal carcinoma?

    Institute of Scientific and Technical Information of China (English)

    WANG Hao; CAO Fu-ao; GONG Hai-feng; ZHENG Jian-ming; FU Chuan-gang

    2010-01-01

    Background Neoadjuvant chemoradiation is now considered the standard care for locally advanced rectal carcinoma (T3-4 or/and N1-2 lesions), but the accuracy of staging examinations including endorectal ultrasonography (ERUS) and MRI is far from excellent. In addition, the above staging equipment or professionals who perform the examinations may not be available in some hospitals, while preoperative colonoscopy and biopsy are usually obtainable in most hospitals.The objective of the present study was to investigate the clinical and pathological characteristics of locally advanced rectal carcinoma and identify candidates for neoadjuvant chemoradiation.Methods This was a retrospective study. Patients who were treated for rectal cancer at Changhai Hospital from January 1999 to July 2008 were identified from our prospectively collected database. Statistical analysis was performed using SPSS Software System (version 15.0). The Mann-Whitney test, chi-square test and multivariate Logistic regression analysis were performed,Results A total of 1005 cases were included in this research, of which 761 cases were identified as locally advanced rectal carcinoma depending on postoperative TNM staging. The results of multivariate Logistic regression analysis indicated seven independent risk factors that could be used to predict a locally advanced rectal carcinoma independently: a high grade (including poor differentiation and undifferentiation) (OR: 3.856; 95% CI: 2.064 to 7.204;P=0.000); large tumor size (OR: 2.455; 95% CI: 1.755 to 3.436; P=0.000); elevated preoperative serum CEA level (OR:1.823; 95% CI: 1.309 to 2.537; P=0.000); non-polypoid tumor type (OR: 1.758; 95% CI: 1.273 to 2.427; P=0.001); the absence of synchronous polyps (OR: 1.602; 95% CI: 1.103 to 2.327; P=0.013); the absence of blood in stool (OR: 1.659;95% CI: 1.049 to 2.624; P=0.030); and a greater circumferential tumor extent (OR: 1.813; 95% CI: 1.055 to 3,113;P=0.031). Based on these findings, a Logistic

  8. Aggressive behaviour of solid-pseudopapillary tumor of the pancreas in adults:A case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Solid-pseudopapillary tumor (SPT) is a rare neoplasm of the pancreas that usually occurs in young females.It is generally considered a low-grade malignant tumor that can remain asymptomatic for several years.The occurrence of infiltrating varieties of 5PT is around 10%-15%.Between 1986 and 2006,282 cystic tumors of the pancreas were observed.Among them a SPT was diagnosed in 8 patients (2.8%) with only one infiltrating variety.This was diagnosed in a 49-year-old female 13 years after the sonographic evidence of a small pancreatic cystic lesion interpreted as a pseudocyst.The tumor invaded a long segment of the portalmesenteric vein confluence,and was removed with a total pancreatectomy,resection of the portal vein and reconstruction with the internal jugular vein.Histological examination confirmed the R-0 resection of the primary SPT,although a vascular invasion was demonstrated.The postoperative course was uneventful,but 32 mo after surgery the patient experienced diffuse liver metastases.Chemotherapy with different drugs was started.The patient is alive and symptom-free,with stable disease,75 mo after surgery.Twenty-five patients with invasion of the portal vein and/or of mesenteric vessels were retrieved from the literature,16 recent patients with tumor relapse after potentially curative resection were also retrieved.The best treatment remains a radical resection whenever possible,even in locally advanced or metastatic disease.The role of chemotherapy,and/or radiotherapy,is still to be defined.

  9. NATO Advanced Study Institute on Relativistic and Electron Correlation Effects in Molecules and Solids

    CERN Document Server

    1994-01-01

    The NATO Advanced Study Institute (ASI) on "R@lativistic and Electron Correlation Effects in Molecules and Solids", co-sponsored by Simon Fraser University (SFU) and the Natural Sciences and Engineering Research Council of Canada (NSERC) was held Aug 10- 21, 1992 at the University of British Columbia (UBC), Vancouver, Canada. A total of 90 lecturers and students with backgrounds in Chemistry, Physics, Mathematics and various interdisciplinary subjects attended the ASI. In my proposal submitted to NATO for financial support for this ASI, I pointed out that a NATO ASI on the effects of relativity in many-electron systems was held ten years ago, [See G.L. Malli, (ed) Relativistic Effects in Atoms, Molecules and Solids, Plenum Press, Vol B87, New York, 1983]. Moreover, at a NATO Advanced Research Workshop (ARW) on advanced methods for molecular electronic structure "an assessment of state-of­ the-art of Electron Correlation ... " was carried out [see C.E. Dykstra, (ed), Advanced Theories and Computational Approa...

  10. Radiobiologic significance of apoptosis and micronucleation in quiescent cells within solid tumors following γ-ray irradiation

    International Nuclear Information System (INIS)

    Purpose: To determine the frequency of apoptosis in quiescent (Q) cells within solid tumors following γ-ray irradiation, using four different tumor cell lines. In addition, to assess the significance of detecting apoptosis in these cell lines. Methods and Materials: C3H/He mice bearing SCC VII or FM3A tumors, Balb/c mice bearing EMT6/KU tumors, and C57BL mice bearing EL4 tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. The mice then received γ-ray irradiation at a dose of 4-25 Gy while alive or after tumor clamping. Immediately after irradiation, the tumors were excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (=Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, 6 hours after irradiation, tumor cell suspensions obtained in the same manner were fixed. The apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequency in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. Results: In total cells, SCC VII, FM3A, and EMT6/KU cells showed reasonable relationships between MN frequency and surviving fraction (SF). However, fewer micronuclei were induced in EL4 cells than the other cell lines. In contrast, a comparatively close relationship between apoptosis frequency and SF was found in total cells of EL4 cell line. Less apoptosis was observed in the other cell lines. Quiescent tumor cells exhibited significantly lower values of MN and apoptosis frequency probably due to their large hypoxic fraction, similar to total tumor cells on clamped irradiation. Conclusion: γ-ray irradiation induced MN formation in SCC VII, FM3A, and EMT6/KU tumor cells, and the apoptosis was marked in EL4 cells compared with

  11. The impact of weakly bound 89Zr on preclinical studies: Non-specific accumulation in solid tumors and aspergillus infection

    International Nuclear Information System (INIS)

    Preclinical studies involving 89Zr often report significant bone accumulation, which is associated with dissociation of the radiometal from the tracer. However, experiments determining the uptake of unbound 89Zr in disease models are not performed as routine controls. The purpose of the present study was to investigate the impact of free or weakly bound 89Zr on PET quantifications in disease models, in order to determine if such control experiments are warranted. Methods: Chemical studies were carried out to find a 89Zr compound that would solubilize the 89Zr as a weak chelate, thus mimicking free or weakly bound 89Zr released in circulation. 89Zr oxalate had the desired characteristics, and was injected into mice bearing FaDu and HT29 solid tumor xenografts, and mice infected in the lungs with the mold Aspergillus fumigatus, as well as in healthy controls (naïve). PET/CT or PET/MR imaging followed to quantify the distribution of the radionuclide in the disease models. Results: 89Zr oxalate was found to have a plasma half-life of 5.1 ± 2.3 h, accumulating mainly in the bones of all animals. Both tumor types accumulated 89Zr on the order of 2‐4 %ID/cm3, which is comparable to EPR-mediated accumulation of certain species. In the aspergillosis model, the concentration of 89Zr in lung tissue of the naïve animals was 6.0 ± 1.1 %ID/g. This was significantly different from that of the animals with advanced disease, showing 11.6 ± 1.8 %ID/g. Conclusions: Given the high levels of 89Zr accumulation in the disease sites in the present study, we recommend control experiments mapping the biodistribution of free 89Zr in any preclinical study employing 89Zr where bone uptake is observed. Aqueous 89Zr oxalate appears to be a suitable compound for such studies. This is especially relevant in studies where the tracer accumulation is based upon passive targeting, such as EPR

  12. Dendritic Cell-Based Adjuvant Vaccination Targeting Wilms’ Tumor 1 in Patients with Advanced Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Shigetaka Shimodaira

    2015-12-01

    Full Text Available Despite significant recent advances in the development of immune checkpoint inhibitors, the treatment of advanced colorectal cancer involving metastasis to distant organs remains challenging. We conducted a phase I study to investigate the safety and immunogenicity of Wilms’ tumor (WT1 class I/II peptides-pulsed dendritic cell DC vaccination for patients with advanced colorectal cancer. Standard treatment comprising surgical resection and chemotherapy was followed by one course of seven biweekly administrations of 1–2 × 107 DCs with 1–2 KE of OK-432 (streptococcal preparation in three patients. Clinical efficacy was confirmed based on WT1 expression using immunohistochemistry on paraffin-embedded tissues and immune monitoring using tetramer analysis and enzyme-linked immunosorbent spot (ELISPOT assays. WT1 expression with human leukocyte antigen (HLA-class I molecules was detected in surgical resected tissues. Adverse reactions to DC vaccinations were tolerable under an adjuvant setting. WT1-specific cytotoxic T cells were detected by both modified WT1-peptide/HLA-A*24:02 tetramer analysis and/or interferon-γ-producing cells through the use of ELISPOT assays after the first DC vaccination. Immunity acquired from DC vaccination persisted for two years with prolonged disease-free and overall survival. The present study indicated that DC vaccination targeting WT1 demonstrated the safety and immunogenicity as an adjuvant therapy in patients with resectable advanced colorectal cancer.

  13. A fluid biopsy as investigating technology for the fluid phase of solid tumors

    Science.gov (United States)

    Kuhn, Peter; Bethel, Kelly

    2012-02-01

    Reliable measurement of internal bodily substances and structures is one of the cornerstones of modern medicine. Progress in cancer medicine, like that in many medical fields, must encompass and take advantage of progress in the physical sciences. Historically, the development and refinement of physical sciences-based detection of biological entities precedes periods of great advancements in therapies. To treat broken limbs and arthritis, we are indebted to Conrad Roentgen's discovery of x-rays by which we can evaluate the bones; to apply gamma knife therapy for cancer, we are indebted to Marie Curie's discoveries about radioactivity by which we can eradicate tumors; to manage the complications of diabetes, we are indebted to Tom Clemens, Ames Pharmaceuticals and Dick Bernstein's refinement of direct blood glucose measurement technology by which we can count, hour-to-hour, the waxing and waning of blood sugar levels; to understand anything at all on the cellular level, we are indebted to Antonie van Leeuwenhoek's microscope, by which we can see our cells. The application of physical sciences perspectives to biological and medical problems has a long and productive history. As of late, however, the increasing compartmentalization of science and exponential increases of knowledge in both arenas has resulted in a rift between the two. The NCI has initiated a research network establishing multiple centers of investigation, the Physical Sciences in Oncology Centers (http://physics.cancer.gov), which seek to mend the rift. Each headed by a pair of investigators, one in the physical sciences and one in the biological sciences, the centers seek to bring the advances and breakthroughs of the physical sciences world to bear on the question of cancer. This issue of physical biology contains a series of articles exploring the utility and applicability of a new method for measuring cancer as it spreads, developed at the Scripps Physical Oncology Center. Although some progress

  14. Oxaliplatin in Treating Young Patients With Recurrent Solid Tumors That Have Not Responded to Previous Treatment

    Science.gov (United States)

    2013-06-04

    Childhood Central Nervous System Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Hepatoblastoma; Childhood Hepatocellular Carcinoma; Childhood High-grade Cerebral Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Recurrent Adrenocortical Carcinoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Colon Cancer; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Nasopharyngeal Cancer; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer

  15. Special issue of clinical pharmacology: advances and applications in new protein therapeutics modulating tumor immunity

    Directory of Open Access Journals (Sweden)

    Frankel AE

    2013-11-01

    Full Text Available Arthur E Frankel Department of Internal Medicine, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA Until recent decades, the role of the immune system in harnessing tumor growth was based on anecdotal observations of increased cancers in immune-compromised patients, the benefits of graft-versus-leukemia in allogeneic stem cell transplants, and the limited but reproducible anticancer activity of several lymphokines, including interferon and interleukin (IL-2. Vaccine studies and infusions of "activated" lymphocytes yielded variable clinical responses and disease control. An improved understanding of the molecular and cell mechanisms of the innate and adaptive immune system in cancer-bearing animals and the discovery of an immune-suppressive tumor microenvironment then led to development and testing of a battery of new drug and cell-based approaches to trigger antitumor immunity. This issue of Clinical Pharmacology: Advances and Applications highlights some of the new protein-based compounds that are radically changing the cancer therapeutic landscape. The purpose of this collection of reviews is to inform the readership regarding the importance of the seismic change in cancer therapeutics and stimulate efforts to find novel niches and combinations of agents similar to recent advances in the application of cancer pathway inhibitors.

  16. Identification of a panel of tumor-associated antigens from breast carcinoma cell lines, solid tumors and testis cDNA libraries displayed on lambda phage

    Directory of Open Access Journals (Sweden)

    Cianfriglia Maurizio

    2004-11-01

    Full Text Available Abstract Background Tumor-associated antigens recognized by humoral effectors of the immune system are a very attractive target for human cancer diagnostics and therapy. Recent advances in molecular techniques have led to molecular definition of immunogenic tumor proteins based on their reactivity with autologous patient sera (SEREX. Methods Several high complexity phage-displayed cDNA libraries from breast carcinomas, human testis and breast carcinoma cell lines MCF-7, MDA-MB-468 were constructed. The cDNAs were expressed in the libraries as fusion to bacteriophage lambda protein D. Lambda-displayed libraries were efficiently screened with sera from patients with breast cancer. Results A panel of 21 clones representing 18 different antigens, including eight proteins of unknown function, was identified. Three of these antigens (T7-1, T11-3 and T11-9 were found to be overexpressed in tumors as compared to normal breast. A serological analysis of the 21 different antigens revealed a strong cancer-related profile for at least five clones (T6-2, T6-7, T7-1, T9-21 and T9-27. Conclusions Preliminary results indicate that patient serum reactivity against five of the antigens is associated with tumor disease. The novel T7-1 antigen, which is overexpressed in breast tumors and recognized specifically by breast cancer patient sera, is potentially useful in cancer diagnosis.

  17. Advances in identification and application of tumor antigen inducing anti-cancer responses

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    @@ Tumor antigen is one of the important bases of tumor immunotherapy[1]. With the discovery of novel tumor antigens, interest in specific immunotherapy for treatment of malignancies has increased substantially. Nowadays more and more scientists paid close attention to various tumor antigens with their roles or/and applications in anti-cancer immune responses, immune tolerance, tumor markers, tumor immunotherapy and so on. Here we discussed the classification of tumor antigens and summarized the technologies of identification and application of tumor antigens.

  18. Tumor de Frantz-Gruber, un tumor sólido pseudopapilar del páncreas poco frecuente Frantz-Gruber Tumor, An Infrecuent Solid Pseudopapillary Tumor Of The Pancreas

    Directory of Open Access Journals (Sweden)

    Humberto Álvarez-Pertuz

    2011-09-01

    Full Text Available El tumor de Frantz - Gruber es una masa sólida pseudopapilar del páncreas, poco común y con bajo potencial de malignidad, descrita por primera vez por Franz en 1959.¹ Predomina en mujeres entre la 3era y 4ta década de vida. La sintomatología está dada principalmente por efecto de masa y se caracteriza por dolor vago y sensación de plenitud. El diagnóstico radiológico incluye estudios como tomografía axial computarizada (TAC y resonancia magnética, y los estudios histológicos confirman la sospecha clínica. El abordaje es quirúrgico en la mayoría de los casos e incluye una resección completa del tumor. La presencia de metástasis hepática no es infrecuente. La sobrevida a 5 años es por arriba del 90%.² Se reporta el caso de un paciente de 15 años, sin antecedentes patológicos o quirúrgicos, visto en el Servicio de Emergencias por epigastralgia y vómitos. Un ultrasonido (US abdominal demostró una lesión en la cola pancreática, luego por TAC y US endoscópico se logró documentar una masa de aspecto quístico y contenido denso que abarca también el cuerpo del páncreas. Se recomendó abordaje quirúrgico; durante la laparotomía exploratoria se halla tumoración mixta sólidoquística. Se practicó pancreatectomía distal y esplenectomía. La evolución y manejo postoperatorio fueron sin complicaciones.The Frantz-Gruber tumor is a rare solid pseudopapilar mass of the pancreas characterized for its low malignant potential, first described by Franz in 1959.1 It occurs mainly in women between the third and fourth decades of life. Symptoms are determined by a mass effect, commonly non-specific abdominal pain and fullness sensation. Radiological diagnosis is mainly based on CT scan and Magnetic Resonance, while the histological findings confirm the clinical suspicion. Surgical management is recommended in most of the cases and implies complete resection of the tumor. Liver metastasis are not uncommon. Five year survival rates

  19. Recent advances in transmissible tumors%传染性肿瘤研究进展

    Institute of Scientific and Technical Information of China (English)

    尹婷婷; 王璐; 王国栋

    2015-01-01

    Transmissible tumors are a class of tumor that can be transmitted between individuals through liv-ing cells. So far, four types of transmissible tumors including canine transmissible venereal tumor (CTVT),Tasmanian devil facial tumor disease (DFTD), soft-shell clams leukemia (SSCL), and hamsters reticulum cell sarcoma (HRCS)have been discovered and identified. In the last decades, these transmissible tumors have been proved to be transmitted through living cells by cytological, histological and genetic studies. CTVT, the oldest mammalian somat-ic cell line, and DFTD originated from Schwann cell have been reported to avoid immunological recognition by down-regulatingMHC expression, while a high copy number of Steamer retrotransposon is commonly exist in SSCL. In recent years, the whole-genome sequencing of CTVT and DFTD have been completed which facilitates studies on the mechanisms of tumorigenesis, transmission and evolution of transmissible tumors at the whole-genome level. In this review, we summarize the recent advances in transmissible tumors and discuss the research focus in next decade.%传染性肿瘤是一类以活细胞形式在个体间异体传播的肿瘤。至今已发现并确定4种,即犬类生殖器传染性肿瘤(Canine transmissible venereal tumor, CTVT)、袋獾面部肿瘤(Tasmanian devil facial tumor disease, DFTD)、海螂血液传染性肿瘤(Soft-shell clams leukemia, SSCL)及仓鼠传染性肿瘤(Hamsters reticulum cell sarcoma, HRCS)。过去几十年,在细胞学、组织学、遗传学等方面的研究证明传染性肿瘤是以活细胞进行传播,CTVT是已知的最古老的哺乳动物体细胞系,DFTD来源于施旺细胞,两者均通过下调 MHC基因表达逃避宿主免疫识别,而在SSCL中普遍存在一个转座子多拷贝数变异。近几年来,DFTD和CTVT基因组测序工作相继完成,有助于从全基因组水平研究传染性肿瘤的发生、传染和进化机制。本文总结了传染性肿

  20. Molecular imaging using Cu-ATSM and FDG in solid canine tumors

    DEFF Research Database (Denmark)

    Hansen, Anders Elias

    Tumor hypoxia is one of the key factors in the development of aggressive and treatment resistant tumors. The negative effects of tumor hypoxia are mediated both by the direct lack of molecular oxygen for therapeutic efficacy and by pro- teomic and genomic changes induced in hypoxic tumor cells....... Identification of hypoxic tumor and intratumoral hypoxic regions therefore hold the potential to serve as a basis for individualized treatment protocols, including image guided radiation therapy. The current PhD project was undertaken to study tumor hypoxia in cancer bearing dogs, with the aims of 1) identifying...... the potential of implementing canine cancer patients in translational research on tumor hypoxia. 2) Non- invasively evaluate the hypoxia positron emission tomography (PET) tracer 64 Copper(II)diacetyl-bis(N 4 -methylthiosemicarbazone) ( 64 Cu-ATSM), including the comparison to non-invasive measures of tumor...

  1. A New Biological Feature of Natural Killer Cells: The Recognition of Solid Tumor-Derived Cancer Stem Cells

    Science.gov (United States)

    Tallerico, Rossana; Garofalo, Cinzia; Carbone, Ennio

    2016-01-01

    Natural killer (NK) cells are classified as a member of the innate lymphoid cells (ILCs) group 1. ILCs have been recently identified and grouped on the basis of their phenotypical and functional characteristics. They are effectors of innate immunity and are involved in secondary lymphoid organ generation and tissue remodeling. NK cells are powerful cytotoxic lymphocytes able to recognize and eliminate tumor- and virus-infected cells by limiting their spread and tissue damage. The recognition of tumor cells is mediated by both activating and inhibitory receptors. While in hematological malignancies the role played by NK cells is widely known, their role in recognizing solid tumors remains unclear. Recently, tumor cell populations have been divided into two compartments: cancer-initiating cells (CICs) or cancer stem cells (CSCs) and senescent tumor cells. Here, CSC will be used. CSCs are a small subset of malignant cells with stem-like properties that are involved in tumor maintenance and recurrence due to their ability to survive to traditional therapies; they are, moreover, poorly recognized by T lymphocytes. Recent data showed that NK cells recognize in vitro cancer-initiating cells derived from colon cancer, glioblastoma, and melanoma. However, more in vivo studies are urgently required to fully understand whether these new antitumor NK cells with cytotoxic capability may be considered in the design of new immunotherapeutic interventions. PMID:27242786

  2. Development of advanced version of ACTDOR software for determination of radioactivity content of solid radioactive waste

    International Nuclear Information System (INIS)

    It is a mandatory requirement of regulatory authority to know the activity content of radioactive solid waste disposed to the environment, which include assorted solid wastes and spent resins used in ion-exchange columns of process systems. This involves assessment of radioactivity content and the specification of radionuclides in the waste package before it is disposed in Near Surface Disposal Facility (NSDF). In house methods were developed at different nuclear power stations in the country to estimate the activity of the radioactive waste being generated and disposed. ACTDOR software was implemented and used at some nuclear power stations. To bring uniformity in the method of activity estimation, it was recommended to use ACTDOR at all the nuclear power stations. A Graphical User Interface (GUI) based user friendly version of ACTDOR software with additional features has been developed recently. This paper presents the development and the various features of the advanced ACTDOR software. ACTDOR is a software developed to quantify the radioactivity of solid waste in cylindrical geometry by measuring its external gamma radiation. It works on gamma shielding principles. ACTDOR software is developed in FORTRAN and the software is functioning in TEXT USER INTERFACE MODE. The advanced version of ACTDOR works in GUI MODE and has been developed with Visual Basic as Front End and Microsoft Access as Back End

  3. Advances in Tumor Screening, Imaging, and Avatar Technologies for High-Grade Serous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Anders eOhman

    2014-11-01

    Full Text Available The majority of high-grade serous ovarian carcinoma cases are detected in advanced stages when treatment options are limited. Surgery is less effective at eradicating the disease when it is widespread, resulting in high rates of disease relapse and chemoresistance. Current screening techniques are ineffective for early tumor detection and consequently, BRCA mutations carriers, with an increased risk for developing high-grade serous ovarian cancer, elect to undergo risk-reducing surgery. While prophylactic surgery is associated with a significant reduction in the risk of cancer development, it also results in surgical menopause and significant adverse side effects. The development of efficient early-stage screening protocols and imaging technologies is critical to improving the outcome and quality of life for current patients and women at increased risk. In addition, more accurate animal models are necessary in order to provide relevant in vivo testing systems and advance our understanding of the disease origin and progression. Moreover, both genetically engineered and tumor xenograft animal models enable the preclinical testing of novel imaging techniques and molecularly targeted therapies as they become available. Recent advances in xenograft technologies have made possible the creation of avatar mice, personalized tumorgrafts, which can be used as therapy testing surrogates for individual patients prior to or during treatment. High-grade serous ovarian cancer may be an ideal candidate for use with avatar models based on key characteristics of the tumorgraft platform. This review explores multiple strategies, including novel imaging and screening technologies in both patients and animal models, aimed at detecting cancer in the early stages and improving the disease prognosis.

