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Sample records for total metabolic tumor

  1. Tumor Macroenvironment and Metabolism

    OpenAIRE

    Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S.; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-01-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organ...

  2. Tumor macroenvironment and metabolism.

    Science.gov (United States)

    Al-Zoughbi, Wael; Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-04-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%-20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient's outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Tumor Metabolism of Malignant Gliomas

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    Ru, Peng; Williams, Terence M.; Chakravarti, Arnab; Guo, Deliang, E-mail: deliang.guo@osumc.edu [Department of Radiation Oncology, Ohio State University Comprehensive Cancer Center & Arthur G James Cancer Hospital, Columbus, OH 43012 (United States)

    2013-11-08

    Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation.

  4. Tumor Metabolism of Malignant Gliomas

    International Nuclear Information System (INIS)

    Ru, Peng; Williams, Terence M.; Chakravarti, Arnab; Guo, Deliang

    2013-01-01

    Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation

  5. Baseline Metabolic Tumor Volume and Total Lesion Glycolysis Are Associated With Survival Outcomes in Patients With Locally Advanced Pancreatic Cancer Receiving Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Dholakia, Avani S. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Chaudhry, Muhammad; Leal, Jeffrey P. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Chang, Daniel T. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Raman, Siva P. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hacker-Prietz, Amy [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Su, Zheng; Pai, Jonathan [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Oteiza, Katharine E.; Griffith, Mary E. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Wahl, Richard L. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Tryggestad, Erik [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Pawlik, Timothy [Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Laheru, Daniel A. [Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Wolfgang, Christopher L. [Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Koong, Albert C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); and others

    2014-07-01

    Purpose: Although previous studies have demonstrated the prognostic value of positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer has yet to be well established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT). Materials and Methods: Thirty-two patients with LAPC in a prospective clinical trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of 6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUV{sub max} and SUV{sub peak}) on pre-SBRT PET scans were calculated using custom-designed software. Disease was measured at a threshold based on the liver SUV, using the equation Liver{sub mean} + [2 × Liver{sub sd}]. Median values of PET parameters were used as cutoffs when assessing their prognostic potential through Cox regression analyses. Results: Of the 32 patients, the majority were male (n=19, 59%), 65 years or older (n=21, 66%), and had tumors located in the pancreatic head (n=27, 84%). Twenty-seven patients (84%) received induction gemcitabine prior to SBRT. Median overall survival for the entire cohort was 18.8 months (95% confidence interval [CI], 15.7-22.0). An MTV of 26.8 cm{sup 3} or greater (hazard ratio [HR] 4.46, 95% CI 1.64-5.88, P<.003) and TLG of 70.9 or greater (HR 3.08, 95% CI 1.18-8.02, P<.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19-22.21, P=.029) and TLG (HR 3.34, 95% CI 1.07-10.48, P=.038) remained independently associated with overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG are potential predictive factors for overall survival in patients with LAPC and may assist in

  6. Baseline Metabolic Tumor Volume and Total Lesion Glycolysis Are Associated With Survival Outcomes in Patients With Locally Advanced Pancreatic Cancer Receiving Stereotactic Body Radiation Therapy

    International Nuclear Information System (INIS)

    Dholakia, Avani S.; Chaudhry, Muhammad; Leal, Jeffrey P.; Chang, Daniel T.; Raman, Siva P.; Hacker-Prietz, Amy; Su, Zheng; Pai, Jonathan; Oteiza, Katharine E.; Griffith, Mary E.; Wahl, Richard L.; Tryggestad, Erik; Pawlik, Timothy; Laheru, Daniel A.; Wolfgang, Christopher L.; Koong, Albert C.

    2014-01-01

    Purpose: Although previous studies have demonstrated the prognostic value of positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer has yet to be well established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT). Materials and Methods: Thirty-two patients with LAPC in a prospective clinical trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of 6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUV max and SUV peak ) on pre-SBRT PET scans were calculated using custom-designed software. Disease was measured at a threshold based on the liver SUV, using the equation Liver mean + [2 × Liver sd ]. Median values of PET parameters were used as cutoffs when assessing their prognostic potential through Cox regression analyses. Results: Of the 32 patients, the majority were male (n=19, 59%), 65 years or older (n=21, 66%), and had tumors located in the pancreatic head (n=27, 84%). Twenty-seven patients (84%) received induction gemcitabine prior to SBRT. Median overall survival for the entire cohort was 18.8 months (95% confidence interval [CI], 15.7-22.0). An MTV of 26.8 cm 3 or greater (hazard ratio [HR] 4.46, 95% CI 1.64-5.88, P<.003) and TLG of 70.9 or greater (HR 3.08, 95% CI 1.18-8.02, P<.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19-22.21, P=.029) and TLG (HR 3.34, 95% CI 1.07-10.48, P=.038) remained independently associated with overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG are potential predictive factors for overall survival in patients with LAPC and may assist in tailoring therapy

  7. [The cancer tumor: a metabolic parasite?].

    Science.gov (United States)

    Icard, Philippe; Lincet, Hubert

    2013-05-01

    Cancer cells activate glycolysis, glutaminolysis and β-oxidation to promote their biosynthesis. The low activity of pyruvate kinase, reexpressed in its embryonic isoform PKM2, generates a bottleneck at the end of glycolysis, which reorients glucose catabolism towards formation of molecules implied in numerous synthesis: ribose for nucleic acids, glycerol for lipid synthesis, etc. However, a part of glucose is transformed in pyruvate, which also comes from aminoacids catabolism. Due to the inhibition of pyruvate dehydrogenase, pyruvate is preferentially transformed into lactate, either in the presence of oxygen (Warburg effect). Lactate dehydrogenase reaction furnishes lactic acid, which acidifies the tumoral microenvironment, a process which favors the cellular growth and regenerates NAD(+), a crucial cofactor for the functioning of various metabolic pathways (glycolysis, DNA synthesis and repair…). Cancer cells consume a lot of glutamine, which replenish Krebs cycle (coupled with ATP production), and/or furnishes aspartate for nucleotides synthesis. This particular metabolism is sustained by activation of oncogenes (Myc, AKT, etc.) and suppressors inactivation (P53, PTEN…). Like a parasite, cells draw on reserves of the host to supply their own biosynthesis, while they secrete waste products (NO, polyamines, ammonia, lactate…) that promote cellular growth. A "symbiotic" cooperation could be established between tumor cells themselves, and/or with environmental cells, to maximize ATP production in relation with resources and oxygen concentration.

  8. Famine versus feast: understanding the metabolism of tumors in vivo.

    Science.gov (United States)

    Mayers, Jared R; Vander Heiden, Matthew G

    2015-03-01

    To fuel unregulated proliferation, cancer cells alter metabolism to support macromolecule biosynthesis. Cell culture studies have revealed how different oncogenic mutations and nutrients impact metabolism. Glucose and glutamine are the primary fuels used in vitro; however, recent studies have suggested that utilization of other amino acids as well as lipids and protein can also be important to cancer cells. Early investigations of tumor metabolism are translating these findings to the biology of whole tumors and suggest that additional complexity exists beyond nutrient availability alone in vivo. Whole-body metabolism and tumor heterogeneity also influence the metabolism of tumor cells, and successful targeting of metabolism for cancer therapy will require an understanding of tumor metabolism in vivo. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Nature and Nurture: What Determines Tumor Metabolic Phenotypes?

    Science.gov (United States)

    Mayers, Jared R; Vander Heiden, Matthew G

    2017-06-15

    Understanding the genetic basis of cancer has led to therapies that target driver mutations and has helped match patients with more personalized drugs. Oncogenic mutations influence tumor metabolism, but other tumor characteristics can also contribute to their metabolic phenotypes. Comparison of isogenic lung and pancreas tumor models suggests that use of some metabolic pathways is defined by lineage rather than by driver mutation. Lung tumors catabolize circulating branched chain amino acids (BCAA) to extract nitrogen for nonessential amino acid and nucleotide synthesis, whereas pancreatic cancer obtains amino acids from catabolism of extracellular protein. These differences in amino acid metabolism translate into distinct pathway dependencies, as genetic disruption of the enzymes responsible for utilization of BCAA nitrogen limits the growth of lung tumors, but not pancreatic tumors. These data argue that some cancer metabolic phenotypes are defined by cancer tissue-of-origin and environment and that these features constrain the influence of genetic mutations on metabolism. A better understanding of the factors defining tumor nutrient utilization could be exploited to help improve cancer therapy. Cancer Res; 77(12); 3131-4. ©2017 AACR . ©2017 American Association for Cancer Research.

  10. Magnetic Resonance Spectroscopic Imaging of Tumor Metabolic Markers for Cancer Diagnosis, Metabolic Phenotyping, and Characterization of Tumor Microenvironment

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    Qiuhong He

    2004-01-01

    Full Text Available Cancer cells display heterogeneous genetic characteristics, depending on the tumor dynamic microenvironment. Abnormal tumor vasculature and poor tissue oxygenation generate a fraction of hypoxic tumor cells that have selective advantages in metastasis and invasion and often resist chemo- and radiation therapies. The genetic alterations acquired by tumors modify their biochemical pathways, which results in abnormal tumor metabolism. An elevation in glycolysis known as the “Warburg effect” and changes in lipid synthesis and oxidation occur. Magnetic resonance spectroscopy (MRS has been used to study tumor metabolism in preclinical animal models and in clinical research on human breast, brain, and prostate cancers. This technique can identify specific genetic and metabolic changes that occur in malignant tumors. Therefore, the metabolic markers, detectable by MRS, not only provide information on biochemical changes but also define different metabolic tumor phenotypes. When combined with the contrast-enhanced Magnetic Resonance Imaging (MRI, which has a high sensitivity for cancer diagnosis, in vivo magnetic resonance spectroscopic imaging (MRSI improves the diagnostic specificity of malignant human cancers and is becoming an important clinical tool for cancer management and care. This article reviews the MRSI techniques as molecular imaging methods to detect and quantify metabolic changes in various tumor tissue types, especially in extracranial tumor tissues that contain high concentrations of fat. MRI/MRSI methods have been used to characterize tumor microenvironments in terms of blood volume and vessel permeability. Measurements of tissue oxygenation and glycolytic rates by MRS also are described to illustrate the capability of the MR technology in probing molecular information non-invasively in tumor tissues and its important potential for studying molecular mechanisms of human cancers in physiological conditions.

  11. Kidney cancer progression linked to shifts in tumor metabolism

    Science.gov (United States)

    Investigators in The Cancer Genome Atlas Research Network have uncovered a connection between how tumor cells use energy from metabolic processes and the aggressiveness of the most common form of kidney cancer, clear cell renal cell carcinoma.

  12. Effects of exercise on tumor physiology and metabolism

    DEFF Research Database (Denmark)

    Pedersen, Line; Christensen, Jesper Frank; Hojman, Pernille

    2015-01-01

    . Here, we review the body of literature describing exercise intervention studies performed in rodent tumor models and elaborate on potential mechanistic effects of exercise on tumor physiology. Exercise has been shown to reduce tumor incidence, tumor multiplicity, and tumor growth across numerous...... different transplantable, chemically induced or genetic tumor models. We propose 4 emerging mechanistic effects of exercise, including (1) vascularization and blood perfusion, (2) immune function, (3) tumor metabolism, and (4) muscle-to-cancer cross-talk, and discuss these in details. In conclusion......, exercise training has the potential to be a beneficial and integrated component of cancer management, but has yet to fully elucidate its potential. Understanding the mechanistic effects of exercise on tumor physiology is warranted. Insight into these mechanistic effects is emerging, but experimental...

  13. Effects of exercise on tumor physiology and metabolism.

    Science.gov (United States)

    Pedersen, Line; Christensen, Jesper Frank; Hojman, Pernille

    2015-01-01

    Exercise is a potent regulator of a range of physiological processes in most tissues. Solid epidemiological data show that exercise training can reduce disease risk and mortality for several cancer diagnoses, suggesting that exercise training may directly regulate tumor physiology and metabolism. Here, we review the body of literature describing exercise intervention studies performed in rodent tumor models and elaborate on potential mechanistic effects of exercise on tumor physiology. Exercise has been shown to reduce tumor incidence, tumor multiplicity, and tumor growth across numerous different transplantable, chemically induced or genetic tumor models. We propose 4 emerging mechanistic effects of exercise, including (1) vascularization and blood perfusion, (2) immune function, (3) tumor metabolism, and (4) muscle-to-cancer cross-talk, and discuss these in details. In conclusion, exercise training has the potential to be a beneficial and integrated component of cancer management, but has yet to fully elucidate its potential. Understanding the mechanistic effects of exercise on tumor physiology is warranted. Insight into these mechanistic effects is emerging, but experimental intervention studies are still needed to verify the cause-effect relationship between these mechanisms and the control of tumor growth.

  14. Analysis of metabolic change by Tl-201 SPECT in brain tumors treated with stereotactic radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Sugo, Nobuo [Toho Univ., Tokyo (Japan). School of Medicine

    1996-03-01

    The time course for changes in Tl-201 uptake and tumor size was studied correlatively. A total of 24 cases of brain tumors was enrolled in the study. Three detector type scanner, PRISM 3000 was used. SPECT scanning was started 10 min after intravenous administration of 111 MBq of Tl-201, and sequentially repeated every 1 min for 16 min. Tl-201 radioactivity was counted in two regions of interest (ROI). One was an area encircling the tumor, and the other, an area in the contralateral hemisphere that served as control. Tl index (TI) was calculated by this formula: TI=T-C/C, where T is the count in the tumor and C, the count in the control area. The size of a given tumor was represented by its maximum diameter as determined by CT or MRI. The TI and the tumor size were compared before and after radiosurgery. In all cases, a decrease in TI was seen earlier than a reduction in tumor size. Among malignant tumors, the TI decrease took place as early as one week, and rapidly reached the lowest level. On the other hand, in benign tumors, it took as long as 6 to 12 months for the decrease of the TI to be evident; the subsequent was very slow. The difference between malignant and benign tumors of the brain is attributed to the fact that high dose irradiation of the malignant, radiosensitive tumors causes deep disturbances in cell metabolism that lead to cell death. By contrast, irradiation of a benign tumor with low radiosensitivity does not affect the cellular metabolism, but injures the vascular wall, leading to gradual stenosis or obliteration of the vessels in the tumor. These data strongly suggest that the rapid and marked decrease of malignant tumors after stereotactic radiosurgery is the result of a direct injury to the malignant cells, and that the rather slow and insufficient diminution of benign tumors can be attributed to diminished blood supply to the tumor. (author)

  15. Glycemic Variation in Tumor Patients with Total Parenteral Nutrition

    Directory of Open Access Journals (Sweden)

    Jin-Cheng Yang

    2015-01-01

    Full Text Available Background: Hyperglycemia is associated with poor clinical outcomes and mortality in several patients. However, studies evaluating hyperglycemia variation in tumor patients receiving total parenteral nutrition (TPN are scarce. The aim of this study was to assess the relationship between glycemia and tumor kinds with TPN by monitoring glycemic variation in tumor patients. Methods: This retrospective clinical trial selected 312 patients with various cancer types, whose unique nutrition treatment was TPN during the monitoring period. All patients had blood glucose (BG values assessed at least six times daily during the TPN infusion. The glycemic variation before and after TPN was set as the indicator to evaluate the factors influencing BG. Results: The clinical trial lasted 7.5 ± 3.0 days adjusted for age, gender, family cancer history and blood types. There were six cancer types: Hepatic carcinoma (HC, 21.8%, rectal carcinoma (17.3%, colon carcinoma (CC, 14.7%, gastric carcinoma (29.8%, pancreatic carcinoma (11.5%, and duodenal carcinoma (DC, 4.8%. The patients were divided into diabetes and nondiabetes groups. No statistical differences in TPN glucose content between diabetes and nondiabetes groups were found; however, the tumor types affected by BG values were obvious. With increasing BG values, DC, HC and CC were more represented than other tumor types in this sequence in diabetic individuals, as well as in the nondiabetic group. BG was inclined to be more easily influenced in the nondiabetes group. Other factors did not impact BG values, including gender, body mass index, and TPN infusion duration time. Conclusions: When tumor patients are treated with TPN, BG levels should be monitored according to different types of tumors, besides differentiating diabetes or nondiabetes patients. Special BG control is needed for DC, HC and CC in both diabetic and nondiabetic patients. If BG overtly increases, positive measurements are needed to control BG

  16. Altered oxidative stress and carbohydrate metabolism in canine mammary tumors

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    K. Jayasri

    2016-12-01

    Full Text Available Aim: Mammary tumors are the most prevalent type of neoplasms in canines. Even though cancer induced metabolic alterations are well established, the clinical data describing the metabolic profiles of animal tumors is not available. Hence, our present investigation was carried out with the aim of studying changes in carbohydrate metabolism along with the level of oxidative stress in canine mammary tumors. Materials and Methods: Fresh mammary tumor tissues along with the adjacent healthy tissues were collected from the college surgical ward. The levels of thiobarbituric acid reactive substances (TBARS, glutathione, protein, hexose, hexokinase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, and glucose-6-phosphate dehydrogenase (G6PD were analyzed in all the tissues. The results were analyzed statistically. Results: More than two-fold increase in TBARS and three-fold increase in glutathione levels were observed in neoplastic tissues. Hexokinase activity and hexose concentration (175% was found to be increased, whereas glucose-6-phosphatase (33%, fructose-1, 6-bisphosphatase (42%, and G6PD (5 fold activities were reduced in tumor mass compared to control. Conclusion: Finally, it was revealed that lipid peroxidation was increased with differentially altered carbohydrate metabolism in canine mammary tumors.

  17. Metabolic changes in tumor cells and tumor-associated macrophages: A mutual relationship.

    Science.gov (United States)

    Netea-Maier, Romana T; Smit, Johannes W A; Netea, Mihai G

    2018-01-28

    In order to adapt to the reduced availability of nutrients and oxygen in the tumor microenvironment and the increased requirements of energy and building blocks necessary for maintaining their high proliferation rate, malignant cells undergo metabolic changes that result in an increased production of lactate, nitric oxide, reactive oxygen species, prostaglandins and other byproducts of arachidonic acid metabolism that influence both the composition of the inflammatory microenvironment and the function of the tumor-associated macrophages (TAMs). In response to cues present in the TME, among which products of altered tumor cell metabolism, TAMs are also required to reprogram their metabolism, with activation of glycolysis, fatty acid synthesis and altered nitrogen cycle metabolism. These changes result in functional reprogramming of TAMs which includes changes in the production of cytokines and angiogenetic factors, and contribute to the tumor progression and metastasis. Understanding the metabolic changes governing the intricate relationship between the tumor cells and the TAMs represents an essential step towards developing novel therapeutic approaches targeting the metabolic reprogramming of the immune cells to potentiate their tumoricidal potential and to circumvent therapy resistance. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Drug discovery strategies in the field of tumor energy metabolism: Limitations by metabolic flexibility and metabolic resistance to chemotherapy.

    Science.gov (United States)

    Amoedo, N D; Obre, E; Rossignol, R

    2017-08-01

    The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro. Such contradictory findings raised several questions concerning the optimization of drug discovery strategies in the field of cancer metabolism. For instance, the cell culture models in 2D or 3D might already show strong limitations to mimic the tumor micro- and macro-environment. The microenvironment of tumors is composed of cancer cells of variegated metabolic profiles, supporting local metabolic exchanges and symbiosis, but also of immune cells and stroma that further interact with and reshape cancer cell metabolism. The macroenvironment includes the different tissues of the organism, capable of exchanging signals and fueling the tumor 'a distance'. Moreover, most metabolic targets were identified from their increased expression in tumor transcriptomic studies, or from targeted analyses looking at the metabolic impact of particular oncogenes or tumor suppressors on selected metabolic pathways. Still, very few targets were identified from in vivo analyses of tumor metabolism in patients because such studies are difficult and adequate imaging methods are only currently being developed for that purpose. For instance, perfusion of patients with [ 13 C]-glucose allows deciphering the metabolomics of tumors and opens a new area in the search for effective targets. Metabolic imaging with positron emission tomography and other techniques that do not involve [ 13 C] can also be used to evaluate tumor

  19. Total Humeral Endoprosthetic Replacement following Excision of Malignant Bone Tumors

    Directory of Open Access Journals (Sweden)

    Suhel Kotwal

    2016-01-01

    Full Text Available Humerus is a common site for malignant tumors. Advances in adjuvant therapies and reconstructive methods provide salvage of the upper limb with improved outcomes. Reports of limb salvage with total humeral replacement in extensive humeral tumors are sparse. We undertook a retrospective study of 20 patients who underwent total humeral endoprosthetic replacement as limb salvage following excision of extensile malignant tumor from 1990 to 2011. With an average followup of 42.9, functional and oncological outcomes were analyzed. Ten patients were still alive at the time of review. Mean estimated blood loss was 1131 mL and duration of surgery was 314 minutes. Deep infection was encountered in one patient requiring debridement while mechanical loosening of ulnar component was identified in one patient. Subluxation of prosthetic humeral head was noted in 3 patients. Mean active shoulder abduction was 12.5° and active flexion was 15°. Incompetence of abduction mechanism was the major determinant of poor active functional outcome. Mean elbow flexion was 103.5° with 30.5° flexion contracture in 10 patients with good and useful hand function. Average MSTS score was 71.5%. Total humeral replacement is a reliable treatment option in restoring mechanical stability and reasonable functional results without compromising patient survival, with low complication rate.

  20. A mechanistic compartmental model for total antibody uptake in tumors.

    Science.gov (United States)

    Thurber, Greg M; Dane Wittrup, K

    2012-12-07

    Antibodies are under development to treat a variety of cancers, such as lymphomas, colon, and breast cancer. A major limitation to greater efficacy for this class of drugs is poor distribution in vivo. Localization of antibodies occurs slowly, often in insufficient therapeutic amounts, and distributes heterogeneously throughout the tumor. While the microdistribution around individual vessels is important for many therapies, the total amount of antibody localized in the tumor is paramount for many applications such as imaging, determining the therapeutic index with antibody drug conjugates, and dosing in radioimmunotherapy. With imaging and pretargeted therapeutic strategies, the time course of uptake is critical in determining when to take an image or deliver a secondary reagent. We present here a simple mechanistic model of antibody uptake and retention that captures the major rates that determine the time course of antibody concentration within a tumor including dose, affinity, plasma clearance, target expression, internalization, permeability, and vascularization. Since many of the parameters are known or can be estimated in vitro, this model can approximate the time course of antibody concentration in tumors to aid in experimental design, data interpretation, and strategies to improve localization. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness

    Energy Technology Data Exchange (ETDEWEB)

    Vasseur, Sophie; Tomasini, Richard; Tournaire, Roselyne; Iovanna, Juan L. [INSERM U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, 163 Avenue de Luminy, BP 915,13288 Marseille cedex 9 (France)

    2010-12-16

    Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis.

  2. Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness

    International Nuclear Information System (INIS)

    Vasseur, Sophie; Tomasini, Richard; Tournaire, Roselyne; Iovanna, Juan L.

    2010-01-01

    Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis

  3. Influence of the Tumor Microenvironment on Cancer Cells Metabolic Reprogramming

    Directory of Open Access Journals (Sweden)

    Victoire Gouirand

    2018-04-01

    Full Text Available As with castles, tumor cells are fortified by surrounding non-malignant cells, such as cancer-associated fibroblasts, immune cells, but also nerve fibers and extracellular matrix. In most cancers, this fortification creates a considerable solid pressure which limits oxygen and nutrient delivery to the tumor cells and causes a hypoxic and nutritional stress. Consequently, tumor cells have to adapt their metabolism to survive and proliferate in this harsh microenvironment. To satisfy their need in energy and biomass, tumor cells develop new capacities to benefit from metabolites of the microenvironment, either by their uptake through the macropinocytosis process or through metabolite transporters, or by a cross-talk with stromal cells and capture of extracellular vesicles that are released by the neighboring cells. However, the microenvironments of primary tumor and metastatic niches differ tremendously in their cellular/acellular components and available nutrients. Therefore, cancer cells must develop a metabolic flexibility conferring on them the ability to satisfy their biomass and energetic demands at both primary and metastasis sites. In this review, we propose a brief overview of how proliferating cancer cells take advantage of their surrounding microenvironment to satisfy their high metabolic demand at both primary and metastasis sites.

  4. Deliberate total parathyroidectomy: a potentially novel therapy for tumor-induced hypophosphatemic osteomalacia.

    Science.gov (United States)

    Bhadada, Sanjay K; Palnitkar, Saroj; Qiu, Shijing; Parikh, Nayana; Talpos, Gary B; Rao, Sudhaker D

    2013-11-01

    Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic metabolic bone disorder that can be cured by removing or ablating the offending tumor. However, when the tumor cannot be localized, lifelong therapy with oral phosphate and calcitriol or cinacalcet with close monitoring is required. A 56-year-old man was diagnosed with TIO in 1990. Initial therapy consisted of oral phosphate and calcitriol with symptomatic and biochemical improvement and healing of osteomalacia. Eight years later, hypercalcemic hyperparathyroidism developed, requiring subtotal parathyroidectomy with a transient increase in serum phosphate and normalization of serum calcium and PTH. Recurrent hypercalcemic hyperparathyroidism developed after 10 years of medical therapy. A deliberate total parathyroidectomy produced a prompt rise in serum phosphate into the normal range > 3.0 mg/dL and remained normal during the next 4 years of follow-up, despite continued very high serum fibroblast growth factor-23 levels throughout the 23-year follow-up. We report an unusual case of a TIO patient with long-term follow-up who developed recurrent hypercalcemic hyperparathyroidism on long-term oral phosphate therapy. Deliberate total parathyroidectomy normalized serum phosphate despite persistently elevated fibroblast growth factor-23 levels. Total parathyroidectomy offers a potentially novel therapy in some patients with TIO in whom medical therapy is not feasible or the tumor is unresectable.

  5. [Punish or cherish: p53, metabolism and tumor suppression].

    Science.gov (United States)

    Albagli, Olivier

    2015-10-01

    The p53 gene is essential for tumor suppression, but how it does so remains unclear. Upon genotoxic or oncogenic stresses, increased p53 activity induces transient cell cycle arrest, senescence or apoptosis, the three cornerstones of the so-called triumvirate. Accordingly, it has long been thought that p53 suppresses tumorigenesis by somehow counteracting cell proliferation or survival. However, several recently described genetically modified mice indicate that p53 can suppress tumorigenesis without triggering these three responses. Rather, as an important mechanism for tumor suppression, these mutant mice point to the ability of p53 to prevent the Warburg effect, that is to dampen glycolysis and foster mitochondrial respiration. Interestingly, these metabolic functions of p53 rely, in part, on its "unstressed" (basal) expression, a feature shared by its mechanistically linked anti-oxydant function. Together, these "conservative" activities of p53 may prevent tumor initiation by promoting and maintaining a normal oxidative metabolism and hence underly the "daily" tumor suppression by p53 in most cells. Conversely, destructive activities elicited by high p53 levels and leading to senescence or apoptosis provide a shield against partially or overtly transformed cells. This last situation, although relatively infrequent throughout life, is usual in experimental settings, which could explain the disproportionally high number of data implicating the triumvirate in tumor suppression by p53. © 2015 médecine/sciences – Inserm.

  6. Ovarian tumor-initiating cells display a flexible metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Angela S. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Roberts, Paul C. [Biomedical Science and Pathobiology, Virginia Tech, Blacksburg, VA (United States); Frisard, Madlyn I. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Hulver, Matthew W., E-mail: hulvermw@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Schmelz, Eva M., E-mail: eschmelz@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States)

    2014-10-15

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L{sub FFLv} (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth.

  7. Ovarian tumor-initiating cells display a flexible metabolism

    International Nuclear Information System (INIS)

    Anderson, Angela S.; Roberts, Paul C.; Frisard, Madlyn I.; Hulver, Matthew W.; Schmelz, Eva M.

    2014-01-01

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L FFLv (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth

  8. Magnetic resonance imaging of tumor oxygenation and metabolic profile

    DEFF Research Database (Denmark)

    Krishna, Murali C.; Matsumoto, Shingo; Saito, Keita

    2013-01-01

    The tumor microenvironment is distinct from normal tissue as a result of abnormal vascular network characterized by hypoxia, low pH, high interstitial fluid pressure and elevated glycolytic activity. This poses a barrier to treatments including radiation therapy and chemotherapy. Imaging methods...... spectroscopic imaging. Imaging pO2 in tumors is now a robust pre-clinical imaging modality with potential for implementation clinically. Pre-clinical studies and an initial clinical study with hyperpolarized metabolic MR have been successful and suggest that the method may be part of image-guided radiotherapy...

  9. Metabolic changes in tumor cells and tumor-associated macrophages: A mutual relationship

    NARCIS (Netherlands)

    Netea-Maier, R.T.; Smit, J.W.A.; Netea, M.G.

    2018-01-01

    In order to adapt to the reduced availability of nutrients and oxygen in the tumor microenvironment and the increased requirements of energy and building blocks necessary for maintaining their high proliferation rate, malignant cells undergo metabolic changes that result in an increased production

  10. Quantifying metabolic heterogeneity in head and neck tumors in real time: 2-DG uptake is highest in hypoxic tumor regions.

    Directory of Open Access Journals (Sweden)

    Erica C Nakajima

    Full Text Available Intratumoral metabolic heterogeneity may increase the likelihood of treatment failure due to the presence of a subset of resistant tumor cells. Using a head and neck squamous cell carcinoma (HNSCC xenograft model and a real-time fluorescence imaging approach, we tested the hypothesis that tumors are metabolically heterogeneous, and that tumor hypoxia alters patterns of glucose uptake within the tumor.Cal33 cells were grown as xenograft tumors (n = 16 in nude mice after identification of this cell line's metabolic response to hypoxia. Tumor uptake of fluorescent markers identifying hypoxia, glucose import, or vascularity was imaged simultaneously using fluorescent molecular tomography. The variability of intratumoral 2-deoxyglucose (IR800-2-DG concentration was used to assess tumor metabolic heterogeneity, which was further investigated using immunohistochemistry for expression of key metabolic enzymes. HNSCC tumors in patients were assessed for intratumoral variability of (18F-fluorodeoxyglucose ((18F-FDG uptake in clinical PET scans.IR800-2-DG uptake in hypoxic regions of Cal33 tumors was 2.04 times higher compared to the whole tumor (p = 0.0001. IR800-2-DG uptake in tumors containing hypoxic regions was more heterogeneous as compared to tumors lacking a hypoxic signal. Immunohistochemistry staining for HIF-1α, carbonic anhydrase 9, and ATP synthase subunit 5β confirmed xenograft metabolic heterogeneity. We detected heterogeneous (18F-FDG uptake within patient HNSCC tumors, and the degree of heterogeneity varied amongst tumors.Hypoxia is associated with increased intratumoral metabolic heterogeneity. (18F-FDG PET scans may be used to stratify patients according to the metabolic heterogeneity within their tumors, which could be an indicator of prognosis.

  11. The altered glucose metabolism in tumor and a tumor acidic microenvironment associated with extracellular matrix metalloproteinase inducer and monocarboxylate transporters

    Science.gov (United States)

    Li, Xiaofeng; Yu, Xiaozhou; Dai, Dong; Song, Xiuyu; Xu, Wengui

    2016-01-01

    Extracellular matrix metalloproteinase inducer, also knowns as cluster of differentiation 147 (CD147) or basigin, is a widely distributed cell surface glycoprotein that is involved in numerous physiological and pathological functions, especially in tumor invasion and metastasis. Monocarboxylate transporters (MCTs) catalyze the proton-linked transport of monocarboxylates such as L-lactate across the plasma membrane to preserve the intracellular pH and maintain cell homeostasis. As a chaperone to some MCT isoforms, CD147 overexpression significantly contributes to the metabolic transformation of tumor. This overexpression is characterized by accelerated aerobic glycolysis and lactate efflux, and it eventually provides the tumor cells with a metabolic advantage and an invasive phenotype in the acidic tumor microenvironment. This review highlights the roles of CD147 and MCTs in tumor cell metabolism and the associated molecular mechanisms. The regulation of CD147 and MCTs may prove to be with a therapeutic potential for tumors through the metabolic modification of the tumor microenvironment. PMID:27009812

  12. Prospective Evaluation of Changes in Tumor Size and Tumor Metabolism in Patients with Advanced Gastric Cancer Undergoing Chemotherapy: Association and Clinical Implication.

    Science.gov (United States)

    Park, Seongyeol; Ha, Seunggyun; Kwon, Hyun Woo; Kim, Woo Hyoung; Kim, Tae-Yong; Oh, Do-Youn; Cheon, Gi Jeong; Bang, Yung-Jue

    2017-06-01

    A change in tumor size is a well-validated and commonly used value for evaluating response to chemotherapy in cancer. Metabolic changes induced by chemotherapy are related to prognosis in several tumor types. However, the clinical implication of metabolic changes in patients with advanced gastric cancer (AGC) undergoing chemotherapy remains unclear. We aimed to evaluate response of tumor size and metabolism in AGC during chemotherapy and to reveal the relationship between them in view of their impact on patient survival. Methods: We prospectively enrolled patients with AGC before the initiation of first-line palliative chemotherapy. Using baseline and follow-up contrast-enhanced CT and 18 F-FDG PET, we assessed the tumor diameter, SUV max , and total lesion glycolysis in each lesion and their changes during chemotherapy at the same time. We included all lesions with the maximal longest diameters over 1 cm on CT, and each lesion was evaluated by matched 18 F-FDG PET. We analyzed the association between changes in tumor metabolism and tumor size and performed outcome analysis on overall survival (OS) and progression-free survival (PFS). Results: Seventy-four patients were enrolled, and the number of all lesions included in this study was 620. Compared with adenocarcinomas, poorly cohesive carcinomas demonstrated lower SUV max irrespective of tumor size ( P chemotherapy had a linear correlation with the changes in tumor size of each lesion, and a 30% tumor size reduction was associated with a 50% SUV max reduction ( P chemotherapy correlated with changes in tumor size in AGC. Considering both changes in metabolism and size could help predict a more accurate prognosis for AGC patients undergoing chemotherapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  13. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism.

    Science.gov (United States)

    Zhao, Hongyun; Yang, Lifeng; Baddour, Joelle; Achreja, Abhinav; Bernard, Vincent; Moss, Tyler; Marini, Juan C; Tudawe, Thavisha; Seviour, Elena G; San Lucas, F Anthony; Alvarez, Hector; Gupta, Sonal; Maiti, Sourindra N; Cooper, Laurence; Peehl, Donna; Ram, Prahlad T; Maitra, Anirban; Nagrath, Deepak

    2016-02-27

    Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate that exosomes secreted by patient-derived CAFs can strikingly reprogram the metabolic machinery following their uptake by cancer cells. We find that CAF-derived exosomes (CDEs) inhibit mitochondrial oxidative phosphorylation, thereby increasing glycolysis and glutamine-dependent reductive carboxylation in cancer cells. Through 13C-labeled isotope labeling experiments we elucidate that exosomes supply amino acids to nutrient-deprived cancer cells in a mechanism similar to macropinocytosis, albeit without the previously described dependence on oncogenic-Kras signaling. Using intra-exosomal metabolomics, we provide compelling evidence that CDEs contain intact metabolites, including amino acids, lipids, and TCA-cycle intermediates that are avidly utilized by cancer cells for central carbon metabolism and promoting tumor growth under nutrient deprivation or nutrient stressed conditions.

  14. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism

    Science.gov (United States)

    Zhao, Hongyun; Yang, Lifeng; Baddour, Joelle; Achreja, Abhinav; Bernard, Vincent; Moss, Tyler; Marini, Juan C; Tudawe, Thavisha; Seviour, Elena G; San Lucas, F Anthony; Alvarez, Hector; Gupta, Sonal; Maiti, Sourindra N; Cooper, Laurence; Peehl, Donna; Ram, Prahlad T; Maitra, Anirban; Nagrath, Deepak

    2016-01-01

    Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate that exosomes secreted by patient-derived CAFs can strikingly reprogram the metabolic machinery following their uptake by cancer cells. We find that CAF-derived exosomes (CDEs) inhibit mitochondrial oxidative phosphorylation, thereby increasing glycolysis and glutamine-dependent reductive carboxylation in cancer cells. Through 13C-labeled isotope labeling experiments we elucidate that exosomes supply amino acids to nutrient-deprived cancer cells in a mechanism similar to macropinocytosis, albeit without the previously described dependence on oncogenic-Kras signaling. Using intra-exosomal metabolomics, we provide compelling evidence that CDEs contain intact metabolites, including amino acids, lipids, and TCA-cycle intermediates that are avidly utilized by cancer cells for central carbon metabolism and promoting tumor growth under nutrient deprivation or nutrient stressed conditions. DOI: http://dx.doi.org/10.7554/eLife.10250.001 PMID:26920219

  15. Metabolic imaging of tumor for diagnosis and response for therapy

    Science.gov (United States)

    Zagaynova, Elena; Shirmanova, Marina; Lukina, Maria; Dudenkova, Varvara; Ignatova, Nadezgda; Elagin, Vadim; Shlivko, Irena; Scheslavsky, Vladislav; Orlinskay, Natalia

    2018-02-01

    Nonlinear optical microscopy combined with fluorescence lifetime imaging is a non-invasive imaging technique, based on the study of fluorescence decay times of naturally occurring fluorescent molecules, enabling a noninvasive investigation of the biological tissue with subcellular resolution. Cancer exhibits altered cellular metabolism, which affects the autofluorescence of metabolic cofactors NAD(P)H and FAD. In this study features of tumor metabolism in different systems of organization (from cell culture to patient lesion) was showed. The observed differences in the relative contributions of free NAD(P)H and FAD testify to an increased a glycolytic metabolism in cancer cells compare to fibroblasts. In 3D spheroids, the cells of the proliferating zone had greater a1 and lower tm values than the cells of the quiescent zone, which likely is a consequence of their higher glycolytic rate. During the growth of colorectal cancer in the experimental mouse model, the contribution of the free component of NAD(P)H was increased. Dysplastic nevus and melanoma is characterized by raised contribution of free NADH compare to healthy skin. Therefore, melanoma cells had very short value of τ1.

  16. Tumor metabolism, the ketogenic diet and β-hydroxybutyrate: novel approaches to adjuvant brain tumor therapy

    Directory of Open Access Journals (Sweden)

    Eric C. Woolf

    2016-11-01

    Full Text Available Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD. The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma.

  17. Pyrrolizidine Alkaloids: Metabolic Activation Pathways Leading to Liver Tumor Initiation.

    Science.gov (United States)

    Fu, Peter P

    2017-01-17

    Pyrrolizidine alkaloids (PAs) and PA N-oxides are a class of phytochemical carcinogens contained in over 6000 plant species spread around the world. It has been estimated that approximately half of the 660 PAs and PA N-oxides that have been characterized are cytotoxic, genotoxic, and tumorigenic. It was recently determined that a genotoxic mechanism of liver tumor initiation mediated by PA-derived DNA adducts is a common metabolic activation pathway of a number of PAs. We proposed this set of PA-derived DNA adducts could be a common biological biomarker of PA exposure and a potential biomarker of PA-induced liver tumor formation. We have also found that several reactive secondary pyrrolic metabolites can dissociate and interconvert to other secondary pyrrolic metabolites, resulting in the formation of the same exogenous DNA adducts. This present perspective reports the current progress on these new findings and proposes future research needed for obtaining a greater understanding of the role of this activation pathway and validating the use of this set of PA-derived DNA adducts as a biological biomarker of PA-induced liver tumor initiation.

  18. Response of melanoma tumor phospholipid metabolism to chloroethyle nitrosourea: a high resolution proton NMR spectroscopy study.

    Science.gov (United States)

    Morvan, Daniel; Demidem, Aïcha; Madelmont, Jean-Claude

    2003-07-01

    Phospholipid metabolism is tightly involved in tumor growth regulation and tumor cell survival. The response of phospholipid metabolism to chloroethyle nitrosourea treatment is investigated in a murine B16 melanoma model. Measurements of phospholipid derivatives are performed on intact tumor tissue samples using one- and two-dimensional proton NMR spectroscopy. During the tumor growth inhibition phase under treatment, tumors overexpress phosphocholine, phosphoethanolamine, glycerophosphocholine and glycerophosphoethanolamine, whereas phosphatidylcholine and phosphatidylethanolamine levels are maintained to control levels. During re-growth, which remained quantitatively much below control growth, chloroethyle nitrosourea-treated melanoma tumors overexpress phosphocholine and phosphoethanolamine only. In treated melanoma, phosphatidylcholine levels show an inverse relationship with tumor growth rates. In conclusion, chloroethyle nitrosourea-treated melanoma tumors maintain their phosphatidylcholine levels and exhibit transformed phospholipid metabolism phenotype, by mechanisms that could participate in tumor cell survival.

  19. Predictive value of PET response combined with baseline metabolic tumor volume in peripheral T-cell lymphoma patients

    DEFF Research Database (Denmark)

    Cottereau, Anne-Segolene; El-Galaly, Tarec C; Becker, Stéphanie

    2018-01-01

    Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive non-Hodgkin lymphomas with poor outcomes with current therapy. We investigated if response assessed with Positron Emission Tomography/computed tomography (PET/CT) combined with baseline total metabolic tumor volume (TMTV) co...

  20. Tumor de la vulva, vulvectomía radical Vulvar tumor, total vulvectomy

    Directory of Open Access Journals (Sweden)

    Asbel Alfredo Vicente de la Cruz

    2011-09-01

    Full Text Available Los tumores de la vulva no son una rareza entre los cánceres que afectan a las féminas, pero tampoco son de los más frecuentes. Se presenta el caso de una mujer de 59 años, que en el año 2000 se le diagnostica carcinoma epidermoide del clítoris, en 2004 se vuelve a intervenir por recidiva tumoral, y en 2009 acude a nuestra consulta nuevamente y es cuando se decide realizarle vulvectomía y resección de vagina y todo el sistema ginecológico. Concluyó la intervención con una talla vesical extraperitoneal. El tumor se extiende hasta la porción inicial de la vagina y uretra. Se trata de un tumor maligno, bien diferenciado, que se ha comportado en una forma no habitual, con recidivas locales, cuando en apariencia el tumor había sido resecado en toda su extensión, y en esta última oportunidad, a pesar de ser un estadio avanzado, no hemos encontrado metástasis ni multicentricidad del tumor. La evolución posoperatoria fue sin complicaciones y se dio de alta al quinto día.The vulvar tumors are not uncommon among the different types of cancer involving females, but neither are the more frequent ones. This is the case of a female aged 59 that in 2000 is diagnosed with epidermoid carcinoma of clitoris, in 2004 is re-operated on by tumor relapse, and in 2009 she came again to our consultation and a vulvectomy, vagina resection and all gynecological system are carried out. Intervention concluded with an extraperitoneal vesical cutting. The tumor extends up to the initial portion of vagina and urethra. It is a malignant and well-differentiated tumor behaved in non habitual way with local relapses, when apparently the tumor was resected in all its extent, and in this last change, despite and advanced stage, there were neither tumor metastases nor multi-centralization. The postoperative course was free of complications receiving the discharge at fifth day.

  1. Studies on Ferrokinetics and Copper Metabolism in Various Malignant Tumors

    International Nuclear Information System (INIS)

    Kim, Yong Kyu

    1967-01-01

    Anemia is a usual finding in advanced malignant diseases. Various mechanisms were reported as to be involved in the development of anemia of this kind, and they may differ in individual cases. Tumor anemias may be due, for instance, to chronic blood loss, shortened life span of the red blood cells or a decreased hemopoiesis in the bone marrow. The serum iron and copper levels, total iron binding capacity, apparent half survival of 51 Cr-labelled red blood cells were measurement with the ferrokinetic studies using 59 Fe in 64 patients with various malignant tumors. Following were the results: 1) The serum iron levels were decreased in all cases. There existed no correlation between the serum iron levels and the severity of the diseases. 2) The serum copper levels were increased, particularly in lung cancer, rectal cancer, hepatoma and various sarcomas. There was also no correlation between the serum copper levels and the severity of the diseases. 3) The serum iron levels appeared to be inversely proportional to the serum copper levels. 4) The total iron binding capacities were within normal limits in all cases. There were also no correlations between the total iron binding capacities, serum iron levels and the severity of the diseases. 5) The patients could be classified according the ferrokinetic patterns, namely, that of iron deficiency anemia in 10 cases, that of refractory anemia in 6 cases, normal in 1 case and that of atypical abnormal in 9 cases. 6) Apparent half survival time of 51 Cr-labelled red blood cells were definitely shortened in half of the cases.

  2. Correlation between metabolic tumor volume and pathologic tumor volume in squamous cell carcinoma of the oral cavity

    International Nuclear Information System (INIS)

    Murphy, James D.; Chisholm, Karen M.; Daly, Megan E.; Wiegner, Ellen A.; Truong, Daniel; Iagaru, Andrei; Maxim, Peter G.; Loo, Billy W.; Graves, Edward E.; Kaplan, Michael J.; Kong, Christina; Le, Quynh-Thu

    2011-01-01

    Purpose: To explore the relationship between pathologic tumor volume and volume estimated from different tumor segmentation techniques on 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in oral cavity cancer. Materials and methods: Twenty-three patients with squamous cell carcinoma of the oral tongue had PET–CT scans before definitive surgery. Pathologic tumor volume was estimated from surgical specimens. Metabolic tumor volume (MTV) was defined from PET–CT scans as the volume of tumor above a given SUV threshold. Multiple SUV thresholds were explored including absolute SUV thresholds, relative SUV thresholds, and gradient-based techniques. Results: Multiple MTV’s were associated with pathologic tumor volume; however the correlation was poor (R 2 range 0.29–0.58). The ideal SUV threshold, defined as the SUV that generates an MTV equal to pathologic tumor volume, was independently associated with maximum SUV (p = 0.0005) and tumor grade (p = 0.024). MTV defined as a function of maximum SUV and tumor grade improved the prediction of pathologic tumor volume (R 2 = 0.63). Conclusions: Common SUV thresholds fail to predict pathologic tumor volume in head and neck cancer. The optimal technique that allows for integration of PET–CT with radiation treatment planning remains to be defined. Future investigation should incorporate biomarkers such as tumor grade into definitions of MTV.

  3. TRAP1 Regulation of Cancer Metabolism: Dual Role as Oncogene or Tumor Suppressor

    Directory of Open Access Journals (Sweden)

    Danilo Swann Matassa

    2018-04-01

    Full Text Available Metabolic reprogramming is an important issue in tumor biology. An unexpected inter- and intra-tumor metabolic heterogeneity has been strictly correlated to tumor outcome. Tumor Necrosis Factor Receptor-Associated Protein 1 (TRAP1 is a molecular chaperone involved in the regulation of energetic metabolism in cancer cells. This protein is highly expressed in several cancers, such as glioblastoma, colon, breast, prostate and lung cancers and is often associated with drug resistance. However, TRAP1 is also downregulated in specific tumors, such as ovarian, bladder and renal cancers, where its lower expression is correlated with the worst prognoses and chemoresistance. TRAP1 is the only mitochondrial member of the Heat Shock Protein 90 (HSP90 family that directly interacts with respiratory complexes, contributing to their stability and activity but it is still unclear if such interactions lead to reduced or increased respiratory capacity. The role of TRAP1 is to enhance or suppress oxidative phosphorylation; the effects of such regulation on tumor development and progression are controversial. These observations encourage the study of the mechanisms responsible for the dualist role of TRAP1 as an oncogene or oncosuppressor in specific tumor types. In this review, TRAP1 puzzling functions were recapitulated with a special focus on the correlation between metabolic reprogramming and tumor outcome. We wanted to investigate whether metabolism-targeting drugs can efficiently interfere with tumor progression and whether they might be combined with chemotherapeutics or molecular-targeted agents to counteract drug resistance and reduce therapeutic failure.

  4. Anti-tumor effect of total body irradiation of low doses on WHT/Ht mice

    International Nuclear Information System (INIS)

    Miyamoto, Miyako; Sakamoto, Kiyohiko

    1987-01-01

    The effect of low dose (0.05 - 1.0 Gy) of total body irradiation (TBI) on non-tumor bearing and tumor bearing mice were investigated. Mice received TBI of 0.1 Gy during 6 - 12 hours before tumor cell inoculation demonstrated to need larger number of tumor cells (approximately 2.5 times) for 50 per cent tumor incidence, compared to recipient mice not to receive TBI. On the other hand, in tumor bearing mice given 0.1 Gy of TBI only tumor cell killing effect was not detected, however enhancement of tumor cell killing effect and prolonged growth delay were observed when tumor bearing mice were treated with 0.1 Gy of TBI in combined with local irradiation on tumors, especially cell killing effect was remarkable in dose range over 6 Gy of local exposure. The mechanism of the effect of 0.1 Gy TBI is considered to be host mediated reactions from the other our experimental results. (author)

  5. Contributions of Cell Metabolism and H+ Diffusion to the Acidic pH of Tumors

    Directory of Open Access Journals (Sweden)

    Paul A. Schornack

    2003-03-01

    Full Text Available The tumor microenvironment is hypoxic and acidic. These conditions have a significant impact on tumor progression and response to therapies. There is strong evidence that tumor hypoxia results from inefficient perfusion due to a chaotic vasculature. Consequently, some tumor regions are well oxygenated and others are hypoxic. It is commonly believed that hypoxic regions are acidic due to a stimulation of glycolysis through hypoxia, yet this is not yet demonstrated. The current study investigates the causes of tumor acidity by determining acid production rates and the mechanism of diffusion for H+ equivalents through model systems. Two breast cancer cell lines were investigated with divergent metabolic profiles: nonmetastatic MCF-7/s and highly metastatic MDA-mb-435 cells. Glycolysis and acid production are inhibited by oxygen in MCF-7/s cells, but not in MDA-mb-435 cells. Tumors of MDAmb-435 cells are significantly more acidic than are tumors of MCF-7/s cells, suggesting that tumor acidity is primarily caused by endogenous metabolism, not the lack of oxygen. Metabolically produced protons are shown to diffuse in association with mobile buffers, in concordance with previous studies. The metabolic and diffusion data were analyzed using a reaction-diffusion model to demonstrate that the consequent pH profiles conform well to measured pH values for tumors of these two cell lines.

  6. Quantitative HRMAS proton total correlation spectroscopy applied to cultured melanoma cells treated by chloroethyl nitrosourea: demonstration of phospholipid metabolism alterations.

    Science.gov (United States)

    Morvan, Daniel; Demidem, Aicha; Papon, Janine; Madelmont, Jean Claude

    2003-02-01

    Recent NMR spectroscopy developments, such as high-resolution magic angle spinning (HRMAS) probes and correlation-enhanced 2D sequences, now allow improved investigations of phospholipid (Plp) metabolism. Using these modalities we previously demonstrated that a mouse-bearing melanoma tumor responded to chloroethyl nitrosourea (CENU) treatment in vivo by altering its Plp metabolism. The aims of the present study were to investigate whether HRMAS proton total correlation spectroscopy (TOCSY) could be used as a quantitative technique to probe Plp metabolism, and to determine the Plp metabolism response of cultured B16 melanoma cells to CENU treatment in vitro. The exploited TOCSY signals of Plp derivatives arose from scalar coupling among the protons of neighbor methylene groups within base headgroups (choline and ethanolamine). For strongly expressed Plp derivatives, TOCSY signals were compared to saturation recovery signals and demonstrated a linear relationship. HRMAS proton TOCSY was thus used to provide concentrations of Plp derivatives during long-term follow-up of CENU-treated cell cultures. Strong Plp metabolism alteration was observed in treated cultured cells in vitro involving a down-regulation of phosphocholine, and a dramatic and irreversible increase of phosphoethanolamine. These findings are discussed in relation to previous in vivo data, and to Plp metabolism enzymatic involvement. Copyright 2003 Wiley-Liss, Inc.

  7. In vitro antioxidant, antibacterial and anti-tumor activities of total ...

    African Journals Online (AJOL)

    Purpose: To investigate the in vitro antioxidant, antibacterial and anti-tumor activities of total flavonoids from Elsholtzia densa Benth of Sichuan Province, China. Methods: The total flavonoids of Elsholtzia densa Bent were extracted utilizing the ultrasonic extraction method, and purified by D101 macroporous adsorption resin ...

  8. Tumor microenvironment and metabolic synergy in breast cancers: critical importance of mitochondrial fuels and function.

    Science.gov (United States)

    Martinez-Outschoorn, Ubaldo; Sotgia, Federica; Lisanti, Michael P

    2014-04-01

    Metabolic synergy or metabolic coupling between glycolytic stromal cells (Warburg effect) and oxidative cancer cells occurs in human breast cancers and promotes tumor growth. The Warburg effect or aerobic glycolysis is the catabolism of glucose to lactate to obtain adenosine triphosphate (ATP). This review summarizes the main findings on this stromal metabolic phenotype, and the associated signaling pathways, as well as the critical role of oxidative stress and autophagy, all of which promote carcinoma cell mitochondrial metabolism and tumor growth. Loss of Caveolin 1 (Cav-1) and the upregulation of monocarboxylate transporter 4 (MCT4) in stromal cells are novel markers of the Warburg effect and metabolic synergy between stromal and carcinoma cells. MCT4 and Cav-1 are also breast cancer prognostic biomarkers. Reactive oxygen species (ROS) are key mediators of the stromal Warburg effect. High ROS also favors cancer cell mitochondrial metabolism and tumorigenesis, and anti-oxidants can reverse this altered stromal and carcinoma metabolism. A pseudo-hypoxic state with glycolysis and low mitochondrial metabolism in the absence of hypoxia is a common feature in breast cancer. High ROS induces loss of Cav-1 in stromal cells and is sufficient to generate a pseudo-hypoxic state. Loss of Cav-1 in the stroma drives glycolysis and lactate extrusion via HIF-1α stabilization and the upregulation of MCT4. Stromal cells with loss of Cav-1 and/or high expression of MCT4 also show a catabolic phenotype, with enhanced macroautophagy. This catabolic state in stromal cells is driven by hypoxia-inducible factor (HIF)-1α, nuclear factor κB (NFκB), and JNK activation and high ROS generation. A feed-forward loop in stromal cells regulates pseudo-hypoxia and metabolic synergy, with Cav-1, MCT4, HIF-1α, NFκB, and ROS as its key elements. Metabolic synergy also may occur between cancer cells and cells in distant organs from the tumor. Cancer cachexia, which is due to severe organismal

  9. 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

  10. Cancer Metabolism and Tumor Heterogeneity: Imaging Perspectives Using MR Imaging and Spectroscopy

    OpenAIRE

    Lin, Gigin; Keshari, Kayvan R.; Park, Jae Mo

    2017-01-01

    Cancer cells reprogram their metabolism to maintain viability via genetic mutations and epigenetic alterations, expressing overall dynamic heterogeneity. The complex relaxation mechanisms of nuclear spins provide unique and convertible tissue contrasts, making magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) pertinent imaging tools in both clinics and research. In this review, we summarized MR methods that visualize tumor characteristics and its metabolic phenotypes ...

  11. Advanced Imaging Approaches to Characterize Stromal and Metabolic Changes in In Vivo Mammary Tumor Models

    Science.gov (United States)

    2015-02-01

    Bird , L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, N. Ramanujam, Metabolic mapping of MCF10A human breast cells...1   Award Number: W81XWH-12-1-0025 TITLE: Advanced Imaging Approaches to Characterize Stromal and Metabolic Changes in In Vivo Mammary... Metabolic Changes in In Vivo Mammary Tumor Models 5b. GRANT NUMBER BC112240 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Betty Diamond 5d. PROJECT NUMBER

  12. Total mixed ration in exercising horse: digestibility and nitrogen metabolism

    Directory of Open Access Journals (Sweden)

    L. Magni

    2010-04-01

    Full Text Available The aim of this study was to evaluate the apparent digestibility of a total mixed ration (TMR versus a traditional mixed hay/cereals diet. Four adult trained Standardbred geldings – BW = 478±37 kg - were used. The two diets consisted of 20 kg of a commercial TMR - corn silage, alfalfa hay, wet brewers’ grain, oat, apple pomace, molasses cane, soybean oil and mineral/vitamin supplement - (Diet 1 or 7 kg of meadow hay and 4.5 kg of cereal-mix - corn, oat, barley and protein/mineral/vitamin supplement - (Diet 2. The trial was conducted according to a Latin Square design (2x2. After an adaptation period of four weeks, total faeces and urine were collected for 6 days. Both feed and faeces samples were analysed for DM, OM, CP, EE, CF, NDF, ADF, cellulose, hemicellulose, ADL and GE. Data were analysed by ANOVA. The apparent digestibility and nitrogen balance of the two diets were compared. DM, OM, CP and GE apparent digestibility were significantly different between the diets, with higher values for unifeed diet than traditional diet. Energy requirement was satisfied by both diets (96.54 vs 95.55 MJ. Nitrogen balance showed negative values in both diets (- 61.67 vs - 9.05, but the hay/cereals supplemented diet showed the best protein utilisation.

  13. Patients with old age or proximal tumors benefit from metabolic syndrome in early stage gastric cancer.

    Directory of Open Access Journals (Sweden)

    Xiao-li Wei

    Full Text Available BACKGROUND: Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated. METHODS: Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed. RESULTS: Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P=0.036. Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P=0.009 in multivariate analysis or patients with proximal gastric cancer (P=0.047 in multivariate analysis. No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P=0.052 in univariate analysis. CONCLUSIONS: Metabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors.

  14. Regulatory T cells as suppressors of anti-tumor immunity: Role of metabolism.

    Science.gov (United States)

    De Rosa, Veronica; Di Rella, Francesca; Di Giacomo, Antonio; Matarese, Giuseppe

    2017-06-01

    Novel concepts in immunometabolism support the hypothesis that glucose consumption is also used to modulate anti-tumor immune responses, favoring growth and expansion of specific cellular subsets defined in the past as suppressor T cells and currently reborn as regulatory T (Treg) cells. During the 1920s, Otto Warburg and colleagues observed that tumors consumed high amounts of glucose compared to normal tissues, even in the presence of oxygen and completely functioning mitochondria. However, the role of the Warburg Effect is still not completely understood, particularly in the context of an ongoing anti-tumor immune response. Current experimental evidence suggests that tumor-derived metabolic restrictions can drive T cell hyporesponsiveness and immune tolerance. For example, several glycolytic enzymes, deregulated in cancer, contribute to tumor progression independently from their canonical metabolic activity. Indeed, they can control apoptosis, gene expression and activation of specific intracellular pathways, thus suggesting a direct link between metabolic switches and pro-tumorigenic transcriptional programs. Focus of this review is to define the specific metabolic pathways controlling Treg cell immunobiology in the context of anti-tumor immunity and tumor progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. 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.

  16. Enhanced responses to tumor immunization following total body irradiation are time-dependent.

    Directory of Open Access Journals (Sweden)

    Adi Diab

    Full Text Available The development of successful cancer vaccines is contingent on the ability to induce effective and persistent anti-tumor immunity against self-antigens that do not typically elicit immune responses. In this study, we examine the effects of a non-myeloablative dose of total body irradiation on the ability of tumor-naïve mice to respond to DNA vaccines against melanoma. We demonstrate that irradiation followed by lymphocyte infusion results in a dramatic increase in responsiveness to tumor vaccination, with augmentation of T cell responses to tumor antigens and tumor eradication. In irradiated mice, infused CD8(+ T cells expand in an environment that is relatively depleted in regulatory T cells, and this correlates with improved CD8(+ T cell functionality. We also observe an increase in the frequency of dendritic cells displaying an activated phenotype within lymphoid organs in the first 24 hours after irradiation. Intriguingly, both the relative decrease in regulatory T cells and increase in activated dendritic cells correspond with a brief window of augmented responsiveness to immunization. After this 24 hour window, the numbers of dendritic cells decline, as does the ability of mice to respond to immunizations. When immunizations are initiated within the period of augmented dendritic cell activation, mice develop anti-tumor responses that show increased durability as well as magnitude, and this approach leads to improved survival in experiments with mice bearing established tumors as well as in a spontaneous melanoma model. We conclude that irradiation can produce potent immune adjuvant effects independent of its ability to induce tumor ablation, and that the timing of immunization and lymphocyte infusion in the irradiated host are crucial for generating optimal anti-tumor immunity. Clinical strategies using these approaches must therefore optimize such parameters, as the correct timing of infusion and vaccination may mean the difference

  17. Characterization of Metabolic, Diffusion, and Perfusion Properties in GBM: Contrast-Enhancing versus Non-Enhancing Tumor.

    Science.gov (United States)

    Autry, Adam; Phillips, Joanna J; Maleschlijski, Stojan; Roy, Ritu; Molinaro, Annette M; Chang, Susan M; Cha, Soonmee; Lupo, Janine M; Nelson, Sarah J

    2017-12-01

    Although the contrast-enhancing (CE) lesion on T 1 -weighted MR images is widely used as a surrogate for glioblastoma (GBM), there are also non-enhancing regions of infiltrative tumor within the T 2 -weighted lesion, which elude radiologic detection. Because non-enhancing GBM (Enh-) challenges clinical patient management as latent disease, this study sought to characterize ex vivo metabolic profiles from Enh- and CE GBM (Enh+) samples, alongside histological and in vivo MR parameters, to assist in defining criteria for estimating total tumor burden. Fifty-six patients with newly diagnosed GBM received a multi-parametric pre-surgical MR examination. Targets for obtaining image-guided tissue samples were defined based on in vivo parameters that were suspicious for tumor. The actual location from where tissue samples were obtained was recorded, and half of each sample was analyzed for histopathology while the other half was scanned using HR-MAS spectroscopy. The Enh+ and Enh- tumor samples demonstrated comparable mitotic activity, but also significant heterogeneity in microvascular morphology. Ex vivo spectroscopic parameters indicated similar levels of total choline and N-acetylaspartate between these contrast-based radiographic subtypes of GBM, and characteristic differences in the levels of myo-inositol, creatine/phosphocreatine, and phosphoethanolamine. Analysis of in vivo parameters at the sample locations were consistent with histological and ex vivo metabolic data. The similarity between ex vivo levels of choline and NAA, and between in vivo levels of choline, NAA and nADC in Enh+ and Enh- tumor, indicate that these parameters can be used in defining non-invasive metrics of total tumor burden for patients with GBM. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Characterization of Metabolic, Diffusion, and Perfusion Properties in GBM: Contrast-Enhancing versus Non-Enhancing Tumor

    Directory of Open Access Journals (Sweden)

    Adam Autry

    2017-12-01

    Full Text Available BACKGROUND: Although the contrast-enhancing (CE lesion on T1-weighted MR images is widely used as a surrogate for glioblastoma (GBM, there are also non-enhancing regions of infiltrative tumor within the T2-weighted lesion, which elude radiologic detection. Because non-enhancing GBM (Enh− challenges clinical patient management as latent disease, this study sought to characterize ex vivo metabolic profiles from Enh− and CE GBM (Enh+ samples, alongside histological and in vivo MR parameters, to assist in defining criteria for estimating total tumor burden. Methods: Fifty-six patients with newly diagnosed GBM received a multi-parametric pre-surgical MR examination. Targets for obtaining image-guided tissue samples were defined based on in vivo parameters that were suspicious for tumor. The actual location from where tissue samples were obtained was recorded, and half of each sample was analyzed for histopathology while the other half was scanned using HR-MAS spectroscopy. Results: The Enh+ and Enh− tumor samples demonstrated comparable mitotic activity, but also significant heterogeneity in microvascular morphology. Ex vivo spectroscopic parameters indicated similar levels of total choline and N-acetylaspartate between these contrast-based radiographic subtypes of GBM, and characteristic differences in the levels of myo-inositol, creatine/phosphocreatine, and phosphoethanolamine. Analysis of in vivo parameters at the sample locations were consistent with histological and ex vivo metabolic data. CONCLUSIONS: The similarity between ex vivo levels of choline and NAA, and between in vivo levels of choline, NAA and nADC in Enh+ and Enh− tumor, indicate that these parameters can be used in defining non-invasive metrics of total tumor burden for patients with GBM.

  19. The effect of low-dose total body irradiation on tumor control

    International Nuclear Information System (INIS)

    Sakamoto, Kiyohiko; Miyamoto, Miyako; Watabe, Nobuyuki.