  4. APOPTOSIS AND PROLIFERATION OF TUMOR CELLS IN LOCALLY ADVANCED CERVICAL CANCER AFTER NEOADJUVANT INTRAARTERIAL CHEMOTHERAPY

    Institute of Scientific and Technical Information of China (English)

    朱雪琼; 岳天孚; 惠京; 张颖; 王德华

    2003-01-01

    Objective: Through observing the clinical response to neoadjuvant intraarterial chemotherapy in locally advanced cervical cancer and investigating the changes of p53 protein expression, proliferation and apoptosis of tumor cells after chemotherapy, to study the relationship between biological markers and chemotherapeutic response. Methods: 20 women with locally advanced squamous cervical cancer received consecutive infusion chemotherapy of five days of cisplatin and adriamycin via the superselective uterine artery. The response to chemotherapy was evaluated by gynecologic examination and ultrasonography 3 weeks after chemotherapy. The changes of apoptotic index (AI), proliferation index (PI) and p53 expression of tumor cells were detected by immunohistochemical technique. Results: The clinical response rate of locally advanced squamous cervical cancer to uterine artery infusion chemotherapy was 70%. No change of PI was found 3 weeks after treatment, but AI significantly increased from 2.79±0.76 to 4.29±1.13 (P<0.01), and AI/PI from 5.68±1.21 to 9.00±1.95 (P<0.05). On the contrary, the expression of p53 was significantly decreased (P<0.05). Patients who responded to chemotherapy showed higher PI before chemotherapy and significantly increased AI and AI/PI after chemotherapy than non-responders (P<0.05). Conclusion: Higher PI was an indication for neoadjuvant intraarterial chemotherapy. One more cycle of chemotherapy should be given to those who have significantly increased AI or AI/PI after chemotherapy, while definite treatment such as surgery or/and radiotherapy should be immediately given to those patients without increased AI or AI/PI.

  5. Integrated municipal solid waste scenario model using advanced pretreatment and waste to energy processes

    International Nuclear Information System (INIS)

    Highlights: • Appropriate solution for MSW management in new and future EU countries. • Decrease of landfill disposal applying an Integrated MSW approach. • Technological impediments and environmental assessment. - Abstract: In this paper an Integrated Municipal Solid Waste scenario model (IMSW-SM) with a potential practical application in the waste management sector is analyzed. The model takes into account quantification and characterization of Municipal Solid Waste (MSW) streams from different sources, selective collection (SC), advanced mechanical sorting, material recovery and advanced thermal treatment. The paper provides a unique chain of advanced waste pretreatment stages of fully commingled waste streams, leading to an original set of suggestions and future contributions to a sustainable IMSWS, taking into account real data and EU principles. The selection of the input data was made on MSW management real case studies from two European regions. Four scenarios were developed varying mainly SC strategies and thermal treatment options. The results offer useful directions for decision makers in order to calibrate modern strategies in different realities

  6. Overview of the role of nanotechnological innovations in the detection and treatment of solid tumors

    Directory of Open Access Journals (Sweden)

    Frank D

    2014-01-01

    , nanotheranostics, antineoplastic drugs, poor aqueous solubility, solid tumors

  7. Detección molecular de enfermedad mínima residual en melanoma y otros tumores sólidos Molecular detection of minimal residual disease in melanoma and solid tumors

    Directory of Open Access Journals (Sweden)

    Valeria Vázquez

    2009-02-01

    Full Text Available La disponibilidad de métodos altamente sensibles y específicos para la detección de enfermedad mínima residual en pacientes con tumores sólidos podría tener importantes consecuencias pronósticas y terapéuticas. Uno de los métodos más usados para la detección molecular de células cancerosas es la técnica de RT-PCR, que permite la amplificación de secuencias de ARNm específicas de distintos tejidos. La misma fue aplicada por primera vez en la detección de células tumorales circulantes en sangre periférica de pacientes con melanoma avanzado, poco tiempo después fue adaptada para la búsqueda de enfermedad mínima residual en otros tumores sólidos. El objetivo de la presente revisión es evaluar la información publicada desde el primer estudio sobre este tema en 1991 y analizar el valor clínico de los hallazgos obtenidos. Se discute también la importancia del manejo de la muestra y de la estandarización de los procedimientos de RT-PCR.The availability of highly sensitive and specific methods for the detection of minimal residual disease in patients with solid tumors may have important prognostic and therapeutic implications. One of the most widely used methods for the molecular detection of cancer cells is the RT-PCR technique, which leads to the amplification of tissue-specific mRNA. It was firstly applied in the detection of circulating tumor cells in peripheral blood of patients with advanced melanoma; and soon it was adapted for the detection of minimal residual disease in other solid tumors. The aim of the present review is to evaluate the published data since the first study in 1991 and to analyze the clinical value of the findings obtained. The importance of sample handling and standardization of RT-PCR procedures is also discussed.

  8. Data on combination effect of PEG-coated gold nanoparticles and non-thermal plasma inhibit growth of solid tumors.

    Science.gov (United States)

    Kaushik, Nagendra Kumar; Kaushik, Neha; Yoo, Ki Chun; Uddin, Nizam; Kim, Ju Sung; Lee, Su Jae; Choi, Eun Ha

    2016-12-01

    Highly resistant tumor cells are hard to treat at low doses of plasma. Therefore, researchers have gained more attention to development of enhancers for plasma therapy. Some enhancers could improve the efficacy of plasma towards selectivity of cancer cells damage. In this dataset, we report the application of low doses of PEG-coated gold nanoparticles with addition of plasma treatment. This data consists of the effect of PEG-coated GNP and cold plasma on two solid tumor cell lines T98G glioblastoma and A549 lung adenocarcinoma. Cell proliferation, frequency of cancer stem cell population studies by this co-treatment was reported. Finally, we included in this dataset the effect of co-treatment in vivo, using tumor xenograft nude mice models. The data supplied in this article supports the accompanying publication "Low doses of PEG-coated gold nanoparticles sensitize solid tumors to cold plasma by blocking the PI3K/AKT-driven signaling axis to suppress cellular transformation by inhibiting growth and EMT" (N. K. Kaushik, N. Kaushik, K. C. Yoo, N Uddin, J. S. Kim, S. J. Lee et al., 2016) [1]. PMID:27668278

  9. Tumor lysis syndrome following transarterial chemoembolization for advanced hepatocellular carcinoma:report of one case%原发性肝癌TACE术后肿瘤坏死综合征一例

    Institute of Scientific and Technical Information of China (English)

    贾中芝; 田丰; 蒋国民

    2014-01-01

    Tumor lysis syndrome (TLS) results from a sudden and rapid release of nuclear and cytoplasmic degradation products from malignant cells. It is a rare complication in adult patients with solid tumors who are undergoing treatment. Herein, the authors present a case with advanced hepatocellular carcinoma (HCC) who developed TLS after transarterial chemoembolization (TACE), which was successfully treated with aggressive fluid administration, oral allopurinol and urine alkalization, hemodialysis and other supportive therapies. TLS following TACE should be suspected in HCC patients who has large and rapidly-growing lesion.

  10. Advanced materials for solid state hydrogen storage: “Thermal engineering issues”

    International Nuclear Information System (INIS)

    Hydrogen has been widely recognized as the “Energy Carrier” of the future. Efficient, reliable, economical and safe storage and delivery of hydrogen form important aspects in achieving success of the “Hydrogen Economy”. Gravimetric and volumetric storage capacities become important when one considers portable and mobile applications of hydrogen. In the case of solid state hydrogen storage, the gas is reversibly embedded (by physisorption and/or chemisorption) in a solid matrix. A wide variety of materials such as intermetallics, physisorbents, complex hydrides/alanates, metal organic frameworks, etc. have been investigated as possible storage media. This paper discusses the feasibility of lithium– and sodium–aluminum hydrides with emphasis on their thermodynamic and thermo-physical properties. Drawbacks such as poor heat transfer characteristics and poor kinetics demand special attention to the thermal design of solid state storage devices. - Highlights: • Advanced materials suitable for solid state hydrogen storage are discussed. • Issues related to thermodynamic and thermo-physical properties of hydriding materials are brought out. • Hydriding and dehydriding behavior including sorption kinetics of complex hydrides with emphasis on alanates are explained

  11. Solid tumors provide niche-specific conditions that lead to preferential growth of Salmonella

    Science.gov (United States)

    Silva-Valenzuela, Cecilia A.; Desai, Prerak T.; Molina-Quiroz, Roberto C.; Pezoa, David; Zhang, Yong; Porwollik, Steffen; Zhao, Ming; Hoffman, Robert M.; Contreras, Inés; Santiviago, Carlos A.; McClelland, Michael

    2016-01-01

    Therapeutic attenuated strains of Salmonella Typhimurium target and eradicate tumors in mouse models. However, the mechanism of S. Typhimurium for tumor targeting is still poorly understood. We performed a high-throughput screening of single-gene deletion mutants of S. Typhimurium in an orthotopic, syngeneic murine mammary model of breast cancer. The mutants under selection in this system were classified into functional categories to identify bacterial processes involved in Salmonella accumulation within tumors. Niche-specific genes involved in preferential tumor colonization were identified and exemplars were confirmed by competitive infection assays. Our results show that the chemotaxis gene cheY and the motility genes motAB confer an advantage for colonization of Salmonella within orthotopic syngeneic breast tumors. In addition, eutC, a gene belonging to the ethanolamine metabolic pathway, also confers an advantage for Salmonella within tumors, perhaps by exploiting either ethanolamine or an alternative nutrient in the inflamed tumor environment. PMID:27145267

  12. Potentiation of mitomycin C and porfiromycin antitumor activity in solid tumor models by recombinant human interleukin 1 alpha.

    Science.gov (United States)

    Braunschweiger, P G; Jones, S A; Johnson, C S; Furmanski, P

    1991-10-15

    The time- and dose-dependent effects of recombinant human interleukin 1 alpha (IL-1 alpha) on the antitumor activity of mitomycin C (MMC) and porfiromycin (PORF) were studied in RIF-1 and Panc02 solid tumor model systems. IL-1 alpha produced dose-dependent sensitization of clonogenic RIF-1 tumor cells to MMC in vivo. IL-1 alpha chemosensitization was highly schedule dependent, and the most efficacious schedules produced dose-modifying factors of 3.6 and 5.1 for MMC and PORF, respectively. More than additive clonogenic cell kill after IL-1 alpha-chemotherapy combinations reflected increased cellular sensitivity to MMC and PORF. The combinations also produced marked decreases in the yield of viable tumor cells, suggesting that the bioreductive drugs may have also potentiated the microvascular injury and ischemia produced by IL-1 alpha. Dexamethasone inhibited and ketoconazole, an inhibitor of corticosterone biosynthesis, enhanced IL-1 alpha-mediated chemosensitization in these models. IL-1 alpha mediated chemosensitization to MMC, and PORF was also demonstrated by tumor growth inhibition in the RIF-1 model and increased survival of mice in the spontaneously metastasizing Panc02 system. Chemosensitization of bone marrow spleen colony-forming units was not seen. IL-1 alpha (1000 units/ml) had no effect on MMC and PORF cytotoxicity in RIF-1 and PORF cell lines in vitro. The results indicate that the tumor-specific IL-1 alpha-induced pathophysiologies can sensitize solid tumors to agents which are preferentially activated, retained, and cytotoxic to cells under hypoxic conditions. Our results suggest that strategies combining bioreductively activated hypoxic cell cytotoxins and biological agents might offer efficacious alternatives or adjuvants to conventional combination approaches. PMID:1913664

  13. A block matching-based registration algorithm for localization of locally advanced lung tumors

    Science.gov (United States)

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2014-01-01

    Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm3), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%; p < 0.001). Left

  14. Development of an advanced bond coat for solid oxide fuel cell interconnector applications

    Science.gov (United States)

    Yeh, An-Chou; Chen, Yu-Ming; Liu, Chien-Kuo; Shong, Wei-Ja

    2015-11-01

    An advanced bond coat has been developed for solid oxide fuel cell interconnector applications; a low thermal expansion superalloy has been selected as the substrate, and the newly developed bond coat is applied between the substrate and the LSM top coat. The bond coat composition is designed to be near thermodynamic equilibrium with the substrate to minimize interdiffusion with the substrate while providing oxidation protection for the substrate. The bond coat exhibits good oxidation resistance, a low area specific resistance, and a low thermal expansion coefficient at 800 °C; experimental results indicate that interdiffusion between the bond coat and the substrate can be hindered.

  15. Applied solid state science advances in materials and device research 6

    CERN Document Server

    Wolfe, Raymond

    2013-01-01

    Applied Solid State Science: Advances in Materials and Device Research, Volume 6 covers the application of composites in electronic systems. The book discusses different types of composite-composite materials consisting of finely dispersed mixtures of metals and insulators; composite devices in which two distinct semiconductor devices are combined in one package; and composite glass fibers with the core and cladding differing in their optical properties. The text describes articles dealing with properties that can be achieved in versatile materials; light-emitting diodes and photodetectors th

  16. Applied solid state science advances in materials and device research 2

    CERN Document Server

    Wolfe, Raymond

    2013-01-01

    Applied Solid State Science: Advances in Materials and Device Research, Volume 2 covers topics about complex oxide materials such as the garnets, which dominate the field of magnetoelasticity and are among the most important laser hosts, and sodalite, which is one of the classic photochromic materials. The book discusses the physics of the interactions of electromagnetic, elastic, and spin waves in single crystal magnetic insulators. The text then describes the mechanism on which inorganic photochromic materials are based, as observed in a variety of materials in single crystal, powder, and gl

  17. Draft environmental impact statement: Space Shuttle Advanced Solid Rocket Motor Program

    Science.gov (United States)

    1988-01-01

    The proposed action is design, development, testing, and evaluation of Advanced Solid Rocket Motors (ASRM) to replace the motors currently used to launch the Space Shuttle. The proposed action includes design, construction, and operation of new government-owned, contractor-operated facilities for manufacturing and testing the ASRM's. The proposed action also includes transport of propellant-filled rocket motor segments from the manufacturing facility to the testing and launch sites and the return of used and/or refurbished segments to the manufacturing site.

  18. Monolithic solid oxide fuel cell technology advancement for coal-based power generation

    Energy Technology Data Exchange (ETDEWEB)

    1992-04-14

    The program is conducted by a team consisting of AiResearch Los Angeles Division of Allied-Signal Aerospace Company and Argonne National Laboratory (ANL). The objective of the program is to advance materials and fabrication methodologies to develop a monolithic solid oxide fuel cell (MSOFC) system capable of meeting performance, life, and cost goals for coal-based power generation. The program focuses on materials research and development, fabrication process development, cell/stack performance testing and characterization, cost and system analysis, and quality development.

  19. Squalamine inhibits angiogenesis and solid tumor growth in vivo and perturbs embryonic vasculature.

    Science.gov (United States)

    Sills, A K; Williams, J I; Tyler, B M; Epstein, D S; Sipos, E P; Davis, J D; McLane, M P; Pitchford, S; Cheshire, K; Gannon, F H; Kinney, W A; Chao, T L; Donowitz, M; Laterra, J; Zasloff, M; Brem, H

    1998-07-01

    The novel aminosterol, squalamine, inhibits angiogenesis and tumor growth in multiple animal models. This effect is mediated, at least in part, by blocking mitogen-induced proliferation and migration of endothelial cells, thus preventing neovascularization of the tumor. Squalamine has no observable effect on unstimulated endothelial cells, is not directly cytotoxic to tumor cells, does not alter mitogen production by tumor cells, and has no obvious effects on the growth of newborn vertebrates. Squalamine was also found to have remarkable effects on the primitive vascular bed of the chick chorioallantoic membrane, which has striking similarities to tumor capillaries. Squalamine may thus be well suited for treatment of tumors and other diseases characterized by neovascularization in humans. PMID:9661892

  20. New approach for treatment of advanced malignant tumors: combination of chemotherapy and photodynamic therapy

    Science.gov (United States)

    Wang, Lian-xing; Ju, Hua-lamg; Chem, Zhem-ming

    1995-03-01

    Eighty-three patients suffering from moderate or advanced malignant tumors were treated by combined chemotherapy and photodynamic therapy (PDT) in our hospital. The short term result of such management is very promising, the effectiveness seems to be nearly 100% and the general responsive rate is 79.5% (CR + PR). If compared with another group of 84 similar patients whom were treated with PDT alone, the short term efficacy is 85.7% while the general response rate is 54.7% (P statistic. The better result of the combined approach is probably due to the action of the chemotherapeutic agent, potentially blocking the mitosis of the cellular cycle at certain phases of the cancer cells, making the cell membrane become more permeable to the photochemical agent, HPD, and eliciting a better cancerocidal effect.

  1. Preliminary Study of Oxygen-Enhanced Longitudinal Relaxation in MRI: A Potential Novel Biomarker of Oxygenation Changes in Solid Tumors

    International Nuclear Information System (INIS)

    Purpose: There is considerable interest in developing non-invasive methods of mapping tumor hypoxia. Changes in tissue oxygen concentration produce proportional changes in the magnetic resonance imaging (MRI) longitudinal relaxation rate (R1). This technique has been used previously to evaluate oxygen delivery to healthy tissues and is distinct from blood oxygenation level-dependent (BOLD) imaging. Here we report application of this method to detect alteration in tumor oxygenation status. Methods and materials: Ten patients with advanced cancer of the abdomen and pelvis underwent serial measurement of tumor R1 while breathing medical air (21% oxygen) followed by 100% oxygen (oxygen-enhanced MRI). Gadolinium-based dynamic contrast-enhanced MRI was then performed to compare the spatial distribution of perfusion with that of oxygen-induced ΔR1. Results: ΔR1 showed significant increases of 0.021 to 0.058 s-1 in eight patients with either locally recurrent tumor from cervical and hepatocellular carcinomas or metastases from ovarian and colorectal carcinomas. In general, there was congruency between perfusion and oxygen concentration. However, regional mismatch was observed in some tumor cores. Here, moderate gadolinium uptake (consistent with moderate perfusion) was associated with low area under the ΔR1 curve (consistent with minimal increase in oxygen concentration). Conclusions: These results provide evidence that oxygen-enhanced longitudinal relaxation can monitor changes in tumor oxygen concentration. The technique shows promise in identifying hypoxic regions within tumors and may enable spatial mapping of change in tumor oxygen concentration.

  2. Emergent Stratification in Solid Tumors Selects for Reduced Cohesion of Tumor Cells: A Multi-Cell, Virtual-Tissue Model of Tumor Evolution Using CompuCell3D.

    Directory of Open Access Journals (Sweden)

    Maciej H Swat

    Full Text Available Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution. Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors.

  3. 实体瘤外周血循环肿瘤细胞与转移相关性的研究进展%Relationship between circulating tumor cells in peripheral blood of solid tumor and metastasis

    Institute of Scientific and Technical Information of China (English)

    任传利; 韩崇旭; 王大新

    2011-01-01

    目的:总结实体瘤外周血中循环肿瘤细胞(CTC)和转移相关性的研究进展.方法:以"循环肿瘤细胞、实体瘤、转移"为关键词,检索2000-01-2010-10PubMed、Science Direct、Ovid、Springer、CNKI和维普等数据库的相关文献.纳入标准:关于实体瘤CTC与转移密切相关的分子机制、临床相关性的文献.共纳入分析42篇文献.结果:随着分子生物学和材料技术的发展,越来越多的方法有效地富集和鉴定不同类型实体瘤外周血CTC.细胞基因水平证实CTC具有恶性生物学特性,CTC自身基因和转移相关蛋白谱的表达,肿瘤微环境、免疫系统等因素影响着CTC远处器官转移灶的形成.CTC数目、特定基因、蛋白的表达与治疗疗效、预后等具有相关性.结论:研究CTC参与血液播散转移的机制,为全面、准确地阐明恶性实体瘤转移的机制、个体化的治疗提供新的工具.%OBJECTIVE: To review of the studies the relationship between circulating tumor cells (CTC)in peripheral blood of solid tumors and the mechanism of metastasis. METHODS: Keyword: circulating tumor cell (CTC), solid tumors, metastasis. Retrieval system: PubMed, Ovid, Science Direct, Springer, CNKI,Weipu Data. The time limit: 2000-01- 2010-10. The enrolled criteria: about the relationship between CTC in peripheral blood of solid tumors and the mechanism of metastasis, its clinical relevance. Overall, 42 literatures were cited. RESULTS: As the development of the advanced technique of molecular biology and material,more and more methods can be used to enrich and identify CTC. It is reported that cytogenetic evidence that CTC in patients with carcinoma are malignant. The gene and related metastatic protein profile in CTC,tumor microenvironment, immune system can influence on tumor metastasis. The number of CTC, the expression of specific genes and proteins have a relationship with the effect of treatment and evaluation of prognosis. CONCLUSION: The study

  4. Epidermal growth factor receptor as a predictor of tumor downstaging in locally advanced rectal cancer patients treated with preoperative chemoradiotherapy

    International Nuclear Information System (INIS)

    Purpose: To examine retrospectively whether levels of epidermal growth factor receptor (EGFR) expression can predict tumor downstaging after preoperative chemoradiotherapy in patients with locally advanced rectal cancer. Methods and Materials: A total of 183 patients with rectal cancer (cT3-T4 or N+) were enrolled in this study. Preoperative chemoradiotherapy consisted of 50.4 Gy of pelvic radiation with concurrent 5-fluorouracil and leucovorin bolus intravenous chemotherapy in 94 patients or oral capecitabine and leucovorin in 89 patients. EGFR expression in pretreatment paraffin-embedded tumor biopsy specimens was assessed by immunohistochemistry. EGFR expression was determined from the intensity and extent of staining. Tumor downstaging was defined as a reduction of at least one T-stage level. Results: Tumor downstaging occurred in 97 patients (53%), and the tumors showed a pathologic complete response in 27 patients (15%). Positive EGFR expression was observed in 140 (76%) of 183 patients. EGFR expression levels were low in 113 patients (62%) and high in 70 patients (38%). On logistic regression analysis, the significant predictive factor for increased tumor downstaging was a low level of EGFR expression and preoperative chemotherapy using oral capecitabine (odds ratio, 0.437; p 0.012 vs. odds ratio, 3.235; p < 0.001, respectively). Conclusion: A high level of EGFR expression may be a significant predictive molecular marker for decreased tumor downstaging after preoperative chemoradiotherapy in locally advanced rectal cancer

  5. Applications of lipid nanocarriers for solid tumors therapy: literature review; Aplicacoes das nanoparticulas lipidicas no tratamento de tumores solidos: revisao de literatura

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Lidiane Correia de; Souza, Leonardo Gomes; Marreto, Ricardo Neves; Lima, Eliana Martins; Taveira, Stephania Fleury [Universidade Federal de Goias (UFG), Goiania, GO (Brazil). Fac. de Farmacia; Taveira, Eliseu Jose Fleury, E-mail: stephaniafleury@gmail.com [Hospital Erasto Gaertner, Curitiba, PR (Brazil). Oncologia Clinica

    2012-07-01

    Introduction: Lipid nanocarriers are systems used to target drugs to its site of action and have attracted attention of the scientific community because they are biocompatible and biodegradable. These systems can target drugs to solid tumors, providing sustained drug release in the site of action, thus increasing the utility of the antineoplastic chemotherapy. Objective: To review the available literature on in vivo experiments with lipid nanocarriers containing cytotoxic drugs for solid tumors treatment. Method: A search study was carried out in Pubmed{sup R} database from 2007 to 2011, with subject descriptors: liposomes, lipid nanoparticles, cancer and in vivo, with the boolean operator 'and' among them, in English. Results: 1,595 papers related to the use of liposomes and 77 related to lipid nanoparticles were found. Few studies reported in vivo experiments with lipid nanoparticles (28 papers) compared to liposomes (472 papers), since liposomes were developed two decades before lipid nanoparticles. Four liposomal medicines have already been approved and are used in the clinic while only one medicine containing lipid nanoparticles is in phase I of clinical studies. Conclusion: The number of papers related to the use of nanotechnology for cancer treatment is increasing rapidly, making important to know the different kinds of nanocarriers and, especially, those which are already used in the clinic. There are only few clinical studies on lipid nanocarriers; however, these systems present an enormous potential to improve the clinical practice in oncology. (author)

  6. Combined detection of serum tumor markers for differential diagnosis of solid lesions located at the pancreatic head

    Institute of Scientific and Technical Information of China (English)

    Quan Liao; Yu-Pei Zhao; Ying-Chi Yang; Li-Jun Li; Xiao Long; Shao-Mei Han

    2007-01-01

    BACKGROUND:The differential diagnosis of solid lesions located at the pancreatic head is very important for choosing therapies and setting up surgical tactics. This study was designed to evaluate the clinical signiifcance of combined measurement of multiple serum tumor markers and the application of the receiver-operating characteristic (ROC) curves in the differential diagnosis of solid lesions located at the pancreatic head. METHODS:The serum levels of CA19-9, CA242, CA50 and carcinoembryonic antigen (CEA) in 112 patients with carcinoma of the pancreatic head and 38 patients with focal chronic pancreatitis in the pancreatic head were measured with ELISA. The sensitivity, speciifcity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of the four serum tumor markers were calculated. The ROC curves for the four serum tumor markers were constructed and the area under the curve (AUC) was calculated. RESULTS:The AUCs of CA19-9, CA242, CA50 and CEA were 0.805, 0.749, 0.738 and 0.705; the PLRs were 1.91, 3.43, 5.09 and 5.46; and the NLRs were 0.41, 0.56, 0.59 and 0.71, respectively. Combined measurements increased the diagnostic speciifcity, and parallel combined testing increased the diagnostic sensitivity. CONCLUSIONS:Combined measurement of serum tumor markers CA19-9, CA242, CA50 and CEA is valuable in differential diagnosis of solid lesions located at the pancreatic head, and CA19-9 has the best diagnostic ability. Combined measurements can increase the speciifcity of diagnosis. Evaluation with the ROC curve is better than the sensitivity or speciifcity alone and the results are more integrated and objective.