    1987-01-01

    Total body irradiation (TBI) is considered to bring about an immunosuppressive effect on an organism, on the basis of data obtained from sublethal doses of TBI. However, there are no data on how low-dose TBI affects an organism. Over the last five years, we have been studying the effects of low-dose TBI on normal or tumor-bearing mice and the immunological background of these effects. In experimental studies, an increase in the TD50 value (the number of cells required for a tumor incidence of 50 %) in mice exposed to 10 rad was recognized and showed a remarkable increase at 6 hours to 15 hours after irradiation. TBI of 10 rad also showed an enhancement effect on tumor cell killing when given 12 hours before local tumor irradiation. In order to clarify the mechanism of this kind of effect, some immunological studies were performed using several immunological procedures, and the results suggested that 10 rad of TBI caused increasing tumor immunity in irradiated mice. Clinical trials in some patients with advanced tumors are now being undertaken on the basis of these experimental data, and the effect of TBI on tumor control appears promising, although it is too early to draw conclusions. (author)

  20. Prognostic value of baseline metabolic tumor volume in early stage Hodgkin's lymphoma in the standard arm of H10 trial

    DEFF Research Database (Denmark)

    Cottereau, Anne Ségolène; Versari, Annibale; Loft, Annika

    2018-01-01

    and compared to baseline characteristics, staging classifications and iPET2. A total of 258 patients were eligible, 101 favorable and 157 unfavorable. The median follow-up was 55 months, with 27 PFS and 12 OS events. TMTV was prognosticator of PFS (p...We tested baseline PET/CT as a measure of total tumor burden in order to better identify high risk patients in early-stage Hodgkin's lymphoma (HL). Stage I-II HL patients enrolled in the standard arm (combined modality treatment) of the H10 trial (NCT00433433) with available baseline PET...... and interim PET (iPET2) after two cycles of doxorubicine, bleomycin, vinblastine, dacarbazine were included. Total metabolic tumor volume (TMTV) was measured on baseline PET. IPET2 findings were reported negative (DS1-3) or positive (DS4-5) with the Deauville scale. The prognostic value of TMTV was evaluated...

  1. Tumor regression with a combination of drugs interfering with the tumor metabolism: efficacy of hydroxycitrate, lipoic acid and capsaicin.

    Science.gov (United States)

    Schwartz, Laurent; Guais, Adeline; Israël, Maurice; Junod, Bernard; Steyaert, Jean-Marc; Crespi, Elisabetta; Baronzio, Gianfranco; Abolhassani, Mohammad

    2013-04-01

    Cellular metabolic alterations are now well described as implicated in cancer and some strategies are currently developed to target these different pathways. In previous papers, we demonstrated that a combination of molecules (namely alpha-lipoic acid and hydroxycitrate, i.e. Metabloc™) targeting the cancer metabolism markedly decreased tumor cell growth in mice. In this work, we demonstrate that the addition of capsaicin further delays tumor growth in mice in a dose dependant manner. This is true for the three animal model tested: lung (LLC) cancer, bladder cancer (MBT-2) and melanoma B16F10. There was no apparent side effect of this ternary combination. The addition of a fourth drug (octreotide) is even more effective resulting in tumor regression in mice bearing LLC cancer. These four compounds are all known to target the cellular metabolism not its DNA. The efficacy, the apparent lack of toxicity, the long clinical track records of these medications in human medicine, all points toward the need for a clinical trial. The dramatic efficacy of treatment suggests that cancer may simply be a disease of dysregulated cellular metabolism.

  2. Total body fat as a possible indicator of metabolic syndrome in adults

    Directory of Open Access Journals (Sweden)

    Edgar Navarro Lechuga

    2016-09-01

    Full Text Available Introduction: The metabolic syndrome is a set of factors related to insulin resistance, which increases the likelihood of coronary events. It is important timely onset identifying to reduce its prevalence. Objective: To explore the percentage of total body fat as indicator of metabolic syndrome in adults from Soledad, Colombia. Material and Methods: Cross-sectional study. n=99 adults (non-pregnant, nor subjects with psychomotor disturbances. Blood samples were taken: total cholesterol, HDL; triglycerides and glucose. Waist circumference, Body Mass Index and body fat by bioimpedance and skinfold thickness were measured. Diagnosis of metabolic syndrome was made according to NHLBI/AHA, ATP III and IDF criteria. Subjects with and without metabolic syndrome according to total body fat averages were compared. Results: The average percentage of body fat was higher (p0.05 in the classification according to ATP III in women, where the average fat percentage was 39.31 % in those with metabolic syndrome and 37.7% in those not suffering. Conclusions: Subjects with metabolic syndrome have higher mean total body fat, significantly, compared with those who did not, so it could be considered the values of total body fat obtained by bioimpedance as future indicators of metabolic syndrome, both as screening and control.

  3. Effects of total solar eclipse on the behavioural and metabolic activities of tropical intertidal animals

    Digital Repository Service at National Institute of Oceanography (India)

    Parulekar, A.H.; Ansari, Z.A.; Verlecar, X.N.; Harkantra, S.N.

    To study the effects of total solar eclipse of 16th Feb. 1980, on the behaviour and metabolic activities of intertidal invertebrates - nematodes, gastropods and bivalves - having different habitat preference a set of relevant observations, covering...

  4. Metabolic tumor burden as marker of outcome in advanced EGFR wild-type NSCLC patients treated with erlotinib

    DEFF Research Database (Denmark)

    Winther-Larsen, Anne; Fledelius, Joan; Sorensen, Boe Sandahl

    2016-01-01

    OBJECTIVES: Accurate estimation of the prognosis of advanced non-small cell lung cancer (NSCLC) patients is essential before initiation of palliative treatment; especially in the second and third-line setting. This study was conducted in order to evaluate tumor burden measured on an 2'-deoxy-2...... a prospectively collected cohort. An F-18-FDG-PET/CT scan was conducted prior to erlotinib treatment and tumor burden was measured in terms of metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Median values of MTV and TLG were used for dichotomization of patients. Survival outcome was compared...... between groups.RESULTS: MTV and TLG could be measured in 49 patients. High values of MTV and TLG were significantly correlated with shorter PFS (p

  5. Anti-tumor potential of total alkaloid extract of Prosopis juliflora DC ...

    African Journals Online (AJOL)

    The total alkaloid extract from Prosopis juliflora DC. leaves was obtained using acid/base modified extraction method. The in vitro anti-tumor potential of the extract was evaluated using MTT (3-(4,5- dimethythiazol-2yl)2,5-diphenyl tetrazolium bromide) based cytotoxicity monitoring after 24, 48 and 72 h exposure of the ...

  6. Steroid metabolism and steroid receptors in dimethylbenz(a)anthracene-induced rat mammary tumors

    International Nuclear Information System (INIS)

    Eechaute, W.; de Thibault de Boesinghe, L.; Lacroix, E.

    1983-01-01

    Mammary tumors were induced in rats by treatment with dimethylbenz(a)anthracene. Cytosol receptors for 17 beta-estradiol and progesterone were estimated by means of sucrose density gradient centrifugation, and the metabolism of [ 14 C]progesterone, [ 14 C]testosterone, and 17 beta-[ 14 C]estradiol by minced tumor tissue was studied. The estradiol receptor (ER) and progesterone receptor (PR) levels of the tumors varied considerably from less than 5 to 48 fmol/mg protein for ER and to 243 fmol/mg protein for PR. Considering a receptor level lower than 5 fmol/mg protein to be negative, four groups of tumors were found: ER-negative and PR-negative; ER-positive and PR-negative; ER-negative and PR-positive; ER-positive and PR-positive. In dimethylbenz(a)anthracene-induced tumor tissue, high 5 alpha-reductase and 20 alpha-hydroxysteroid dehydrogenase activities and somewhat lower 3 alpha-hydroxysteroid dehydrogenase and 6 alpha-hydroxylase activities were found. No aromatization was detectable. Steroids, especially estradiol, were also metabolized in a high degree to unextractable metabolites. It was concluded that steroid metabolism of dimethylbenz(a)anthracene-induced rat mammary tumors was not related to the ER and/or PR concentration of tumor tissue

  7. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism

    Directory of Open Access Journals (Sweden)

    Mirco Galiè

    2007-11-01

    Full Text Available Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG positron emission tomography (PET, we mapped in vivo the vascular supply and glucose metabolism in syngeneic experimental models of carcinoma and mesenchymal tumor. We found that in both tumor histotypes, regions with high vascular perfusion exhibited a significantly lower FDG uptake. This reciprocity was more conspicuous in carcinomas than in mesenchymal tumors, and regions with a high-vascular/low-FDG uptake pattern roughly overlapped with a stromal capsule and intratumoral large connectival septa. Accordingly, mesenchymal tumors exhibited a higher vascular perfusion and a lower FDG uptake than carcinomas. Thus, we provide in vivo evidence of vascular/metabolic reciprocity between epithelial and mesenchymal histotypes in tumors, suggesting a new intriguing aspect of epithelial-stromal interaction. Our results suggests that FDG-PET-based clinical analysis can underestimate the malignity or tumor extension of carcinomas exhibiting any trait of “mesenchymalization” such as desmoplasia or epithelial-mesenchymal transition.

  8. Obesity and Cancer Metabolism: A Perspective on Interacting Tumor-Intrinsic and Extrinsic Factors.

    Science.gov (United States)

    Doerstling, Steven S; O'Flanagan, Ciara H; Hursting, Stephen D

    2017-01-01

    Obesity is associated with increased risk and poor prognosis of many types of cancers. Several obesity-related host factors involved in systemic metabolism can influence tumor initiation, progression, and/or response to therapy, and these have been implicated as key contributors to the complex effects of obesity on cancer incidence and outcomes. Such host factors include systemic metabolic regulators including insulin, insulin-like growth factor 1, adipokines, inflammation-related molecules, and steroid hormones, as well as the cellular and structural components of the tumor microenvironment, particularly adipose tissue. These secreted and structural host factors are extrinsic to, and interact with, the intrinsic metabolic characteristics of cancer cells to influence their growth and spread. This review will focus on the interplay of these tumor cell-intrinsic and extrinsic factors in the context of energy balance, with the objective of identifying new intervention targets for preventing obesity-associated cancer.

  9. ATF4-Induced Metabolic Reprograming Is a Synthetic Vulnerability of the p62-Deficient Tumor Stroma.

    Science.gov (United States)

    Linares, Juan F; Cordes, Thekla; Duran, Angeles; Reina-Campos, Miguel; Valencia, Tania; Ahn, Christopher S; Castilla, Elias A; Moscat, Jorge; Metallo, Christian M; Diaz-Meco, Maria T

    2017-12-05

    Tumors undergo nutrient stress and need to reprogram their metabolism to survive. The stroma may play a critical role in this process by providing nutrients to support the epithelial compartment of the tumor. Here we show that p62 deficiency in stromal fibroblasts promotes resistance to glutamine deprivation by the direct control of ATF4 stability through its p62-mediated polyubiquitination. ATF4 upregulation by p62 deficiency in the stroma activates glucose carbon flux through a pyruvate carboxylase-asparagine synthase cascade that results in asparagine generation as a source of nitrogen for stroma and tumor epithelial proliferation. Thus, p62 directly targets nuclear transcription factors to control metabolic reprogramming in the microenvironment and repress tumorigenesis, and identifies ATF4 as a synthetic vulnerability in p62-deficient tumor stroma. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Interrogation of metabolic and oxygen states of tumors with fiber-based luminescence lifetime spectroscopy.

    Science.gov (United States)

    Lukina, Maria; Orlova, Anna; Shirmanova, Marina; Shirokov, Daniil; Pavlikov, Anton; Neubauer, Antje; Studier, Hauke; Becker, Wolfgang; Zagaynova, Elena; Yoshihara, Toshitada; Tobita, Seiji; Shcheslavskiy, Vladislav

    2017-02-15

    The study of metabolic and oxygen states of cells in a tumor in vivo is crucial for understanding of the mechanisms responsible for tumor development and provides background for the relevant tumor's treatment. Here, we show that a specially designed implantable fiber-optic probe provides a promising tool for optical interrogation of metabolic and oxygen states of a tumor in vivo. In our experiments, the excitation light from a ps diode laser source is delivered to the sample through an exchangeable tip via a multimode fiber, and the emission light is transferred to the detector by another multimode fiber. Fluorescence lifetime of a nicotinamid adenine dinucleotide (NAD(P)H) and phosphorescence lifetime of an oxygen sensor based on an iridium (III) complex of enzothienylpyridine (BTPDM1) are explored both in model experiment in solutions and in living mice.

  11. Cancer Metabolism and Tumor Heterogeneity: Imaging Perspectives Using MR Imaging and Spectroscopy

    Directory of Open Access Journals (Sweden)

    Gigin Lin

    2017-01-01

    Full Text Available Cancer cells reprogram their metabolism to maintain viability via genetic mutations and epigenetic alterations, expressing overall dynamic heterogeneity. The complex relaxation mechanisms of nuclear spins provide unique and convertible tissue contrasts, making magnetic resonance imaging (MRI and magnetic resonance spectroscopy (MRS pertinent imaging tools in both clinics and research. In this review, we summarized MR methods that visualize tumor characteristics and its metabolic phenotypes on an anatomical, microvascular, microstructural, microenvironmental, and metabolomics scale. The review will progress from the utilities of basic spin-relaxation contrasts in cancer imaging to more advanced imaging methods that measure tumor-distinctive parameters such as perfusion, water diffusion, magnetic susceptibility, oxygenation, acidosis, redox state, and cell death. Analytical methods to assess tumor heterogeneity are also reviewed in brief. Although the clinical utility of tumor heterogeneity from imaging is debatable, the quantification of tumor heterogeneity using functional and metabolic MR images with development of robust analytical methods and improved MR methods may offer more critical roles of tumor heterogeneity data in clinics. MRI/MRS can also provide insightful information on pharmacometabolomics, biomarker discovery, disease diagnosis and prognosis, and treatment response. With these future directions in mind, we anticipate the widespread utilization of these MR-based techniques in studying in vivo cancer biology to better address significant clinical needs.

  12. Peculiarities of antioxidant system and iron metabolism in organism during development of tumor resistance to cisplatin.

    Science.gov (United States)

    Chekhun, V F; Lozovska, Y V; Burlaka, A P; Lukyanova, N Y; Todor, I N; Naleskina, L A

    2014-09-01

    To study in vivo the peculiarities of changes of iron metabolism and antioxidant system in dynamics of growth of Guerin carcinoma with different sensitivity to cisplatin. In order to evaluate the content of metallothionein-1 (MT-1) in tumor homogenates and blood serum of rats with cisplatin-sensitive and cisplatin-resistant Guerin carcinoma the immunoenzyme method was used. The evaluation of ceruloplasmin activity, content of "free iron" complexes, superoxide and NO-generating acti-vity of NADPH-oxidase and iNOS activity in neutrophils, blood serum and tumor homogenates was measured by EPR-spectro-scopy. Maximal accumulation of MT-1 in blood serum and tumor, more pronounced in resistant strain, at the border of latent and exponential phase of growth has been shown that is the evidence of protective role of this protein in the respect to the generation of free radical compounds. It has been determined that in animals with cisplatin-resistant strain of Guerin carcinoma, increase of "free iron" complexes is more apparent both on the level of tumor and organism on the background on increase of CP/TR ratio that is the consequence of organism antioxidant protection system disorder. Mentioned changes in metabolism of iron with its accumulation in tumor and further reprogramming of mitochondria metabolism and activity of NADPH-oxidase for non-transformed cells are favorable conditions for the formation of oxidative phenotype of tumor.

  13. 13C and 31P NMR [Nuclear Magnetic Resonance] studies of prostate tumor metabolism

    International Nuclear Information System (INIS)

    Sillerud, L.O.; Halliday, K.R.; Freyer, J.P; Griffey, R.H.; Fenoglio-Preiser, C.

    1989-01-01

    The current research on prostate cancer by NMR spectroscopy and microscopy will most significantly contribute to tumor diagnosis and characterization only if sound biochemical models of tumor metabolism are established and tested. Prior searches focused on universal markers of malignancy, have to date, revealed no universal markers by any method. It is unlikely that NMRS will succeed where other methods have failed, however, NMR spectroscopy does provide a non-invasive means to analyze multiple compounds simultaneously in vivo. In order to fully evaluate the ability of NMRS to differentiate non-malignant from malignant tissues it is necessary to determine sufficient multiple parameters from specific, well-diagnosed, histological tumor types that, in comparison to normal tissue and non-neoplastic, non-normal pathologies from which the given neoplasm must be differentiated, one has enough degrees of freedom to make a mathematically and statistically significant determination. Confounding factors may consist of tumor heterogeneity arising from regional variations in differentiation, ischemia, necrosis, hemorrhage, inflammation and the presence of intermingled normal tissue. One related aspect of our work is the development of { 13 C}- 1 H metabolic imaging of 13 C for metabolic characterization, with enhanced spatial localization (46). This should markedly extend the range of potential clinical NMR uses because the spatial variation in prostate metabolism may prove to be just as important in tumor diagnoses as bulk (volume-averaged) properties themselves. It is our hope that NMRS and spectroscopic imaging will reveal a sound correlation between prostate metabolism and tumor properties that will be clinically straightforward and useful for diagnosis

  14. Dealing with hunger: Metabolic stress responses in tumors

    Directory of Open Access Journals (Sweden)

    Michael A Reid

    2013-01-01

    Full Text Available Increased nutrient uptake and usage is a hallmark of many human malignancies. During the course of tumorigenesis, cancer cells often outstrip their local nutrient supply leading to periods of nutrient deprivation. Interestingly, cancer cells often develop strategies to adapt and survive these challenging conditions. Accordingly, understanding these processes is critical for developing therapies that target cancer metabolism. Exciting new progress has been made in elucidating the mechanisms used by cancer cells under nutrient restricted conditions. In this review, we highlight recent studies that have brought insight into how cancer cells deal with low nutrient environments.

  15. Novel small molecule drugs inhibit tumor cell metabolism and show potent anti-tumorigenic potential

    DEFF Research Database (Denmark)

    Trojel-Hansen, Christina; Erichsen, Kamille Dumong; Christensen, Mette Knak

    2011-01-01

    oxyphenisatine analogs TOP001 and TOP216 exert their anti-cancer effect by affecting tumor cell metabolism and inducing intracellular amino acid deprivation, leading to a block of cell proliferation. GCN2-mediated phosphorylation of eIF2a as well as mTOR pathway inhibition supports the above notion. In addition...

  16. Novel small molecule drugs inhibit tumor cell metabolism and show potent anti-tumorigenic potential

    DEFF Research Database (Denmark)

    Trojel-Hansen, Christina; Erichsen, Kamille Dumong; Christensen, Mette Knak

    2011-01-01

    oxyphenisatine analogs TOP001 and TOP216 exert their anti-cancer effect by affecting tumor cell metabolism and inducing intracellular amino acid deprivation, leading to a block of cell proliferation. GCN2-mediated phosphorylation of eIF2α as well as mTOR pathway inhibition supports the above notion. In addition...

  17. Rb and p53 Liver Functions Are Essential for Xenobiotic Metabolism and Tumor Suppression

    NARCIS (Netherlands)

    Nantasanti, Sathidpak; Toussaint, Mathilda J. M.; Youssef, Sameh A.; Tooten, Peter C. J.; de Bruin, Alain

    2016-01-01

    The tumor suppressors Retinoblastoma (Rb) and p53 are frequently inactivated in liver diseases, such as hepatocellular carcinomas (HCC) or infections with Hepatitis B or C viruses. Here, we discovered a novel role for Rb and p53 in xenobiotic metabolism, which represent a key function of the liver

  18. Evolution of Tumor Metabolism might Reflect Carcinogenesis as a Reverse Evolution process (Dismantling of Multicellularity)

    Energy Technology Data Exchange (ETDEWEB)

    Alfarouk, Khalid O., E-mail: Alfarouk@Hala-alfarouk.org [Department of Evolution of Tumor Metabolism and Pharmacology, Hala Alfarouk Cancer Center, Khartoum 11123 (Sudan); Shayoub, Mohammed E.A. [Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum 11111 (Sudan); Muddathir, Abdel Khalig [Department of Pharmacognosy, Faculty of Pharmacy, University of Khartoum, Khartoum 11111 (Sudan); Elhassan, Gamal O. [General Directorate of Pharmacy, Federal Ministry of Health, Khartoum 11111 (Sudan); Bashir, Adil H.H. [Department of Evolution of Tumor Metabolism and Pharmacology, Hala Alfarouk Cancer Center, Khartoum 11123 (Sudan); Al Jawda Medical Hospital, Khartoum 11111 (Sudan)

    2011-07-22

    Carcinogenesis occurs through a series of steps from normal into benign and finally malignant phenotype. This cancer evolutionary trajectory has been accompanied by similar metabolic transformation from normal metabolism into Pasteur and/or Crabtree-Effects into Warburg-Effect and finally Cannibalism and/or Lactate-Symbiosis. Due to lactate production as an end-product of glycolysis, tumor colonies acquire new phenotypes that rely on lactate as energetic fuel. Presence of Warburg-Effect indicates that some tumor cells undergo partial (if not complete) de-endosymbiosis and so cancer cells have been become unicellular microorganism (anti-Dollo's Law) specially when they evolve to develop cannibalism as way of metabolism while oxidative types of cells that rely on lactate, as their energetic fuel, might represent extra-endosymbiosis. Thus, at the end, the cancer colony could be considered as integrated metabolic ecosystem. Proper understanding of tumor metabolism will contribute to discover potential anticancer agents besides conventional chemotherapy.

  19. Multimodality assessment of breast tumor physiology and metabolism

    Science.gov (United States)

    Chaudhry, Muhammad; Rosen, Mark; Schultz, Susan; Englander, Sarah; Sehgal, S.; Tomaszewski, M.; Schnall, Mitchell

    2005-04-01

    The objective is to compare power Doppler sonography (PD) and dynamic contrast-enhanced MRI (MR) and PET SUV in assessing the vascularity of benign and malignant breast lesions. Sixty two patients with 89 lesions (59 malignant lesions, 30 benign lesions) were evaluated by PD, MRI (MR) and PET SUV prior to surgery. Each imaging modality was evaluated independently. Lesion vascularity on PD was graded as avascular, intermediately vascular, or hypervascular. On MR, degree of maximal enhancement (minimal, moderate, or marked) and the kinetic pattern of enhancement (persistent, plateau, washout) were graded separately. For malignant lesions, PET SUV values were correlated with MRI kinetics. Gamma variable analysis was performed to assess the degree of correlation. Of the 89 lesions 44 were invasive ductal carcinoma, 2 were intraductal cancers, 6 were invasive lobular carcinoma, and 7 were invasive cancers with mixture of ductal and lobular features. There was a high degree of correlation between degree of maximal enhancement and enhancement kinetics on MRI (G=0.074, pInvasive malignancy demonstrated moderate correlation between SUV and MRI kinetics (G=0.64, p=0.14). There is a variable degree of correlation between various imaging modalities in assessing breast lesion vascularity. Further evaluation on the relationship between subjective reader assessment and objective quantitative image analysis is required to elucidate the differences in these measures of breast tumor physiology. This work was supported in part by the NIH grant P01CA085424-03.

  20. The Effects of Angelica Sinensis Polysaccharide on Tumor Growth and Iron Metabolism by Regulating Hepcidin in Tumor-Bearing Mice

    Directory of Open Access Journals (Sweden)

    Feng Ren

    2018-05-01

    Full Text Available Background/Aims: Iron plays a fundamental role in cell biology and its concentration must be precisely regulated. It is well documented that excess iron burden contributes to the occurrence and progression of cancer. Hepcidin secreted by liver plays an essential role in orchestrating iron metabolism. In the present study, we aimed to investigate the ability of angelica sinensis polysaccharide (ASP to decrease iron burden in tumor-bearing mice and the mechanism of ASP regulation hepcidin expression. Methods: Western blot, RT-PCR, immunohistochemistry (IHC, and enzyme-linked immunosorbent assay (ELISA were used to detect the regulation of hepcidin and related cytokines by ASP. The role of ASP in tumor proliferation was investigated using in vivo assays. Iron depositions and iron concentrations in organs were determined by hematoxylin-eosin (H&E staining and atomic absorption spectrophotometer. Results: We found that ASP could inhibit tumor growth in mice xenografted with 4T1 and H22 cancer cells. In vivo experiments also showed that ASP could potently regulate hepcidin expression in liver and serum and decrease iron burden in liver, spleen and grafted tumors in mouse model. Treatment with ASP in hepatic cell lines reproduced comparable results in decreasing hepcidin as in mouse liver. Furthermore, we found that ASP markedly suppressed the expression of interleukin-6 (IL-6, JAK2, p-STAT3, and p-SMAD1/5/8 in liver, suggesting that JAK/STAT and BMP-SMAD pathways were involved in the regulation of hepcidin expression by ASP. We also found down-regulation of iron-related cytokines in ASP treated mice. Conclusion: The present study provides new evidence that ASP decreases hepcidin expression, which can reduce iron burden and inhibit tumor proliferation. These findings might aid ASP developed as a potential candidate for cancer treatment in patients with iron overload.

  1. Nano-sized metabolic precursors for heterogeneous tumor-targeting strategy using bioorthogonal click chemistry in vivo.

    Science.gov (United States)

    Lee, Sangmin; Jung, Seulhee; Koo, Heebeom; Na, Jin Hee; Yoon, Hong Yeol; Shim, Man Kyu; Park, Jooho; Kim, Jong-Ho; Lee, Seulki; Pomper, Martin G; Kwon, Ick Chan; Ahn, Cheol-Hee; Kim, Kwangmeyung

    2017-12-01

    Herein, we developed nano-sized metabolic precursors (Nano-MPs) for new tumor-targeting strategy to overcome the intrinsic limitations of biological ligands such as the limited number of biological receptors and the heterogeneity in tumor tissues. We conjugated the azide group-containing metabolic precursors, triacetylated N-azidoacetyl-d-mannosamine to generation 4 poly(amidoamine) dendrimer backbone. The nano-sized dendrimer of Nano-MPs could generate azide groups on the surface of tumor cells homogeneously regardless of cell types via metabolic glycoengineering. Importantly, these exogenously generated 'artificial chemical receptors' containing azide groups could be used for bioorthogonal click chemistry, regardless of phenotypes of different tumor cells. Furthermore, in tumor-bearing mice models, Nano-MPs could be mainly localized at the target tumor tissues by the enhanced permeation and retention (EPR) effect, and they successfully generated azide groups on tumor cells in vivo after an intravenous injection. Finally, we showed that these azide groups on tumor tissues could be used as 'artificial chemical receptors' that were conjugated to bioorthogonal chemical group-containing liposomes via in vivo click chemistry in heterogeneous tumor-bearing mice. Therefore, overall results demonstrated that our nano-sized metabolic precursors could be extensively applied to new alternative tumor-targeting technique for molecular imaging and drug delivery system, regardless of the phenotype of heterogeneous tumor cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Arctigenin preferentially induces tumor cell death under glucose deprivation by inhibiting cellular energy metabolism.

    Science.gov (United States)

    Gu, Yuan; Qi, Chunting; Sun, Xiaoxiao; Ma, Xiuquan; Zhang, Haohao; Hu, Lihong; Yuan, Junying; Yu, Qiang

    2012-08-15

    Selectively eradicating cancer cells with minimum adverse effects on normal cells is a major challenge in the development of anticancer therapy. We hypothesize that nutrient-limiting conditions frequently encountered by cancer cells in poorly vascularized solid tumors might provide an opportunity for developing selective therapy. In this study, we investigated the function and molecular mechanisms of a natural compound, arctigenin, in regulating tumor cell growth. We demonstrated that arctigenin selectively promoted glucose-starved A549 tumor cells to undergo necrosis by inhibiting mitochondrial respiration. In doing so, arctigenin elevated cellular level of reactive oxygen species (ROS) and blocked cellular energy metabolism in the glucose-starved tumor cells. We also demonstrated that cellular ROS generation was caused by intracellular ATP depletion and played an essential role in the arctigenin-induced tumor cell death under the glucose-limiting condition. Furthermore, we combined arctigenin with the glucose analogue 2-deoxyglucose (2DG) and examined their effects on tumor cell growth. Interestingly, this combination displayed preferential cell-death inducing activity against tumor cells compared to normal cells. Hence, we propose that the combination of arctigenin and 2DG may represent a promising new cancer therapy with minimal normal tissue toxicity. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  3. Stereological quantification of tumor volume, mean nuclear volume and total number of melanoma cells correlated with morbidity and mortality

    DEFF Research Database (Denmark)

    Bønnelykke-Behrndtz, Marie Louise; Sørensen, Flemming Brandt; Damsgaard, Tine Engberg

    2008-01-01

    potential indicators of prognosis. Sixty patients who underwent surgery at the Department of Plastic Surgery, Aarhus University Hospital, from 1991 to 1994 were included in the study. Total tumor volume was estimated by the Cavalieri technique, total number of tumor cells by the optical dissector principle...... showed a significant impact on both disease-free survival (p=0.001) and mortality (p=0.009). In conclusion, tumor volume and total number of cancer cells were highly reproducible but did not add additional, independent prognostic information regarding the study population.......Stereological quantification of tumor volume, total number of tumor cells and mean nuclear volume provides unbiased data, regardless of the three-dimensional shape of the melanocytic lesion. The aim of the present study was to investigate whether these variables are reproducible and may represent...

  4. Expression Profile of Genes Related to Drug Metabolism in Human Brain Tumors.

    Directory of Open Access Journals (Sweden)

    Pantelis Stavrinou

    Full Text Available Endogenous and exogenous compounds as well as carcinogens are metabolized and detoxified by phase I and II enzymes, the activity of which could be crucial to the inactivation and hence susceptibility to carcinogenic factors. The expression of these enzymes in human brain tumor tissue has not been investigated sufficiently. We studied the association between tumor pathology and the expression profile of seven phase I and II drug metabolizing genes (CYP1A1, CYP1B1, ALDH3A1, AOX1, GSTP1, GSTT1 and GSTM3 and some of their proteins.Using qRT-PCR and western blotting analysis the gene and protein expression in a cohort of 77 tumors were investigated. The major tumor subtypes were meningioma, astrocytoma and brain metastases, -the later all adenocarcinomas from a lung primary.Meningeal tumors showed higher expression levels for AOX1, CYP1B1, GSTM3 and GSTP1. For AOX1, GSTM and GSTP1 this could be verified on a protein level as well. A negative correlation between the WHO degree of malignancy and the strength of expression was identified on both transcriptional and translational level for AOX1, GSTM3 and GSTP1, although the results could have been biased by the prevalence of meningiomas and glioblastomas in the inevitably bipolar distribution of the WHO grades. A correlation between the gene expression and the protein product was observed for AOX1, GSTP1 and GSTM3 in astrocytomas.The various CNS tumors show different patterns of drug metabolizing gene expression. Our results suggest that the most important factor governing the expression of these enzymes is the histological subtype and to a far lesser extent the degree of malignancy itself.

  5. Bone marrow transplantation in the patients with malignant tumor. Studies on supralethal total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Tatsuno, Ikuro; Saito, Yasuo

    1984-11-01

    Based on evidence gained from ten patients of allogeneic bone marrow transplantation (BMT) and eight patients of autologous BMT, recent knowledge on literatures of BMT and total body irradiation (TBI) is summarized. Interstitial pneumonia after BMT has a strong correlation with TBI. Low dose-rate and fractionation of TBI are seemed to reduce the lung injury, thereby reducing the incidence of nonleukemia deaths. BMT is applied to not only acute leukemia, malignant lymphoma and solid tumors but also to chronic leukemia. It is emphasized that several of the important prognostic factors are within the control of the transplantation team.

  6. Nerve Sheath Tumors in Neurofibromatosis Type 1: Assessment of Whole-Body Metabolic Tumor Burden Using F-18-FDG PET/CT.

    Directory of Open Access Journals (Sweden)

    Johannes Salamon

    Full Text Available To determine the metabolically active whole-body tumor volume (WB-MTV on F-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG PET/CT in individuals with neurofibromatosis type 1 (NF1 using a three-dimensional (3D segmentation and computerized volumetry technique, and to compare PET WB-MTV between patients with benign and malignant peripheral nerve sheath tumors (PNSTs.Thirty-six NF1 patients (18 patients with malignant PNSTs and 18 age- and sex-matched controls with benign PNSTs were examined by F-18-FDG PET/CT. WB-MTV, whole-body total lesion glycolysis (WB-TLG and a set of semi-quantitative imaging-based parameters were analyzed both on a per-patient and a per-lesion basis.On a per-lesion basis, malignant PNSTs demonstrated both a significantly higher MTV and TLG than benign PNSTs (p < 0.0001. On a per-patient basis, WB-MTV and WB-TLG were significantly higher in patients with malignant PNSTs compared to patients with benign PNSTs (p < 0.001. ROC analysis showed that MTV and TLG could be used to differentiate between benign and malignant tumors.WB-MTV and WB-TLG may identify malignant change and may have the potential to provide a basis for investigating molecular biomarkers that correlate with metabolically active disease manifestations. Further evaluation will determine the potential clinical impact of these PET-based parameters in NF1.

  7. Metabolic 19F MRI an dynamic 18F PET for chemotherapy monitoring in experimental tumors

    International Nuclear Information System (INIS)

    Brix, G.; Haberkorn, U.; Bellemann, M.E.

    1999-01-01

    The efficient clinical use of chemotherapeutic agents requires the assessment of the uptake and metabolism of the drugs in the tumor as well as in the various organs of the body by using noninvasive imaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET). In this overview, we present different metabolic 19 F MRI and dynamic 18 F PET techniques for noninvasive monitoring of fluorine-containing anticancer drugs and evaluate their potentials and limitations within the framework of experimental animal studies. (orig.) [de

  8. Relationship between pretreatment level of plasma Epstein-Barr virus DNA, tumor burden, and metabolic activity in advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Ma, Brigette; King, Ann; Lo, Y.M. Dennis; Yau, Y.Y.; Zee, Benny; Hui, Edwin P.; Leung, Sing F.; Mo, Frankie; Kam, Michael K.; Ahuja, Anil; Kwan, Wing H.; Chan, Anthony

    2006-01-01

    Purpose: Plasma Epstein-Barr virus DNA (pEBV DNA) is an important prognostic marker in nasopharyngeal carcinoma (NPC). This study tested the hypotheses that pEBV DNA reflects tumor burden and metabolic activity by evaluating its relationship with tumor volume and 18 F-fluorodeoxyglucose ( 18 F-FDG) uptake in NPC. Methods and Materials: Pre-treatment pEBV DNA analysis, 18 F-FDG positron emission tomography-computed tomography scan (PET-CT) and magnetic resonance imaging (MRI) of the head and neck were performed in 57 patients. Net volume (cm 3 ) of the primary tumor (T vol ) and regional nodes (N vol ) were quantified on MRI. 18 F-FDG uptake was expressed as the maximum standardized uptake value (SUV max ) at the primary tumor (T suv ) and regional nodes (N suv ). Lesions with SUV max ≥ 2.5 were considered malignant. Relationship between SUV max , natural logarithm (log) of pEBV DNA, and square root (sq) of MRI volumes was analyzed using the Wilcoxon test. A linear regression model was constructed to test for any interaction between variables and disease stage. Results: Log-pEBV DNA showed significant correlation with sq-T vol (r = 0.393), sq-N vol (r = 0.452), total tumor volume (sq-Total vol = T vol + N vol , r = 0.554), T suv (r = 0.276), N suv (r = 0.434), and total SUV max (Total suv = T suv + N suv , r = 0.457). Likewise, sq-T vol was correlated to T suv (r 0.426), and sq-N vol with N suv (r = 0.651). Regression analysis showed that only log-pEBV DNA was significantly associated with sq-Total vol (p vol was significantly associated with T suv (p = 0.002; parameter estimate = 3.923; 95% confidence interval = 1.498-6.348). Conclusion: This study supports the hypothesis that cell-free plasma EBV DNA is a marker of tumor burden in EBV-related NPC

  9. Differential expression of metabolic genes in tumor and stromal components of primary and metastatic loci in pancreatic adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Nina V Chaika

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States with a five-year survival rate of 6%. It is characterized by extremely aggressive tumor growth rate and high incidence of metastasis. One of the most common and profound biochemical phenotypes of animal and human cancer cells is their ability to metabolize glucose at high rates, even under aerobic conditions. However, the contribution of metabolic interrelationships between tumor cells and cells of the surrounding microenvironment to the progression of cancer is not well understood. We evaluated differential expression of metabolic genes and, hence, metabolic pathways in primary tumor and metastases of patients with pancreatic adenocarcinoma.We analyzed the metabolic gene (those involved in glycolysis, tri-carboxylic acid pathway, pentose-phosphate pathway and fatty acid metabolism expression profiles of primary and metastatic lesions from pancreatic cancer patients by gene expression arrays. We observed two principal results: genes that were upregulated in primary and most of the metastatic lesions; and genes that were upregulated only in specific metastatic lesions in a site-specific manner. Immunohistochemical (IHC analyses of several metabolic gene products confirmed the gene expression patterns at the protein level. The IHC analyses also revealed differential tumor and stromal expression patterns of metabolic enzymes that were correlated with the metastasis sites.Here, we present the first comprehensive studies that establish differential metabolic status of tumor and stromal components and elevation of aerobic glycolysis gene expression in pancreatic cancer.

  10. Tumor-stroma metabolic relationship based on lactate shuttle can sustain prostate cancer progression

    International Nuclear Information System (INIS)

    Sanità, Patrizia; Capulli, Mattia; Teti, Anna; Galatioto, Giuseppe Paradiso; Vicentini, Carlo; Chiarugi, Paola; Bologna, Mauro; Angelucci, Adriano

    2014-01-01

    Cancer cell adopts peculiar metabolic strategies aimed to sustain the continuous proliferation in an environment characterized by relevant fluctuations in oxygen and nutrient levels. Monocarboxylate transporters MCT1 and MCT4 can drive such adaptation permitting the transport across plasma membrane of different monocarboxylic acids involved in energy metabolism. Role of MCTs in tumor-stroma metabolic relationship was investigated in vitro and in vivo using transformed prostate epithelial cells, carcinoma cell lines and normal fibroblasts. Moreover prostate tissues from carcinoma and benign hypertrophy cases were analyzed for individuating clinical-pathological implications of MCT1 and MCT4 expression. Transformed prostate epithelial (TPE) and prostate cancer (PCa) cells express both MCT1 and MCT4 and demonstrated variable dependence on aerobic glycolysis for maintaining their proliferative rate. In glucose-restriction the presence of L-lactate determined, after 24 h of treatment, in PCa cells the up-regulation of MCT1 and of cytochrome c oxidase subunit I (COX1), and reduced the activation of AMP-activated protein kinase respect to untreated cells. The blockade of MCT1 function, performed by si RNA silencing, determined an appreciable antiproliferative effect when L-lactate was utilized as energetic fuel. Accordingly L-lactate released by high glycolytic human diploid fibroblasts WI-38 sustained survival and growth of TPE and PCa cells in low glucose culture medium. In parallel, the treatment with conditioned medium from PCa cells was sufficient to induce glycolytic metabolism in WI-38 cells, with upregulation of HIF-1a and MCT4. Co-injection of PCa cells with high glycolytic WI-38 fibroblasts determined an impressive increase in tumor growth rate in a xenograft model that was abrogated by MCT1 silencing in PCa cells. The possible interplay based on L-lactate shuttle between tumor and stroma was confirmed also in human PCa tissue where we observed a positive

  11. MHC-I modulation due to changes in tumor cell metabolism regulates tumor sensitivity to CTL and NK cells

    Science.gov (United States)

    Catalán, Elena; Charni, Seyma; Jaime, Paula; Aguiló, Juan Ignacio; Enríquez, José Antonio; Naval, Javier; Pardo, Julián; Villalba, Martín; Anel, Alberto

    2015-01-01

    Tumor cells have a tendency to use glucose fermentation to obtain energy instead of mitochondrial oxidative phosphorylation (OXPHOS). We demonstrated that this phenotype correlated with loss of ERK5 expression and with reduced MHC class I expression. Consequently, tumor cells could evade cytotoxic T lymphocyte (CTL)-mediated immune surveillance, but also increase their sensitivity to natural killer (NK) cells. These outcomes were evaluated using two cellular models: leukemic EL4 cells and L929 transformed fibroblasts and their derived ρ° cell lines, which lack mitochondrial DNA. We have also used a L929 cell sub-line that spontaneously lost matrix attachment (L929dt), reminiscent of metastasis generation, that also downregulated MHC-I and ERK5 expression. MHC-I expression is lower in ρ° cells than in the parental cell lines, but they were equally sensitive to CTL. On the contrary, ρ° cells were more sensitive to activated NK cells than parental cells. On the other hand, L929dt cells were resistant to CTL and NK cells, showed reduced viability when forced to perform OXPHOS, and surviving cells increased MHC-I expression and became sensitive to CTL. The present results suggest that when the reduction in MHC-I levels in tumor cells due to glycolytic metabolism is partial, the increase in sensitivity to NK cells seems to predominate. However, when tumor cells completely lose MHC-I expression, the combination of treatments that increase OXPHOS with CTL-mediated immunotherapy could be a promising therapeutic approach. PMID:25949869

  12. MHC-I modulation due to changes in tumor cell metabolism regulates tumor sensitivity to CTL and NK cells.

    Science.gov (United States)

    Catalán, Elena; Charni, Seyma; Jaime, Paula; Aguiló, Juan Ignacio; Enríquez, José Antonio; Naval, Javier; Pardo, Julián; Villalba, Martín; Anel, Alberto

    2015-01-01

    Tumor cells have a tendency to use glucose fermentation to obtain energy instead of mitochondrial oxidative phosphorylation (OXPHOS). We demonstrated that this phenotype correlated with loss of ERK5 expression and with reduced MHC class I expression. Consequently, tumor cells could evade cytotoxic T lymphocyte (CTL)-mediated immune surveillance, but also increase their sensitivity to natural killer (NK) cells. These outcomes were evaluated using two cellular models: leukemic EL4 cells and L929 transformed fibroblasts and their derived ρ° cell lines, which lack mitochondrial DNA. We have also used a L929 cell sub-line that spontaneously lost matrix attachment (L929dt), reminiscent of metastasis generation, that also downregulated MHC-I and ERK5 expression. MHC-I expression is lower in ρ° cells than in the parental cell lines, but they were equally sensitive to CTL. On the contrary, ρ° cells were more sensitive to activated NK cells than parental cells. On the other hand, L929dt cells were resistant to CTL and NK cells, showed reduced viability when forced to perform OXPHOS, and surviving cells increased MHC-I expression and became sensitive to CTL. The present results suggest that when the reduction in MHC-I levels in tumor cells due to glycolytic metabolism is partial, the increase in sensitivity to NK cells seems to predominate. However, when tumor cells completely lose MHC-I expression, the combination of treatments that increase OXPHOS with CTL-mediated immunotherapy could be a promising therapeutic approach.

  13. Radiographic and metabolic response rates following image-guided stereotactic radiotherapy for lung tumors

    International Nuclear Information System (INIS)

    Mohammed, Nasiruddin; Grills, Inga S.; Wong, Ching-Yee Oliver; Galerani, Ana Paula; Chao, Kenneth; Welsh, Robert; Chmielewski, Gary; Yan Di; Kestin, Larry L.

    2011-01-01

    Purpose: To evaluate radiographic and metabolic response after stereotactic body radiotherapy (SBRT) for early lung tumors. Materials and methods: Thirty-nine tumors were treated prospectively with SBRT (dose = 48-60 Gy, 4-5 Fx). Thirty-six cases were primary NSCLC (T1N0 = 67%; T2N0 = 25%); three cases were solitary metastases. Patients were followed using CT and PET at 6, 16, and 52 weeks post-SBRT, with CT follow-up thereafter. RECIST and EORTC criteria were used to evaluate CT and PET responses. Results: At median follow-up of 9 months (0.4-26), RECIST complete response (CR), partial response (PR), and stable disease (SD) rates were 3%, 43%, 54% at 6 weeks; 15%, 38%, 46% at 16 weeks; 27%, 64%, 9% at 52 weeks. Mean baseline tumor volume was reduced by 46%, 70%, 87%, and 96%, respectively at 6, 16, 52, and 72 weeks. Mean baseline maximum standardized uptake value (SUV) was 8.3 (1.1-20.3) and reduced to 3.4, 3.0, and 3.7 at 6, 16, and 52 weeks after SBRT. EORTC metabolic CR/PR, SD, and progressive disease rates were 67%, 22%, 11% at 6 weeks; 86%, 10%, 3% at 16 weeks; 95%, 5%, 0% at 52 weeks. Conclusions: SBRT yields excellent RECIST and EORTC based response. Metabolic response is rapid however radiographic response occurs even after 1-year post treatment.

  14. Light contamination during the dark phase in "photoperiodically controlled" animal rooms: effect on tumor growth and metabolism in rats.

    Science.gov (United States)

    Dauchy, R T; Sauer, L A; Blask, D E; Vaughan, G M

    1997-10-01

    Enhanced neoplastic growth and metabolism have been reported in animals maintained in a constant light (24L:0D) environment. Results from this laboratory indicate that tumor growth is directly dependent upon increased ambient blood concentrations of arachidonic and linoleic acids, particularly linoleic acid. Tumor linoleic acid utilization and production if its putative mitogenic metabolite, 13-hydroxyoctadecadienoic acid (13-HODE), are suppressed by the circadian neurohormone melatonin, the production of which is itself regulated by light in all mammals. This study was performed to determine whether minimal light contamination (0.2 lux) in an animal room during an otherwise normal dark phase may disrupt normal circadian production of melatonin and affect tumor growth and metabolism. Animals of groups I (12L:12D), II (12L:12-h light-contaminated dark phase), and III (24L:0D) had plasma total fatty acid (TFA), linoleic acid (LA), and melatonin concentrations measured prior to tumor implantation; groups I and II had daily cycles in plasma TFA and LA values, whereas group III had constant values throughout the day. The integrated mean TFA and LA values for the entire day were similar in all groups. Although group-I animals had a normal nocturnal surge of melatonin (127.0 pg/ml) at 2400 h, the nocturnal amplitude was suppressed in group-II animals (16.0 pg/ml); circadian variation in melatonin concentration was not seen in group-III animals (7.4 pg/ml). At 12 weeks of age, rats had the Morris hepatoma 7288CTC implanted as "tissue-isolated" tumors grown subcutaneously. Latency to onset of palpable tumor mass for groups I, II, and III was 11, 9, and 5 days respectively. Tumor growth rates were 0.72 +/- 0.09, 1.30 +/- 0.15, and 1.48 +/- 0.17 g/d (mean +/- SD, n = 6/group) in groups I, II, and III respectively. Arteriovenous difference measurements for TFA and LA across the tumors were 4.22 +/- 0.89 and 0.83 +/- 0.18 (group I), 8.26 +/- 0.66 and 1.64 +/- 0.13 (group II

  15. Hypoxia Pathway Proteins As Central Mediators of Metabolism in the Tumor Cells and Their Microenvironment

    Directory of Open Access Journals (Sweden)

    Sundary Sormendi

    2018-01-01

    Full Text Available Low oxygen tension or hypoxia is a determining factor in the course of many different processes in animals, including when tissue expansion and cellular metabolism result in high oxygen demands that exceed its supply. This is mainly happening when cells actively proliferate and the proliferating mass becomes distant from the blood vessels, such as in growing tumors. Metabolic alterations in response to hypoxia can be triggered in a direct manner, such as the switch from oxidative phosphorylation to glycolysis or inhibition of fatty acid desaturation. However, as the modulated action of hypoxia-inducible factors or the oxygen sensors (prolyl hydroxylase domain-containing enzymes can also lead to changes in enzyme expression, these metabolic changes can also be indirect. With this review, we want to summarize our current knowledge of the hypoxia-induced changes in metabolism during cancer development, how they are affected in the tumor cells and in the cells of the microenvironment, most prominently in immune cells.

  16. The effect of alterations in total coenzyme A on metabolic pathways in the liver and heart

    International Nuclear Information System (INIS)

    Schlosser, C.A.S.

    1989-01-01

    The first set of experiments involved in vitro experiments using primary cultures of rat hepatocytes. A range of conditions were developed which resulted in cell cultures with variations in total CoA over a range of 1.3 to 2.9 nmol/mg protein with identical hormonal activation which simulated metabolic stress. Elevations of total CoA levels above that of controls due to preincubation with cyanamide plus pantothenate were correlated with diminished rates of total ketone body production, 3-hydroxybutyrate production and ratios of 3 hydroxybutyrate/acetoactetate with palmitate as substrate. In contrast, cells with elevated total CoA levels had higher rates of [ 14 C] CO 2 production from radioactive palmitate which implied greater flux of acetyl CoA units into the TCA cycle and less to the pathway of ketogenesis. The second set of experiments were designed to alter total CoA levels in vivo by maintaining rats on a chronic ethanol diet with or without pantothenate-supplementation. The effect of alterations of CoA on mitochondrial metabolism was evaluated by measuring substrate oxidation rates in liver and heat mitochondria as well as ketone body production with palmitoyl-1-carnitine as substrate

  17. Rb and p53 Liver Functions Are Essential for Xenobiotic Metabolism and Tumor Suppression.

    Directory of Open Access Journals (Sweden)

    Sathidpak Nantasanti

    Full Text Available The tumor suppressors Retinoblastoma (Rb and p53 are frequently inactivated in liver diseases, such as hepatocellular carcinomas (HCC or infections with Hepatitis B or C viruses. Here, we discovered a novel role for Rb and p53 in xenobiotic metabolism, which represent a key function of the liver for metabolizing therapeutic drugs or toxins. We demonstrate that Rb and p53 cooperate to metabolize the xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC. DDC is metabolized mainly by cytochrome P450 (Cyp3a enzymes resulting in inhibition of heme synthesis and accumulation of protoporphyrin, an intermediate of heme pathway. Protoporphyrin accumulation causes bile injury and ductular reaction. We show that loss of Rb and p53 resulted in reduced Cyp3a expression decreased accumulation of protoporphyrin and consequently less ductular reaction in livers of mice fed with DDC for 3 weeks. These findings provide strong evidence that synergistic functions of Rb and p53 are essential for metabolism of DDC. Because Rb and p53 functions are frequently disabled in liver diseases, our results suggest that liver patients might have altered ability to remove toxins or properly metabolize therapeutic drugs. Strikingly the reduced biliary injury towards the oxidative stress inducer DCC was accompanied by enhanced hepatocellular injury and formation of HCCs in Rb and p53 deficient livers. The increase in hepatocellular injury might be related to reduce protoporphyrin accumulation, because protoporphrin is well known for its anti-oxidative activity. Furthermore our results indicate that Rb and p53 not only function as tumor suppressors in response to carcinogenic injury, but also in response to non-carcinogenic injury such as DDC.

  18. Comparison of planar, PET and well-counter measurements of total tumor radioactivity in a mouse xenograft model.

    Science.gov (United States)

    Green, Michael V; Seidel, Jurgen; Williams, Mark R; Wong, Karen J; Ton, Anita; Basuli, Falguni; Choyke, Peter L; Jagoda, Elaine M

    2017-10-01

    Quantitative small animal radionuclide imaging studies are often carried out with the intention of estimating the total radioactivity content of various tissues such as the radioactivity content of mouse xenograft tumors exposed to putative diagnostic or therapeutic agents. We show that for at least one specific application, positron projection imaging (PPI) and PET yield comparable estimates of absolute total tumor activity and that both of these estimates are highly correlated with direct well-counting of these same tumors. These findings further suggest that in this particular application, PPI is a far more efficient data acquisition and processing methodology than PET. Forty-one athymic mice were implanted with PC3 human prostate cancer cells transfected with prostate-specific membrane antigen (PSMA (+)) and one additional animal (for a total of 42) with a control blank vector (PSMA (-)). All animals were injected with [ 18 F] DCFPyl, a ligand for PSMA, and imaged for total tumor radioactivity with PET and PPI. The tumors were then removed, assayed by well counting for total radioactivity and the values between these methods intercompared. PET, PPI and well-counter estimates of total tumor radioactivity were highly correlated (R 2 >0.98) with regression line slopes near unity (0.95radioactivity can be measured with PET or PPI with an accuracy comparable to well counting if certain experimental and pharmacokinetic conditions are met. In this particular application, PPI is significantly more efficient than PET in making these measurements. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Tumor xenotransplantation in Wistar rats after treatment with cyclophosphamide and total lymphoid irradiation

    International Nuclear Information System (INIS)

    Hoogenhout, J.; Kazem, I.; Jerusalem, C.R.; Bakkeren, J.A.J.; de Jong, J.; Kal, H.B.; van Munster, P.J.J.

    1982-01-01

    Three-month-old male Wistar rats were treated with cyclophosphamide and total lymphoid irradiation, and C22LR mouse osteosarcoma was transplanted into the rats. The effects of immunosuppression were monitored by lymphocyte counts, serum IgG determinations, phytohemagglutinin (PHA) and concanavalin A (Con A) responses, measurement of the proportion of B cells, and histopathological studies of the lymphoid organs. At eight days after treatment, the lymphocyte counts, IgG levels, and PHA and Con A values were decreased. Mitotic activity started in the depleted B and T cell areas of the peripheral lymphatic organs two weeks after treatment. There was a 94% graft take of the osteosarcoma. It was determined that the optimum time for tumor xenograft transplantation is 4 days after treatment. The duration of growth was 11 days, and this was followed by regression up to day 21

  20. Total thyroidectomy: a clue to understanding the metabolic changes induced by subclinical hyperthyroidism?

    Science.gov (United States)

    Bel Lassen, Pierre; Kyrilli, Aglaia; Lytrivi, Maria; Ruiz Patino, Maria; Corvilain, Bernard

    2017-02-01

    The effects of endogenous subclinical hyperthyroidism (eSCH) on heart and bone have been well documented. There are only limited data available regarding the impact of eSCH on weight regulation and lipid metabolism. Our aim was to evaluate the changes in body weight and metabolic parameters after total thyroidectomy in patients with pre-operative eSCH compared with pre-operative patients with euthyroid (EUT). A retrospective study of 505 patients who underwent total thyroidectomy for benign multinodular goitre in an academic hospital in Brussels (Belgium) was performed. Two hundred and 25 patients were included (eSCH group: n = 74; EUT group: n = 151). The mean follow-up time was 26·1 ± 0·8 months and was similar in both groups. Absolute BMI gain was significantly greater in the eSCH group than in the EUT group (1·11 ± 0·17 vs 0·33 ± 0·13 kg/m 2 ; P = 0·003). A significant increase in LDL cholesterol was observed in the eSCH group (16·1 ± 3·8 mg/dl; P effect of eSCH on body weight regulation and lipid metabolism. © 2016 John Wiley & Sons Ltd.

  1. Functional imaging to monitor vascular and metabolic response in canine head and neck tumors during fractionated radiotherapy.

    Science.gov (United States)

    Rødal, Jan; Rusten, Espen; Søvik, Åste; Skogmo, Hege Kippenes; Malinen, Eirik

    2013-10-01

    Radiotherapy causes alterations in tumor biology, and non-invasive early assessment of such alterations may become useful for identifying treatment resistant disease. The purpose of the current work is to assess changes in vascular and metabolic features derived from functional imaging of canine head and neck tumors during fractionated radiotherapy. Material and methods. Three dogs with spontaneous head and neck tumors received intensity-modulated radiotherapy (IMRT). Contrast-enhanced cone beam computed tomography (CE-CBCT) at the treatment unit was performed at five treatment fractions. Dynamic (18)FDG-PET (D-PET) was performed prior to the start of radiotherapy, at mid-treatment and at 3-12 weeks after the completion of treatment. Tumor contrast enhancement in the CE-CBCT images was used as a surrogate for tumor vasculature. Vascular and metabolic tumor parameters were further obtained from the D-PET images. Changes in these tumor parameters were assessed, with emphasis on intra-tumoral distributions. Results. For all three patients, metabolic imaging parameters obtained from D-PET decreased from the pre- to the inter-therapy session. Correspondingly, for two of three patients, vascular imaging parameters obtained from both CE-CBCT and D-PET increased. Only one of the tumors showed a clear metabolic response after therapy. No systematic changes in the intra-tumor heterogeneity in the imaging parameters were found. Conclusion. Changes in vascular and metabolic parameters could be detected by the current functional imaging methods. Vascular tumor features from CE-CBCT and D-PET corresponded well. CE-CBCT is a potential method for easy response assessment when the patient is at the treatment unit.

  2. Metabolic Control Analysis aimed at the ribose synthesis pathways of tumor cells: a new strategy for antitumor drug development

    NARCIS (Netherlands)

    Boren, Joan; Montoya, Antonio Ramos; de Atauri, Pedro; Comin-Anduix, Begoña; Cortes, Antonio; Centelles, Josep J.; Frederiks, Wilma M.; van Noorden, Cornelis J. F.; Cascante, Marta

    2002-01-01

    Metabolic control analysis predicts that effects on tumor growth are likely to be obtained with lower concentrations of drug, if an enzyme with a high control coefficient on tumor growth is being inhibited. Here we measure glucose-6-phosphate dehydrogenase (G6PDH) control coefficient on in vivo

  3. Ethanol exposure induces the cancer-associated fibroblast phenotype and lethal tumor metabolism

    Science.gov (United States)

    Sanchez-Alvarez, Rosa; Martinez-Outschoorn, Ubaldo E.; Lin, Zhao; Lamb, Rebecca; Hulit, James; Howell, Anthony; Sotgia, Federica; Rubin, Emanuel; Lisanti, Michael P.

    2013-01-01

    Little is known about how alcohol consumption promotes the onset of human breast cancer(s). One hypothesis is that ethanol induces metabolic changes in the tumor microenvironment, which then enhances epithelial tumor growth. To experimentally test this hypothesis, we used a co-culture system consisting of human breast cancer cells (MCF7) and hTERT-immortalized fibroblasts. Here, we show that ethanol treatment (100 mM) promotes ROS production and oxidative stress in cancer-associated fibroblasts, which is sufficient to induce myofibroblastic differentiation. Oxidative stress in stromal fibroblasts also results in the onset of autophagy/mitophagy, driving the induction of ketone body production in the tumor microenvironment. Interestingly, ethanol has just the opposite effect in epithelial cancer cells, where it confers autophagy resistance, elevates mitochondrial biogenesis and induces key enzymes associated with ketone re-utilization (ACAT1/OXCT1). During co-culture, ethanol treatment also converts MCF7 cells from an ER(+) to an ER(-) status, which is thought to be associated with “stemness,” more aggressive behavior and a worse prognosis. Thus, ethanol treatment induces ketone production in cancer-associated fibroblasts and ketone re-utilization in epithelial cancer cells, fueling tumor cell growth via oxidative mitochondrial metabolism (OXPHOS). This “two-compartment” metabolic model is consistent with previous historical observations that ethanol is first converted to acetaldehyde (which induces oxidative stress) and then ultimately to acetyl-CoA (a high-energy mitochondrial fuel), or can be used to synthesize ketone bodies. As such, our results provide a novel mechanism by which alcohol consumption could metabolically convert “low-risk” breast cancer patients to “high-risk” status, explaining tumor recurrence or disease progression. Hence, our findings have clear implications for both breast cancer prevention and therapy. Remarkably, our results

  4. Can ratio of the biggest tumor diameter to total tumor diameter be a new parameter in the differential diagnosis of agressive and favorable multifocal papillary thyroid microcarcinoma?

    Science.gov (United States)

    Tam, Abbas Ali; Özdemir, Didem; Çuhacı, Neslihan; Başer, Hüsniye; Dirikoç, Ahmet; Aydın, Cevdet; Yazgan, Aylin Kılıç; Ersoy, Reyhan; Çakır, Bekir

    2017-02-01

    In this study, we aimed to evaluate the usefulness of a new parameter -ratio of the biggest tumor diameter to total tumor diameter- for the differentiation of agressive and favorable papillary thyroid microcarcinomas (PTMC). The diameter of the biggest tumor focus was taken as the primary tumor diameter. Total tumor diameter was calculated as the sum of the maximal diameter of each lesion. Ratio of primary tumor diameter to total tumor diameter was defined as tumor diameter ratio (TDR). Positive and negative predictive value, sensitivity and specificity of TDR to predict capsular invasion, extrathyroidal extension (ETE) and lymph node metastasis (LNM) were determined. Mean TDR was significantly lower in multifocal PTMC patients with capsular invasion, ETE, lymphovascular invasion and LNM compared to patients without these features. The sensitivities of TDR for the detection of LNM, ETE and capsular invasion were 100%, 100% and 94.2%, respectively. Specificity of TDR was 86.2% for LNM, 88% for ETE and 94.7% for capsular invasion. Best cut off values of TDR that can predict capsular invasion, ETE and LNM in multifocal PTMC were 0.62, 0.57 and 0.56, respectively. Multifocal papillary thyroid carcinoma patients with capsular invasion, ETE and LNM had significantly lower mean TDR when compared to ones without these features. Decreased TDR was associated with capsular invasion, ETE and LNM in patients with multifocal PTMC and PTC. This new parameter might be particularly helpful for the detection of aggressive behavior in multifocal PTMCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Metabolism of 64Cu and transfer of 125I-MT in the bearing liver ascites tumor (H22) mice

    International Nuclear Information System (INIS)

    Huai Qing; Fang Xingwang; Wang Wenqing

    1998-01-01

    The metabolism of 64 Cu in some tissues of the bearing liver ascites tumor mice has been studied. The liver in normal and tumor bearing mice preferentially accumulates intravenous injection copper, however, the liver in the later mice accumulates much less copper than that of the former. It suggests that in the bearing ascites tumor mice, ascites tumor influences the metabolism of copper. It is found that the content of 64 Cu in the tumor cell is more than 85% in ascites tumor. Gel filtration profile of mice liver homogenate on Sephadex G-75 shows that injected 64 Cu is mainly bound with metallothionein. The tissues uptake of 125 I-labelled (Cd, Zn)-MT which is given in abdominal cavity are also reported. Of the tissues studied, the ascites tumor and kidney accumulate the highest concentration of given 125 I-MT, since over 20% of entire dose accumulated in them. After 125 I-MT is given, it soon goes into ascites tumor, and reaches the maximum in ascites as well as in tumor cell. Therefore, 125 I-MT can go through the membrane of tumor cell and reaches in the tumor cell

  6. Comparison of planar, PET and well-counter measurements of total tumor radioactivity in a mouse xenograft model

    International Nuclear Information System (INIS)

    Green, Michael V.; Seidel, Jurgen; Williams, Mark R.; Wong, Karen J.; Ton, Anita; Basuli, Falguni; Choyke, Peter L.; Jagoda, Elaine M.

    2017-01-01

    Introduction: Quantitative small animal radionuclide imaging studies are often carried out with the intention of estimating the total radioactivity content of various tissues such as the radioactivity content of mouse xenograft tumors exposed to putative diagnostic or therapeutic agents. We show that for at least one specific application, positron projection imaging (PPI) and PET yield comparable estimates of absolute total tumor activity and that both of these estimates are highly correlated with direct well-counting of these same tumors. These findings further suggest that in this particular application, PPI is a far more efficient data acquisition and processing methodology than PET. Methods: Forty-one athymic mice were implanted with PC3 human prostate cancer cells transfected with prostate-specific membrane antigen (PSMA (+)) and one additional animal (for a total of 42) with a control blank vector (PSMA (−)). All animals were injected with [ 18 F] DCFPyl, a ligand for PSMA, and imaged for total tumor radioactivity with PET and PPI. The tumors were then removed, assayed by well counting for total radioactivity and the values between these methods intercompared. Results: PET, PPI and well-counter estimates of total tumor radioactivity were highly correlated (R 2 > 0.98) with regression line slopes near unity (0.95 < slope ≤ 1.02) and intercepts near zero (−0.001 MBq ≤ intercept ≤0.004 MBq). Conclusion: Total mouse xenograft tumor radioactivity can be measured with PET or PPI with an accuracy comparable to well counting if certain experimental and pharmacokinetic conditions are met. In this particular application, PPI is significantly more efficient than PET in making these measurements.

  7. Adenocarcinomas of the esophagus: Response to chemoradiotherapy is associated with decrease of metabolic tumor volume as measured on PET-CT

    International Nuclear Information System (INIS)

    Roedl, Johannes B.; Colen, Rivka R.; Holalkere, Nagaraj S.; Fischman, Alan J.; Choi, Noah C.; Blake, Michael A.

    2008-01-01

    Purpose: We determined whether evaluation of treatment response is feasible by measuring metabolic tumor volume parameters on 18F-FDG (Fluorodeoxyglucose) PET-CT (Positron emission tomography-Computed tomography). We compared the response evaluation based on metabolic tumor volume parameters to a histopathologic and clinical response evaluation (clinical response criteria: RECIST criteria = Response evaluation criteria in solid tumors, and WHO criteria = World health organization). Patients and methods: A total of 51 study subjects with adenocarcinomas (Type I due to Siewert classification) of the esophagus underwent PET-CT scans before and after neoadjuvant chemoradiotherapy. Tumor volume, maximum and mean standardized uptake values (SUV) were assessed before and after chemoradiotherapy. Furthermore, the total lesion glycolysis (TLG) was calculated by multiplying the tumor volume by the mean SUV of the volume. Clinical response evaluation was performed with endoscopic ultrasound and CT using RECIST and WHO criteria. The reference standard for treatment response was the postsurgical histopathology. Results: The decrease of tumor volume between the pre- and post-treatment PET-CT scans was a better predictor of histopathologic response and survival than the decrease of the SUV and of the clinical response evaluation based on RECIST and WHO criteria. The highest accuracy, however, was achieved when using the TLG for the identification of treatment responders. A decrease of the TLG by >78% between pre- and post-therapy scans predicted histopathologic response with a sensitivity and specificity of 91% and 93%, respectively. Conclusions: Tumor volume and TLG can be used to assess treatment response and survival in patients with esophageal adenocarcinoma

  8. Impact of hypoxia and the metabolic microenvironment on radiotherapy of solid tumors. Introduction of a multiinstitutional research project

    International Nuclear Information System (INIS)

    Zips, D.; Petersen, C.; Adam, M.; Molls, M.; Philbrook, C.; Flentje, M.; Haase, A.; Schmitt, P.; Mueller-Klieser, W.; Thews, O.; Walenta, S.; Baumann, M.