  7. The ubiquitin+proteasome protein degradation pathway as a therapeutic strategy in the treatment of solid tumor malignancies.

    Science.gov (United States)

    Driscoll, James J; Minter, Alex; Driscoll, Daniel A; Burris, Jason K

    2011-02-01

    A concept that currently steers the development of cancer therapies has been that agents directed against specific proteins that facilitate tumorigenesis or maintain a malignant phenotype will have greater efficacy, less toxicity and a more sustained response relative to traditional cytotoxic chemotherapeutic agents. The clinical success of the targeted agent Imatinib mesylate as an inhibitor of the tyrosine kinase associated with the breakpoint cluster region-Abelson oncogene locus (BCR-ABL) in the treatment of Philadelphia-positive chronic myelogenous leukemia (CML) has served as a paradigm. While intellectually gratifying, the selective targeting of a single driver event by a small molecule, e.g., kinase inhibitor, to dampen a tumor-promoting pathway in the treatment of solid tumors is limited by many factors. Focus can alternatively be placed on targeting fundamental cellular processes that regulate multiple events, e.g., protein degradation, through the Ubiquitin (Ub)+Proteasome System (UPS). The UPS plays a critical role in modulating numerous cellular proteins to regulate cellular processes such as signal transduction, growth, proliferation, differentiation and apoptosis. Clinical success with the proteasome inhibitor bortezomib revolutionized treatment of B-cell lineage malignancies such as Multiple Myeloma (MM). However, many patients harbor primary resistance and do not respond to bortezomib and those that do respond inevitably develop resistance (secondary resistance). The lack of clinical efficacy of proteasome inhibitors in the treatment of solid tumors may be linked mechanistically to the resistance detected during treatment of hematologic malignancies. Potential mechanisms of resistance and means to improve the response to proteasome inhibitors in solid tumors are discussed.

  8. Outcome of Surgical Treatment for Metastatic Vertebra Bone Tumor in Advanced Lung Cancer

    Directory of Open Access Journals (Sweden)

    Akiko Fukuhara

    2010-03-01

    Full Text Available Background: Spinal metastases of patients with advanced stage lung cancer are an important target for palliative therapy, because their incidence is high, and they often cause severe symptoms and worsen the quality of life. Surgery is one of the most effective treatment options, but the indication of surgery is unclear as the procedure is invasive and patients with spinal metastasis have a rather short life expectancy. Furthermore, there have been few studies that have focused on lung cancer with poor prognosis. Methods: We reviewed all of the cases of lung cancer from January 1999 to July 2007 in the Department of Respiratory Medicine, Kyoto University Hospital, Japan. Thirteen patients with metastatic spinal tumor of lung cancer underwent surgery, and all of them had a poor performance status score (3 or 4. Results: Neurological improvement by at least 1 Frankel grade was seen in 10 of 14 cases (71%. Improvement of the movement capacity was noted in 9 of 14 cases (64%, and pain improvement was noted in 12 of 14 (86%. Median postoperative survival was 5 months (1–25 months. In particular, the group with a good postoperative performance status score (0–2 was shown to have a better median postoperative survival of 13 months. Conclusions: Surgical treatment for symptomatic metastatic spinal tumor of lung cancer can improve quality of life in a substantially high percentage of patients. Surgery should be considered even if preoperative performance status is poor.

  9. Imetelstat Sodium in Treating Younger Patients With Relapsed or Refractory Solid Tumors

    Science.gov (United States)

    2014-06-03

    Childhood Hepatoblastoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Rhabdomyosarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

  10. Tissue distribution and efficacy of gold nanorods coupled with laser induced photoplasmonic therapy in ehrlich carcinoma solid tumor model.

    Directory of Open Access Journals (Sweden)

    Mostafa A El-Sayed

    Full Text Available Gold nanorods (GNR within tumor microregions are characterized by their ability to absorb near IR light and emit heat in what is called photoplasmonic effect. Yet, the efficacy of nanoparticles is limited due to intratumoral tissue distribution reasons. In addition, distribution of GNRs to normal tissue might result in non specific toxicity. In the current study, we are assessing the intratumoral and tissue distribution of PEGylated GNRs on the top of its antitumor characteristics when given intravenously or intratumoral to solid tumor bearing mice and coupled with laser photoplasmonic sessions. PEGylated GNRs with a longitudinal size of less than 100 nm were prepared with aspect ratio of 4.6 showing strong surface plasmon absorption at wavelength 800 nm. Pharmacokinetics of GNR after single I.V. administration (0.1 mg/kg showed very short systemic circulating time (less than 3 h. On the other hand, tissue distribution of I.V. GNR (0.1 mg/kg to normal animals showed preferential deposition in spleen tissue. Repeated administration of I.V. GNR resulted in preferential accumulation in both liver and spleen tissues. In addition, I.V. administration of GNR to Ehrlich carcinoma tumor bearing mice resulted in similar tissue distribution; tumor accumulation and anti-tumor effect compared to intratumoral administration. In conclusion, the concentration of GNR achieved within tumors microregions after I.V. administration was comparable to I.T. administration and sufficient to elicit tumoral growth arrest when coupled with laser-aided photoplasmonic treatment.

  11. The downregulation of Mcl-1 via USP9X inhibition sensitizes solid tumors to Bcl-xl inhibition

    International Nuclear Information System (INIS)

    It has been shown in many solid tumors that the overexpression of the pro-survival Bcl-2 family members Bcl-xL and Mcl-1 confers resistance to a variety of chemotherapeutic agents. Mcl-1 is a critical survival protein in a variety of cell lineages and is critically regulated via ubiquitination. The Mcl-1, Bcl-xL and USP9X expression patterns in human lung and colon adenocarcinomas were evaluated via immunohistochemistry. Interaction between USP9X and Mcl-1 was demonstrated by immunoprecipitation-western blotting. The protein expression profiles of Mcl-1, Bcl-xL and USP9X in multiple cancer cell lines were determined by western blotting. Annexin-V staining and cleaved PARP western blotting were used to assay for apoptosis. The cellular toxicities after various treatments were measured via the XTT assay. In our current analysis of colon and lung cancer samples, we demonstrate that Mcl-1 and Bcl-xL are overexpressed and also co-exist in many tumors and that the expression levels of both genes correlate with the clinical staging. The downregulation of Mcl-1 or Bcl-xL via RNAi was found to increase the sensitivity of the tumor cells to chemotherapy. Furthermore, our analyses revealed that USP9X expression correlates with that of Mcl-1 in human cancer tissue samples. We additionally found that the USP9X inhibitor WP1130 promotes Mcl-1 degradation and increases tumor cell sensitivity to chemotherapies. Moreover, the combination of WP1130 and ABT-737, a well-documented Bcl-xL inhibitor, demonstrated a chemotherapeutic synergy and promoted apoptosis in different tumor cells. Mcl-1, Bcl-xL and USP9X overexpression are tumor survival mechanisms protective against chemotherapy. USP9X inhibition increases tumor cell sensitivity to various chemotherapeutic agents including Bcl-2/Bcl-xL inhibitors

  12. Combining [(11)C]-AnxA5 PET Imaging with Serum Biomarkers for Improved Detection in Live Mice of Modest Cell Death in Human Solid Tumor Xenografts

    OpenAIRE

    Q. Cheng; Lu, L; Grafström, J; Olofsson, MH; Thorell, JO; Samén, E; K. Johansson; Ahlzén, HS; Stone-Elander, S; Linder, S; Arnér, Elias S.J.

    2012-01-01

    BACKGROUND: In vivo imaging using Annexin A5-based radioligands is a powerful technique for visualizing massive cell death, but has been less successful in monitoring the modest cell death typically seen in solid tumors after chemotherapy. Here we combined dynamic positron emission tomography (PET) imaging using Annexin A5 with a serum-based apoptosis marker, for improved sensitivity and specificity in assessment of chemotherapy-induced cell death in a solid tumor model. METHODOLOGY/...

  13. Tumor Imaging in Patients with Advanced Tumors Using a New 99mTc-Radiolabeled Vitamin B12 Derivative

    DEFF Research Database (Denmark)

    Sah, Bert-Ram; Schibli, Roger; Waibel, Robert;

    2014-01-01

    of the lung, 3 with squamous cell carcinomas of the hypopharyngeal region, 1 with prostate adenocarcinoma, 1 with breast, and 1 with colon adenocarcinoma. RESULTS: The median age of the study group was 61 ± 11 y. Six of 10 patients showed positive tumor uptake on (99m)Tc-PAMA-cobalamin whole-body scintigraphy...... with various metastatic tumors. METHODS: Ten patients with biopsy-proven metastatic cancer were included. Dynamic imaging was started immediately after injection of 300-500 MBq of (99m)Tc-PAMA-cobalamin, and whole-body scintigrams were obtained at 10, 30, 60, 120, and 240 min and after 24 h. The relative tumor...

  14. The combined effect of electroporation and borocaptate in boron neutron capture therapy for murine solid tumors

    International Nuclear Information System (INIS)

    10B-Enriched borocaptate (BSH) was administered intraperitoneally to SCCVII tumor-bearing C3H/He mice. Electroporation (EP) was conducted by using a tweezers-type electrode. The 10B contents in tumors were measured by prompt γ-ray spectrometry. The colony formation assay was applied to investigate the antitumor effects of boron neutron capture therapy (BNCT) and thereby to estimate the intratumor localization of BSH. The 10B concentrations in tumors decreased with time following BSH administration, falling to 5.4(±0.1) ppm at 3 h, whereas EP treatment (3 repetitions) 15 min after BSH injection delayed the clearance of BSH from tumors, and the 10B level remained at 19.4(±0.9) ppm at 3 h. The effect of BNCT increased with the 10B concentration in tumors, and the combination with EP showed a remarkably large cell killing effect even at 3 h after BSH injection. The effect of BNCT, i.e., slope coefficient of the cell survival curve of tumors, without EP was proportional to tumor 10B level (r=0.982), and that of BSH-BNCT combined with EP lay close to the same correlation line. However, tumors subjected to EP after BSH injection did not show high radiosensitivity when irradiated after conversion to a single cell suspension by enzymatic digestion. This indicates that the increase of the BNCT effect by EP was a consequence of enclosure of BSH in the interstitial space of tumor tissue and not within tumor cells. This is different from a previous in vitro study. The combination of EP and BNCT may be clinically useful, if a procedure to limit EP to the tumor region becomes available or if an alternative similar method is employed. (author)

  15. Immunohistochemical detection of HIF-1α and CAIX in advanced head-and-neck cancer. Prognostic role and correlation with tumor markers and tumor oxygenation parameters

    International Nuclear Information System (INIS)

    Background: tumor hypoxia has an impact on the outcome of cancer patients treated with radiotherapy. The validity of endogenous markers such as hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase isozyme IX (CAIX) to detect therapeutically relevant levels of hypoxia within tumors is controversially discussed. Furthermore, the association of these hypoxia markers with tumor markers or tumor oxygenation parameters is of importance for understanding the relationship between the different factors. Patients and methods: tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radio(chemo)therapy were assessed by immunohistochemistry for the expression of HIF-1α and CAIX. The relationships of both markers with tumor oxygenation parameters, molecular factors like P53, OPN, VEGF, VHL, survivin, and Ki67 levels, and clinical parameters were studied. Results: bivariate analysis showed a significant correlation of HIF-1α expression with high P53 and high OPN expression, high serum VEGF levels, and low VHL and low Ki67 expression. The CAIX expression was inversely correlated with pH value and directly correlated with T-stage. However, no correlation was found between HIF-1α and CAIX expression. Neither in a univariate Cox proportional hazard regression nor in a Kaplan-Meier analysis did expression of HIF-1α or CAIX have a significant impact on clinical outcome. However, in a Kaplan-Meier analysis, the combination of both factors showed that patients with intratumoral overexpression of either HIF-1α or CAIX or both markers died on average 2 years earlier than patients whose tumors had low expression of both factors (p < 0.05). Conclusion: expression of HIF-1α and CAIX was correlated with different tumor parameters. Only combined HIF-1α and CAIX expression was significantly predictive of patients' overall survival. (orig.)

  16. An Overview of Combustion Mechanisms and Flame Structures for Advanced Solid Propellants

    Science.gov (United States)

    Beckstead, M. W.

    2000-01-01

    Ammonium perchlorate (AP) and cyclotretamethylenetetranitramine (HMX) are two solid ingredients often used in modern solid propellants. Although these two ingredients have very similar burning rates as monopropellants, they lead to significantly different characteristics when combined with binders to form propellants. Part of the purpose of this paper is to relate the observed combustion characteristics to the postulated flame structures and mechanisms for AP and HMX propellants that apparently lead to these similarities and differences. For AP composite, the primary diffusion flame is more energetic than the monopropellant flame, leading to an increase in burning rate over the monopropellant rate. In contrast the HMX primary diffusion flame is less energetic than the HMX monopropellant flame and ultimately leads to a propellant rate significantly less than the monopropellant rate in composite propellants. During the past decade the search for more energetic propellants and more environmentally acceptable propellants is leading to the development of propellants based on ingredients other than AP and HMX. The objective of this paper is to utilize the more familiar combustion characteristics of AP and HMX containing propellants to project the combustion characteristics of propellants made up of more advanced ingredients. The principal conclusion reached is that most advanced ingredients appear to burn by combustion mechanisms similar to HMX containing propellants rather than AP propellants.

  17. Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia

    Science.gov (United States)

    2016-07-20

    Hepatoblastoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Kidney Neoplasm; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

  18. Evaluation of uptake and distribution of gold nanoparticles in solid tumors

    Science.gov (United States)

    England, Christopheri G.; Gobin, André M.; Frieboes, Hermann B.

    2015-11-01

    Although nanotherapeutics offer a targeted and potentially less toxic alternative to systemic chemotherapy in cancer treatment, nanotherapeutic transport is typically hindered by abnormal characteristics of tumor tissue. Once nanoparticles targeted to tumor cells arrive in the circulation of tumor vasculature, they must extravasate from irregular vessels and diffuse through the tissue to ideally reach all malignant cells in cytotoxic concentrations. The enhanced permeability and retention effect can be leveraged to promote extravasation of appropriately sized particles from tumor vasculature; however, therapeutic success remains elusive partly due to inadequate intra-tumoral transport promoting heterogeneous nanoparticle uptake and distribution. Irregular tumor vasculature not only hinders particle transport but also sustains hypoxic tissue kregions with quiescent cells, which may be unaffected by cycle-dependent chemotherapeutics released from nanoparticles and thus regrow tumor tissue following nanotherapy. Furthermore, a large proportion of systemically injected nanoparticles may become sequestered by the reticulo-endothelial system, resulting in overall diminished efficacy. We review recent work evaluating the uptake and distribution of gold nanoparticles in pre-clinical tumor models, with the goal to help improve nanotherapy outcomes. We also examine the potential role of novel layered gold nanoparticles designed to address some of these critical issues, assessing their uptake and transport in cancerous tissue.

  19. Solid state fermentation for production of microbial cellulases: Recent advances and improvement strategies.

    Science.gov (United States)

    Behera, Sudhanshu S; Ray, Ramesh C

    2016-05-01

    Lignocellulose is the most plentiful non-food biomass and one of the most inexhaustible renewable resources on the planet, which is an alternative sustainable energy source for the production of second generation biofuels. Lignocelluloses are composed of cellulose, hemicellulose and lignin, in which the sugar polymers account for a large portion of the biomass. Cellulases belong to the glycoside hydrolase family and catalyze the hydrolysis of glyosidic linkages depolymerizing cellulose to fermentable sugars. They are multi-enzymatic complex proteins and require the synergistic action of three key enzymes: endoglucanase (E.C. 3.2.1.4), exoglucanase (E.C. 3.2.1.176) (E.C. 3.2.1.91) and β-glucosidase (E.C. 3.2.1.21) for the depolymerization of cellulose to glucose. Solid state fermentation, which holds growth of microorganisms on moist solid substrates in the absence of free flowing water, has gained considerable attention of late due its several advantages over submerged fermentation. The review summarizes the critical analysis of recent literature covering production of cellulase in solid state fermentation using advance technologies such as consolidated bioprocessing, metabolic engineering and strain improvement, and circumscribes the strategies to improve the enzyme yield. PMID:26601764

  20. Treating solid dairy manure using microwave-enhanced advanced oxidation process.

    Science.gov (United States)

    Kenge, Anju A; Liao, Ping H; Lo, Kwang V

    2009-08-01

    The microwave enhanced advanced oxidation process (MW/H(2)O(2)-AOP) was used to treat separated solid dairy manure for nutrient release and solids reduction. The MW/H(2)O(2)-AOP was conducted at a microwave temperature of 120 degrees C for 10 minutes, and at three pH conditions of 3.5, 7.3 and 12. The hydrogen peroxide dosage at approximately 2 mL per 1% TS for a 30 mL sample was used in this study, reflecting a range of 0.53-0.75 g H(2)O(2)/g dry sludge. The results indicated that substantial quantities of nutrients could be released into the solution at pH of 3.5. However, at neutral and basic conditions only volatile fatty acids and soluble chemical oxygen demand could be released. The analyses on orthophosphate, soluble chemical oxygen demands and volatile fatty acids were re-examined for dairy manure. It was found that the orthophosphate concentration for untreated samples at a higher % total solids (TS) was suppressed and lesser than actual. To overcome this difficulty, the initial orthophosphate concentration had to be measured at 0.5% TS.

  1. Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy.

    Science.gov (United States)

    Han, Dai Hoon; Joo, Dong Jin; Kim, Myoung Soo; Choi, Gi Hong; Choi, Jin Sub; Park, Young Nyun; Seong, Jinsil; Han, Kwang Hyub; Kim, Soon Il

    2016-09-01

    Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3-12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10-22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis. PMID:27401662

  2. Temsirolimus and Vinorelbine Ditartrate in Treating Patients With Unresectable or Metastatic Solid Tumors

    Science.gov (United States)

    2016-06-09

    Extensive Stage Small Cell Lung Cancer; Hereditary Paraganglioma; Male Breast Cancer; Malignant Paraganglioma; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Pheochromocytoma; Pancreatic Polypeptide Tumor; Recurrent Breast Cancer; Recurrent Cervical Cancer; Recurrent Endometrial Carcinoma; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Neuroendocrine Carcinoma of the Skin; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pheochromocytoma; Recurrent Prostate Cancer; Recurrent Renal Cell Cancer; Recurrent Small Cell Lung Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Regional Pheochromocytoma; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage III Neuroendocrine Carcinoma of the Skin; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Prostate Cancer; Stage III Renal Cell Cancer; Stage III Uterine Sarcoma; Stage IIIA Breast Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Breast Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Endometrial Carcinoma; Stage IV Neuroendocrine Carcinoma of the Skin; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IV Uterine Sarcoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer; Thyroid Gland Medullary Carcinoma

  3. Influences of neoadjuvant chemotherapy for serum tumor markers, invasion and metastasis related indexes of patients with advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    Chuan-Xi Chen

    2016-01-01

    Objective:To explore and analyze the influences on neoadjuvant chemotherapy for serum tumor markers, invasion and metastasis related indexes of patients with advanced breast cancer.Methods:Patients with advanced breast cancer who had been treated in our hospital from February 2010 to February 2014 were randomly selected as research objects. They were randomly divided into control group (conventional surgical treatment group) and observation group (neoadjuant chemotherapy group). There were 32 cases of each group. Then, the changes of the different periods of serum tumor markers, invasion and metastasis related indexes in pretherapy and post-treatment of patients with advanced breast cancer in the two groups were observed.Results:The postoperative serum tumor markers, invasion and metastasis related indexes in different periods of the observation group were all lower than those of the control group, and the postoperative evaluation indexes of the two groups had significant difference. Conclusions:Neoadjuvant chemotherapy has great influences on serum tumor markers, invasion and metastasis related indexes of patients with advanced breast cancer and possesses high clinical application values.

  4. Germline polymorphisms may act as predictors of response to preoperative chemoradiation in locally advanced T3 rectal tumors

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise G; Nielsen, Jens N; Lindebjerg, Jan;

    2007-01-01

    PURPOSE: Patients with locally advanced T3 rectal tumors who present with complete pathologic response to preoperative chemoradiation have a low rate of local recurrence and an excellent prognosis. Predictive markers for complete pathologic response are needed with the perspective of improving in...

  5. Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors

    International Nuclear Information System (INIS)

    Several stromal cell subtypes including macrophages contribute to tumor progression by inducing epithelial-mesenchymal transition (EMT) at the invasive front, a mechanism also linked to metastasis. Tumor associated macrophages (TAM) reside mainly at the invasive front but they also infiltrate tumors and in this process they mainly assume a tumor promoting phenotype. In this study, we asked if TAMs also regulate EMT intratumorally. We found that TAMs through TGF-β signaling and activation of the β-catenin pathway can induce EMT in intratumoral cancer cells. We depleted macrophages in F9-teratocarcinoma bearing mice using clodronate-liposomes and analyzed the tumors for correlations between gene and protein expression of EMT-associated and macrophage markers. The functional relationship between TAMs and EMT was characterized in vitro in the murine F9 and mammary gland NMuMG cells, using a conditioned medium culture approach. The clinical relevance of our findings was evaluated on a tissue microarray cohort representing 491 patients with non-small cell lung cancer (NSCLC). Gene expression analysis of F9-teratocarcinomas revealed a positive correlation between TAM-densities and mesenchymal marker expression. Moreover, immunohistochemistry showed that TAMs cluster with EMT phenotype cells in the tumors. In vitro, long term exposure of F9-and NMuMG-cells to macrophage-conditioned medium led to decreased expression of the epithelial adhesion protein E-cadherin, activation of the EMT-mediating β-catenin pathway, increased expression of mesenchymal markers and an invasive phenotype. In a candidate based screen, macrophage-derived TGF-β was identified as the main inducer of this EMT-associated phenotype. Lastly, immunohistochemical analysis of NSCLC patient samples identified a positive correlation between intratumoral macrophage densities, EMT markers, intraepithelial TGF-β levels and tumor grade. Data presented here identify a novel role for macrophages in EMT

  6. Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors

    Directory of Open Access Journals (Sweden)

    Bonde Anne-Katrine

    2012-01-01

    Full Text Available Abstract Background Several stromal cell subtypes including macrophages contribute to tumor progression by inducing epithelial-mesenchymal transition (EMT at the invasive front, a mechanism also linked to metastasis. Tumor associated macrophages (TAM reside mainly at the invasive front but they also infiltrate tumors and in this process they mainly assume a tumor promoting phenotype. In this study, we asked if TAMs also regulate EMT intratumorally. We found that TAMs through TGF-β signaling and activation of the β-catenin pathway can induce EMT in intratumoral cancer cells. Methods We depleted macrophages in F9-teratocarcinoma bearing mice using clodronate-liposomes and analyzed the tumors for correlations between gene and protein expression of EMT-associated and macrophage markers. The functional relationship between TAMs and EMT was characterized in vitro in the murine F9 and mammary gland NMuMG cells, using a conditioned medium culture approach. The clinical relevance of our findings was evaluated on a tissue microarray cohort representing 491 patients with non-small cell lung cancer (NSCLC. Results Gene expression analysis of F9-teratocarcinomas revealed a positive correlation between TAM-densities and mesenchymal marker expression. Moreover, immunohistochemistry showed that TAMs cluster with EMT phenotype cells in the tumors. In vitro, long term exposure of F9-and NMuMG-cells to macrophage-conditioned medium led to decreased expression of the epithelial adhesion protein E-cadherin, activation of the EMT-mediating β-catenin pathway, increased expression of mesenchymal markers and an invasive phenotype. In a candidate based screen, macrophage-derived TGF-β was identified as the main inducer of this EMT-associated phenotype. Lastly, immunohistochemical analysis of NSCLC patient samples identified a positive correlation between intratumoral macrophage densities, EMT markers, intraepithelial TGF-β levels and tumor grade. Conclusions Data

  7. Radiotherapy and high-dose chemotherapy in advanced Ewing's tumors

    Energy Technology Data Exchange (ETDEWEB)

    Pape, H.; Glag, M.; Gripp, S.; Wittkamp, M.; Schmitt, G. [Duesseldorf Univ. (Germany). Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie; Laws, H.J.; Kaik, B. van; Goebel, U. [Duesseldorf Univ. (Germany). Abt. Paediatrische Haematologie und Onkologie; Burdach, S. [Halle Univ. (Germany). Abt. Paediatrie; Juergens, H. [Muenster Univ. (Germany). Abt. Paediatrische Hematologie und Onkologie

    1999-10-01

    Background: Ewing's tumors are sensitive to radio- and chemotherapy. Patients with multifocal disease suffer a poor prognosis. Patients presenting primary bone marrow involvement or bone metastases at diagnosis herald a 3-year disease-free survival below 15%. The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) has established the following indications for high-dose therapy in advanced Ewing's tumors: Patients with primary multifocal bone disease, patients with early (<2 years after diagnosis) or multifocal relapse. Patients and Method: As of 1987, 83 patients have been treated in the EICESS group, 39 of them at the transplant center in Duesseldorf, who have been analyzed here. All individuals received 4 courses of induction chemotherapy with EVAJA and stem cell collection after course 3 and 4. Consolidation radiotherapy of the involved bone compartments was administered in a hyperfractionated regimen 2 times 1.6 Gy per day, up to 22.4 Gy simultaneously to course 5 and 22.4 Gy to course 6 of chemotherapy. The myeloablative chemotherapy consisted of melphalan and etoposide (ME) in combination with 12 Gy TBI (Hyper-ME) oder Double-ME with whole lung irradiation up to 18 Gy (without TBI). Results: The survival probability at 40 months was 31% (44% DOD; 15% DOC). Pelvic infiltration did not reach prognostic relevance in this cohort. Radiotherapy encompassed 75% of the bone marrow at maximum (average 20%). Engraftment was not affected by radiotherapy. Conclusion: High-dose chemotherapy can improve outcome in poor prognostic advanced Ewing's tumors. The disease itself remains the main problem. The expected engraftment problems after intensive radiotherapy in large volumes of bone marrow can be overcome by stem cell reinfusion. (orig.) [German] Hintergrund: Ewing-Tumoren sind radio- und chemosensibel. Im metastasierten Stadium ist die Prognose schlecht. Patienten mit Knochen- oder Knochenmarkinfiltration haben nach drei Jahren eine

  8. Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy

    Directory of Open Access Journals (Sweden)

    Bracko Matej

    2010-02-01

    Full Text Available Abstract Background Electrochemotherapy treats tumors by combining specific chemotherapeutic drugs with an intracellular target and electric pulses, which increases drug uptake into the tumor cells. Electrochemotherapy has been successfully used for treatment of easily accessible superficial tumor nodules. In this paper, we present the first case of deep-seated tumor electrochemotherapy based on numerical treatment planning. Methods The aim of our study was to treat a melanoma metastasis in the thigh of a patient. Treatment planning for electrode positioning and electrical pulse parameters was performed for two different electrode configurations: one with four and another with five long needle electrodes. During the procedure, the four electrode treatment plan was adopted and the patient was treated accordingly by electrochemotherapy with bleomycin. The response to treatment was clinically and radiographically evaluated. Due to a partial response of the treated tumor, the metastasis was surgically removed after 2 months and pathological analysis was performed. Results A partial response of the tumor to electrochemotherapy was obtained. Histologically, the metastasis showed partial necrosis due to electrochemotherapy, estimated to represent 40-50% of the tumor. Based on the data obtained, we re-evaluated the electrical treatment parameters in order to correlate the treatment plan with the clinical response. Electrode positions in the numerical model were updated according to the actual positions during treatment. We compared the maximum value of the measured electric current with the current predicted by the model and good agreement was obtained. Finally, tumor coverage with an electric field above the reversible threshold was recalculated and determined to be approximately 94%. Therefore, according to the calculations, a small volume of tumor cells remained viable after electrochemotherapy, and these were sufficient for tumor regrowth

  9. Comprehensive Screening of Gene Copy Number Aberrations in Formalin-Fixed, Paraffin-Embedded Solid Tumors Using Molecular Inversion Probe-Based Single-Nucleotide Polymorphism Array.

    Science.gov (United States)

    Singh, Rajesh R; Mehrotra, Meenakshi; Chen, Hui; Almohammedsalim, Alaa A; Sahin, Ayesagul; Bosamra, Alex; Patel, Keyur P; Routbort, Mark J; Lu, Xinyan; Ronald, Abraham; Mishra, Bal Mukund; Virani, Shumaila; Medeiros, L Jeffrey; Luthra, Rajyalakshmi

    2016-09-01

    Gene copy number aberrations (CNAs) represent a major class of cancer-related genomic alterations that drive solid tumors. Comprehensive and sensitive detection of CNAs is challenging because of often low quality and quantity of DNA isolated from the formalin-fixed, paraffin-embedded (FFPE) solid tumor samples. Here, in a clinical molecular diagnostic laboratory, we tested the utility and validated a molecular inversion probe-based (MIP) array to routinely screen for CNAs in solid tumors. Using low-input FFPE DNA, the array detects genome-wide CNAs with a special focus on 900 cancer-related genes. A cohort of 76 solid tumors of various types and tumor cellularity (20% to 100%), and four cancer cell lines were used. These harbored CNAs in clinically important genes (ERBB2, EGFR, FGFR1, KRAS, MYC) as detected by orthogonal techniques like next-generation sequencing or fluorescence in situ hybridization. Results of the MIP array were concordant with results from orthogonal techniques, and also provided additional information regarding the allelic nature of the CNAs. Limit-of-detection and assay reproducibility studies showed a high degree of sensitivity and reproducibility of detection, respectively. FFPE compatibility, ability to detect CNAs with high sensitivity, accuracy, and provide valuable information such as loss of heterozygosity along with relatively short turnaround times makes the MIP array a desirable clinical platform for routine screening of solid tumors in a clinical laboratory. PMID:27392636

  10. [Incidence and Risk Assessment of Tumor Lysis Syndrome in Patients with Advanced Germ Cell Cancer].

    Science.gov (United States)

    Kurobe, Masahiro; Kawai, Koji; Tanaka, Ken; Ichioka, Daishi; Yoshino, Takayuki; Kandori, Shuya; Kawahara, Takashi; Waku, Natsui; Takaoka, Ei-Ichirou; Kojima, Takahiro; Joraku, Akira; Suetomi, Takahiro; Miyazaki, Jun; Nishiyama, Hiroyuki

    2016-05-01

    Tumor lysis syndrome (TLS) is a major oncological emergency. TLS is common in patients with hematological malignancies, but it can occur across a spectrum of cancer types. Germ cell tumors (GCT) have rapid cancer cell turnover and often present with bulky metastasis. The international TLS expert consensus panel has recommended guidelines for a medical decision tree to assign low, intermediate and high risk to patients with cancer at risk for TLS. GCT is classified as intermediate risk for TLS, and the patients who have other TLS risks factors are classified to be at high risk for TLS. In this study, we retrospectively analyzed 67 patients with metastatic GCT who were treated with induction chemotherapy at Tsukuba University Hospital between 2000 and 2013. Thirty-one, 15 and 21 patients were classified with good-, intermediate- and poor-prognosis disease, respectively, according to the International Germ Cell Cancer Collaborative Group criteria. Twelve patients (18%) were classified to be at high risk for TLS, and two patients were treated with allopurinol or rasburicase as prophylaxes for TLS. They did not show progression to laboratory TLS (L-TLS). In the remaining 10 TLS high-risk patients, three (30%) patients developed L-TLS after chemotherapy and started receiving oral allopurinol. As a result, no patients developed clinical TLS (C-TLS). In this study, 30% of TLS-high risk patients developed L-TLS without prophylactic treatment. Therefore, it is important to conduct TLS-risk stratification and consider prophylaxis such as rasburicase for advanced GCT patients at induction chemotherapy. PMID:27320114

  11. Associations Between Epidermal Growth Factor Receptor Gene Mutation and Serum Tumor Markers in Advanced Lung Adenocarcinomas:A Retrospective Study

    Institute of Scientific and Technical Information of China (English)

    Ying-qiu Pan; Wei-wu Shi; Dan-ping Xu; Hui-hui Xu; Mei-ying Zhou; Wei-hua Yan

    2014-01-01

    Objective To investigate the associations between epidermal growth factor receptor (EGFR) gene mutations and serum tumor markers in advanced lung adenocarcinomas. Methods We investigated the association between EGFR gene mutations and clinical features, including serum tumor marker levels, in 97 advanced lung adenocarcinomas patients who did not undergo the treatment of EGFR tyrosine kinase inhibitors. EGFR gene mutation was detected by real-time PCR at exons 18, 19, 20, and 21. Serum tumor marker concentrations were analyzed by chemiluminescence assay kit at the same time. Results EGFR gene mutations were detected in 42 (43%) advanced lung adenocarcinoma patients. Gender (P=0.003), smoking status (P=0.001), and abnormal serum status of carcinoembryonic antigen (CEA, P=0.028) were significantly associated with EGFR gene mutation incidence. Multivariate analysis showed the abnormal CEA level in serum was independently associated with the incidence of EGFR gene mutation (P=0.046) with an odds ratio of 2.613 (95%CI:1.018-6.710). However, receiver operating characteristic (ROC) curve analysis revealed CEA was not an ideal predictive marker for EGFR gene mutation status in advanced lung adenocarcinoma (the area under the ROC curve was 0.608, P=0.069). Conclusions EGFR gene mutation status is significantly associated with serum CEA status in advanced lung adenocarcinmoas. However, serum CEA is not an ideal predictor for EGFR mutation.

  12. The relationship between glasgow prognostic score and serum tumor markers in patients with advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Glasgow Prognostic Score (GPS) has been reported as a powerful prognostic tool for patients with advanced non–small cell lung cancer (NSCLC). The aim of this study was to assess the relationship between GPS and prognosis related tumor markers in patients with advanced NSCLC. We included 138 advanced NSCLC patients and twenty healthy controls in the study. GPS was calculated by combined serum C-reactive protein (CRP) and albumin. Three serum tumor markers, which included cytokeratin 19 fragment antigen 21-1 (CYFRA21–1), carcinoembryonic antigen (CEA) and tissue polypeptide specific antigen (TPS), were detected by enzyme-linked immunosorbent assay (ELISA). GPS and tumor markers were all assessed before chemotherapy. All patients received at least 2 courses of cisplatin-based chemotherapy. After that, 2 to 5 years follow-up was conducted. Median levels of CYFRA21–1 were 1.5 ng/ml (0.1–3.1 ng/ml) in healthy controls, and 4.6 ng/ml (0.7–35.2 ng/ml) in GPS 0 advanced NSCLC, 11.2 ng/ml (0.4–89.2) ng/ml in GPS 1 advanced NSCLC, and 15.7 ng/ml (2.9–134.6 ng/ml) in GPS 2 advanced NSCLC, respectively. Median levels of CYFRA21-1 were higher in NSCLC patients than in healthy controls, and CYFRA21-1 increased gradually according to GPS category in NSCLC patients (P < 0.05). Similar results were found for median levels of CEA and TPS in healthy controls and NSCLC patients (P < 0.05). In NSCLC patients, positive correlations were found between CYFRA21-1 and GPS, CEA and GPS, TPS and GPS. The Spearman’s rank correlation coefficient were 0.67 (P < 0.05), 0.61 (P < 0.05) and 0.55 (P < 0.05), respectively. Survival analyses showed GPS was an independent prognostic factor for advanced NSCLC. CYFRA21-1(>3.3 ng/ml) and TPS (>80 U/l) were related with the prognosis of advanced NSCLC by univariate analyses, but multivariate analyses showed CYFRA21-1, TPS and CEA were not the independent prognostic factors for advanced NSCLC. Our results showed GPS were positive correlated

  13. Advanced multi-fuelled solid oxide fuel cells (ASOFCs) using functional nanocomposites for polygeneration

    Energy Technology Data Exchange (ETDEWEB)

    Raza, Rizwan [Department of Physics, COMSATS Institute of Information Technology, Lahore (Pakistan); Department of Energy Technology, Royal Institute of Technology, Stockholm (Sweden); Qin, Haiying; Samavati, Mahrokh; Zhu, Bin [Department of Energy Technology, Royal Institute of Technology, Stockholm (Sweden); Liu, Qinghua [Tianjin Laboratory for Chemical Engineering (Tianjin University), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072 (China); Lima, Raquel B. [Department of Fiber and Polymer Technology, Royal Institute of Technology, KTH, 10044, Stockholm (Sweden)

    2011-11-15

    An advanced multifuelled solid oxide fuel cell (ASOFC) with a functional nanocomposite was developed and tested for use in a polygeneration system. Several different types of fuel, for example, gaseous (hydrogen and biogas) and liquid fuels (bio-ethanol and bio-methanol), were used in the experiments. Maximum power densities of 1000, 300, 600, 550 mW cm{sup -2} were achieved using hydrogen, bio-gas, bio-methanol, and bio-ethanol, respectively, in the ASOFC. Electrical and total efficiencies of 54% and 80% were achieved using the single cell with hydrogen fuel. These results show that the use of a multi-fuelled system for polygeneration is a promising means of generating sustainable power. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  14. Reorientation phenomena in imidazolium methyl sulfonate as probed by advanced solid-state NMR.

    Science.gov (United States)

    Goward, Gillian R; Saalwächter, Kay; Fischbach, Ingrid; Spiess, Hans Wolfgang

    2003-01-01

    Evidence for reorientation of imidazolium rings in imidazolium methylsulfonate is demonstrated using solid-state NMR. This material is a model system for exciting new proton-conducting materials based on imidazole. Two advanced NMR methods, including 1H-13C and 1H-15N recoupled polarization transfer with dipolar sideband pattern analysis and analysis of the coalescence of 13C lineshapes are used to characterize the ring reorientation. The process is found to occur at temperatures well below the melting point of the salt, between 240 and 380 K, and is described by a single activation energy, of 38+/-5 kJ/mol. This material is considered as a model system for quantifying the ring reorientation process, which is often proposed to be the rate-limiting step in proton transport in imidazole-based proton conducting materials.

  15. Recent Advances in the Use of Sodium Borohydride as a Solid State Hydrogen Store

    Directory of Open Access Journals (Sweden)

    Jianfeng Mao

    2015-01-01

    Full Text Available The development of new practical hydrogen storage materials with high volumetric and gravimetric hydrogen densities is necessary to implement fuel cell technology for both mobile and stationary applications. NaBH4, owing to its low cost and high hydrogen density (10.6 wt%, has received extensive attention as a promising hydrogen storage medium. However, its practical use is hampered by its high thermodynamic stability and slow hydrogen exchange kinetics. Recent developments have been made in promoting H2 release and tuning the thermodynamics of the thermal decomposition of solid NaBH4. These conceptual advances offer a positive outlook for using NaBH4-based materials as viable hydrogen storage carriers for mobile applications. This review summarizes contemporary progress in this field with a focus on the fundamental dehydrogenation and rehydrogenation pathways and properties and on material design strategies towards improved kinetics and thermodynamics such as catalytic doping, nano-engineering, additive destabilization and chemical modification.

  16. Solid Waste Management Requirements Definition for Advanced Life Support Missions: Results

    Science.gov (United States)

    Alazraki, Michael P.; Hogan, John; Levri, Julie; Fisher, John; Drysdale, Alan

    2002-01-01

    Prior to determining what Solid Waste Management (SWM) technologies should be researched and developed by the Advanced Life Support (ALS) Project for future missions, there is a need to define SWM requirements. Because future waste streams will be highly mission-dependent, missions need to be defined prior to developing SWM requirements. The SWM Working Group has used the mission architecture outlined in the System Integration, Modeling and Analysis (SIMA) Element Reference Missions Document (RMD) as a starting point in the requirement development process. The missions examined include the International Space Station (ISS), a Mars Dual Lander mission, and a Mars Base. The SWM Element has also identified common SWM functionalities needed for future missions. These functionalities include: acceptance, transport, processing, storage, monitoring and control, and disposal. Requirements in each of these six areas are currently being developed for the selected missions. This paper reviews the results of this ongoing effort and identifies mission-dependent resource recovery requirements.

  17. Advanced control approach for hybrid systems based on solid oxide fuel cells

    International Nuclear Information System (INIS)

    Highlights: • Advanced new control system for SOFC based hybrid plants. • Proportional–Integral approach with feed-forward technology. • Good control of fuel cell temperature. • All critical properties maintained inside safe conditions. - Abstract: This paper shows a new advanced control approach for operations in hybrid systems equipped with solid oxide fuel cell technology. This new tool, which combines feed-forward and standard proportional–integral techniques, controls the system during load changes avoiding failures and stress conditions detrimental to component life. This approach was selected to combine simplicity and good control performance. Moreover, the new approach presented in this paper eliminates the need for mass flow rate meters and other expensive probes, as usually required for a commercial plant. Compared to previous works, better performance is achieved in controlling fuel cell temperature (maximum gradient significantly lower than 3 K/min), reducing the pressure gap between cathode and anode sides (at least a 30% decrease during transient operations), and generating a higher safe margin (at least a 10% increase) for the Steam-to-Carbon Ratio. This new control system was developed and optimized using a hybrid system transient model implemented, validated and tested within previous works. The plant, comprising the coupling of a tubular solid oxide fuel cell stack with a microturbine, is equipped with a bypass valve able to connect the compressor outlet with the turbine inlet duct for rotational speed control. Following model development and tuning activities, several operative conditions were considered to show the new control system increased performance compared to previous tools (the same hybrid system model was used with the new control approach). Special attention was devoted to electrical load steps and ramps considering significant changes in ambient conditions

  18. Design and application of solid, dense backfill advanced mining technology with two pre-driving entries

    Institute of Scientific and Technical Information of China (English)

    Zhang Qiang; Zhang Jixiong; Guo Shuai; Gao Rui; Li Weikang

    2015-01-01

    New solid backfill mining technology provides unique technical advantages for‘three-under’ coal min-ing which refers to coal resources trapped under buildings, railways, and water bodies. This technology has a much higher recovery rate and can effectively control the surface subsidence. However, successful application of this technology depends heavily on geological conditions. To avoid the disadvantages asso-ciated with downward mining and overhead backfilling with this new technology, a new advanced solid backfill mining design with two pre-driving entries is proposed here to ensure the backfill effect. Taking Huayuan coal mine as an example, this paper tests the double gob-side entries retaining with no pillar left scheme and optimizes an integrated technology setup for backfill mining and gob-side entry retain-ing. Field applications show that the recovery rate increased from 40%for strip mining to 85%for backfill mining. Moreover, the new backfill technology allowed for better control over the surrounding rock deformation caused by the gob-side entry retaining effect and better control of ground subsidence as compared to strip mining.

  19. Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours

    Science.gov (United States)

    Bahleda, Rastislav; Hollebecque, Antoine; Varga, Andrea; Gazzah, Anas; Massard, Christophe; Deutsch, Eric; Amellal, Nadia; Farace, Françoise; Ould-Kaci, Mahmoud; Roux, Flavien; Marzin, Kristell; Soria, Jean-Charles

    2015-01-01

    Background: This Phase I study evaluated continuous- and intermittent-dosing (every other week) of afatinib plus nintedanib in patients with advanced solid tumours. Methods: In the dose-escalation phase (n=45), maximum tolerated doses (MTDs) were determined for continuous/intermittent afatinib 10, 20, 30 or 40 mg once daily plus continuous nintedanib 150 or 200 mg twice daily. Secondary objectives included safety and efficacy. Clinical activity of continuous afatinib plus nintedanib at the MTD was further evaluated in an expansion phase (n=25). Results: The most frequent dose-limiting toxicities were diarrhoea (11%) and transaminase elevations (7%). Maximum tolerated doses were afatinib 30 mg continuously plus nintedanib 150 mg, and afatinib 40 mg intermittently plus nintedanib 150 mg. Treatment-related adverse events (mostly Grade ⩽3) included diarrhoea (98%), asthenia (64%), nausea (62%) and vomiting (60%). In the dose-escalation phase, two patients had partial responses (PRs) and 27 (60%) had stable disease (SD). In the expansion phase, one complete response and three PRs were observed (all non-small cell lung cancer), with SD in 13 (52%) patients. No pharmacokinetic interactions were observed. Conclusions: MTDs of continuous or intermittent afatinib plus nintedanib demonstrated a manageable safety profile with proactive management of diarrhoea. Antitumour activity was observed in patients with solid tumours. PMID:26512876

  20. Requirements Development Issues for Advanced Life Support Systems: Solid Waste Management

    Science.gov (United States)

    Levri, Julie A.; Fisher, John W.; Alazraki, Michael P.; Hogan, John A.

    2002-01-01

    Long duration missions pose substantial new challenges for solid waste management in Advanced Life Support (ALS) systems. These possibly include storing large volumes of waste material in a safe manner, rendering wastes stable or sterilized for extended periods of time, and/or processing wastes for recovery of vital resources. This is further complicated because future missions remain ill-defined with respect to waste stream quantity, composition and generation schedule. Without definitive knowledge of this information, development of requirements is hampered. Additionally, even if waste streams were well characterized, other operational and processing needs require clarification (e.g. resource recovery requirements, planetary protection constraints). Therefore, the development of solid waste management (SWM) subsystem requirements for long duration space missions is an inherently uncertain, complex and iterative process. The intent of this paper is to address some of the difficulties in writing requirements for missions that are not completely defined. This paper discusses an approach and motivation for ALS SWM requirements development, the characteristics of effective requirements, and the presence of those characteristics in requirements that are developed for uncertain missions. Associated drivers for life support system technological capability are also presented. A general means of requirements forecasting is discussed, including successive modification of requirements and the need to consider requirements integration among subsystems.

  1. Alterations of Lymphoid Enhancer Factor-1 Isoform Expression in Solid Tumors and Acute Leukemias

    Institute of Scientific and Technical Information of China (English)

    Wenbing WANG; Carsten M(U)LLER-TIDOW; Ping JI; Bj(o)rn STEFFEN; Ralf METZGER; Paul M. SCHNEIDER; Hartmut HALFTER; Mark SCHRADER; Wolfgang E. BERDEL; Hubert SERVE

    2005-01-01

    Two major transcripts of lymphoid enhancer factor-1 (LEF-1) have been described. The long isoform with β-catenin binding domain functions as a transcriptional enhancer factor. The short isoform derives from an intronic promoter and exhibits dominant negative activity. Recently, alterations of LEF- 1isoforms distribution have been described in colon cancer. In the current study we employed a quantitative real-time reverse transcription PCR method (TaqMan) to analyze expression of LEF-1 isoforms in a large cohort of human tumor (n=304) and tumor-free control samples (n=56). The highest expression level of LEF-1 was found in carcinoma samples whereas brain cancer samples expressed little. Expression of LEF1 was different in distinct cancer types. For example, the mRNA level of LEF-1 was lower in testicular tumor samples compared with tumor-free control samples. Besides epithelial cancers, significant LEF-1expression was also found in hematopoietic cells. In hematological malignancies, overall LEF-1 level was higher in lymphocytic leukemias compared with myeloid leukemias and normal hematopoiesis. However,acute myeloid leukemia and acute lymphocytic leukemia showed a significantly increased fraction of the oncogenic LEF-1 compared with chronic lymphocytic leukemia and chronic myeloid leukemia. Taken together,these data suggest that LEF-1 is abundantly expressed in human tumors and the ratio of the oncogenic and the dominant negative short isoform altered not only in carcinomas but also in leukemia.