    2004-01-01

    Background: recent developments in imaging technology and tumor biology have led to new techniques to detect hypoxia and related alterations of the metabolic microenvironment in tumors. However, whether these new methods can predict radiobiological hypoxia and outcome after fractionated radiotherapy still awaits experimental evaluation. Material and methods: the present article will introduce a multiinstitutional research project addressing the impact of hypoxia and the metabolic microenvironment on radiotherapy of solid tumors. The four laboratories involved are situated at the universities of Dresden, Mainz, Munich and Wuerzburg, Germany. Results: the joint scientific project started to collect data obtained on a set of ten different human tumor xenografts growing in nude mice by applying various imaging techniques to detect tumor hypoxia and related parameters of the metabolic microenvironment. These techniques include magnetic resonance imaging and spectroscopy, metabolic mapping with quantitative bioluminescence and single-photon imaging, histological multiparameter analysis of biochemical hypoxia, perfusion and vasculature, and immunohistochemistry of factors related to angiogenesis, invasion and metastasis. To evaluate the different methods, baseline functional radiobiological data including radiobiological hypoxic fraction and outcome after fractionated irradiation will be determined. Conclusion: besides increasing our understanding of tumor biology, the project will focus on new, clinically applicable strategies for microenvironment profiling and will help to identify those patients that might benefit from targeted interventions to improve tumor oxygenation. (orig.)

  9. Sorafenib metabolism is significantly altered in the liver tumor tissue of hepatocellular carcinoma patient.

    Directory of Open Access Journals (Sweden)

    Ling Ye

    Full Text Available BACKGROUND: Sorafenib, the drug used as first line treatment for hepatocellular carcinoma (HCC, is metabolized by cytochrome P450 (CYP 3A4-mediated oxidation and uridine diphosphate glucuronosyl transferase (UGT 1A9-mediated glucuronidation. Liver diseases are associated with reduced CYP and UGT activities, which can considerably affect drug metabolism, leading to drug toxicity. Thus, understanding the metabolism of therapeutic compounds in patients with liver diseases is necessary. However, the metabolism characteristic of sorafenib has not been systematically determined in HCC patients. METHODS: Sorafenib metabolism was tested in the pooled and individual tumor hepatic microsomes (THLMs and adjacent normal hepatic microsomes (NHLMs of HCC patients (n = 18. Commercial hepatic microsomes (CHLMs were used as a control. In addition, CYP3A4 and UGT1A9 protein expression in different tissues were measured by Western blotting. RESULTS: The mean rates of oxidation and glucuronidation of sorafenib were significantly decreased in the pooled THLMs compared with those in NHLMs and CHLMs. The maximal velocity (Vmax of sorafenib oxidation and glucuronidation were approximately 25-fold and 2-fold decreased in the pooled THLMs, respectively, with unchanged Km values. The oxidation of sorafenib in individual THLMs sample was significantly decreased (ranging from 7 to 67-fold than that in corresponding NHLMs sample. The reduction of glucuronidation in THLMs was observed in 15 out of 18 patients' samples. Additionally, the level of CYP3A4 and UGT1A9 expression were both notably decreased in the pooled THLMs. CONCLUSIONS: Sorafenib metabolism was remarkably decreased in THLMs. This result was associated with the down regulation of the protein expression of CYP3A4 and UGT1A9.

  10. Glucose Metabolism Gene Expression Patterns and Tumor Uptake of 18F-Fluorodeoxyglucose After Radiation Treatment

    International Nuclear Information System (INIS)

    Wilson, George D.; Thibodeau, Bryan J.; Fortier, Laura E.; Pruetz, Barbara L.; Galoforo, Sandra; Baschnagel, Andrew M.; Chunta, John; Oliver Wong, Ching Yee; Yan, Di; Marples, Brian; Huang, Jiayi

    2014-01-01

    Purpose: To investigate whether radiation treatment influences the expression of glucose metabolism genes and compromises the potential use of 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a tool to monitor the early response of head and neck cancer xenografts to radiation therapy (RT). Methods and Materials: Low passage head and neck squamous cancer cells (UT14) were injected to the flanks of female nu/nu mice to generate xenografts. After tumors reached a size of 500 mm 3 they were treated with either sham RT or 15 Gy in 1 fraction. At different time points, days 3, 9, and 16 for controls and days 4, 7, 12, 21, 30, and 40 after irradiation, 2 to 3 mice were assessed with dynamic FDG-PET acquisition over 2 hours. Immediately after the FDG-PET the tumors were harvested for global gene expression analysis and immunohistochemical evaluation of GLUT1 and HK2. Different analytic parameters were used to process the dynamic PET data. Results: Radiation had no effect on key genes involved in FDG uptake and metabolism but did alter other genes in the HIF1α and glucose transport–related pathways. In contrast to the lack of effect on gene expression, changes in the protein expression patterns of the key genes GLUT1/SLC2A1 and HK2 were observed after radiation treatment. The changes in GLUT1 protein expression showed some correlation with dynamic FDG-PET parameters, such as the kinetic index. Conclusion: 18 F-fluorodeoxyglucose positron emission tomography changes after RT would seem to represent an altered metabolic state and not a direct effect on the key genes regulating FDG uptake and metabolism

  11. Prognostic implications of total hemispheric glucose metabolism ratio in cerebro-cerebellar diaschisis

    DEFF Research Database (Denmark)

    Segtnan, Eivind Antonsen; Grupe, Peter; Jarden, Jens Ole

    2017-01-01

    and 9 women aged 35-77 years) with 10 single scans from healthy controls aged 43-75 years. Dedicated 3D-segmentation software was used to obtain total hemispheric glucose metabolic ratios (THGr) by dividing total hemispheric (18)F-fluorodeoxyglucose (FDG) uptake in each diaschitic hemisphere, i.......e., the ipsilateral cerebral hemisphere (THGr(Ce)) and the contralateral cerebellar hemisphere (THGr(Cb)), to its respective contralateral side. Receiver operating characteristic (ROC) analysis was performed to determine optimal cut-offs for combinations of THGr(Ce) and THGr(Cb). Two independent observers obtained...... data for reproducibility analysis, and THGr values were compared with qualitative assessment of diaschisis performed by a PET neuroimaging specialist. RESULTS: Qualitative analysis confirmed cerebro-cerebellar diaschisis in all glioblastoma PET studies performed within one year of death. Healthy...

  12. Functional and oncologic outcomes after excision of the total femur in primary bone tumors: Results with a low cost total femur prosthesis

    Directory of Open Access Journals (Sweden)

    Ajay Puri

    2012-01-01

    Full Text Available Background: The extent of tumor may necessitate resection of the complete femur rarely to achieve adequate oncologic clearance in bone sarcomas. We present our experience with reconstruction in such cases using an indigenously manufactured, low-cost, total femoral prosthesis (TFP. We assessed the complications of the procedure, the oncologic and functional outcomes, and implant survival. Materials and Methods: Eight patients (four males and four females with a mean age of 32 years, operated between December 2003 and June 2009, had a TFP implanted. The diagnosis included osteogenic sarcoma (5, Ewing′s sarcoma (1, and chondrosarcoma (2. Mean followup was 33 months (9-72 months for all and 40 months (24-72 months in survivors. They were evaluated by Musculoskeletal Tumor Society score, implant survival as well as patient survival. Results: There was one local recurrence and five of seven patients are currently alive at the time of last followup. The Musculoskeletal Tumor Society score for patients ranged from 21 to 25 with a mean of 24 (80%. The implant survival was 88% at 5 years with only one TFP needing removal because of infection. Conclusions: A TFP in appropriately indicated patients with malignant bone tumors is oncologically safe. A locally manufactured, cost-effective implant provided consistent and predictable results after excision of the total femur with good functional outcomes.

  13. 31P nuclear magnetic resonance spectroscopy studies of tumor energy metabolism and its relationship to intracapillary oxyhemoglobin saturation status and tumor hypoxia.

    Science.gov (United States)

    Rofstad, E K; DeMuth, P; Fenton, B M; Sutherland, R M

    1988-10-01

    Relationships between tumor bioenergetic status on the one hand and intracapillary oxyhemoglobin (HbO2) saturation status and fraction of radiobiologically hypoxic cells on the other were studied using two murine sarcoma lines (KHT, RIF-1) and two human ovarian carcinoma xenograft lines (MLS, OWI). Tumor energy metabolism was studied in vivo by 31P nuclear magnetic resonance (NMR) spectroscopy and the resonance area ratio (PCr + NTP beta)/Pi was used as parameter for bioenergetic status. Intracapillary HbO2 saturation status reflects the oxygen supply conditions in tumors and was measured in vitro using a cryospectrophotometric method. The KHT, RIF-1, and MLS lines showed decreasing bioenergetic status, i.e., decreasing PCr and NTP beta resonances and an increasing Pi resonance, with increasing tumor volume, whereas the OWI line showed no changes in these resonances during tumor growth. The volume-dependence of the HbO2 saturation status differed similarly among the tumor lines; HbO2 saturation status decreased with increasing tumor volume for the KHT, RIF-1, and MLS lines and was independent of tumor volume for the OWI line. Moreover, linear correlations were found between bioenergetic status and HbO2 saturation status for individual tumors of the KHT, RIF-1, and MLS lines. These observations together indicated a direct relationship between 31P-NMR spectral parameters and tumor oxygen supply conditions. However, this relationship was not identical for the different tumor lines, suggesting that it was influenced by intrinsic properties of the tumor cells such as rate of respiration and ability to survive under hypoxia. Similarly, there was no correlation between bioenergetic status and fraction of radiobiologically hypoxic cells across the four tumor lines. This indicates that 31P-NMR spectroscopy data have to be supplemented with other data, e.g., rate of oxygen consumption, cell survival time under hypoxic stress, and/or fraction of metabolically active

  14. New Aspects of an Old Drug – Diclofenac Targets MYC and Glucose Metabolism in Tumor Cells

    Science.gov (United States)

    Gottfried, Eva; Lang, Sven A.; Renner, Kathrin; Bosserhoff, Anja; Gronwald, Wolfram; Rehli, Michael; Einhell, Sabine; Gedig, Isabel; Singer, Katrin; Seilbeck, Anton; Mackensen, Andreas; Grauer, Oliver; Hau, Peter; Dettmer, Katja; Andreesen, Reinhard; Oefner, Peter J.; Kreutz, Marina

    2013-01-01

    Non-steroidal anti-inflammatory drugs such as diclofenac exhibit potent anticancer effects. Up to now these effects were mainly attributed to its classical role as COX-inhibitor. Here we show novel COX-independent effects of diclofenac. Diclofenac significantly diminished MYC expression and modulated glucose metabolism resulting in impaired melanoma, leukemia, and carcinoma cell line proliferation in vitro and reduced melanoma growth in vivo. In contrast, the non-selective COX inhibitor aspirin and the COX-2 specific inhibitor NS-398 had no effect on MYC expression and glucose metabolism. Diclofenac significantly decreased glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and monocarboxylate transporter 1 (MCT1) gene expression in line with a decrease in glucose uptake and lactate secretion. A significant intracellular accumulation of lactate by diclofenac preceded the observed effect on gene expression, suggesting a direct inhibitory effect of diclofenac on lactate efflux. While intracellular lactate accumulation impairs cellular proliferation and gene expression, it does not inhibit MYC expression as evidenced by the lack of MYC regulation by the MCT inhibitor α-cyano-4-hydroxycinnamic acid. Finally, in a cell line with a tetracycline-regulated c-MYC gene, diclofenac decreased proliferation both in the presence and absence of c-MYC. Thus, diclofenac targets tumor cell proliferation via two mechanisms, that is inhibition of MYC and lactate transport. Based on these results, diclofenac holds potential as a clinically applicable MYC and glycolysis inhibitor supporting established tumor therapies. PMID:23874405

  15. Effect of elevated total CoA levels on metabolic pathways in cultured hepatocytes

    International Nuclear Information System (INIS)

    Steffen, C.A.; Smith, C.M.

    1987-01-01

    Livers from fasted rats have 30% higher total CoA levels than fed rats. To determine whether this increase of total CoA influences metabolism, the rates of gluconeogenesis, fatty acid oxidation and ketogenesis were measured in hepatocytes with cyanamide (CYM) or pantothenate (PA) deficient medium used to vary total CoA levels independently of hormonal status. Primary cultures of rat hepatocytes were incubated 14 hrs with Bt 2 cAMP, dexamethasone + theophylline in PA deficient medium or with CYM (500 μM) + PA, rinsed and preincubated 0.5 hr to remove the CYM. Hepatocytes treated with CYM had total CoA levels 10-24% higher than PA deficient cells and lower rates of glucose production from lactate + pyruvate (L/P) or from alanine (0.23 +/- 0.05 and 0.089 +/- 0.02 μm/mg protein, respectively in CYM treated cells compared to 0.33 +/- 0.06 and 0.130 +/- 0.006 in PA deficient cells). This decrease was not due to CYM per se, as the direct addition of CYM stimulated glucose production from L/P. CYM treated cells with 15-40% higher total CoA and 30% higher fatty acyl-CoA levels had the same rates of [ 14 C]-palmitate oxidation as PA deficient cells. However, rates of ketogenesis were lower in CYM treated cells (163 +/- 11 nm/mg compared to 217 +/- 14 nm/mg protein). These results suggest that physiological alterations of hepatic total CoA levels are not necessary for fasting rates of gluconeogenesis, fatty acid oxidation and ketogenesis

  16. Noninvasive Evaluation of Metabolic Tumor Volume in Lewis Lung Carcinoma Tumor-Bearing C57BL/6 Mice with Micro-PET and the Radiotracers 18F-Alfatide and 18F-FDG: A Comparative Analysis.

    Directory of Open Access Journals (Sweden)

    Yu-Chun Wei

    Full Text Available To explore the value of a new simple lyophilized kit for labeling PRGD2 peptide (18F-ALF-NOTA-PRGD2, denoted as 18F-alfatide in the determination of metabolic tumor volume (MTV with micro-PET in lewis lung carcinoma (LLC tumor-bearing C57BL/6 mice verified by pathologic examination and compared with those using 18F-fluorodeoxyglucose (FDG PET.All LLC tumor-bearing C57BL/6 mice underwent two attenuation-corrected whole-body micro-PET scans with the radiotracers 18F-alfatide and 18F-FDG within two days. 18F-alfatide metabolic tumor volume (VRGD and 18F-FDG metabolic tumor volume (VFDG were manually delineated slice by slice on PET images. Pathologic tumor volume (VPath was measured in vitro after the xenografts were removed.A total of 37 mice with NSCLC xenografts were enrolled and 33 of them underwent 18F-alfatide PET, and 35 of them underwent 18F-FDG PET and all underwent pathological examination. The mean ± standard deviation of VPath, VRGD, and VFDG were 0.59±0.32 cm3 (range,0.13~1.64 cm3, 0.61±0.37 cm3 (range,0.15~1.86 cm3, and 1.24±0.53 cm3 (range,0.17~2.20 cm3, respectively. VPath vs. VRGD, VPath vs. VFDG, and VRGD vs. VFDG comparisons were t = -0.145, P = 0.885, t = -6.239, P<0.001, and t = -5.661, P<0.001, respectively. No significant difference was found between VPath and VRGD. VFDG was much larger than VRGD and VPath. VRGD seemed more approximate to the pathologic gross tumor volume. Furthermore, VPath was more strongly correlated with VRGD (R = 0.964,P<0.001 than with VFDG (R = 0.584,P<0.001.18F-alfatide PET provided a better estimation of gross tumor volume than 18F-FDG PET in LLC tumor-bearing C57BL/6 mice.

  17. PPARα inhibition modulates multiple reprogrammed metabolic pathways in kidney cancer and attenuates tumor growth.

    Science.gov (United States)

    Abu Aboud, Omran; Donohoe, Dallas; Bultman, Scott; Fitch, Mark; Riiff, Tim; Hellerstein, Marc; Weiss, Robert H

    2015-06-01

    Kidney cancer [renal cell carcinoma (RCC)] is the sixth-most-common cancer in the United States, and its incidence is increasing. The current progression-free survival for patients with advanced RCC rarely extends beyond 1-2 yr due to the development of therapeutic resistance. We previously identified peroxisome proliferator-activating receptor-α (PPARα) as a potential therapeutic target for this disease and showed that a specific PPARα antagonist, GW6471, induced apoptosis and cell cycle arrest at G0/G1 in RCC cell lines associated with attenuation of cell cycle regulatory proteins. We now extend that work and show that PPARα inhibition attenuates components of RCC metabolic reprogramming, capitalizing on the Warburg effect. The specific PPARα inhibitor GW6471, as well as a siRNA specific to PPARα, attenuates the enhanced fatty acid oxidation and oxidative phosphorylation associated with glycolysis inhibition, and PPARα antagonism also blocks the enhanced glycolysis that has been observed in RCC cells; this effect did not occur in normal human kidney epithelial cells. Such cell type-specific inhibition of glycolysis corresponds with changes in protein levels of the oncogene c-Myc and has promising clinical implications. Furthermore, we show that treatment with GW6471 results in RCC tumor growth attenuation in a xenograft mouse model, with minimal obvious toxicity, a finding associated with the expected on-target effects on c-Myc. These studies demonstrate that several pivotal cancer-relevant metabolic pathways are inhibited by PPARα antagonism. Our data support the concept that targeting PPARα, with or without concurrent inhibition of glycolysis, is a potential novel and effective therapeutic approach for RCC that targets metabolic reprogramming in this tumor.

  18. Comparison of metabolic ratios of urinary estrogens between benign and malignant thyroid tumors in postmenopausal women

    Science.gov (United States)

    2013-01-01

    Background Estrogen metabolism may be associated with the pathophysiological development of papillary thyroid carcinoma (PTC). Methods To evaluate the differential estrogen metabolism between benign and malignant PTCs, estrogen profiling by gas chromatography–mass spectrometry was applied to urine samples from postmenopausal patients with 9 benign tumors and 18 malignant stage I and III/IV PTCs. Results The urinary concentration of 2-methoxyestradiol was significantly lower in the stage I malignant patients (3.5-fold; P 3.5-fold difference; P < 0.002). In particular, the estriol/16α-OH-estrone ratio differentiated between the benign and early-stage malignant patients (P < 0.01). Conclusions Increased 16α-hydroxylation and/or a decreased 2-/16α-ratio, as well increased reductive 17β-HSD, with regard to estrogen metabolism could provide potential biomarkers. The devised profiles could be useful for differentiating malignant thyroid carcinomas from benign adenomas in postmenopausal women. PMID:24156385

  19. Association between textural and morphological tumor indices on baseline PET-CT and early metabolic response on interim PET-CT in bulky malignant lymphomas.

    Science.gov (United States)

    Ben Bouallègue, Fayçal; Tabaa, Yassine Al; Kafrouni, Marilyne; Cartron, Guillaume; Vauchot, Fabien; Mariano-Goulart, Denis

    2017-09-01

    We investigated whether metabolic, textural, and morphological tumoral indices evaluated on baseline PET-CT were predictive of early metabolic response on interim PET-CT in a cohort of patients with bulky Hodgkin and non-Hodgkin malignant lymphomas. This retrospective study included 57 patients referred for initial PET-CT examination. In-house dedicated software was used to delineate tumor contours using a fixed 30% threshold of SUV max and then to compute tumoral metabolic parameters (SUV max, mean, peak, standard deviation, skewness and kurtosis, metabolic tumoral volume (MTV), total lesion glycolysis, and area under the curve of the cumulative histogram), textural parameters (Moran's and Geary's indices, energy, entropy, contrast, correlation derived from the gray-level co-occurrence matrix, area under the curve of the power spectral density, auto-correlation distance, and granularity), and shape parameters (surface, asphericity, convexity, surfacic extension, and 2D and 3D fractal dimensions). Early metabolic response was assessed on interim PET-CT using the Deauville 5-point scale and patients were ranked according to the Lugano classification as complete or not complete metabolic responders. The impact of the segmentation method (alternate threshold at 41%) and image resolution (Gaussian postsmoothing of 3, 5, and 7 mm) was investigated. The association of the proposed parameters with early response was assessed in univariate and multivariate analyses. Their added predictive value was explored using supervised classification by support vector machines (SVM). We evaluated in leave-one-out cross-validation three SVMs admitting as input features (a) MTV, (b) MTV + histological type, and (c) MTV + histology + relevant texture/shape indices. Features associated with complete metabolic response were low MTV (P = 0.01), low TLG (P = 0.003), high power spectral density AUC (P = 0.007), high surfacic extension (P = 0.006), low 2D fractal dimension (P

  20. Assessment of therapeutic response and treatment planning for brain tumors using metabolic and physiological MRI.

    Science.gov (United States)

    Nelson, Sarah J

    2011-07-01

    MRI is routinely used for diagnosis, treatment planning and assessment of response to therapy for patients with glioma. Gliomas are spatially heterogeneous and infiltrative lesions that are quite variable in terms of their response to therapy. Patients classified as having low-grade histology have a median overall survival of 7 years or more, but need to be monitored carefully to make sure that their tumor does not upgrade to a more malignant phenotype. Patients with the most aggressive grade IV histology have a median overall survival of 12-15 months and often undergo multiple surgeries and adjuvant therapies in an attempt to control their disease. Despite improvements in the spatial resolution and sensitivity of anatomic images, there remain considerable ambiguities in the interpretation of changes in the size of the gadolinium-enhancing lesion on T(1) -weighted images as a measure of treatment response, and in differentiating between treatment effects and infiltrating tumor within the larger T(2) lesion. The planning of focal therapies, such as surgery, radiation and targeted drug delivery, as well as a more reliable assessment of the response to therapy, would benefit considerably from the integration of metabolic and physiological imaging techniques into routine clinical MR examinations. Advanced methods that have been shown to provide valuable data for patients with glioma are diffusion, perfusion and spectroscopic imaging. Multiparametric examinations that include the acquisition of such data are able to assess tumor cellularity, hypoxia, disruption of normal tissue architecture, changes in vascular density and vessel permeability, in addition to the standard measures of changes in the volume of enhancing and nonenhancing anatomic lesions. This is particularly critical for the interpretation of the results of Phase I and Phase II clinical trials of novel therapies, which are increasingly including agents that are designed to have anti-angiogenic and anti

  1. Joint association of physical activity in leisure and total sitting time with metabolic syndrome amongst 15,235 Danish adults

    DEFF Research Database (Denmark)

    Petersen, Christina Bjørk; Nielsen, Asser Jon; Bauman, Adrian

    2014-01-01

    and total daily sitting time were assessed by self-report in 15,235 men and women in the Danish Health Examination Survey 2007-2008. Associations between leisure time physical activity, total sitting time and metabolic syndrome were investigated in logistic regression analysis. RESULTS: Adjusted odds ratios......BACKGROUND: Recent studies suggest that physical inactivity as well as sitting time are associated with metabolic syndrome. Our aim was to examine joint associations of leisure time physical activity and total daily sitting time with metabolic syndrome. METHODS: Leisure time physical activity...... (OR) for metabolic syndrome were 2.14 (95% CI: 1.88-2.43) amongst participants who were inactive in leisure time compared to the most active, and 1.42 (95% CI: 1.26-1.61) amongst those who sat for ≥10h/day compared to physical activity, sitting time...

  2. Functional Response of Tumor Vasculature to PaCO2: Determination of Total and Microvascular Blood Volume by MRI

    Directory of Open Access Journals (Sweden)

    Scott D. Packard

    2003-07-01

    Full Text Available In order to identify differences in functional activity, we compared the reactivity of glioma vasculature and the native cerebral vasculature to both dilate and constrict in response to altered PaCO2. Gliomas were generated by unilateral implantation of U87MGdEGFR human glioma tumor cells into the striatum of adult female athymic rats. Relative changes in total and microvascular cerebral blood volume were determined by steady state contrast agent-enhanced magnetic resonance imaging for transitions from normocarbia to hypercarbia and hypocarbia. Although hypercarbia induced a significant increase in both total and microvascular blood volume in normal brain and glioma, reactivity of glioma vasculature was significantly blunted in comparison to normal striatum; glioma total CBV increased by 0.6±0.1%/mm Hg CO2 whereas normal striatum increased by 1.5±0.2%/mm Hg CO2, (P < .0001, group t-test. Reactivity of microvascular blood volume was also significantly blunted. In contrast, hypocarbia decreased both total and microvascular blood volumes more in glioma than in normal striatum. These results indicate that cerebral blood vessels derived by tumor-directed angiogenesis do retain reactivity to CO2. Furthermore, reduced reactivity of tumor vessels to a single physiological perturbation, such as hypercarbia, should not be construed as a generalized reduction of functional activity of the tumor vascular bed.

  3. Role of interleukin 1 and tumor necrosis factor on energy metabolism in rabbits

    International Nuclear Information System (INIS)

    Tredget, E.E.; Yu, Y.M.; Zhong, S.; Burini, R.; Okusawa, S.; Gelfand, J.A.; Dinarello, C.A.; Young, V.R.; Burke, J.F.

    1988-01-01

    A study of the combined effects of intravenous infusion of the recombinant cytokines beta-interleukin 1 (IL-1) and alpha-tumor necrosis factor (TNF) on energy substrate metabolism in awake, conditioned, adult rabbits was performed. After a 2-h basal or control period, 48-h fasted rabbits were administered TNF and IL-1 as a bolus (5 micrograms/kg) followed by a continuous intravenous infusion (25 ng.kg-1.min-1) for 3 h. Significant increases in plasma lactate (P less than 0.01), glucose (P less than 0.01), and triglycerides (P less than 0.05) occurred during the combined infusion of IL-1 and TNF, whereas neither cytokine alone had no effect. There was a 33% increase in the rate of glucose appearance (P less than 0.05), but glucose clearance was not altered compared with the control period. Glucose oxidation increased during the combined cytokine infusion period and glucose recycling increased by 600% (P less than 0.002). Lactic acidosis and decreased oxygen consumption, as a result of the cytokine infusions, indicated development of anaerobic glycolytic metabolism. A reduction in the activity state of hepatic mitochondrial pyruvate dehydrogenase (65 vs. 82% in control animals, P less than 0.05) was consistent with the observed increase in anaerobic glycolysis. Thus the combined infusion of IL-1 and TNF in rabbits produces metabolic manifestations seen in severe injury and sepsis in human patients and, as such, may account for the profound alterations of energy metabolism seen in these conditions

  4. Role of interleukin 1 and tumor necrosis factor on energy metabolism in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Tredget, E.E.; Yu, Y.M.; Zhong, S.; Burini, R.; Okusawa, S.; Gelfand, J.A.; Dinarello, C.A.; Young, V.R.; Burke, J.F.

    1988-12-01

    A study of the combined effects of intravenous infusion of the recombinant cytokines beta-interleukin 1 (IL-1) and alpha-tumor necrosis factor (TNF) on energy substrate metabolism in awake, conditioned, adult rabbits was performed. After a 2-h basal or control period, 48-h fasted rabbits were administered TNF and IL-1 as a bolus (5 micrograms/kg) followed by a continuous intravenous infusion (25 ng.kg-1.min-1) for 3 h. Significant increases in plasma lactate (P less than 0.01), glucose (P less than 0.01), and triglycerides (P less than 0.05) occurred during the combined infusion of IL-1 and TNF, whereas neither cytokine alone had no effect. There was a 33% increase in the rate of glucose appearance (P less than 0.05), but glucose clearance was not altered compared with the control period. Glucose oxidation increased during the combined cytokine infusion period and glucose recycling increased by 600% (P less than 0.002). Lactic acidosis and decreased oxygen consumption, as a result of the cytokine infusions, indicated development of anaerobic glycolytic metabolism. A reduction in the activity state of hepatic mitochondrial pyruvate dehydrogenase (65 vs. 82% in control animals, P less than 0.05) was consistent with the observed increase in anaerobic glycolysis. Thus the combined infusion of IL-1 and TNF in rabbits produces metabolic manifestations seen in severe injury and sepsis in human patients and, as such, may account for the profound alterations of energy metabolism seen in these conditions.

  5. Characteristics Studies of 125I- and total PSA antibody's Binding with prostate specific antigen (PSA) in Human Uterus Tumors

    International Nuclear Information System (INIS)

    Al-Mudaffar, S.; Al-Salihi, J.

    2005-01-01

    Two groups of uterus tumors (benign and malignant) postmenopausal patients were used to investigate the presence of prostate specific antigen (PSA). Preliminary experiments were performed to follow the binding of '1 25 I-anti total PSA antibody with PSA in uterus tissues homogenates of the two groups with their corresponding antigen and found to be (8.8,7.1%) for benign and malignant tumors, respectively. An Immuno Radio Metric Assay (IRMA) procedure was developed for measuring PSA in benign and malignant uterus tumors homogenates. The optimum conditions of the binding of 125 I-anti total PSA antibody with PSA were as follows: PSA concentration (150,200 μg protein),tracer antibody concentration (125,250 μg protein), p H (7.6,7.2), temp (15,25?C) and time (1.5 hrs) for postmenopausal benign and malignant uterus tumors tissue homogenates, respectively. The use of different concentrations of Na + and Mg 2+ ions were shown to cause an increase in the binding at concentration of (125,75 mΜ) of Na 1+ ions (75,225 mΜ) of Mg 2+ ions for benign and malignant uterus tumors homogenates, respectively, while the use of different concentrations of urea and polyethylene glycol (PEG) Caused a decrease in the binding with the increase in the concentration of each of urea and PEG in the both cases

  6. Total Body Capacitance for Estimating Human Basal Metabolic Rate in an Egyptian Population

    Science.gov (United States)

    M. Abdel-Mageed, Samir; I. Mohamed, Ehab

    2016-01-01

    Determining basal metabolic rate (BMR) is important for estimating total energy needs in the human being yet, concerns have been raised regarding the suitability of sex-specific equations based on age and weight for its calculation on an individual or population basis. It has been shown that body cell mass (BCM) is the body compartment responsible for BMR. The objectives of this study were to investigate the relationship between total body capacitance (TBC), which is considered as an expression for BCM, and BMR and to develop a formula for calculating BMR in comparison with widely used equations. Fifty healthy nonsmoking male volunteers [mean age (± SD): 24.93 ± 4.15 year and body mass index (BMI): 25.63 ± 3.59 kg/m2] and an equal number of healthy nonsmoking females matched for age and BMI were recruited for the study. TBC and BMR were measured for all participants using octopolar bioelectric impedance analysis and indirect calorimetry techniques, respectively. A significant regressing equation based on the covariates: sex, weight, and TBC for estimating BMR was derived (R=0.96, SEE=48.59 kcal, and P<0.0001), which will be useful for nutritional and health status assessment for both individuals and populations. PMID:27127453

  7. Dietary fat modulation of mammary tumor growth and metabolism demonstrated by 31P-nuclear magnetic resonance

    International Nuclear Information System (INIS)

    Erickson, K.L.; Buckman, D.K.; Hubbard, N.E.; Ross, B.

    1986-01-01

    The relationship of dietary fat concentration and saturation on the growth and metabolic activity of line 168 was studied using syngeneic mice fed 6 experimental diets before and during tumor growth. Tumor latency was significantly greater for mice fed a diet containing the minimum of essential fatty acids (EFA, 0.5% corn oil) or 8% coconut oil (SF) than for mice fed 8 or 20% safflower oil (PUF) or 20% SF. Changes in dietary fat resulted in alterations of tumor cell and serum fatty acid composition but not the number of inflammatory cells infiltrating the tumor. 31 P-surface coil NMR was used to measure possible changes in tumor metabolism in vivo. Although pH decreased from 7.2 to 6.6 as the tumor volume increased, there was no difference in pH among dietary groups. There was an inverse relationship between both sugar phosphate (SP)/Pi and ATP/Pi ratios and tumor volume; those ratios for mice fed an EFA deficient or minimal EFA diet decreased at a different rate than ratios for mice fed diets with additional fat. Tumors of mice fed diets containing no or a low level (0.3%) of 18:2 had higher SP/ATP ratios than mice fed diets containing a moderate level (∼ 4%) of 18:2. Thus, high levels of dietary fat had a significant effect on promotion of mammary tumors during early stages of tumor growth. Differences in tumor volume associated with dietary fat may be related to changes in the levels of high energy phosphate metabolites

  8. Anti-tumor activity of metformin: from metabolic and epigenetic perspectives

    Science.gov (United States)

    Zhai, Yansheng; Tong, Chong; Liu, Min; Ma, Lixin; Yu, Xiaolan; Li, Shanshan

    2017-01-01

    Metformin has been used to treat type 2 diabetes for over 50 years. Epidemiological, preclinical and clinical studies suggest that metformin treatment reduces cancer incidence in diabetes patients. Due to its potential as an anti-cancer agent and its low cost, metformin has gained intense research interest. Its traditional anti-cancer mechanisms involve both indirect and direct insulin-dependent pathways. Here, we discussed the anti-tumor mechanism of metformin from the aspects of cell metabolism and epigenetic modifications. The effects of metformin on anti-cancer immunity and apoptosis were also described. Understanding these mechanisms will shed lights on application of metformin in clinical trials and development of anti-cancer therapy. PMID:27902459

  9. Increased Serotonin Signaling Contributes to the Warburg Effect in Pancreatic Tumor Cells Under Metabolic Stress and Promotes Growth of Pancreatic Tumors in Mice.

    Science.gov (United States)

    Jiang, Shu-Heng; Li, Jun; Dong, Fang-Yuan; Yang, Jian-Yu; Liu, De-Jun; Yang, Xiao-Mei; Wang, Ya-Hui; Yang, Min-Wei; Fu, Xue-Liang; Zhang, Xiao-Xin; Li, Qing; Pang, Xiu-Feng; Huo, Yan-Miao; Li, Jiao; Zhang, Jun-Feng; Lee, Ho-Young; Lee, Su-Jae; Qin, Wen-Xin; Gu, Jian-Ren; Sun, Yong-Wei; Zhang, Zhi-Gang

    2017-07-01

    Desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors. We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras G12D/+ /Trp53 R172H/+ /Pdx1-Cre (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples. We also analyzed expression levels of proteins involved in 5-HT synthesis and degradation by immunohistochemical analysis of a tissue microarray containing 311 PDAC specimens, and associated expression levels with patient survival times. 5-HT level in 14 matched PDAC tumor and non-tumor tissues were analyzed by ELISA. PDAC cell lines were incubated with 5-HT and cell survival and apoptosis were measured. We analyzed expression of the 5-HT receptor HTR2B in PDAC cells and effects of receptor agonists and antagonists, as well as HTR2B knockdown with small hairpin RNAs. We determined the effects of 5-HT stimulation on gene expression profiles of BxPC-3 cells. Regulation of glycolysis by 5-HT signaling via HTR2B was assessed by immunofluorescence and immunoprecipitation analyses, as well as by determination of the extracellular acid ratio, glucose consumption, and lactate production. Primary PDACs, with or without exposure to SB204741 (a selective antagonist of HTR2B), were grown as xenograft tumors in mice, and SB204741 was administered to tumor-bearing KPC mice; tumor growth and metabolism were measured by imaging analyses. In immunohistochemical analysis of a tissue microarray of PDAC specimens, increased levels of TPH1 and decreased level of MAOA, which regulate 5-HT synthesis and degradation, correlated with stage and size of PDACs and shorter patient survival time. We found levels

  10. Genetic variation in hormone metabolizing genes and risk of testicular germ cell tumors.

    Science.gov (United States)

    Figueroa, Jonine D; Sakoda, Lori C; Graubard, Barry I; Chanock, Stephen; Rubertone, Mark V; Erickson, R Loren; McGlynn, Katherine A

    2008-11-01

    Testicular germ cell tumors (TGCT) that arise in young men are composed of two histologic types, seminomas and nonseminomas. Risk patterns for the two types appear to be similar and may be related to either endogenous or exogenous hormonal exposures in utero. Why similar risk patterns would result in different histologic types is unclear, but could be related to varying genetic susceptibility profiles. Genetic variation in hormone metabolizing genes could potentially modify hormonal exposures, and thereby affect which histologic type a man develops. To examine this hypothesis, 33 single nucleotide polymorphisms (SNPs) in four hormone metabolism candidate genes (CYP1A1, CYP17A1, HSD17B1, HSD17B4) and the androgen receptor gene (AR) were genotyped. Associations with TGCT were evaluated among 577 TGCT cases (254 seminoma, 323 nonseminoma) and 707 controls from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study. There were no significant associations with TGCT overall based on a test using an additive model. However, compared to homozygotes of the most common allele, two nonredundant SNPs in CYP1A1 were inversely associated with nonseminoma: CYP1A1 promoter SNP rs4886605 OR = 0.75 (95% CI = 0.54-1.04) among the heterozygotes and OR = 0.37, 95% CI = 0.12-1.11 among the homozygotes with a p-value for trend = 0.02; rs2606345 intron 1 SNP, OR = 0.69 (95% CI = 0.51-0.93) among heterozygotes and OR = 0.70 (95% CI = 0.42-1.17) among homozygotes, with a p-value for trend = 0.02. Caution in interpretation is warranted until findings are replicated in other studies; however, the results suggest that genetic variation in CYP1A1 may be associated with nonseminoma.

  11. Metabolic Profiling of Total Physical Activity and Sedentary Behavior in Community-Dwelling Men.

    Directory of Open Access Journals (Sweden)

    Kota Fukai

    Full Text Available Physical activity is known to be preventive against various non-communicable diseases. We investigated the relationship between daily physical activity level and plasma metabolites using a targeted metabolomics approach in a population-based study.A total of 1,193 participants (male, aged 35 to 74 years with fasting blood samples were selected from the baseline survey of a cohort study. Information on daily total physical activity, classified into four levels by quartile of metabolic equivalent scores, and sedentary behavior, defined as hours of sitting per day, was collected through a self-administered questionnaire. Plasma metabolite concentrations were quantified by capillary electrophoresis mass spectrometry method. We performed linear regression analysis models with multivariable adjustment and corrected p-values for multiple testing in the original population (n = 808. The robustness of the results was confirmed by replication analysis in a separate population (n = 385 created by random allocation.Higher levels of total physical activity were associated with various metabolite concentrations, including lower concentrations of amino acids and their derivatives, and higher concentrations of pipecolate (FDR p <0.05 in original population. The findings persisted after adjustment for age, body mass index, smoking, alcohol intake, and energy intake. Isoleucine, leucine, valine, 4-methyl-2-oxoisopentanoate, 2-oxoisopentanoate, alanine, and proline concentrations were lower with a shorter sitting time.Physical activity is related to various plasma metabolites, including known biomarkers for future insulin resistance or type 2 diabetes. These metabolites might potentially play a key role in the protective effects of higher physical activity and/or less sedentary behavior on non-communicable diseases.

  12. Metabolomics by proton nuclear magnetic resonance spectroscopy of the response to chloroethylnitrosourea reveals drug efficacy and tumor adaptive metabolic pathways.

    Science.gov (United States)

    Morvan, Daniel; Demidem, Aicha

    2007-03-01

    Metabolomics of tumors may allow discovery of tumor biomarkers and metabolic therapeutic targets. Metabolomics by two-dimensional proton high-resolution magic angle spinning nuclear magnetic resonance spectroscopy was applied to investigate metabolite disorders following treatment by chloroethylnitrosourea of murine B16 melanoma (n = 33) and 3LL pulmonary carcinoma (n = 31) in vivo. Treated tumors of both types resumed growth after a delay. Nitrosoureas provoke DNA damage but the metabolic consequences of genotoxic stress are little known yet. Although some differences were observed in the metabolite profile of untreated tumor types, the prominent metabolic features of the response to nitrosourea were common to both. During the growth inhibition phase, there was an accumulation of glucose (more than x10; P < 0.05), glutamine (x3 to 4; P < 0.01), and aspartate (x2 to 5; P < 0.01). This response testified to nucleoside de novo synthesis down-regulation and drug efficacy. However, this phase also involved the increase in alanine (P < 0.001 in B16 melanoma), the decrease in succinate (P < 0.001), and the accumulation of serine-derived metabolites (glycine, phosphoethanolamine, and formate; P < 0.01). This response witnessed the activation of pathways implicated in energy production and resumption of nucleotide de novo synthesis, thus metabolic pathways of DNA repair and adaptation to treatment. During the growth recovery phase, it remained polyunsaturated fatty acid accumulation (x1.5 to 2; P < 0.05) and reduced utilization of glucose compared with glutamine (P < 0.05), a metabolic fingerprint of adaptation. Thus, this study provides the proof of principle that metabolomics of tumor response to an anticancer agent may help discover metabolic pathways of drug efficacy and adaptation to treatment.

  13. Scaling dynamic response and destructive metabolism in an immunosurveillant anti-tumor system modulated by different external periodic interventions.

    Directory of Open Access Journals (Sweden)

    Yuanzhi Shao

    Full Text Available On the basis of two universal power-law scaling laws, i.e. the scaling dynamic hysteresis in physics and the allometric scaling metabolism in biosystem, we studied the dynamic response and the evolution of an immunosurveillant anti-tumor system subjected to a periodic external intervention, which is equivalent to the scheme of a radiotherapy or chemotherapy, within the framework of the growth dynamics of tumor. Under the modulation of either an abrupt or a gradual change external intervention, the population density of tumors exhibits a dynamic hysteresis to the intervention. The area of dynamic hysteresis loop characterizes a sort of dissipative-therapeutic relationship of the dynamic responding of treated tumors with the dose consumption of accumulated external intervention per cycle of therapy. Scaling the area of dynamic hysteresis loops against the intensity of an external intervention, we deduced a characteristic quantity which was defined as the theoretical therapeutic effectiveness of treated tumor and related with the destructive metabolism of tumor under treatment. The calculated dose-effectiveness profiles, namely the dose cumulant per cycle of intervention versus the therapeutic effectiveness, could be well scaled into a universal quadratic formula regardless of either an abrupt or a gradual change intervention involved. We present a new concept, i.e., the therapy-effect matrix and the dose cumulant matrix, to expound the new finding observed in the growth and regression dynamics of a modulated anti-tumor system.

  14. Effect of selenodiglutathione on the metabolism of canine mammary tumor cells

    International Nuclear Information System (INIS)

    Fico-Santoro, M.; Lebowitz, A.; Milner, J.A.

    1986-01-01

    Selenodiglutathione (SDG) has been shown to be an effective inhibitor of tumor growth. The present studies were designed to evaluate altered metabolism in canine mammary tumor cells (CMT-13) exposed to various concentrations of SDG. Addition of SDG at 0.025 μg Se/ml did not inhibit growth of CMT-13 cells after 24 h of incubation. At this concentration of SDG, approximately 25% of 75 Se- 35 S-SDG was retained in these tumor cells after 24 h of incubation. The nuclear fraction contained 96% of the 75 Se and 35 S radioactivity. The ratio of 75 Se to 35 S was 1 to 4.5 in the whole cell and in the nuclear fraction. SDG increased glutathione peroxidase activity by 40% compared to CMT-13 cells not exposed to SDG. Glutathione reductase activity was decreased by 63% by the addition of SDG. In addition, supplemental SDG resulted in a 55% decrease in GSH content but did not alter GSSG concentrations. After 4d of incubation, SDG at 0.1 and 0.5 μg Se/ml caused a 43 and 58% inhibition of growth of CMT-13 cells. Addition of GSH (100μM) partially prevented, 68% and 54%, the growth inhibition caused by SDG at concentrations of 0.1 and 0.5 μg Se per ml respectively during the 4d incubation period. Preincubation of CMT-13 cells with GSH for 48 h before addition of SDG (0.5 μg Se/ml) completely prevented the growth inhibition caused by this seleno-compound

  15. Tumor image signatures and habitats: a processing pipeline of multimodality metabolic and physiological images.

    Science.gov (United States)

    You, Daekeun; Kim, Michelle M; Aryal, Madhava P; Parmar, Hemant; Piert, Morand; Lawrence, Theodore S; Cao, Yue

    2018-01-01

    To create tumor "habitats" from the "signatures" discovered from multimodality metabolic and physiological images, we developed a framework of a processing pipeline. The processing pipeline consists of six major steps: (1) creating superpixels as a spatial unit in a tumor volume; (2) forming a data matrix [Formula: see text] containing all multimodality image parameters at superpixels; (3) forming and clustering a covariance or correlation matrix [Formula: see text] of the image parameters to discover major image "signatures;" (4) clustering the superpixels and organizing the parameter order of the [Formula: see text] matrix according to the one found in step 3; (5) creating "habitats" in the image space from the superpixels associated with the "signatures;" and (6) pooling and clustering a matrix consisting of correlation coefficients of each pair of image parameters from all patients to discover subgroup patterns of the tumors. The pipeline was applied to a dataset of multimodality images in glioblastoma (GBM) first, which consisted of 10 image parameters. Three major image "signatures" were identified. The three major "habitats" plus their overlaps were created. To test generalizability of the processing pipeline, a second image dataset from GBM, acquired on the scanners different from the first one, was processed. Also, to demonstrate the clinical association of image-defined "signatures" and "habitats," the patterns of recurrence of the patients were analyzed together with image parameters acquired prechemoradiation therapy. An association of the recurrence patterns with image-defined "signatures" and "habitats" was revealed. These image-defined "signatures" and "habitats" can be used to guide stereotactic tissue biopsy for genetic and mutation status analysis and to analyze for prediction of treatment outcomes, e.g., patterns of failure.

  16. Synergistic effects between catalase inhibitors and modulators of nitric oxide metabolism on tumor cell apoptosis.

    Science.gov (United States)

    Scheit, Katrin; Bauer, Georg

    2014-10-01

    Inhibitors of catalase (such as ascorbate, methyldopa, salicylic acid and neutralizing antibodies) synergize with modulators of nitric oxide (NO) metabolism (such as arginine, arginase inhibitor, NO synthase-inducing interferons and NO dioxygenase inhibitors) in the singlet oxygen-mediated inactivation of tumor cell protective catalase. This is followed by reactive oxygen species (ROS)-dependent apoptosis induction. TGF-beta, NADPH oxidase-1, NO synthase, dual oxidase-1 and caspase-9 are characterized as essential catalysts in this process. The FAS receptor and caspase-8 are required for amplification of ROS signaling triggered by individual compounds, but are dispensable when the synergistic effect is established. Our findings explain the antitumor effects of catalase inhibitors and of compounds that target NO metabolism, as well as their synergy. These data may have an impact on epidemiological studies related to secondary plant compounds and open new perspectives for the establishment of novel antitumor drugs and for the improvement of established chemotherapeutics. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  17. Phase transitions in tumor growth: IV relationship between metabolic rate and fractal dimension of human tumor cells

    Science.gov (United States)

    Betancourt-Mar, J. A.; Llanos-Pérez, J. A.; Cocho, G.; Mansilla, R.; Martin, R. R.; Montero, S.; Nieto-Villar, J. M.

    2017-05-01

    By the use of thermodynamics formalism of irreversible processes, complex systems theory and systems biology, it is derived a relationship between the production of entropy per unit time, the fractal dimension and the tumor growth rate for human tumors cells. The thermodynamics framework developed demonstrates that, the dissipation function is a Landau potential and also the Lyapunov function of the dynamical behavior of tumor growth, which indicate the directional character, stability and robustness of the phenomenon. The entropy production rate may be used as a quantitative index of the metastatic potential of tumors. The current theoretical framework will hopefully provide a better understanding of cancer and contribute to improvements in cancer treatment.

  18. Embedding filtering criteria into a wrapper marker selection method for brain tumor classification: an application on metabolic peak area ratios

    International Nuclear Information System (INIS)

    Kounelakis, M G; Zervakis, M E; Giakos, G C; Postma, G J; Buydens, L M C; Kotsiakis, X

    2011-01-01

    The purpose of this study is to identify reliable sets of metabolic markers that provide accurate classification of complex brain tumors and facilitate the process of clinical diagnosis. Several ratios of metabolites are tested alone or in combination with imaging markers. A wrapper feature selection and classification methodology is studied, employing Fisher's criterion for ranking the markers. The set of extracted markers that express statistical significance is further studied in terms of biological behavior with respect to the brain tumor type and grade. The outcome of this study indicates that the proposed method by exploiting the intrinsic properties of data can actually reveal reliable and biologically relevant sets of metabolic markers, which form an important adjunct toward a more accurate type and grade discrimination of complex brain tumors

  19. 68Ga-PSMA-11 PET/CT-derived metabolic parameters for determination of whole-body tumor burden and treatment response in prostate cancer.

    Science.gov (United States)

    Schmidkonz, Christian; Cordes, Michael; Schmidt, Daniela; Bäuerle, Tobias; Goetz, Theresa Ida; Beck, Michael; Prante, Olaf; Cavallaro, Alexander; Uder, Michael; Wullich, Bernd; Goebell, Peter; Kuwert, Torsten; Ritt, Philipp

    2018-05-03

    We aimed at evaluating the role of 68 Ga-PSMA-11 PET/CT-derived metabolic parameters for assessment of whole-body tumor burden and its capability to determine therapeutic response in patients with prostate cancer. A total of 142 patients with biochemical recurrence of prostate cancer underwent PET/CT with [ 68 Ga]Ga-PSMA-HBED-CC ( 68 Ga-PSMA-11). Quantitative assessment of all 641 68 Ga-PSMA-11-positive lesions in the field of view was performed to calculate PSMA-derived parameters, including whole-body PSMA tumor volume (PSMA-TV) and whole-body total lesion PSMA (TL-PSMA), as well as the established SUVmax and SUVmean values. All PET-derived parameters were tested for correlation with serum PSA levels and for association with Gleason scores. In 23 patients who underwent 68 Ga-PSMA-11 PET/CT before and after therapy with either external beam radiation, androgen deprivation, or docetaxel chemotherapy, SUVmax and TL-PSMA were compared to radiographic response assessment of CT images based on RECIST 1.1 criteria and to biochemical response determined by changes of serum PSA levels. PSMA-TV and TL-PSMA demonstrated a significant correlation with serum PSA levels (P PET and biochemical response was 87% (95% confidence interval, 0.66-0.97; Cohen's κ = 0.78; P PET and CT were most likely due to limitations of CT and RECIST in rating small lymph nodes as metastases, as well as bone involvement, which was sometimes not detectable in CT. 68 Ga-PSMA-11 PET/CT-derived metabolic tumor parameters showed promising results for evaluation of treatment response. Especially, TL-PSMA demonstrated higher agreement rates with biochemical response compared to SUVmax. Larger, ideally prospective trials are needed to help to reveal the full potential of metabolic parameters derived from PET imaging with 68 Ga-PSMA-11.

  20. Fluorescence imaging of bombesin and transferrin receptor expression is comparable to 18F-FDG PET in early detection of sorafenib-induced changes in tumor metabolism.

    Directory of Open Access Journals (Sweden)

    Jen-Chieh Tseng

    Full Text Available Physical measurement of tumor volume reduction is the most commonly used approach to assess tumor progression and treatment efficacy in mouse tumor models. However, it is relatively insensitive, and often requires long treatment courses to achieve gross physical tumor destruction. As alternatives, several non-invasive imaging methods such as bioluminescence imaging (BLI, fluorescence imaging (FLI and positron emission tomography (PET have been developed for more accurate measurement. As tumors have elevated glucose metabolism, 18F-fludeoxyglucose (18F-FDG has become a sensitive PET imaging tracer for cancer detection, diagnosis, and efficacy assessment by measuring alterations in glucose metabolism. In particular, the ability of 18F-FDG imaging to detect drug-induced effects on tumor metabolism at a very early phase has dramatically improved the speed of decision-making regarding treatment efficacy. Here we demonstrated an approach with FLI that offers not only comparable performance to PET imaging, but also provides additional benefits, including ease of use, imaging throughput, probe stability, and the potential for multiplex imaging. In this report, we used sorafenib, a tyrosine kinase inhibitor clinically approved for cancer therapy, for treatment of a mouse tumor xenograft model. The drug is known to block several key signaling pathways involved in tumor metabolism. We first identified an appropriate sorafenib dose, 40 mg/kg (daily on days 0-4 and 7-10, that retained ultimate therapeutic efficacy yet provided a 2-3 day window post-treatment for imaging early, subtle metabolic changes prior to gross tumor regression. We then used 18F-FDG PET as the gold standard for assessing the effects of sorafenib treatment on tumor metabolism and compared this to results obtained by measurement of tumor size, tumor BLI, and tumor FLI changes. PET imaging showed ~55-60% inhibition of tumor uptake of 18F-FDG as early as days 2 and 3 post-treatment, without

  1. Lactate is a mediator of metabolic cooperation between stromal carcinoma associated fibroblasts and glycolytic tumor cells in the tumor microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Rattigan, Yanique I.; Patel, Brijesh B. [Graduate School of Biomedical Sciences, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901 (United States); Department of Pharmacology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901 (United States); Ackerstaff, Ellen [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (United States); Sukenick, George [Molecular Pharmacology and Chemistry Research Program, Sloan-Kettering Institute, 415 E 68th Street, New York, NY 10065 (United States); Koutcher, Jason A. [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (United States); Glod, John W. [Graduate School of Biomedical Sciences, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901 (United States); Department of Pharmacology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901 (United States); Department of Pediatric Oncology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901 (United States); and others

    2012-02-15

    Human mesenchymal stem cells (hMSCs) are bone marrow-derived stromal cells, which play a role in tumor progression. We have shown earlier that breast cancer cells secrete higher levels of interleukin-6 (IL-6) under hypoxia, leading to the recruitment of hMSCs towards hypoxic tumor cells. We found that (i) MDA-MB-231 cells secrete significantly higher levels of lactate (3-fold more) under hypoxia (1% O{sub 2}) than under 20% O{sub 2} and (ii) lactate recruits hMSCs towards tumor cells by activating signaling pathways to enhance migration. The mRNA and protein expression of functional MCT1 in hMSCs is increased in response to lactate exposure. Thus, we hypothesized that hMSCs and stromal carcinoma associated fibroblasts (CAFs) in the tumor microenvironment have the capacity to take up lactate expelled from tumor cells and use it as a source of energy. Our {sup 13}C NMR spectroscopic measurements indicate that {sup 13}C-lactate is converted to {sup 13}C-alpha ketoglutarate in hMSCs and CAFs supporting this hypothesis. To our knowledge this is the first in vitro model system demonstrating that hMSCs and CAFs can utilize lactate produced by tumor cells.

  2. Lactate is a mediator of metabolic cooperation between stromal carcinoma associated fibroblasts and glycolytic tumor cells in the tumor microenvironment

    International Nuclear Information System (INIS)

    Rattigan, Yanique I.; Patel, Brijesh B.; Ackerstaff, Ellen; Sukenick, George; Koutcher, Jason A.; Glod, John W.

    2012-01-01

    Human mesenchymal stem cells (hMSCs) are bone marrow-derived stromal cells, which play a role in tumor progression. We have shown earlier that breast cancer cells secrete higher levels of interleukin-6 (IL-6) under hypoxia, leading to the recruitment of hMSCs towards hypoxic tumor cells. We found that (i) MDA-MB-231 cells secrete significantly higher levels of lactate (3-fold more) under hypoxia (1% O 2 ) than under 20% O 2 and (ii) lactate recruits hMSCs towards tumor cells by activating signaling pathways to enhance migration. The mRNA and protein expression of functional MCT1 in hMSCs is increased in response to lactate exposure. Thus, we hypothesized that hMSCs and stromal carcinoma associated fibroblasts (CAFs) in the tumor microenvironment have the capacity to take up lactate expelled from tumor cells and use it as a source of energy. Our 13 C NMR spectroscopic measurements indicate that 13 C-lactate is converted to 13 C-alpha ketoglutarate in hMSCs and CAFs supporting this hypothesis. To our knowledge this is the first in vitro model system demonstrating that hMSCs and CAFs can utilize lactate produced by tumor cells.

  3. Comparison of 1H-MRS-detected metabolic characteristics in single metastatic brain tumors of different origin

    International Nuclear Information System (INIS)

    Chernov, M.F.; Ono, Yuko; Kubo, Osami; Hori, Tomokatsu

    2006-01-01

    Various types of intracranial metastases exhibit different growth patterns, which can be reflected in their metabolic characteristics and investigated noninvasively by proton magnetic resonance spectroscopy ( 1 H-MRS). The objective of the present study was comparison of the 1 H-MRS-detected metabolic parameters in brain metastases of different origin. Twenty-five patients (15 men and 10 women; mean age, 62.0 years) with single, previously nontreated metastatic brain tumors were investigated by long-echo single-voxel volume-selected 1 H-MRS. The primary cancer was located in the lungs (10 cases), colon and rectum (8 cases), breast (3 cases), kidney (2 cases), prostate (1 case), and cardiac muscle (1 case). Comparison of clinical and radiological variables, including type of tumor contrast enhancement and extension of peritumoral edema, did not disclose statistically significant differences in metastatic brain tumors of different origin. At the same time, comparison of 1 H-MRS-detected metabolic characteristics revealed that metastases of colorectal carcinoma have greater content of mobile lipids (Lip) compared to other neoplasms. In conclusion, high Lip content in the viable brain metastases of colorectal carcinoma can be used as an additional diagnostic clue for noninvasive identification of these tumors and should be taken into consideration in cases of 1 H-MRS-based differentiation of their recurrence and radiation-induced necrosis after radiosurgical or radiotherapeutic treatment. (author)

  4. Acute Metabolic Alkalosis Enhances Response of C3H Mouse Mammary Tumors to the Weak Base Mitoxantrone

    Directory of Open Access Journals (Sweden)

    Natarajan Raghunand

    2001-01-01

    Full Text Available Uptake of weak acid and weak base chemotherapeutic drugs by tumors is greatly influenced by the tumor extracellular/interstitial pH (pHe, the intracellular pH (pHi maintained by the tumor cells, and by the ionization properties of the drug itself. The acid-outside plasmalemmal pH gradient in tumors acts to exclude weak base drugs like the anthracyclines, anthraquinones, and vinca alkaloids from the cells, leading to a substantial degree of “physiological drug resistance” in tumors. We have induced acute metabolic alkalosis in C3H tumor-bearing C3H/hen mice, by gavage and by intraperitoneal (i.p. administration of NaHCO3. 31P magnetic resonance spectroscopic measurements of 3-aminopropylphosphonate show increases of up to 0.6 pH units in tumor pHe, and 0.2 to 0.3 pH units in hind leg tissue pHe, within 2 hours of i.p. administration of NaHCO3. Theoretical calculations of mitoxantrone uptake into tumor and normal (hind leg tissue at the measured pH, and pHI values indicate that a gain in therapeutic index of up to 3.3-fold is possible with NaHCO3 pretreatment. Treatment of C3H tumor-bearing mice with 12 mg/kg mitoxantrone resulted in a tumor growth delay of 9 days, whereas combined NaHCO3mitoxantrone therapy resulted in an enhancement of the TGD to 16 days.

  5. Antioxidant Activities of Total Phenols of Prunella vulgaris L. in Vitro and in Tumor-bearing Mice

    Directory of Open Access Journals (Sweden)

    Feng Shi

    2010-12-01

    Full Text Available Prunella vulgaris L. (PV, Labiatae is known as a self-heal herb. The different extracts of dried spikes were studied for the best antioxidant active compounds. The 60% ethanol extract (P-60 showed strong antioxidant activity based on the results of 2,2’-azino-di(3-ethylbenzthiazoline-6-sulfonic acid (ABTS˙+, 2,2-diphenyl-1-picrylhydrazyl (DPPH and ferric reducing antioxidant power (FRAP assay methods. High performance liquid chromatography (HPLC and LC/MS analysis showed that the main active compounds in P-60 were phenols, such as caffeic acid, rosmarinic acid, rutin and quercetin. Total phenols were highly correlated with the antioxidant activity (R2 = 0.9988 in ABTS˙+; 0.6284 in DPPH and 0.9673 FRAP tests. P-60 could inhibit significantly the tumor growth in C57BL/6 mice. It can also been showed that increased superoxide dismutase (SOD activity and decreased malondialdehyde (MDA content in serum of tumor-bearing mice. These results suggested that P-60 extract had high antioxidant activity in vitro and in vivo and total phenols played an important role in antioxidant activity for inhibition of tumor growth.

  6. Glucose metabolism via the pentose phosphate pathway, glycolysis and Krebs cycle in an orthotopic mouse model of human brain tumors.

    Science.gov (United States)

    Marin-Valencia, Isaac; Cho, Steve K; Rakheja, Dinesh; Hatanpaa, Kimmo J; Kapur, Payal; Mashimo, Tomoyuki; Jindal, Ashish; Vemireddy, Vamsidhara; Good, Levi B; Raisanen, Jack; Sun, Xiankai; Mickey, Bruce; Choi, Changho; Takahashi, Masaya; Togao, Osamu; Pascual, Juan M; Deberardinis, Ralph J; Maher, Elizabeth A; Malloy, Craig R; Bachoo, Robert M

    2012-10-01

    It has been hypothesized that increased flux through the pentose phosphate pathway (PPP) is required to support the metabolic demands of rapid malignant cell growth. Using orthotopic mouse models of human glioblastoma (GBM) and renal cell carcinoma metastatic to brain, we estimated the activity of the PPP relative to glycolysis by infusing [1,2-(13) C(2) ]glucose. The [3-(13) C]lactate/[2,3-(13) C(2) ]lactate ratio was similar for both the GBM and brain metastasis and their respective surrounding brains (GBM, 0.197 ± 0.011 and 0.195 ± 0.033, respectively (p = 1); metastasis: 0.126 and 0.119 ± 0.033, respectively). This suggests that the rate of glycolysis is significantly greater than the PPP flux in these tumors, and that the PPP flux into the lactate pool is similar in both tumors. Remarkably, (13) C-(13) C coupling was observed in molecules derived from Krebs cycle intermediates in both tumor types, denoting glucose oxidation. In the renal cell carcinoma, in contrast with GBM, (13) C multiplets of γ-aminobutyric acid (GABA) differed from its precursor glutamate, suggesting that GABA did not derive from a common glutamate precursor pool. In addition, the orthotopic renal tumor, the patient's primary renal mass and brain metastasis were all strongly immunopositive for the 67-kDa isoform of glutamate decarboxylase, as were 84% of tumors on a renal cell carcinoma tissue microarray of the same histology, suggesting that GABA synthesis is cell autonomous in at least a subset of renal cell carcinomas. Taken together, these data demonstrate that (13) C-labeled glucose can be used in orthotopic mouse models to study tumor metabolism in vivo and to ascertain new metabolic targets for cancer diagnosis and therapy. Copyright © 2012 John Wiley & Sons, Ltd.

  7. A Cross-Species Analysis in Pancreatic Neuroendocrine Tumors Reveals Molecular Subtypes with Distinctive Clinical, Metastatic, Developmental, and Metabolic Characteristics

    Science.gov (United States)

    Sadanandam, Anguraj; Wullschleger, Stephan; Lyssiotis, Costas A.; Grötzinger, Carsten; Barbi, Stefano; Bersani, Samantha; Körner, Jan; Wafy, Ismael; Mafficini, Andrea; Lawlor, Rita T.; Simbolo, Michele; Asara, John M.; Bläker, Hendrik; Cantley, Lewis C.; Wiedenmann, Bertram; Scarpa, Aldo; Hanahan, Douglas

    2016-01-01

    Seeking to assess the representative and instructive value of an engineered mouse model of pancreatic neuroendocrine tumors (PanNET) for its cognate human cancer, we profiled and compared mRNA and miRNA transcriptomes of tumors from both. Mouse PanNET tumors could be classified into two distinctive subtypes, well-differentiated islet/insulinoma tumors (IT) and poorly differentiated tumors associated with liver metastases, dubbed metastasis-like primary (MLP). Human PanNETs were independently classified into these same two subtypes, along with a third, specific gene mutation–enriched subtype. The MLP subtypes in human and mouse were similar to liver metastases in terms of miRNA and mRNA transcriptome profiles and signature genes. The human/mouse MLP subtypes also similarly expressed genes known to regulate early pancreas development, whereas the IT subtypes expressed genes characteristic of mature islet cells, suggesting different tumorigenesis pathways. In addition, these subtypes exhibit distinct metabolic profiles marked by differential pyruvate metabolism, substantiating the significance of their separate identities. SIGNIFICANCE This study involves a comprehensive cross-species integrated analysis of multi-omics profiles and histology to stratify PanNETs into subtypes with distinctive characteristics. We provide support for the RIP1-TAG2 mouse model as representative of its cognate human cancer with prospects to better understand PanNET heterogeneity and consider future applications of personalized cancer therapy. PMID:26446169

  8. Ruxolitinib combined with vorinostat suppresses tumor growth and alters metabolic phenotype in hematological diseases.

    Science.gov (United States)

    Civallero, Monica; Cosenza, Maria; Pozzi, Samantha; Sacchi, Stefano

    2017-11-28

    JAK-2 dysregulation plays an important role as an oncogenic driver, and is thus a promising therapeutic target in hematological malignancies. Ruxolitinib is a pyrrolo[2.3-d]pyrimidine derivative with inhibitory activity against JAK1 and JAK2, moderate activity against TYK2, and minor activity against JAK3. Vorinostat is an HDAC inhibitor that reduces JAK-2 expression, thus affecting JAK-2 mRNA expression and increasing JAK-2 proteasomal deterioration. Here we hypothesized that the combination of ruxolitinib and vorinostat could have synergistic effects against hematological disease. We tested combinations of low doses of ruxolitinib and vorinostat in 12 cell lines, and observed highly synergistic cytotoxic action in six cell lines, which was maintained for up to 120 h in the presence of stromal cells. The sensitivity of the six cell lines may be explained by the broad effects of the drug combination, which can affect various targets. Treatment with the combination of ruxolitinib and vorinostat appeared to induce a possible reversal of the Warburg effect, with associated ROS production, apoptotic events, and growth inhibition. Decreased glucose metabolism may have markedly sensitized the six more susceptible cell lines to combined treatment. Therapeutic inhibition of the JAK/STAT pathway seems to offer substantial anti-tumor benefit, and combined therapy with ruxolitinib and vorinostat may represent a promising novel therapeutic modality for hematological neoplasms.

  9. Modulation of Tumor Cell Metabolism by Laser Photochemotherapy with Cisplatin or Zoledronic Acid In Vitro.

    Science.gov (United States)

    Heymann, Paul Günther Baptist; Henkenius, Katharina Sabine Elisabeth; Ziebart, Thomas; Braun, Andreas; Hirthammer, Klara; Halling, Frank; Neff, Andreas; Mandic, Robert

    2018-03-01

    Laser photochemotherapy is a new approach in cancer treatment using low-level laser therapy (LLLT) to enhance the effect of chemotherapy. In order to evaluate the effect of LLLT on tumor cells, HeLa cells were treated with cisplatin or zoledronic acid (ZA) followed by LLLT. Cell viability was evaluated with 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay. Oxidative phosphorylation and glycolysis were measured using extracellular flux analysis. Immunocytochemistry of heat-shock protein 70 (HSP70) and western blot analysis were performed. LLLT alone increased viability and was associated with lower oxidative phosphorylation but higher glycolysis rates. Cisplatin and ZA alone lowered cell viability, glycolysis and oxidative phosphorylation. This effect was significantly enhanced in conjunction with LLLT and was accompanied by reduced oxidative phosphorylation and collapse of glycolysis. Our observations indicate that LLLT may raise the cytotoxicity of cisplatin and ZA by modulating cellular metabolism, pointing to a possible application in cancer treatment. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Laparoscopic total gastrectomy for a giant gastrointestinal stromal tumor (GIST) with acute massive gastrointestinal bleeding: a case report.

    Science.gov (United States)

    Kermansaravi, Mohammad; Rokhgireh, Samaneh; Darabi, Sattar; Pazouki, Abdolreza

    2017-09-01

    Gastrointestinal stromal tumors (GISTs) include 80% of gastrointestinal mesenchymal tumors that originate from interstitial Cajal cells and include 0.1-3% of GI malignancies, and the stomach is the most commonly involved organ. The only potentially curative treatment is surgical resection with clear margins. Although laparoscopic resection of small GISTs is a standard treatment, there is controversy about laparoscopic surgical resection for large and giant GISTs. A 52-year-old woman, a known case of large GIST of the stomach that was under neoadjuvant imatinib therapy, was admitted to the emergency department due to acute massive gastrointestinal bleeding (GIB). The patient underwent laparoscopic total gastrectomy and received adjuvant imatinib after surgery. Laparoscopic resection is a safe and feasible method in large and giant GISTs with oncologic and long-term outcomes comparable to open surgery, and with better short-term outcomes.

  11. Comparison of Venous Thromboembolism after Total Artificial Joint Replacement between Musculoskeletal Tumors and Osteoarthritis of the Knee by a Single Surgeon.

    Directory of Open Access Journals (Sweden)

    Dong Fu

    Full Text Available The purpose of this study was to compare and evaluate the event of VTE (Venous Thromboembolism Event after total artificial joint replacement between two groups diagnosed with either musculoskeletal tumors or osteoarthritis (OA of the knee. From 2004 to 2014, a total of 1,402 patients (308 in tumor group, 1,094 in OA group were involved in this study. The rate of asymptomatic DVT (Deep vein thrombosis was significantly higher in tumor group when compared with OA group. Though both the incidence of symptomatic DVT and PE (Pulmonary embolism were slightly higher in tumor group, no significant difference was detected. Tumor patients suffered an almost equal risk of VTE compared with OA patients except a higher rate of asymptomatic DVT after total artificial joint replacement. For patients with tumor, no significant association was observed between any potential risk factor and DVT.

  12. Metabolic and vascular effects of tumor necrosis factor-alpha blockade with etanercept in obese patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Dominguez, Helena; Storgaard, Heidi; Rask-Madsen, Christian

    2005-01-01

    OBJECTIVE: The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) impairs insulin action in insulin-sensitive tissues, such as fat, muscle and endothelium, and causes endothelial dysfunction. We hypothesized that TNF-alpha blockade with etanercept could reverse vascular and metabolic...... glucose uptake remained unchanged as well. Beta-cell function tended to improve. CONCLUSION: Although short-term etanercept treatment had a significant beneficial effect on systemic inflammatory markers, no improvement of vascular or metabolic insulin sensitivity was observed....

  13. Total physical activity volume, physical activity intensity, and metabolic syndrome: 1999-2004 National Health and Nutrition Examination Survey.

    Science.gov (United States)

    Churilla, James R; Fitzhugh, Eugene C

    2012-02-01

    This study examined the association of total physical activity volume (TPAV) and physical activity (PA) from three domains [leisure-time physical activity (LTPA), domestic, transportation] with metabolic syndrome. We also investigated the relationship between LTPA intensity and metabolic syndrome risk. Sample included adults who participated in the 1999-2004 National Health and Nutrition Examination Survey. Physical activity measures were created for TPAV, LTPA, domestic PA, and transportational PA. For each, a six-level measure based upon no PA (level 1) and quintiles (levels 2-6) of metabolic equivalents (MET)·min·wk(-1) was created. A three-level variable associated with the current Department of Health and Human Services (DHHS) PA recommendation was also created. SAS and SUDAAN were used for the statistical analysis. Adults reporting the greatest volume of TPAV and LTPA were found to be 36% [odds ratio (OR) 0.64; 95% confidence interval (CI) 0.49-0.83] and 42% (OR 0.58; 95% CI 0.43-0.77), respectively, less likely to have metabolic syndrome. Domestic and transportational PA provided no specific level of protection from metabolic syndrome. Those reporting a TPAV that met the DHHS PA recommendation were found to be 33% (OR 0.67; 95%; CI 0.55-0.83) less likely to have metabolic syndrome compared to their sedentary counterparts. Adults reporting engaging in only vigorous-intensity LTPA were found to be 37% (OR 0.63; 95 CI 0.42-0.96) to 56% (OR 0.44; 95% CI 0.29-0.67) less likely to have metabolic syndrome. Volume, intensity, and domain of PA may all play important roles in reducing the prevalence and risk of metabolic syndrome.

  14. Metabolic impact of partial volume correction of [18F]FDG PET-CT oncological studies on the assessment of tumor response to treatment.

    Science.gov (United States)

    Stefano, A; Gallivanone, F; Messa, C; Gilardi, M C; Gastiglioni, I

    2014-12-01

    The aim of this work is to evaluate the metabolic impact of Partial Volume Correction (PVC) on the measurement of the Standard Uptake Value (SUV) from [18F]FDG PET-CT oncological studies for treatment monitoring purpose. Twenty-nine breast cancer patients with bone lesions (42 lesions in total) underwent [18F]FDG PET-CT studies after surgical resection of breast cancer primitives, and before (PET-II) chemotherapy and hormone treatment. PVC of bone lesion uptake was performed on the two [18F]FDG PET-CT studies, using a method based on Recovery Coefficients (RC) and on an automatic measurement of lesion metabolic volume. Body-weight average SUV was calculated for each lesion, with and without PVC. The accuracy, reproducibility, clinical feasibility and the metabolic impact on treatment response of the considered PVC method was evaluated. The PVC method was found clinically feasible in bone lesions, with an accuracy of 93% for lesion sphere-equivalent diameter >1 cm. Applying PVC, average SUV values increased, from 7% up to 154% considering both PET-I and PET-II studies, proving the need of the correction. As main finding, PVC modified the therapy response classification in 6 cases according to EORTC 1999 classification and in 5 cases according to PERCIST 1.0 classification. PVC has an important metabolic impact on the assessment of tumor response to treatment by [18F]FDG PET-CT oncological studies.

  15. Thermodynamics of the living organisms. Allometric relationship between the total metabolic energy, chemical energy and body temperature in mammals

    Science.gov (United States)

    Atanasov, Atanas Todorov

    2017-11-01

    The study present relationship between the total metabolic energy (ETME(c), J) derived as a function of body chemical energy (Gchem, J) and absolute temperature (Tb, K) in mammals: ETME(c) =Gchem (Tb/Tn). In formula the temperature Tn =2.73K appears normalization temperature. The calculated total metabolic energy ETME(c) differs negligible from the total metabolic energy ETME(J), received as a product between the basal metabolic rate (Pm, J/s) and the lifespan (Tls, s) of mammals: ETME = Pm×Tls. The physical nature and biological mean of the normalization temperature (Tn, K) is unclear. It is made the hypothesis that the kTn energy (where k= 1.3806×10-23 J/K -Boltzmann constant) presents energy of excitation states (modes) in biomolecules and body structures that could be in equilibrium with chemical energy accumulated in body. This means that the accumulated chemical energy allows trough all body molecules and structures to propagate excitations states with kTn energy with wavelength in the rage of width of biological membranes. The accumulated in biomolecules chemical energy maintains spread of the excited states through biomolecules without loss of energy.

  16. Extraction and purification of total flavonoids from pine needles of Cedrus deodara contribute to anti-tumor in vitro.

    Science.gov (United States)

    Shi, Xiaofeng; Liu, Dongyan; Zhang, Junmin; Hu, Pengbin; Shen, Wei; Fan, Bin; Ma, Quhuan; Wang, Xindi

    2016-07-26

    Cedrus deodara is one of the traditional Chinese medicinal herbs that exhibits a line of biological activities. The current study extracted the total flavonoids from the pine needles of Cedrus deodara (TFPNCD), and investigated its anti-cancer effects in tumor cell lines. The total flavonoids was extracted from pine needles of Cedrus deodara by ethanol hot refluxing and purified by HPD722 macroporous resin. The contents of total flavonoids and the active ingredients of TFPNCD were analyzed through UV and HPLC. MTT assay was used to investigate its inhibitory effect on tumor cell lines. The flow cytometry was employed to determine the apoptosis and cell cycle distribution after treated TFPNCD on HepG2 cells. The TFPNCD, in which the contents of total flavonoid reached up to 54.28 %, and the major ingredients of myricetin, quercetin, kaempferol and isorhamnetin in TFPNCD were 1.89, 2.01, 2.94 and 1.22 mg/g, respectively. The MTT assays demonstrated that TFPNCD inhibited the growth of HepG2 cells in a dose-dependent manner, with the IC50 values of 114.12 μg/mL. By comparison, TFPNCD inhibited the proliferation to a less extent in human cervical carcinoma HeLa, gastric cancer MKN28 cells, glioma SHG-44 cells and lung carcinoma A549 than HepG2 cells. We found that even at the lower doses, the total flavonoids effectively inhibited the proliferation of HepG2 cells. Comparison of IC50 values implicated that HepG2 cells might be more sensitive to the treatment with total flavonoids. TFPNCD was able to increase the population of HepG2 cells in G0 /G1 phase. Meanwhile, TFPNCD treatment increased the percentage of apoptotic HepG2 cells. These data suggested that TFPNCD might have therapeutic potential in cancer through the regulation of cell cycle and apoptosis.

  17. Increased total-Tau levels in cerebrospinal fluid of pediatric hydrocephalus and brain tumor patients

    NARCIS (Netherlands)

    de Bont, Judith M.; Vanderstichele, Hugo; Reddingius, Roel E.; Pieters, Rob; van Gool, Stefdan W.

    Total Tau (t-Tau), hyperphosphorylated Tau (p-Tau((181P))) and beta-amyloid((1-42)) in cerebrospinal fluid (CSF) have shown to be markers of neuronal and axonal degeneration in various neurological and neurodegenerative diseases. The aim of this study was to evaluate the influence of the presence of

  18. Anti-tumor potential of total alkaloid extract of Prosopis juliflora DC ...

    African Journals Online (AJOL)

    Jane

    2011-08-15

    Aug 15, 2011 ... Cancer is the second leading cause of death in the world. (Madhusudan and .... formula and from that the percentage of cytotoxicity and IC50 values ... complete media were treated as positive and negative controls, .... Cytotoxic effect of total alkaloid extract of P. juliflora leaves against cancer (black bars).

  19. A liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumor

    Directory of Open Access Journals (Sweden)

    Xun Bao

    2018-02-01

    Full Text Available A rapid, sensitive, and robust reversed-phase liquid chromatography with tandem mass spectrometry method was developed and validated for the determination of total and unbound ceritinib, a second-generation ALK inhibitor, in patient plasma and brain tumor tissue samples. Sample preparation involved simple protein precipitation with acetonitrile. Chromatographic separation was achieved on a Waters ACQUITY UPLC BEH C18 column using a 4-min gradient elution consisting of mobile phase A (0.1% formic acid in water and mobile phase B (0.1% formic acid in acetonitrile, at a flow rate of 0.4 mL/min. Ceritinib and the internal standard ([13C6]ceritinib were monitored using multiple reaction monitoring mode under positive electrospray ionization. The lower limit of quantitation (LLOQ was 1 nM of ceritinib in plasma. The calibration curve was linear over ceritinib concentration range of 1–2000 nM in plasma. The intra- and inter-day precision and accuracy were within the generally accepted criteria for bioanalytical method (<15%. The method was successfully applied to assess ceritinib brain tumor penetration, as assessed by the unbound drug brain concentration to unbound drug plasma concentration ratio, in patients with brain tumors.

  20. Metabolism of indole alkaloid tumor promoter, (-)-indolactam V, which has the fundamental structure of teleocidins, by rat liver microsomes

    Energy Technology Data Exchange (ETDEWEB)

    Hagiwara, N.; Irie, K.; Tokuda, H.; Koshimizu, K.

    1987-07-01

    Metabolic activation and/or deactivation of indole alkaloid tumor promoter, (-)-indolactam V (ILV), was examined using rat liver microsomes. Reaction of ILV with the microsomes supplemented with NADPH and MgCl/sub 2/ gave three major metabolites, which were identified as (-)-N13-desmethylindolactam V and two diastereomers of (-)-2-oxyindolactam V at C-3. The tumor-promoting activities of these metabolites were evaluated by induction of Epstein-Barr virus early antigen and inhibition of specific binding of (/sup 3/H)-12-O-tetradecanoylphorbol-13-acetate to a mouse epidermal particulate fraction, and proved to be conspicuously lower than that of ILV. These results demonstrate that the metabolism of ILV results in detoxification, and that it itself is the tumor-promoting entity. Studies on the enzymes concerned with this metabolism suggested the involvement of cytochrome P-450-containing mixed-function oxidases. Similar deactivation seems to be possible by skin, where the mixed-function oxidases are known to exist.

  1. III. Cellular ultrastructures in situ as key to understanding tumor energy metabolism: biological significance of the Warburg effect.

    Science.gov (United States)

    Witkiewicz, Halina; Oh, Phil; Schnitzer, Jan E

    2013-01-01

    Despite the universality of metabolic pathways, malignant cells were found to have their metabolism reprogrammed to generate energy by glycolysis even under normal oxygen concentrations (the Warburg effect). Therefore, the pathway energetically 18 times less efficient than oxidative phosphorylation was implicated to match increased energy requirements of growing tumors. The paradox was explained by an abnormally high rate of glucose uptake, assuming unlimited availability of substrates for tumor growth in vivo. However, ultrastructural analysis of tumor vasculature morphogenesis showed that the growing tissue regions did not have continuous blood supply and intermittently depended on autophagy for survival. Erythrogenic autophagy, and resulting ATP generation by glycolysis, appeared critical to initiating vasculature formation where it was missing. This study focused on ultrastructural features that reflected metabolic switch from aerobic to anaerobic. Morphological differences between and within different types of cells were evident in tissue sections. In cells undergoing nucleo-cytoplasmic conversion into erythrosomes (erythrogenesis), gradual changes led to replacing mitochondria with peroxisomes, through an intermediate form connected to endoplasmic reticulum. Those findings related to the issue of peroxisome biogenesis and to the phenomenon of hemogenic endothelium. Mitochondria were compacted also during mitosis. In vivo, cells that lost and others that retained capability to use oxygen coexisted side-by-side; both types were important for vasculature morphogenesis and tissue growth. Once passable, the new vasculature segment could deliver external oxygen and nutrients. Nutritional and redox status of microenvironment had similar effect on metabolism of malignant and non-malignant cells demonstrating the necessity to maintain structure-energy equivalence in all living cells. The role of glycolysis in initiating vasculature formation, and in progression of

  2. Investigation into the acute effects of total and partial energy restriction on postprandial metabolism among overweight/obese participants.

    Science.gov (United States)

    Antoni, Rona; Johnston, Kelly L; Collins, Adam L; Robertson, M Denise

    2016-03-28

    The intermittent energy restriction (IER) approach to weight loss involves short periods of substantial (75-100 %) energy restriction (ER) interspersed with normal eating. This study aimed to characterise the early metabolic response to these varying degrees of ER, which occurs acutely and prior to weight loss. Ten (three female) healthy, overweight/obese participants (36 (SEM 5) years; 29·0 (sem 1·1) kg/m2) took part in this acute three-way cross-over study. Participants completed three 1-d dietary interventions in a randomised order with a 1-week washout period: isoenergetic intake, partial 75 % ER and total 100 % ER. Fasting and postprandial (6-h) metabolic responses to a liquid test meal were assessed the following morning via serial blood sampling and indirect calorimetry. Food intake was also recorded for two subsequent days of ad libitum intake. Relative to the isoenergetic control, postprandial glucose responses were increased following total ER (+142 %; P=0·015) and to a lesser extent after partial ER (+76 %; P=0·051). There was also a delay in the glucose time to peak after total ER only (P=0·024). Both total and partial ER interventions produced comparable reductions in postprandial TAG responses (-75 and -59 %, respectively; both Pobese participants. Further investigations are required to establish how metabolism adapts over time to the repeated perturbations experienced during IER, as well as the implications for long-term health.

  3. Metabolic Symbiosis and Immunomodulation: How Tumor Cell-Derived Lactate May Disturb Innate and Adaptive Immune Responses

    Directory of Open Access Journals (Sweden)

    Alexandre Morrot

    2018-03-01

    Full Text Available The tumor microenvironment (TME is composed by cellular and non-cellular components. Examples include the following: (i bone marrow-derived inflammatory cells, (ii fibroblasts, (iii blood vessels, (iv immune cells, and (v extracellular matrix components. In most cases, this combination of components may result in an inhospitable environment, in which a significant retrenchment in nutrients and oxygen considerably disturbs cell metabolism. Cancer cells are characterized by an enhanced uptake and utilization of glucose, a phenomenon described by Otto Warburg over 90 years ago. One of the main products of this reprogrammed cell metabolism is lactate. “Lactagenic” or lactate-producing cancer cells are characterized by their immunomodulatory properties, since lactate, the end product of the aerobic glycolysis, besides acting as an inducer of cellular signaling phenomena to influence cellular fate, might also play a role as an immunosuppressive metabolite. Over the last 10 years, it has been well accepted that in the TME, the lactate secreted by transformed cells is able to compromise the function and/or assembly of an effective immune response against tumors. Herein, we will discuss recent advances regarding the deleterious effect of high concentrations of lactate on the tumor-infiltrating immune cells, which might characterize an innovative way of understanding the tumor-immune privilege.

  4. Total Alkaloids of Sophora alopecuroides Inhibit Growth and Induce Apoptosis in Human Cervical Tumor HeLa Cells In vitro.

    Science.gov (United States)

    Li, Jian-Guang; Yang, Xiao-Yi; Huang, Wei

    2016-05-01

    Uygur females of Xinjiang have the higher incidence of cervical tumor in the country. Alkaloids are the major active ingredients in Sophora alopecuroides, and its antitumor effect was recognized by the medical profession. Xinjiang is the main site of S. alopecuroides production in China so these plants are abundant in the region. Studies on the antitumor properties of total alkaloids of S. alopecuroides (TASA) can take full use of the traditional folk medicine in antitumor unique utility. To explore the effects of TASA on proliferation and apoptosis of human cervical tumor HeLa cells in vitro. TASA was extracted, purified, and each monomer component was analyzed by high-performance liquid chromatography. The effect of TASA at different concentrations on the survival of HeLa cells was determined after 24 h using the Cell Counting Kit-8. In addition, cells were photographed using an inverted microscope to document morphological changes. The effect of TASA on apoptotic rate of HeLa cells was assessed by flow cytometry. Monomers of TASA were found to be sophoridine, matrine, and sophocarpine. On treatment with 8.75 mg/ml of TASA, more than 50% of HeLa cells died, and cell death rate increased further with longer incubation. The apoptotic rates of HeLa cells in the experimental groups were 16.0% and 33.3% at concentrations of 6.25 mg/ml and 12.50 mg/ml, respectively. TASA can induce apoptosis in cervical tumor HeLa cells, and it has obvious inhibitory effects on cell growth. Total alkaloids of Sophora alopecuroides (TASA) exhibits anti-human cervical tumor propertiesMonomer component of TASA was analyzed by high-performance liquid chromatography, and its main effect component are sophoridine, matrine, and sophocarpineTASA inhibits growth and induces apoptosis in HeLa cells. Abbreviations used: TASA: Total alkaloids of S. alopecuroides, CCK-8: Cell Counting Kit-8, FBS: Fetal bovine serum, PBS: Phosphate buffered saline, DMEM: Dulbecco's modified Eagle medium.

  5. Oral treatment with a rattlesnake native polypeptide crotamine efficiently inhibits the tumor growth with no potential toxicity for the host animal and with suggestive positive effects on animal metabolic profile.

    Science.gov (United States)

    Campeiro, Joana D; Marinovic, Marcelo P; Carapeto, Fernando Cintra; Dal Mas, Caroline; Monte, Gabriela Guilherme; Carvalho Porta, Lucas; Nering, Marcela B; Oliveira, Eduardo B; Hayashi, Mirian A F

    2018-02-01

    The efficacy of crotamine as antitumoral was first demonstrated by daily intraperitoneal (IP) injections of low doses of this toxin in an animal model bearing melanoma tumors. Significant inhibition of tumor growth and increased lifespan of mice bearing tumor was also noticed after 21 consecutive days of this daily IP administration of crotamine. However, due to the limited acceptance of treatments by IP route in clinical conditions, herein, we evaluated the antitumor effect of this native polypeptide employing the oral route. The efficacy of crotamine in inhibiting the melanoma growth in vivo, even after passing through the gastrointestinal tract of the animal, was confirmed here. In addition, biochemical biomarkers and also histopathological analysis showed both the absence of any potential toxic effects in tissues or organs of the animal in which the highest accumulation of crotamine is expected. Interestingly, a reduction of weight gain was observed mainly in animals with tumor treated with crotamine by IP route, but not by oral administration. Albeit, oral administered crotamine was able to significantly decrease the body weight gain of healthy animals without tumor. Taking advantage of this same experimental animal models receiving crotamine by oral route, it was possible to show metabolic changes as the increased capacity of glucose clearance, which was accompanied by a reduction of the total cholesterol, and by increased high-density lipoprotein levels, both observed mainly in the absence of tumor. Triglycerides and low-density lipoprotein were also significantly decreased, but only in the absence of tumor. Taken together, these data suggest a clear trend for metabolic positive effects and mischaracterize unhealthy condition of animals, with or without tumors, treated with crotamine for 21 days. In addition, this study confirmed the efficacy of crotamine administered by oral route as antitumor agent, which besides the additional advantage of

  6. Tumor metabolism and perfusion ratio assessed by 18F-FDG PET/CT and DCE-MRI in breast cancer patients: Correlation with tumor subtype and histologic prognostic factors

    Energy Technology Data Exchange (ETDEWEB)

    An, Young-Sil [Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine (Korea, Republic of); Kang, Doo Kyoung [Department of Radiology, Ajou University School of Medicine (Korea, Republic of); Jung, Yong Sik; Han, Sehwan [Department of Surgery, Ajou University School of Medicine (Korea, Republic of); Kim, Tae Hee, E-mail: medhand@ajou.ac.kr [Department of Radiology, Ajou University School of Medicine (Korea, Republic of)

    2015-07-15

    Highlights: • In non-triple negative breast cancer, metabolic parameter (SUVmax) was significantly correlated with perfusion parameters (Kep and Ve). • In triple negative cancers, any perfusion parameters did not correlated with metabolic parameters. • Higher SUVmax, higher SUVmax/Ktrans, higher MTV50/Ktrans, higher TLG50/Ktrans, higher TLG50/Ve ratios were significantly correlated with TNBC. • In triple negative breast cancer, perfusion and metabolic parameters are not significantly correlated. • Triple negative breast cancer showed higher metabolic–perfusion ratios compared to non-triple negative breast cancer. - Abstract: Objective: Our purpose was to evaluate whether breast cancer with high metabolic–perfusion ratio would be associated with poor histopathologic prognostic factors and whether triple negative breast cancer (TNBC) would show high metabolic–perfusion ratio compared to non-triple negative breast cancer (non-TNBC). Methods: From March 2011 to November 2011, 67 females with invasive ductal carcinoma of breast who underwent both MRI and 18F-FDG PET/CT were included. Perfusion parameters including Ktrans, Kep and Ve were acquired from Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Metabolic parameters including the standardized uptake value (SUV) and volumetric metabolic parameters including metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were obtained from F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). Results: In non-TNBC, SUVmax was significantly correlated with Kep (ρ = 0.298, p = 0.036) and Ve (ρ = −0.286, p = 0.044). In TNBC, there was no significant correlation between all perfusion and metabolic parameters. Compared to non-TNBC, higher SUVmax (10.2 vs 5.3, p < 0.001), higher SUVmax/Ktrans (56.02 vs 20.3, p < 0.001), higher MTV50/Ktrans (7.8 vs 16.54, p < 0.001), higher TLG50/Ktrans (36.49 vs 12.3, p < 0.001), higher TLG50/Ve (91.34 vs 27.1 p = 0.022) were

  7. Vigorous exercise is associated with superior metabolic profiles in polycystic ovary syndrome independent of total exercise expenditure.

    Science.gov (United States)

    Greenwood, Eleni A; Noel, Martha W; Kao, Chia-Ning; Shinkai, Kanade; Pasch, Lauri A; Cedars, Marcelle I; Huddleston, Heather G

    2016-02-01

    To characterize metabolic features of women with polycystic ovary syndrome (PCOS) by exercise behavior and determine relative health benefits of different exercise intensities. Cross-sectional study. Tertiary academic institution. Three hundred and twenty-six women aged 14-52 years-old with PCOS by Rotterdam criteria examined between 2006 and 2013. International Physical Activity Questionnaire (IPAQ) administered to classify patients into three groups based on Department of Health and Human Services (DHHS) Guidelines of vigorous, moderate, and inactive, along with physical examination and serum testing. Blood pressure, body mass index (BMI), waist circumference, fasting lipids, fasting glucose and insulin, 2-hour 75-gram oral glucose tolerance, homeostatic model assessment of insulin resistance (HOMA-IR). The DHHS guidelines for adequate physical activity were met by 182 (56%) women. Compared with moderate exercisers and inactive women, the vigorous exercisers had lower BMI and lower HOMA-IR; higher levels of high-density lipoprotein cholesterol and sex hormone-binding globulin; and a reduced prevalence of the metabolic syndrome. In a multivariate logistic regression analysis controlling for age, BMI, and total energy expenditure, every hour of vigorous exercise reduced a patient's odds of metabolic syndrome by 22% (odds ratio 0.78; 95% confidence interval, 0.62, 0.99). Women with PCOS who met DHHS guidelines for exercise demonstrated superior metabolic health parameters. Vigorous but not moderate activity is associated with reduced odds of the metabolic syndrome, independent of age, BMI, and total energy expenditure. PCOS patients should be encouraged to meet activity guidelines via vigorous physical activity. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  8. Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy

    Directory of Open Access Journals (Sweden)

    Claire M. Doskey

    2016-12-01

    Full Text Available Ascorbate (AscH− functions as a versatile reducing agent. At pharmacological doses (P-AscH−; [plasma AscH−] ≥≈20 mM, achievable through intravenous delivery, oxidation of P-AscH− can produce a high flux of H2O2 in tumors. Catalase is the major enzyme for detoxifying high concentrations of H2O2. We hypothesize that sensitivity of tumor cells to P-AscH− compared to normal cells is due to their lower capacity to metabolize H2O2. Rate constants for removal of H2O2 (kcell and catalase activities were determined for 15 tumor and 10 normal cell lines of various tissue types. A differential in the capacity of cells to remove H2O2 was revealed, with the average kcell for normal cells being twice that of tumor cells. The ED50 (50% clonogenic survival of P-AscH− correlated directly with kcell and catalase activity. Catalase activity could present a promising indicator of which tumors may respond to P-AscH−.

  9. Serum total bilirubin levels are negatively correlated with metabolic syndrome in aged Chinese women: a community-based study.

    Science.gov (United States)

    Zhong, P; Sun, D M; Wu, D H; Li, T M; Liu, X Y; Liu, H Y

    2017-01-26

    We evaluated serum total bilirubin levels as a predictor for metabolic syndrome (MetS) and investigated the relationship between serum total bilirubin levels and MetS prevalence. This cross-sectional study included 1728 participants over 65 years of age from Eastern China. Anthropometric data, lifestyle information, and previous medical history were collected. We then measured serum levels of fasting blood-glucose, total cholesterol, triglycerides, and total bilirubin, as well as alanine aminotransferase activity. The prevalence of MetS and each of its individual component were calculated per quartile of total bilirubin level. Logistic regression was used to assess the correlation between serum total bilirubin levels and MetS. Total bilirubin level in the women who did not have MetS was significantly higher than in those who had MetS (Pbilirubin quartiles were linearly and negatively correlated with MetS prevalence and hypertriglyceridemia (HTG) in females (Pbilirubin was an independent predictor of MetS for females (OR: 0.910, 95%CI: 0.863-0.960; P=0.001). The present study suggests that physiological levels of serum total bilirubin might be an independent risk factor for aged Chinese women, and the prevalence of MetS and HTG are negatively correlated to serum total bilirubin levels.

  10. The use of phase sequence image sets to reconstruct the total volume occupied by a mobile lung tumor

    International Nuclear Information System (INIS)

    Gagne, Isabelle M.; Robinson, Don M.; Halperin, Ross; Roa, Wilson

    2005-01-01

    The use of phase sequence image (PSI) sets to reveal the total volume occupied by a mobile target is presented. Isocontrast composite clinical target volumes (CCTVs) may be constructed from PSI sets in order to reveal the total volume occupied by a mobile target during the course of its travel. The ability of the CCTV technique to properly account for target motion is demonstrated by comparison to contours of the true total volume occupied (TVO) for a number of experimental phantom geometries. Finally, using real patient data, the clinical utility of the CCTV technique to properly account for internal tumor motion while minimizing the volume of healthy lung tissue irradiated is assessed by comparison to the standard approach of applying safety margins. Results of the phantom study reveal that CCTV cross sections constructed at the 20% isocontrast level yield good agreement with the total cross sections (TXO) of mobile targets. These CCTVs conform well to the TVOs of the moving targets examined whereby the addition of small uniform margins ensures complete circumscription of the TVO with the inclusion of minimal amounts of surrounding external volumes. The CCTV technique is seen to be clearly superior to the common practice of the addition of safety margins to individual CTV contours in order to account for internal target motion. Margins required with the CCTV technique are eight to ten times smaller than those required with individual CTVs

  11. Whole-genome sequencing of a malignant granular cell tumor with metabolic response to pazopanib

    Science.gov (United States)

    Wei, Lei; Liu, Song; Conroy, Jeffrey; Wang, Jianmin; Papanicolau-Sengos, Antonios; Glenn, Sean T.; Murakami, Mitsuko; Liu, Lu; Hu, Qiang; Conroy, Jacob; Miles, Kiersten Marie; Nowak, David E.; Liu, Biao; Qin, Maochun; Bshara, Wiam; Omilian, Angela R.; Head, Karen; Bianchi, Michael; Burgher, Blake; Darlak, Christopher; Kane, John; Merzianu, Mihai; Cheney, Richard; Fabiano, Andrew; Salerno, Kilian; Talati, Chetasi; Khushalani, Nikhil I.; Trump, Donald L.; Johnson, Candace S.; Morrison, Carl D.

    2015-01-01

    Granular cell tumors are an uncommon soft tissue neoplasm. Malignant granular cell tumors comprise T transitions, particularly when immediately preceded by a 5′ G. A loss-of-function mutation was detected in a newly recognized tumor suppressor candidate, BRD7. No mutations were found in known targets of pazopanib. However, we identified a receptor tyrosine kinase pathway mutation in GFRA2 that warrants further evaluation. To the best of our knowledge, this is only the second reported case of a malignant granular cell tumor exhibiting a response to pazopanib, and the first whole-genome sequencing of this uncommon tumor type. The findings provide insight into the genetic basis of malignant granular cell tumors and identify potential targets for further investigation. PMID:27148567

  12. Parental smoking and risk of childhood brain tumors by functional polymorphisms in polycyclic aromatic hydrocarbon metabolism genes.

    Directory of Open Access Journals (Sweden)

    Jessica L Barrington-Trimis

    Full Text Available BACKGROUND: A recent meta-analysis suggested an association between exposure to paternal smoking during pregnancy and childhood brain tumor risk, but no studies have evaluated whether this association differs by polymorphisms in genes that metabolize tobacco-smoke chemicals. METHODS: We assessed 9 functional polymorphisms in 6 genes that affect the metabolism of polycyclic aromatic hydrocarbons (PAH to evaluate potential interactions with parental smoking during pregnancy in a population-based case-control study of childhood brain tumors. Cases (N = 202 were ≤10 years old, diagnosed from 1984-1991 and identified in three Surveillance, Epidemiology, and End Results (SEER registries in the western U.S. Controls in the same regions (N = 286 were frequency matched by age, sex, and study center. DNA for genotyping was obtained from archived newborn dried blood spots. RESULTS: We found positive interaction odds ratios (ORs for both maternal and paternal smoking during pregnancy, EPHX1 H139R, and childhood brain tumors (P(interaction = 0.02; 0.10, such that children with the high-risk (greater PAH activation genotype were at a higher risk of brain tumors relative to children with the low-risk genotype when exposed to tobacco smoke during pregnancy. A dose-response pattern for paternal smoking was observed among children with the EPHX1 H139R high-risk genotype only (OR(no exposure = 1.0; OR(≤3 hours/day = 1.32, 95% CI: 0.52-3.34; OR(>3 hours/day = 3.18, 95% CI: 0.92-11.0; P(trend = 0.07. CONCLUSION: Parental smoking during pregnancy may be a risk factor for childhood brain tumors among genetically susceptible children who more rapidly activate PAH in tobacco smoke.

  13. Ethanol exposure induces the cancer-associated fibroblast phenotype and lethal tumor metabolism: implications for breast cancer prevention.

    Science.gov (United States)

    Sanchez-Alvarez, Rosa; Martinez-Outschoorn, Ubaldo E; Lin, Zhao; Lamb, Rebecca; Hulit, James; Howell, Anthony; Sotgia, Federica; Rubin, Emanuel; Lisanti, Michael P

    2013-01-15

    Little is known about how alcohol consumption promotes the onset of human breast cancer(s). One hypothesis is that ethanol induces metabolic changes in the tumor microenvironment, which then enhances epithelial tumor growth. To experimentally test this hypothesis, we used a co-culture system consisting of human breast cancer cells (MCF7) and hTERT-immortalized fibroblasts. Here, we show that ethanol treatment (100 mM) promotes ROS production and oxidative stress in cancer-associated fibroblasts, which is sufficient to induce myofibroblastic differentiation. Oxidative stress in stromal fibroblasts also results in the onset of autophagy/mitophagy, driving the induction of ketone body production in the tumor microenvironment. Interestingly, ethanol has just the opposite effect in epithelial cancer cells, where it confers autophagy resistance, elevates mitochondrial biogenesis and induces key enzymes associated with ketone re-utilization (ACAT1/OXCT1). During co-culture, ethanol treatment also converts MCF7 cells from an ER(+) to an ER(-) status, which is thought to be associated with "stemness," more aggressive behavior and a worse prognosis. Thus, ethanol treatment induces ketone production in cancer-associated fibroblasts and ketone re-utilization in epithelial cancer cells, fueling tumor cell growth via oxidative mitochondrial metabolism (OXPHOS). This "two-compartment" metabolic model is consistent with previous historical observations that ethanol is first converted to acetaldehyde (which induces oxidative stress) and then ultimately to acetyl-CoA (a high-energy mitochondrial fuel), or can be used to synthesize ketone bodies. As such, our results provide a novel mechanism by which alcohol consumption could metabolically convert "low-risk" breast cancer patients to "high-risk" status, explaining tumor recurrence or disease progression. Hence, our findings have clear implications for both breast cancer prevention and therapy. Remarkably, our results also show that

  14. Total {sup 18}F-dopa PET tumour uptake reflects metabolic endocrine tumour activity in patients with a carcinoid tumour

    Energy Technology Data Exchange (ETDEWEB)

    Fiebrich, Helle-Brit; Walenkamp, Annemiek M.; Vries, Elisabeth G.E. de [University Medical Centre Groningen, Department of Medical Oncology, Groningen (Netherlands); Jong, Johan R. de; Koopmans, Klaas Pieter; Dierckx, Rudi A.J.O.; Brouwers, Adrienne H. [University Medical Centre Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Kema, Ido P. [University Medical Centre Groningen, Department of Laboratory Medicine, Groningen (Netherlands); Sluiter, Wim; Links, Thera P. [University Medical Centre Groningen, Department of Endocrinology, Groningen (Netherlands)

    2011-10-15

    Positron emission tomography (PET) using 6-[{sup 18}F]fluoro-L-dihydroxyphenylalanine ({sup 18}F-dopa) has an excellent sensitivity to detect carcinoid tumour lesions. {sup 18}F-dopa tumour uptake and the levels of biochemical tumour markers are mediated by tumour endocrine metabolic activity. We evaluated whether total {sup 18}F-dopa tumour uptake on PET, defined as whole-body metabolic tumour burden (WBMTB), reflects tumour load per patient, as measured with tumour markers. Seventy-seven consecutive carcinoid patients who underwent an {sup 18}F-dopa PET scan in two previously published studies were analysed. For all tumour lesions mean standardised uptake values (SUVs) at 40% of the maximal SUV and tumour volume on {sup 18}F-dopa PET were determined and multiplied to calculate a metabolic burden per lesion. WBMTB was the sum of the metabolic burden of all individual lesions per patient. The 24-h urinary serotonin, urine and plasma 5-hydroxindoleacetic acid (5-HIAA), catecholamines (nor)epinephrine, dopamine and their metabolites, measured in urine and plasma, and serum chromogranin A served as tumour markers. All but 1 were evaluable for WBMTB; 74 patients had metastatic disease. {sup 18}F-dopa PET detected 979 lesions. SUV{sub max} on {sup 18}F-dopa PET varied up to 29-fold between individual lesions within the same patients. WBMTB correlated with urinary serotonin (r = 0.51) and urinary and plasma 5-HIAA (r = 0.78 and 0.66). WBMTB also correlated with urinary norepinephrine, epinephrine, dopamine and plasma dopamine, but not with serum chromogranin A. Tumour load per patient measured with {sup 18}F-dopa PET correlates with tumour markers of the serotonin and catecholamine pathway in urine and plasma in carcinoid patients, reflecting metabolic tumour activity. (orig.)

  15. Synthetic dosage lethality in the human metabolic network is highly predictive of tumor growth and cancer patient survival.

    Science.gov (United States)

    Megchelenbrink, Wout; Katzir, Rotem; Lu, Xiaowen; Ruppin, Eytan; Notebaart, Richard A

    2015-09-29

    Synthetic dosage lethality (SDL) denotes a genetic interaction between two genes whereby the underexpression of gene A combined with the overexpression of gene B is lethal. SDLs offer a promising way to kill cancer cells by inhibiting the activity of SDL partners of activated oncogenes in tumors, which are often difficult to target directly. As experimental genome-wide SDL screens are still scarce, here we introduce a network-level computational modeling framework that quantitatively predicts human SDLs in metabolism. For each enzyme pair (A, B) we systematically knock out the flux through A combined with a stepwise flux increase through B and search for pairs that reduce cellular growth more than when either enzyme is perturbed individually. The predictive signal of the emerging network of 12,000 SDLs is demonstrated in five different ways. (i) It can be successfully used to predict gene essentiality in shRNA cancer cell line screens. Moving to clinical tumors, we show that (ii) SDLs are significantly underrepresented in tumors. Furthermore, breast cancer tumors with SDLs active (iii) have smaller sizes and (iv) result in increased patient survival, indicating that activation of SDLs increases cancer vulnerability. Finally, (v) patient survival improves when multiple SDLs are present, pointing to a cumulative effect. This study lays the basis for quantitative identification of cancer SDLs in a model-based mechanistic manner. The approach presented can be used to identify SDLs in species and cell types in which "omics" data necessary for data-driven identification are missing.

  16. Antitumor and chemosensitizing action of dichloroacetate implicates modulation of tumor microenvironment: A role of reorganized glucose metabolism, cell survival regulation and macrophage differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra, E-mail: sukhmahendrasingh@yahoo.com

    2013-11-15

    Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, which is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. - Highlights: • DCA modulates tumor progression and chemoresistance. • DCA alters molecules regulating cell survival, glucose metabolism and MDR. • DCA reconstitutes biophysical and cellular composition of tumor microenvironment.

  17. Antitumor and chemosensitizing action of dichloroacetate implicates modulation of tumor microenvironment: A role of reorganized glucose metabolism, cell survival regulation and macrophage differentiation

    International Nuclear Information System (INIS)

    Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra

    2013-01-01

    Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, which is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. - Highlights: • DCA modulates tumor progression and chemoresistance. • DCA alters molecules regulating cell survival, glucose metabolism and MDR. • DCA reconstitutes biophysical and cellular composition of tumor microenvironment.

  18. Tumor-initiating cells of breast and prostate origin show alterations in the expression of genes related to iron metabolism

    Czech Academy of Sciences Publication Activity Database

    Rychtarčíková, Zuzana; Lettlová, Sandra; Tomkova, Veronika; Korenková, Vlasta; Langerová, Lucie; Simonova, Ekaterina; Zjablovskaja, Polina; Alberich-Jorda, Meritxell; Neužil, Jiří; Truksa, Jaroslav

    2017-01-01

    Roč. 8, č. 4 (2017), s. 6376-6398 ISSN 1949-2553 R&D Projects: GA ČR GA13-28830S; GA ČR GA15-03796S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 ; RVO:68378050 Keywords : tumor-initiating cells * breast cancer * iron metabolism Subject RIV: FD - Oncology ; Hematology; EB - Genetics ; Molecular Biology (UMG-J) OBOR OECD: Cell biology; Cell biology (UMG-J) Impact factor: 5.168, year: 2016

  19. Metabolic observations during the treatment of obese patients by periods of total starvation

    NARCIS (Netherlands)

    Riet, H.G. van; Schwarz, F.; Kinderen, P.J. der; Veeman, W.

    Ten very obese female patients were treated by periods of total starvation lasting 10 days each. In the interval between these starvation periods, a diet of 600 calories was given. Twenty-one periods were completed, 6 patients went through 3 periods each. The fasting was generally well tolerated;

  20. Effects of reactive oxygen species on metabolism monitored by longitudinal 1H single voxel MRS follow-up in patients with mitochondrial disease or cerebral tumors

    International Nuclear Information System (INIS)

    Constans, J M; Collet, S; Hossu, G; Courtheoux, P; Guillamo, J S; Lechapt-Zalcman, E; Valable, S; Lacombe, S; Houee Levin, C; Gauduel, Y A; Dou, W; Ruan, S; Barre, L; Rioult, F; Derlon, J M; Chapon, F; Fong, V; Kauffmann, F

    2011-01-01

    Free radicals, or Reactive Oxygen Species (ROS), have an effect on energy and glycolytic metabolism, mitochondrial function, lipid metabolism, necrosis and apoptosis, cell proliferation, and infiltration. These changes could be monitored longitudinally (every 4 months over 6 years) in humans with glial brain tumors (low and high grade) after therapy, using conventional magnetic resonance imaging (MRI) and spectroscopy (MRS) and MR perfusion. Some examples of early clinical data from longitudinal follow-up monitoring in humans of energy and glycolytic metabolism, lipid metabolism, necrosis, proliferation, and infiltration measured by conventional MRI, MRS and perfusion, and positron emission tomography (PET) are shown in glial brain tumors after therapy. Despite the difficulty, the variability and unknown factors, these repeated measurements give us a better insight into the nature of the different processes, tumor progression and therapeutic response.

  1. Effects of reactive oxygen species on metabolism monitored by longitudinal {sup 1}H single voxel MRS follow-up in patients with mitochondrial disease or cerebral tumors

    Energy Technology Data Exchange (ETDEWEB)

    Constans, J M; Collet, S; Hossu, G; Courtheoux, P [MRI Unit, Caen University Hospital, Caen, Normandy (France); Guillamo, J S; Lechapt-Zalcman, E; Valable, S [CERVOxy Group, CI-NAPS, UMR 6232 CI-NAPS, Cyceron, Caen, Normandy (France); Lacombe, S; Houee Levin, C [Paris-Sud 11 University-CNRS, Orsay (France); Gauduel, Y A [LOA, Ecole Polytechnique - ENSTA ParisTech, Palaiseau (France); Dou, W [Tsinghua University, Beijing (China); Ruan, S [CReSTIC EA 3804, IUT Troyes, Troyes (France); Barre, L [GDMTEP, Group CI-NAPS, UMR 6232 CI-NAPS, Cyceron, Caen (France); Rioult, F [CNRS UMR 6072, GREYC, Caen, Normandy (France); Derlon, J M [Neurosurgery and Neurology, Caen University Hospital, Caen, Normandy (France); Chapon, F [Pathology, Caen University Hospital, Caen, Normandy (France); Fong, V [Caen University (France); Kauffmann, F, E-mail: constans-jm@chu-caen.fr [Mathematics LMNO CNRS UMR 6139, Caen University, Caen, Normandy (France)

    2011-01-01

    Free radicals, or Reactive Oxygen Species (ROS), have an effect on energy and glycolytic metabolism, mitochondrial function, lipid metabolism, necrosis and apoptosis, cell proliferation, and infiltration. These changes could be monitored longitudinally (every 4 months over 6 years) in humans with glial brain tumors (low and high grade) after therapy, using conventional magnetic resonance imaging (MRI) and spectroscopy (MRS) and MR perfusion. Some examples of early clinical data from longitudinal follow-up monitoring in humans of energy and glycolytic metabolism, lipid metabolism, necrosis, proliferation, and infiltration measured by conventional MRI, MRS and perfusion, and positron emission tomography (PET) are shown in glial brain tumors after therapy. Despite the difficulty, the variability and unknown factors, these repeated measurements give us a better insight into the nature of the different processes, tumor progression and therapeutic response.

  2. 31-P Relaxation times of metabolic compounds in tumors grafted in nude mice

    International Nuclear Information System (INIS)

    Remy, C.; Benabid, A.L.; Jacrot, M.; Riondel, J.; Albrand, J.P.; Decorps, M.

    1985-08-01

    The observation that water proton relaxation rates were longer in tumors than in normal tissues provided a basis for the detection of human tumors by the NMR imaging technique. To evaluate the potentiality of 31-P NMR spectroscopy as a diagnostic tool of the pathological state of tissues, T1 and T2 relaxation times have been measured for the phosphates of ATP, inorganic phosphate (Pi), phosphomonoesters (PME) and phosphocreatine (PCr) in the 31-P NMR spectra obtained in vivo for normal rat brain and rat brain tumors implanted in nude mice

  3. Antiproliferative activity in tumor cell lines, antioxidant capacity and total phenolic, flavonoid and tannin contents of Myrciaria floribunda

    Directory of Open Access Journals (Sweden)

    LUIS A.C. TIETBOHL

    Full Text Available ABSTRACT Myrciaria floribunda (H. West ex Willd. O. Berg, Myrtaceae, is a native plant species of the Atlantic Rain Forest, from north to south of Brazil. The lyophilized ethyl acetate extract from the leaves of M. floribunda was investigated for its antiproliferative activity in tumor cell lines, antioxidant capacity and its total phenolic, flavonoid and tannin contents. Antiproliferative activity was tested in vitro against seven human cancer cells and against immortalized human skin keratinocytes line (HaCat, no cancer cell. Antioxidant activity was determined using 1-diphenyl-2-picrylhydrazyl (DPPH radical scavenging and oxygen radical absorbing capacity (ORAC assays and total phenolic, flavonoid and tannin contents were determined by spectrophotometric techniques. Ethyl acetate extract of M. floribunda exhibited antiproliferative activity against cancer cell lines with total growth inhibition (TGI between 69.70 and 172.10 µg/mL. For HaCat cell, TGI value was 213.60 µg/mL. M. floribunda showed a strong antioxidant potential: EC50 of 45.89±0.42 µg/mL and 0.55±0.05 mmol TE/g for DPPH and ORAC, respectively. Total phenolic content was 0.23±0.013g gallic acid equivalents (GAE/g extract and exhibited 13.10±1.60% of tannins content. The content of flavonoid was 24.08±0.44% expressed as rutin equivalents. These results provide a direction for further researches about the antitumoral potential of M. floribunda.

  4. Glucose Metabolism Gene Expression Patterns and Tumor Uptake of {sup 18}F-Fluorodeoxyglucose After Radiation Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, George D., E-mail: george.wilson@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States); Thibodeau, Bryan J.; Fortier, Laura E.; Pruetz, Barbara L. [Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States); Galoforo, Sandra; Baschnagel, Andrew M.; Chunta, John [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Oliver Wong, Ching Yee [Department of Diagnostic Radiology and Molecular Imaging Medicine, William Beaumont Hospital, Royal Oak, Michigan (United States); Yan, Di; Marples, Brian [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Huang, Jiayi [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2014-11-01

    Purpose: To investigate whether radiation treatment influences the expression of glucose metabolism genes and compromises the potential use of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a tool to monitor the early response of head and neck cancer xenografts to radiation therapy (RT). Methods and Materials: Low passage head and neck squamous cancer cells (UT14) were injected to the flanks of female nu/nu mice to generate xenografts. After tumors reached a size of 500 mm{sup 3} they were treated with either sham RT or 15 Gy in 1 fraction. At different time points, days 3, 9, and 16 for controls and days 4, 7, 12, 21, 30, and 40 after irradiation, 2 to 3 mice were assessed with dynamic FDG-PET acquisition over 2 hours. Immediately after the FDG-PET the tumors were harvested for global gene expression analysis and immunohistochemical evaluation of GLUT1 and HK2. Different analytic parameters were used to process the dynamic PET data. Results: Radiation had no effect on key genes involved in FDG uptake and metabolism but did alter other genes in the HIF1α and glucose transport–related pathways. In contrast to the lack of effect on gene expression, changes in the protein expression patterns of the key genes GLUT1/SLC2A1 and HK2 were observed after radiation treatment. The changes in GLUT1 protein expression showed some correlation with dynamic FDG-PET parameters, such as the kinetic index. Conclusion: {sup 18}F-fluorodeoxyglucose positron emission tomography changes after RT would seem to represent an altered metabolic state and not a direct effect on the key genes regulating FDG uptake and metabolism.

  5. Eliminating animal facility light-at-night contamination and its effect on circadian regulation of rodent physiology, tumor growth, and metabolism: a challenge in the relocation of a cancer research laboratory.

    Science.gov (United States)

    Dauchy, Robert T; Dupepe, Lynell M; Ooms, Tara G; Dauchy, Erin M; Hill, Cody R; Mao, Lulu; Belancio, Victoria P; Slakey, Lauren M; Hill, Steven M; Blask, David E

    2011-05-01

    Appropriate laboratory animal facility lighting and lighting protocols are essential for maintaining the health and wellbeing of laboratory animals and ensuring the credible outcome of scientific investigations. Our recent experience in relocating to a new laboratory facility illustrates the importance of these considerations. Previous studies in our laboratory demonstrated that animal room contamination with light-at-night (LAN) of as little as 0.2 lx at rodent eye level during an otherwise normal dark-phase disrupted host circadian rhythms and stimulated the metabolism and proliferation of human cancer xenografts in rats. Here we examined how simple improvements in facility design at our new location completely eliminated dark-phase LAN contamination and restored normal circadian rhythms in nontumor-bearing rats and normal tumor metabolism and growth in host rats bearing tissue-isolated MCF7(SR(-)) human breast tumor xenografts or 7288CTC rodent hepatomas. Reducing LAN contamination in the animal quarters from 24.5 ± 2.5 lx to nondetectable levels (complete darkness) restored normal circadian regulation of rodent arterial blood melatonin, glucose, total fatty and linoleic acid concentrations, tumor uptake of O(2), glucose, total fatty acid and CO(2) production and tumor levels of cAMP, triglycerides, free fatty acids, phospholipids, and cholesterol esters, as well as extracellular-signal-regulated kinase, mitogen-activated protein kinase, serine-threonine protein kinase, glycogen synthase kinase 3β, γ-histone 2AX, and proliferating cell nuclear antigen.

  6. Effect of Brain Tumor Presence During Radiation on Tissue Toxicity: Transcriptomic and Metabolic Changes.

    Science.gov (United States)

    Zawaski, Janice A; Sabek, Omaima M; Voicu, Horatiu; Eastwood Leung, Hon-Chiu; Gaber, M Waleed

    2017-11-15

    Radiation therapy (RT) causes functional and transcriptomic changes in the brain; however, most studies have been carried out in normal rodent brains. Here, the long-term effect of irradiation and tumor presence during radiation was investigated. Male Wistar rats ∼7 weeks old were divided into 3 groups: sham implant, RT+sham implant, and RT+tumor implant (C6 glioma). Hypofractionated irradiation (8 or 6 Gy/day for 5 days) was localized to a 1-cm strip of cranium starting 5 days after implantation, resulting in complete tumor regression and prolonged survival. Biopsy of tissue was performed in the implant area 65 days after implantation. RNA was hybridized to GeneChip Rat Exon 1.0 ST array. Data were analyzed using significant analysis of microarrays and ingenuity pathway analysis. 1 H magnetic resonance spectroscopy ( 1 H-MRS) imaging was performed in the implantation site 65 to 70 days after implantation using a 9.4 T Biospec magnetic resonance imaging scanner with a quadrature rat brain array. Immunohistochemical staining for astrogliosis, HMG-CoA synthase 2, γ-aminobutyric acid (GABA) and taurine was performed at ∼65 days after implantation. Eighty-four genes had a false discovery rate <3.5%. We compared RT+tumor implant with RT+sham implant animals. The tumor presence affected networks associated with cancer/cell morphology/tissue morphology. 1 H-MRS showed significant reduction in taurine levels (P<.04) at the implantation site in both groups. However, the RT+tumor group also showed significant increase in levels of neurotransmitter GABA (P=.02). Hippocampal taurine levels were only significantly reduced in the RT+tumor group (P=.03). HMG-CoA synthase 2, GABA and taurine levels were confirmed using staining. Glial fibrillary acidic protein staining demonstrated a significant increase in inflammation that was heightened in the RT+tumor group. Our data indicate that tumor presence during radiation significantly affects long-term functional

  7. Metabolism

    Science.gov (United States)

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  8. Inhibition of Tumor Growth of Human Hepatocellular Carcinoma HepG2 Cells in a Nude Mouse Xenograft Model by the Total Flavonoids from Arachniodes exilis

    Directory of Open Access Journals (Sweden)

    Huimin Li

    2017-01-01

    Full Text Available A tumor growth model of human hepatocellular carcinoma HepG2 cells in nude mice was employed to investigate the antitumor activity of the total flavonoids extracted from Arachniodes exilis (TFAE in vivo. Several biochemical assays including hematoxylin-eosin (HE staining, immunohistochemistry, and Western blot were performed to elucidate the mechanism of action of total flavonoids extracted from Arachniodes exilis (TFAE. The results showed that TFAE effectively inhibited the tumor growth of hepatocellular carcinoma in nude mice and had no significant effect on body weight, blood system, and functions of liver and kidney. Expression levels of proapoptotic proteins Bax and cleaved caspase-3 remarkably increased while the expressions of Bcl-2, HIF-1α, and VEGF were suppressed by TFAE. These results suggested that the antitumor potential of TFEA was implied by the apoptosis of tumor cells and the inhibition of angiogenesis in tumor tissue.

  9. Targeting the sugar metabolism of tumors with a first-in-class 6-phosphofructo-2-kinase (PFKFB4) inhibitor.

    Science.gov (United States)

    Chesney, Jason; Clark, Jennifer; Lanceta, Lilibeth; Trent, John O; Telang, Sucheta

    2015-07-20

    Human tumors exhibit increased glucose uptake and metabolism as a result of high demand for ATP and anabolic substrates and this metabolotype is a negative prognostic indicator for survival. Recent studies have demonstrated that cancer cells from several tissue origins and genetic backgrounds require the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4), a regulatory enzyme that synthesizes an allosteric activator of glycolysis, fructose-2,6-bisphosphate. We report the discovery of a first-in-class PFKFB4 inhibitor, 5-(n-(8-methoxy-4-quinolyl)amino)pentyl nitrate (5MPN), using structure-based virtual computational screening. We find that 5MPN is a selective inhibitor of PFKFB4 that suppresses the glycolysis and proliferation of multiple human cancer cell lines but not non-transformed epithelial cells in vitro. Importantly, 5MPN has high oral bioavailability and per os administration of a non-toxic dose of 5MPN suppresses the glucose metabolism and growth of tumors in mice.

  10. Evaluation of apoptosis and micronucleation induced by reactor neutron beams with two different cadmium ratios in total and quiescent cell populations within solid tumors

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Ono, Koji; Sakurai, Yoshinori; Takagaki, Masao; Kobayashi, Tooru; Kinashi, Yuko; Suzuki, Minoru

    2001-01-01

    Purpose: Response of quiescent (Q) and total tumor cells in solid tumors to reactor neutron beam irradiation with two different cadmium (Cd) ratios was examined in terms of micronucleus (MN) frequency and apoptosis frequency, using four different tumor cell lines. Methods and Materials: C57BL mice bearing EL4 tumors, C3H/He mice bearing SCC VII or FM3A tumors, and Balb/c mice bearing EMT6/KU tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty min after i.p. injection of sodium borocaptate- 10 B (BSH), or 3 h after oral administration of p-boronophenylalanine- 10 B (BPA), the tumors were irradiated with neutron beams. The tumors without 10 B-compound administration were irradiated with neutron beams or γ-rays. This neutron beam irradiation was performed using neutrons with two different Cd ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the MN frequency in cells without BrdU labeling (=Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, for apoptosis assay, 6 h after irradiation, tumor cell suspensions obtained in the same manner were fixed, and the apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequencies in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. Results: Without 10 B-compounds, the sensitivity difference between total and Q cells was reduced by neutron beam irradiation. Under our particular neutron beam irradiation condition, relative biological effectiveness (RBE) of neutrons was larger in Q cells than in total cells, and the RBE values were larger for low Cd-ratio than high Cd-ratio neutrons. With 10 B-compounds, both frequencies were increased for each cell population, especially for total cells. BPA

  11. Prognostic value of PET/CT in lung cancer. Study of survival and tumor metabolic characterization

    International Nuclear Information System (INIS)

    Ladron de Guevara, David; Fuentes Anibal; Farina, Ciro; Corral, Camilo; Pefaur, Raul

    2013-01-01

    PET/CT (Positron emission tomography/computed tomography) is a hybrid image modality widely used in oncology, for staging, therapy evaluation or follow up. Aim: To evaluate the prognostic value of PET/CT in lung cancer. Material and Methods: Retrospective review of PET/CT records, selecting 51 patients with a lung malignancy, mass or nodule referred for PET/CT between December 2008 and December 2010. All had pathological confirmation of malignancy and had not been treated previously. Age, gender, body mass index, radiological features of lung tumor and metastases, and lung tumor 18 F-fluoro-2-deoxy-d-glucose uptake using the SUV (Standardized uptake value) index were recorded. Survival was analyzed using Kaplan-Meier curves and a Cox proportional regression analysis. Results: Pathology confirmed the presence of lung cancer in 47 patients aged 30 to 88 years. Four patients (7.8%) had other type of tumors such as carcinoid or lymphoma. Fifty percent of lung cancer patients died during a mean observation lapse of 18 months (range: 2-34 months). Patients with metastases, local lymph node involvement, a lung tumor size ≥ 3 cm and high tumor uptake (SUVmax > 6) had significantly lower survival. Occurrence of metastases was the only independent prognostic factor in the Cox regression. A lung lesion with a SUVmax ≥ 12 was always associated to hilar/mediastinal lymph node involvement. Conclusions: PET/CT imaging gives important prognostic information in lung cancer patients

  12. Analysis of protective and cytotoxic immune responses in vivo against metabolically inactivated and untreated cells of a mutagenized tumor line (requirements for tumor immunogenicity)

    International Nuclear Information System (INIS)

    Wehrmaker, A.; Lehmann, V.; Droege, W.

    1986-01-01

    The immunogenicity of a mutagenized subline (ESb-D) of the weakly immunogenic T-cell lymphoma L 5178 Y ESb has been characterized. The injection of 10(6) ESb-D cells ip did not establish lethal tumors in untreated DBA/2 mice but established tumors in sublethally irradiated mice. Injection of ESb-D cells into otherwise untreated DBA/2 mice established also a state of protective immunity against the subsequent injection of otherwise lethal doses of ESb tumor cells. Protection was only obtained after injection of intact but not UV-irradiated or mitomycin-C-treated ESb-D cells. A direct T-cell-mediated cytotoxic activity was also demonstrable in the spleen cells of DBA/2 mice after injection of ESb-D cells but not ESb cells. The cytotoxic activity was variant specific for ESb-D target cells, and it was induced only with intact but not UV-irradiated or mitomycin C-treated ESb-D cells. This suggested that the induction of protective and cytotoxic immunity may require the persistence of the antigen or unusually high antigen doses. The in vivo priming for a secondary in vitro cytotoxic response, in contrast, was achieved with intact and also with mitomycin C-treated ESb-D cells but again not with UV-irradiated ESb-D cells. This indicated that the metabolic activity was a minimal requirement for the in vivo immunogenicity of the ESb-D tumor line. The secondary cytotoxic activity was demonstrable on ESb-D and ESb target cells and could be restimulated in vitro about equally well with ESb-D and ESb cells. But the in vivo priming was again only obtained with ESb-D cells and not with ESb cells. These experiments thus demonstrated that the requirements for immunogenicity are more stringent in vivo than in vitro, and more stringent for the induction of direct cytotoxic and protective immunity in vivo than for the in vivo priming for secondary in vitro responses

  13. Investigating tumor perfusion and metabolism using multiple hyperpolarized 13C compounds: HP001, pyruvate and urea

    DEFF Research Database (Denmark)

    von Morze, Cornelius; Larson, Peder E.Z.; Hu, Simon

    2012-01-01

    The metabolically inactive hyperpolarized agents HP001 (bis-1,1-(hydroxymethyl)-[1-13C]cyclopropane-d8) and urea enable a new type of perfusion magnetic resonance imaging based on a direct signal source that is background-free. The addition of perfusion information to metabolic information obtained...... (T1=95 s ex vivo, 32 s in vivo at 3 T) using a pulse sequence with balanced steady-state free precession and ramped flip angle over time for efficient utilization of the hyperpolarized magnetization and three-dimensional echo-planar spectroscopic imaging of urea copolarized with [1-13C...... of separate dynamic HP001 imaging and copolarized pyruvate/urea imaging were compared. A strong and significant correlation (R=0.73, P=.02) detected between the urea and HP001 data confirmed the value of copolarizing urea with pyruvate for simultaneous assessment of perfusion and metabolism....