  2. Using Optical Spectroscopy to Longitudinally Monitor Physiological Changes within Solid Tumors

    Directory of Open Access Journals (Sweden)

    Karthik Vishwanath

    2009-09-01

    Full Text Available The feasibility of using quantitative diffuse reflectance spectroscopy to longitudinally monitor physiological response to cancer therapy was evaluated in a preclinical model. This study included two groups of nude mice bearing 4T1 flank tumors (N = 50, half of which were treated with a maximum tolerated dose of doxorubicin (DOX. Diffuse reflectance spectra were collected from tumors during a period of 2 weeks using a fiber-optic probe coupled to a spectrometer. These spectra were quantified using an inverse scalable Monte Carlo model of light transport in tissue to extract the concentrations of oxygenated, deoxygenated hemoglobin (dHb, and a wavelength mean reduced scattering coefficient (. The tumor growth rates of the treated and control groups were nearly identical, as were changes in the scattering parameter during this time frame. However, tumors treated with DOX showed a transient but significant increase in blood oxygen saturation. A comparison between the optically derived and immunohistochemical end points in a subset of the 50 animals showed that the temporal kinetics of dHb concentration and were highly concordant with those of hypoxic and necrotic fractions, respectively. In conclusion, optical methods could function as a “screening” technology in longitudinal studies of small animal tumor models to accelerate development and testing of new anticancer drugs. This technique could isolate specific landmark time points at which more expensive and sophisticated imaging methods or immunohistochemistry could be performed.

  3. Testicular tumors

    Directory of Open Access Journals (Sweden)

    Giovanni Rosti

    2011-12-01

    Full Text Available Germ cell tumors of the testes represent a unique paradigm of diseases which can be cured even in extremely advanced phase. Unfortunately, this makes them unique among adult solid tumors. Seminoma and non seminoma are relatively rare with approximatively 25,000 patients in Europe per year, but numbers are increasing world wide. Different strategies are needed depending on stage and prognostic scores. Seminoma is extremely sensitive to radiation therapy and chemotherapy, while all germ cell tumors show a very good response to chemotherapy. Clinical stage I seminoma is currently treated with radiation, single course carboplatin or surveillance policy. Clinical stage I non seminoma can also be approached with different strategies such as retroperitoneal lymph node dissection, observation or one-two courses of standard chemotherapy. Stage II seminoma may be treated with either radiation or chemotherapy, while for all advanced stages chemotherapy is mandatory. Since the mid-eighties PEB (Cisplatin, Etoposide and Bleomycin is the regimen of choice and no other schedule has proved superior in terms of efficacy. Surgery on the residual disease is crucial to the whole strategy and should be performed or attempted in all cases. Consequently, the correct treatment strategy for these tumors does not depend only on the ability of a single physician, but on a skilled team specialized in this particular tumor. Second line therapies (VeIP, PEI, TIP can cure 25%–40% of patients, but improved strategies for resistant tumors are desperately needed. High-dose chemotherapy has shown very good results in some studies while being less impressive in others. In any case, it should remain an option for relapsing patients and could be used in some cases of upfront chemotherapy in patients with slow marker decline, but this should only be considered in referring centers.

  4. Genistein increases epidermal growth factor receptor signaling and promotes tumor progression in advanced human prostate cancer.

    Directory of Open Access Journals (Sweden)

    Hisae Nakamura

    Full Text Available Genistein is an isoflavone found in soy, and its chemo-preventive and -therapeutic effects have been well established from in vitro studies. Recently, however, its therapeutic actions in vivo have been questioned due to contradictory reports from animal studies, which rely on rodent models or implantation of cell lines into animals. To clarify in vivo effects of genistein in advanced prostate cancer patients, we developed a patient-derived prostate cancer xenograft model, in which a clinical prostatectomy sample was grafted into immune deficient mice. Our results showed an increased lymph node (LN and secondary organ metastases in genistein-treated mice compared to untreated controls. Interestingly, invasive malignant cells aggregated to form islands/micrometastasis only in the secondary organs of the genistein-treated groups, not in the untreated control group. To understand the underlying mechanism for metastatic progression, we examined cell proliferation and apoptosis on paraffin-sections. Immunohistological data show that tumors of genistein-treated groups have more proliferating and fewer apoptotic cancer cells than those of the untreated group. Our immunoblotting data suggest that increased proliferation and metastasis are linked to enhanced activities of tyrosine kinases, EGFR and its downstream Src, in genistein-treated groups. Despite the chemopreventive effects proposed by earlier in vitro studies, the cancer promoting effect of genistein observed here suggests the need for careful selection of patients and safer planning of clinical trials.

  5. Effectiveness and safety of proton beam therapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sung Uk; Park, Joong-Won; Kim, Tae Hyun; Kim, Yeon-Joo; Woo, Sang Myung; Koh, Young-Hwan; Lee, Woo Jin; Park, Sang-Jae; Kim, Dae Yong; Kim, Chang-Min [National Cancer Center, Center for Liver Cancer, Research Institute and Hospital, Goyang-si, Gyeonggi-do (Korea, Republic of)

    2014-09-15

    To evaluate the clinical effectiveness and safety of proton beam therapy (PBT) in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). Twenty-seven HCC patients with PVTT underwent PBT, including 22 patients with modified International Union Against Cancer (mUICC) stage IVA,five patients with stage IVB primary tumors, and 16 with main PVTT. A median dose of 55 GyE (range, 50-66 GyE) in 20-22 fractions was delivered to a target volume encompassing both the PVTT and primary tumor. Overall, treatment was well tolerated, with no toxicity of grade ≥ 3. Median overall survival (OS) times in all patients and in stage IVA patients were 13.2 months and 16 months, respectively. Assessments of PVTT response showed complete response in 0 of 27 (0 %) patients, partial response in 15 (55.6 %), stable disease in 10 (37 %), and progressive disease in 2 (7.4 %) patients, with an objective response rate of 55.6 %. PVTT responders showed significantly higher actuarial 1-year local progression-free survival (LPFS; 85.6 % vs. 51.3 %), relapse-free survival (RFS; 20 % vs. 0 %) and OS (80 % vs. 25 %) rates than nonresponders (p < 0.05 each). Multivariate analysis showed that PVTT response and mUICC stage were independent prognostic factors for OS. Our data suggest that PBT could improve LPFS, RFS, and OS in advanced HCC patients with PVTT and it is feasible and safe for these patients. (orig.) [German] In der vorliegenden Arbeit wurde versucht, die klinische Wirksamkeit und Sicherheit der Protonenstrahltherapie (PBT) fuer Patienten mit fortgeschrittenem Leberzellkarzinom (HCC) in Verbindung mit Portadertumorthrombosen (PVTT) zu bewerten. Ausgefuehrt wurde die PBT fuer 27 HCC-Patienten mit PVTT, einschliesslich 22 Patienten im mUICC-Stadium (''International Union Against Cancer'') IVA sowie 5 Patienten mit Primaertumor im Stadium IVB und 16 Patienten mit PVTT im primaeren Stadium nach der geaenderten UICC-Klassifikation. Eine

  6. Clinical study of co-treatment with DC-CIK cells for advanced solid carcinomas%树突状细胞联合CIK细胞应用于晚期恶性实体瘤治疗的临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    Tao Yang; Ying Xiang; Yucheng Li; Jianghe Shao; Qiying Li; Huiqing Yu

    2011-01-01

    Objective: The aim of this study was to observe the therapeutic effect of cytokine induced killer (CIK) cells in combination with dendritic cells (DCs) on advanced solid carcinoma patients. Methods: Isolated peripheral blood mononuclear cells (PBMCs) from 110 advanced solid tumor patients. Added granulocyte-macrophage colony-stimulating factor (GM-CSF),tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) to adherent cells to induce DCs, and sensitized DCs with antigens of autologous tumor cells or extrinsic tumor cell lines. Cultured suspending cells with interferon-γ(IFN-y), interleukin-2 (IL-2) and CD3 monoclonal antibody (CD3 McAb) to prepare CIK cells, then co-cultured with DCs. After analyzing the phenotype and checking tumor markers and immune function, the autologous CIK cells and DCs were transfused into the cancer patients.Results: Forty-two patients with measurable nidus, 2 achieved complete remission (CR), 9 partial remission (PR) and 15 stable disease (SD), while 37 patients with immeasurable nidus, 25 had efficient response. The tumor markers and immune function both improved significantly compared with those before treatment. Conclusion: DCs and CIK cells combinational treatment is safe and effective on advanced solid carcinoma and provide a new and efficacious immunity therapeutic methods for the cancer patients.

  7. Solid-pseudopapillary tumor of the pancreas: Clinical experience and literature review

    Institute of Scientific and Technical Information of China (English)

    Hsueh-Lien Huang; Shou-Chuan Shih; Wen-Hsiung Chang; Tsang-En Wang; Ming-Jen Chen; Yu-Jan Chan

    2005-01-01

    AIM: To evaluate the clinical presentations of solidpseudopapillary tumor of the pancreas (SPT) and examine the diagnosis, treatment, low grade malignant potential of this rare disease.METHODS: We retrospectively reviewed a series of seven patients with SPT managed in our hospital between July 1990 and October 2003. Six females and one male with mean age of 31 years (range 13 to 50 years) were diagnosed with SPT at our institution.RESULTS: Clinical presentation included a palpable abdominal mass in two patients and vague abdominal discomfort in another two. Two patients were asymptomatic;their tumors were found incidentally on abdominal sonographic examination for other reasons. The final patient was admitted with hemoperitoneum secondary to tumor rupture. The mean diameter of the tumors in the seven patients was 10.5 cm (range 5 to 20 cm). The lesions were located in the body and tail in five cases and in the head of the pancreas in two. Surgical procedures included distal pancreatectomy (3), distal pancreatectomy with splenectomy (2), pancreaticoduodenectomy (1) and a pylorus-preserving Whipple procedure (1). There were gross adhesions or histological evidence of infiltration to the adjacent pancreas and/or splenic capsule in four cases. None of the patients received adjuvant therapy.The mean follow up was 7 years (range 0.5 to 14 years).One patient developed multiple liver metastases after 14 years of follow up.CONCLUSION: SPT is a rare tumor that behaves less aggressively than other pancreatic tumor. However, in cases with local invasion, long-term follow up is advisable.

  8. Optimizing the Delivery of Short-Lived Alpha Particle-Emitting Isotopes to Solid Tumors

    International Nuclear Information System (INIS)

    The underlying hypothesis of this project was that optimal alpha emitter-based radioimmunotherapy (RAIT) could be achieved by pairing the physical half-life of the radioisotope to the biological half-life of the targeting vehicle. The project had two specific aims. The first aim was to create and optimize the therapeutic efficacy of 211At-SAPS-C6.5 diabody conjugates. The second aim was to develop bispecific-targeting strategies that increase the specificity and efficacy of alpha-emitter-based RAIT. In the performance of the first aim, we created 211At-SAPS-C6.5 diabody conjugates that specifically targeted the HER2 tumor associated antigen. In evaluating these immunoconjugates we determined that they were capable of efficient tumor targeting and therapeutic efficacy of established human tumor xenografts growing in immunodeficient mice. We also determined that therapeutic doses were associated with late renal toxicity, likely due to the role of the kidneys in the systemic elimination o f these agents. We are currently performing more studies focused on better understanding the observed toxicity. In the second aim, we successfully generated bispecific single-chain Fv (bs-scFv) molecules that co-targeted HER2 and HER3 or HER2 and HER4. The in vitro kinetics and in vivo tumor-targeting properties of these molecules were evaluated. These studies revealed that the bs-scFv molecules selectively localized in vitro on tumor cells that expressed both antigens and were capable of effective tumor localization in in vivo studies

  9. STAT3 as a target for inducing apoptosis in solid and hematological tumors

    Institute of Scientific and Technical Information of China (English)

    Khandaker Al Zaid Siddiquee; James Turkson

    2008-01-01

    Studies in the past few years have provided compelling evidence for the critical role of aberrant Signal Transducer and Activator of Transcription 3 (STAT3) in malignant transformation and tumorigenesis. Thus, it is now generally accepted that STAT3 is one of the critical players in human cancer formation and represents a valid target for novel anticancer drug design. This review focuses on aberrant STAT3 and its role in promoting tumor cell survival and supporting the malignant phenotype. A brief evaluation of the current strategies targeting STAT3 for the development of novel anticancer agents against human tumors harboring constitutively active STAT3 will also be presented.

  10. An Adaptive Multigrid Algorithm for Simulating Solid Tumor Growth Using Mixture Models

    OpenAIRE

    Wise, S.M.; Lowengrub, J.S.; Cristini, V

    2011-01-01

    In this paper we give the details of the numerical solution of a three-dimensional multispecies diffuse interface model of tumor growth, which was derived in (Wise et al., J. Theor. Biol. 253 (2008)) and used to study the development of glioma in (Frieboes et al., NeuroImage 37 (2007) and tumor invasion in (Bearer et al., Cancer Research, 69 (2009)) and (Frieboes et al., J. Theor. Biol. 264 (2010)). The model has a thermodynamic basis, is related to recently developed mixture models, and is c...

  11. Advances in solid-catalytic and non-catalytic technologies for biodiesel production

    International Nuclear Information System (INIS)

    Highlights: • The recent technologies for promoting biodiesel synthesis were elucidated. • The design of catalyst consideration of biodiesel production was proposed. • The recent advances and remaining difficulties in biodiesel synthesis were outlined. • The future research trend in biodiesel synthesis was highlighted. - Abstract: The insecure supply of fossil fuel coerces the scientific society to keep a vision to boost investments in the renewable energy sector. Among the many renewable fuels currently available around the world, biodiesel offers an immediate impact in our energy. In fact, a huge interest in related research indicates a promising future for the biodiesel technology. Heterogeneous catalyzed production of biodiesel has emerged as a preferred route as it is environmentally benign needs no water washing and product separation is much easier. The number of well-defined catalyst complexes that are able to catalyze transesterification reactions efficiently has been significantly expanded in recent years. The activity of catalysts, specifically in application to solid acid/base catalyst in transesterification reaction depends on their structure, strength of basicity/acidity, surface area as well as the stability of catalyst. There are various process intensification technologies based on the use of alternate energy sources such as ultrasound and microwave. The latest advances in research and development related to biodiesel production is represented by non-catalytic supercritical method and focussed exclusively on these processes as forthcoming transesterification processes. The latest developments in this field featuring highly active catalyst complexes are outlined in this review. The knowledge of more extensive research on advances in biofuels will allow a deeper insight into the mechanism of these technologies toward meeting the critical energy challenges in future

  12. The Effects of Severe Hypoxia on Glycolytic Flux and Enzyme Activity in a Model of Solid Tumors.

    Science.gov (United States)

    Smith, Hannah; Board, Mary; Pellagatti, Andrea; Turley, Helen; Boultwood, Jacqueline; Callaghan, Richard

    2016-08-01

    Solid tumors contend with, and adapt to, a hostile micro-environment that includes limited availability of nutrient fuels and oxygen. The presence of hypoxia (O2 <5%) stabilizes the transcription factor Hif1 and results in numerous cellular adaptations including increased flux of glucose through glycolysis. Increasingly, more sophisticated analysis of tumor oxygenation has revealed large gradients of oxygen tension and significant regions under severe hypoxia (O2 ∼0.1%). The present investigation has demonstrated a significant increase in the glycolytic flux rate when tumor spheroids were exposed to 0.1% O2 . The severe hypoxia was associated with uniform pimonidazole adduct formation and elevated levels of Hif1α and c-Myc. This resulted in elevated expression of GLUT and MCT transporters, in addition to increased activity of PFK1 in comparison to that observed in normoxia. However, the protein expression and enzymatic capacity of HK2, G6PDH, PK, and LDH were all reduced by severe hypoxia. Clearly, the effects of exposure to severe hypoxia lead to a significantly abridged Hif1 response, yet one still able to elevate glycolytic flux and prevent loss of intermediates to anabolism. J. Cell. Biochem. 117: 1890-1901, 2016. © 2016 Wiley Periodicals, Inc. PMID:26755257

  13. 5-[125I]iodo-2'-deoxyuridine in the radiotherapy of solid CNS tumors in rats

    International Nuclear Information System (INIS)

    We have been investigating the therapeutic efficacy of the thymidine analog 5-iodo-2'-deoxyuridine (IUdR) when radiolabeled with the Auger electron emitter 125I in rats bearing intrathecal (i.t.) or intracerebral (i.c.) 9L gliosarcoma solid tumors. [125I]IUdR was infused i.t. (via subarachnoid catheters) or intracerebrally over a 5- or 2-day period; equimolar concentrations of [127I]IUdR were infused into control animals. High-leg paralysis and/or survival were followed over time. The results indicate that compared with [127I]IUdR, rats bearing intrathecal tumors and infused i.t. with [125I]IUdR showed significant prolongation of the onset of medium paralysis (15.2 versus 9 days). Similarly, the median survival of rats bearing intracerebral tumors and infused i.c. with [125I]IUdR was significantly increased (24 versus 17 days). The data substantiate the antineoplastic potential of [125I]IUdR and indicate a promising role for this radiopharmaceutical in the treatment of CNS cancers. (orig.)

  14. A Phase 2 Study of Cediranib in Combination With Olaparib in Advanced Solid Tumors

    Science.gov (United States)

    2016-09-30

    Estrogen Receptor Negative; HER2/Neu Negative; Metastatic Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Small Cell Lung Carcinoma; Stage III Pancreatic Cancer; Stage IIIA Breast Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Small Cell Lung Carcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Small Cell Lung Carcinoma; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Small Cell Lung Carcinoma; Stage IVA Pancreatic Cancer; Stage IVB Pancreatic Cancer; Triple-Negative Breast Carcinoma

  15. Synergy of topotecan in combination with vincristine for treatment of pediatric solid tumor xenografts

    NARCIS (Netherlands)

    Thompson, J; George, EO; Poquette, CA; Cheshire, PJ; Richmond, LB; Stewart, CF; Houghton, PJ

    1999-01-01

    Topotecan and vincristine were evaluated alone or in combination against 13 independent xenografts and 1 vincristine-resistant derivative, representing childhood neuroblastoma (n = 6), rhabdomyosarcoma (n = 5), or brain tumors (n = 3), Topotecan was given by i.v. bolus on a schedule found previously

  16. Vaccine Therapy and Pembrolizumab in Treating Patients With Solid Tumors That Have Failed Prior Therapy

    Science.gov (United States)

    2016-07-07

    Adult Solid Neoplasm; Bladder Carcinoma; Colon Carcinoma; Estrogen Receptor Negative; Head and Neck Squamous Cell Carcinoma; Hepatocellular Carcinoma; HER2/Neu Negative; Melanoma; Non-Small Cell Lung Carcinoma; Pancreatic Carcinoma; Progesterone Receptor Negative; Rectal Carcinoma; Renal Cell Carcinoma; Soft Tissue Sarcoma; Triple-Negative Breast Carcinoma

  17. Forebyggelse af skeletrelaterede hændelser hos patienter med knoglemetastaser ved solide tumorer

    DEFF Research Database (Denmark)

    Kamby, Claus; Tarp, Simon; Mellemgaard, Anders;

    2014-01-01

    This article is based on a systematic literature search and meta-analyses of clinical data regarding effects of bisphosphonates (BP) and denosumab (DS) on preventing skeletal related events (SRE) in patients with bone metastases from solid tumours. Although there are pharmacological differences...

  18. Present status and recent advances in living donor liver transplantation for malignant hepatic tumors

    Institute of Scientific and Technical Information of China (English)

    Jian-Min Qin; Yasutsugu Takada; Shinji Uemoto; Koichi Tanaka

    2008-01-01

    BACKGROUND:Living donor liver transplantation (LDLT) has been increasingly used to treat hepatic tumors worldwide in recent years, and is currently the most effective alternative to deceased donor liver transplantation to overcome the problem of organ shortage. LDLT has played an enormous role in treating early malignant hepatic tumors. But the indication of LDLT for malignant hepatic tumors is based on indeifnite criteria. This review summarizes the recent studies in LDLT for treating malignant hepatic tumors. DATA SOURCES:A literature research of the PubMed database was conducted and research articles were reviewed. RESULTS:The current data on LDLT for malignant hepatic tumors, combined with our hospital experience, indicated that if a patient with hepatocellular carcinoma (HCC) who meets with the conventional Milan criteria cannot undergo tumor resection because of poorly preserved liver function, and a cadaveric graft is dififcult to obtain within six months, LDLT may be selected. In a patient with recurrence of HCC after conventional therapies, feasibility, optimal timing, and efifcacy of LDLT as a second-line treatment should be determined. CONCLUSIONS:Tumor recurrence is related to the biological behavior and staging of the tumor. New immunosuppressors which have anti-tumor effects and inhibit the immune system need to be developed. The indications of LDLT for hepatic malignant tumors should be selected meticulously.

  19. Locally advanced rectal cancer: Value of ADC mapping in prediction of tumor response to radiochemotherapy

    International Nuclear Information System (INIS)

    Purpose: To evaluate the diagnostic performance of quantitative apparent diffusion coefficient (ADC) measurements, in the assessment of the therapeutic response to chemo-radiation therapy (CRT) in patients with locally advanced rectal cancer, by analyzing post CRT values of ADC, in relation to tumor regression grade (TRG) obtained by histopathologic evaluation of the rectal specimen. Methods: This prospective study was approved by an Institutional Review Board, and informed consent was obtained from all patients. Thirty-one patients with locally advanced rectal cancer underwent pre and post CRT MR imaging at 1.5 T. ADC values were measured in regions of interest (ROIs) drawn independently by two radiologists, blinded to the pathology results, on three slices of the pre and post CRT DW-MR image sets with the corresponding T2 weighted images (T2WI) available for anatomic reference. The two readers’ measurements were compared for differences in ADC values, inter-observer variability (measured as the intraclass correlation coefficient; ICC) and the ADC distributions of responders vs non-responders. The diagnostic performance of ADC in the prediction of the response to CRT was evaluated by calculating the area under the ROC curve (AUC) and the optimal cut-off values. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were assessed. Results: The two readers showed an overall strong agreement in measuring ADC values. For both readers, no differences in ADC pre-treatment measurements were observed between responders and non-responders. For reader 1, the post-CRT ADC and the ΔADC presented the higher AUC (0.823 and 0.803, respectively), while Δ%ADC provided the lower AUC value (0.682). The optimal cutoff point was 1.294 s/mm2 for post-CRT measures (sensitivity = 86.4%, specificity = 66.7%, PPV = 86.4%, NPV = 66.7%), 0.500 for ΔADC (sensitivity = 81.8%, specificity = 66.7%, PPV = 85.7%, NPV = 60.0%) and 59.3% for

  20. Advances in nanotechnology in tumor thermal ablation%纳米技术在肿瘤热消融领域的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘士榕; 梁萍

    2015-01-01

    肿瘤热消融治疗技术发展快速,已成为继外科手术之后的一项有效治疗手段,但其在疗效及安全性方面也存在一定的局限性。随着各种新型纳米粒子的不断出现,纳米医学在肿瘤诊疗领域迅速发展,并取得了丰硕的成果。本文综述纳米技术在肿瘤热消融治疗领域的主要研究进展,为局部热消融联合纳米技术治疗肿瘤提供信息。%In recent years, local thermal ablation technique has become an effective method in treatment of solid tumors. However, each technique has its certain limitations that may prevent their widespread use in clinical applications. With rapid development of new types of nanoparticles, nanomedicine has made rapid progress in thefield of tumor diagnosis and treatment. Main advances in the application of nanotechnology combined local thermal ablation are reviewed in this paper in order to provide more information for it.

  1. Clinical trial of combination therapy using systemic interleukin-2 infusion and low-dose tumor irradiation for advanced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Although recent progress in surgical techniques and interventional radiology enables patients with hepatocellular carcinoma (HCC) to survive longer, there are still many who cannot receive them due to disease progression. We are currently investigating the therapeutic efficacy of the combination of systemic recombinant interleukin-2 (IL-2) administration and local tumor irradiation for HCC patients in the advanced stage. First, the results of the basic experiment to analyze the optimal dose and timing of IL-2 infusion were demonstrated. Intensive administration of high-dose IL-2 caused acute death, whereas intermittent low-dose IL-2 administration resulted in complete tumor regression followed by the acquisition of tumor-specific immunity. Our data suggested that the tumor-bearing state increased the responsiveness to IL-2 treatment, and that an excessively high-dose regimen is not prerequisite for the optimal IL-2 treatment. With regard to the effectiveness of radiotherapy for HCC, human hepatoma cells exhibited apoptotic death when hepatoma cells were cocultured with LAK cells, or were irradiated in vitro with relatively low-dose irradiation. These results suggested the possible synergistic effect of killer cells and low-dose irradiation. Finally, we presented six eligible cases of advanced HCC treated by combination therapy of IL-2 infusion and local low-dose tumor irradiation. Direct anti-tumor effects were one CR, one MR, two NC, and two PD. One CR case and a NC case have survived now for longer than 40 months. In all cases, NK cell activity increased prominently, and side effects wee mild flu-like symptoms except macroscopic hematuria and moderate VLS-like symptoms in two cases in which therapy was continued for longer than 2 years. Hepatic reserve function like prothrombin time or hepaplastic time improved. The apparent clinical effectiveness of the combination therapy presented here might give promising hints for a new therapeutic strategy for HCC. (author)

  2. Impact of Rechallenge with Imatinib in Patients with Advanced Gastrointestinal Stromal Tumor after Failure of Imatinib and Sunitinib

    OpenAIRE

    Akira Sawaki; Tatsuo Kanda; Yoshito Komatsu; Toshirou Nishida

    2014-01-01

    Purpose. This retrospective, nonrandomized study investigated the effect of imatinib rechallenge plus best supportive care (BSC) on overall survival after imatinib and sunitinib treatment for patients with locally advanced or metastatic gastrointestinal stromal tumor (GIST). Methods. Twenty-six patients who had previously been exposed to both imatinib and sunitinib were enrolled in this study. The treatment regimen was BSC with or without imatinib, based on the patient's choice after discussi...