  14. Effects of total vitamin A, vitamin C, and fruit intake on risk for metabolic syndrome in Korean women and men.

    Science.gov (United States)

    Park, Sunmin; Ham, Jung-O; Lee, Byung-Kook

    2015-01-01

    The question of whether the consumption of antioxidants prevents and alleviates metabolic syndrome (MetS) by reducing insulin resistance remains controversial. The aim of this study was to assess whether the intake of vitamin A (including β-carotene), vitamin C, fruits, or vegetables was negatively associated with MetS in Korean adults aged ≥ 20 y. We conducted a cross-sectional study of 27,656 adults ≥ 20 y of age who participated in the 2007-2012 Korean National Health and Nutrition Examination Survey. Daily intake of vitamin A and vitamin C was assessed by 24-h recall, and the consumption of fruits and vegetables was determined using a food frequency questionnaire. Odds ratios (ORs) for MetS were calculated for log2-transformed vitamin A and C intake values and for the interaction of sex with vitamin A and C intake, after covariate adjustment. Interactions were seen between total vitamin A and C intake and sex for MetS. With a twofold increase in total vitamin A and C intake in women, the ORs (95% confidence intervals) for metabolic syndrome were 0.942 (0.901-0.985) and 0.933 (0.883-0.987), indicating decreases of 5.8% and 6.7% in MetS, respectively. There were no equivalent decreases in men. Women in the second and highest tertiles of fruit intake exhibited 17.5% and 21.8% lower incidences of MetS, respectively, compared with women in the lowest tertile. The intake of total vitamin A and C, as well as moderate and high fruit intake, may have alleviated MetS in women, but not in men, in a representative sample of the general South Korean population. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Early prediction of therapy response and disease free survival after induction chemotherapy in stage III non-small cell lung cancer by FDG-PET: Correlation between tumor FDG-metabolism and morphometric tumor response

    International Nuclear Information System (INIS)

    Baum, R.P.; Schmuecking, M.; Niesen, A.; Przetak, C.; Griesinger, F.

    2002-01-01

    Aim: Chemotherapy with Docetaxel and Carboplatin (DC) has shown high response rates in advanced non-small cell lung cancer (NSCLC). Histologic tumor response after chemotherapy or combined chemoradiotherapy is strongly associated with systemic tumor control and potentially cure. Metabolic tumor response assessed by FDG-PET after induction VIP-chemotherapy has been shown to be predictive of outcome in NSCLC. The aim of the present study was to correlate the tumor FDG metabolism as measured by F-18 FDG-PET with morphometric findings after DC induction chemotherapy plus Erythropoietin (10,000 IU Epo s.c. three times a week). Material and Methods: In this prospective multicenter study, 54 patients with NSCLC stage IIIA (9 patients) or IIIB (45 patients) were enrolled and received neoadjuvant treatment with D 100 mg/m 2 d1 and C AUC 7.5 d2 q21 days for 4 cycles prior to surgery. Postoperatively, all patients received adjuvant radiotherapy. WB-PET-studies (ECAT Exact 47) were obtained p.i. of 400 MBq F-18 FDG. Standardized uptake values (SUV), metabolic tumor diameter (MTD) and metabolic tumor index (MTI SUV x MTD) were assessed. Image fusion of PET and CT data was applied on a HERMES computer. Results: Of 54 enrolled patients, 46 were evaluable for response by CT. 30/46 patients (65%) achieved complete remission (CR, 1 patient) or partial remission (PR 29 patients.). Of the 46 patients, 37 patients completed neoadjuvant chemotherapy (Chx) and were studied before and after Chx by FDG-PET. 14 (30% of the 46 evaluable patients) had SUV < 2.5, corresponding to metabolic complete remission (mCR), 23 had PR or stable disease (non-mCR); in 9 patients, PET was not performed because of progressive disease demonstrated by CT. The R0-resection rate was 56% (27/48 evaluable patients). Of the 14 patients with metabolic CR, 9 were evaluated by morphometry. All had regression grades III (no vital tumor cells) or grade IIB (< 10% vital tumor cells and induced apoptosis). With a median

  16. Reversal of uremic tumoral calcinosis by optimization of clinical treatment of bone and mineral metabolism disorder

    Directory of Open Access Journals (Sweden)

    Mariana Espiga Maioli

    Full Text Available Abstract Tumoral calcinosis is an uncommon type of extraosseous calcification characterized by large rubbery or cystic masses containing calcium-phosphate deposits. The condition prevails in the periarticular tissue with preservation of osteoarticular structures. Elevated calcium-phosphorus products and severe secondary hyperparathyroidism are present in most patients with uremic tumoral calcionosis (UTC. Case report of an obese secondary to chronic glomerulonephritis, undergoing continuous ambulatory peritoneal dialysis (CAPD reported the appearance of painless tumors in the medial surface of fifth finger and left arm. Tumoral calcinosis was confirmed by left biceps biopsy. Poor adherence to CAPD. The patient was transferred to the "tidal" modality of peritoneal dialysis and after was treated by hemodialysis, despite the persistence of severe hyperparathyroidism progressive reduction of UTC until near to its complete disappearance. Nowadays, one year after patient received deceased-donor kidney transplantation, he presents with an improvement in secondary hyperparathyroidism. UTC should be included in the elucidation of periarticular calcification of every patient on dialysis. Relevant laboratory findings such as secondary hyperparathyroidism and elevated calcium- phosphorus products in the presence of periarticular calcification should draw attention to the diagnosis of UTC.

  17. Hypoxia and tumor metabolism in radiation oncology: Targets visualized by positron emission tomography

    NARCIS (Netherlands)

    Wijsman, R.; Kaanders, J.H.A.M.; Oyen, W.J.G.; Bussink, J.

    2013-01-01

    Due to the amazing leap of technology in radiation oncology in the past few years, cancer treatment will become more individualized. Molecular imaging with PET contributed to this with its many tracers available, each of them visualizing a specific feature of a tumor and its microenvironment

  18. KRAS Genotype Correlates with Proteasome Inhibitor Ixazomib Activity in Preclinical In Vivo Models of Colon and Non-Small Cell Lung Cancer: Potential Role of Tumor Metabolism.

    Directory of Open Access Journals (Sweden)

    Nibedita Chattopadhyay

    Full Text Available In non-clinical studies, the proteasome inhibitor ixazomib inhibits cell growth in a broad panel of solid tumor cell lines in vitro. In contrast, antitumor activity in xenograft tumors is model-dependent, with some solid tumors showing no response to ixazomib. In this study we examined factors responsible for ixazomib sensitivity or resistance using mouse xenograft models. A survey of 14 non-small cell lung cancer (NSCLC and 6 colon xenografts showed a striking relationship between ixazomib activity and KRAS genotype; tumors with wild-type (WT KRAS were more sensitive to ixazomib than tumors harboring KRAS activating mutations. To confirm the association between KRAS genotype and ixazomib sensitivity, we used SW48 isogenic colon cancer cell lines. Either KRAS-G13D or KRAS-G12V mutations were introduced into KRAS-WT SW48 cells to generate cells that stably express activated KRAS. SW48 KRAS WT tumors, but neither SW48-KRAS-G13D tumors nor SW48-KRAS-G12V tumors, were sensitive to ixazomib in vivo. Since activated KRAS is known to be associated with metabolic reprogramming, we compared metabolite profiling of SW48-WT and SW48-KRAS-G13D tumors treated with or without ixazomib. Prior to treatment there were significant metabolic differences between SW48 WT and SW48-KRAS-G13D tumors, reflecting higher oxidative stress and glucose utilization in the KRAS-G13D tumors. Ixazomib treatment resulted in significant metabolic regulation, and some of these changes were specific to KRAS WT tumors. Depletion of free amino acid pools and activation of GCN2-eIF2α-pathways were observed both in tumor types. However, changes in lipid beta oxidation were observed in only the KRAS WT tumors. The non-clinical data presented here show a correlation between KRAS genotype and ixazomib sensitivity in NSCLC and colon xenografts and provide new evidence of regulation of key metabolic pathways by proteasome inhibition.

  19. KRAS Genotype Correlates with Proteasome Inhibitor Ixazomib Activity in Preclinical In Vivo Models of Colon and Non-Small Cell Lung Cancer: Potential Role of Tumor Metabolism.

    Science.gov (United States)

    Chattopadhyay, Nibedita; Berger, Allison J; Koenig, Erik; Bannerman, Bret; Garnsey, James; Bernard, Hugues; Hales, Paul; Maldonado Lopez, Angel; Yang, Yu; Donelan, Jill; Jordan, Kristen; Tirrell, Stephen; Stringer, Bradley; Xia, Cindy; Hather, Greg; Galvin, Katherine; Manfredi, Mark; Rhodes, Nelson; Amidon, Ben

    2015-01-01

    In non-clinical studies, the proteasome inhibitor ixazomib inhibits cell growth in a broad panel of solid tumor cell lines in vitro. In contrast, antitumor activity in xenograft tumors is model-dependent, with some solid tumors showing no response to ixazomib. In this study we examined factors responsible for ixazomib sensitivity or resistance using mouse xenograft models. A survey of 14 non-small cell lung cancer (NSCLC) and 6 colon xenografts showed a striking relationship between ixazomib activity and KRAS genotype; tumors with wild-type (WT) KRAS were more sensitive to ixazomib than tumors harboring KRAS activating mutations. To confirm the association between KRAS genotype and ixazomib sensitivity, we used SW48 isogenic colon cancer cell lines. Either KRAS-G13D or KRAS-G12V mutations were introduced into KRAS-WT SW48 cells to generate cells that stably express activated KRAS. SW48 KRAS WT tumors, but neither SW48-KRAS-G13D tumors nor SW48-KRAS-G12V tumors, were sensitive to ixazomib in vivo. Since activated KRAS is known to be associated with metabolic reprogramming, we compared metabolite profiling of SW48-WT and SW48-KRAS-G13D tumors treated with or without ixazomib. Prior to treatment there were significant metabolic differences between SW48 WT and SW48-KRAS-G13D tumors, reflecting higher oxidative stress and glucose utilization in the KRAS-G13D tumors. Ixazomib treatment resulted in significant metabolic regulation, and some of these changes were specific to KRAS WT tumors. Depletion of free amino acid pools and activation of GCN2-eIF2α-pathways were observed both in tumor types. However, changes in lipid beta oxidation were observed in only the KRAS WT tumors. The non-clinical data presented here show a correlation between KRAS genotype and ixazomib sensitivity in NSCLC and colon xenografts and provide new evidence of regulation of key metabolic pathways by proteasome inhibition.

  20. Riboflavin carrier protein-targeted fluorescent USPIO for the assessment of vascular metabolism in tumors

    NARCIS (Netherlands)

    Jayapaul, J.; Arns, S.; Lederle, W.; Lammers, Twan Gerardus Gertudis Maria; Comba, P.; Gätjens, J.; Kiessling, F.

    2012-01-01

    Abstract Riboflavin (Rf) and its metabolic analogs flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are essential for normal cellular growth and function. Their intracellular transport is regulated by the riboflavin carrier protein (RCP), which has been shown to be over-expressed by

  1. Original communication: Basal metabolic rate in children with a solid tumor

    NARCIS (Netherlands)

    Broeder, den E.; Oeseburg, B.; Lippens, R.J.J.; Staveren, van W.A.; Sengers, R.C.A.; Hof, van 't M.A.; Tolboom, J.J.M.

    2001-01-01

    Objective: To study the level of and changes in basal metabolic rate (BMR) in children with a solid tumour at diagnosis and during treatment in order to provide a more accurate estimate of energy requirements for nutritional support. Design: An observational study. Setting: Tertiary care at the

  2. Can metabolic tumor parameters on primary staging 18F-FDG PET/CT aid in risk stratification of primary central nervous system lymphomas for patient management as a prognostic model?

    Science.gov (United States)

    Okuyucu, K; Alagoz, E; Ince, S; Ozaydin, S; Arslan, N

    Primary central nervous system (CNS) lymphoma is an aggressive and fatal extranodal non-Hodgkin lymphoma jailed in CNS at initial diagnosis. Its prognosis is poor and the disease has a fatal outcome when compared with systemic non-Hodgkin lymphoma. A few baseline risk stratification scoring systems have been suggested to estimate the prognosis mainly based on serum lactate dehydrogenase level,age, Karnofsky performance score, involvement of deep brain structures and cerebrospinal fluid protein concentration. 18 F-FDG PET/CT has a high prognostic value with respect to overall survival and disease-free survival in many cancers and lymphomas. We aimed to investigate metabolic tumor indexes on primary staging 18 F-FDG PET/CT as prognostic markers in primary CNS lymphoma. Fourteen patients with primary CNS diffuse large B-cell lymphoma (stage i) were enrolled in this retrospective cohort study. Primary staging 18 F-FDG PET/CT was performed and quantitative parameters like maximum standardized uptake value, average standardized uptake value, metabolic tumor volume and total lesion glycolysis (TLG) were calculated for all patients before the treatment. Cox regression models were performed to determine their relation with survival time. In the evaluation of all potential risk factors impacting recurrence/metastases (age, sex, serum lactate dehydrogenase, involvement of deep brain structures, maximum standardized uptake value, average standardized uptake value, metabolic tumor volume, and TLG) with univariate analysis, TLG remained statistically significant (P=.02). Metabolic tumor parameters are useful in prognosis estimation of primary CNS lymphomas, especially TLG, which is the most important one and may play a role in patient management. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  3. Vitamin D metabolism and effects on pluripotency genes and cell differentiation in testicular germ cell tumors in vitro and in vivo

    DEFF Research Database (Denmark)

    Blomberg Jensen, Martin; Jørgensen, Anne; Nielsen, John Erik

    2012-01-01

    and express pluripotency factors (NANOG/OCT4). Vitamin D (VD) is metabolized in the testes, and here, we examined VD metabolism in TGCT differentiation and pluripotency regulation. We established that the VD receptor (VDR) and VD-metabolizing enzymes are expressed in human fetal germ cells, CIS, and invasive......) treatment in vivo. These novel findings show that VD metabolism is involved in the mesodermal transition during differentiation of cancer cells with embryonic stem cell characteristics, which points to a function for VD during early embryonic development and possibly in the pathogenesis of TGCTs.......Testicular germ cell tumors (TGCTs) are classified as either seminomas or nonseminomas. Both tumors originate from carcinoma in situ (CIS) cells, which are derived from transformed fetal gonocytes. CIS, seminoma, and the undifferentiated embryonal carcinoma (EC) retain an embryonic phenotype...

  4. Metabolism

    Science.gov (United States)

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  5. Analysis of primary tumor metabolic volume during chemoradiotherapy in locally advanced non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Roengvoraphoj, Olarn; Eze, Chukwuka; Li, Minglun; Dantes, Maurice; Taugner, Julian [LMU Munich, Department of Radiation Oncology, University Hospital, Munich (Germany); Wijaya, Cherylina [Asklepios Fachkliniken Muenchen-Gauting, Department of Pulmonology, Munich (Germany); Tufman, Amanda; Huber, Rudolf Maria [Ludwig-Maximilians-University of Munich and Thoracic Oncology Centre Munich, Respiratory Medicine and Thoracic Oncology, Internal Medicine V, Munich (Germany); German Centre for Lung Research (DZL CPC-M) (Germany); Belka, Claus; Manapov, Farkhad [LMU Munich, Department of Radiation Oncology, University Hospital, Munich (Germany); German Centre for Lung Research (DZL CPC-M) (Germany)

    2018-02-15

    Positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-d-glucose integrated with computed tomography (18F-FDG-PET/CT) has an established role in the initial diagnosis and staging of lung cancer. However, a prognostic value of PET/CT during multimodality treatment has not yet been fully clarified. This study evaluated the role of primary tumor metabolic volume (PT-MV) changes on PET/CT before, during, and after chemoradiotherapy (CRT). A total of 65 patients with non-small-cell lung cancer (NSCLC) UICC stage IIIA/B (TNM 7th Edition) were treated with definitive chemoradiotherapy (sequential or concurrent setting). PET/CT was acquired before the start, at the end of the third week, and 6 weeks following CRT. Median overall survival (OS) for the entire cohort was 16 months (95% confidence interval [CI]: 12-20). In all, 60 (92.3%) patients were eligible for pre-treatment (pre-PT-MV), 28 (43%) for mid-treatment (mid-PT-MV), and 53 (81.5%) for post-treatment (post-PT-MV) volume analysis. Patients with pre-PT-MV >63 cm{sup 3} had worse OS (p < 0.0001). A reduction from mid-PT-MV to post-PT-MV of >15% improved OS (p = 0.001). In addition, patients with post-PT-MV > 25 cm{sup 3} had significantly worse outcome (p = 0.001). On multivariate analysis, performance status (p = 0.002, hazard ratio [HR] 0.007; 95% CI 0.00-0.158), pre-PT-MV1 < 63 cm{sup 3} (p = 0.027, HR 3.98; 95% CI 1.17-13.49), post-PT-MV < 25 cm{sup 3} (p = 0.013, HR 11.90; 95% CI 1.70-83.27), and a reduction from mid-PT-MV to post-PT-MV > 15% (p = 0.004, HR 0.25; 95% CI 0.02-0.31) correlated with improved OS. Our results demonstrated that pre- and post-treatment PT-MV, as well as an at least 15% reduction in mid- to post-PT-MV, significantly correlates with OS in patients with inoperable locally advanced NSCLC. (orig.) [German] Die kombinierte Positronenemissionstomographie (PET) mit {sup 18}F-2-Fluor-2-desoxy-D-Glukose und Computertomographie ({sup 18}F-FDG-PET/CT) hat sich in der initialen

  6. Dynamic scenario of metabolic pathway adaptation in tumors and therapeutic approach.

    Science.gov (United States)

    Peppicelli, Silvia; Bianchini, Francesca; Calorini, Lido

    2015-01-01

    Cancer cells need to regulate their metabolic program to fuel several activities, including unlimited proliferation, resistance to cell death, invasion and metastasis. The aim of this work is to revise this complex scenario. Starting from proliferating cancer cells located in well-oxygenated regions, they may express the so-called "Warburg effect" or aerobic glycolysis, meaning that although a plenty of oxygen is available, cancer cells choose glycolysis, the sole pathway that allows a biomass formation and DNA duplication, needed for cell division. Although oxygen does not represent the primary font of energy, diffusion rate reduces oxygen tension and the emerging hypoxia promotes "anaerobic glycolysis" through the hypoxia inducible factor-1α-dependent up-regulation. The acquired hypoxic phenotype is endowed with high resistance to cell death and high migration capacities, although these cells are less proliferating. Cells using aerobic or anaerobic glycolysis survive only in case they extrude acidic metabolites acidifying the extracellular space. Acidosis drives cancer cells from glycolysis to OxPhos, and OxPhos transforms the available alternative substrates into energy used to fuel migration and distant organ colonization. Thus, metabolic adaptations sustain different energy-requiring ability of cancer cells, but render them responsive to perturbations by anti-metabolic agents, such as inhibitors of glycolysis and/or OxPhos.

  7. A Metabolism-Based Synergy for Total Coumarin Extract of Radix Angelicae Dahuricae and Ligustrazine on Migraine Treatment in Rats

    Directory of Open Access Journals (Sweden)

    Shan Feng

    2018-04-01

    Full Text Available Radix Angelicae dahuricae, containing coumarins, which might affect cytochrome P450 enzyme (CYP450 activity, has been co-administered with ligustrazine, a substrate of CYP450s, for the clinical treatment of migraine. However, whether a pharmacokinetic-based synergy exists between Radix Angelicae dahuricae and ligustrazine is still unknown. In this study, the total coumarin extract (TCE of Radix Angelicae dahuricae (50 mg/kg, orally reinforced the anti-migraine activity of ligustrazine by declining head scratching, plasma calcitonin gene-related peptide, and serum nitric oxide, as well as increasing plasma endothelin levels in rats (p < 0.05. Moreover, the pharmacokinetic study reflected that TCE potentiated the area under the concentration–time curve of ligustrazine and prolonged its mean retention time in rats (p < 0.05. Besides, the IC50 for TCE, imperatorin and isoimperatorin inhibiting ligustrazine metabolism were 5.0 ± 1.02, 1.35 ± 0.46, 4.81 ± 1.14 µg/mL in human liver microsomes, and 13.69 ± 1.11, 1.19 ± 1.09, 1.69 ± 1.17 µg/mL in rat liver microsomes, respectively. Moreover, imperatorin and isoimperatorin were CYP450s inhibitors with IC50 < 10 µM for CYP1A2, 2C9, 2D6, and 3A4. Therefore, this study concluded that Radix Angelicae dahuricae could increase ligustrazine plasma concentration and then reinforce its pharmacological effect by inhibiting its metabolism through interference with CYP450s. This could be one mechanism for the synergy between Radix Angelicae dahuricae and ligustrazine on migraine treatment.

  8. SU-F-R-42: Association of Radiomic and Metabolic Tumor Volumes in Radiation Treatment of Glioblastoma Multiforme

    International Nuclear Information System (INIS)

    Lopez, C; Nagornaya, N; Parra, N; Kwon, D; Ishkanian, F; Markoe, A; Maudsley, A; Stoyanova, R

    2016-01-01

    Purpose: High-throughput extraction of imaging and metabolomic quantitative features from MRI and MR Spectroscopy Imaging (MRSI) of Glioblastoma Multiforme (GBM) results in tens of variables per patient. In radiotherapy (RT) of GBM, the relevant metabolic tumor volumes (MTVs) are related to aberrant levels of N-acetyl Aspartate (NAA) and Choline (Cho). Corresponding Clinical Target Volumes (CTVs) for RT planning are based on Contrast Enhancing T1-weighted MRI (CE-T1w) and T2-weighted/Fluid Attenuated Inversion Recovery (FLAIR) MRI. The objective is to build a framework for investigation of associations between imaging, CTV, and MTV features better understanding of the underlying information in the CTVs and dependencies between these volumes. Methods: Necrotic portions, enhancing lesion and edema were manually contoured on T1w/T2w images for 17 GBM patients. CTVs and MTVs for NAA (MTV NAA ) and Cho (MTV Cho ) were constructed. Tumors were scored categorically for ten semantic imaging traits by neuroradiologist. All features were investigated for redundancy. Two-way correlations between imaging and RT/MTV features were visualized as heat maps. Associations between MTV NAA , MTV Cho and imaging features were studied using Spearman correlation. Results: 39 imaging features were computed per patient. Half of the imaging traits were replaced with automatically extracted continuous variables. 21 features were extracted from MTVs/CTVs. There were a high number (43) of significant correlations of imaging with CTVs/MTV NAA while very few (10) significant correlations were with CTVs/MTV Cho . MTV NAA was found to be closely associated with MRI volumes, MTV Cho remains elusive for characterization with imaging. Conclusion: A framework for investigation of co-dependency between MRI and RT/metabolic features is established. A series of semantic imaging traits were replaced with automatically extracted continuous variables. The approach will allow for exploration of relationships

  9. SU-F-R-42: Association of Radiomic and Metabolic Tumor Volumes in Radiation Treatment of Glioblastoma Multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, C; Nagornaya, N; Parra, N; Kwon, D; Ishkanian, F; Markoe, A; Maudsley, A; Stoyanova, R [University of Miami, Miami, Florida (United States)

    2016-06-15

    Purpose: High-throughput extraction of imaging and metabolomic quantitative features from MRI and MR Spectroscopy Imaging (MRSI) of Glioblastoma Multiforme (GBM) results in tens of variables per patient. In radiotherapy (RT) of GBM, the relevant metabolic tumor volumes (MTVs) are related to aberrant levels of N-acetyl Aspartate (NAA) and Choline (Cho). Corresponding Clinical Target Volumes (CTVs) for RT planning are based on Contrast Enhancing T1-weighted MRI (CE-T1w) and T2-weighted/Fluid Attenuated Inversion Recovery (FLAIR) MRI. The objective is to build a framework for investigation of associations between imaging, CTV, and MTV features better understanding of the underlying information in the CTVs and dependencies between these volumes. Methods: Necrotic portions, enhancing lesion and edema were manually contoured on T1w/T2w images for 17 GBM patients. CTVs and MTVs for NAA (MTV{sub NAA}) and Cho (MTV{sub Cho}) were constructed. Tumors were scored categorically for ten semantic imaging traits by neuroradiologist. All features were investigated for redundancy. Two-way correlations between imaging and RT/MTV features were visualized as heat maps. Associations between MTV{sub NAA}, MTV{sub Cho} and imaging features were studied using Spearman correlation. Results: 39 imaging features were computed per patient. Half of the imaging traits were replaced with automatically extracted continuous variables. 21 features were extracted from MTVs/CTVs. There were a high number (43) of significant correlations of imaging with CTVs/MTV{sub NAA} while very few (10) significant correlations were with CTVs/MTV{sub Cho}. MTV{sub NAA} was found to be closely associated with MRI volumes, MTV{sub Cho} remains elusive for characterization with imaging. Conclusion: A framework for investigation of co-dependency between MRI and RT/metabolic features is established. A series of semantic imaging traits were replaced with automatically extracted continuous variables. The approach will

  10. Does the pretreatment tumor sampling location correspond with metabolic activity on 18F-FDG PET/CT in breast cancer patients scheduled for neoadjuvant chemotherapy?

    Energy Technology Data Exchange (ETDEWEB)

    Koolen, Bas B., E-mail: b.koolen@nki.nl [Department of Nuclear Medicine, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Department of Surgical Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Elshof, Lotte E. [Department of Nuclear Medicine, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Department of Surgical Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Loo, Claudette E. [Department of Radiology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Wesseling, Jelle [Department of Pathology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Vrancken Peeters, Marie-Jeanne T.F.D. [Department of Surgical Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Vogel, Wouter V. [Department of Nuclear Medicine, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Rutgers, Emiel J.Th. [Department of Surgical Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Valdés Olmos, Renato A. [Department of Nuclear Medicine, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands)

    2013-12-01

    Purpose: To define the correlation between the core biopsy location and the area with highest metabolic activity on 18F-FDG PET/CT in stage II–III breast cancer patients before neoadjuvant chemotherapy. Also, we would like to select a subgroup of patients in which PET/CT information may optimize tumor sampling. Methods: A PET/CT in prone position was acquired in 199 patients with 203 tumors. The distance and relative difference in standardized uptake value (SUV) between core biopsy localization (indicated by a marker) and area with highest degree of FDG uptake were evaluated. A distance ≥2 cm and a relative difference in SUV ≥25% were considered clinically relevant and a combination of both was defined as non-correspondence. Non-correspondence for different tumor characteristics (TNM stage, lesion morphology on MRI and PET/CT, histology, subtype, grade, and Ki-67) was assessed. Results: Non-correspondence was found in 28 (14%) of 203 tumors. Non-correspondence was significantly associated with T-stage, lesion morphology on MRI and PET/CT, tumor diameter, and histologic type. It was more often seen in tumors with a higher T-stage (p = 0.028), diffuse (non-mass) and multifocal tumors on MRI (p = 0.001), diffuse and multifocal tumors on PET/CT (p < 0.001), tumors >3 cm (p < 0.001), and lobular carcinomas (p < 0.001). No association was found with other features. Conclusion: Non-correspondence between the core biopsy location and area with highest FDG uptake is regularly seen in stage II–III breast cancer patients. PET/CT information and possibly FDG-guided biopsies are most likely to improve pretreatment tumor sampling in tumors >3 cm, lobular carcinomas, and diffuse and multifocal tumors.

  11. Application of the total reflection X-ray fluorescence method to the elemental analysis of brain tumors of different types and grades of malignancy

    International Nuclear Information System (INIS)

    Lankosz, M.W.; Grzelak, M.; Ostachowicz, B.; Wandzilak, A.; Szczerbowska-Boruchowska, M.; Wrobel, P.; Radwanska, E.; Adamek, D.

    2014-01-01

    The process of carcinogenesis may influence normal biochemical reactions leading to alterations in the elemental composition of the tissue. Total reflection X-ray fluorescence analysis (TXRF) was applied to the elemental analysis of different brain tumors. The following elements were present in all the neoplastic tissues analyzed: K, Ca, Fe, Cu, Zn and Rb. The results of the analysis showed that the elemental composition of a relatively small fragment of tissue represents satisfactorily the biochemical “signature” of a cancer. On the basis of the element concentrations determined, it was possible to differentiate between some types of brain tumors. - Highlights: • Elemental composition represents the biochemical signature of brain cancer. • The element levels differentiate some types of brain tumors. • TXRF spectrometry is a useful tool for elemental trace analysis of brain cancer

  12. Prediction of cardiovascular and total mortality in Chinese type 2 diabetic patients by the WHO definition for the metabolic syndrome.

    Science.gov (United States)

    Ko, G T-C; So, W-Y; Chan, N N; Chan, W-B; Tong, P C-Y; Li, J; Yeung, V; Chow, C-C; Ozaki, R; Ma, R C-W; Cockram, C S; Chan, J C-N

    2006-01-01

    The aim of this study is to investigate the prevalence of metabolic syndrome (MES) in type 2 diabetic patients and the predictive values of the World Health Organization (WHO) and National Cholesterol Education Programme (NCEP) definitions and the individual components of the MES on total and cardiovascular mortality. A prospective analysis of a consecutive cohort of 5202 Chinese type 2 diabetic patients recruited between July 1994 and April 2001. The prevalence of the MES was 49.2-58.1% depending on the use of various criteria. There were 189 deaths (men: 100 and women: 89) in these 5205 patients during a median (interquartile range) follow-up period of 2.1 (0.3-3.6 years). Of these, 164 (87%) were classified as cardiovascular deaths. Using the NCEP criterion, patients with MES had a death rate similar to those without (3.51 vs. 3.85%). By contrast, based on the WHO criteria, patients with MES had a higher mortality rate than those without (4.3 vs. 2.4%, p = 0.002). Compared to patients with neither NCEP- nor WHO-defined MES, only the group with MES defined by the WHO, but not NCEP, criterion had significantly higher mortality rate (2.6 vs. 6.8%, p hypertension, low BMI and albuminuria were the key predictors for these adverse events. In Chinese type 2 diabetic patients, the WHO criterion has a better discriminative power over the NCEP criterion for predicting death. Among the various components of the MES defined either by WHO or NCEP, hypertension, albuminuria and low BMI were the main predictors of cardiovascular and total mortality.

  13. Radio-induced neuropathology: from early effects to late sequelae. Rat behavioural and metabolic studies after sublethal total body irradiation

    International Nuclear Information System (INIS)

    Martigne, A.P.

    2010-05-01

    The radioresistance dogma of Central Nervous System (CNS) is now obsolete. Recent progress in neuroscience allow us to reconsider the radiation-induced cognitive dysfunctions observed after radiation therapy or after a nuclear accident, and to devise appropriate diagnostic and therapeutic means. We have developed a Rat model to study the effects of total body irradiation at a sublethal dose (4.5 Gy). This leads to impaired learning and memory of a task being acquired during the first month - which is prevented by administration of a radioprotector (amifostine) - while it does not appear to affect retrograde memory. Early, an apoptotic wave occurs in the sub-ventricular zone, 5 to 9 hours after exposure, while neuro-genesis is suppressed. Two days after irradiation, the metabolic study conducted by NMR HRMAS (High Resolution Magic Angle Spinning) suggests the presence of cerebral oedema and the study of brain lipids in liquid NMR confirms the membrane damages (elevated cholesterol and phospholipids). The lipid profile is then normalized while a gliosis appears. Finally, 1 month post-irradiation, the elevation of GABA, an inhibitory neurotransmitter, in 2 separate brain structures, occurs simultaneously with a taurine decrease in the hippocampus that lasts 6 months. Our integrated model allows validating bio-markers measurable in vivo NMR spectroscopy - the next experimental stage - and testing new radiation-protective agents. (author)

  14. Local tumor control and cosmetic outcome following breast-conserving surgery and radiation up to a total dose of 56 Gy without boost in breast cancer patients

    International Nuclear Information System (INIS)

    Bayerl, A.

    2001-01-01

    Purpose: To evaluate overall survival, local tumor control and cosmetic outcome after breast-conserving surgery followed by radiotherapy without boost irradiation. Patients and Methods: In a retrospective study 270 breast cancer patients were treated with breast conserving surgery combined with a homogenous radiation of the tumor bearing breast up to a total dose of 56 Gy without local boost irradiation. Mean follow-up was 48 months. Local tumor control, side effects, cosmetic results and contentment with treatment were assessed using physical examinations and interviews based on a standardized questionnaire. Results: Cause-specific survival at 5 years after treatment was 88.3%, actuarial disease-free survival at 5 years was 76.1%. Within 23 to 78 months after treatment 12 patients suffered from ipsilateral breast recurrence. The actuarial freedom from local recurrence (single tumor manifestation) was 96.8% at 5 years after treatment, 89% at 10 years. The occurrence of local failures was not significantly correlated to tumor size, margins, grading, nodal status, age or lymphangiosis. 15.6% of the patients developed distant metastases. In all patients treatment was performed without interruption. Side effects were predominantly of mild degree, no severe side effects were detected. 73% of physicians and 81% of patients scored their cosmetic outcome as excellent or good. 93% of patients would again decide in favor of this procedure. Whereas, use of adjuvant chemotherapy as well as subcutaneous reconstruction of breast tissue did not significantly affect breast cosmesis, analysis demonstrated impaired cosmetic results related to a larger breast size. Conclusion: The data of this study show that tumor control achieved by breast conserving surgery in combination with a radiation technique up to a total dose of 56 Gy which omits boost irradiation is within the range of literature data. Side effects of the therapy were tolerable. The treatment displayed a good

  15. FDG-PET Response Prediction in Pediatric Hodgkin’s Lymphoma: Impact of Metabolically Defined Tumor Volumes and Individualized SUV Measurements on the Positive Predictive Value

    Energy Technology Data Exchange (ETDEWEB)

    Hussien, Amr Elsayed M. [Department of Nuclear Medicine (KME), Forschungszentrum Jülich, Medical Faculty, Heinrich-Heine-University Düsseldorf, Jülich, 52426 (Germany); Department of Nuclear Medicine, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, 40225 (Germany); Furth, Christian [Department of Radiology and Nuclear Medicine, Medical School, Otto-von-Guericke University Magdeburg, Magdeburg, 39120 (Germany); Schönberger, Stefan [Department of Pediatric Oncology, Hematology and Clinical Immunology, University Children’s Hospital, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, 40225 (Germany); Hundsdoerfer, Patrick [Department of Pediatric Oncology and Hematology, Charité Campus Virchow, Humboldt-University Berlin, Berlin, 13353 (Germany); Steffen, Ingo G.; Amthauer, Holger [Department of Radiology and Nuclear Medicine, Medical School, Otto-von-Guericke University Magdeburg, Magdeburg, 39120 (Germany); Müller, Hans-Wilhelm; Hautzel, Hubertus, E-mail: h.hautzel@fz-juelich.de [Department of Nuclear Medicine (KME), Forschungszentrum Jülich, Medical Faculty, Heinrich-Heine-University Düsseldorf, Jülich, 52426 (Germany); Department of Nuclear Medicine, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, 40225 (Germany)

    2015-01-28

    Background: In pediatric Hodgkin’s lymphoma (pHL) early response-to-therapy prediction is metabolically assessed by (18)F-FDG PET carrying an excellent negative predictive value (NPV) but an impaired positive predictive value (PPV). Aim of this study was to improve the PPV while keeping the optimal NPV. A comparison of different PET data analyses was performed applying individualized standardized uptake values (SUV), PET-derived metabolic tumor volume (MTV) and the product of both parameters, termed total lesion glycolysis (TLG); Methods: One-hundred-eight PET datasets (PET1, n = 54; PET2, n = 54) of 54 children were analysed by visual and semi-quantitative means. SUVmax, SUVmean, MTV and TLG were obtained the results of both PETs and the relative change from PET1 to PET2 (Δ in %) were compared for their capability of identifying responders and non-responders using receiver operating characteristics (ROC)-curves. In consideration of individual variations in noise and contrasts levels all parameters were additionally obtained after threshold correction to lean body mass and background; Results: All semi-quantitative SUV estimates obtained at PET2 were significantly superior to the visual PET2 analysis. However, ΔSUVmax revealed the best results (area under the curve, 0.92; p < 0.001; sensitivity 100%; specificity 85.4%; PPV 46.2%; NPV 100%; accuracy, 87.0%) but was not significantly superior to SUVmax-estimation at PET2 and ΔTLGmax. Likewise, the lean body mass and background individualization of the datasets did not impove the results of the ROC analyses; Conclusions: Sophisticated semi-quantitative PET measures in early response assessment of pHL patients do not perform significantly better than the previously proposed ΔSUVmax. All analytical strategies failed to improve the impaired PPV to a clinically acceptable level while preserving the excellent NPV.

  16. FDG-PET Response Prediction in Pediatric Hodgkin’s Lymphoma: Impact of Metabolically Defined Tumor Volumes and Individualized SUV Measurements on the Positive Predictive Value

    International Nuclear Information System (INIS)

    Hussien, Amr Elsayed M.; Furth, Christian; Schönberger, Stefan; Hundsdoerfer, Patrick; Steffen, Ingo G.; Amthauer, Holger; Müller, Hans-Wilhelm; Hautzel, Hubertus

    2015-01-01

    Background: In pediatric Hodgkin’s lymphoma (pHL) early response-to-therapy prediction is metabolically assessed by (18)F-FDG PET carrying an excellent negative predictive value (NPV) but an impaired positive predictive value (PPV). Aim of this study was to improve the PPV while keeping the optimal NPV. A comparison of different PET data analyses was performed applying individualized standardized uptake values (SUV), PET-derived metabolic tumor volume (MTV) and the product of both parameters, termed total lesion glycolysis (TLG); Methods: One-hundred-eight PET datasets (PET1, n = 54; PET2, n = 54) of 54 children were analysed by visual and semi-quantitative means. SUVmax, SUVmean, MTV and TLG were obtained the results of both PETs and the relative change from PET1 to PET2 (Δ in %) were compared for their capability of identifying responders and non-responders using receiver operating characteristics (ROC)-curves. In consideration of individual variations in noise and contrasts levels all parameters were additionally obtained after threshold correction to lean body mass and background; Results: All semi-quantitative SUV estimates obtained at PET2 were significantly superior to the visual PET2 analysis. However, ΔSUVmax revealed the best results (area under the curve, 0.92; p < 0.001; sensitivity 100%; specificity 85.4%; PPV 46.2%; NPV 100%; accuracy, 87.0%) but was not significantly superior to SUVmax-estimation at PET2 and ΔTLGmax. Likewise, the lean body mass and background individualization of the datasets did not impove the results of the ROC analyses; Conclusions: Sophisticated semi-quantitative PET measures in early response assessment of pHL patients do not perform significantly better than the previously proposed ΔSUVmax. All analytical strategies failed to improve the impaired PPV to a clinically acceptable level while preserving the excellent NPV

  17. Net-based data transfer and automatic image fusion of metabolic (PET) and morphologic (CT/MRI) images for radiosurgical planning of brain tumors

    International Nuclear Information System (INIS)

    Baum, R.P.; Przetak, C.; Schmuecking, M.; Klener, G.; Surber, G.; Hamm, K.

    2002-01-01

    Aim: The main purpose of radiosurgery in comparison to conventional radiotherapy of brain tumors is to reach a higher radiation dose in the tumor and sparing normal brain tissue as much as possible. To reach this aim it is crucial to define the target volume extremely accurately. For this purpose, MRI and CT examinations are used for radiotherapy planning. In certain cases, however, metabolic information obtained by positron emission tomography (PET) may be useful to achieve a higher therapeutic accuracy by sparing important brain structures. This can be the case, i.e. in low grade astrocytomas for exact delineation of vital tumor as well as in differentiating scaring tissue from tumor recurrence and edema after operation. For this purpose, radiolabeled aminoacid analogues (e.g. C-11 methionine) and recently O-2-[ 18 F] Fluorethyl-L-Tyrosin (F-18 FET) have been introduced as PET tracers to detect the area of highest tumor metabolism which allows to obtain additional information as compared to FDG-PET that reflects the local glucose metabolism. In these cases, anatomical and metabolic data have to be combined with the technique of digital image fusion to exactly determine the target volume, the isodoses and the area where the highest dose has to be applied. Materials: We have set up a data transfer from the PET Center of the Zentralklinik Bad Berka with the Department of Stereotactic Radiation at the Helios Klinik Erfurt (distance approx. 25 km) to enable this kind of image fusion. PET data (ECAT EXACT 47, Siemens/CTI) are transferred to a workstation (NOVALIS) in the Dept. of Stereotactic Radiation to be co-registered with the CT or MRI data of the patient. All PET images are in DICOM format (obtained by using a HERMES computer, Nuclear Diagnostics, Sweden) and can easily be introduced into the NOVALIS workstation. The software uses the optimation of mutual information to achieve a good fusion quality. Sometimes manual corrections have to be performed to get an

  18. Accurate, safe, and rapid method of intraoperative tumor identification for totally laparoscopic distal gastrectomy: injection of mixed fluid of sodium hyaluronate and patent blue.

    Science.gov (United States)

    Nakagawa, Masatoshi; Ehara, Kazuhisa; Ueno, Masaki; Tanaka, Tsuyoshi; Kaida, Sachiko; Udagawa, Harushi

    2014-04-01

    In totally laparoscopic distal gastrectomy, determining the resection line with safe proximal margins is often difficult, particularly for tumors located in a relatively upper area. This is because, in contrast to open surgery, identifying lesions by palpating or opening the stomach is essentially impossible. This study introduces a useful method of tumor identification that is accurate, safe, and rapid. On the operation day, after inducing general anesthesia, a mixture of sodium hyaluronate and patent blue is injected into the submucosal layer of the proximal margin. When resecting stomach, all marker spots should be on the resected side. In all cases, the proximal margin is examined histologically by using frozen sections during the operation. From October 2009 to September 2011, a prospective study that evaluated this method was performed. A total of 34 patients who underwent totally laparoscopic distal gastrectomy were enrolled in this study. Approximately 5 min was required to complete the procedure. Proximal margins were negative in all cases, and the mean ± standard deviation length of the proximal margin was 23.5 ± 12.8 mm. No side effects, such as allergy, were encountered. As a method of tumor identification for totally laparoscopic distal gastrectomy, this procedure appears accurate, safe, and rapid.

  19. Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life

    Directory of Open Access Journals (Sweden)

    Glen Daniel

    2009-05-01

    Full Text Available Abstract Background The intravenous co-infusion of labradimil, a metabolically stable bradykinin B2 receptor agonist, has been shown to temporarily enhance the transvascular delivery of small chemotherapy drugs, such as carboplatin, across the blood-brain tumor barrier. It has been thought that the primary mechanism by which labradimil does so is by acting selectively on tumor microvasculature to increase the local transvascular flow rate across the blood-brain tumor barrier. This mechanism of action does not explain why, in the clinical setting, carboplatin dosing based on patient renal function over-estimates the carboplatin dose required for target carboplatin exposure. In this study we investigated the systemic actions of labradimil, as well as other bradykinin B2 receptor agonists with a range of metabolic stabilities, in context of the local actions of the respective B2 receptor agonists on the blood-brain tumor barrier of rodent malignant gliomas. Methods Using dynamic contrast-enhanced MRI, the pharmacokinetics of gadolinium-diethyltriaminepentaacetic acid (Gd-DTPA, a small MRI contrast agent, were imaged in rodents bearing orthotopic RG-2 malignant gliomas. Baseline blood and brain tumor tissue pharmacokinetics were imaged with the 1st bolus of Gd-DTPA over the first hour, and then re-imaged with a 2nd bolus of Gd-DTPA over the second hour, during which normal saline or a bradykinin B2 receptor agonist was infused intravenously for 15 minutes. Changes in mean arterial blood pressure were recorded. Imaging data was analyzed using both qualitative and quantitative methods. Results The decrease in systemic blood pressure correlated with the known metabolic stability of the bradykinin B2 receptor agonist infused. Metabolically stable bradykinin B2 agonists, methionine-lysine-bradykinin and labradimil, had differential effects on the transvascular flow rate of Gd-DTPA across the blood-brain tumor barrier. Both methionine

  20. Out of Warburg effect: An effective cancer treatment targeting the tumor specific metabolism and dysregulated pH.

    Science.gov (United States)

    Schwartz, Laurent; Seyfried, Thomas; Alfarouk, Khalid O; Da Veiga Moreira, Jorgelindo; Fais, Stefano

    2017-04-01

    As stated by Otto Warburg nearly a century ago, cancer is a metabolic disease, a fermentation caused by malfunctioning mitochondria, resulting in increased anabolism and decreased catabolism. Treatment should, therefore, aim at restoring the energy yield. To decrease anabolism, glucose uptake should be reduced (ketogenic diet). To increase catabolism, the oxidative phosphorylation should be restored. Treatment with a combination of α-lipoic acid and hydroxycitrate has been shown to be effective in multiple animal models. This treatment, in combination with conventional chemotherapy, has yielded extremely encouraging results in glioblastoma, brain metastasis and lung cancer. Randomized trials are necessary to confirm these preliminary data. The major limitation is the fact that the combination of α-lipoic acid and hydroxycitrate can only be effective if the mitochondria are still present and/or functional. That may not be the case in the most aggressive tumors. The increased intracellular alkalosis is a strong mitogenic signal, which bypasses most inhibitory signals. Concomitant correction of this alkalosis may be a very effective treatment in case of mitochondrial failure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Targeted Serum Metabolite Profiling Identifies Metabolic Signatures in Patients with Alzheimer's Disease, Normal Pressure Hydrocephalus and Brain Tumor

    Directory of Open Access Journals (Sweden)

    Matej Orešič

    2018-01-01

    Full Text Available Progression to AD is preceded by elevated levels of 2,4-dihydroxybutanoic acid (2,4-DHB, implicating hypoxia in early pathogenesis. Since hypoxia may play a role in multiple CNS disorders, we investigated serum metabolite profiles across three disorders, AD, Normal Pressure Hydrocephalus (NPH and brain tumors (BT. Blood samples were collected from 27 NPH and 20 BT patients. The profiles of 21 metabolites were examined. Additionally, data from 37 AD patients and 46 controls from a previous study were analyzed together with the newly acquired data. No differences in 2,4-DHB were found across AD, NPH and BT samples. In the BT group, the fatty acids were increased as compared to HC and NPH groups, while the ketone body 3-hydroxybutyrate was increased as compared to AD. Glutamic acid was increased in AD as compared to the HC group. In the AD group, 3-hydroxybutyrate tended to be decreased with respect to all other groups (mean values −30% or more, but the differences were not statistically significant. Serine was increased in NPH as compared to BT. In conclusion, AD, NPH and BT have different metabolic profiles. This preliminary study may help in identifying the blood based markers that are specific to these three CNS diseases.

  2. A phylogenetic analysis of basal metabolism, total evaporative water loss, and life-history among foxes from desert and mesic regions

    NARCIS (Netherlands)

    Williams, JB; Munoz-Garcia, A; Ostrowski, S; Tieleman, BI

    We measured basal metabolic rate (BMR) and total evaporative water loss (TEWL) of species of foxes that exist on the Arabian Peninsula, Blanford's fox (Vulpes cana) and two subspecies of Red fox (Vulpes vulpes). Combining these data with that on other canids from the literature, we searched for

  3. Repeatability and individual correlates of basal metabolic rate and total evaporative water loss in birds : A case study in European stonechats

    NARCIS (Netherlands)

    Versteegh, Maaike A.; Heim, Barbara; Dingemanse, Niels J.; Tieleman, B. Irene

    Basal metabolic rate (BMR) and total evaporative water loss (TEWL) are thought to have evolved in conjunction with life history traits and are often assumed to be characteristic features of an animal. Physiological traits can show large intraindividual variation at short and long timescales, yet

  4. Bone Metabolism after Total Hip Revision Surgery with Impacted Grafting: Evaluation using H215O and [18F]fluoride PET; A Pilot Study

    NARCIS (Netherlands)

    Temmerman, Olivier; Raijmakers, Pieter; Heyligers, Ide; Comans, Emile; Lubberink, Mark; Teule, Gerrit; Lammertsma, Adriaan

    2008-01-01

    Purpose: To evaluate bone blood flow and bone formation in patients after total hip revision surgery with impacted bone grafting using H2 15O and [18F]fluoride positron emission tomography (PET). Procedures: To asses bone blood flow and bone metabolism in bone allograft after impaction grafting,

  5. Effects of Focal vs Total Cryotherapy and Minimum Tumor Temperature on Patient-reported Quality of Life Compared With Active Surveillance in Patients With Prostate Cancer.

    Science.gov (United States)

    Werneburg, Glenn T; Kongnyuy, Michael; Halpern, Daniel M; Salcedo, Jose M; Chen, Connie; LeSueur, Amanda; Kosinski, Kaitlin E; Schiff, Jeffrey T; Corcoran, Anthony T; Katz, Aaron E

    2018-03-01

    To investigate the effects of focal (hemiablation) or total cryotherapy and minimum tumor temperature on patient-reported quality of life (QoL) in patients with prostate cancer. An Institutional Review Board-approved database was reviewed for patients who underwent cryotherapy or active surveillance (AS). QoL questionnaire responses were collected and scores were analyzed for differences between focal and total cryotherapy and between very cold (total of 197 patients responded to a total of 547 questionnaires. Focal and total cryotherapy patients had initially lower sexual function scores relative to AS (year 1 mean difference focal: -31.7, P total: -48.1, P total cryotherapy sexual function scores were not statistically significantly different from the AS cohort by postprocedural year 4. Very cold and moderate-cold temperatures led to initially lower sexual function scores relative to AS (year 1 very cold: -38.1, P total cryotherapy and between very cold and moderate-cold temperature groups. Focal cryotherapy and moderate-cold (≥-76°C) temperature were associated with favorable sexual function relative to total cryotherapy and very cold temperature, respectively. No significant differences in urinary function or bowel habits were observed between groups. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Prognostic significance of metabolic tumor burden by positron emission tomography/computed tomography in patients with relapsed/refractory diffuse large B-cell lymphoma.

    Science.gov (United States)

    Tateishi, Ukihide; Tatsumi, Mitsuaki; Terauchi, Takashi; Ando, Kiyoshi; Niitsu, Nozomi; Kim, Won Seog; Suh, Cheolwon; Ogura, Michinori; Tobinai, Kensei

    2015-02-01

    The aim of the present study was to investigate the feasibility of measuring metabolic tumor burden using [F-18] fluorodeoxyglucose ((18) F-FDG) positron emission tomography/computed tomography (PET/CT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) treated with bendamustine-rituximab. Because the standardized uptake value is a critical parameter of tumor characterization, we carried out a phantom study of (18) F-FDG PET/CT to ensure quality control for 28 machines in the 24 institutions (Japan, 17 institutions; Korea, 7 institutions) participating in our clinical study. Fifty-five patients with relapsed or refractory DLBCL were enrolled. The (18) F-FDG PET/CT was acquired before treatment, after two cycles, and after the last treatment cycle. Treatment response was assessed after two cycles and after the last cycle using the Lugano classification. Using this classification, remission was complete in 15 patients (27%) and incomplete in 40 patients (73%) after two cycles of therapy, and remission was complete in 32 patients (58%) and incomplete in 23 patients (42%) after the last treatment cycle. The percentage change in all PET/CT parameters except for the area under the curve of the cumulative standardized uptake value-volume histogram was significantly greater in complete response patients than in non-complete response patients after two cycles and the last cycle. The Cox proportional hazard model and best subset selection method revealed that the percentage change of the sum of total lesion glycolysis after the last cycle (relative risk, 5.24; P = 0.003) was an independent predictor of progression-free survival. The percent change of sum of total lesion glycolysis, calculated from PET/CT, can be used to quantify the response to treatment and can predict progression-free survival after the last treatment cycle in patients with relapsed or refractory DLBCL treated with bendamustine-rituximab. © 2014 The Authors. Cancer Science

  7. Studies on metabolism of total glucosides of paeony from Paeoniae Radix Alba in rats by UPLC-Q-TOF-MS/MS.

    Science.gov (United States)

    Cao, Wenli; Wang, Xinguo; Li, Haojie; Shi, Xuliang; Fan, Wencheng; Zhao, Shaohua; Liu, Minyan; Niu, Liying

    2015-11-01

    Total glucosides of paeony are the active constituents of Paeoniae Radix Alba. In this study, a novel strategy was proposed to find more metabolites and the differences between paeoniflorin, albiflorin and total glucosides of paeony (TGP). This strategy was characterized as follows: firstly, the animals were divided into three groups (paeoniflorin, albiflorin and TGP) to identify the source of TGP metabolites from paeoniflorin or albiflorin; secondly, a generic information-dependent acquisition scan for the low-level metabolites was triggered by the multiple mass defect filter and dynamic background subtraction; thirdly, the metabolites were identified with a combination of data-processing methods including mass defect filtering, neutral loss filtering and product ion filtering; finally, a comparative study was used in the metabolism of paeoniflorin, albiflorin and TGP. Based on the strategy, 18 metabolites of TGP, 10 metabolites of paeoniflorin and 13 metabolites of albiflorin were identified respectively. The results indicated that the hydrolysis, conjugation reaction and oxidization were the major metabolic pathways, and the metabolic sites were the glycosidic linkage, the ester bond and the benzene ring. This study is first to explore the metabolism of TGP, and these findings enhance our understanding of the metabolism and the interactions of paeoniflrin and albiflorin in TGP. Copyright © 2015 John Wiley & Sons, Ltd.

  8. EPR oxygen imaging and hyperpolarized 13C MRI of pyruvate metabolism as non-invasive biomarkers of tumor treatment response to a glycolysis inhibitor 3-bromopyruvate

    Science.gov (United States)

    Matsumoto, Shingo; Saito, Keita; Yasui, Hironobu; Morris, H. Douglas; Munasinghe, Jeeva P.; Lizak, Martin; Merkle, Hellmut; Ardenkjaer-Larsen, Jan Henrik; Choudhuri, Rajani; Devasahayam, Nallathamby; Subramanian, Sankaran; Koretsky, Alan P.; Mitchell, James B.; Krishna, Murali C.

    2012-01-01

    The hypoxic nature of tumors results in treatment resistance and poor prognosis. To spare limited oxygen for more crucial pathways, hypoxic cancerous cells suppress mitochondrial oxidative phosphorylation, and promote glycolysis for energy production. Thereby, inhibition of glycolysis has the potential to overcome treatment resistance of hypoxic tumors. Here, EPR imaging was used to evaluate oxygen dependent efficacy on hypoxia-sensitive drug. The small molecule 3-bromopyruvate (3-BP) blocks glycolysis pathway by inhibiting hypoxia inducible enzymes, and enhanced cytotoxicity of 3-BP under hypoxic conditions has been reported in vitro. However, the efficacy of 3-BP was substantially attenuated in hypoxic tumor regions (pO2 < 10 mmHg) in vivo using squamous cell carcinoma (SCCVII)-bearing mouse model. Metabolic MRI studies using hyperpolarized 13C-labeled pyruvate showed that monocarboxylate transporter-1 (MCT1) is the major transporter for pyruvate and the analog 3-BP in SCCVII tumor. The discrepant results between in vitro and in vivo data were attributed to biphasic oxygen dependent expression of MCT1 in vivo. Expression of MCT1 was enhanced in moderately hypoxic (8–15 mmHg) tumor regions, but down regulated in severely hypoxic (< 5 mmHg) tumor regions. These results emphasize the importance of non-invasive imaging biomarkers to confirm the action of hypoxia-activated drugs. PMID:22692861

  9. Individualized risk assessment in neuroblastoma. Does the tumoral metabolic activity on 123I-MIBG SPECT predict the outcome?

    International Nuclear Information System (INIS)

    Rogasch, Julian M.M.; Furth, Christian; Wedel, Florian; Brenner, Winfried; Amthauer, Holger; Schatka, Imke; Hundsdoerfer, Patrick; Hofheinz, Frank; Krueger, Paul-Christian; Lode, Holger; Eggert, Angelika

    2017-01-01

    Risk-adapted treatment in children with neuroblastoma (NB) is based on clinical and genetic factors. This study evaluated the metabolic tumour volume (MTV) and its asphericity (ASP) in pretherapeutic 123 I-MIBG SPECT for individualized image-based prediction of outcome. This retrospective study included 23 children (11 girls, 12 boys; median age 1.8 years, range 0.3-6.8 years) with newly diagnosed NB consecutively examined with pretherapeutic 123 I-MIBG SPECT. Primary tumour MTV and ASP were defined using semiautomatic thresholds. Cox regression analysis, receiver operating characteristic analysis (cut-off determination) and Kaplan-Meier analysis with the log-rank test for event-free survival (EFS) were performed for ASP, MTV, laboratory parameters (including urinary homovanillic acid-to-creatinine ratio, HVA/C), and clinical (age, stage) and genetic factors. Predictive accuracy of the optimal multifactorial model was determined in terms of Harrell's C and likelihood ratio χ 2 . Median follow-up was 36 months (range 7-107 months; eight patients showed disease progression/relapse, four patients died). The only significant predictors of EFS in the univariate Cox regression analysis were ASP (p = 0.029; hazard ratio, HR, 1.032 for a one unit increase), MTV (p = 0.038; HR 1.012) and MYCN amplification status (p = 0.047; HR 4.67). The mean EFS in patients with high ASP (>32.0%) and low ASP were 21 and 88 months, respectively (p = 0.013), and in those with high MTV (>46.7 ml) and low MTV were 22 and 87 months, respectively (p = 0.023). A combined risk model of either high ASP and high HVA/C or high MTV and high HVA/C best predicted EFS. In this exploratory study, pretherapeutic image-derived and laboratory markers of tumoral metabolic activity in NB (ASP, MTV, urinary HVA/C) allowed the identification of children with a high and low risk of progression/relapse under current therapy. (orig.)

  10. Individualized risk assessment in neuroblastoma. Does the tumoral metabolic activity on {sup 123}I-MIBG SPECT predict the outcome?

    Energy Technology Data Exchange (ETDEWEB)

    Rogasch, Julian M.M.; Furth, Christian; Wedel, Florian; Brenner, Winfried; Amthauer, Holger; Schatka, Imke [Charite - Universitaetsmedizin Berlin, Department of Nuclear Medicine, Berlin (Germany); Hundsdoerfer, Patrick [Charite - Universitaetsmedizin Berlin, Department of Pediatric Oncology/Hematology, Berlin (Germany); Berlin Institute of Health (BIH), Berlin (Germany); Hofheinz, Frank [Helmholtz Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, PET Center, Dresden (Germany); Krueger, Paul-Christian [University Medicine Greifswald, Institute for Diagnostic Radiology and Neuroradiology, Greifswald (Germany); Lode, Holger [University Medicine Greifswald, Department of Pediatric Oncology and Hematology, Greifswald (Germany); Eggert, Angelika [Charite - Universitaetsmedizin Berlin, Department of Pediatric Oncology/Hematology, Berlin (Germany)

    2017-12-15

    Risk-adapted treatment in children with neuroblastoma (NB) is based on clinical and genetic factors. This study evaluated the metabolic tumour volume (MTV) and its asphericity (ASP) in pretherapeutic {sup 123}I-MIBG SPECT for individualized image-based prediction of outcome. This retrospective study included 23 children (11 girls, 12 boys; median age 1.8 years, range 0.3-6.8 years) with newly diagnosed NB consecutively examined with pretherapeutic {sup 123}I-MIBG SPECT. Primary tumour MTV and ASP were defined using semiautomatic thresholds. Cox regression analysis, receiver operating characteristic analysis (cut-off determination) and Kaplan-Meier analysis with the log-rank test for event-free survival (EFS) were performed for ASP, MTV, laboratory parameters (including urinary homovanillic acid-to-creatinine ratio, HVA/C), and clinical (age, stage) and genetic factors. Predictive accuracy of the optimal multifactorial model was determined in terms of Harrell's C and likelihood ratio χ {sup 2}. Median follow-up was 36 months (range 7-107 months; eight patients showed disease progression/relapse, four patients died). The only significant predictors of EFS in the univariate Cox regression analysis were ASP (p = 0.029; hazard ratio, HR, 1.032 for a one unit increase), MTV (p = 0.038; HR 1.012) and MYCN amplification status (p = 0.047; HR 4.67). The mean EFS in patients with high ASP (>32.0%) and low ASP were 21 and 88 months, respectively (p = 0.013), and in those with high MTV (>46.7 ml) and low MTV were 22 and 87 months, respectively (p = 0.023). A combined risk model of either high ASP and high HVA/C or high MTV and high HVA/C best predicted EFS. In this exploratory study, pretherapeutic image-derived and laboratory markers of tumoral metabolic activity in NB (ASP, MTV, urinary HVA/C) allowed the identification of children with a high and low risk of progression/relapse under current therapy. (orig.)

  11. Assessment of treatment response by total tumor volume and global apparent diffusion coefficient using diffusion-weighted MRI in patients with metastatic bone disease: a feasibility study.

    Directory of Open Access Journals (Sweden)

    Matthew D Blackledge

    Full Text Available We describe our semi-automatic segmentation of whole-body diffusion-weighted MRI (WBDWI using a Markov random field (MRF model to derive tumor total diffusion volume (tDV and associated global apparent diffusion coefficient (gADC; and demonstrate the feasibility of using these indices for assessing tumor burden and response to treatment in patients with bone metastases. WBDWI was performed on eleven patients diagnosed with bone metastases from breast and prostate cancers before and after anti-cancer therapies. Semi-automatic segmentation incorporating a MRF model was performed in all patients below the C4 vertebra by an experienced radiologist with over eight years of clinical experience in body DWI. Changes in tDV and gADC distributions were compared with overall response determined by all imaging, tumor markers and clinical findings at serial follow up. The segmentation technique was possible in all patients although erroneous volumes of interest were generated in one patient because of poor fat suppression in the pelvis, requiring manual correction. Responding patients showed a larger increase in gADC (median change = +0.18, range = -0.07 to +0.78 × 10(-3 mm2/s after treatment compared to non-responding patients (median change = -0.02, range = -0.10 to +0.05 × 10(-3 mm2/s, p = 0.05, Mann-Whitney test, whereas non-responding patients showed a significantly larger increase in tDV (median change = +26%, range = +3 to +284% compared to responding patients (median change = -50%, range = -85 to +27%, p = 0.02, Mann-Whitney test. Semi-automatic segmentation of WBDWI is feasible for metastatic bone disease in this pilot cohort of 11 patients, and could be used to quantify tumor total diffusion volume and median global ADC for assessing response to treatment.

  12. In Vivo PET Assay of Tumor Glutamine Flux and Metabolism: In-Human Trial of 18F-(2S,4R)-4-Fluoroglutamine.

    Science.gov (United States)

    Dunphy, Mark P S; Harding, James J; Venneti, Sriram; Zhang, Hanwen; Burnazi, Eva M; Bromberg, Jacqueline; Omuro, Antonio M; Hsieh, James J; Mellinghoff, Ingo K; Staton, Kevin; Pressl, Christina; Beattie, Bradley J; Zanzonico, Pat B; Gerecitano, John F; Kelsen, David P; Weber, Wolfgang; Lyashchenko, Serge K; Kung, Hank F; Lewis, Jason S

    2018-05-01

    Purpose To assess the clinical safety, pharmacokinetics, and tumor imaging characteristics of fluorine 18-(2S,4R)-4-fluoroglutamine (FGln), a glutamine analog radiologic imaging agent. Materials and Methods This study was approved by the institutional review board and conducted under a U.S. Food and Drug Administration-approved Investigational New Drug application in accordance with the Helsinki Declaration and the Health Insurance Portability and Accountability Act. All patients provided written informed consent. Between January 2013 and October 2016, 25 adult patients with cancer received an intravenous bolus of FGln tracer (mean, 244 MBq ± 118, <100 μg) followed by positron emission tomography (PET) and blood radioassays. Patient data were summarized with descriptive statistics. FGln biodistribution and plasma amino acid levels in nonfasting patients (n = 13) were compared with those from patients who fasted at least 8 hours before injection (n = 12) by using nonparametric one-way analysis of variance with Bonferroni correction. Tumor FGln avidity versus fluorodeoxyglucose (FDG) avidity in patients with paired PET scans (n = 15) was evaluated with the Fisher exact test. P < .05 was considered indicative of a statistically significant difference. Results FGln PET depicted tumors of different cancer types (breast, pancreas, renal, neuroendocrine, lung, colon, lymphoma, bile duct, or glioma) in 17 of the 25 patients, predominantly clinically aggressive tumors with genetic mutations implicated in abnormal glutamine metabolism. Acute fasting had no significant effect on FGln biodistribution and plasma amino acid levels. FGln-avid tumors were uniformly FDG-avid but not vice versa (P = .07). Patients experienced no adverse effects. Conclusion Preliminary human FGln PET trial results provide clinical validation of abnormal glutamine metabolism as a potential tumor biomarker for targeted radiotracer imaging in several different cancer types. © RSNA, 2018 Online

  13. miR-125b acts as a tumor suppressor in chondrosarcoma cells by the sensitization to doxorubicin through direct targeting the ErbB2-regulated glucose metabolism.

    Science.gov (United States)

    Tang, Xian-ye; Zheng, Wei; Ding, Min; Guo, Kai-jin; Yuan, Feng; Feng, Hu; Deng, Bin; Sun, Wei; Hou, Yang; Gao, Lu

    2016-01-01

    Chondrosarcoma is the second most common type of primary bone malignancy in the United States after osteosarcoma. Surgical resections of these tumors are the only effective treatment to chondrosarcoma patients due to their resistance to conventional chemo- and radiotherapy. In this study, miR-125b was found to perform its tumor-suppressor function to inhibit glucose metabolism via the direct targeting of oncogene, ErbB2. We report miR-125b was downregulated in both chondrosarcoma patient samples and cell lines. The total 20 Asian chondrosarcoma patients showed significantly downregulated miR-125b expression compared with normal tissues. Meanwhile, miR-125 was downregulated in chondrosarcoma cells and doxorubicin resistant cells. Overexpression of miR-125 enhanced the sensitivity of both parental and doxorubicin resistant cells to doxorubicin through direct targeting on the ErbB2-mediated upregulation of glycolysis in chondrosarcoma cells. Moreover, restoration of the expression of ErbB2 and glucose metabolic enzymes in miR-125 pretransfected cells recovered the susceptibility to doxorubicin. Our study will provide a novel aspect on the overcoming chemoresistance in human chondrosarcoma cells and may help in the development of therapeutic strategies for the treatments of patients.

  14. Metabolic tumor volume measured by F 18 FDG PET/CT can further stratify the prognosis of patients with stage IV Non Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Su Woong; Kim, Ja Hae; Chong, Ar I; Kwon, Seong Young; Min, Jung Joon; Song, Ho Chun; Bom, Hee Seung [Chonnam National Univ. Hwasun Hospital, Gwangju (Korea, Republic of)

    2012-12-15

    This study aimed to further stratify prognostic factors in patients with stage IV non small cell lung cancer (NSCLC) by measuring their metabolic tumor volume (MTV) using F 18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). The subjects of this retrospective study were 57 patients with stage IV NSCLC. MTV, total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) were measured on F 18 FDG PET/CT in both the primary lung lesion as well as metastatic lesions in torso. Optimal cutoff values of PET parameters were mea measured by receiver operating characteristic (ROC) curve anal analysis. Kaplan Meier survival (PET). The univariate and multivariate cox proportional hazards models were used to select the significant prognostic factors. Univariate analysis showed that both MTV and TLG of primary lung lesion (MTV lung and TLG lung) were significant factors for prediction of PFS ( <0.001 =0.038, respectively). Patients showing lower values of MTV lung and TLG lung than the cutoff values had significantly longer mean PFS than those with higher values. hazard ratios (95% confidence interval) of MTV lung and TLG lung measured by univariate analysis were 6.4 (2.5 16.3) and 2.4 (1.0 5.5), respectively. multivariate analysis revealed that MTV lung was the only significant factor for prediction of prognosis. Hazard ratio was 13,5 (1.6 111.1, =0,016). patients with stage IV NSCLC could be further stratified into subgroups of significantly better and worse prognosis by MTV of primary lung lesion.

  15. Metabolic tumor volume measured by F 18 FDG PET/CT can further stratify the prognosis of patients with stage IV Non Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Yoo, Su Woong; Kim, Ja Hae; Chong, Ar I; Kwon, Seong Young; Min, Jung Joon; Song, Ho Chun; Bom, Hee Seung

    2012-01-01

    This study aimed to further stratify prognostic factors in patients with stage IV non small cell lung cancer (NSCLC) by measuring their metabolic tumor volume (MTV) using F 18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). The subjects of this retrospective study were 57 patients with stage IV NSCLC. MTV, total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) were measured on F 18 FDG PET/CT in both the primary lung lesion as well as metastatic lesions in torso. Optimal cutoff values of PET parameters were mea measured by receiver operating characteristic (ROC) curve anal analysis. Kaplan Meier survival (PET). The univariate and multivariate cox proportional hazards models were used to select the significant prognostic factors. Univariate analysis showed that both MTV and TLG of primary lung lesion (MTV lung and TLG lung) were significant factors for prediction of PFS ( <0.001 =0.038, respectively). Patients showing lower values of MTV lung and TLG lung than the cutoff values had significantly longer mean PFS than those with higher values. hazard ratios (95% confidence interval) of MTV lung and TLG lung measured by univariate analysis were 6.4 (2.5 16.3) and 2.4 (1.0 5.5), respectively. multivariate analysis revealed that MTV lung was the only significant factor for prediction of prognosis. Hazard ratio was 13,5 (1.6 111.1, =0,016). patients with stage IV NSCLC could be further stratified into subgroups of significantly better and worse prognosis by MTV of primary lung lesion

  16. A prospective randomized comparison of continuous hemihepatic with intermittent total hepatic inflow occlusion in hepatectomy for liver tumors.

    Science.gov (United States)

    Liang, Guanlin; Wen, Tianfu; Yan, Lunan; Li, B O; Wu, Guochang; Yang, Jian; Lu, Bo; Chen, Zheyu; Liao, Zhixue; Ran, Shun; Yu, Zhang

    2009-01-01

    To evaluate whether continuous hemihepatic inflow occlusion (HHO) during hepatectomy can be safer than and be as effective as intermittent total hepatic inflow occlusion (THO) in reducing blood loss. Eighty patients undergoing liver resections were included in a prospective randomized study comparing the intra- and postoperative course under THO (n=40) or HHO (n=40). THO was performed with periods of 20 minutes of occlusion and 5 minutes of releasing, while HHO was performed with continuous occlusion. The surface area of liver transection, amount of blood loss, measurements of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and postoperative evolution were recorded. The two groups were similar at entry in terms of preoperative liver function and in the proportion of patients experiencing major hepatectomy. The total ischemic time of the two groups was similar (p=0.37), but the operative time in the THO group was longer than in the HHO group (p=0.02). No significant difference was found between the HHO and THO group in blood loss during liver parenchyma transection (p=0.14), the elevations of ALT and AST on the first postoperative day (ALT: p=0.12; AST: p=0.66) and postoperative morbidity (p=0.35). On the basis of our findings, if it is feasible, continuous HHO is recommended for complex liver resection.

  17. Risk-stratifying capacity of PET/CT metabolic tumor volume in stage IIIA non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Finkle, Joshua H.; Jo, Stephanie Y.; Yuan, Cindy; Pu, Yonglin [University of Chicago, Department of Radiology, Chicago, IL (United States); Ferguson, Mark K. [University of Chicago, Department of Surgery, Chicago, IL (United States); Liu, Hai-Yan [First Hospital of Shanxi Medical University, Department of Nuclear Medicine, Taiyuan, Shanxi (China); Zhang, Chenpeng [Shanghai Jiao Tong University, Department of Nuclear Medicine, RenJi Hospital, School of Medicine, Shanghai (China); Zhu, Xuee [Nanjing Medical University, Department of Radiology, BenQ Medical Center, Nanjing, Jiangsu Province (China)

    2017-08-15

    Stage IIIA non-small cell lung cancer (NSCLC) is heterogeneous in tumor burden, and its treatment is variable. Whole-body metabolic tumor volume (MTV{sub WB}) has been shown to be an independent prognostic index for overall survival (OS). However, the potential of MTV{sub WB} to risk-stratify stage IIIA NSCLC has previously been unknown. If we can identify subgroups within the stage exhibiting significant OS differences using MTV{sub WB}, MTV{sub WB} may lead to adjustments in patients' risk profile evaluations and may, therefore, influence clinical decision making regarding treatment. We estimated the risk-stratifying capacity of MTV{sub WB} in stage IIIA by comparing OS of stratified stage IIIA with stage IIB and IIIB NSCLC. We performed a retrospective review of 330 patients with clinical stage IIB, IIIA, and IIIB NSCLC diagnosed between 2004 and 2014. The patients' clinical TNM stage, initial MTV{sub WB}, and long-term survival data were collected. Patients with TNM stage IIIA disease were stratified by MTV{sub WB}. The optimal MTV{sub WB} cutoff value for stage IIIA patients was calculated using sequential log-rank tests. Univariate and multivariate cox regression analyses and Kaplan-Meier OS analysis with log-rank tests were performed. The optimal MTV{sub WB} cut-point was 29.2 mL for the risk-stratification of stage IIIA. We identified statistically significant differences in OS between stage IIB and IIIA patients (p < 0.01), between IIIA and IIIB patients (p < 0.01), and between the stage IIIA patients with low MTV{sub WB} (below 29.2 mL) and the stage IIIA patients with high MTV{sub WB} (above 29.2 mL) (p < 0.01). There was no OS difference between the low MTV{sub WB} stage IIIA and the cohort of stage IIB patients (p = 0.485), or between the high MTV{sub WB} stage IIIA patients and the cohort of stage IIIB patients (p = 0.459). Similar risk-stratification capacity of MTV{sub WB} was observed in a large range of cutoff values from 15 to 55 mL in

  18. Metabolic study of paeoniflorin and total paeony glucosides from Paeoniae Radix Rubra in rats by high-performance liquid chromatography coupled with sequential mass spectrometry.

    Science.gov (United States)

    Zhu, Lijun; Sun, Shanshan; Hu, Yanxi; Liu, Yufeng

    2018-04-01

    A clear understanding of the metabolism of Traditional Chinese Medicines is extremely important in their rational clinical application and effective material foundation research. A novel and reliable strategy was performed to find more metabolites of paeoniflorin, determine the metabolites of total paeony glucosides (TPG) by means of determining those metabolites of paeoniflorin, and compare the metabolism differences between paeoniflorin and TPG by intragastric administration. This strategy was characterized as follows. Firstly, the rats were divided into two groups (the paeoniflorin group and the TPG group) to find differences in metabolism mechanisms between paeoniflorin and TPG. Secondly, UPLC-FT-ICR MS and UPLC-Q-TOF MS 2 were applied to obtain accurate molecular weight and structural information, respectively. Thirdly, the metabolites were tentatively identified by a combination of data-processing methods including mass defect screening, characteristic neutral loss screening and product ion screening. Finally, a comparative study was employed in the metabolism of paeoniflorin and TPG. Based on the strategy, 18 metabolites of paeoniflorin (including four new compounds) and 11 metabolites of TPG (including two new compounds) were identified. In all of the identified metabolites of paeoniflorin, two metabolites in rat plasma, four metabolites in rat urine and six metabolites in rat feces were found for the first time after paeoniflorin administration. The results indicate that hydrolyzation of the ester bond and glucosidic band and conjugation with glucuronide were the major metabolic pathways of paeoniflorin. The metabolites of paeoniflorin and TPG in rat plasma, urine and feces have been detected for the first time after intragastric administration. The results may contribute to a better understanding of the metabolism mechanism and provide a scientific rationale for researching the material basis of paeoniflorin and TPG in vivo. Copyright © 2017 John Wiley

  19. Neo-angiogenesis metabolic biomarker of tumor-genesis tracking by infrared joystick contact imaging in personalized homecare system

    Science.gov (United States)

    Szu, Harold; Hoekstra, Philip; Landa, Joseph; Vydelingum, Nadarajen A.

    2014-05-01

    We describe an strong>affordable, harmless, and administrative (AHA) metabolic biomarker (MBM)strong> for homecare cancer screening. It may save hundreds of thousands of women's and thousands of men's lives every year from breast cancer and melanoma. The goal is to increase the specificity ofstrong> infrared (IR)strong> imagery to reduce the strong>false alarm rate (FAR). strong>The patient's hands are immersed in icy cold water, about 11oC, for 30 seconds. We then compare two IR images, taken before and after the cold stimulus, and the difference reveals an enhanced signal and noise ratio (SNR) at tumorigenesis sites since the contraction of capillaries under cold challenge is natural to healthy capillaries, except those newly built capillaries during angiogenesis (Folkman, Nature 1995). Concomitant with the genome and the phenome (molecular signaling by phosphor-mediate protein causing inflammation by strong>platelet activating factor (PAF)strong> that transform cells from benign to malignant is the amplification of strong>nitric oxide (NO)strong> syntheses, a short-lived reactive oxygen species (ROS) that dilates regional blood vessels; superseding normal autonomic nervous system regulation. A rapidly growing tumor site might implicate accumulation of strong>ROSstrong>, for which strong>NOstrong> can rapidly stretch the capillary bed system usually having thinning muscular lining known as strong>Neo-Angiogenesis (NA)strong> that could behave like strong>Leaky In-situ Faucet Effect (LIFE)strong> in response to cold challenge. To emphasize the state of art knowledge of strong>NAstrong>, we mentioned in passing the first generation of an anticapillary growth drug, strong>Avastinstrong> by Genetech; it is an antibody protein that is injected for metastasis, while the second generation drug; strong>Sorafenibstrong> by Bayers (2001) and strong>Sutentstrong> by Pfizer (2000) both target molecular signaling loci to block receptor associated tyrosine kinase induced

  20. Dose-dependent effects of calorie restriction on gene expression, metabolism, and tumor progression are partially mediated by insulin-like growth factor-1

    International Nuclear Information System (INIS)

    Nogueira, Leticia M; Lavigne, Jackie A; Chandramouli, Gadisetti V R; Lui, Huaitian; Barrett, J Carl; Hursting, Stephen D

    2012-01-01

    . Exogenous IGF-1 rescued the hepatic expression of several metabolic genes and pathways affected by CR. Exogenous IGF-1 also rescued the expression of several metabolism- and cancer-related genes affected by CR in the mammary gland. Furthermore, exogenous IGF-1 partially reversed the mammary tumor inhibitory effects of 30% CR. We conclude that several genes and pathways, particularly those associated with macronutrient and steroid hormone metabolism, are associated with the anticancer effects of CR, and that reduced IGF-1 levels can account, at least in part, for many of the effects of CR on gene expression and mammary tumor burden

  1. Early Change in Metabolic Tumor Heterogeneity during Chemoradiotherapy and Its Prognostic Value for Patients with Locally Advanced Non-Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Xinzhe Dong

    Full Text Available To observe the early change of metabolic tumor heterogeneity during chemoradiotherapy and to determine its prognostic value for patients with locally advanced non-small cell lung cancer (NSCLC.From January 2007 to March 2010, 58 patients with NSCLC were included who were received 18F-fluorodeoxyglucose (18F-FDG PET/CT before and following 40 Gy radiotherapy with the concurrent cisplatin-based chemotherapy (CCRT. Primary tumor FDG uptake heterogeneity was determined using global and local scale textural features extracted from standardized uptake value (SUV histogram analysis (coefficient of variation [COV], skewness, kurtosis, area under the curve of the cumulative SUV histogram [AUC-CSH] and normalized gray-level co-occurrence matrix (contrast, dissimilarity, entropy, homogeneity. SUVmax and metabolic tumor volume (MTV were also evaluated. Correlations were analyzed between parameters on baseline or during treatments with tumor response, progression-free survival (PFS, and overall survival (OS.Compared with non-responders, responders showed significantly greater pre-treatment COV, contrast and MTV (AUC = 0.781, 0.804, 0.686, respectively. Receiver-operating-characteristic curve analysis showed that early change of tumor textural analysis serves as a response predictor with higher sensitivity (73.2%~92.1% and specificity (80.0%~83.6% than baseline parameters. Change in AUC-CSH and dissimilarity during CCRT could also predict response with optimal cut-off values (33.0% and 28.7%, respectively. The patients with greater changes in contrast and AUC-CSH had significantly higher 5-year OS (P = 0.008, P = 0.034 and PFS (P = 0.007, P = 0.039. In multivariate analysis, only change in contrast was found as the independent prognostic factor of PFS (HR 0.476, P = 0.021 and OS (HR 0.519, P = 0.015.The metabolic tumor heterogeneity change during CCRT characterized by global and local scale textural features may be valuable for predicting treatment response

  2. Effects of 2-Deoxy-D-Glucose on Metabolic Status, Proliferative Capacity and Growth Rate of FSall Tumor: Observations made by In Vivo 31P-Nuclear Magnetic Resonance Spectroscopy and Flow Cytometry

    International Nuclear Information System (INIS)

    Chang, Hye Sook; Choi, Eun Kyung; Cho, Jeong Gill; Lim, Tae Hwan; Lee, Tae Keun; Yi, Yun; Cho, Young Joo; Kim, Gon Sup

    1991-01-01

    The effect of 2-deoxy-d-glucose (2-DDG) on C 3 H mouse fibrosarcoma (FSall) was studied. Metabolic status, especially for energy metabolism, was studied using in vivo 31 P-MRS, proliferative capacity was observed on flow cytometry (FC) and growth rate was measured after transplantation of 106 viable tumor cells in the dorsum of foot of C 3 Hf/Sed mice. One gram of 2-DDG per kg of body weight was injected intraperitoneally on 12th day of implantation. Average tumor size on 12th day of implantation was 250mm 3 . Growth rate of FSall tumor was measured by tumor doubling time between tumor age 5-12 days was 0.84 days with slope 0.828 and tumor doubling time between tumor age 13-28 days was 3.2 days with slope 0.218 in control group. After 2-DDG injection, tumor doubling time was elongated to 5.1 days with slope 0.136. The effect of 2-DDG studied in vivo 31 P-MRS suggested that the increase of phosphomonoester (PME) and inorganic phosphate (Pi) by increasing size of tumor, slowed down after 2-DDG injection. Flow cytometry showed significantly increased S-phase and G 2 +M phase fraction suggesting increased proliferative capacity of tumor cells in the presence of 2-DDG. Authors observed an interesting effect 2-DDG on FSall tumor and attempt to utilize as an adjunct for radiotherapy

  3. Formation and utilization of acetoin, an unusual product of pyruvate metabolism by Ehrlich and AS30-D tumor mitochondria.

    Science.gov (United States)

    Baggetto, L G; Lehninger, A L

    1987-07-15

    [14C]Pyruvate was rapidly non-oxidatively decarboxylated by Ehrlich tumor mitochondria at a rate of 40 nmol/min/mg of protein in the presence or absence of ADP. A search for decarboxylation products led to significant amounts of acetoin formed when Ehrlich tumor mitochondria were incubated with 1 mM [14C] pyruvate in the presence of ATP. Added acetoin to aerobic tumor mitochondria was rapidly utilized in the presence of ATP at a rate of 65 nmol/min/mg of protein. Citrate has been found as a product of acetoin utilization and was exported from the tumor mitochondria. Acetoin has been found in the ascitic liquid of Ehrlich and AS30-D tumor-bearing animals. These unusual reactions were not observed in control rat liver mitochondria.

  4. Paternal B Vitamin Intake Is a Determinant of Growth, Hepatic Lipid Metabolism and Intestinal Tumor Volume in Female Apc1638N Mouse Offspring.

    Directory of Open Access Journals (Sweden)

    Julia A Sabet

    Full Text Available The importance of maternal nutrition to offspring health and risk of disease is well established. Emerging evidence suggests paternal diet may affect offspring health as well.In the current study we sought to determine whether modulating pre-conception paternal B vitamin intake alters intestinal tumor formation in offspring. Additionally, we sought to identify potential mechanisms for the observed weight differential among offspring by profiling hepatic gene expression and lipid content.Male Apc1638N mice (prone to intestinal tumor formation were fed diets containing replete (control, CTRL, mildly deficient (DEF, or supplemental (SUPP quantities of vitamins B2, B6, B12, and folate for 8 weeks before mating with control-fed wild type females. Wild type offspring were euthanized at weaning and hepatic gene expression profiled. Apc1638N offspring were fed a replete diet and euthanized at 28 weeks of age to assess tumor burden.No differences in intestinal tumor incidence or burden were found between male Apc1638N offspring of different paternal diet groups. Although in female Apc1638N offspring there were no differences in tumor incidence or multiplicity, a stepwise increase in tumor volume with increasing paternal B vitamin intake was observed. Interestingly, female offspring of SUPP and DEF fathers had a significantly lower body weight than those of CTRL fed fathers. Moreover, hepatic trigylcerides and cholesterol were elevated 3-fold in adult female offspring of SUPP fathers. Weanling offspring of the same fathers displayed altered expression of several key lipid-metabolism genes. Hundreds of differentially methylated regions were identified in the paternal sperm in response to DEF and SUPP diets. Aside from a few genes including Igf2, there was a striking lack of overlap between these genes differentially methylated in sperm and differentially expressed in offspring.In this animal model, modulation of paternal B vitamin intake prior to mating

  5. Preliminary studies of urinary metabolic profile in rats after acute total body homogeneous irradiation by 60Co γ-rays

    International Nuclear Information System (INIS)

    Zhang Huifang; Yang Biao; Guo Yuefeng; Guo Wanlong; Xing Lihong

    2011-01-01

    To detect the metabolic profile of rats urinary by use of 1 h-NMR, the rats were irradiated by 60 Cy γ-rays with a dose of 7 Gy (0.7 Gy/min). And the data was processed by principal components analysis (PCA) and partial least square discriminate analysis (PLS-DA). The results demonstrated that there were obvious differences in urine metabolites before and after irradiation, and the main metabolites included lactate, acetate, succinate, citrate, creatinine, trimethylamine-N-oxide and taurine. The relative content of lactate, acetate, creatinine and trimethylamine-N-oxide increased significantly on the first day following quickly decreasing on the second and third days, but increasing on the fourth day after irradiation. On the first three days after irradiation, the relative content of succinate and citrate had trending down, but had an ascending tendency on the fourth day. The relative content of taurine was basically stable but higher than pre-radiation. In conclusion, 1 H-NMR combined with PCA and PLS-DA provides a good research method to detect the urinary metabolic profile in rats before and after irradiation. (authors)

  6. Metabolic Tumor Volume as a Prognostic Imaging-Based Biomarker for Head-and-Neck Cancer: Pilot Results From Radiation Therapy Oncology Group Protocol 0522

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, David L., E-mail: david.schwartz@utsw.edu [Department of Radiation Oncology, University of Texas Southwestern School of Medicine, Dallas, Texas (United States); Harris, Jonathan [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Yao, Min [Department of Radiation Oncology, Case Western Reserve University School of Medicine, Cleveland, Ohio (United States); Rosenthal, David I. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Opanowski, Adam; Levering, Anthony [American College of Radiology Imaging Network, Philadelphia, Pennsylvania (United States); Ang, K. Kian [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Trotti, Andy M. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Garden, Adam S. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Jones, Christopher U. [Sutter Medical Group, Sacramento, California (United States); Harari, Paul [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Foote, Robert [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Holland, John [Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon (United States); Zhang, Qiang [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Le, Quynh-Thu [Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, California (United States)

    2015-03-15

    Purpose: To evaluate candidate fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging biomarkers for head-and-neck chemoradiotherapy outcomes in the cooperative group trial setting. Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 0522 patients consenting to a secondary FDG-PET/CT substudy were serially imaged at baseline and 8 weeks after radiation. Maximum standardized uptake value (SUVmax), SUV peak (mean SUV within a 1-cm sphere centered on SUVmax), and metabolic tumor volume (MTV) using 40% of SUVmax as threshold were obtained from primary tumor and involved nodes. Results: Of 940 patients entered onto RTOG 0522, 74 were analyzable for this substudy. Neither high baseline SUVmax nor SUVpeak from primary or nodal disease were associated with poor treatment outcomes. However, primary tumor MTV above the cohort median was associated with worse local-regional control (hazard ratio 4.01, 95% confidence interval 1.28-12.52, P=.02) and progression-free survival (hazard ratio 2.34, 95% confidence interval 1.02-5.37, P=.05). Although MTV and T stage seemed to correlate (mean MTV 6.4, 13.2, and 26.8 for T2, T3, and T4 tumors, respectively), MTV remained a strong independent prognostic factor for progression-free survival in bivariate analysis that included T stage. Primary MTV remained prognostic in p16-associated oropharyngeal cancer cases, although sample size was limited. Conclusion: High baseline primary tumor MTV was associated with worse treatment outcomes in this limited patient subset of RTOG 0522. Additional confirmatory work will be required to validate primary tumor MTV as a prognostic imaging biomarker for patient stratification in future trials.

  7. Prognostic value of metabolic tumor volume as measured by fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography in nasopharyngeal carcinoma.

    Science.gov (United States)

    Yoon, Young-Ho; Lee, Seok-Hwan; Hong, Sung-Lyong; Kim, Seong-Jang; Roh, Hwan-Jung; Cho, Kyu-Sup

    2014-10-01

    The prognostic value of the tumor burden characterized by the metabolic tumor volume (MTV) remains under investigation in nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the prognostic value of the maximum standardized uptake value (SUVmax ) and MTV according to metabolic volume threshold as measured by positron emission tomography (PET)/computed tomography (CT), and other clinical factors, in patients with NPC. This study was a retrospective chart review. We evaluated the association of SUVmax , MTV2.5 , MTV3.0 , and other clinical factors with overall survival (OS) using Kaplan-Meier and Cox regression models. (MTV2.5 and MTV3.0 are the volume of hypermetabolic tissue within the regions of gross tumor volumes with a SUV value greater than the threshold values of 2.5 and 3.0, respectively.) Higher MTV2.5 of 31.45 cm(3) and MTV3.0 of 23.01 cm(3) were associated with an increased risk of death (hazard ratio [HR] = 5.028; p = 0.029), although no significant relationship was found between SUVmax and OS. Interestingly, MTV3.0 was associated with OS in both the differentiated and undifferentiated groups, although MTV2.5 was only associated with OS in the undifferentiated group. Among the clinical parameters, only radiotherapy was associated with longer OS (HR = 12.124; p < 0.001). The MTV and radiotherapy could be prognostic values associated with OS. Particularly, MTV2.5 and MTV3.0 might be valuable metabolic parameters for predicting long-term survival in patients with NPC. Furthermore, MTV3.0 may be more useful because it can be applied irrespective of pathologic subtype. © 2014 ARS-AAOA, LLC.

  8. Metabolic tumor burden quantified on [{sup 18}F]FDG PET/CT improves TNM staging of lung cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Lapa, Paula; Isidoro, Jorge; Costa, Gracinda [Centro Hospitalar e Universitario de Coimbra, Nuclear Medicine Department, Coimbra (Portugal); Oliveiros, Barbara [University of Coimbra, Laboratory of Biostatistics and Medical Informatics, Faculty of Medicine, Coimbra (Portugal); University of Coimbra, Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine, Coimbra (Portugal); Marques, Margarida [University of Coimbra, Laboratory of Biostatistics and Medical Informatics, Faculty of Medicine, Coimbra (Portugal); Centro Hospitalar e Universitario de Coimbra, Technology and Information Systems Department, Coimbra (Portugal); Caseiro Alves, Filipe [Centro Hospitalar e Universitario de Coimbra, Radiology Department, Coimbra (Portugal); Nascimento Costa, J.M. [University of Coimbra, University Oncology Clinic, Faculty of Medicine, Coimbra (Portugal); Lima, Joao Pedroso de [Centro Hospitalar e Universitario de Coimbra, Nuclear Medicine Department, Coimbra (Portugal); University of Coimbra, Institute of Nuclear Sciences Applied to Health-ICNAS, Coimbra (Portugal)

    2017-12-15

    The purpose of our study was to test a new staging algorithm, combining clinical TNM staging (cTNM) with whole-body metabolic active tumor volume (MATV-WB), with the goal of improving prognostic ability and stratification power. Initial staging [{sup 18}F]FDG PET/CT of 278 non-small cell lung cancer (NSCLC) patients, performed between January/2011 and April/2016, 74(26.6%) women, 204(73.4%) men; aged 34-88 years (mean ± SD:66 ± 10), was retrospectively evaluated, and MATV-WB was quantified. Each patient's follow-up time was recorded: 0.7-83.6 months (mean ± SD:25.1 ± 20.3). MATV-WB was an independent and statistically-significant predictor of overall survival (p < 0.001). The overall survival predictive ability of MATV-WB (C index: mean ± SD = 0.7071 ± 0.0009) was not worse than cTNM (C index: mean ± SD = 0.7031 ± 0.007) (Z = -0.143, p = 0.773). Estimated mean survival times of 56.3 ± 3.0 (95%CI:50.40-62.23) and 21.7 ± 2.2 months (95%CI:17.34-25.98) (Log-Rank = 77.48, p < 0.001), one-year survival rate of 86.8% and of 52.8%, and five-year survival rate of 53.6% and no survivors, were determined, respectively, for patients with MATV-WB < 49.5 and MATV-WB ≥ 49.5. Patients with MATV-WB ≥ 49.5 had a mortality risk 2.9-5.8 times higher than those with MATV-WB < 49.5 (HR = 4.12, p < 0.001). MATV-WB cutoff points were also determined for each cTNM stage: 23.7(I), 49.5(II), 52(III), 48.8(IV) (p = 0.029, p = 0.227, p = 0.025 and p = 0.001, respectively). At stages I, III and IV there was a statistically-significant difference in the estimated mean overall survival time between groups of patients defined by the cutoff points (p = 0.007, p = 0.004 and p < 0.001, respectively). At stage II (p = 0.365), there was a clinically-significant difference of about 12 months between the groups. In all cTNM stages, patients with MATV-WB ≥ cutoff points had lower survival rates. Combined clinical TNM-PET staging (cTNM-P) was then tested: Stage I < 23.7; Stage I

  9. Influence of physical activity on the metabolism and the total body content of sodium and potassium in the rat

    International Nuclear Information System (INIS)

    Yeh, J.K.; Yasumura, A.; Aloia, J.F.

    1986-01-01

    The purpose of this study was to investigate the effect of exercise (EX) and immobilization (IMB) on the absorption, excretion and total body content of sodium (TBNa) and potassium (TBK). Female Sprague Dawley rats 5 weeks old were divided into four groups: EX; Control (CON); EX with pair feeding to the level equal to the CON (EX-P); IMB by sciatica denervation. The nutritional balance study data was taken 5 weeks into the experimental period and the animals were sacrificed after 5 additional weeks of experimentation. The carcasses were kept frozen and used for total body composition by neutron activation. The results of the total body composition show that EX resulted in an increase, IMB resulted in a decrease, of the TBNa and TBK. There was no significant difference in TBNa of TBK, between the EX and the EX-P groups even though, the food intake was higher in the EX group. The results of the nutritional balance study confirmed the results of the total body composition

  10. Plasma total odd-chain fatty acids in the monitoring of disorders of propionate, methylmalonate and biotin metabolism

    NARCIS (Netherlands)

    Coker, M.; de Klerk, J. B.; Poll-The, B. T.; Huijmans, J. G.; Duran, M.

    1996-01-01

    Total plasma odd-numbered long-chain fatty acids were analysed in patients with methylmalonic acidaemia (vitamin B12-responsive and unresponsive), combined methylmalonic acidaemia/homocystinuria (CblC), propionic acidaemia (both neonatal-onset and late-onset), biotinidase deficiency and

  11. Tumor Delineation and Quantitative Assessment of Glucose Metabolic Rate within Histologic Subtypes of Non-Small Cell Lung Cancer by Using Dynamic 18F Fluorodeoxyglucose PET.

    Science.gov (United States)

    Meijer, Tineke W H; de Geus-Oei, Lioe-Fee; Visser, Eric P; Oyen, Wim J G; Looijen-Salamon, Monika G; Visvikis, Dimitris; Verhagen, Ad F T M; Bussink, Johan; Vriens, Dennis

    2017-05-01

    Purpose To assess whether dynamic fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET) has added value over static 18 F-FDG PET for tumor delineation in non-small cell lung cancer (NSCLC) radiation therapy planning by using pathology volumes as the reference standard and to compare pharmacokinetic rate constants of 18 F-FDG metabolism, including regional variation, between NSCLC histologic subtypes. Materials and Methods The study was approved by the institutional review board. Patients gave written informed consent. In this prospective observational study, 1-hour dynamic 18 F-FDG PET/computed tomographic examinations were performed in 35 patients (36 resectable NSCLCs) between 2009 and 2014. Static and parametric images of glucose metabolic rate were obtained to determine lesion volumes by using three delineation strategies. Pathology volume was calculated from three orthogonal dimensions (n = 32). Whole tumor and regional rate constants and blood volume fraction (V B ) were computed by using compartment modeling. Results Pathology volumes were larger than PET volumes (median difference, 8.7-25.2 cm 3 ; Wilcoxon signed rank test, P PET images is in best agreement with pathology volume and could be useful for NSCLC autocontouring. Differences in glycolytic rate and V B between SCC and AC are relevant for research in targeting agents and radiation therapy dose escalation. © RSNA, 2016 Online supplemental material is available for this article.

  12. Metabolic syndrome as a risk factor for total hip or knee replacement due to primary osteoarthritis: a prospective cohort study (the HUNT study and the Norwegian Arthroplasty Register).

    Science.gov (United States)

    Hellevik, Alf Inge; Johnsen, Marianne Bakke; Langhammer, Arnulf; Baste, Valborg; Furnes, Ove; Storheim, Kjersti; Zwart, John Anker; Flugsrud, Gunnar Birkeland; Nordsletten, Lars

    2018-01-01

    Biochemical changes associated with obesity may accelerate osteoarthritis beyond the effect of mechanical factors. This study investigated whether metabolic syndrome and its components (visceral obesity, hypertension, dyslipidemia and insulin resistance) were risk factors for subsequent total hip replacement (THR) or total knee replacement (TKR) due to primary osteoarthritis. In this prospective cohort study, data from the second survey of the Nord-Trøndelag Health Study 2 (HUNT2) were linked to the Norwegian Arthroplasty Register for identification of the outcome of THR or TKR. The analyses were stratified by age (<50, 50-69.9 and ≥70 years) and adjusted for gender, body mass index, smoking, physical activity and education. Of the 62,661 participants, 12,593 (20.1%) were identified as having metabolic syndrome, and we recorded 1,840 (2.9%) THRs and 1,111 (1.8%) TKRs during a mean follow-up time of 15.4 years. Cox regression analyses did not show any association between full metabolic syndrome and THR or TKR, except in persons <50 years with metabolic syndrome who had a decreased risk of THR (hazard ratio [HR] 0.58, 95% CI 0.40-0.83). However, when including only participants whose exposure status did not change during follow-up, this protective association was no longer significant. Increased waist circumference was associated with increased risk of TKR in participants <50 years (HR 1.62, 95% CI 1.10-2.39) and 50-69.9 years (HR 1.43, 95% CI 1.14-1.80). Hypertension significantly increased the risk of TKR in participants <50 years (HR 1.38, 95% CI 1.05-1.81), and this risk was greater for men. This study found an increased risk of TKR in men <50 years with hypertension and persons <70 years with increased waist circumference. Apart from this, neither metabolic syndrome nor its components were associated with increased risk of THR or TKR due to primary osteoarthritis.

  13. Metabolic syndrome as a risk factor for total hip or knee replacement due to primary osteoarthritis: a prospective cohort study (the HUNT study and the Norwegian Arthroplasty Register

    Directory of Open Access Journals (Sweden)

    Hellevik AI

    2018-01-01

    Full Text Available Alf Inge Hellevik,1,2 Marianne Bakke Johnsen,3,4 Arnulf Langhammer,1 Valborg Baste,5 Ove Furnes,6,7 Kjersti Storheim,3,4 John Anker Zwart,3,4 Gunnar Birkeland Flugsrud,2 Lars Nordsletten2,4 1The HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology, Levanger, 2Division of Orthopaedic Surgery, Oslo University Hospital, Oslo, 3Research and Communication Unit for Musculoskeletal Health, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, 4Faculty of Medicine, University of Oslo, Oslo, 5Uni Research Health, Bergen, 6The Norwegian Arthroplasty Register, Department of Orthopedic Surgery, Haukeland University Hospital, Bergen, 7Department of Clinical Medicine, Institute of Medicine and Dentistry, University of Bergen, Bergen, Norway Objective: Biochemical changes associated with obesity may accelerate osteoarthritis beyond the effect of mechanical factors. This study investigated whether metabolic syndrome and its components (visceral obesity, hypertension, dyslipidemia and insulin resistance were risk factors for subsequent total hip replacement (THR or total knee replacement (TKR due to primary osteoarthritis.Design: In this prospective cohort study, data from the second survey of the Nord-Trøndelag Health Study 2 (HUNT2 were linked to the Norwegian Arthroplasty Register for identification of the outcome of THR or TKR. The analyses were stratified by age (<50, 50–69.9 and ≥70 years and adjusted for gender, body mass index, smoking, physical activity and education.Results: Of the 62,661 participants, 12,593 (20.1% were identified as having metabolic syndrome, and we recorded 1,840 (2.9% THRs and 1,111 (1.8% TKRs during a mean follow-up time of 15.4 years. Cox regression analyses did not show any association between full metabolic syndrome and THR or TKR, except in persons <50 years with metabolic syndrome who had a decreased risk

  14. Giant cell tumor with secondary aneurysmal bone cyst shows heterogeneous metabolic pattern on {sup 18}F-FDG PET.CT: A case reort

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hee Jeong; Kwon, Seong Young; Yoon, Yeon Hong [Chonnam National University Hwasun Hospital, Huasun (Korea, Republic of); Cho, Sang Geon; Kim, Jahae; Song, Ho Chun; Kim, Sung Sun; Park, Jin Gyoon [Chonnam National University Hospital, Gwangju (Korea, Republic of)

    2016-12-15

    Giant cell tumor (GCT) is a generally benign bone tumor accounting for approximately 5 % of all primary bone neoplasms. Cystic components in GCTs that indicate secondary aneurysmal bone cysts (ABCs) are reported in 14 % of GCTs. Although both of them have been described separately in previous reports that may show considerable fluorodeoxyglucose (FDG) uptake despite their benign nature, the findings of GCT with secondary ABC on 18F-FDG positron emission tomography/computed tomography (PET/CT) have not been well-known. We report a case of GCT with secondary ABC in a 26-year-old woman. 18F-FDG PET/CT revealed a heterogeneous hypermetabolic lesion in the left proximal femur with the maximum standardized uptake value of 4.7. The solid components of the tumor showed higher FDG uptake than the cystic components. These observations suggest that the ABC components in GCTs show heterogeneous metabolic patterns on {sup 18}F-FDG PET/CT.

  15. Giant cell tumor with secondary aneurysmal bone cyst shows heterogeneous metabolic pattern on "1"8F-FDG PET.CT: A case reort

    International Nuclear Information System (INIS)

    Park, Hee Jeong; Kwon, Seong Young; Yoon, Yeon Hong; Cho, Sang Geon; Kim, Jahae; Song, Ho Chun; Kim, Sung Sun; Park, Jin Gyoon

    2016-01-01

    Giant cell tumor (GCT) is a generally benign bone tumor accounting for approximately 5 % of all primary bone neoplasms. Cystic components in GCTs that indicate secondary aneurysmal bone cysts (ABCs) are reported in 14 % of GCTs. Although both of them have been described separately in previous reports that may show considerable fluorodeoxyglucose (FDG) uptake despite their benign nature, the findings of GCT with secondary ABC on 18F-FDG positron emission tomography/computed tomography (PET/CT) have not been well-known. We report a case of GCT with secondary ABC in a 26-year-old woman. 18F-FDG PET/CT revealed a heterogeneous hypermetabolic lesion in the left proximal femur with the maximum standardized uptake value of 4.7. The solid components of the tumor showed higher FDG uptake than the cystic components. These observations suggest that the ABC components in GCTs show heterogeneous metabolic patterns on "1"8F-FDG PET/CT

  16. Prognostic value of metabolic tumour volume and total lesion glycolysis in 18F-FDG PET/CT scans in locally advanced breast cancer staging.

    Science.gov (United States)

    Jiménez-Ballvé, A; García García-Esquinas, M; Salsidua-Arroyo, O; Serrano-Palacio, A; García-Sáenz, J A; Ortega Candil, A; Fuentes Ferrer, M E; Rodríguez Rey, C; Román-Santamaría, J M; Moreno, F; Carreras-Delgado, J L

    To determine whether metabolic tumour volume (MTV) and total lesion glycolysis (TLG) are able to predict recurrence risk in locally advanced breast cancer (LABC) patients. Retrospective study of LABC patients who undertook neoadjuvant, local and adjuvant treatment and follow up. A 18 F-FDG PET/CT study for initial staging was performed analysing in this study different metabolic parameters (MTV, TLG, SUVmax and SUVmed) both in the primary tumour (T) as well as in axillary nodes (N) and whole-body (WB). Forty females were included between January 2010-2011; follow up until January 2015 was completed. The average follow-up was 46 months. Twenty percent presented recurrence: local disease (n=2) and distant metastasis (n=6); 3 patients died (38% of the patients which recurred and 7.5% from the total). SUVmax, MTV and TLG, in T, N and WB, were higher in those patients with recurrence. The MTV and TLG parameters in the tumour (T) were related to the recurrence rate (P=.020 and P=.028, respectively); whereas SUVmax in the lymph nodes (N) was significantly related (P=.008) to the recurrence rate. The best cut-off points to predict recurrence where: MTV T ≥19.3cm 3 , TLG T≥74.4g and SUVmax N≥13.8, being 10-12 times more likely to recidivate when these thresholds where exceeded. Tumour grade was the only clinical-pathological variable which was related to recurrence probability (p=.035). In this study of LABC patients the metabolic parameters which have a better relationship with recurrence rate are: MTV and TLG in the primary tumour, SUVmax in the regional lymph node disease and whole-body PET data. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  17. A case report of an ampullary tumor presenting with spontaneous perforation of an aberrant bile duct and treated with total laparoscopic pancreaticoduodenectomy

    Directory of Open Access Journals (Sweden)

    Kaplan Mehmet

    2012-07-01

    Full Text Available Abstract Background This case report discusses a patient who presented with bile peritonitis due to spontaneous perforation of an aberrant bile duct that originated in the triangular ligament of the liver. It was associated with an ampullary tumor and treated with total laparoscopic pancreaticoduodenectomy (TLPD. Case report A 58-year-old male patient was admitted to the emergency department of Medical Park Gaziantep Hospital in September 2009 with acute abdominal findings. He underwent an urgent laparoscopy, and, interestingly, bile peritonitis due to the rupture of an aberrant bile duct in the triangular ligament was noted. After laparoscopic treatment of the acute conditions, the follow-up examinations of the patient showed the finding of obstructive jaundice. Endoscopic retrograde cholangio-pancreatography revealed a 1-cm polypoid mass located at the ampulla of Vater (duodenal papilla with possible extension to the ampullary sphincter. A stent was inserted for temporary biliary drainage, and subsequent endoscopic biopsy showed the pathological finding of adenocarcinoma. After waiting for a 1-month period for the peritonitis to heal, the patient underwent pylorus-preserving TLPD and was discharged without any major complications on postoperative day 7. Conclusion In patients with bile peritonitis, it should be considered that the localization of the perforation may be in an aberrant bile duct localized at the triangular ligament and the etiology may be associated with an obstructing periampullary tumor. Laparoscopic pancreaticoduodenectomy is a feasible operative procedure in carefully selected patients. This technique can achieve adequate margins and follows oncological principles. Randomized comparative studies are needed to establish the superiority of minimally invasive surgery over traditional open surgery.

  18. Studies on the utility and mechanism of the V-79 cell metabolic cooperation assay for tumor promoters

    International Nuclear Information System (INIS)

    Hartman, T.G.

    1985-01-01

    Cigarette smoke condensate and its fractions were tested for activity in the V-79 Metabolic Cooperation Assay to determine the usefulness of the assay for analysis of a complex mixture and to compare the results obtained with previously conducted in vivo promoter assays. The whole condensate and several of its fractions were positive in the assay. In general, the Metabolic Cooperation Assay results were comparable to previously published results obtained on mouse skin. The effect of cell density, phorbol 12-myrystate-13-acetate (PMA) exposure time, concentration, pre-exposure and binding activity on the recovery of mutant V-79 Chinese hamster lung fibroblasts in the Metabolic Cooperation Assay was determined. A PMA exposure interval of only 1 minute resulted in maximum recovery of mutant cells. PMA began to inhibit metabolic cooperation at an exposure concentration of 0.1 ng/ml. Pre-exposure of cells to PMA increased the recovery of both post-PMA-treated and non-treated mutant cells in a dose-dependent manner. 3 H-PMA was rapidly bound to or taken up by the V-79 cells under assay conditions. The effect of calcium antagonists and representative compounds from several classes of anti-promoters including anti-inflammatory sterols, protease inhibitors, retinoids and cyclic nucleotides on metabolic determined. Each compound was tested for its effect on metabolic cooperation and also for its ability to reverse or modify the inhibitory properties of PMA on inter-cellular communication. Of all the compounds tested only cyclic adenosine monophosphate (cAMP) was able to antagonize the inhibitory effect of PMA

  19. Metabolic and improved organ scan studies. II. Nitrogen-13 labeled compounds used as in-vivo probes for enzyme therapy and as tumor localizing and organ imaging agents

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    A number of 13 N-labeled compounds have been enzymatically synthesized and are being evaluated as tumor and/or organ localizing agents. 13 N-Ammonia, produced after cyclotron generation of 13 N-nitrate and subsequent reduction was used to enzymatically aminate the appropriate substrate to yield 13 N-L-glutamic acid, L-glutamine, L-asparagine, L-valine, L-leucine and L-alanine. The use of 13 N-asparagine as a myocardial scanning agent and as a tumor localizing agent in asparaginase-sensitive tumors is discussed. Two imaging devices were used to study the effectiveness of the compounds as localizing agents. For static whole body distribution studies, a dual-detector high energy gamma ray (HEG) rectilinear scanner, equipped with constant response collimators was employed. The uniformity of response of this system permits quantitative determination of the amount of 13 N activity present in the organ or tumor of interest. The total organ kinetic imaging monitor (TOKIM) gamma camera system was used for dynamic studies covering smaller areas of the subject's body

  20. N-Acetylcysteine Supplementation Controls Total Antioxidant Capacity, Creatine Kinase, Lactate, and Tumor Necrotic Factor-Alpha against Oxidative Stress Induced by Graded Exercise in Sedentary Men

    Directory of Open Access Journals (Sweden)

    Donrawee Leelarungrayub

    2011-01-01

    Full Text Available Aim of this study was to evaluate the effects of short-term (7 days N-acetylcysteine (NAC at 1,200 mg daily supplementation on muscle fatigue, maximal oxygen uptake (VO2max, total antioxidant capacity (TAC, lactate, creatine kinase (CK, and tumor necrotic factor-alpha (TNF-α. Twenty-nine sedentary men (13 controls; 16 in the supplement group from a randomized control were included. At before and after supplementation, fatigue index (FI was evaluated in the quadriceps muscle, and performed a graded exercise treadmill test to induce oxidative stress, and as a measure of VO2max. Blood samples were taken before exercise and 20 minutes after it at before and after supplementation, to determine TAC, CK, lactate, and TNF-α levels. Results showed that FI and VO2max increased significantly in the supplement group. After exercise decreased the levels of TAC and increased lactate, CK, and TNF-α of both groups at before supplementation. After supplementation, lactate, CK, and TNF-α levels significantly increased and TAC decreased after exercise in the control group. Whereas the TAC and lactate levels did not change significantly, but CK and TNF-α increased significantly in the supplement group. Therefore, this results showed that NAC improved the muscle fatigue, VO2max, maintained TAC, controlled lactate production, but had no influence on CK and TNF-α.

  1. Comparison of Pu metabolism and pulmonary tumors in dogs and rats exposed to 239PuO2

    International Nuclear Information System (INIS)

    Mahaffey, J.A.; Sanders, C.L.; Dagle, G.E.; Park, J.F.

    The dose-effect relationships of dogs and rats exposed by inhalation to 239 PuO 2 were compared to evaluate parameters that may provide a better understanding for extrapolating these laboratory animal results to humans. Comparisons were made on animals with lifetime lung doses between 1400 and 11,000 rad. Parameters compared included survival; Pu clearance and translocation; and time of occurrence, incidence and histopathology of pulmonary tumors. The group means for lifetime dose to lung were not significantly different between dogs and rats, but when survival time was expressed as the percentage of maximum life expectancy (MLE), the mean survival time of dogs was 40% of MLE and of rats was 56% of MLE. Lung tumors were the causes of death in 84% of the dogs and 54% of the rats; the mean survival time to lung tumor was 44% of MLE for dogs, compared to 57% of MLE for rats. Whole-body clearance of plutonium was slower in dogs. More Pu translocated to the thoracic lymph nodes, liver, and skeleton in the dogs than in rats. Estimates of species differences in lung clearance were dependent on the methods of estimating initial lung burden. There were parameters with qualitative and quantitative similarities in dogs and rats. Quantitative differences between species, generally within a factor of two, suggested that more reliable dosimetry estimates are needed to make quantitative extrapolation between species

  2. Urinary and Serum Metabolomics Analyses Uncover That Total Glucosides of Paeony Protect Liver against Acute Injury Potentially via Reprogramming of Multiple Metabolic Pathways

    Directory of Open Access Journals (Sweden)

    Haojie Li

    2017-01-01

    Full Text Available Total glucosides of paeony (TGP have been confirmed to be hepatoprotective. However, the underlying mechanism is largely unclear. In this study, we investigated the metabolic profiles of urine and serum in rats with carbon tetrachloride- (CCl4- induced experimental liver injury and TGP administration by using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS. The vehicle or a single dose of TGP was intragastrically administered to Wistar rats once a day for 14 consecutive days. To induce ALI, 50% CCl4 was injected intraperitoneally into these rats 2 hours after the last time administration of saline of TGP at the 14th day. The results indicated that TGP administration could protect rats from CCl4-induced ALI and alanine aminotransferase (ALT and aspartate aminotransferase (AST elevation, as well as hepatocyte apoptosis and inflammation. Furthermore, metabolomics analysis showed that TGP treatment significantly attenuated CCl4-triggered deregulation of multiple metabolites in both urine and serum, including glycine, alanine, proline, and glutamine. Metabolite set enrichment and pathway analyses demonstrated that amino acid cycling and glutathione metabolism were two main pathways involved in CCl4-induced experimental liver injury and TGP administration. Taken together, these findings revealed that regulation of metabolites potentially plays a pivotal role in the protective effect of TGP on ALI.

  3. Improvements in glucose metabolism early after gastric bypass surgery are not explained by increases in total bile acids and fibroblast growth factor 19 concentrations

    DEFF Research Database (Denmark)

    Jørgensen, Nils B; Dirksen, Carsten; Bojsen-Møller, Kirstine N

    2015-01-01

    Context: Bile acids and fibroblast growth factor 19 (FGF19) have been suggested as key mediators of the improvements in glucose metabolism after Roux-en-Y gastric bypass (RYGB). Objective: To describe fasting and postprandial state total bile acid (TBA) and FGF19 concentrations before and after...... (T2D) patients and 12 normal glucose tolerant (NGT) subjects participated in the study. Intervention: A 4-hour liquid meal test was performed before and 1 week, 3 months, and 1 year after RYGB. Main Outcome Measures: We measured fasting and postprandial TBA and FGF19 concentrations. Results: Fasting...... TBA concentrations decreased in NGT subjects (P TBA was decreased in NGT subjects 1 week after RYGB (before surgery, 567...

  4. Cerebral blood flow and metabolism during controlled hypotension with sodium-nitroprusside and general anaesthesia for total hip replacement a.m. Charnley

    International Nuclear Information System (INIS)

    Buenemann, L.; Jensen, K.; Thomsen, L.; Riisager, S.

    1987-01-01

    Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRo 2 ) were studied during hypotension induced with sodium nitroprusside (SNP) in 10 patients undergoing total hip replacement a.m. Charnley. Cerebral blood flow was measured using an injection of xenon-133 into an arm vein. The decay curve was detected by five scintillation counters placed over each hemisphere and analysed with the Novo 10a cerebrograph. Blood samples were drawn from the radial artery and the jugular venous bulb to calculate the CMRo 2 . In the gropu as a whole, there were significant decreases in mean arterial pressure and in cerebrovascular resistance. There were no significant changes, in either CBF or CMRo 2 in the gropu as a whole, but there were substantial individual differences. In conclusion, the use of SNP-induced hypotension for extracranial surgery should be used only in patients monitored closely. (author)

  5. Beneficial Phytochemicals with Anti-Tumor Potential Revealed through Metabolic Profiling of New Red Pigmented Lettuces (Lactuca sativa L.

    Directory of Open Access Journals (Sweden)

    Xiao-Xiao Qin

    2018-04-01

    Full Text Available The present study aimed to compare polyphenols among red lettuce cultivars and identify suitable cultivars for the development and utilization of healthy vegetables. Polyphenols, mineral elements, and antioxidant activity were analyzed in the leaves of six red pigmented lettuce (Lactuca sativa L. cultivars; thereafter, we assessed the anti-tumor effects of cultivar B-2, which displayed the highest antioxidant activity. Quadrupole–Orbitrap mass spectrometry analysis revealed four classes of polyphenols in these cultivars. The composition and contents of these metabolites varied significantly among cultivars and primarily depended on leaf color. The B-2 cultivar had the highest antioxidant potential than others because it contained the highest levels of polyphenols, especially anthocyanin, flavone, and phenolic acid; furthermore, this cultivar displayed anti-tumor effects against the human lung adenocarcinoma cell line A549, human hepatoma cell line Bel7402, human cancer colorectal adenoma cell line HCT-8, and HT-29 human colon cancer cell line. Hence, the new red-leaf lettuce cultivar B-2 has a distinct metabolite profile, with high potential for development and utilization of natural phytochemical and mineral resources in lettuces and can be used as a nutrient-dense food product.

  6. Beneficial Phytochemicals with Anti-Tumor Potential Revealed through Metabolic Profiling of New Red Pigmented Lettuces (Lactuca sativa L.).

    Science.gov (United States)

    Qin, Xiao-Xiao; Zhang, Ming-Yue; Han, Ying-Yan; Hao, Jing-Hong; Liu, Chao-Jie; Fan, Shuang-Xi

    2018-04-11

    The present study aimed to compare polyphenols among red lettuce cultivars and identify suitable cultivars for the development and utilization of healthy vegetables. Polyphenols, mineral elements, and antioxidant activity were analyzed in the leaves of six red pigmented lettuce ( Lactuca sativa L.) cultivars; thereafter, we assessed the anti-tumor effects of cultivar B-2, which displayed the highest antioxidant activity. Quadrupole-Orbitrap mass spectrometry analysis revealed four classes of polyphenols in these cultivars. The composition and contents of these metabolites varied significantly among cultivars and primarily depended on leaf color. The B-2 cultivar had the highest antioxidant potential than others because it contained the highest levels of polyphenols, especially anthocyanin, flavone, and phenolic acid; furthermore, this cultivar displayed anti-tumor effects against the human lung adenocarcinoma cell line A549, human hepatoma cell line Bel7402, human cancer colorectal adenoma cell line HCT-8, and HT-29 human colon cancer cell line. Hence, the new red-leaf lettuce cultivar B-2 has a distinct metabolite profile, with high potential for development and utilization of natural phytochemical and mineral resources in lettuces and can be used as a nutrient-dense food product.

  7. Higher Total Protein Intake and Change in Total Protein Intake Affect Body Composition but Not Metabolic Syndrome Indexes in Middle-Aged Overweight and Obese Adults Who Perform Resistance and Aerobic Exercise for 36 Weeks.

    Science.gov (United States)

    Campbell, Wayne W; Kim, Jung Eun; Amankwaah, Akua F; Gordon, Susannah L; Weinheimer-Haus, Eileen M

    2015-09-01

    Studies assessing the effects of protein supplementation on changes in body composition (BC) and health rarely consider the impact of total protein intake (TPro) or the change in TPro (CTPro) from participants' usual diets. This secondary data analysis assessed the impact of TPro and CTPro on changes in BC and metabolic syndrome (MetS) indexes in overweight and obese middle-aged adults who participated in an exercise training program. Men and women [n = 117; age: 50 ± 0.7 y, body mass index (BMI; in kg/m(2)): 30.1 ± 0.3; means ± SEs] performed resistance exercise 2 d/wk and aerobic exercise 1 d/wk and consumed an unrestricted diet along with 200-kcal supplements (0, 10, 20, or 30 g whey protein) twice daily for 36 wk. Protein intake was assessed via 4-d food records. Multiple linear regression model and stratified analysis were applied for data analyses. Among all subjects, TPro and CTPro were inversely associated (P exercise training, higher TPro promoted positive changes in BC but not in MetS indexes in overweight and obese middle-aged adults. Changes in TPro from before to during the intervention also influenced BC responses and should be considered in future research when different TPro is achieved via diet or supplements. This trial was registered at clinicaltrials.gov as NCT00812409. © 2015 American Society for Nutrition.

  8. Measuring treatment response to systemic therapy and predicting outcome in biliary tract cancer: comparing tumor size, volume, density, and metabolism.

    Science.gov (United States)

    Sahani, Dushyant V; Hayano, Koichi; Galluzzo, Anna; Zhu, Andrew X

    2015-04-01

    The purpose of this study was to evaluate the response of biliary tract cancer treated with multidrug chemotherapy using FDG PET in comparison with morphologic and density changes. In this phase II clinical trial, 28 patients with unresectable or metastatic biliary tract cancers treated with gemcitabine and oxaliplatin combined with bevacizumab (GEMOX-B) underwent FDG PET and contrast-enhanced CT at baseline and after the second cycle of the therapy (8 weeks). A single reviewer recorded tumor maximum standardized uptake value (SUVmax) along with size, volume (3D-sphere), and density. The percentage changes of the parameters were compared with progression-free survival at 7 months. Overall survival was compared with the percentage change of SUVmax. After 8 weeks, measurable reductions (±SD) in size (7.05±4.19 to 5.52±3.28 cm, -21.70%), volume (411.38±540.08 to 212.41±293.45 cm3, -48.36%), and density (60.76±20.65 to 50.68±16.89 HU, -15.59%) were noted along with a substantial drop in SUVmax (5.95±1.95 to 3.36±1.28, -43.52%). The SUVmax change showed positive correlations with tumor size change (R2=0.39, p=0.0004) and volumetric change (R2=0.34, p=0.001). Patients who showed a larger drop in SUVmax at 8 weeks correlated with favorable progression-free survival (p=0.02). ROC analysis showed that a 45% reduction in SUVmax was the best cutoff value to detect favorable progression-free survival patients. When we used this cutoff value, Kaplan-Meier analysis showed that patients with tumors showing greater reduction in SUVmax had favorable progression-free survival and overall survival (p=0.0009, p=0.03). In biliary tract cancers treated with GEMOX-B, the reduction of SUVmax after therapy is a better predictor for survival than morphologic and density changes.

  9. Comparative evaluation of SUV, tumor-to-blood standard uptake ratio (SUR), and dual time point measurements for assessment of the metabolic uptake rate in FDG PET.

    Science.gov (United States)

    Hofheinz, Frank; Hoff, Jörg van den; Steffen, Ingo G; Lougovski, Alexandr; Ego, Kilian; Amthauer, Holger; Apostolova, Ivayla

    2016-12-01

    We have demonstrated recently that the tumor-to-blood standard uptake ratio (SUR) is superior to tumor standardized uptake value (SUV) as a surrogate of the metabolic uptake rate K m of fluorodeoxyglucose (FDG), overcoming several of the known shortcomings of the SUV approach: excellent linear correlation of SUR and K m from Patlak analysis was found using dynamic imaging of liver metastases. However, due to the perfectly standardized uptake period used for SUR determination and the comparatively short uptake period, these results are not automatically valid and applicable for clinical whole-body examinations in which the uptake periods (T) are distinctly longer and can vary considerably. Therefore, the aim of this work was to investigate the correlation between SUR derived from clinical static whole-body scans and K m-surrogate derived from dual time point (DTP) measurements. DTP (18)F-FDG PET/CT was performed in 90 consecutive patients with histologically proven non-small cell lung cancer (NSCLC). In the PET images, the primary tumor was delineated with an adaptive threshold method. For determination of the blood SUV, an aorta region of interest (ROI) was delineated manually in the attenuation CT and transferred to the PET image. Blood SUV was computed as the mean value of the aorta ROI. SUR values were computed as ratio of tumor SUV and blood SUV. SUR values from the early time point of each DTP measurement were scan time corrected to 75 min postinjection (SURtc). As surrogate of K m, we used the SUR(T) slope, K slope, derived from DTP measurements since it is proportional to the latter under the given circumstances. The correlation of SUV and SURtc with K slope was investigated. The prognostic value of SUV, SURtc, and K slope for overall survival (OS) and progression-free survival (PFS) was investigated with univariate Cox regression in a homogeneous subgroup (N=31) treated with primary chemoradiation. Correlation analysis revealed for both, SUV and SURtc, a

  10. Role of arachidonic acid metabolism in transcriptional induction of tumor necrosis factor gene expression by phorbol ester

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, J.; Spriggs, D.; Imamura, K.; Stone, R.; Luebbers, R.; Kufe, D.

    1989-01-01

    The treatment of human HL-60 promyelocytic leukemia cells with 12-0 tetradecanoylphorbol-13-acetate (TPA) is associated with induction of tumor necrosis factor (TNF) transcripts. The study reported here has examined TPA-induced signaling mechanisms responsible for the regulation of TNF gene expression in these cells. Run-on assays demonstrated that TPA increases TNS mRNA levels by transcriptional activation of this gene. The induction of TNF transcripts by TPA was inhibited by the isoquinolinesulfonamide derivative H7 but not by HA1004, suggesting that this effect of TPA is mediated by activation of protein kinase C. TPA treatment also resulted in increased arachidonic acid release. Moreover, inhibitors of phospholipase, A/sub 2/ blocked both the increase in arachidonic acid release and the induction of TNF transcripts. These findings suggest that TPA induces TNF gene expression through the formation of arachidonic acid metabolites. Although indomethacin had no detectable effect on this induction of TNF transcripts, ketoconazole, an inhibitor of 5-lipoxygenase, blocked TPA-induced increases in TNF mRNA levels. Moreover, TNF mRNA levels were increased by the 5-lipoxygenase metabolite leukotriene B/sub 4/. In contrast, the cyclooxygenase metabolite prostaglandin E/sub 2/ inhibited the induction of TNF transcripts by TPA. Taken together, these results suggest that TPA induces TNF gene expression through the arachidonic acid cascade and that the level of TNF transcripts is regulated by metabolites of the pathway, leukotriene B/sub 4/ and prostaglandin E/sub 2/.

  11. Short-term role of the dietary total antioxidant capacity in two hypocaloric regimes on obese with metabolic syndrome symptoms: the RESMENA randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Lopez-Legarrea Patricia

    2013-02-01

    Full Text Available Abstract Background Dietary strategies seem to be the most prescribed therapy in order to counteract obesity regarding not only calorie restriction, but also bioactive ingredients and the composition of the consumed foods. Dietary total antioxidant capacity (TAC is gaining importance in order to assess the quality of the diet. Methods Ninety-six obese adults presenting metabolic syndrome (MetS symptoms completed an 8-week intervention trial to evaluate the effects of a novel dietary program with changes in the nutrient distribution and meal frequency and to compare it with a dietary pattern based on the American Heart Association (AHA guidelines. Anthropometric and biochemical parameters were assessed at baseline and at the endpoint of the study, in addition to 48-hours food dietary records. Results Both diets equally (p > 0.05 improved MetS manifestations. Dietary TAC was the component which showed the major influence on body weight (p = 0.034, body mass index (p = 0.026, waist circumference (p = 0.083 and fat mass (p = 0.015 reductions. Transaminases (ALT and AST levels (p = 0.062 and p = 0.004, respectively were associated with lower TAC values. Conclusion RESMENA diet was as effective as AHA pattern for reducing MetS features. Dietary TAC was the most contributing factor involved in body weight and obesity related markers reduction. Trial registration http://www.clinicaltrials.gov; NCT01087086

  12. Trend overtime of total haemoglobin, iron metabolism and trace minerals in veal calves fed high amounts of two different solid feeds

    Directory of Open Access Journals (Sweden)

    Anna-Lisa Stefani

    2010-01-01

    Full Text Available Fifty Polish Friesian veal calves were administrated high amounts of two different solid feeds (maize grain and a mix diet containing 10% of straw and 8% of soy in addition to the traditional milk replacer diet. Compared to the mix diet, maize grain had a lower content of iron, copper and zinc and a minor fibre level. Effects of the two diets on calves’ blood haemoglobin, iron, iron metabolism parameters, copper and zinc concentrations were studied. Haemoglobin concentration resulted higher at the end of the fattening for calves fed the mix diet, as expected. Values remained, however, within ranges that allowed acceptable carcass paleness. Haematic iron, unsaturated iron binding capacity (UIBC and total iron binding capacity (TIBC levels were not significantly different between the two solid feeds. Lower copper and zinc blood concentrations resulted for calves fed the mix diet were likely due to the feed fibre interfering with the bioavailability of the two minerals, according to what happens for iron.

  13. Satisfactory spinal anesthesia with a total of 1.5 mg of bupivacaine for transurethral resection of bladder tumor in an elderly patient.

    Science.gov (United States)

    Namba, Yoshimichi; Yamakage, Michiaki; Tanaka, Yoshinori

    2016-01-01

    Spinal anesthesia is popular for endoscopic urological surgery. Many patients undergoing urological surgery are elderly. It is important to limit the dose to reduce any resultant hemodynamic effect. We present a case in which incremental administration of 0.1 % bupivacaine up to 1.5 mg was sufficient to produce satisfactory spinal anesthesia for transurethral resection of bladder tumor (TURBT).