  3. Pathological predictive factors for tumor response in locally advanced breast carcinomas treated with anthracyclin-based neoadjuvant chemotherapy

    OpenAIRE

    Trupti Patel; Anuja Gupta; Manoj Shah

    2013-01-01

    Aim: Neoadjuvant chemotherapy (NACT) is used as a primary treatment for locally advanced breast carcinoma (LABC) and also extended to operable breast cancer. The aim of this study was to evaluate the predictive value of different histological parameters in core biopsy of LABC patients treated with anthracycline-based chemotherapy regimen. Pathological assessment of the excised tumor bed is the gold standard and is essential for identifying the group of patients with pathologic complete respon...

  4. Association Between the Cytogenetic Profile of Tumor Cells and Response to Preoperative Radiochemotherapy in Locally Advanced Rectal Cancer

    OpenAIRE

    González-González, María; Garcia, Jacinto; Alcazar, José A.; Gutiérrez, María L; Gónzalez, Luis M.; Bengoechea, Oscar; Abad, María M.; Santos-Briz, Angel; Blanco, Oscar; Martín, Manuela; Rodríguez, Ana; Fuentes, Manuel; Muñoz-Bellvis, Luis; ORFAO, ALBERTO; Sayagues, Jose M.

    2014-01-01

    Abstract Neoadjuvant radiochemotherapy to locally advanced rectal carcinoma patients has proven efficient in a high percentage of cases. Despite this, some patients show nonresponse or even disease progression. Recent studies suggest that different genetic alterations may be associated with sensitivity versus resistance of rectal cancer tumor cells to neoadjuvant therapy. We investigated the relationship between intratumoral pathways of clonal evolution as assessed by interphase fluorescence ...

  5. The occurrence of recruitment supported from the finding of an increase in radiosensitivity of quiescent cells in solid tumors after fractionated irradiation with X-rays

    International Nuclear Information System (INIS)

    We examined the behavior of quiescent cells in solid tumors irradiated twice at various intervals with X-rays, using our recently developed method for selectively detecting the response of quiescent cells in solid tumors. To determine the labeling indices of tumors at the second irradiation, each mouse group included mice that were continuously administered BrdU until just before the second irradiation using mini-osmotic pumps which had been implanted before the first irradiation. Radiosensitivity of total tumor cells at the second irradiation decreased in proportion to the increase in interval time. However, radiosensitivity of quiescent cells was raised with increase in the interval time. In addition, the labeling index at the second irradiation was higher than that at the first irradiation. These findings supported the occurrence of recruitment from quiescent to proliferating state during fractionated irradiation. (author)

  6. Application of tumor-node-metastasis staging 2002 version in locally advanced hepatocellular carcinoma: is it predictive of surgical outcome?

    International Nuclear Information System (INIS)

    Locally advanced (pT3-4N0M0) hepatocellular carcinoma (HCC) is a heterogeneous group of tumors, which consists of four different categories, including HCC with 'multiple tumors more than 5 cm', 'major vascular invasion', 'invasion of adjacent organs', and 'perforation of visceral peritoneum'. The aim of our study was to verify whether the 2002 version of the Tumor-Node-Metastasis staging system could predict surgical outcomes in patients with locally advanced HCC. We retrospectively reviewed 298 patients with pT3-4N0M0 HCC who underwent hepatic resection from 1993 to 2000 in an academic tertiary hospital. Overall survival (OS) and cumulative recurrence rate (CRR) of the four categories of locally advanced HCC patients were compared. In multivariate analysis, major vascular invasion was identified as the most significant factor (HR = 3.291, 95% CI 2.362-4.584, P < 0.001) followed by cirrhosis status on OS, and was found to be the only independent factor of CRR (HR = 2.242, 95% CI 1.811-3.358, P < 0.001) in patients with locally advanced HCC. Among the four categories of locally advanced HCC, OS was significantly worse, and CRR was significantly higher in patients with HCC with major vascular invasion (pT3) than with multiple tumors more than 5 cm (pT3); or tumor invasion of adjacent organs (pT4); or perforation of visceral peritoneum (pT4). No significant differences were observed in OS or CRR between the latter three groups of patients. HCC with major vascular invasion, which are classified as pT3 under the current TNM staging, have the worst prognosis when compared with the other categories of pT3-4 disease. There is a need to redefine the T classification and to stratify locally advanced HCC

  7. Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

    Science.gov (United States)

    2016-07-10

    Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

  8. Some implications of Scale Relativity theory in avascular stages of growth of solid tumors in the presence of an immune system response.

    Science.gov (United States)

    Buzea, C Gh; Agop, M; Moraru, Evelina; Stana, Bogdan A; Gîrţu, Manuela; Iancu, D

    2011-08-01

    We present a traveling-wave analysis of a reduced mathematical model describing the growth of a solid tumor in the presence of an immune system response in the framework of Scale Relativity theory. Attention is focused upon the attack of tumor cells by tumor-infiltrating cytotoxic lymphocytes (TICLs), in a small multicellular tumor, without necrosis and at some stage prior to (tumor-induced) angiogenesis. For a particular choice of parameters, the underlying system of partial differential equations is able to simulate the well-documented phenomenon of cancer dormancy and propagation of a perturbation in the tumor cell concentration by cnoidal modes, by depicting spatially heterogeneous tumor cell distributions that are characterized by a relatively small total number of tumor cells. This behavior is consistent with several immunomorphological investigations. Moreover, the alteration of certain parameters of the model is enough to induce soliton like modes and soliton packets into the system, which in turn result in tumor invasion in the form of a standard traveling wave. In the same framework of Scale Relativity theory, a very important feature of malignant tumors also results, that even in avascular stages they might propagate and invade healthy tissues, by means of a diffusion on a Newtonian fluid.

  9. Molecular cytogenetic analysis of formalin-fixed, paraffin-embedded solid tumors by comparative genomic hybridization after universal DNA-amplification

    OpenAIRE

    Speicher, Michael R.; Manoir, Stanislas du; Schröck, Evelin; Holtgreve-Grez, Heidi; Schoell, B; Lengauer, Christoph; Cremer, Thomas; Ried, Thomas

    1993-01-01

    We present a technique which allows the detection and chromosomal localization of DNA sequence copy number changes in solid tumor genomes from frozen sections and paraffin embedded, formalin fixed specimens. Based on comparative genomic hybridization and on universal DNA amplification procedures this technique is possible even if only a few tumor cells are available. We demonstrate the feasibility of this method to visualize complete and partial chromosome gains and losses and gene amplificat...

  10. Advance in diagnosis of female genital tract tumor with laser fluorescence

    Science.gov (United States)

    Ding, Ai-Hua; Tseng, Quen; Lian, Shao-Hui

    1998-11-01

    In order to improve the diagnostic accuracy of malignant tumors with laser fluorescence, in 1996, our group successfully created the computerized laser fluorescence spectrograph type II with more reliable images shown overshadowing the naked eye method before 74 cases of female genital tract diseases had been examined by the LFS II resulting in 10 positive cases which were also proven pathologically as malignant tumors, without nay false negative, 3 cases presented suspicious positive but all were proven pathologically as non-tumors lesions, the false positive rate was 4 percent. Our work showed that the method of LFS II can provide a more rapid and accurate diagnosis for the clinical malignant tumors.

  11. Influência de Agaricus blazei Murrill sobre o tumor sólido de Ehrlich e linfonodos poplíteos de camundongos Influence of Agaricus blazei Murrill in solid Ehrlich tumor and popliteal lymph nodes in mice

    Directory of Open Access Journals (Sweden)

    D. Verçosa Junior

    2007-02-01

    Full Text Available Estudou-se a influência do tratamento diário com filtrado aquoso de Agaricus blazei Murrill (ABM (25mg/ml, via oral, por 17 e 57 dias, em camundongos inoculados com tumor sólido de Ehrlich (TSE por meio da curva de crescimento tumoral, do peso relativo do tumor, da contagem de regiões organizadoras de nucléolos (AgNORs e dos padrões histológicos das massas tumorais e linfonodos poplíteos. Os animais que ingeriram o extrato aquoso do ABM por 57 dias apresentaram menor (P0,05 entre os animais tratados e não tratados.The influence of daily administration of Agaricus blazei Murrill (ABM aqueous solution (25mg/ml during 17 and 57 days in mice bearing solid Ehrlich tumor was studied. Tumoral growth, tumoral and spleenic relative weights, nucleoly organization regions AgNORs values and tumor and popliteal lymph nodes histopathology were daily evaluated. The animals that received ABM during 57 days showed lower values (P0.05 between treated and non-treated animals. No difference in microscopic evaluation of the tumors in treated and non-treated animals was seen and metastasis in popliteal nodes of the tumor occurred in all the animals.

  12. Somatic mutagenesis with a Sleeping Beauty transposon system leads to solid tumor formation in zebrafish.

    Directory of Open Access Journals (Sweden)

    Maura McGrail

    Full Text Available Large-scale sequencing of human cancer genomes and mouse transposon-induced tumors has identified a vast number of genes mutated in different cancers. One of the outstanding challenges in this field is to determine which genes, when mutated, contribute to cellular transformation and tumor progression. To identify new and conserved genes that drive tumorigenesis we have developed a novel cancer model in a distantly related vertebrate species, the zebrafish, Danio rerio. The Sleeping Beauty (SB T2/Onc transposon system was adapted for somatic mutagenesis in zebrafish. The carp ß-actin promoter was cloned into T2/Onc to create T2/OncZ. Two transgenic zebrafish lines that contain large concatemers of T2/OncZ were isolated by injection of linear DNA into the zebrafish embryo. The T2/OncZ transposons were mobilized throughout the zebrafish genome from the transgene array by injecting SB11 transposase RNA at the 1-cell stage. Alternatively, the T2/OncZ zebrafish were crossed to a transgenic line that constitutively expresses SB11 transposase. T2/OncZ transposon integration sites were cloned by ligation-mediated PCR and sequenced on a Genome Analyzer II. Between 700-6800 unique integration events in individual fish were mapped to the zebrafish genome. The data show that introduction of transposase by transgene expression or RNA injection results in an even distribution of transposon re-integration events across the zebrafish genome. SB11 mRNA injection resulted in neoplasms in 10% of adult fish at ∼10 months of age. T2/OncZ-induced zebrafish tumors contain many mutated genes in common with human and mouse cancer genes. These analyses validate our mutagenesis approach and provide additional support for the involvement of these genes in human cancers. The zebrafish T2/OncZ cancer model will be useful for identifying novel and conserved genetic drivers of human cancers.

  13. Advanced Si solid phase crystallization for vertical channel in vertical NANDs

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sangsoo [Department of Materials Science and Engineering and Inter-university Semiconductor Research Center, Seoul National University, Seoul 151-742 (Korea, Republic of); Son, Yong-Hoon [Department of Materials Science and Engineering and Inter-university Semiconductor Research Center, Seoul National University, Seoul 151-742 (Korea, Republic of); Semiconductor R and D Center, Samsung Electronics Co., Ltd., Hwasung 445-701 (Korea, Republic of); Hwang, Kihyun; Shin, Yoo Gyun [Semiconductor R and D Center, Samsung Electronics Co., Ltd., Hwasung 445-701 (Korea, Republic of); Yoon, Euijoon, E-mail: eyoon@snu.ac.kr [Department of Materials Science and Engineering and Inter-university Semiconductor Research Center, Seoul National University, Seoul 151-742 (Korea, Republic of); Energy Semiconductor Research Center, Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270 (Korea, Republic of)

    2014-07-01

    The advanced solid phase crystallization (SPC) method using the SiGe/Si bi-layer structure is proposed to obtain high-mobility poly-Si thin-film transistors in next generation vertical NAND (VNAND) devices. During the SPC process, the top SiGe thin film acts as a selective nucleation layer to induce surface nucleation and equiaxial microstructure. Subsequently, this SiGe thin film microstructure is propagated to the underlying Si thin film by epitaxy-like growth. The initial nucleation at the SiGe surface was clearly observed by in situ transmission electron microscopy (TEM) when heating up to 600 °C. The equiaxial microstructures of both SiGe nucleation and Si channel layers were shown in the crystallized bi-layer plan-view TEM measurements. Based on these experimental results, the large-grained and less-defective Si microstructure is expected to form near the channel region of each VNAND cell transistor, which may improve the electrical characteristics.

  14. On the behaviour of foreign particles at an advancing solid-liquid interface

    Science.gov (United States)

    Pötschke, Jürgen; Rogge, Volker

    1989-03-01

    The present paper describes a theoretical approach to the behaviour at advancing solid-liquid interfaces of foreign particles present in the melt as a separate phase. The temperature field and the influence of a contaminant in the melt were taken into account. The equations which arose were solved numerically. The numerical data can be described with satisfactory accuracy by a function, so that the result can be communicated in the form of a self-contained expression. The use of this equation is found to be in good agreement with recent measurements of latex particles in water: the model gives the critical solidification velocity at which the latex particles of a specific size are only just pushed along by the ice front. An assessment of other measured values given in the literature is not possible since the material values and experimental parameters are not completely known. To consolidate the theory, therefore, further quantitative measurements of systems with known material values, interfacial free energies in particular, are required.

  15. NATO Advanced Study Institute on Laser Interactions with Atoms, Solids,and Plasmas

    CERN Document Server

    1994-01-01

    The aim of this NATO Advanced Study Institute was to bring together scientists and students working in the field of laser matter interactions in order to review and stimulate developmentoffundamental science with ultra-short pulse lasers. New techniques of pulse compression and colliding-pulse mode-locking have made possible the construction of lasers with pulse lengths in the femtosecond range. Such lasers are now in operation at several research laboratories in Europe and the United States. These laser facilities present a new and exciting research direction with both pure and applied science components. In this ASI the emphasis is on fundamental processes occurring in the interaction of short laser pulses with atoms, molecules, solids, and plasmas. In the case of laser-atom (molecule) interactions, high power lasers provide the first access to extreme high-intensity conditions above 10'8 Watts/em', a new frontier for nonlinear interaction of photons with atoms and molecules. New phenomena observed include ...

  16. Advanced Si solid phase crystallization for vertical channel in vertical NANDs

    Directory of Open Access Journals (Sweden)

    Sangsoo Lee

    2014-07-01

    Full Text Available The advanced solid phase crystallization (SPC method using the SiGe/Si bi-layer structure is proposed to obtain high-mobility poly-Si thin-film transistors in next generation vertical NAND (VNAND devices. During the SPC process, the top SiGe thin film acts as a selective nucleation layer to induce surface nucleation and equiaxial microstructure. Subsequently, this SiGe thin film microstructure is propagated to the underlying Si thin film by epitaxy-like growth. The initial nucleation at the SiGe surface was clearly observed by in situ transmission electron microscopy (TEM when heating up to 600 °C. The equiaxial microstructures of both SiGe nucleation and Si channel layers were shown in the crystallized bi-layer plan-view TEM measurements. Based on these experimental results, the large-grained and less-defective Si microstructure is expected to form near the channel region of each VNAND cell transistor, which may improve the electrical characteristics.

  17. Role of denosumab in the management of skeletal complications in patients with bone metastases from solid tumors

    Directory of Open Access Journals (Sweden)

    Stopeck AT

    2012-04-01

    Full Text Available Ursa Brown-Glaberman, Alison T StopeckUniversity of Arizona Cancer Center, Tucson, AZ, USAAbstract: Skeletal-related events (SREs including pain, fractures, and hypercalcemia are a major source of morbidity for cancer patients with bone metastases. The receptor activator of NF-κB ligand (RANKL is a key mediator of osteoclast formation and activity in normal bone physiology as well as cancer-induced bone resorption. The first commercially available drug that specifically targets and inhibits the RANKL pathway is denosumab, a fully human monoclonal antibody that binds and neutralizes RANKL, thereby inhibiting osteoclast function. In this review, we summarize the major studies leading to the US Food and Drug Administration-approval of denosumab for the prevention of SREs in patients with bone metastases from solid tumors. Further, we discuss the role of denosumab in the prevention and treatment of SREs and bone loss in cancer patients. As a monoclonal antibody, denosumab has several advantages over bisphosphonates, including improved efficacy, better tolerability, and the convenience of administration by subcutaneous injection. In addition, as denosumab has no known renal toxicity, it may be the preferred choice over bisphosphonates in patients with baseline renal insufficiency or receiving nephrotoxic therapies. However, other toxicities, including osteonecrosis of the jaw and hypocalcemia, appear to be class effects of agents that potently inhibit osteoclast activity and are associated with both denosumab and bisphosphonate use. The data presented highlight the differences associated with intravenous bisphosphonate and denosumab use as well as confirm the essential role bone-modifying agents play in maintaining the quality of life for patients with bone metastases.Keywords: denosumab, bone metastases, solid tumor, breast cancer, prostate cancer, skeletal related events, skeletal complications 

  18. Postmastectomy electron-beam-rotation irradiation in locally advanced breast cancer. Prognostic factors of locoregional tumor control

    International Nuclear Information System (INIS)

    Background: Different radiotherapy techniques are used for postmastectomy irradiation. We review the results with the electron-beam-rotation technique in advanced breast cancer patients. Main endpoint was local tumor control. Patients and Methods: From 1990 to 1998 119 patients with adverse pathology features (pT3 17% of patients, pT4 42%, multicentricity 36%, pN≥3 positive nodes and/or pN1biii 81%, close margins 30%) underwent electron-beam-rotation irradiation of the chest wall with daily fractions of 2.0-2.5 Gy per day to 50 Gy total dose after modified radical mastectomy and axillary lymph nodes dissection. A local boost of 10 Gy and/or irradiation of locoregional lymph nodes were applied depending on the completeness of resection and lymph node involvement. Results: After a median follow-up of 73 months for patients at risk the 5-year local tumor control, local tumor control first event, disease-free, and overall survival were 82%, 92%, 57%, and 63% (Kaplan Meier analysis), respectively. Significant predictors of poor local tumor control were maximal tumor diameter ≥5 cm (p=0.01), 'close margins' or residual tumor (p<0.01), four or more involved axillary lymph nodes (p=0.02), two or more involved lymph node levels (p=0.04), negative estrogen receptor status (p=0.03), and high-grade histopathology (GIIb-III, p<0.01). The subgroup analysis showed a high local failure rate of 37% for high-grade (GIIb-III) and estrogen receptor negative tumors, whereas no local recurrence was found in low-grade (GI-IIa) and receptor positive tumors (p=0.01). The multivariate analysis revealed maximal tumor diameter ≥5 cm, four or more involved axillary lymph nodes and high-grade histopathology (GIIb-III) as independent predictors of poor local tumor control. Conclusion: In high-risk breast cancer patients postmastectomy irradiation with the electron-beam-rotation technique is an effective therapy, resulting in a 5-year local failure rate of 8%. Intensified local therapy

  19. PLGA Nanoparticles for Ultrasound-Mediated Gene Delivery to Solid Tumors

    Directory of Open Access Journals (Sweden)

    Marxa Figueiredo

    2012-01-01

    Full Text Available This paper focuses on novel approaches in the field of nanotechnology-based carriers utilizing ultrasound stimuli as a means to spatially target gene delivery in vivo, using nanoparticles made with either poly(lactic-co-glycolic acid (PLGA or other polymers. We specifically discuss the potential for gene delivery by particles that are echogenic (amenable to destruction by ultrasound composed either of polymers (PLGA, polystyrene or other contrast agent materials (Optison, SonoVue microbubbles. The use of ultrasound is an efficient tool to further enhance gene delivery by PLGA or other echogenic particles in vivo. Echogenic PLGA nanoparticles are an attractive strategy for ultrasound-mediated gene delivery since this polymer is currently approved by the US Food and Drug Administration for drug delivery and diagnostics in cancer, cardiovascular disease, and also other applications such as vaccines and tissue engineering. This paper will review recent successes and the potential of applying PLGA nanoparticles for gene delivery, which include (a echogenic PLGA used with ultrasound to enhance local gene delivery in tumors or muscle and (b PLGA nanoparticles currently under development, which could benefit in the future from ultrasound-enhanced tumor targeted gene delivery.

  20. Not All Next Generation Sequencing Diagnostics are Created Equal: Understanding the Nuances of Solid Tumor Assay Design for Somatic Mutation Detection

    Energy Technology Data Exchange (ETDEWEB)

    Gray, Phillip N., E-mail: pgray@ambrygen.com; Dunlop, Charles L.M.; Elliott, Aaron M. [Ambry Genetics, 15 Argonaut, Aliso Viejo, CA 92656 (United States)

    2015-07-17

    The molecular characterization of tumors using next generation sequencing (NGS) is an emerging diagnostic tool that is quickly becoming an integral part of clinical decision making. Cancer genomic profiling involves significant challenges including DNA quality and quantity, tumor heterogeneity, and the need to detect a wide variety of complex genetic mutations. Most available comprehensive diagnostic tests rely on primer based amplification or probe based capture methods coupled with NGS to detect hotspot mutation sites or whole regions implicated in disease. These tumor panels utilize highly customized bioinformatics pipelines to perform the difficult task of accurately calling cancer relevant alterations such as single nucleotide variations, small indels or large genomic alterations from the NGS data. In this review, we will discuss the challenges of solid tumor assay design/analysis and report a case study that highlights the need to include complementary technologies (i.e., arrays) and germline analysis in tumor testing to reliably identify copy number alterations and actionable variants.

  1. Not All Next Generation Sequencing Diagnostics are Created Equal: Understanding the Nuances of Solid Tumor Assay Design for Somatic Mutation Detection

    International Nuclear Information System (INIS)

    The molecular characterization of tumors using next generation sequencing (NGS) is an emerging diagnostic tool that is quickly becoming an integral part of clinical decision making. Cancer genomic profiling involves significant challenges including DNA quality and quantity, tumor heterogeneity, and the need to detect a wide variety of complex genetic mutations. Most available comprehensive diagnostic tests rely on primer based amplification or probe based capture methods coupled with NGS to detect hotspot mutation sites or whole regions implicated in disease. These tumor panels utilize highly customized bioinformatics pipelines to perform the difficult task of accurately calling cancer relevant alterations such as single nucleotide variations, small indels or large genomic alterations from the NGS data. In this review, we will discuss the challenges of solid tumor assay design/analysis and report a case study that highlights the need to include complementary technologies (i.e., arrays) and germline analysis in tumor testing to reliably identify copy number alterations and actionable variants

  2. Peptide Receptor Radionuclide Therapy with (90)Y-DOTATOC and (177)Lu-DOTATOC in Advanced Neuroendocrine Tumors: Results from a Danish Cohort Treated in Switzerland

    DEFF Research Database (Denmark)

    Pfeifer, Andreas Klaus; Gregersen, Tine; Grønbæk, Henning;

    2011-01-01

    Limited therapeutic options have highlighted the demand for new treatment modalities for patients with advanced neuroendocrine tumors (NET). Promising results of initial studies have warranted the implementation of peptide receptor radionuclide therapy (PRRT) in clinical practice. However...

  3. Peptide receptor radionuclide therapy with Y-DOTATOC and (177)Lu-DOTATOC in advanced neuroendocrine tumors: results from a Danish cohort treated in Switzerland

    DEFF Research Database (Denmark)

    Pfeifer, Andreas Klaus; Gregersen, Tine; Grønbæk, Henning;

    2011-01-01

    Limited therapeutic options have highlighted the demand for new treatment modalities for patients with advanced neuroendocrine tumors (NET). Promising results of initial studies have warranted the implementation of peptide receptor radionuclide therapy (PRRT) in clinical practice. However...