  14. The early predictive value of a decrease of metabolic tumor volume in repeated 18F-FDG PET/CT for recurrence of locally advanced non-small cell lung cancer with concurrent radiochemotherapy

    International Nuclear Information System (INIS)

    Huang, Wei; Liu, Bo; Fan, Min; Zhou, Tao; Fu, Zheng; Zhang, Zicheng; Li, Hongsheng; Li, Baosheng

    2015-01-01

    Highlights: •The patients underwent the second FDG PET during the early stage of concurrent chemoradiotherapy (CCRT). •To our knowledge, this could be the first study showing that the repeated FDG PET during the early stage of CCRT has added value by being a prognostic factor for recurrence of the locally advanced NSCLC patients. •This is a result of continuous research. •The decrease of MTV was the only significant risk factor for recurrence. -- Abstract: Purpose: The aim of this study is to investigate the value of [ 18 F] fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F FDG PET/CT) to predict recurrence of patients with locally advanced non-small cell lung cancer (NSCLC) during the early stage of concurrent chemoradiotherapy (CCRT). Methods: A total of 53 stage III NSCLC patients without diabetics or undergoing surgery were enrolled in the prospective study. Those patients were evaluated by FDG PET before and following 40 Gy radiotherapy (RT) with a concurrent cisplatin-based heterogeneous chemotherapy regimen. Semiquantitative assessment was used to determine maximum and mean SUVs (SUVmax/SUVmean) and metabolic tumor volume (MTV) of the primary tumor. The prognostic significance of PET/CT parameters and other clinical variables was assessed using Cox regression analyses. The cutoffs of PET/CT parameters which have been determined by the previous study were used to separate the groups with Kaplan–Meier curves. Results: Recurrence rates at 1- and 2-years were 18.9% (10/53) and 50.9% (27/53) for all patients, respectively. Cox regression analysis showed that the only prognostic factor for recurrence was a decrease of MTV. Using the cutoff of 29.7%, a decrease of MTV can separate the patients into 2 groups with Kaplan–Meier curve successfully. Conclusion: The prospective study has reinforced the early predictive value of MTV in repeated 18 F-FDG PET/CT for recurrence in a subgroup of locally advanced NSCLC who underwent CCRT. A

  15. Development of a Microfluidic-Based Optical Sensing Device for Label-Free Detection of Circulating Tumor Cells (CTCs Through Their Lactic Acid Metabolism

    Directory of Open Access Journals (Sweden)

    Tzu-Keng Chiu

    2015-03-01

    Full Text Available This study reports a microfluidic-based optical sensing device for label-free detection of circulating tumor cells (CTCs, a rare cell species in blood circulation. Based on the metabolic features of cancer cells, live CTCs can be quantified indirectly through their lactic acid production. Compared with the conventional schemes for CTC detection, this label-free approach could prevent the biological bias due to the heterogeneity of the surface antigens on cancer cells. In this study, a microfluidic device was proposed to generate uniform water-in-oil cell-encapsulating micro-droplets, followed by the fluorescence-based optical detection of lactic acid produced within the micro-droplets. To test its feasibility to quantify cancer cells, experiments were carried out. Results showed that the detection signals were proportional to the number of cancer cells within the micro-droplets, whereas such signals were insensitive to the existence and number of leukocytes within. To further demonstrate its feasibility for cancer cell detection, the cancer cells with known cell number in a cell suspension was detected based on the method. Results revealed that there was no significant difference between the detected number and the real number of cancer cells. As a whole, the proposed method opens up a new route to detect live CTCs in a label-free manner.

  16. Effect of Peptide Receptor Radionuclide Therapy on Somatostatin Receptor Status and Glucose Metabolism in Neuroendocrine Tumors: Intraindividual Comparison of Ga-68 DOTANOC PET/CT and F-18 FDG PET/CT

    Science.gov (United States)

    Oh, Sowon; Prasad, Vikas; Lee, Dong Soo; Baum, R. P.

    2011-01-01

    The heterogeneous nature of the neuroendocrine tumors (NET) makes it challenging to find one uniformly applicable management protocol which is especially true for diagnosis. The discovery of the overexpression of somatostatin receptors (SMS-R) on neuroendocrine tumor cells lead to the generalized and rapid acceptance of radiolabeled somatostatin receptor analogs for staging and restaging of NET as well as for Peptide Receptor Radionuclide Therapy (PRRNT) using Y-90 and Lu-177 DOTATATE/DOTATOC. In this present work we tried to look in to the effect of PRRNT on the glucose metabolism assessed by F-18 FDG PET/CT and SMS-R density assessed by Ga-68 DOTANOC PET/CT. We observed a complex relationship between the somatostatin receptor expression and glucose metabolism with only 56% (77/138) of the lesions showing match, while the others show mismatch between the receptor status and metabolism. The match between receptor expression and glucose metabolism increases with the grade of NET. In grade 3 NET, there is a concurrence between the changes in glucose metabolism and somatostatin receptor expression. PRRNT was found to be more effective in lesions with higher receptor expression. PMID:22121482

  17. Low 25(OH)D3 levels are associated with total adiposity, metabolic syndrome, and hypertension in Caucasian children and adolescents.

    Science.gov (United States)

    Pacifico, L; Anania, C; Osborn, J F; Ferraro, F; Bonci, E; Olivero, E; Chiesa, C

    2011-10-01

    Evidence of the association between vitamin D and cardiovascular risk factors in the young is limited. We therefore assessed the relationships between circulating 25-hydroxyvitamin D(3) (25(OH)D(3)) and metabolic syndrome (MetS), its components, and early atherosclerotic changes in 452 (304 overweight/obese and 148 healthy, normal weight) Caucasian children. We determined serum 25(OH)D(3) concentrations in relation to MetS, its components (central obesity, hypertension, low high-density lipoprotein (HDL)-cholesterol, hypertriglyceridemia, glucose impairment, and/or insulin resistance (IR)), and impairment of flow-mediated vasodilatation (FMD) and increased carotid intima-media thickness (cIMT) - two markers of subclinical atherosclerosis. Higher 25(OH)D(3) was significantly associated with a reduced presence of MetS. Obesity, central obesity, hypertension, hypertriglyceridemia, low HDL-cholesterol, IR, and MetS were all associated with increased odds of having low 25(OH)D(3) levels, after adjustment for age, sex, and Tanner stage. After additional adjustment for SDS-body mass index, elevated blood pressure (BP) and MetS remained significantly associated with low vitamin D status. The adjusted odds ratio (95% confidence interval) for those in the lowest (27 ng/ml) of 25(OH)D(3) for hypertension was 1.72 (1.02-2.92), and for MetS, it was 2.30 (1.20-4.40). A similar pattern of association between 25(OH)D(3), high BP, and MetS was observed when models were adjusted for waist circumference. No correlation was found between 25(OH)D(3) concentrations and either FMD or cIMT. Low 25(OH)D(3) levels in Caucasian children are inversely related to total adiposity, MetS, and hypertension.

  18. PET and endocrine tumors

    International Nuclear Information System (INIS)

    Rigo, P.; Belhocine, T.; Hustinx, R.; Foidart-Willems, J.

    2000-01-01

    The authors review the main indications of PET examination, and specifically of 18 FDG, in the assessment of endocrine tumors: of the thyroid, of the parathyroid, of the adrenal and of the pituitary glands. Neuroendocrine tumors, gastro-entero-pancreatic or carcinoid tumors are also under the scope. Usually, the most differentiated tumors show only poor uptake of the FDG as they have a weak metabolic and proliferative activity. In the assessment of endocrine tumors, FDG-PET should be used only after most specific nuclear examinations been performed. (author)

  19. III. Cellular ultrastructures in situ as key to understanding tumor energy metabolism: biological significance of the Warburg effect [v1; ref status: indexed, http://f1000r.es/a0

    Directory of Open Access Journals (Sweden)

    Halina Witkiewicz

    2013-01-01

    Full Text Available Despite the universality of metabolic pathways, malignant cells were found to have their metabolism reprogrammed to generate energy by glycolysis even under normal oxygen concentrations (the Warburg effect. Therefore, the pathway energetically 18 times less efficient than oxidative phosphorylation was implicated to match increased energy requirements of growing tumors. The paradox was explained by an abnormally high rate of glucose uptake, assuming unlimited availability of substrates for tumor growth in vivo. However, ultrastructural analysis of tumor vasculature morphogenesis showed that the growing tissue regions did not have continuous blood supply and intermittently depended on autophagy for survival. Erythrogenic autophagy, and resulting ATP generation by glycolysis, appeared critical to initiating vasculature formation where it was missing. This study focused on ultrastructural features that reflected metabolic switch from aerobic to anaerobic. Morphological differences between and within different types of cells were evident in tissue sections. In cells undergoing nucleo-cytoplasmic conversion into erythrosomes (erythrogenesis, gradual changes led to replacing mitochondria with peroxisomes, through an intermediate form connected to endoplasmic reticulum. Those findings related to the issue of peroxisome biogenesis and to the phenomenon of hemogenic endothelium. Mitochondria were compacted also during mitosis. In vivo, cells that lost and others that retained capability to use oxygen coexisted side-by-side; both types were important for vasculature morphogenesis and tissue growth. Once passable, the new vasculature segment could deliver external oxygen and nutrients. Nutritional and redox status of microenvironment had similar effect on metabolism of malignant and non-malignant cells demonstrating the necessity to maintain structure-energy equivalence in all living cells. The role of glycolysis in initiating vasculature formation, and in

  20. Early hemodynamics and metabolic changes after total abdominal evisceration for experimental multivisceral transplantation Efeitos hemodinâmicos e metabólicos iniciais da evisceração abdominal total para transplante multivisceral experimental

    Directory of Open Access Journals (Sweden)

    Ruy J. Cruz Junior

    2009-04-01

    Full Text Available PURPOSE: Multivisceral transplantation (MVTx has been accepted as standard therapeutic modality for patients with short-bowel syndrome associated with irreversible liver failure. Even nowadays, experimental models of MVTx grounds high incidence of intraoperative or early recipient mortality. Despite the known deleterious effects of hepatosplanchnic exenteration the impact of this procedure on systemic hemodynamics and metabolism remains to be determined. METHODS: Nine dogs (20.1±0.5 kg were subjected to an en bloc resection of all abdominal organs including, stomach, duodenum, pancreas, liver, spleen, small bowel, and colon. A woven double velour vascular graft was interposed between the suprahepatic and infrahepatic vena cava. Systemic hemodynamic were evaluated through a Swan-Ganz catheter, ultrasonic flowprobes, and arterial lines. Systemic O2-derived variables, glucose, and lactate metabolism were analyzed throughout the experiment. RESULTS: Complete abdominal exenteration was associated with significant reduction in cardiac output, and mean arterial pressure (57% and 14%, respectively. Two hours after reperfusion a significant reduction in arterial pH and glucose were also observed. Oxygen consumption remained unaltered during the first two hours of the experiment, with a significant increase of lactate levels (1.4±0.3 vs. 7.6±0.4, pOBJETIVO: O transplante multivisceral (MVTx é preconizado como tratamento de escolha em pacientes com síndrome do intestine curto associado com falência hepática irreverssível. Modelos experimentais de MVTx apresentam altas taxas de mortalidade intra-operatória e nas primeiras horas apos a reperfusão. Apesar dos deletérios efeitos hemodinâmicos da exenteração abdominal, o impacto deste procedimento na perfusão e no metabolismo sistêmico ainda esta por ser determinado. MÉTODOS: Nove cães (20.1±0.5 kg foram submetidos a ressecção em bloco de todos os orgãos abdominais incluindo, est

  1. A fully automatic, threshold-based segmentation method for the estimation of the Metabolic Tumor Volume from PET images: validation on 3D printed anthropomorphic oncological lesions

    Science.gov (United States)

    Gallivanone, F.; Interlenghi, M.; Canervari, C.; Castiglioni, I.

    2016-01-01

    18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET) is a standard functional diagnostic technique to in vivo image cancer. Different quantitative paramters can be extracted from PET images and used as in vivo cancer biomarkers. Between PET biomarkers Metabolic Tumor Volume (MTV) has gained an important role in particular considering the development of patient-personalized radiotherapy treatment for non-homogeneous dose delivery. Different imaging processing methods have been developed to define MTV. The different proposed PET segmentation strategies were validated in ideal condition (e.g. in spherical objects with uniform radioactivity concentration), while the majority of cancer lesions doesn't fulfill these requirements. In this context, this work has a twofold objective: 1) to implement and optimize a fully automatic, threshold-based segmentation method for the estimation of MTV, feasible in clinical practice 2) to develop a strategy to obtain anthropomorphic phantoms, including non-spherical and non-uniform objects, miming realistic oncological patient conditions. The developed PET segmentation algorithm combines an automatic threshold-based algorithm for the definition of MTV and a k-means clustering algorithm for the estimation of the background. The method is based on parameters always available in clinical studies and was calibrated using NEMA IQ Phantom. Validation of the method was performed both in ideal (e.g. in spherical objects with uniform radioactivity concentration) and non-ideal (e.g. in non-spherical objects with a non-uniform radioactivity concentration) conditions. The strategy to obtain a phantom with synthetic realistic lesions (e.g. with irregular shape and a non-homogeneous uptake) consisted into the combined use of standard anthropomorphic phantoms commercially and irregular molds generated using 3D printer technology and filled with a radioactive chromatic alginate. The proposed segmentation algorithm was feasible in a

  2. A phylogenetic analysis of basal metabolism, total evaporative water loss, and life-history among foxes from desert and mesic regions.

    Science.gov (United States)

    Williams, J B; Muñoz-Garcia, A; Ostrowski, S; Tieleman, B I

    2004-01-01

    We measured basal metabolic rate (BMR) and total evaporative water loss (TEWL) of species of foxes that exist on the Arabian Peninsula, Blanford's fox (Vulpes cana) and two subspecies of Red fox (Vulpes vulpes). Combining these data with that on other canids from the literature, we searched for specialization of physiological traits among desert foxes using both conventional least squares regression and regressions based on phylogenetic independent contrasts. Further, we explored the consequences of reduced body size of foxes on life history parameters such as litter size and neonate mass. For Blanford's foxes, Red foxes from the central desert of Arabia, and Red foxes from the more mesic Asir mountains, body mass averaged 1,285 +/- 52 g, 1,967 +/- 289 g, and 3,060 +/- 482 g, respectively, whereas mean BMR, during summer, was 304.5 +/- 32.3 kJ/day, 418.0 +/- 32.4 kJ/day, and 724.1 +/- 120.2 kJ/day (+/- SD). An analysis of covariance with body mass as a covariate showed no statistical differences in BMR among foxes. Analysis of covariance indicated that Red fox from the Asir mountains had a higher TEWL than Red foxes from central Arabia or than Blanford's foxes also from the mountains. Comparisons of all species of desert and mesic foxes showed no significant differences in BMR, nor did desert foxes have a significantly lower BMR than other carnivores. TEWL of desert foxes was lower than other more mesic carnivores; deviations in TEWL ranged from -17.7% for the Fennec fox (Fennecus zerda) to -57.4% for the Kit fox (Vulpes velox). Although desert foxes have a BMR comparable to other more mesic species, it appears that desert foxes do have a smaller body mass, lowering overall energy requirements. We attribute this reduction in body size to the "resource limitation hypothesis" whereby natural selection favors smaller individuals in a resource-limited environment, especially during periods of severe food shortage. However, until common garden experiments are performed

  3. Multiparametric MR assessment of pediatric brain tumors

    International Nuclear Information System (INIS)

    Tzika, A.A.; Astrakas, L.G.; Zarifi, M.K.; Petridou, N.; Young-Poussaint, T.; Goumnerova, L.; Black, P.McL.; Zurakowski, D.; Anthony, D.C.

    2003-01-01

    MR assessment of pediatric brain tumors has expanded to include physiologic information related to cellular metabolites, hemodynamic and diffusion parameters. The purpose of this study was to investigate the relationship between MR and proton MR spectroscopic imaging in children with primary brain tumors. Twenty-one patients (mean age 9 years) with histologically verified brain tumors underwent conventional MR imaging, hemodynamic MR imaging (HMRI) and proton MR spectroscopic imaging (MRSI). Fourteen patients also had diffusion-weighted MR imaging (DWMRI). Metabolic indices including choline-containing compounds (Cho), total creatine (tCr) and lipids/lactate (L) were derived by proton MRSI, relative cerebral blood volume (rCBV) by HMRI, and apparent tissue water diffusion coefficients (ADC) by DWMRI. Variables were examined by linear regression and correlation as well as by ANOVA. Cho (suggestive of tumor cellularity and proliferative activity) correlated positively with rCBV, while the relationship between Cho and ADC (suggestive of cellular density) was inverse (P<0.001). The relationship between rCBV and ADC was also inverse (P=0.004). Cho and lipids (suggestive of necrosis and/or apoptosis) were not significantly correlated (P=0.51). A positive relationship was found between lipids and ADC (P=0.002). The relationships between Cho, rCBV, ADC and lipids signify that tumor physiology is influenced by the tumor's physical and chemical environment. Normalized Cho and lipids distinguished high-grade from low-grade tumors (P<0.05). Multiparametric MR imaging using MRSI, HMRI and DWMRI enhances assessment of brain tumors in children and improves our understanding of tumor physiology while promising to distinguish higher- from lower-malignancy tumors, a distinction that is particularly clinically important among inoperable tumors. (orig.)

  4. Role of G308 promoter variant of tumor necrosis factor alpha gene on weight loss and metabolic parameters after a high monounsaturated versus a high polyunsaturated fat hypocaloric diets.

    Science.gov (United States)

    de Luis, Daniel A; Aller, Rocío; Izaola, Olatz; Gonzalez Sagrado, Manuel; Conde, Rosa

    2013-09-07

    The aim of our study was to investigate the influence of G-308 promoter variant of the tumor necrosis factor (TNF) alpha gene on metabolic changes and weight loss secondary to a high monounsaturated fat vs a high polyunsaturated fat hypocaloric diet in obese subjects. A sample of 261 obese subjects were enrolled in a consecutive prospective way, from May 2011 to July 2012 in a tertiary hospital. In the basal visit, patients were randomly allocated during 3 months to Diet M (high monounsaturated fat hypocaloric diet) and Diet P (high polyunsaturated fat hypocaloric diet). One hundred and ninety seven patients (73.2%) had the genotype G-308G and 64 (26.8%) patients had the genotype G-308A. There were no significant differences between the effects (on weight, body mass index (BMI), waist circumference, fat mass) in either genotype group with both diets. With the diet type P and in genotype G-308G, glucose levels (-6.7(22.1)mg/dl vs -3.7(2.2)mg/dl: p = 0.02), HOMA-R (-0.6(2.1)units vs -0.26(3.1)units: p = 0.01), insulin levels (-1.7(6.6)UI/L vs -0.6(7.1)UI/L: p = 0.009), total cholesterol levels (-15.3(31.1)mg/dl vs -8.4(22.1)mg/dl: p = 0.01), LDL cholesterol levels (-10.7(28.1)mg/dl vs -3.8(21.1)mg/dl: p = 0.008) and triglycerides (-12.1(52.1)mg/dl vs -6.6(43.1)mg/dl: p = 0.02) decreased. Carriers of the G-308G promoter variant of TNF alpha gene have a better metabolic response than A-308 obese with a high polyunsaturated fat hypocaloric diet. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  5. Correlation between resting state fMRI total neuronal activity and PET metabolism in healthy controls and patients with disorders of consciousness.

    Science.gov (United States)

    Soddu, Andrea; Gómez, Francisco; Heine, Lizette; Di Perri, Carol; Bahri, Mohamed Ali; Voss, Henning U; Bruno, Marie-Aurélie; Vanhaudenhuyse, Audrey; Phillips, Christophe; Demertzi, Athena; Chatelle, Camille; Schrouff, Jessica; Thibaut, Aurore; Charland-Verville, Vanessa; Noirhomme, Quentin; Salmon, Eric; Tshibanda, Jean-Flory Luaba; Schiff, Nicholas D; Laureys, Steven

    2016-01-01

    The mildly invasive 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established imaging technique to measure 'resting state' cerebral metabolism. This technique made it possible to assess changes in metabolic activity in clinical applications, such as the study of severe brain injury and disorders of consciousness. We assessed the possibility of creating functional MRI activity maps, which could estimate the relative levels of activity in FDG-PET cerebral metabolic maps. If no metabolic absolute measures can be extracted, our approach may still be of clinical use in centers without access to FDG-PET. It also overcomes the problem of recognizing individual networks of independent component selection in functional magnetic resonance imaging (fMRI) resting state analysis. We extracted resting state fMRI functional connectivity maps using independent component analysis and combined only components of neuronal origin. To assess neuronality of components a classification based on support vector machine (SVM) was used. We compared the generated maps with the FDG-PET maps in 16 healthy controls, 11 vegetative state/unresponsive wakefulness syndrome patients and four locked-in patients. The results show a significant similarity with ρ = 0.75 ± 0.05 for healthy controls and ρ = 0.58 ± 0.09 for vegetative state/unresponsive wakefulness syndrome patients between the FDG-PET and the fMRI based maps. FDG-PET, fMRI neuronal maps, and the conjunction analysis show decreases in frontoparietal and medial regions in vegetative patients with respect to controls. Subsequent analysis in locked-in syndrome patients produced also consistent maps with healthy controls. The constructed resting state fMRI functional connectivity map points toward the possibility for fMRI resting state to estimate relative levels of activity in a metabolic map.

  6. Correlating tumor metabolic progression index measured by serial FDG PET-CT, apparent diffusion coefficient measured by magnetic resonance imaging (MRI) and blood genomics to patient’s outcome in advanced colorectal cancer: the CORIOLAN study

    International Nuclear Information System (INIS)

    Deleporte, Amelie; Charette, Nicolas; Machiels, Godelieve; Piccart, Martine; Flamen, Patrick; Hendlisz, Alain; Paesmans, Marianne; Garcia, Camilo; Vandeputte, Caroline; Lemort, Marc; Engelholm, Jean-Luc; Hoerner, Frederic; Aftimos, Philippe; Awada, Ahmad

    2014-01-01

    Metastatic colorectal cancer (mCRC) may present various behaviours that define different courses of tumor evolution. There is presently no available tool designed to assess tumor aggressiveness, despite the fact that this is considered to have a major impact on patient outcome. CORIOLAN is a single-arm prospective interventional non-therapeutic study aiming mainly to assess the natural tumor metabolic progression index (TMPI) measured by serial FDG PET-CT without any intercurrent antitumor therapy as a prognostic factor for overall survival (OS) in patients with mCRC. Secondary objectives of the study aim to test the TMPI as a prognostic marker for progression-free survival (PFS), to assess the prognostic value of baseline tumor FDG uptake on PFS and OS, to compare TMPI to classical clinico-biological assessment of prognosis, and to test the prognostic value on OS and PFS of MRI-based apparent diffusion coefficient (ADC) and variation of vADC using voxel-based diffusion maps. Additionally, this study intends to identify genomic and epigenetic factors that correlate with progression of tumors and the OS of patients with mCRC. Consequently, this analysis will provide information about the signaling pathways that determine the natural and therapy-free course of the disease. Finally, it would be of great interest to investigate whether in a population of patients with mCRC, for which at present no known effective therapy is available, tumor aggressiveness is related to elevated levels of circulating tumor cells (CTCs) and to patient outcome. Tumor aggressiveness is one of the major determinants of patient outcome in advanced disease. Despite its importance, supported by findings reported in the literature of extreme outcomes for patients with mCRC treated with chemotherapy, no objective tool allows clinicians to base treatment decisions on this factor. The CORIOLAN study will characterize TMPI using FDG-PET-based metabolic imaging of patients with chemorefractory m

  7. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  8. Osteomalacia inducida por tumor: hemangiopericitoma rinosinusal Tumor-induced osteomalacia: rhinosinusal hemangiopericytoma

    Directory of Open Access Journals (Sweden)

    Enriqueta M. Serafini

    2013-02-01

    Full Text Available La osteomalacia inducida por tumor es una rara enfermedad del metabolismo óseo caracterizada por el aumento en la excreción de fosfato a nivel renal seguido de hipofosfatemia. Es causada por agentes fosfatúricos producidos por determinados tumores. La resección total del tumor resulta en la completa reversión de las anormalidades bioquímicas, la desaparición de las manifestaciones clínicas y los hallazgos en los estudios por imágenes. Presentamos el caso de un varón de 61 años con cuadro clínico y laboratorio compatibles con osteomalacia oncogénica inducida por tumor mesenquimático de localización rinosinusal. En nuestro caso el diagnóstico histológico correspondió a una neoplasia de tipo vascular: hemangiopericitoma.Tumor-induced osteomalacia is a rare disease of bone metabolism. The characteristic of this disease is an increase in phosphate excretion followed by hypophosphatemia, due to phosphaturic agents produced by different types of tumors. Tumor resection results in complete resolution of clinical, biochemical and radiological abnormalities. We present the case of a 61 year old man with signs, symptoms and laboratory findings consistent with oncogenic osteomalacia due to a rhino-sinusal mesenchymal tumor. The histological diagnosis showed a vascular neoplasm: hemangiopericytoma.

  9. Metabolic Reprogramming in Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Raquel Guimaraes Coelho

    2018-03-01

    Full Text Available Among all the adaptations of cancer cells, their ability to change metabolism from the oxidative to the glycolytic phenotype is a hallmark called the Warburg effect. Studies on tumor metabolism show that improved glycolysis and glutaminolysis are necessary to maintain rapid cell proliferation, tumor progression, and resistance to cell death. Thyroid neoplasms are common endocrine tumors that are more prevalent in women and elderly individuals. The incidence of thyroid cancer has increased in the Past decades, and recent findings describing the metabolic profiles of thyroid tumors have emerged. Currently, several drugs are in development or clinical trials that target the altered metabolic pathways of tumors are undergoing. We present a review of the metabolic reprogramming in cancerous thyroid tissues with a focus on the factors that promote enhanced glycolysis and the possible identification of promising metabolic targets in thyroid cancer.

  10. Metabolic Reprogramming in Thyroid Carcinoma

    Science.gov (United States)

    Coelho, Raquel Guimaraes; Fortunato, Rodrigo S.; Carvalho, Denise P.

    2018-01-01

    Among all the adaptations of cancer cells, their ability to change metabolism from the oxidative to the glycolytic phenotype is a hallmark called the Warburg effect. Studies on tumor metabolism show that improved glycolysis and glutaminolysis are necessary to maintain rapid cell proliferation, tumor progression, and resistance to cell death. Thyroid neoplasms are common endocrine tumors that are more prevalent in women and elderly individuals. The incidence of thyroid cancer has increased in the Past decades, and recent findings describing the metabolic profiles of thyroid tumors have emerged. Currently, several drugs are in development or clinical trials that target the altered metabolic pathways of tumors are undergoing. We present a review of the metabolic reprogramming in cancerous thyroid tissues with a focus on the factors that promote enhanced glycolysis and the possible identification of promising metabolic targets in thyroid cancer. PMID:29629339

  11. Analysis of 18F-FDG PET mapping in malignant tumor patients with depression by SPM

    International Nuclear Information System (INIS)

    Su Liang; Zuo Chuantao; Guan Yihui; Zhao Jun; Shi Shenxun

    2005-01-01

    Objective: To investigate brain 18 F-fluorodeoxyglucose (FDG) PET mapping in malignant tumor patients with depressive emotion. Methods: 18 F-FDG PET imaging was performed in 21 malignant tumor patients (tumor group) and 21 healthy controls (control group). All were evaluated by self-rating depression scale (SDS)and 24 questions Hamilton rating scale for depression (HAMD). Results: (1) The standard total score of SDS and HAMD of the tumor group were higher than those of the control group (P 18 F-FDG PET imagings. The abnormalities of glucose metabolism might be related to their depressive emotion. (authors)

  12. Volumetry based biomarker speed of growth: Quantifying the change of total tumor volume in whole-body magnetic resonance imaging over time improves risk stratification of smoldering multiple myeloma patients.

    Science.gov (United States)

    Wennmann, Markus; Kintzelé, Laurent; Piraud, Marie; Menze, Bjoern H; Hielscher, Thomas; Hofmanninger, Johannes; Wagner, Barbara; Kauczor, Hans-Ulrich; Merz, Maximilian; Hillengass, Jens; Langs, Georg; Weber, Marc-André

    2018-05-18

    The purpose of this study was to improve risk stratification of smoldering multiple myeloma patients, introducing new 3D-volumetry based imaging biomarkers derived from whole-body MRI. Two-hundred twenty whole-body MRIs from 63 patients with smoldering multiple myeloma were retrospectively analyzed and all focal lesions >5mm were manually segmented for volume quantification. The imaging biomarkers total tumor volume, speed of growth (development of the total tumor volume over time), number of focal lesions, development of the number of focal lesions over time and the recent imaging biomarker '>1 focal lesion' of the International Myeloma Working Group were compared, taking 2-year progression rate, sensitivity and false positive rate into account. Speed of growth, using a cutoff of 114mm 3 /month, was able to isolate a high-risk group with a 2-year progression rate of 82.5%. Additionally, it showed by far the highest sensitivity in this study and in comparison to other biomarkers in the literature, detecting 63.2% of patients who progress within 2 years. Furthermore, its false positive rate (8.7%) was much lower compared to the recent imaging biomarker '>1 focal lesion' of the International Myeloma Working Group. Therefore, speed of growth is the preferable imaging biomarker for risk stratification of smoldering multiple myeloma patients.

  13. Monitoring therapy with MEK inhibitor U0126 in a novel Wilms tumor model in Wt1 knockout Igf2 transgenic mice using 18F-FDG PET with dual-contrast enhanced CT and MRI: early metabolic response without inhibition of tumor growth.

    Science.gov (United States)

    Flores, Leo G; Yeh, Hsin-Hsien; Soghomonyan, Suren; Young, Daniel; Bankson, James; Hu, Qianghua; Alauddin, Mian; Huff, Vicki; Gelovani, Juri G

    2013-04-01

    The understanding of the role of genetic alterations in Wilms tumor development could be greatly advanced using a genetically engineered mouse models that can replicate the development and progression of this disease in human patients and can be monitored using non-invasive structural and molecular imaging optimized for renal tumors. Repetitive dual-contrast computed tomography (CT; intravenous and intraperitoneal contrast), T2-weighted magnetic resonance imaging (MRI), and delayed 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) positron emission tomography (PET) were utilized for characterization of Igf2 biallelic expression/Wt1 knockout mouse model of Wilms tumor. For CT imaging, Ioversol 678 mg/ml in 200 μl was administered i.p. followed by 100 μl injected intravenously at 20 and 15 min prior to imaging, respectively. Static PET imaging studies were acquired at 1, 2, and 3 h after i.v. administration of (18)F-FDG (400 μCi). Coronal and sagittal T1-weighted images (TE/TR 8.5/620 ms) were acquired before and immediately after i.v. injection of 0.4 ml/kg gadopentetate dimeglumine followed by T2-weighted images (TE/TR 60/300 ms). Tumor tissue samples were characterized by histopathology and immunohistochemistry for Glut1, FASN, Ki67, and CD34. In addition, six Wt1-Igf2 mice were treated with a mitogen-activated protein kinase (MEK) inhibitor U0126 (50 μmol/kg i.p.) every 4 days for 6 weeks. (18)F-FDG PET/CT imaging was repeated at different days after initiation of therapy with U0126. The percent change of initial tumor volume and SUV was compared to non-treated historic control animals. Overall, the best tumor-to-adjacent kidney contrast as well as soft tissue contrast for other abdominal organs was achieved using T2-weighted MRI. Delayed (18)F-FDG PET (3-h post (18)F-FDG administration) and dual-contrast CT (intravenous and intraperitoneal contrast) provided a more accurate anatomic and metabolic characterization of Wilms tumors in Wt1-Igf2 mice

  14. EPR oxygen imaging and hyperpolarized (13) C MRI of pyruvate metabolism as noninvasive biomarkers of tumor treatment response to a glycolysis inhibitor 3-bromopyruvate

    DEFF Research Database (Denmark)

    Matsumoto, Shingo; Saito, Keita; Yasui, Hironobu

    2013-01-01

    The hypoxic nature of tumors results in treatment resistance and poor prognosis. To spare limited oxygen for more crucial pathways, hypoxic cancerous cells suppress mitochondrial oxidative phosphorylation and promote glycolysis for energy production. Thereby, inhibition of glycolysis has...... the potential to overcome treatment resistance of hypoxic tumors. Here, EPR imaging was used to evaluate oxygen dependent efficacy on hypoxia-sensitive drug. The small molecule 3-bromopyruvate blocks glycolysis pathway by inhibiting hypoxia inducible enzymes and enhanced cytotoxicity of 3-bromopyruvate under...

  15. EPR oxygen imaging and hyperpolarized 13C MRI of pyruvate metabolism as noninvasive biomarkers of tumor treatment response to a glycolysis inhibitor 3-bromopyruvate.

    Science.gov (United States)

    Matsumoto, Shingo; Saito, Keita; Yasui, Hironobu; Morris, H Douglas; Munasinghe, Jeeva P; Lizak, Martin; Merkle, Hellmut; Ardenkjaer-Larsen, Jan Henrik; Choudhuri, Rajani; Devasahayam, Nallathamby; Subramanian, Sankaran; Koretsky, Alan P; Mitchell, James B; Krishna, Murali C

    2013-05-01

    The hypoxic nature of tumors results in treatment resistance and poor prognosis. To spare limited oxygen for more crucial pathways, hypoxic cancerous cells suppress mitochondrial oxidative phosphorylation and promote glycolysis for energy production. Thereby, inhibition of glycolysis has the potential to overcome treatment resistance of hypoxic tumors. Here, EPR imaging was used to evaluate oxygen dependent efficacy on hypoxia-sensitive drug. The small molecule 3-bromopyruvate blocks glycolysis pathway by inhibiting hypoxia inducible enzymes and enhanced cytotoxicity of 3-bromopyruvate under hypoxic conditions has been reported in vitro. However, the efficacy of 3-bromopyruvate was substantially attenuated in hypoxic tumor regions (pO23-bromopyruvate in SCCVII tumor. The discrepant results between in vitro and in vivo data were attributed to biphasic oxygen dependent expression of monocarboxylate transporter-1 in vivo. Expression of monocarboxylate transporter-1 was enhanced in moderately hypoxic (8-15 mmHg) tumor regions but down regulated in severely hypoxic (<5 mmHg) tumor regions. These results emphasize the importance of noninvasive imaging biomarkers to confirm the action of hypoxia-activated drugs. Copyright © 2012 Wiley Periodicals, Inc.

  16. Bone tumors

    International Nuclear Information System (INIS)

    Unni, K.K.

    1988-01-01

    This book contains the proceedings on bone tumors. Topics covered include: Bone tumor imaging: Contribution of CT and MRI, staging of bone tumors, perind cell tumors of bone, and metastatic bone disease

  17. Toward the Elucidation of the Metabolism of 15-E2-Isoprostane: The Total Synthesis of the Methyl Ester of a Potential Central Metabolite

    Czech Academy of Sciences Publication Activity Database

    Jahn, Ullrich; Dinca, E.

    2010-01-01

    Roč. 75, č. 13 (2010), s. 4480-4491 ISSN 0022-3263 Grant - others:DFG(DE) Ja896/3-1 Institutional research plan: CEZ:AV0Z40550506 Keywords : isoprostane * total synthesis * radical anion cyclization Subject RIV: CC - Organic Chemistry Impact factor: 4.002, year: 2010

  18. Peripheral blood corticotropin-releasing factor, adrenocorticotropic hormone and cytokine (Interleukin Beta, Interleukin 6, tumor necrosis factor alpha) levels after high- and low-dose total-body irradiation in humans

    International Nuclear Information System (INIS)

    Girinsky, T.A.; Pallardy, M.; Comoy, E.; Benassi, T.; Roger, R.; Ganem, G.; Socie, G.; Cossett, J.M.; Magdelenat, H.

    1994-01-01

    Total-body irradiation (TBI) induces an increase in levels of granulocytes and cortisol in blood. To explore the underlying mechanisms, we studied 26 patients who had TBI prior to bone marrow transplantation. Our findings suggest that only a high dose of TBI (10 Gy) was capable of activating the hypothalamopituitary area since corticotropin-releasing factor and blood adrenocorticotropic hormone levels increased at the end of the TBI. There was a concomitant increase in the levels of interleukin 6 and tumor necrosis factor in blood, suggesting that these cytokines might activate the hypothalamo-pituitary adrenal axis. Interleukin 1 was not detected. Since vascular injury is a common after radiation treatment, it is possible that interleukin 6 was secreted by endothelial cells. The exact mechanisms of the production of cyctokines induced by ionizing radiation remain to be determined. 25 refs., 1 fig

  19. Imaging metabolic heterogeneity in cancer.

    Science.gov (United States)

    Sengupta, Debanti; Pratx, Guillem

    2016-01-06

    As our knowledge of cancer metabolism has increased, it has become apparent that cancer metabolic processes are extremely heterogeneous. The reasons behind this heterogeneity include genetic diversity, the existence of multiple and redundant metabolic pathways, altered microenvironmental conditions, and so on. As a result, methods in the clinic and beyond have been developed in order to image and study tumor metabolism in the in vivo and in vitro regimes. Both regimes provide unique advantages and challenges, and may be used to provide a picture of tumor metabolic heterogeneity that is spatially and temporally comprehensive. Taken together, these methods may hold the key to appropriate cancer diagnoses and treatments in the future.

  20. Walnuts lower TRAMP prostate tumor growth by altering IGF-1, energy and cholesterol metabolism and is not due to their fatty acids

    Science.gov (United States)

    Dietary changes could potentially reduce prostate cancer morbidity and mortality. Prostate tumor size, gene expression, metabolite and plasma responses to a 100 g of fat/kg diet (whole walnuts, walnut oil and other oils; balanced for macronutrients, tocopherols (a-and ' ) for 18 weeks were assessed ...

  1. Prognostic value of tumor burden measurement using the number of tumors in non-surgical patients with non-small cell lung cancer

    International Nuclear Information System (INIS)

    Zhang, Hao; Wroblewski, Kristen; Pu, Yonglin

    2012-01-01

    Background: No study to test the feasibility and prognostic value of the number of primary tumors, the number of positive lymph nodes, and the total number of tumors in the whole body as tumor burden measurements on FDG PET/CT imaging has been reported. Purpose: To determine whether the number of tumors seen in 18F-FDG PET scans can be a prognostic factor in non-surgical patients with non-small cell lung cancer (NSCLC). Material and Methods: One hundred and forty patients with histologically proven NSCLC and baseline 18F-FDG PET scan before therapy were identified in this retrospective analysis. The total number of tumors (TTn) in the whole body, the number of primary tumors (Tn), positive lymph nodes (Nn), and distant metastases (Mn), along with the maximum standardized uptake values (SUVmax) of the tumors were measured. Inter-observer variability of the total number of tumors, counted by two radiologists, was assessed. Survival analyses were performed to determine the prognostic value of the number of tumors. Results: Concordance correlation coefficients for the TTn, Tn, Nn, and Mn were all greater than 0.85. TTn and Nn were strong prognostic factors of NSCLC patients' overall survival (OS). In univariate Cox regression models, gender, stage, TTn, Nn, and Mn were statistically significant factors (P = 0.016, 0.032, 4. Conclusion: Measuring the number of tumors on FDG PET imaging is easy to perform with minimal inter-observer variability. The total number of tumors and number of nodal metastases, as metabolic tumor burden measurements in 18F-FDG PET/CT, are prognostic markers independent of clinical stage, age, gender, and SUV measurement in non-surgical patients with NSCLC

  2. Total and high molecular weight (HMW) adiponectin levels and measures of glucose and lipid metabolism following pioglitazone treatment in a randomized placebo-controlled study in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Frystyk, Jan; Højlund, Kurt

    2008-01-01

    and controls and examined possible mechanisms for increased insulin sensitivity during pioglitazone treatment. STUDY SUBJECTS: Thirty PCOS patients randomized to pioglitazone, 30 mg/day, or placebo for 16 weeks and 14 weight-matched healthy females were studied. DESIGN: Total and HMW adiponectin levels were...... measured, and euglycaemic hyperinsulinaemic clamps and indirect calorimetry were performed. Delta-values denoted changes during pioglitazone treatment (16 weeks--basal). RESULTS: Pretreatment adiponectin levels were decreased in PCOS patients vs. controls (P ...OBJECTIVE: Recent studies suggested that the effect of adiponectin on insulin-stimulated glucose metabolism is mediated primarily by the high molecular weight (HMW) form of adiponectin. In the present study we evaluated total and HMW adiponectin in polycystic ovary syndrome (PCOS) patients...

  3. The circulating concentration and ratio of total and high molecular weight adiponectin in post-menopausal women with and without osteoporosis and its association with body mass index and biochemical markers of bone metabolism.

    Science.gov (United States)

    Sodi, R; Hazell, M J; Durham, B H; Rees, C; Ranganath, L R; Fraser, W D

    2009-09-01

    There is increasing evidence suggesting that adiponectin plays a role in the regulation of bone metabolism. This was a cross-sectional study of 34 post-menopausal women with and 37 without osteoporosis. All subjects had body mass index (BMI), bone mineral density (BMD), total-, high molecular weight (HMW)-adiponectin and their ratio, osteoprotegerin (OPG), a marker of bone resorption (betaCTX) and formation (P1NP) measured. We observed a positive correlation between BMI and BMD (r=0.44, plean subjects but there was no difference between those with or without osteoporosis. There were significant negative correlations between HMW/total-adiponectin ratio and BMI (r=-0.27, p=0.030) and with OPG (r=-0.44, pproduction of OPG thereby affecting osteoclasts mediated bone resorption.

  4. Tumor Volume and Metabolism of Prostate Cancer Determined by Proton Magnetic Resonance Spectroscopic Imaging at 3T Without Endorectal Coil Reveal Potential Clinical Implications in the Context of Radiation Oncology

    International Nuclear Information System (INIS)

    Crehange, Gilles; Parfait, Sebastien; Liegard, Melanie; Maingon, Philippe; Ben Salem, Douraied; Cochet, Alexandre; Funes de la Vega, Mathilde; Cormier, Luc; Bonnetain, Franck; Mirjolet, Celine; Brunotte, Francois; Walker, Paul M.

    2011-01-01

    Purpose: To determine whether a relationship exists between the tumor volume (TV) or relative choline content determined using magnetic resonance spectroscopy imaging (MRSI) at 3T and the clinical prognostic parameters for patients with localized prostate cancer (PCa). Methods and Materials: A total of 72 men (mean age, 67.8 ± 6.2 years) were stratified as having low-risk (n = 26), intermediate-risk (n = 24), or high-risk (n = 22) PCa. MRSI was performed at 3T using a phased-array coil. Spectra are expressed as the total choline/citrate, total choline plus creatine/citrate, and total choline plus polyamines plus creatine/citrate ratios. The mean ratio of the most pathologic voxels and the MRSI-based TV were also determined. Results: The mean values of the total choline/citrate, total choline plus creatine/citrate, and total choline plus polyamine plus creatine/citrate ratios were greater for Stage T2b or greater tumors vs. Stage T2a or less tumors: 7.53 ± 13.60 vs. 2.31 ± 5.65 (p = .018), 8.98 ± 14.58 vs. 2.56 ± 5.70 (p = .016), and 10.32 ± 15.47 vs. 3.55 ± 6.16 (p = .014), respectively. The mean MRSI-based TV for Stage T2b or greater and Stage T2a or less tumors was significantly different (2.23 ± 2.62 cm 3 vs. 1.26 ± 2.06 cm 3 , respectively; p = .030). This TV correlated with increased prostate-specific antigen levels (odds ratio, 1.293; p = .012). Patients with high-risk PCa had a larger TV than did the patients with intermediate-risk PCa. A similar result was found for the intermediate-risk group compared with the low-risk group (odds ratio, 1.225; p = .041). Conclusion: Biomarkers expressing the relative choline content and TV were significant parameters for the localization of PCa and could be helpful for determining the prognosis more accurately.

  5. El factor de necrosis tumoral-α, la resistencia a la insulina, el metabolismo de lipoproteínas y la obesidad en humanos Tumor necrosis factor-α, insulin resistance, the lipoprotein metabolism and obesity in humans

    OpenAIRE

    M.ª M. Ramírez Alvarado; C. Sánchez Roitz

    2012-01-01

    En la obesidad el tejido adiposo produce moléculas proinflamatorias como el Factor de Necrosis tumoral-α, que tiene efectos locales en la fisiología del adipocito y efectos sistémicos en otros órganos. Muchos estudios relacionando TNF-α, obesidad, resistencia a la insulina y metabolismo lipídico se han realizado en ratas, conejos y perros, pero los resultados observados en varios de estos estudios han sido contradictorios y muchos de ellos no se han logrado reproducir en humanos, lo...

  6. Analysis of the inhibitory effects of VP-16-213 (etoposide) and podophyllotoxin on thymidine transport and metabolism in Ehrlich ascites tumor cells in vitro

    International Nuclear Information System (INIS)

    Yalowich, J.C.; Goldman, I.D.

    1984-01-01

    Uptake of 3 H after exposure of cells to [ 3 H]-thymidine is characterized by a rapid initial velocity that approximates membrane transport followed by a slower rate of uptake that parallels the accumulation of phosphorylated derivatives of thymidine, primarily thymidine triphosphate, within the cell. The high rate of thymidine transport relative to thymidine metabolism to the triphosphate within the cell decreases as the extracellular nucleoside concentration is reduced due to a much greater decrease in membrane transport than the subsequent metabolic step. Hence, as extracellular thymidine is decreased, transport becomes increasingly rate limiting to metabolism within the cell. VP-16-213 (etoposide) or podophyllotoxin inhibits the initial uptake rate for thymidine and, as a consequence, inhibits the intracellular formation of thymidine triphosphate. When extracellular thymidine is high, inhibitory effects on transport are transient, and the net rate of thymidine triphosphate accumulation within drug-treated cells rapidly approaches a velocity comparable to that of control cells, indicating no direct VP-16-213 or podophyllotoxin effect on nucleoside and nucleotide phosphorylation. When extracellular thymidine is reduced so that transport is rate limiting to metabolism, the duration of the inhibitory effects of VP-16-213 on thymidine triphosphate formation is prolonged. A secondary effect of VP-16-213 becomes manifest beyond 10 min of incubation with [3H]thymidine with the virtual complete cessation of thymidine incorporation into the acid precipitate without any change in the thymidine triphosphate level. This late effect is not observed with podophyllotoxin and indicates a direct effect of VP-16-213 on DNA synthesis that is distinct from the earlier inhibitory effect on thymidine phosphorylation, which is secondary to membrane transport

  7. Total protein

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003483.htm Total protein To use the sharing features on this page, please enable JavaScript. The total protein test measures the total amount of two classes ...

  8. Tumor lysis syndrome in children

    International Nuclear Information System (INIS)

    Suarez, Amaranto

    2004-01-01

    Tumor lysis syndrome is a metabolic emergency characterized by electrolyte alteration with or without acute renal failure. It occurs mainly in patients with malignant tumors that have a high growth fraction, or after cytotoxic therapy, as a result of the massive degradation of malignant cells and the release of high amounts of intracellular elements that exceed the capacity of renal excretion. The objective of the treatment is the prevention of nephropathy due to uric acid deposits, and the correction of metabolic acidosis and electrolyte alterations. This paper reviews the incidence, the physiopathology, and the treatment of tumor lysis syndrome in children

  9. Effects of nonstructural carbohydrates and protein sources on intake, apparent total tract digestibility, and ruminal metabolism in vivo and in vitro with high-concentrate beef cattle diets.

    Science.gov (United States)

    Rotger, A; Ferret, A; Calsamiglia, S; Manteca, X

    2006-05-01

    To investigate the effects of synchronizing nonstructural carbohydrate (NSC) and protein degradation on intake and rumen microbial fermentation, four ruminally fistulated Holstein heifers (BW = 132.3 +/- 1.61 kg) fed high-concentrate diets were assigned to a 4 x 4 Latin square design with a 2 x 2 factorial arrangement of treatments studied in vivo and in vitro with a dual-flow continuous culture system. Two NSC sources (barley and corn) and 2 protein sources [soybean meal (SBM) and sunflower meal (SFM)] differing in their rate and extent of ruminal degradation were combined resulting in a synchronized rapid fermentation diet (barley-SFM), a synchronized slow fermentation diet (corn-SBM), and 2 unsynchronized diets with a rapidly and a slowly fermenting component (barley-SBM, and corn-SFM). In vitro, the fermentation profile was studied at a constant pH of 6.2, and at a variable pH with 12 h at pH 6.4 and 12 h at pH 5.8. Synchronization tended to result in greater true OM digestion (P = 0.072), VFA concentration (P = 0.067), and microbial N flow (P = 0.092) in vitro, but had no effects on in vivo fermentation pattern or on apparent total tract digestibility. The NSC source affected the efficiency of microbial protein synthesis in vitro, tending to be greater (P = 0.07) for barley-based diets, and in vivo, the NSC source tended to affect intake. Dry matter and OM intake tended to be greater (P > or = 0.06) for corn- than barley-based diets. Ammonia N concentration was lower in vitro (P = 0.006) and tended to be lower in vivo (P = 0.07) for corn- than barley-based diets. In vitro, pH could be reduced from 6.4 to 5.8 for 12 h/d without any effect on ruminal fermentation or microbial protein synthesis. In summary, ruminal synchronization seemed to have positive effects on in vitro fermentation, but in vivo recycling of endogenous N or intake differences could compensate for these effects.

  10. Cancer Cell Metabolism: One Hallmark, Many Faces

    OpenAIRE

    Cantor, Jason R.; Sabatini, David M.

    2012-01-01

    Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. Although many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and nongenetic factors such as the tumor microenvironment. However, a single model of altered tumor metabolism does not describe the sum of metabolic changes that can support cell growth. Instead, the diversity of such chang...

  11. Effects of Walker 256 carcinoma on metabolic alterations during the evolution of pregnancy.

    Science.gov (United States)

    Cintra-Gomes, M C; Cury, L; Parreira, M R; Elias, C F; Areas, M A

    1990-01-01

    The control of pregnant cancer patients is difficult because it involves both mother and fetus, and the metabolic alterations in the cancer host induce a massive mobilization of nutrients diverted to the neoplastic cells. The purpose of the present study was to determine the evolution of the Walker 256 carcinoma in pregnant rats and its consequences on fetal development. The results showed that the tumors displayed a very rapid rate of growth and induced a reduction in fetal weights in the pregnant tumor-bearing rats. The tumor-bearing and pregnant tumor-bearing groups showed a decrease in blood glucose and total serum protein, suggesting an increase in energy utilization of these substrates and synthetic activity by the tumoral cells. An imbalance between protein synthesis and catabolism may occur in the tumor-bearing rats which may be related to the degree of nutritional depletion.

  12. Tumor-associated antigens identified by mRNA expression profiling induce protective anti-tumor immunity

    DEFF Research Database (Denmark)

    Mathiassen, S; Lauemøller, S L; Ruhwald, M

    2001-01-01

    Defined tumor-associated antigens (TAA) are attractive targets for anti-tumor immunotherapy. Here, we describe a novel genome-wide approach to identify multiple TAA from any given tumor. A panel of transplantable thymomas was established from an inbred p53-/- mouse strain. The resulting tumors were...... of autoimmune reactions were observed. Thus, it appears possible to evaluate the entire metabolism of any given tumor and use this information rationally to identify multiple epitopes of value in the generation of tumor-specific immunotherapy. We expect that human tumors express similar tumor-specific metabolic...

  13. Comparison of F-18-FDG PET/CT findings between pancreatic solid pseudopapillary tumor and pancreatic ductal adenocarcinoma

    International Nuclear Information System (INIS)

    Kim, Yong-il; Kim, Seok-ki; Paeng, Jin Chul; Lee, Ho-Young

    2014-01-01

    Objective: Pancreatic solid pseudopapillary tumor (SPT) is a rare benign tumor. Little data are available on positron emission tomographic/computed tomographic (PET/CT) characteristics of this tumor. Therefore, we analyzed the metabolic characteristics of SPT using F-18-FDG PET/CT and compared the results with those of pancreatic ductal adenocarcinoma. Methods: We retrospectively reviewed the records of 11 SPT patients and 46 patients with ductal adenocarcinoma. Ten SPT patients had primary tumors and 1 patient had metastatic SPT. Maximum standardized uptake value (max SUV), mean SUV, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor-to-background ratio (TBR) were evaluated. Mann–Whitney U test between pancreatic SPT and ductal adenocarcinoma was performed. In addition, age, gender and tumor size-adjusted analysis of covariance (ANCOVA) was done between pancreatic SPT and ductal adenocarcinoma. Results: Compared with pancreatic ductal adenocarcinomas, SPTs had significantly higher tumor size-adjusted MTV and TLG. MTV and TLG values were significantly correlated with T-stage of the SPTs. In 1 SPT patient, metastases in the liver and mesentery were revealed by intense uptake of FDG on F-18-FDG PET/CT, and after PET/CT had suggested the presence of pancreatic SPT. Conclusion: We recommend that SPT be considered when a solid pancreatic mass with increased FDG metabolism is encountered on PET/CT. F-18-FDG PET/CT may be useful in detecting subtle metastases of SPT

  14. Analytical Validation of a Highly Quantitative, Sensitive, Accurate, and Reproducible Assay (HERmark® for the Measurement of HER2 Total Protein and HER2 Homodimers in FFPE Breast Cancer Tumor Specimens

    Directory of Open Access Journals (Sweden)

    Jeffrey S. Larson

    2010-01-01

    Full Text Available We report here the results of the analytical validation of assays that measure HER2 total protein (H2T and HER2 homodimer (H2D expression in Formalin Fixed Paraffin Embedded (FFPE breast cancer tumors as well as cell line controls. The assays are based on the VeraTag technology platform and are commercially available through a central CAP-accredited clinical reference laboratory. The accuracy of H2T measurements spans a broad dynamic range (2-3 logs as evaluated by comparison with cross-validating technologies. The measurement of H2T expression demonstrates a sensitivity that is approximately 7–10 times greater than conventional immunohistochemistry (IHC (HercepTest. The HERmark assay is a quantitative assay that sensitively and reproducibly measures continuous H2T and H2D protein expression levels and therefore may have the potential to stratify patients more accurately with respect to response to HER2-targeted therapies than current methods which rely on semiquantitative protein measurements (IHC or on indirect assessments of gene amplification (FISH.

  15. Can adaptive threshold-based metabolic tumor volume (MTV) and lean body mass corrected standard uptake value (SUL) predict prognosis in head and neck cancer patients treated with definitive radiotherapy/chemoradiotherapy?

    Science.gov (United States)

    Akagunduz, Ozlem Ozkaya; Savas, Recep; Yalman, Deniz; Kocacelebi, Kenan; Esassolak, Mustafa

    2015-11-01

    To evaluate the predictive value of adaptive threshold-based metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax) and maximum lean body mass corrected SUV (SULmax) measured on pretreatment positron emission tomography and computed tomography (PET/CT) imaging in head and neck cancer patients treated with definitive radiotherapy/chemoradiotherapy. Pretreatment PET/CT of the 62 patients with locally advanced head and neck cancer who were treated consecutively between May 2010 and February 2013 were reviewed retrospectively. The maximum FDG uptake of the primary tumor was defined according to SUVmax and SULmax. Multiple threshold levels between 60% and 10% of the SUVmax and SULmax were tested with intervals of 5% to 10% in order to define the most suitable threshold value for the metabolic activity of each patient's tumor (adaptive threshold). MTV was calculated according to this value. We evaluated the relationship of mean values of MTV, SUVmax and SULmax with treatment response, local recurrence, distant metastasis and disease-related death. Receiver-operating characteristic (ROC) curve analysis was done to obtain optimal predictive cut-off values for MTV and SULmax which were found to have a predictive value. Local recurrence-free (LRFS), disease-free (DFS) and overall survival (OS) were examined according to these cut-offs. Forty six patients had complete response, 15 had partial response, and 1 had stable disease 6 weeks after the completion of treatment. Median follow-up of the entire cohort was 18 months. Of 46 complete responders 10 had local recurrence, and of 16 partial or no responders 10 had local progression. Eighteen patients died. Adaptive threshold-based MTV had significant predictive value for treatment response (p=0.011), local recurrence/progression (p=0.050), and disease-related death (p=0.024). SULmax had a predictive value for local recurrence/progression (p=0.030). ROC curves analysis revealed a cut-off value of 14.00 mL for

  16. The prognostic value of metabolic tumor volume in FDG PET/CT evaluation of post-operative survival in patients with esophageal squamous cell cancer

    International Nuclear Information System (INIS)

    Zhu Wanqi; Yu Jinming; Sun Xiaorong; Xing Ligang; Xie Peng; Sun Xindong; Guo Hongbo; Yang Guoren; Kong Li

    2011-01-01

    Objective: To evaluate the prognostic value of MTV on 18 F-FDG PET/CT in patients with esophageal cancer. Methods: Forty-nine patients with esophageal cancer underwent 18 F-FDG PET/CT scan before surgery. The median follow-up time for the patients was 29 months (range, 8-57 months). The prognostic significance of MTV, age, sex, histologic grade, SUV max of the primary tumor, tumor size measured on PET/CT, T stage, N stage, M stage, American Joint Committee on Cancer (AJCC) stage, number and location of lymph nodes metastases were assessed by Kaplan-Meier analysis and multivariate Cox model. Results: In the univariate analysis, AJCC stage (χ 2 =16.206, hazard ratio (HR)=1.177, P<0.001), N stage (χ 2 =9.536, HR=10.833, P=0.002), T stage (χ 2 =5.810, HR=2.397, P=0.016), number of lymph nodes metastases (χ 2 =11.423, HR=1.567, P=0.001), and MTV (χ 2 =3.872, HR=2.433, P=0.049) were significant predictors of survival.Multivariate analysis showed that MTV and AJCC stage were independent predictors of survival (χ 2 =4.525, HR 1.170, P=0.033; χ 2 =4.875, HR=3.071, P=0.027). Kaplan-Meier survival curves revealed longer survival time of low-MTV group as compared to high-MTV group (Log-rank, χ 2 =4.186, P=0.041). Conclusion: MTV on 18 F-FDG PET/CT may be an independent prognostic factor in patients with esophageal cancer. (authors)

  17. Development of 18F-FDG ([F-18]-2-fluoro-2-deoxy-D-glucose) injection for imaging of tumor reflecting glucose metabolism. Results of preclinical studies

    International Nuclear Information System (INIS)

    Ino, Sento; Shimada, Takayuki; Kanagawa, Masaru; Suzuki, Noriaki; Kondo, Susumu; Shirakami, Yoshifumi; Ito, Osamu; Kato-Azuma, Makoto

    1999-01-01

    Fluorine-18-2-fluoro-2-deoxy-D-glucose ( 18 F-FDG) injection was prepared by a modification of a method originally developed by Hamacher et al. The dosage form is the injectable solution (2 ml) containing 185 MBq of 18 F-FDG at a calibration time. Preclinical studies of the agent were performed. Its radiochemical purity is more than 95% and expiration time is 4 hours after the calibration time at ambient temperature. No toxicity was observed with up to 200 mg/kg and 100 mg/kg of non-radioactive FDG intravenously injected to rats and dogs in single dose toxicity tests, respectively. Biodistribution studies demonstrated that the radioactivity was mainly distributed into brain (3.0 to 3.3% I.D./Organ at 30 minutes) and heart (4.2 to 5.8% I.D./Organ at 1 to 3 hours) after intravenous injection of the agent to normal rats. In a tumor transplanted mouse model (colon 26), tumor uptake was 10.9±3.5% I.D./g at 1 hr after intravenous injection of the agent, the radioactivity was retained until 3 hours. The radiation absorbed dose was estimated according to the MIRD Pamphlet based on the biodistribution data both in humans reported by Mejia et al. and rats described in this report. The radiation absorbed dose was not higher than those of commercially available radiopharmaceuticals. In conclusion, the 18 F-FDG injection is expected to be useful for further clinical application. (author)

  18. CNS tumors: postoperative evaluation

    International Nuclear Information System (INIS)

    Dayanir, Y.

    2012-01-01

    Full text: Imaging assessment of brain tumors following surgery is complex and depends upon several factors, including the location of the tumor, the surgical procedure and the disease process for which it was performed. Depending upon these factors, one or a combination of complementary imaging modalities may be required to demonstrate any clinically relevant situation, to assist the surgeon in deciding if repeat surgery is necessary. Conventional magnetic resonance imaging (MRI) can show the shape, size, signal intensity, and enhancement of a brain tumor. It has been widely used to diagnose and differentiate brain tumors and to assess the surgery outcomes. Longitudinal MRI scans have also been applied for the assessment of treatment and response to surgery. The newly developed MRI techniques, including diffusion weighted imaging (DWI), perfusion weighted imaging (PWI) and magnetic resonance spectroscopy (MRS), have the potential to provide the molecular, functional and metabolic information of preoperative and postoperative brain tumors. Postoperative diffusion and perfusion magnetic resonance imaging are especially useful in predicting early functional recovery from new deficits after brain tumor surgery.This lecture will stress the principles, applications, and pitfalls of conventional as well as newly developing functional imaging techniques following operation of brain tumors

  19. Total algorithms

    NARCIS (Netherlands)

    Tel, G.

    We define the notion of total algorithms for networks of processes. A total algorithm enforces that a "decision" is taken by a subset of the processes, and that participation of all processes is required to reach this decision. Total algorithms are an important building block in the design of

  20. INPP4B-mediated tumor resistance is associated with modulation of glucose metabolism via hexokinase 2 regulation in laryngeal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Min, Joong Won [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Kwang Il [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Hyun-Ah; Kim, Eun-Kyu; Noh, Woo Chul [Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Jeon, Hong Bae [Biomedical Research Institute, MEDIPOST Co., Ltd., Seoul (Korea, Republic of); Cho, Dong-Hyung [Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi-do (Korea, Republic of); Oh, Jeong Su [Department of Genetic Engineering, Sungkyunkwan University, Suwon (Korea, Republic of); Park, In-Chul; Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Jae-Sung, E-mail: jaesung@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2013-10-11

    Highlights: •HIF-1α-regulated INPP4B enhances glycolysis. •INPP4B regulates aerobic glycolysis by inducing HK2 via Akt-mTOR pathway. •Blockage of INPP4B and HK2 sensitizes radioresistant laryngeal cancer cells to radiation and anticancer drug. •INPP4B is associated with HK2 in human laryngeal cancer tissues. -- Abstract: Inositol polyphosphate 4-phosphatase type II (INPP4B) was recently identified as a tumor resistance factor in laryngeal cancer cells. Herein, we show that INPP4B-mediated resistance is associated with increased glycolytic phenotype. INPP4B expression was induced by hypoxia and irradiation. Intriguingly, overexpression of INPP4B enhanced aerobic glycolysis. Of the glycolysis-regulatory genes, hexokinase 2 (HK2) was mainly regulated by INPP4B and this regulation was mediated through the Akt-mTOR pathway. Notably, codepletion of INPP4B and HK2 markedly sensitized radioresistant laryngeal cancer cells to irradiation or anticancer drug. Moreover, INPP4B was significantly associated with HK2 in human laryngeal cancer tissues. Therefore, these results suggest that INPP4B modulates aerobic glycolysis via HK2 regulation in radioresistant laryngeal cancer cells.

  1. Sinus Tumors

    Science.gov (United States)

    ... RESOURCES Medical Societies Patient Education About this Website Font Size + - Home > CONDITIONS > Sinus Tumors Adult Sinusitis Pediatric ... and they vary greatly in location, size and type. Care for these tumors is individualized to each ...

  2. Tumors markers

    International Nuclear Information System (INIS)

    Yamaguchi-Mizumoto, N.H.

    1989-01-01

    In order to study blood and cell components alterations (named tumor markers) that may indicate the presence of a tumor, several methods are presented. Aspects as diagnostic, prognostic, therapeutic value and clinical evaluation are discussed. (M.A.C.)

  3. Wilms tumor

    Science.gov (United States)

    ... suggested. Alternative Names Nephroblastoma; Kidney tumor - Wilms Images Kidney anatomy Wilms tumor References Babaian KN, Delacroix SE, Wood CG, Jonasch E. Kidney cancer. In: Skorecki K, Chertow GM, Marsden PA, ...

  4. Double tracer / double isotope gives Ga-68 dota-noc and F-18 FDG PET / CT. Protocol 1 day in a child with neuroblastoma to determine the clinical state and tumor metabolic state

    International Nuclear Information System (INIS)

    Oliva Gonzalez, Juan P.; Baum, Richard P.