  4. Treatment of locally advanced, high-grade, malignant tumors of major salivary glands

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, S.P.; Marks, J.E.

    1988-04-01

    A retrospective review of 45 patients with Stage III and IV malignant tumors of the major salivary glands was undertaken to determine tumor control and patient survival after treatment with surgery and conventional ionizing-radiation therapy. Eight of the 23 patients received early postoperative radiotherapy after initial surgical resection, with a local control rate of 75%. Twelve of 23 patients had surgery as definitive treatment and the tumor recurred locally in all; seven of these 12 patients were subsequently salvaged by further surgery plus postoperative radiotherapy or by radiotherapy alone, with 58% ultimate local control. The remaining three patients had unresectable tumors at diagnosis and received radiation alone, with a local tumor control rate of 33%. Patients were also analyzed according to the extent of surgical resection prior to radiation therapy and according to radiation dose. Eighty-eight percent of completely resected, 50% of partially resected, and 44% of unresected tumors were locally controlled for an overall local control rate of 61%. The 5-year survival rate was significantly higher for patients with local tumor control than for patients who failed locally (31% vs. 0%).

  5. Advances of MicroRNAs in Translational Medicine and Immunotherapy of Renal Tumors

    Institute of Scientific and Technical Information of China (English)

    HUANG Xin-en

    2016-01-01

    microRNA (miRNA) is an important molecular component for cells under normal and pathological status, and plays an important role in oncobiology, including the improvement of tumor growth, invasion, angiogenesis and immunoescape by inhibiting the expression of gene miRNAs. Translational medicine can accelerate the industrialization process of transforming scientific research into engineering application, and its application in medicine may lead to the fast shortening of distance between basic research and clinical practice. According to the study of miRNAs in translational medicine, it is discovered that the pathological subtypes of relative diseases can be identiifed and patients’ survival time and prognosis can be predicted through the expression proifles of miRNAs in tumors. The invasive examinations can be reduced to realize the diagnosis of tumors by detecting tumor-associated miRNA biomarkers, and miRNAs can be used for clinical treatment of tumors. Renal cell carcinoma (RCC) is a common tumor in urinary system, and application of some specific miRNAs as a biomarker for the complementary diagnosis and treatment as well as evaluation of prognosis has become a hot topic in modern medicine. This study mainly analyzed and summarized the latest development in miRNAs and tumor studies, hoping to provide a theoretical basis for the diagnosis and prognosis of renal cancer.

  6. Recent advances and challenges for diode-pumped solid-state lasers as an inertial fusion energy driver candidate

    International Nuclear Information System (INIS)

    We discuss how solid-state laser technology can serve in the interests of fusion energy beyond the goals of the National Ignition Facility (NIF), which is now being constructed to ignite a deuterium-tritium target to fusion conditions in the laboratory for the first time. We think that advanced solid-state laser technology can offer the repetition-rate and efficiency needed to drive a fusion power plant, in contrast to the single-shot character of NIF. As discuss below, we propose that a gas-cooled, diode-pumped Yb:S-FAP laser can provide a new paradigm for fusion laser technology leading into the next century

  7. Mucinous cystadenoma of the pancreas with predominant stroma creating a solid tumor

    Directory of Open Access Journals (Sweden)

    Ae Lee Won

    2005-09-01

    Full Text Available Abstract Background Mucinous cystic neoplasm (MCN of the pancreas is basically cystic epithelial neoplasm, unilocular or multilocular, occurring almost exclusively in women. Case presentation A 51-year-old female presented with a pancreatic mass incidentally found on the abdominal computed tomography. She underwent distal pancreatectomy. The sectioned surface of the pancreas revealed a circumscribed, whitish gray ovoid firm mass with some cystic spaces. Microscopically, glandular or small cystic structures were scattered in the predominant stroma creating a solid appearance. The subepithelial stromal component was composed of cytologically bland looking spindle cells, which resembled ovarian stroma. The stromal cells were reactive to CD 34, vimentin, progesterone receptor and calretinin. The microscopy was consistent with mucinous cystadenoma of the pancreas. Conclusion This case of mucinous cystadenoma of the pancreas showed very interesting pathology: It was solid rather than cystic, and accompanied by abundant benign transitional epithelia, which was a very unusual and novel finding in the mucinous cystic neoplasm of the pancreas.

  8. Early identification of non-responding locally advanced breast tumors receiving neoadjuvant chemotherapy

    Science.gov (United States)

    Van de Giessen, Martijn; Schaafsma, Boudewijn E.; Charehbili, Ayoub; Smit, Vincent T. H. B. M.; Kroep, Judith R.; Lelieveldt, Boudewijn P. F.; Liefers, Gerrit-Jan; Chan, Alan; Löwik, Clemens W. G. M.; Dijkstra, Jouke; van de Velde, Cornelis J. H.; Wasser, Martin N. J. M.; Vahrmeijer, Alexander L.

    2015-02-01

    Diffuse optical spectroscopy (DOS) may be advantageous for monitoring tumor response during chemotherapy treatment, particularly in the early treatment stages. In this paper we perform a second analysis on the data of a clinical trial with 25 breast cancer patients that received neoadjuvant chemotherapy. Patients were monitored using delayed contrast enhanced MRI and additionally with diffuse optical spectroscopy at baseline, after 1 cycle of chemotherapy, halfway therapy and before surgery. In this analysis hemoglobin content between tumor tissue and healthy tissue of the same breast is compared on all four monitoring time points. Furthermore, the predictive power of the tumor-healthy tissue difference of HbO2 for non-responder prediction is assessed. The difference in HbO2 content between tumor and healthy tissue was statistically significantly higher in responding tumors than in non-responding tumors at baseline (10.88 vs -0.57 μM, P=0.014) and after one cycle of chemotherapy (6.45 vs -1.31 μM, P=0.048). Before surgery this difference had diminished. In the data of this study, classification on the HbO2 difference between tumor and healthy tissue was able to predict tumor (non-)response at baseline and after 1 cycle with an area-under-curve of 0.95 and 0.88, respectively. While this result suggests that tumor response can be predicted before chemotherapy onset, one should be very careful with interpreting these results. A larger patient population is needed to confirm this finding.

  9. Advanced MR diagnostic imaging in pediatric glial cell tumors: from morphological to pathophysiological evaluation

    International Nuclear Information System (INIS)

    Full text: Introduction: The conventional MR imaging is important, and in most cases necessary imaging tool for studying the macroscopic structure, for localization and distribution of a glial brain tumor. It is an integral part of the optimal MR protocol, which further comprises a diffusion, perfusion techniques, techniques for the permeability and oxygenation assessment, as well as MR spectroscopy to the metabolism assessment. What you will learn: Glial brain tumors in children - incidence, histology, classification, diagnosis; Nature and principles of MR diffusion, perfusion, techniques for permeability and oxygenation assessment, MR spectroscopy; Contemporary techniques allowing to obtain not only MR morphological information but also to evaluate the tumor the pathophysiology: the cellular atypia, cellularity, tumor neovascularization, oxygen consumption, metabolism, status of the blood-brain barrier. This assessment determines the biological potential of the tumor, treatment options and prognosis. Discussion: The findings from conventional MR examinations, incl. administration of gadolinium contrast agents are associated with the degree of glioma and can be useful for their classification. Taking into account that from 20% to 45 % of the unenhanced supratentorial gliomas are malignant, some low-grade gliomas enhance (ganglioglioma, pilocytic astrocytoma, oligodendroglioma), 9% of malignant gliomas have no contrast enhancement, and in general, the contrast enhancement is not seen as a reliable indicator for the infiltration extent. The contemporary MR techniques improve the assessment of the pathophysiology of the tumor which is relevant to its histology and biological potential. Conclusion: Modern MR techniques besides purely diagnostic advantages (determine the extent and distribution of glioma), enable: differentiation of tumor recurrence from radiation necrosis; identification of optimal locations for biopsy or operative resection; prognosis, planning and

  10. Advances in the Researches on the Blocking Effect of Chinese Drugs on Tumors

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ Malignant tumors are caused by multiple carcinogenic factors undergoing several stages. The occurrence and development of tumors may be prevented and blocked if some effective interference factors are brought into play.1 At present, there are two main subjects for the researches, that is, blocking the precancerous lesions and blocking the develop-ment of tumors. The former focuses on the removing of carcinogenic factors and on the chemoprophylaxis of cancer, while the latter on the inhibition of cancer cell infiltration and cancerometastasis. These are summarized as follows.

  11. Recent advances in understanding the etiology and pathogenesis of pediatric germ cell tumors

    DEFF Research Database (Denmark)

    Mosbech, Christiane Hammershaimb; Rechnitzer, Catherine; Brok, Jesper S;

    2014-01-01

    Pediatric germ cell tumors (GCTs) are rare neoplasms arising predominantly in the gonads and sacrococcygeal, mediastinal, and intracranial localizations. In this article, we review current knowledge of pathogenesis of pediatric GCTs, which differs from adult/adolescent GCTs. One distinctive feature...... transcription factors OCT-3/4, NANOG, and AP-2γ in germinomas/seminomas/dysgerminomas is consistent with retaining a germ cell phenotype. Teratomas, in contrast, develop through a pathway of aberrant somatic differentiation of immature germ cells, and the yolk sac tumors and choriocarcinomas result from...... of pathogenesis of these fascinating tumors....

  12. Romidepsin in Treating Patients With Lymphoma, Chronic Lymphocytic Leukemia, or Solid Tumors With Liver Dysfunction

    Science.gov (United States)

    2016-08-24

    Adult Mixed Glioma; Adult Pineal Gland Astrocytoma; Adult Solid Neoplasm; AIDS Related Immunoblastic Lymphoma; AIDS-Related Burkitt Lymphoma; AIDS-Related Diffuse Large Cell Lymphoma; AIDS-Related Diffuse Mixed Cell Lymphoma; AIDS-Related Diffuse Small Cleaved Cell Lymphoma; AIDS-Related Hodgkin Lymphoma; AIDS-Related Lymphoblastic Lymphoma; AIDS-Related Lymphoma; AIDS-Related Primary Central Nervous System Lymphoma; Glioma; Lymphoma; Recurrent Adult Brain Neoplasm; Recurrent Adult Soft Tissue Sarcoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Colorectal Carcinoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Recurrent Melanoma; Recurrent Pancreatic Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Thyroid Gland Carcinoma; Refractory Chronic Lymphocytic Leukemia; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

  13. Cyclamen exerts cytotoxicity in solid tumor cell lines: a step toward new anticancer agents?

    Science.gov (United States)

    Yildiz, Mustafa; Bozcu, Hakan; Tokgun, Onur; Karagur, Ege Riza; Akyurt, Oktay; Akca, Hakan

    2013-01-01

    Cyclamen coum is a traditional medicinal plant in the Turkey. Its anticancer properties and whether cyclamen extract induces any cytotoxicity in solid cancer cell lines have not been thoroughly investigated previously. Therefore we examined cytotoxic effects on cervical cancer, HeLa, and non small cell lung cancer cell, H1299, lines. Cyclamen extract induced cellular death of both HeLa and H1299 cells in a dose dependent manner. We also analyzed the capacity of cyclamen extract to induce apoptosis by the TUNEL method. Here, we for the first time report that the extract of Cyclamen coum, an endemic plant for Turkey, can induce cytotoxicity via apoptosis in HeLa and H1299 cells. These results imply that cyclamen extract can be further analyzed to potentially find novel anticancer compounds.

  14. Interactions between three subpopulations of Ehrlich ascites tumor and a P388 murine leukemia in mixed solid tumors in immune competent mice

    DEFF Research Database (Denmark)

    Aabo, K; Vindeløv, L L; Christensen, I B;

    1989-01-01

    day 14, tumor growth curves, cell cycle times (per cent labelled mitoses) and cell cycle distributions (flow cytometric DNA analysis). After 2 weeks of growth of mixed P388/E1.95 tumors, flow cytometric DNA analysis on fine-needle tumor aspirates showed nearly total dominance of P388. This type...

  15. ”Vascular Lock” Causing Splenic Perfusion Defects During Irreversible Electroporation of a Locally Advanced Pancreatic Tumor

    Directory of Open Access Journals (Sweden)

    Anna Maria Ierardi

    2014-11-01

    Full Text Available Context There is little reported experience of irreversible electroporation (IRE of locally advanced pancreatic tumors (LAP. In literature, few data reported complications. In particular vascular vasoconstriction miming splenic infarcts in humans has never been found. Case report This report describes the onset of asymptomatic multiple little splenic perfusion defects after the treatment of a LAP localized in the boby tail portion of the pancreas with the application of five percutaneous probes for IRE, in a 79 year-old man. Splenic artery was regularly patent but entirely trapped in the tumor. Conclusion To the best of our knowledge, until now, no experience concerning percutaneous IRE of pancreatic cancer described that phenomenon. The cause could not be established with certainty and “vascular lock" may be a valid hypothesis. Additional studies are necessary to evaluate its frequency and its exact pathophysiological cause in humans.

  16. Association between the cytogenetic profile of tumor cells and response to preoperative radiochemotherapy in locally advanced rectal cancer.

    Science.gov (United States)

    González-González, María; Garcia, Jacinto; Alcazar, José A; Gutiérrez, María L; Gónzalez, Luis M; Bengoechea, Oscar; Abad, María M; Santos-Briz, Angel; Blanco, Oscar; Martín, Manuela; Rodríguez, Ana; Fuentes, Manuel; Muñoz-Bellvis, Luis; Orfao, Alberto; Sayagues, Jose M

    2014-11-01

    Neoadjuvant radiochemotherapy to locally advanced rectal carcinoma patients has proven efficient in a high percentage of cases. Despite this, some patients show nonresponse or even disease progression. Recent studies suggest that different genetic alterations may be associated with sensitivity versus resistance of rectal cancer tumor cells to neoadjuvant therapy. We investigated the relationship between intratumoral pathways of clonal evolution as assessed by interphase fluorescence in situ hybridization (51 different probes) and response to neoadjuvant radiochemotherapy, evaluated by Dworak criteria in 45 rectal cancer tumors before (n = 45) and after (n = 31) treatment. Losses of chromosomes 1p (44%), 8p (53%), 17p (47%), and 18q (38%) and gains of 1q (49%) and 13q (75%) as well as amplification of 8q (38%) and 20q (47%) chromosomal regions were those specific alterations found at higher frequencies. Significant association (P therapy. A clear association was observed between cytogenetic profile of the ancestral tumor cell clone and response to radiochemotherapy; cases presenting with del(17p) showed a poor response to neoadjuvant treatment (P = 0.03), whereas presence of del(1p) was more frequently observed in responder patients (P = 0.0002). Moreover, a significantly higher number of copies of chromosomes 8q (P = 0.004), 13q (P = 0.003), and 20q (P = 0.002) were found after therapy versus paired pretreatment rectal cancer samples. Our results point out the existence of an association between tumor cytogenetics and response to neoadjuvant therapy in locally advanced rectal cancer. Further studies in larger series of patients are necessary to confirm our results. PMID:25474426

  17. Alpha-emitter radium-223 in the management of solid tumors: current status and future directions.

    Science.gov (United States)

    Nilsson, Sten

    2014-01-01

    Bone metastases, which are commonly seen in patients with advanced cancers, are a major cause of skeletal events, disability, and death. Radium-223 dichloride (radium-223; Xofigo, formerly Alpharadin), a first-in-class, alpha-emitting radiopharmaceutical that selectively targets bone metastases with high-energy short-range alpha-particles, has been approved for the treatment of patients with castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastases. Approval is based on results of the randomized phase III trial Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA), in which radium-223 prolonged overall survival and time to first symptomatic skeletal event versus placebo among patients with CRPC with symptomatic bone metastases and was generally well tolerated, with low myelosuppression rates and manageable gastrointestinal adverse events. Long-term follow-up of the ALSYMPCA safety population showed that the incidence of myelosuppression remained low among patients treated with radium-223, with no additional safety issues of acute myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, or primary bone cancer within approximately 1.5 years after treatment. The radium-223 overall survival benefit and low toxicity make it an effective, well-tolerated, and novel treatment option for CRPC and symptomatic bone metastases and opens the possibility of exploring radium-223 in the treatment of bone metastases from other cancers. A phase I clinical trial of patients with breast and prostate cancer with skeletal metastases demonstrated that radium-223 was safe and well tolerated at all therapeutically relevant dosages. Moreover, a phase IIa trial of patients with advanced breast cancer and progressive bone-dominant disease demonstrated that radium-223 targeted areas of increased bone metabolism and showed biologic activity. PMID:24857093

  18. Integration of chemotherapy into current treatment strategies for brain metastases from solid tumors

    International Nuclear Information System (INIS)

    Patients with brain metastases represent a heterogeneous group where selection of the most appropriate treatment depends on many patient- and disease-related factors. Eventually, a considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. Whole-brain radiotherapy in combination with chemotherapy has recently gained increasing attention and is hoped to augment the palliative effect of whole-brain radiotherapy alone and to extend survival in certain subsets of patients with controlled extracranial disease and good performance status. The randomized trials of whole-brain radiotherapy vs. whole-brain radiotherapy plus chemotherapy suggest that this concept deserves further study, although they failed to improve survival. However, survival might not be the most relevant endpoint in a condition, where most patients die from extracranial progression. Sometimes, the question arises whether patients with newly detected brain metastases and the indication for systemic treatment of extracranial disease can undergo standard systemic chemotherapy with the option of deferred rather than immediate radiotherapy to the brain. The literature contains numerous small reports on this issue, mainly in malignant melanoma, breast cancer, lung cancer and ovarian cancer, but very few sufficiently powered randomized trials. With chemotherapy alone, response rates were mostly in the order of 20–40%. The choice of chemotherapy regimen is often complicated by previous systemic treatment and takes into account the activity of the drugs in extracranial metastatic disease. Because the blood-brain barrier is partially disrupted in most macroscopic metastases, systemically administered agents can gain access to such tumor sites. Our systematic literature review suggests that both chemotherapy and radiochemotherapy for newly diagnosed brain metastases need further critical evaluation before standard clinical implementation. A potential chemotherapy

  19. Integration of chemotherapy into current treatment strategies for brain metastases from solid tumors

    Directory of Open Access Journals (Sweden)

    Thamm Reinhard

    2006-06-01

    Full Text Available Abstract Patients with brain metastases represent a heterogeneous group where selection of the most appropriate treatment depends on many patient- and disease-related factors. Eventually, a considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. Whole-brain radiotherapy in combination with chemotherapy has recently gained increasing attention and is hoped to augment the palliative effect of whole-brain radiotherapy alone and to extend survival in certain subsets of patients with controlled extracranial disease and good performance status. The randomized trials of whole-brain radiotherapy vs. whole-brain radiotherapy plus chemotherapy suggest that this concept deserves further study, although they failed to improve survival. However, survival might not be the most relevant endpoint in a condition, where most patients die from extracranial progression. Sometimes, the question arises whether patients with newly detected brain metastases and the indication for systemic treatment of extracranial disease can undergo standard systemic chemotherapy with the option of deferred rather than immediate radiotherapy to the brain. The literature contains numerous small reports on this issue, mainly in malignant melanoma, breast cancer, lung cancer and ovarian cancer, but very few sufficiently powered randomized trials. With chemotherapy alone, response rates were mostly in the order of 20–40%. The choice of chemotherapy regimen is often complicated by previous systemic treatment and takes into account the activity of the drugs in extracranial metastatic disease. Because the blood-brain barrier is partially disrupted in most macroscopic metastases, systemically administered agents can gain access to such tumor sites. Our systematic literature review suggests that both chemotherapy and radiochemotherapy for newly diagnosed brain metastases need further critical evaluation before standard clinical

  20. Preclinical development of a novel class of CXCR4 antagonist impairing solid tumors growth and metastases.

    Directory of Open Access Journals (Sweden)

    Luigi Portella

    Full Text Available The CXCR4/CXCL12 axis plays a role in cancer metastases, stem cell mobilization and chemosensitization. Proof of concept for efficient CXCR4 inhibition has been demonstrated in stem cell mobilization prior to autologous transplantation in hematological malignancies. Nevertheless CXCR4 inhibitors suitable for prolonged use as required for anticancer therapy are not available. To develop new CXCR4 antagonists a rational, ligand-based approach was taken, distinct from the more commonly used development strategy. A three amino acid motif (Ar-Ar-X in CXCL12, also found in the reverse orientation (X-Ar-Ar in the vMIP-II inhibitory chemokine formed the core of nineteen cyclic peptides evaluated for inhibition of CXCR4-dependent migration, binding, P-ERK1/2-induction and calcium efflux. Peptides R, S and I were chosen for evaluation in in vivo models of lung metastases (B16-CXCR4 and KTM2 murine osteosarcoma cells and growth of a renal cells xenograft. Peptides R, S, and T significantly reduced the association of the 12G5-CXCR4 antibody to the receptor and inhibited CXCL12-induced calcium efflux. The four peptides efficiently inhibited CXCL12-dependent migration at concentrations as low as 10 nM and delayed CXCL12-mediated wound healing in PES43 human melanoma cells. Intraperitoneal treatment with peptides R, I or S drastically reduced the number of B16-CXCR4-derived lung metastases in C57/BL mice. KTM2 osteosarcoma lung metastases were also reduced in Balb/C mice following CXCR4 inhibition. All three peptides significantly inhibited subcutaneous growth of SN12C-EGFP renal cancer cells. A novel class of CXCR4 inhibitory peptides was discovered. Three peptides, R, I and S inhibited lung metastases and primary tumor growth and will be evaluated as anticancer agents.

  1. The outcome and predictive factors of sunitinib therapy in advanced gastrointestinal stromal tumors (GIST) after imatinib failure - one institution study

    International Nuclear Information System (INIS)

    Gastrointestinal stromal tumors (GIST) mutational status is recognized factor related to the results of tyrosine kinase inhibitors therapy such as imatinib (IM) or sunitinib (SU). Arterial hypertension (AH) is common adverse event related to SU, reported as predictive factor in renal cell carcinoma. The aim of the study was to analyze the outcomes and factors predicting results of SU therapy in inoperable/metastatic CD117(+) GIST patients after IM failure. We identified 137 consecutive patients with advanced inoperable/metastatic GIST treated in one center with SU (2nd line treatment). Median follow-up time was 23 months. Additionally, in 39 patients there were analyzed selected constitutive single nucleotide polymorphisms (SNPs) of VEGFA and VEGFR2 genes. One year progression-free survival (PFS; calculated from the start of SU) rate was 42% and median PFS was 43 weeks. The estimated overall survival (OS, calculated both from start of SU or IM) was 74 weeks and 51 months, respectively. One-year PFS was 65% (median 74 weeks) in 55 patients with AH vs. 22% (median 17 weeks) in patients without AH. Patients with primary tumors carrying mutations in KIT exon 9 or wild-type had substantially better 1-year PFS (68% and 57%; median 65.5 and 50.5 weeks, respectively) than patients having tumors with KIT exon 11 or PDGFRA mutations (34% and 15%; median 36.8 and 9 weeks, respectively). We identified two independent factors with significant impact on PFS and OS in univariate and multivariate analysis: primary tumor genotype and presence of AH. The most common adverse events during therapy were: fatigue, AH, hypothyroidism, hand and foot syndrome, mucositis, skin reactions, dyspepsia, and diarrhea. Two deaths were assessed as related to tumor rupture caused by reaction to SU therapy. The presence of C-allele in rs833061 and the T-allele in rs3025039 polymorphism of VEGFA were associated with significantly higher risk of hypothyroidism (OR: 10.0 p = 0.041 and OR: 10.5; p = 0

  2. Soluble tumor necrosis factor receptor 1 and 2 predict outcomes in advanced chronic kidney disease: a prospective cohort study

    OpenAIRE

    Neirynck, Nathalie; Glorieux, Griet; Schepers, Eva; Verbeke, Francis; Vanholder, Raymond

    2015-01-01

    Background : Soluble tumor necrosis factor receptors 1 (sTNFR1) and 2 (sTNFR2) have been associated to progression of renal failure, end stage renal disease and mortality in early stages of chronic kidney disease (CKD), mostly in the context of diabetic nephropathy. The predictive value of these markers in advanced stages of CKD irrespective of the specific causes of kidney disease has not yet been defined. In this study, the relationship between sTNFR1 and sTNFR2 and the risk for adverse car...

  3. Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions)

    Science.gov (United States)

    2016-10-12

    Breast Cancer; Cholangiocarcinoma; Colorectal Cancer; Head and Neck Neoplasms; Lymphoma, Large-Cell, Anaplastic; Melanoma; Neuroendocrine Tumors; Non-Small Cell Lung Cancer; Ovarian Cancer; Pancreatic Cancer; Papillary Thyroid Cancer; Primary Brain Tumors; Renal Cell Carcinoma; Sarcomas; Salivary Gland Cancers; Adult Solid Tumor

  4. Enhanced in Vitro Anti-Tumor Activity of 5-Azacytidine by Entrapment into Solid Lipid Nanoparticles

    Science.gov (United States)

    Jahanfar, Farhad; Hasani, Akbar; Shanebandi, Dariush; Rahmati, Mohammad; Hamishehkar, Hamed

    2016-01-01

    Purpose: In this study the effectiveness of encapsulating of 5-azacytidine into the lipid nanoparticles was investigated and in vitro effect of encapsulated 5-azacytidine studied on MCF-7 cell lines Methods: 5-azacytidine -loaded solid lipid nanoparticles were produced by double emulsification (w/o/w) method by using stearic acid as lipid matrix, soy lecithin and poloxamer 407 as surfactant and co-surfactant respectively. Particle size, zeta potential, surface morphology, entrapment efficiency and kinetic of drug release were studied. In vitro effect of 5-azacytidine on MCF-7 cell line studied by MTT assay, DAPI staining, Rhodamine B relative uptake, and also Real time RT-PCR was performed for studying difference effect of free and encapsulated drug on expression of RARß2 gene. Results: The formulation F5 with 55.84±0.46 % of entrapment efficiency shows zero order kinetic of drug release and selected for in vitro studies; the cytotoxicity of free drug and encapsulated drug in 48 h of incubation have significant difference. DAPI staining shows morphology of apoptotic nucleus in both free and encapsulated drug, Rhodamine B labeled SLNs show time dependency and accumulation of SLNs in cytoplasm. Real time qRT-PCR doesn’t show any significant difference (p>0.05) in expression of RARß2 gene in both cells treated with free or encapsulated drug. Conclusion: The results of the present study indicated that the entrapment of 5-azacytidine into SLNs enhanced its cytotoxicity performance and may pave a way for the future design of a desired dosage form for 5-azacytidine.

  5. CDH1/E-cadherin and solid tumors. An updated gene-disease association analysis using bioinformatics tools.

    Science.gov (United States)

    Abascal, María Florencia; Besso, María José; Rosso, Marina; Mencucci, María Victoria; Aparicio, Evangelina; Szapiro, Gala; Furlong, Laura Inés; Vazquez-Levin, Mónica Hebe

    2016-02-01

    Cancer is a group of diseases that causes millions of deaths worldwide. Among cancers, Solid Tumors (ST) stand-out due to their high incidence and mortality rates. Disruption of cell-cell adhesion is highly relevant during tumor progression. Epithelial-cadherin (protein: E-cadherin, gene: CDH1) is a key molecule in cell-cell adhesion and an abnormal expression or/and function(s) contributes to tumor progression and is altered in ST. A systematic study was carried out to gather and summarize current knowledge on CDH1/E-cadherin and ST using bioinformatics resources. The DisGeNET database was exploited to survey CDH1-associated diseases. Reported mutations in specific ST were obtained by interrogating COSMIC and IntOGen tools. CDH1 Single Nucleotide Polymorphisms (SNP) were retrieved from the dbSNP database. DisGeNET analysis identified 609 genes annotated to ST, among which CDH1 was listed. Using CDH1 as query term, 26 disease concepts were found, 21 of which were neoplasms-related terms. Using DisGeNET ALL Databases, 172 disease concepts were identified. Of those, 80 ST disease-related terms were subjected to manual curation and 75/80 (93.75%) associations were validated. On selected ST, 489 CDH1 somatic mutations were listed in COSMIC and IntOGen databases. Breast neoplasms had the highest CDH1-mutation rate. CDH1 was positioned among the 20 genes with highest mutation frequency and was confirmed as driver gene in breast cancer. Over 14,000 SNP for CDH1 were found in the dbSNP database. This report used DisGeNET to gather/compile current knowledge on gene-disease association for CDH1/E-cadherin and ST; data curation expanded the number of terms that relate them. An updated list of CDH1 somatic mutations was obtained with COSMIC and IntOGen databases and of SNP from dbSNP. This information can be used to further understand the role of CDH1/E-cadherin in health and disease.

  6. SU-E-I-84: Accuracy Comparison of Multi-Modality Image-Based Volumes of Rodent Solid Tumors Using In-Air Micro-CT Image Volume

    International Nuclear Information System (INIS)

    Purpose: Tumor volume is considered as a better predictor for therapy response monitoring and tumor staging over Response Evaluation Criteria In Solid Tumors (RECIST) or World Health Organization (WHO) criteria. In this study, the accuracy of subcutaneous rodent tumor volumes using preclinical magnetic resonance imaging (MRI), micro-computed tomography (micro-CT) and ultrasound (US) equipment and with an external caliper was compared using in-air micro-CT image volume of excised tumors determined as reference tumor volume in our prior study. Methods: MR, US and micro-CT images of subcutaneous SCC4 head and neck tumor xenografts were acquired 4, 6, 9, 11 and 13 days after tumor cell inoculation. Before MR and US scans, caliper measurements were made. After tumors were excised, in-air micro-CT imaging and ex vivo caliper measurements were performed. Tumor volumes were calculated using formula V = (π/6)*a*b*c where a, b and c are the maximum diameters in three perpendicular dimensions determined by the three image modalities and caliper, and compared with reference tumor volume by linear regression analysis as well as Bland-Altman plots. A one-way Analysis of Variance (ANOVA) test was also performed to compare volumes among caliper measurements. Results: The correlation coefficients (R2) of the regression lines for tumor volumes measured by the three imaging modalities and caliper were 0.9939, 0.9669, 0.9806, 0.9274, 0.9619 and 0.9819 for MRI, US and micro-CT, caliperbeforeMRI, caliperbeforeUS and ex vivo caliper respectively. In Bland-Altman plots, the average of tumor volume difference from reference tumor volume (bias) was significant for caliper and micro- CT, but not for MRI and US. Comparison of caliper measurements showed a significant difference (p < 0.05). Conclusion: Using the in-air micro-CT image volume, tumor volume measured by MRI was the most accurate among the three imaging modalities. In vivo caliper volume measurements showed unreliability while ex

  7. SU-E-I-84: Accuracy Comparison of Multi-Modality Image-Based Volumes of Rodent Solid Tumors Using In-Air Micro-CT Image Volume

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y [University of Kansas Hospital, Kansas City, KS (United States); Fullerton, G; Goins, B [University of Texas Health Science Center at San Antonio, San Antonio, TX (United States)

    2015-06-15

    Purpose: Tumor volume is considered as a better predictor for therapy response monitoring and tumor staging over Response Evaluation Criteria In Solid Tumors (RECIST) or World Health Organization (WHO) criteria. In this study, the accuracy of subcutaneous rodent tumor volumes using preclinical magnetic resonance imaging (MRI), micro-computed tomography (micro-CT) and ultrasound (US) equipment and with an external caliper was compared using in-air micro-CT image volume of excised tumors determined as reference tumor volume in our prior study. Methods: MR, US and micro-CT images of subcutaneous SCC4 head and neck tumor xenografts were acquired 4, 6, 9, 11 and 13 days after tumor cell inoculation. Before MR and US scans, caliper measurements were made. After tumors were excised, in-air micro-CT imaging and ex vivo caliper measurements were performed. Tumor volumes were calculated using formula V = (π/6)*a*b*c where a, b and c are the maximum diameters in three perpendicular dimensions determined by the three image modalities and caliper, and compared with reference tumor volume by linear regression analysis as well as Bland-Altman plots. A one-way Analysis of Variance (ANOVA) test was also performed to compare volumes among caliper measurements. Results: The correlation coefficients (R2) of the regression lines for tumor volumes measured by the three imaging modalities and caliper were 0.9939, 0.9669, 0.9806, 0.9274, 0.9619 and 0.9819 for MRI, US and micro-CT, caliperbeforeMRI, caliperbeforeUS and ex vivo caliper respectively. In Bland-Altman plots, the average of tumor volume difference from reference tumor volume (bias) was significant for caliper and micro- CT, but not for MRI and US. Comparison of caliper measurements showed a significant difference (p < 0.05). Conclusion: Using the in-air micro-CT image volume, tumor volume measured by MRI was the most accurate among the three imaging modalities. In vivo caliper volume measurements showed unreliability while ex

  8. Importance of antiresorptive therapies for patients with bone metastases from solid tumors

    International Nuclear Information System (INIS)

    Patients with bone metastases are at risk of skeletal-related events such as pathologic fractures, spinal cord compression, the need for orthopedic surgery to bone, and palliative radiotherapy for severe bone pain. Antiresorptive therapies have demonstrated efficacy for reducing the risk of skeletal-related events and ameliorating bone pain. Despite the well documented clinical benefits of antiresorptive therapies, patient benefits can be limited or compromised by nonadherence with scheduled therapy. Potential reasons for poor compliance include lack of understanding of how antiresorptive therapies work, neglecting the importance of bone health in maintaining quality of life, and being unaware of the potentially debilitating effects of skeletal-related events caused by bone metastases. Indeed, patients may stop therapy after bone pain subsides or discontinue due to generally mild and usually manageable adverse events, leaving them at an increased risk of developing skeletal-related events. In addition, the cost of antiresorptive therapy can be a concern for many patients with cancer. Medical care for patients with cancer requires a coordinated effort between primary care physicians and oncologists. Patients’ medical care teams can be leveraged to help educate them about the importance of adherence to antiresorptive therapy when cancer has metastasized to bone. Because primary care physicians generally have more contact with their patients than oncologists, they are in a unique position to understand patient perceptions and habits that may lead to noncompliance and to help educate patients about the benefits and risks of various antiresorptive therapies in the advanced cancer setting. Therefore, primary care physicians need to be aware of various mechanistic and clinical considerations regarding antiresorptive treatment options

  9. Current advances in mathematical modeling of anti-cancer drug penetration into tumor tissues

    Directory of Open Access Journals (Sweden)

    MunJu eKim

    2013-11-01

    Full Text Available Delivery of anti-cancer drugs to tumor tissues, including their interstitial transport and cellular uptake, is a complex process involving various biochemical, mechanical, and biophysical factors. Mathematical modeling provides a means through which to understand this complexity better, as well as to examine interactions between contributing components in a systematic way via computational simulations and quantitative analyses. In this review, we present the current state of mathematical modeling approaches that address phenomena related to drug delivery. We describe how various types of models were used to predict spatio-temporal distributions of drugs within the tumor tissue, to simulate different ways to overcome barriers to drug transport, or to optimize treatment schedules. Finally, we discuss how integration of mathematical modeling with experimental or clinical data can provide better tools to understand the drug delivery process, in particular to examine the specific tissue- or compound-related factors that limit drug penetration through tumors. Such tools will be important in designing new chemotherapy targets and optimal treatment strategies, as well as in developing non-invasive diagnosis to monitor treatment response and detect tumor recurrence.

  10. Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma.

    Science.gov (United States)

    Theurich, Sebastian; Rothschild, Sacha I; Hoffmann, Michael; Fabri, Mario; Sommer, Andrea; Garcia-Marquez, Maria; Thelen, Martin; Schill, Catherine; Merki, Ramona; Schmid, Thomas; Koeberle, Dieter; Zippelius, Alfred; Baues, Christian; Mauch, Cornelia; Tigges, Christian; Kreuter, Alexander; Borggrefe, Jan; von Bergwelt-Baildon, Michael; Schlaak, Max

    2016-09-01

    Immune checkpoint inhibition with ipilimumab has revolutionized cancer immunotherapy and significantly improved outcomes of patients with advanced malignant melanoma. Local peripheral treatments (LPT), such as radiotherapy or electrochemotherapy, have been shown to modulate systemic immune responses, and preliminary data have raised the hypothesis that the combination of LPT with systemic immune checkpoint blockade might be beneficial. Clinical data from 127 consecutively treated melanoma patients at four cancer centers in Germany and Switzerland were analyzed. Patients received either ipilimumab (n = 82) or ipilimumab and additional LPT (n = 45) if indicated for local tumor control. The addition of LPT to ipilimumab significantly prolonged overall survival (OS; median OS 93 vs. 42 weeks, unadjusted HR, 0.46; P = 0.0028). Adverse immune-related events were not increased by the combination treatment, and LPT-induced local toxicities were in most cases mild. In a multivariable Cox regression analysis, we show that the effect of added LPT on OS remained statistically significant after adjusting for BRAF status, tumor stage, tumor burden, and central nervous system metastases (adjusted HR, 0.56; 95% confidence interval, 0.31-1.01, P = 0.05). Our data suggest that the addition of LPT to ipilimumab is safe and effective in patients with metastatic melanoma irrespective of clinical disease characteristics and known risk factors. Induction of antitumor immune responses is most likely the underlying mechanism and warrants prospective validation. Cancer Immunol Res; 4(9); 744-54. ©2016 AACR. PMID:27466265

  11. Expression of the GLI family genes is associated with tumor progression in advanced lung adenocarcinoma

    OpenAIRE

    Ishikawa, Masashi; Sonobe, Makoto; Imamura, Naoto; Sowa, Terumasa; Shikuma, Kei; Date, Hiroshi

    2014-01-01

    Background The hedgehog (Hh) signaling pathway is aberrantly activated in various cancers. Expression of the GLI family of genes, which encode for transcriptional factors of the Hh pathway, has not been fully assessed in clinical samples of advanced lung adenocarcinoma. In this study, we retrospectively evaluated the expression of the GLI family of genes in advanced stage lung adenocarcinoma samples and determined their relation to patient survival. Methods The levels of GLI1, GLI2, and GLI3 ...

  12. Early sorafenib-induced toxicity is associated with drug exposure and UGTIA9 genetic polymorphism in patients with solid tumors: a preliminary study.

    Directory of Open Access Journals (Sweden)

    Pascaline Boudou-Rouquette

    Full Text Available BACKGROUND: Identifying predictive biomarkers of drug response is of key importance to improve therapy management and drug selection in cancer therapy. To date, the influence of drug exposure and pharmacogenetic variants on sorafenib-induced toxicity remains poorly documented. The aim of this pharmacokinetic/pharmacodynamic (PK/PD study was to investigate the relationship between early toxicity and drug exposure or pharmacogenetic variants in unselected adult outpatients treated with single-agent sorafenib for advanced solid tumors. METHODS: Toxicity was recorded in 54 patients on days 15 and 30 after treatment initiation and sorafenib exposure was assessed in 51 patients. The influence of polymorphisms in CYP3A5, UGT1A9, ABCB1 and ABCG2 was examined in relation to sorafenib exposure and toxicity. Clinical characteristics, drug exposure and pharmacogenetic variants were tested univariately for association with toxicities. Candidate variables with p<0.1 were analyzed in a multivariate analysis. RESULTS: Gender was the sole parameter independently associated with sorafenib exposure (p = 0.0008. Multivariate analysis showed that increased cumulated sorafenib (AUC(cum was independently associated with any grade ≥ 3 toxicity (p = 0.037; UGT1A9 polymorphism (rs17868320 with grade ≥ 2 diarrhea (p = 0.015 and female gender with grade ≥ 2 hand-foot skin reaction (p = 0.018. Using ROC curve, the threshold AUC(cum value of 3,161 mg/L.h was associated with the highest risk to develop any grade ≥ 3 toxicity (p = 0.018. CONCLUSION: In this preliminary study, increased cumulated drug exposure and UGT1A9 polymorphism (rs17868320 identified patients at high risk for early sorafenib-induced severe toxicity. Further PK/PD studies on larger population are warranted to confirm these preliminary results.

  13. Advanced Flow Analysis Tools for Transient Solid Rocket Motor Simulations Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The challenges of designing, developing, and fielding man-rated propulsion systems continue to increase as NASA's mission moves forward with evolving solid...

  14. Comparative therapeutic efficacy of rhenium-188 radiolabeled-liposome and 5-fluorouracil in LS-174T human colon carcinoma solid tumor xenografts.

    Science.gov (United States)

    Hsu, Chin-Wei; Chang, Ya-Jen; Chang, Chih-Hsien; Chen, Liang-Cheng; Lan, Keng-Li; Ting, Gann; Lee, Te-Wei

    2012-10-01

    Nanoliposomes are important carriers capable of packaging drugs for various delivery applications. Rhenium-188-radiolabeled liposome ((188)Re-liposome) has potential for radiotherapy and diagnostic imaging. To evaluate the targeting of (188)Re-liposome, biodistribution, microSPECT/CT, whole-body autoradiography (WBAR), and pharmacokinetics were performed in LS-174T human tumor-bearing mice. The comparative therapeutic efficacy of (188)Re-liposome and 5-fluorouracil (5-FU) was assessed according to inhibition of tumor growth and the survival ratio. The highest uptake of (188)Re-liposome in LS-174T tumor was found at 24 hours by biodistribution and microSPECT/CT imaging, showing a positive correlation for tumor targeting of (188)Re-liposome using the Pearson's correlation analysis (r=0.997). Pharmacokinetics of (188)Re-liposome showed the properties of high circulation time and high bioavailability (mean residence time [MRT]=18.8 hours, area under the curve [AUC]=1371%ID/g·h). For therapeutic efficacy, the tumor-bearing mice treated with (188)Re-liposome (80% maximum tolerated dose [MTD], 23.7 MBq) showed better tumor growth inhibition and longer survival time than those treated with 5-FU (80% MTD, 144 mg/kg). The median survival time for mice treated with (188)Re-liposome (58.5 days; p0.05) and normal saline-treated mice (43.63 days). Dosimetry study revealed that the (188)Re-liposome did not lead to high absorbed doses in normal tissue, but did in small tumors. These results of imaging and biodistribution indicated the highly specific accumulation of tumor after intravenous (i.v.) injection of (188)Re-liposome. The therapeutic efficacy of radiotherapeutics of (188)Re-liposome have been confirmed in a LS-174T solid tumor animal model, which points to the potential benefit and promise of passive nanoliposome delivered radiotherapeutics for cancer treatment.

  15. Chemical structures of swine-manure chars produced under different carbonization conditions investigated by advanced solid-state 13C nuclear magnetic resonance (NMR) spectroscopy

    Science.gov (United States)

    Two types of swine manure chars, hydrothermally-produced hydrochar and slow-pyrolysis pyrochar, and their raw swine manure solid were characterized using advanced 13C solid-state nuclear magnetic resonance (NMR) spectroscopy. Compared with the parent raw swine manure, both hydrochars and pyrochar di...

  16. Accuracy of MRI for estimating residual tumor size after neoadjuvant chemotherapy in locally advanced breast cancer: Relation to response patterns on MRI

    International Nuclear Information System (INIS)

    Background. This study evaluated the accuracy of magnetic resonance imaging (MRI) for estimating residual tumor size after neoadjuvant chemotherapy in patients with locally advanced breast cancer and assessed whether the tumor pattern on MRI after chemotherapy influenced the accuracy of the MRI measurement of the residual tumor size. Patients and methods. Fifty patients who received neoadjuvant chemotherapy with doxorubicin and docetaxel for locally advanced breast cancer were evaluated with MRI before and after chemotherapy. We compared the residual tumor size measured by MRI with the pathologically determined size and investigated the influence of the residual tumor pattern on MRI (shrinkage, nest or rim, and mixed) and pathologic characteristics on the accuracy of the MRI measurement. Results. The correlation coefficient between the residual tumor sizes determined by MRI and by pathology was 0.645. The MRI measurement agreed with the pathologically determined size in 36 patients (72%) and disagreed in 14 patients (28%), overestimating the size in 13 (26%) and underestimating the size in one (2%). Disagreement appeared to be more frequent in the cases showing a nest or rim pattern than in those exhibiting a shrinkage pattern, although this was not statistically significant (p=0.119). Conclusions. MRI is an accurate method for predicting the extent of residual tumor after neoadjuvant chemotherapy; however, it may overestimate the residual disease, especially in cases showing a nest or rim tumor pattern and in those having combined lesions with ductal carcinoma in situ or multiple scattered nodules after neoadjuvant chemotherapy

  17. Recent advances in small molecular, non-polymeric organic hole transporting materials for solid-state DSSC

    Directory of Open Access Journals (Sweden)

    Bui Thanh-Tuan

    2013-10-01

    Full Text Available Issue from thin-film technologies, dye-sensitized solar cells have become one of the most promising technologies in the field of renewable energies. Their success is not only due to their low weight, the possibility of making large flexible surfaces, but also to their photovoltaic efficiency which are found to be more and more significant (>12% with a liquid electrolyte, >7% with a solid organic hole conductor. This short review highlights recent advances in the characteristics and use of low-molecular-weight glass-forming organic materials as hole transporters in all solid-state dye-sensitized solar cells. These materials must feature specific physical and chemical properties that will ensure both the operation of a photovoltaic cell and the easy implementation. This review is an english extended version based on our recent article published in Matériaux & Techniques 101, 102 (2013.

  18. Antitumorigenic potential of linalool is accompanied by modulation of oxidative stress: an in vivo study in sarcoma-180 solid tumor model.

    Science.gov (United States)

    Jana, Samarjit; Patra, Kartick; Sarkar, Shehnaz; Jana, Jagannath; Mukherjee, Gopeswar; Bhattacharjee, Shamee; Mandal, Deba Prasad

    2014-01-01

    Coriander, used as a common food seasoning, contains linalool as the main constituent of its essential oil. In this study, we tested the effect of linalool vis-à-vis that of a conventional chemotherapeutic drug, cyclophosphamide, against solid S-180 tumor-bearing Swiss albino mice. Tumor volume, cell count, cell cycle phase distribution, apoptosis, and proliferation markers indicate that linalool has potent antitumor activity. In vitro and in vivo data suggest that induction of oxidative stress might be responsible for the anticancer effect of linalool. However, interestingly, unlike cyclophosphamide, linalool did not induce myelosuppression or hepatotoxicity in mice as evident from bone marrow cell count, status of hepatic oxidative stress/antioxidant enzymes, and histopathology. Thus, linalool exerted prooxidant effect in tumor tissue and an antioxidant effect in liver. This is also supported by the expression of Nrf-2 and p21, which are considered to be important players in response to oxidative stress. Moreover, administration of linalool modulated the proliferation of spleen cells in tumor-bearing mice challenged with lipopolysaccharide. Finally, the detection of linalool in sera and tumor tissues by HPLC confirmed its bioavailability. In conclusion, linalool showed differential cytotoxicity towards tumor and normal cells in contrast to cyclophosphamide, which is uniformly toxic to both.

  19. Combination angiostatin and endostatin gene transfer induces synergistic antiangiogenic activity in vitro and antitumor efficacy in leukemia and solid tumors in mice.

    Science.gov (United States)

    Scappaticci, F A; Smith, R; Pathak, A; Schloss, D; Lum, B; Cao, Y; Johnson, F; Engleman, E G; Nolan, G P

    2001-02-01

    Angiostatin and endostatin are potent endothelial cell growth inhibitors that have been shown to inhibit angiogenesis in vivo and tumor growth in mice. However, tumor shrinkage requires chronic delivery of large doses of these proteins. Here we report synergistic antitumor activity and survival of animals when these factors are delivered in combination to tumors by retroviral gene transfer. We have demonstrated this efficacy in both murine leukemia and melanoma models. Complete loss of tumorigenicity was seen in 40% of the animals receiving tumors transduced by the combination of angiostatin and endostatin in the leukemia model. The synergy was also demonstrated in vitro on human umbilical vein endothelial cell differentiation and this antiangiogenic activity may suggest a mechanism for the antitumor activity in vivo. These findings imply separate pathways by which angiostatin and endostatin mediate their antiangiogenic effects. Together, these data suggest that a combination of antiangiogenic factors delivered by retroviral gene transfer may produce synergistic antitumor effects in both leukemia and solid tumors, thus avoiding long-term administration of recombinant proteins. The data also suggest that novel combinations of antiangiogenic factors delivered into tumors require further investigation as therapeutic modalities. PMID:11237675

  20. A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas

    Science.gov (United States)

    2016-10-18

    Ewing Sarcoma; Gastrointestinal Tumor; Germ Cell Tumor; Hepatic Tumor; Lymphoma; Wilms Tumor; Rhabdoid Tumor; Clear Cell Carcinoma; Renal Cell Carcinoma; Melanoma; Neuroblastoma; Rhabdomyosarcoma; Non-rhabdomyosarcoma