    2009-01-01

    We report on a 6-year-old carrier of a neuroblastoma. The tumor was diagnosed in March 2004, under the right adrenal gland and confirmed by FNAB, ultrasound, CT and tumor markers. Because of its size and extent of the tumor was inoperable at the time due to which was subject to two cycles of chemotherapy (vincristine, cisplatin, etoposide and cyclophosphamide alternating with vincristine, carboplatin, etoposide and cyclophosphamide). After these two cycles of chemotherapy the patient underwent retroperitoneal surgery getting totally dry right adrenal gland and tumor. After surgery the patient received four additional cycles of chemotherapy until March 2005. During the months of August and September 2005 the patient complained of abdominal pain and were suspected of recurrence. She received ultrasound and CT scan were not conclusive. In December 2005 he made a scan with I-131-MIBG (148 MBq, 4 mCi intravenous, is flat and SPECT imaging performed 24 hours to 6 days after injection) showing only the normal left adrenal gland but not recurrence was visualized, which showed that the tumor did not grasp MIBG. In January 2006 the boy (121 cm.'s Height, weight 21 kg) was referred to the Centre for PET / CT of the Bad Berka Central Clinic in Germany for a PET / CT using Ga-68/DOTA- receptor NOC, a high affinity analogue of somatostatin. The tumor marker NSE was determined in serum before the PET / CT whose outcome was high (24.8 ng / ml, cutoff 15). The patient received 46 MBq (1.24 mCi) of Ga-68 DOTA-NOC intravenous and PET / CT whole body was performed at 75 minutes post-injection. No abnormal uptake was observed which indicated that the appellants had no somatostatin receptors. By having this negative result was decided to perform an additional PET / CT with F-18 FDG (with a low dose of contrast to improve the TAC). After fasting for 6 hours, the patient received 151 MBq (4.1 mCi) of F-18 FDG. A PET / CT whole body was performed at 75 minutes after administration of

  5. The serum levels of tumor marker CA19-9, CEA, CA72-4, and NSE in type 2 diabetes without malignancy and the relations to the metabolic control.

    Science.gov (United States)

    Shang, Xiaojing; Song, Chunqing; Du, Xiaoming; Shao, Hailin; Xu, Donghong; Wang, Xiaolai

    2017-02-01

    To investigate whether there is a difference in carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), carbohydrate antigen 72-4 (CA72-4), and neuron-specific enolase (NSE) between diabetic and non-diabetic patients.  Methods: A retrospective analysis was performed in 268 type 2 diabetic patients and 95 non-diabetic ones, and their serum levels of CA19-9, CEA, CA72-4, and NSE were compared in our endocrine ward at the Tianjin Fourth Central Hospital, Tianjin, Chinaduring the period from January to June 2015. The diabetic patients were divided into 4 groups based on glycosylated hemoglobin (HbA1c) levels to investigate the relationship between levels of tumor markers and glucose status.  Results: Diabetic patients had higher levels of tumor markers than non-diabetic subjects (CA19-9: 13.0 versus 7.25U/mL, p=0.000; CEA: 2.55 versus 2.25 ng/mL, p=0.012; CA72-4: 1.95 versus 1.50U/mL, p=0.001; NSE: 11.64 versus 10.22ng/mL, p=0.000). CA19-9 levels increased in a stepwise manner with poor diabetes status. CEA levels were increased in patients with HbA1c ≥9% and CA72-4 elevation was predominant in patients with poor glycemic control (HbA1c ≥11%). NSE levels were not associated with metabolic parameters.  Conclusion: Serum levels of CA19-9, CEA, CA72-4, and NSE were elevated in type 2 diabetes; however, only CA19-9, CEA, and CA72-4 levels were associated with hyperglycemia.

  6. The serum levels of tumor marker CA19-9, CEA, CA72-4, and NSE in type 2 diabetes without malignancy and the relations to the metabolic control

    Directory of Open Access Journals (Sweden)

    Chunqing Song

    2017-02-01

    Full Text Available Objectives: To investigate whether there is a difference in carbohydrate antigen 19-9 (CA19-9, carcinoembryonic antigen (CEA, carbohydrate antigen 72-4 (CA72-4, and neuron-specific enolase (NSE between diabetic and non-diabetic patients. Methods: A retrospective analysis was performed in 268 type 2 diabetic patients and 95 non-diabetic ones, and their serum levels of CA19-9, CEA, CA72-4, and NSE were compared in our endocrine ward at the Tianjin Fourth Central Hospital, Tianjin, China during the period from January to June 2015. The diabetic patients were divided into 4 groups based on glycosylated hemoglobin (HbA1c levels to investigate the relationship between levels of tumor markers and glucose status. Results: Diabetic patients had higher levels of tumor markers than non-diabetic subjects (CA19-9: 13.0 versus 7.25U/mL, p=0.000; CEA: 2.55 versus 2.25 ng/mL, p=0.012; CA72-4: 1.95 versus 1.50U/mL, p=0.001; NSE: 11.64 versus 10.22ng/mL, p=0.000. CA19-9 levels increased in a stepwise manner with poor diabetes status. CEA levels were increased in patients with HbA1c ≥9% and CA72-4 elevation was predominant in patients with poor glycemic control (HbA1c ≥11%. NSE levels were not associated with metabolic parameters. Conclusion: Serum levels of CA19-9, CEA, CA72-4, and NSE were elevated in type 2 diabetes; however, only CA19-9, CEA, and CA72-4 levels were associated with hyperglycemia.

  7. Wilm's tumor in adulthood

    International Nuclear Information System (INIS)

    Matveev, B.P.; Bukharkin, B.V.; Gotsadze, D.T.

    1984-01-01

    Wilms' tumor occurs extremely rarely in adults. There is no consensus in the literature on the problems of clinical manifestations, diagnosis and treatment of the diseasa. Ten adult patients (aged 16-29) with Wilms' tumor formed the study group. They made up 0.9 per cent of the total number of kidney tumor patients. The peculiarities of the clinical course that distinguish adult nephroblastoma from renal cancer and Wilms' tumor of the infancy were analysed. The latent period appeared to be long. Problems of diagnosis are discussed. Angiography proved to be of the highest diagnostic value. Complex treatment including transperitoneal nephrectory, radiation and chemotherapy was carried out in 7 cases, palliative radiation treatmenchemotherapy andn 3. Unlike pediatric nephroblastomt - i Wilms' tumor in adults was resistant to radiation. Treatment results still remained unsatisfactory: 6 patients died 7-19 months after the beginning of treatment

  8. Spinal tumors

    International Nuclear Information System (INIS)

    Goethem, J.W.M. van; Hauwe, L. van den; Oezsarlak, Oe.; Schepper, A.M.A. de; Parizel, P.M.

    2004-01-01

    Spinal tumors are uncommon lesions but may cause significant morbidity in terms of limb dysfunction. In establishing the differential diagnosis for a spinal lesion, location is the most important feature, but the clinical presentation and the patient's age and gender are also important. Magnetic resonance (MR) imaging plays a central role in the imaging of spinal tumors, easily allowing tumors to be classified as extradural, intradural-extramedullary or intramedullary, which is very useful in tumor characterization. In the evaluation of lesions of the osseous spine both computed tomography (CT) and MR are important. We describe the most common spinal tumors in detail. In general, extradural lesions are the most common with metastasis being the most frequent. Intradural tumors are rare, and the majority is extramedullary, with meningiomas and nerve sheath tumors being the most frequent. Intramedullary tumors are uncommon spinal tumors. Astrocytomas and ependymomas comprise the majority of the intramedullary tumors. The most important tumors are documented with appropriate high quality CT or MR images and the characteristics of these tumors are also summarized in a comprehensive table. Finally we illustrate the use of the new World Health Organization (WHO) classification of neoplasms affecting the central nervous system

  9. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  10. Urogenital tumors

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1994-03-01

    An overview is provided for veterinary care of urogenital tumors in companion animals, especially the dog. Neoplasms discussed include tumors of the kidney, urinary bladder, prostate, testis, ovary, vagina, vulva and the canine transmissible venereal tumor. Topics addressed include description, diagnosis and treatment.

  11. Assessment of tumor energy and oxygenation status by bioluminescence, nuclear magnetic resonance spectroscopy, and cryospectrophotometry.

    Science.gov (United States)

    Mueller-Klieser, W; Schaefer, C; Walenta, S; Rofstad, E K; Fenton, B M; Sutherland, R M

    1990-03-15

    The energy and oxygenation status of tumors from two murine sarcoma lines (KHT, RIF-1) and two human ovarian carcinoma xenograft lines (MLS, OWI) were assessed using three independent techniques. Tumor energy metabolism was investigated in vivo by 31P nuclear magnetic resonance spectroscopy. After nuclear magnetic resonance measurements, tumors were frozen in liquid nitrogen to determine the tissue ATP concentration by imaging bioluminescence and to register the intracapillary oxyhemoglobin (HbO2) saturation using the cryospectrophotometric method. There was a positive correlation between the nucleoside triphosphate beta/total resonance ratio or a negative correlation between the Pi/total resonance ratio and the model ATP concentration obtained by bioluminescence, respectively. This was true for small tumors with no extended necrosis irrespective of tumor type. Moreover, a positive correlation was obtained between the HbO2 saturations and the ATP concentration measured with bioluminescence. The results demonstrate the potential of combined studies using noninvasive, integrating methods and high-resolution imaging techniques for characterizing the metabolic milieu in tumors.

  12. Totally James

    Science.gov (United States)

    Owens, Tom

    2006-01-01

    This article presents an interview with James Howe, author of "The Misfits" and "Totally Joe". In this interview, Howe discusses tolerance, diversity and the parallels between his own life and his literature. Howe's four books in addition to "The Misfits" and "Totally Joe" and his list of recommended books with lesbian, gay, bisexual, transgender,…

  13. Tumor Acidity as Evolutionary Spite

    International Nuclear Information System (INIS)

    Alfarouk, Khalid O.; Muddathir, Abdel Khalig; Shayoub, Mohammed E. A.

    2011-01-01

    Most cancer cells shift their metabolic pathway from a metabolism reflecting the Pasteur-effect into one reflecting the Warburg-effect. This shift creates an acidic microenvironment around the tumor and becomes the driving force for a positive carcinogenesis feedback loop. As a consequence of tumor acidity, the tumor microenvironment encourages a selection of certain cell phenotypes that are able to survive in this caustic environment to the detriment of other cell types. This selection can be described by a process which can be modeled upon spite: the tumor cells reduce their own fitness by making an acidic environment, but this reduces the fitness of their competitors to an even greater extent. Moreover, the environment is an important dimension that further drives this spite process. Thus, diminishing the selective environment most probably interferes with the spite process. Such interference has been recently utilized in cancer treatment

  14. Tumor immunology

    International Nuclear Information System (INIS)

    Otter, W. den

    1987-01-01

    Tumor immunology, the use of immunological techniques for tumor diagnosis and approaches to immunotherapy of cancer are topics covered in this multi-author volume. Part A, 'Tumor Immunology', deals with present views on tumor-associated antigens, the initiation of immune reactions of tumor cells, effector cell killing, tumor cells and suppression of antitumor immunity, and one chapter dealing with the application of mathematical models in tumor immunology. Part B, 'Tumor Diagnosis and Imaging', concerns the use of markers to locate the tumor in vivo, for the histological diagnosis, and for the monitoring of tumor growth. In Part C, 'Immunotherapy', various experimental approaches to immunotherapy are described, such as the use of monoclonal antibodies to target drugs, the use of interleukin-2 and the use of drugs inhibiting suppression. In the final section, the evaluation, a pathologist and a clinician evaluate the possibilities and limitations of tumor immunology and the extent to which it is useful for diagnosis and therapy. refs.; figs.; tabs

  15. Pseudoanaplastic tumors of bone

    Energy Technology Data Exchange (ETDEWEB)

    Bahk, Won-Jong [Uijongbu St. Mary Hospital, The Catholic University of Korea, Department of Orthopaedic Surgery, Gyunggido, 480-821 (Korea); Mirra, Joseph M. [Orthopaedic Hospital, Orthopedic Oncology, Los Angeles, California (United States)

    2004-11-01

    To discuss the concept of pseudoanaplastic tumors of bone, which pathologically show hyperchromatism and marked pleomorphism with quite enlarged, pleomorphic nuclei, but with no to extremely rare, typical mitoses, and to propose guidelines for their diagnosis. From a database of 4,262 bone tumors covering from 1971 to 2001, 15 cases of pseudoanaplastic bone tumors (0.35% of total) were retrieved for clinical, radiographic and pathologic review. Postoperative follow-up after surgical treatment was at least 3 years and a maximum of 7 years. There were eight male and seven female patients. Their ages ranged from 10 to 64 years with average of 29.7 years. Pathologic diagnoses of pseudoanaplastic variants of benign bone tumors included: osteoblastoma (4 cases), giant cell tumor (4 cases), chondromyxoid fibroma (3 cases), fibrous dysplasia (2 cases), fibrous cortical defect (1 case) and aneurysmal bone cyst (1 case). Radiography of all cases showed features of a benign bone lesion. Six cases, one case each of osteoblastoma, fibrous dysplasia, aneurysmal bone cyst, chondromyxoid fibroma, giant cell tumor and osteoblastoma, were initially misdiagnosed as osteosarcoma. The remaining cases were referred for a second opinion to rule out sarcoma. Despite the presence of significant cytologic aberrations, none of our cases showed malignant behavior following simple curettage or removal of bony lesions. Our observation justifies the concept of pseudoanaplasia in some benign bone tumors as in benign soft tissue tumors, especially in their late evolutionary stage when bizarre cytologic alterations strongly mimic a sarcoma. (orig.)

  16. Dose-response relationship between probability of pathologic tumor control and glucose metabolic rate measured with FDG PET after preoperative chemoradiotherapy in locally advanced non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Choi, Noah C.; Fischman, Alan J.; Niemierko, Andrzej; Ryu, Jin-Sook; Lynch, Thomas; Wain, John; Wright, Cameron; Fidias, Panos; Mathisen, Douglas

    2002-01-01

    Purpose: To determine the dose-response relationship between the probability of tumor control on the basis of pathologic tumor response (pTCP) and the residual metabolic rate of glucose (MRglc) in response to preoperative chemoradiotherapy in locally advanced non-small-cell lung cancer and to define the level of residual MRglc that corresponds to pTCP 50% and pTCP ≥95%. Methods and Materials: Quantitative dynamic 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography was performed to measure regional MRglc at the primary lesion before and 2 weeks after preoperative chemoradiotherapy in an initial group of 13 patients with locally advanced NSCLC. A simplified kinetic method was developed subsequently from the initial dynamic study and used in the subsequent 16 patients. The preoperative radiotherapy programs consisted of (1) a split course of 42 Gy in 28 fractions within a period of 28 days using a twice-daily treatment schedule for Stage IIIA(N2) NSCLC (n=18) and (2) standard once-daily radiation schedule of 45-63 Gy in 25-35 fractions during a 5-7-week period (n=11). The preoperative chemotherapy regimens included two cycles of cisplatin, vinblastine, and 5-fluorouracil (n=24), cisplatin and etoposide (n=2), and cisplatin, Taxol, and 5-fluorouracil (n=3). Patients free of tumor progression after preoperative chemoradiotherapy underwent surgery. The degree of residual MRglc measured 2 weeks after preoperative chemoradiotherapy and 2 weeks before surgery was correlated with the pathologic tumor response. The relationship between MRglc and pTCP was modeled using logistic regression. Results: Of 32 patients entered into the study, 29 (16 men and 13 women; 30 lesions) were evaluated for the correlation between residual MRglc and pathologic tumor response. Three patients did not participate in the second study because of a steady decline in general condition. The median age was 60 years (range 42-78). One of the 29 patients had two separate lesions, and

  17. Cancer cell metabolism: one hallmark, many faces.

    Science.gov (United States)

    Cantor, Jason R; Sabatini, David M

    2012-10-01

    Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. Although many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and nongenetic factors such as the tumor microenvironment. However, a single model of altered tumor metabolism does not describe the sum of metabolic changes that can support cell growth. Instead, the diversity of such changes within the metabolic program of a cancer cell can dictate by what means proliferative rewiring is driven, and can also impart heterogeneity in the metabolic dependencies of the cell. A better understanding of this heterogeneity may enable the development and optimization of therapeutic strategies that target tumor metabolism.

  18. Glutaminolysis: A Hallmark of Cancer Metabolism.

    Science.gov (United States)

    Yang, Lifeng; Venneti, Sriram; Nagrath, Deepak

    2017-06-21

    Glutamine is the most abundant circulating amino acid in blood and muscle and is critical for many fundamental cell functions in cancer cells, including synthesis of metabolites that maintain mitochondrial metabolism; generation of antioxidants to remove reactive oxygen species; synthesis of nonessential amino acids (NEAAs), purines, pyrimidines, and fatty acids for cellular replication; and activation of cell signaling. In light of the pleiotropic role of glutamine in cancer cells, a comprehensive understanding of glutamine metabolism is essential for the development of metabolic therapeutic strategies for targeting cancer cells. In this article, we review oncogene-, tumor suppressor-, and tumor microenvironment-mediated regulation of glutamine metabolism in cancer cells. We describe the mechanism of glutamine's regulation of tumor proliferation, metastasis, and global methylation. Furthermore, we highlight the therapeutic potential of glutamine metabolism and emphasize that clinical application of in vivo assessment of glutamine metabolism is critical for identifying new ways to treat patients through glutamine-based metabolic therapy.

  19. Actionable Metabolic Pathways in Heart Failure and Cancer—Lessons From Cancer Cell Metabolism

    Directory of Open Access Journals (Sweden)

    Anja Karlstaedt

    2018-06-01

    Full Text Available Recent advances in cancer cell metabolism provide unprecedented opportunities for a new understanding of heart metabolism and may offer new approaches for the treatment of heart failure. Key questions driving the cancer field to understand how tumor cells reprogram metabolism and to benefit tumorigenesis are also applicable to the heart. Recent experimental and conceptual advances in cancer cell metabolism provide the cardiovascular field with the unique opportunity to target metabolism. This review compares cancer cell metabolism and cardiac metabolism with an emphasis on strategies of cellular adaptation, and how to exploit metabolic changes for therapeutic benefit.

  20. Epilepsy and brain tumors

    Science.gov (United States)

    ENGLOT, DARIO J.; CHANG, EDWARD F.; VECHT, CHARLES J.

    2016-01-01

    Seizures are common in patients with brain tumors, and epilepsy can significantly impact patient quality of life. Therefore, a thorough understanding of rates and predictors of seizures, and the likelihood of seizure freedom after resection, is critical in the treatment of brain tumors. Among all tumor types, seizures are most common with glioneuronal tumors (70–80%), particularly in patients with frontotemporal or insular lesions. Seizures are also common in individuals with glioma, with the highest rates of epilepsy (60–75%) observed in patients with low-grade gliomas located in superficial cortical or insular regions. Approximately 20–50% of patients with meningioma and 20–35% of those with brain metastases also suffer from seizures. After tumor resection, approximately 60–90% are rendered seizure-free, with most favorable seizure outcomes seen in individuals with glioneuronal tumors. Gross total resection, earlier surgical therapy, and a lack of generalized seizures are common predictors of a favorable seizure outcome. With regard to anticonvulsant medication selection, evidence-based guidelines for the treatment of focal epilepsy should be followed, and individual patient factors should also be considered, including patient age, sex, organ dysfunction, comorbidity, or cotherapy. As concomitant chemotherapy commonly forms an essential part of glioma treatment, enzyme-inducing anticonvulsants should be avoided when possible. Seizure freedom is the ultimate goal in the treatment of brain tumor patients with epilepsy, given the adverse effects of seizures on quality of life. PMID:26948360

  1. Dysregulated metabolism contributes to oncogenesis

    Science.gov (United States)

    Hirschey, Matthew D.; DeBerardinis, Ralph J.; Diehl, Anna Mae E.; Drew, Janice E.; Frezza, Christian; Green, Michelle F.; Jones, Lee W.; Ko, Young H.; Le, Anne; Lea, Michael A.; Locasale, Jason W.; Longo, Valter D.; Lyssiotis, Costas A.; McDonnell, Eoin; Mehrmohamadi, Mahya; Michelotti, Gregory; Muralidhar, Vinayak; Murphy, Michael P.; Pedersen, Peter L.; Poore, Brad; Raffaghello, Lizzia; Rathmell, Jeffrey C.; Sivanand, Sharanya; Vander Heiden, Matthew G.; Wellen, Kathryn E.

    2015-01-01

    Cancer is a disease characterized by unrestrained cellular proliferation. In order to sustain growth, cancer cells undergo a complex metabolic rearrangement characterized by changes in metabolic pathways involved in energy production and biosynthetic processes. The relevance of the metabolic transformation of cancer cells has been recently included in the updated version of the review “Hallmarks of Cancer”, where the dysregulation of cellular metabolism was included as an emerging hallmark. While several lines of evidence suggest that metabolic rewiring is orchestrated by the concerted action of oncogenes and tumor suppressor genes, in some circumstances altered metabolism can play a primary role in oncogenesis. Recently, mutations of cytosolic and mitochondrial enzymes involved in key metabolic pathways have been associated with hereditary and sporadic forms of cancer. Together, these results suggest that aberrant metabolism, once seen just as an epiphenomenon of oncogenic reprogramming, plays a key role in oncogenesis with the power to control both genetic and epigenetic events in cells. In this review, we discuss the relationship between metabolism and cancer, as part of a larger effort to identify a broad-spectrum of therapeutic approaches. We focus on major alterations in nutrient metabolism and the emerging link between metabolism and epigenetics. Finally, we discuss potential strategies to manipulate metabolism in cancer and tradeoffs that should be considered. More research on the suite of metabolic alterations in cancer holds the potential to discover novel approaches to treat it. PMID:26454069

  2. Laparoscopic total pancreatectomy

    Science.gov (United States)

    Wang, Xin; Li, Yongbin; Cai, Yunqiang; Liu, Xubao; Peng, Bing

    2017-01-01

    Abstract Rationale: Laparoscopic total pancreatectomy is a complicated surgical procedure and rarely been reported. This study was conducted to investigate the safety and feasibility of laparoscopic total pancreatectomy. Patients and Methods: Three patients underwent laparoscopic total pancreatectomy between May 2014 and August 2015. We reviewed their general demographic data, perioperative details, and short-term outcomes. General morbidity was assessed using Clavien–Dindo classification and delayed gastric emptying (DGE) was evaluated by International Study Group of Pancreatic Surgery (ISGPS) definition. Diagnosis and Outcomes: The indications for laparoscopic total pancreatectomy were intraductal papillary mucinous neoplasm (IPMN) (n = 2) and pancreatic neuroendocrine tumor (PNET) (n = 1). All patients underwent laparoscopic pylorus and spleen-preserving total pancreatectomy, the mean operative time was 490 minutes (range 450–540 minutes), the mean estimated blood loss was 266 mL (range 100–400 minutes); 2 patients suffered from postoperative complication. All the patients recovered uneventfully with conservative treatment and discharged with a mean hospital stay 18 days (range 8–24 days). The short-term (from 108 to 600 days) follow up demonstrated 3 patients had normal and consistent glycated hemoglobin (HbA1c) level with acceptable quality of life. Lessons: Laparoscopic total pancreatectomy is feasible and safe in selected patients and pylorus and spleen preserving technique should be considered. Further prospective randomized studies are needed to obtain a comprehensive understanding the role of laparoscopic technique in total pancreatectomy. PMID:28099344

  3. Prognostic value of whole-body metabolic tumour volume and total lesion glycolysis measured on {sup 18}F-FDG PET/CT in patients with extranodal NK/T-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Choon-Young; Hong, Chae Moon; Kim, Do-Hoon; Son, Seung Hyun; Jeong, Shin Young; Lee, Sang-Woo; Lee, Jaetae; Ahn, Byeong-Cheol [Kyungpook National University School of Medicine and Hospital, Department of Nuclear Medicine, Daegu (Korea, Republic of)

    2013-09-15

    The aim of this study was to determine whether maximum standardized uptake value (SUVmax), whole-body metabolic tumour volume (WBMTV), and whole-body total lesion glycolysis (WBTLG) measured on pretreatment {sup 18}F-FDG PET/CT can predict prognosis in patients with extranodal natural killer/T-cell lymphoma (ENKTL). We conducted a retrospective analysis of 20 patients with newly-diagnosed ENKTL who underwent pretreatment {sup 18}F-FDG PET/CT. WBMTV and WBTLG were measured automatically using the boundaries of voxels presenting SUV > 3.0. Uni- and multivariate analyses for survival and disease progression were performed using clinical variables and PET parameters (SUVmax, WBMTV, and WBTLG). During the follow-up period (median 26.3 months), 12 patients showed disease progression and 10 patients died from the disease. Receiver operating characteristic curve analysis showed cut-off values for SUVmax, WBMTV and WBTLG of 8.1, 14.4 cm{sup 3} and 52.7, respectively. Univariate analysis showed that the International Prognostic Index (IPI) score and PET parameters were significant predictors of overall survival (OS) and progression-free survival (PFS). Multivariate analysis, even after adjustment for the IPI score, showed that high WBMTV was the best predictor of OS and PFS, and high SUVmax and WBTLG were significant predictors of PFS. Our results suggested that the use of PET parameters together with the IPI score may be useful for detailed prediction of prognosis in ENKTL patients. Therefore, despite a lower IPI score, patients with high PET parameter values might be considered candidates for aggressive therapy to improve clinical outcomes. (orig.)

  4. Tumoral tracers

    International Nuclear Information System (INIS)

    Camargo, E.E.

    1979-01-01

    Direct tumor tracers are subdivided in the following categories:metabolite tracers, antitumoral tracers, radioactive proteins and cations. Use of 67 Ga-citrate as a clinically important tumoral tracer is emphasized and gallium-67 whole-body scintigraphy is discussed in detail. (M.A.) [pt

  5. Regulation of Tumor Progression by Programmed Necrosis

    Directory of Open Access Journals (Sweden)

    Su Yeon Lee

    2018-01-01

    Full Text Available Rapidly growing malignant tumors frequently encounter hypoxia and nutrient (e.g., glucose deprivation, which occurs because of insufficient blood supply. This results in necrotic cell death in the core region of solid tumors. Necrotic cells release their cellular cytoplasmic contents into the extracellular space, such as high mobility group box 1 (HMGB1, which is a nonhistone nuclear protein, but acts as a proinflammatory and tumor-promoting cytokine when released by necrotic cells. These released molecules recruit immune and inflammatory cells, which exert tumor-promoting activity by inducing angiogenesis, proliferation, and invasion. Development of a necrotic core in cancer patients is also associated with poor prognosis. Conventionally, necrosis has been thought of as an unregulated process, unlike programmed cell death processes like apoptosis and autophagy. Recently, necrosis has been recognized as a programmed cell death, encompassing processes such as oncosis, necroptosis, and others. Metabolic stress-induced necrosis and its regulatory mechanisms have been poorly investigated until recently. Snail and Dlx-2, EMT-inducing transcription factors, are responsible for metabolic stress-induced necrosis in tumors. Snail and Dlx-2 contribute to tumor progression by promoting necrosis and inducing EMT and oncogenic metabolism. Oncogenic metabolism has been shown to play a role(s in initiating necrosis. Here, we discuss the molecular mechanisms underlying metabolic stress-induced programmed necrosis that promote tumor progression and aggressiveness.

  6. Animal tumors

    International Nuclear Information System (INIS)

    Gillette, E.L.

    1983-01-01

    There are few trained veterinary radiation oncologists and the expense of facilities has limited the extent to which this modality is used. In recent years, a few cobalt teletherapy units and megavoltage x-ray units have been employed in larger veterinary institutions. In addition, some radiation oncologists of human medical institutions are interested and willing to cooperate with veterinarians in the treatment of animal tumors. Carefully designed studies of the response of animal tumors to new modalities serve two valuable purposes. First, these studies may lead to improved tumor control in companion animals. Second, these studies may have important implications to the improvement of therapy of human tumors. Much remains to be learned of animal tumor biology so that appropriate model systems can be described for such studies. Many of the latter studies can be sponsored by agencies interested in the improvement of cancer management

  7. Application of PET in brain tumor

    International Nuclear Information System (INIS)

    Chung, June Key

    2002-01-01

    The annual incidence of primary brain tumors is 7-19 cases per 100,000 people. The unique capacity of visualizing biochemical processes allows PET to determine functional metabolic activities of the brain tumors. Like other malignant tumors, F-18 FDG has been used commonly in the imaging of brain tumors. FDG PET is valuable in grading malignancy, predicting prognosis, monitoring treatment, differentiating tumor recurrence from radiation nucrosis, and detecting primary lesion in metastatric brain tumors. Among amino acids labeled with positron emitters, C-11 methionine is used clinically.Tumor delineation is much better with methionine PET than with FDG PET. Low grade gliomas, in particular, are better evaluated with methionine than with FDG. PET opens another dimension in brain tumor imaging. PET imaging has clearly entered the clinical area with a profound impact on patient care in many indications

  8. Tumor Metabolism and Perfusion in Head and Neck Squamous Cell Carcinoma: Pretreatment Multimodality Imaging With 1H Magnetic Resonance Spectroscopy, Dynamic Contrast-Enhanced MRI, and [18F]FDG-PET

    International Nuclear Information System (INIS)

    Jansen, Jacobus F.A.; Schöder, Heiko; Lee, Nancy Y.; Stambuk, Hilda E.; Wang Ya; Fury, Matthew G.; Patel, Senehal G.; Pfister, David G.; Shah, Jatin P.; Koutcher, Jason A.; Shukla-Dave, Amita

    2012-01-01

    Purpose: To correlate proton magnetic resonance spectroscopy ( 1 H-MRS), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and 18 F-labeled fluorodeoxyglucose positron emission tomography ([ 18 F]FDG PET) of nodal metastases in patients with head and neck squamous cell carcinoma (HNSCC) for assessment of tumor biology. Additionally, pretreatment multimodality imaging was evaluated for its efficacy in predicting short-term response to treatment. Methods and Materials: Metastatic neck nodes were imaged with 1 H-MRS, DCE-MRI, and [ 18 F]FDG PET in 16 patients with newly diagnosed HNSCC, before treatment. Short-term patient radiological response was evaluated at 3 to 4 months. Correlations among 1 H-MRS (choline concentration relative to water [Cho/W]), DCE-MRI (volume transfer constant [K trans ]; volume fraction of the extravascular extracellular space [v e ]; and redistribution rate constant [k ep ]), and [ 18 F]FDG PET (standard uptake value [SUV] and total lesion glycolysis [TLG]) were calculated using nonparametric Spearman rank correlation. To predict short-term responses, logistic regression analysis was performed. Results: A significant positive correlation was found between Cho/W and TLG (ρ = 0.599; p = 0.031). Cho/W correlated negatively with heterogeneity measures of standard deviation std(v e ) (ρ = −0.691; p = 0.004) and std(k ep ) (ρ = −0.704; p = 0.003). Maximum SUV (SUVmax) values correlated strongly with MRI tumor volume (ρ = 0.643; p = 0.007). Logistic regression indicated that std(K trans ) and SUVmean were significant predictors of short-term response (p 1 H-MRS, DCE-MRI, and [ 18 F]FDG PET is feasible in HNSCC patients with nodal metastases. Additionally, combined DCE-MRI and [ 18 F]FDG PET parameters were predictive of short-term response to treatment.

  9. Metabolic complications in oncology

    International Nuclear Information System (INIS)

    Sycova-Mila, Z.

    2012-01-01

    Currently, a lot of space and time is devoted to the therapy of oncologic diseases itself. To reach the good therapy results, complex care of the oncologic patient is needed. Management of complications linked with the disease itself and management of complications emerged after administration of chemotherapy, radiotherapy or targeted therapy, plays a significant role. In addition to infectious, hematological, neurological, cardiac or other complications, metabolic complications are relatively extensive and serious. One of the most frequent metabolic complications in oncology is tumor lysis syndrome, hyperuricemia, hypercalcaemia and syndrome of inappropriate secretion of antidiuretic hormone. (author)

  10. Preliminary study of brain glucose metabolism changes in patients with lung cancer of different histological types.

    Science.gov (United States)

    Li, Wei-Ling; Fu, Chang; Xuan, Ang; Shi, Da-Peng; Gao, Yong-Ju; Zhang, Jie; Xu, Jun-Ling

    2015-02-05

    Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types. One hundred and twenty patients with primary untreated lung cancer, who visited People's Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases), squamous cell carcinoma (43 cases), and small-cell carcinoma (25 cases). The whole body 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM) software, with 50 age-matched and gender-matched healthy controls for comparison. The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255) was larger than those in the adenocarcinoma group (total voxel value 1217) and squamous cell carcinoma group (total voxel value 1292). The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

  11. Preliminary Study of Brain Glucose Metabolism Changes in Patients with Lung Cancer of Different Histological Types

    Directory of Open Access Journals (Sweden)

    Wei-Ling Li

    2015-01-01

    Full Text Available Background: Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types. Methods: One hundred and twenty patients with primary untreated lung cancer, who visited People′s Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases, squamous cell carcinoma (43 cases, and small-cell carcinoma (25 cases. The whole body 18F-fluorodeoxyglucose (18F-FDG positron emission tomography (PET/computed tomography (CT of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM software, with 50 age-matched and gender-matched healthy controls for comparison. Results: The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255 was larger than those in the adenocarcinoma group (total voxel value 1217 and squamous cell carcinoma group (total voxel value 1292. Conclusions: The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

  12. Prognostic significance of preoperative metabolic tumour volume and total lesion glycolysis measured by {sup 18}F-FDG PET/CT in squamous cell carcinoma of the oral cavity

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, In Sun; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl [University of Ulsan College of Medicine, Department of Otolaryngology, Asan Medical Center, Seoul (Korea, Republic of); Kim, Jae Seung [University of Ulsan College of Medicine, Department of Nuclear Medicine, Asan Medical Center, Seoul (Korea, Republic of); Cho, Kyung-Ja [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea, Republic of); Kim, Sang Yoon [University of Ulsan College of Medicine, Department of Otolaryngology, Asan Medical Center, Seoul (Korea, Republic of); Biomedical Research Institute, Korean Institute of Science and Technology, Seoul (Korea, Republic of)

    2014-03-15

    Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from {sup 18}F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers; yet few studies have investigated their clinical and prognostic significance in oral cavity squamous cell carcinoma (OSCC). The present retrospective study evaluated the utility of pretreatment MTV and TLG measured by {sup 18}F-FDG PET/CT to predict survival and occult metastasis (OM) in OSCC. Of 162 patients with OSCC evaluated preoperatively by {sup 18}F-FDG PET/CT, 105 who underwent definitive surgery with or without adjuvant therapy were eligible. Maximum standardized uptake value (SUV{sub max}), MTV and TLG were measured. For calculation of MTV, 3-D regions of interest were drawn and a SUV threshold of 2.5 was used for defining regions. Univariate and multivariate analyses identified clinicopathological and imaging variables associated with OM, disease-free survival (DFS) and overall survival (OS). The median (range) SUV{sub max}, MTV and TLG were 7.3 (0.7-41.9), 4.5 ml (0.7-115.1 ml) and 18.3 g (2.4-224.1 g), respectively. Of 53 patients with clinically negative lymph nodes, OM was detected in 19 (36 %). By univariate and multivariate analyses, MTV (P = 0.018) and TLG (P = 0.011) were both independent predictive factors for OM, although they were not independent of each other. The 4-year DFS and OS rates were 53.0 % and 62.0 %, respectively. Univariate and multivariate analyses revealed that MTV (P = 0.001) and TLG (P = 0.006), with different cut-off levels, were both independent predictive factors for DFS, although they were not independent of each other, and MTV (P = 0.001), TLG (P = 0.002) and the involved resection margin (P = 0.007) were independent predictive factors for OS. Pretreatment MTV and TLG may be useful in stratifying the likelihood of survival and predicting OM in OSCC. (orig.)

  13. Total Thyroidectomy

    Directory of Open Access Journals (Sweden)

    Lopez Moris E

    2016-06-01

    Full Text Available Total thyroidectomy is a surgery that removes all the thyroid tissue from the patient. The suspect of cancer in a thyroid nodule is the most frequent indication and it is presume when previous fine needle puncture is positive or a goiter has significant volume increase or symptomes. Less frequent indications are hyperthyroidism when it is refractory to treatment with Iodine 131 or it is contraindicated, and in cases of symptomatic thyroiditis. The thyroid gland has an important anatomic relation whith the inferior laryngeal nerve and the parathyroid glands, for this reason it is imperative to perform extremely meticulous dissection to recognize each one of these elements and ensure their preservation. It is also essential to maintain strict hemostasis, in order to avoid any postoperative bleeding that could lead to a suffocating neck hematoma, feared complication that represents a surgical emergency and endangers the patient’s life.It is essential to run a formal technique, without skipping steps, and maintain prudence and patience that should rule any surgical act.

  14. Pituitary Tumors

    Science.gov (United States)

    ... Association (ABTA) International RadioSurgery Association National Brain Tumor Society National Institute of Child Health and Human Development ... Definition The pituitary is a small, bean-sized gland ...

  15. Hypothalamic tumor

    Science.gov (United States)

    ... in the brain to reduce spinal fluid pressure. Risks of radiation therapy include damage to healthy brain cells when tumor cells are destroyed. Common side effects from chemotherapy include loss of appetite, nausea and vomiting, and fatigue.

  16. Prediction of breast cancer recurrence using lymph node metabolic and volumetric parameters from {sup 18}F-FDG PET/CT in operable triple-negative breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yong-il [CHA University, Department of Nuclear Medicine, CHA Bundang Medical Center, Seongnam (Korea, Republic of); Seoul National University Hospital, Department of Nuclear Medicine, Seoul (Korea, Republic of); Kim, Yong Joong [Veterans Health Service Medical Center, Seoul (Korea, Republic of); Paeng, Jin Chul; Cheon, Gi Jeong; Lee, Dong Soo [Seoul National University Hospital, Department of Nuclear Medicine, Seoul (Korea, Republic of); Chung, June-Key [Seoul National University Hospital, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University, Cancer Research Institute, Seoul (Korea, Republic of); Kang, Keon Wook [Seoul National University Hospital, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University, Cancer Research Institute, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Biomedical Sciences, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of)

    2017-10-15

    Triple-negative breast cancer has a poor prognosis. We evaluated several metabolic and volumetric parameters from preoperative {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the prognosis of triple-negative breast cancer and compared them with current clinicopathologic parameters. A total of 228 patients with triple-negative breast cancer (mean age 47.0 ± 10.8 years, all women) who had undergone preoperative PET/CT were included. The PET/CT metabolic parameters evaluated included maximum, peak, and mean standardized uptake values (SUVmax, SUVpeak, and SUVmean, respectively). The volumetric parameters evaluated included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Metabolic and volumetric parameters were evaluated separately for tumor (T) and lymph nodes (N). The prognostic value of these parameters was compared with that of clinicopathologic parameters. All lymph node metabolic and volumetric parameters showed significant differences between patients with and without recurrence. However, tumor metabolic and volumetric parameters showed no significant differences. In a univariate survival analysis, all lymph node metabolic and volumetric parameters (SUVmax-N, SUVpeak-N, SUVmean-N, MTV-N, and TLG-N; all P < 0.001), T stage (P = 0.010), N stage (P < 0.001), and TNM stage (P < 0.001) were significant parameters. In a multivariate survival analysis, SUVmax-N (P = 0.005), MTV (P = 0.008), and TLG (P = 0.006) with TNM stage (all P < 0.001) were significant parameters. Lymph node metabolic and volumetric parameters were significant predictors of recurrence in patients with triple-negative breast cancer after surgery. Lymph node metabolic and volumetric parameters were useful parameters for evaluating prognosis in patients with triple-negative breast cancer by {sup 18}F-FDG PET/CT, rather than tumor parameters. (orig.)

  17. Proton MRS detects Metabolic Changes in Hormone Sensitive and Resistant Human Prostate Cancer Model CWR22 and CWR22r

    Science.gov (United States)

    Le, H. Carl; Lupu, Mihaela; Kotedia, Khushali; Rosen, Neal; Solit, David; Koutcher, Jason A.

    2010-01-01

    17-Allylamino, 17-Demethoxygeldanamycin (17-AAG), an effective inhibitor of the heat shock protein hsp90, preferentially inhibiting tumor hsp90 compared to hsp90 from normal cells (1), has shown promising results against several cancers, including hormone resistant prostate cancer. Levels of several oncogenic proteins critical to tumor growth and progression, such as AR (androgen receptor) and HER2/neu, were reduced 4 hours post 17-AAG treatment. Post treatment metabolic changes have also been observed in several tumor cell lines. In this study total choline (t-cho) distributions in hormone sensitive CWR22 and hormone resistant CWR22r prostate cancer xenograft tumors in mice were measured before, 4 hours and 48 hours after a single bolus 17-AAG treatment at 100 mg/kg using proton MRS. Our results show that tumor t-cho levels declined 4 hours after the treatment for CWR22 (P = 0.001) and 48 hours post treatment for CWR22r (P=0.003). Metabolic changes, in particular of t-cho intensity detected by 1H MRSI, are consistent with the observed immunohistochemistry changes, tumor growth inhibition for CWR22r (P=0.01 at 14 days post treatment) and a constant PSA level versus increasing PSA for control CWR22 (P=0.01). Metabolic changes in t-cho by proton MRSI can be used as an early biomarker of response for advanced stage prostate cancer in targeted therapy such as 17-AAG. PMID:19780165

  18. Transmandibular approach to total maxillectomy

    OpenAIRE

    Tiwari, R. M.

    2001-01-01

    Total Maxillectomy through transfacial approach has been practiced in the treatment of Cancer for more than a decade. Its role in T3 - T4 tumors extending posteriorly through gthe bony wall is questionable, since an oncological radical procedure is often not possible. Recurrences in the infratemporal fossa are common. Despite the addition of radiotherapy five year survivals have not significantly improved. Transmandibular approach to Total Maxillectomy overcomes this shortcoming by including ...

  19. Tumor Types: Understanding Brain Tumors

    Science.gov (United States)

    ... May cause excessive secretion of hormones Common among men and women in their 50s-80s Accounts for about 13 percent of all brain tumors Symptoms Headache Depression Vision loss Nausea or vomiting Behavioral and cognitive ...

  20. Radiation-induced rib fracture after stereotactic body radiotherapy with a total dose of 54-56 Gy given in 9-7 fractions for patients with peripheral lung tumor: impact of maximum dose and fraction size.

    Science.gov (United States)

    Aoki, Masahiko; Sato, Mariko; Hirose, Katsumi; Akimoto, Hiroyoshi; Kawaguchi, Hideo; Hatayama, Yoshiomi; Ono, Shuichi; Takai, Yoshihiro

    2015-04-22

    Radiation-induced rib fracture after stereotactic body radiotherapy (SBRT) for lung cancer has been recently reported. However, incidence of radiation-induced rib fracture after SBRT using moderate fraction sizes with a long-term follow-up time are not clarified. We examined incidence and risk factors of radiation-induced rib fracture after SBRT using moderate fraction sizes for the patients with peripherally located lung tumor. During 2003-2008, 41 patients with 42 lung tumors were treated with SBRT to 54-56 Gy in 9-7 fractions. The endpoint in the study was radiation-induced rib fracture detected by CT scan after the treatment. All ribs where the irradiated doses were more than 80% of prescribed dose were selected and contoured to build the dose-volume histograms (DVHs). Comparisons of the several factors obtained from the DVHs and the probabilities of rib fracture calculated by Kaplan-Meier method were performed in the study. Median follow-up time was 68 months. Among 75 contoured ribs, 23 rib fractures were observed in 34% of the patients during 16-48 months after SBRT, however, no patients complained of chest wall pain. The 4-year probabilities of rib fracture for maximum dose of ribs (Dmax) more than and less than 54 Gy were 47.7% and 12.9% (p = 0.0184), and for fraction size of 6, 7 and 8 Gy were 19.5%, 31.2% and 55.7% (p = 0.0458), respectively. Other factors, such as D2cc, mean dose of ribs, V10-55, age, sex, and planning target volume were not significantly different. The doses and fractionations used in this study resulted in no clinically significant rib fractures for this population, but that higher Dmax and dose per fraction treatments resulted in an increase in asymptomatic grade 1 rib fractures.

  1. Radiation-induced rib fracture after stereotactic body radiotherapy with a total dose of 54–56 Gy given in 9–7 fractions for patients with peripheral lung tumor: impact of maximum dose and fraction size

    International Nuclear Information System (INIS)

    Aoki, Masahiko; Sato, Mariko; Hirose, Katsumi; Akimoto, Hiroyoshi; Kawaguchi, Hideo; Hatayama, Yoshiomi; Ono, Shuichi; Takai, Yoshihiro

    2015-01-01

    Radiation-induced rib fracture after stereotactic body radiotherapy (SBRT) for lung cancer has been recently reported. However, incidence of radiation-induced rib fracture after SBRT using moderate fraction sizes with a long-term follow-up time are not clarified. We examined incidence and risk factors of radiation-induced rib fracture after SBRT using moderate fraction sizes for the patients with peripherally located lung tumor. During 2003–2008, 41 patients with 42 lung tumors were treated with SBRT to 54–56 Gy in 9–7 fractions. The endpoint in the study was radiation-induced rib fracture detected by CT scan after the treatment. All ribs where the irradiated doses were more than 80% of prescribed dose were selected and contoured to build the dose-volume histograms (DVHs). Comparisons of the several factors obtained from the DVHs and the probabilities of rib fracture calculated by Kaplan-Meier method were performed in the study. Median follow-up time was 68 months. Among 75 contoured ribs, 23 rib fractures were observed in 34% of the patients during 16–48 months after SBRT, however, no patients complained of chest wall pain. The 4-year probabilities of rib fracture for maximum dose of ribs (Dmax) more than and less than 54 Gy were 47.7% and 12.9% (p = 0.0184), and for fraction size of 6, 7 and 8 Gy were 19.5%, 31.2% and 55.7% (p = 0.0458), respectively. Other factors, such as D2cc, mean dose of ribs, V10–55, age, sex, and planning target volume were not significantly different. The doses and fractionations used in this study resulted in no clinically significant rib fractures for this population, but that higher Dmax and dose per fraction treatments resulted in an increase in asymptomatic grade 1 rib fractures

  2. Tumor immunology.

    Science.gov (United States)

    Mocellin, Simone; Lise, Mario; Nitti, Donato

    2007-01-01

    Advances in tumor immunology are supporting the clinical implementation of several immunological approaches to cancer in the clinical setting. However, the alternate success of current immunotherapeutic regimens underscores the fact that the molecular mechanisms underlying immune-mediated tumor rejection are still poorly understood. Given the complexity of the immune system network and the multidimensionality of tumor/host interactions, the comprehension of tumor immunology might greatly benefit from high-throughput microarray analysis, which can portrait the molecular kinetics of immune response on a genome-wide scale, thus accelerating the discovery pace and ultimately catalyzing the development of new hypotheses in cell biology. Although in its infancy, the implementation of microarray technology in tumor immunology studies has already provided investigators with novel data and intriguing new hypotheses on the molecular cascade leading to an effective immune response against cancer. Although the general principles of microarray-based gene profiling have rapidly spread in the scientific community, the need for mastering this technique to produce meaningful data and correctly interpret the enormous output of information generated by this technology is critical and represents a tremendous challenge for investigators, as outlined in the first section of this book. In the present Chapter, we report on some of the most significant results obtained with the application of DNA microarray in this oncology field.

  3. Pancreatic islet cell tumor

    Science.gov (United States)

    ... cell tumors; Islet of Langerhans tumor; Neuroendocrine tumors; Peptic ulcer - islet cell tumor; Hypoglycemia - islet cell tumor ... stomach acid. Symptoms may include: Abdominal pain Diarrhea ... and small bowel Vomiting blood (occasionally) Glucagonomas make ...

  4. Pathway-specific differences between tumor cell lines and normal and tumor tissue cells

    Directory of Open Access Journals (Sweden)

    Tozeren Aydin

    2006-11-01

    Full Text Available Abstract Background Cell lines are used in experimental investigation of cancer but their capacity to represent tumor cells has yet to be quantified. The aim of the study was to identify significant alterations in pathway usage in cell lines in comparison with normal and tumor tissue. Methods This study utilized a pathway-specific enrichment analysis of publicly accessible microarray data and quantified the gene expression differences between cell lines, tumor, and normal tissue cells for six different tissue types. KEGG pathways that are significantly different between cell lines and tumors, cell lines and normal tissues and tumor and normal tissue were identified through enrichment tests on gene lists obtained using Significance Analysis of Microarrays (SAM. Results Cellular pathways that were significantly upregulated in cell lines compared to tumor cells and normal cells of the same tissue type included ATP synthesis, cell communication, cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism, and proteasome. Results on metabolic pathways suggested an increase in the velocity nucleotide metabolism and RNA production. Pathways that were downregulated in cell lines compared to tumor and normal tissue included cell communication, cell adhesion molecules (CAMs, and ECM-receptor interaction. Only a fraction of the significantly altered genes in tumor-to-normal comparison had similar expressions in cancer cell lines and tumor cells. These genes were tissue-specific and were distributed sparsely among multiple pathways. Conclusion Significantly altered genes in tumors compared to normal tissue were largely tissue specific. Among these genes downregulation was a major trend. In contrast, cell lines contained large sets of significantly upregulated genes that were common to multiple tissue types. Pathway upregulation in cell lines was most pronounced over metabolic pathways including cell nucleotide metabolism and oxidative

  5. Imaging of brain tumors

    International Nuclear Information System (INIS)

    Gaensler, E.H.L.

    1995-01-01

    The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.)

  6. Imaging of brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Gaensler, E H.L. [California Univ., San Francisco, CA (United States). Dept. of Radiology

    1996-12-31

    The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.).

  7. Uncertainces in tumor target definition using PET

    International Nuclear Information System (INIS)

    Kirov, A.

    2013-01-01

    Full text: Introduction: PET entered into the clinics for radiation therapy as a means of displaying the metabolically active part of the tumor. However this advantage, PET has a number of shortcomings that prevent its use for precise determination of the tumor boundaries. What you will learn: The aim of the lecture is to present: the requirements for the accuracy of the determination of tumor boundaries in radiation therapy; the main phenomena which bring uncertainty using PET and a brief overview of methods for segmentation of tumors and their problems

  8. Parotid hybrid tumor

    International Nuclear Information System (INIS)

    Bravo C, Gustavo; Seymour M, Camila; Fernandez R, Lara; Villanueva I, Maria Elena; Scott C, Carlos; Celedon L, Carlos

    2012-01-01

    Tumors of the salivary glands represent 33%-10% of head and neck neoplasms. The most common location is the parotid gland, accounting for 50%-85% of the cases, with 20%-30% of them being malignant. The following are known to be indicative of a malignant tumor: fast growing, painless mass, associated facial paralysis and lymphadenopathy. Most parotid neoplasm derive from a single histological type but eventually the development of more than one type on the same gland can occur. This paper presents a case of a parotid neoplasm with two different histological tumors, with uncharacteristic clinical presentation. The patient presented initially with ear pain and otorrhoea, in the clinical examination highlighted an external auditory canal tumor. The complementary study revealed a parotid neoplasm and a total resection of the gland was performed. The biopsy revealed an adenoid-cystic carcinoma with differentiated basaloid areas. Adjuvant radio-chemotherapy was administered, and the imaging control with PET-CT showed no evidence of recurrence or dissemination of the tumor

  9. Metabolic Syndrome

    Science.gov (United States)

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These conditions ... agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  10. Proton MRS detects metabolic changes in hormone sensitive and resistant human prostate cancer models CWR22 and CWR22r.

    Science.gov (United States)

    Le, H Carl; Lupu, Mihaela; Kotedia, Khushali; Rosen, Neal; Solit, David; Koutcher, Jason A

    2009-11-01

    17-Allylamino, 17-demethoxygeldanamycin (17-AAG), an effective inhibitor of the heat shock protein hsp90, preferentially inhibiting tumor hsp90 compared to hsp90 from normal cells, has shown promising results against several cancers, including hormone-resistant prostate cancer. Levels of several oncogenic proteins critical to tumor growth and progression, such as androgen receptor and HER2/neu, were reduced 4 h post 17-allylamino, 17-demethoxygeldanamycin treatment. Posttreatment metabolic changes have also been observed in several tumor cell lines. In this study, total choline distributions in hormone sensitive CWR22 and hormone resistant CWR22r prostate cancer xenograft tumors in mice were measured before and at 4 h and 48 h after a single-bolus 17-allylamino, 17-demethoxygeldanamycin treatment at 100 mg/kg, using proton MR spectroscopy. Our results show that tumor total choline levels declined 4 h after the treatment for CWR22 (P = 0.001) and 48 h post treatment for CWR22r (P = 0.003). Metabolic changes, in particular of total choline intensity detected by proton magnetic resonance spectroscopic imaging (MRSI), are consistent with the observed immunohistochemistry changes, tumor growth inhibition for CWR22r (P = 0.01 at 14 days post treatment), and a constant prostate specific antigen level versus increasing prostate specific antigen for control CWR22 (P = 0.01). Metabolic changes in total choline by proton MRSI can be used as an early biomarker of response for advanced-stage prostate cancer in targeted therapy such as 17-allylamino, 17-demethoxygeldanamycin. (c) 2009 Wiley-Liss, Inc.

  11. Metabolic syndrome and menopause

    Directory of Open Access Journals (Sweden)

    Jouyandeh Zahra

    2013-01-01

    Full Text Available Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3 criteria to classify subjects as having metabolic syndrome. Results Total prevalence of metabolic syndrome among our subjects was 30.1%. Waist circumference, HDL-cholesterol, fasting blood glucose, diastolic blood pressure ,Systolic blood pressure, and triglyceride were significantly higher among women with metabolic syndrome (P-value Conclusions Our study shows that postmenopausal status is associated with an increased risk of metabolic syndrome. Therefore, to prevent cardiovascular disease there is a need to evaluate metabolic syndrome and its components from the time of the menopause.

  12. Níveis de proteína na dieta de bovinos Nelore de três condições sexuais: consumo, digestibilidades total e parcial, produção microbiana e parâmetros ruminais Increasing crude protein levels in diets of Nellore cattle: intake, ruminal and total tract digestibility, microbial protein synthesis, and ruminal metabolism

    Directory of Open Access Journals (Sweden)

    Robson Magno Liberal Véras

    2007-08-01

    .Twelve Nellore cattle fitted with ruminal and duodenal cannulas were used to investigate the effects of increasing dietary crude protein level (7, 10, 13, and 15% on intake, ruminal and total tract digestibility of nutrients, microbial protein synthesis, degradabilities of corn silage, corn starch, and cottonseed meal, and ruminal metabolism. Animals were blocked by sexual category (heifers, bulls and steers averaging 254.8, 285.1, and 265.6 kg of body weight, respectively and then assigned to one out of three Latin squares. Samples were incubated in the rumen of one animal of each sexual category to estimate ingredient degradability after determination of DM, CP and NDF in the incubation residues. Ruminal fluid was collected before and after-feeding to determine pH and concentration of ammonia while ruminal samples for bacterial isolation were taken 6 hours post-feeding. Blood (BUN and urine (UU were also collected for measurement of urea concentration. The degradation rates of DM and CP were both lower in corn silage than on corn starch and cottonseed meal. The interaction sexual condition x dietary crude protein level was not significant for nutrient intake. With the exception of EE and NFC, no other significant effect of dietary CP level was observed for daily intake of nutrients. Increasing dietary CP level affected total tract digestibilities of DM, OM, CP, NDF, and NFC and also resulted in higher concentrations of BUN and UU. A significant dietary crude protein level x collection time interaction was observed for ruminal NH3 but not for ruminal pH. It was concluded that increasing dietary CP levels affected intake and total tract digestibility of most nutrients.

  13. Energy and Redox Homeostasis in Tumor Cells

    Directory of Open Access Journals (Sweden)

    Marcus Fernandes de Oliveira

    2012-01-01

    Full Text Available Cancer cells display abnormal morphology, chromosomes, and metabolism. This review will focus on the metabolism of tumor cells integrating the available data by way of a functional approach. The first part contains a comprehensive introduction to bioenergetics, mitochondria, and the mechanisms of production and degradation of reactive oxygen species. This will be followed by a discussion on the oxidative metabolism of tumor cells including the morphology, biogenesis, and networking of mitochondria. Tumor cells overexpress proteins that favor fission, such as GTPase dynamin-related protein 1 (Drp1. The interplay between proapoptotic members of the Bcl-2 family that promotes Drp 1-dependent mitochondrial fragmentation and fusogenic antiapoptotic proteins such as Opa-1 will be presented. It will be argued that contrary to the widespread belief that in cancer cells, aerobic glycolysis completely replaces oxidative metabolism, a misrepresentation of Warburg’s original results, mitochondria of tumor cells are fully viable and functional. Cancer cells also carry out oxidative metabolism and generally conform to the orthodox model of ATP production maintaining as well an intact electron transport system. Finally, data will be presented indicating that the key to tumor cell survival in an ROS rich environment depends on the overexpression of antioxidant enzymes and high levels of the nonenzymatic antioxidant scavengers.

  14. Bone tumors

    International Nuclear Information System (INIS)

    Moylan, D.J.; Yelovich, R.M.

    1991-01-01

    Primary bone malignancies are relatively rare with less than 4,000 new cases per year. Multiple myeloma (more correctly a hematologic malignancy) accounts for 40%; osteosarcomas, 28%; chondrosarcomas, 13%; fibrosarcomas arising in bone, 4%; and Ewing's sarcoma, 7%. The authors discuss various treatments for bone tumors, including radiotherapy, chemotherapy and surgery

  15. Wilms Tumor

    Science.gov (United States)

    ... a child's general health and to detect any adverse side effects (such as low red or white blood cell ... medicine needed, which helps reduce long-term side effects. The most common ... can be completely removed by surgery. About 41% of all Wilms tumors are stage ...

  16. Nephrogenic tumors

    International Nuclear Information System (INIS)

    Wiesbauer, P.

    2008-01-01

    Nephroblastomas are the most common malignant renal tumors in childhood. According to the guidelines of the SIOP (Societe Internationale d'Oncologie Pediatrique) and GPOH (Gesellschaft fuer Paediatrische Onkologie und Haematologie) pre-operative chemotherapy can be started without histological confirmation and thus initial imaging studies, in particular ultrasound, play an outstanding role for diagnostic purposes

  17. Solid-pseudo papillary tumor of the pancreas: Frantz's tumor

    International Nuclear Information System (INIS)

    Oliveira, Bruno Righi Rodrigues de; Moreira, Reni Cecilia Lopes; Campos, Marcelo Esteves Chaves

    2010-01-01

    The pseudo papillary solid tumor of the pancreas, also known as Frantz's tumor, is a rare disease, taking place in approximately 0.17% to 2.7% of non-endocrine tumors of the pancreas. Recently, the increase of its incidence has been noted with more than two-thirds of the total cases described in the last 10 years. A possible explanation is a greater knowledge of the disease and a greater uniformity of conceptualization in the last years. Generally, it affects young adult females. In most of the series, the tumor principally attacks the body and tail of the pancreas. The objective of the present report is to present the diagnostic and therapeutic option used in this rare pancreatic tumor of low-grade malignancy. (author)

  18. The metabolic switch of cancer

    Directory of Open Access Journals (Sweden)

    Yuting Ma

    2017-03-01

    Full Text Available Although remarkable progress has been made in oncology research, cancer is still a leading cause of death worldwide. It is well recognized that cancer is a genetic disease, yet metabolic alterations or reprogramming are the major phenotypes associated with the (epi-genetic modifications of cancer cells. Thus, understanding the metabolic changes of tumor cells will facilitate the diagnosis of cancer, alleviate drug resistance and provide novel druggable targets that can lead to cures for cancer. The first Sino-US Symposium on Cancer Metabolism was held in Chongqing on October 10th and 11th, with the theme of “cancer metabolism and precision cancer therapy”. The symposium brought about a dozen keynote speakers each from the US and mainland China, as well as one hundred delegates with an interest in cancer metabolism. This short article will briefly summarize the advances reported during this meeting.

  19. Analysis of aberrant methylation on promoter sequences of tumor suppressor genes and total DNA in sputum samples: a promising tool for early detection of COPD and lung cancer in smokers

    Directory of Open Access Journals (Sweden)

    Guzmán Leda

    2012-07-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is a disorder associated to cigarette smoke and lung cancer (LC. Since epigenetic changes in oncogenes and tumor suppressor genes (TSGs are clearly important in the development of LC. In this study, we hypothesize that tobacco smokers are susceptible for methylation in the promoter region of TSGs in airway epithelial cells when compared with non-smoker subjects. The purpose of this study was to investigate the usefulness of detection of genes promoter methylation in sputum specimens, as a complementary tool to identify LC biomarkers among smokers with early COPD. Methods We determined the amount of DNA in induced sputum from patients with COPD (n = 23, LC (n = 26, as well as in healthy subjects (CTR (n = 33, using a commercial kit for DNA purification, followed by absorbance measurement at 260 nm. The frequency of CDKN2A, CDH1 and MGMT promoter methylation in the same groups was determined by methylation-specific polymerase chain reaction (MSP. The Fisher’s exact test was employed to compare frequency of results between different groups. Results DNA concentration was 7.4 and 5.8 times higher in LC and COPD compared to the (CTR (p  Conclusions We provide evidence that aberrant methylation of TSGs in samples of induced sputum is a useful tool for early diagnostic of lung diseases (LC and COPD in smoker subjects. Virtual slides The abstract MUST finish with the following text: Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1127865005664160

  20. Stromal gastrointestinal tumors (GIST)

    International Nuclear Information System (INIS)

    Balev, B.; Boykova, K.

    2015-01-01

    Full text: GIST are a heterogeneous group of mesenchymal tumors of the gastrointestinal tract with varying tumor grade and frequency of 1: 100 000 per year. Mazur and Clark introduced the term for the first time in 1983. GIST constitute approximately 2% of the tumors in the gastrointestinal tract. The average age is 60 years. The most common locations are the stomach (60%), small intestine (30%), esophagus (1%), and rectum (5%). Learning objective: to demonstrate the imaging characteristics of the disease according to the current ESMO guidelines and to present the diagnostic accuracy of different imaging modalitiesnbased on review of literature and on own observations. GIST originate from interstitial cells (of Cajal) in the GIT wall, belonging to the autonomic nervous system, which is responsible for motility. 90% of GIST show overexpression of the KIT receptor, also known as CD117 or stem cell factor receptor. those that do not express c-KIT mutations, activate mutations in PDGFRA gene. Tumor’s macromorphology determines the imaging features on different modalities. Most of these tumors are exophytic, subepithelial, reach large size and enhance inhomogeneous due to necrosis. They usually do not cause obstruction. Ultrasound as the initiation method shows low sensitivity and specificity in GIST detection, CT with intravenous contrast is the gold standard. MRI contributes with assessing the vascularisation, cellularity and pH. FDG-PET/CT registers the metabolism of intratumoral acidosis. CT is the method of choice in the early diagnosis and determination of resectability of GIST. MRI is an additional method. PET FDG-CT is useful for the monitoring of patients treated with Imatinib

  1. "Cancer tumor".

    Science.gov (United States)

    Bronshtehn, V. A.

    The title is a phrase borrowed from a speech by a Leningrad pressman, V. E. Lvov, who called upon those attending a theoretical conference on ideological issues in astronomy held by the Leningrad Branch of the All-Union Astronomic and Geodetic Society (13 - 4 December 1948), "to make a more radical emphasis on the negative role of relativistic cosmology which is a cancer tumor disintegrating the contemporary astronomy theory, and a major ideological enemy of a materialist astronomy".

  2. [Desmoid tumors in three patients].

    Science.gov (United States)

    Mohos, E; Kovács, T; Brittig, F; Nagy, A

    2001-12-01

    Desmoids are rare tumors of the connective tissue. It develops about 1:1000 times more in patients with familial adenomatous polyposis (FAP, Gardner syndrome) compared to normal population. It has been shown in molecular genetic examinations, that different mutations of the APC gene are responsible for desmoid tumors in FAP. It means, that this disease is one of the extraintestinal manifestations of Gardner syndrome. This tumor has high recurrence rate and is growing rapidly, and as a result it is the second most common cause of death in FAP patients. That is why genetic examination for FAP patients is advised to decide if the patient has higher risk for desmoid formation. If the result of the genetic test is positive, it is advisable to try to slow the progression of polyposis with medical treatment, and so to delay the date of the colectomy because the surgical intervention--and connective tissue damage--can induce desmoid formation in these patients. At the same time it is reasonable to examine and regularly control patients with sporadic desmoid tumors searching for other manifestations of Gardner syndrome (colon, stomach and duodenum polyposis, tumor of papilla Vateri, retinopathy, etc.). Palliative surgery is not indicated in patients with inoperable intraabdominal desmoid tumors, because partial resections (R1, R2, debulking) result in further tumor progression. In these patients medical treatment (sulindac, tamoxifen), chemotherapy (doxorubicin, dacarbazin) and radiotherapy or combination of them can result tumor remission. We describe our three patients (an abdominal wall desmoid four years following Cesarean section; a desmoid tumor in the retroperitoneum and in the pelvis diagnosed three years after total colectomy; and a retroperitoneal and abdominal wall desmoid one year after total colectomy) and etiology, diagnosis and therapy of desmoid tumors are discussed.

  3. Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High Grade Human Brain Tumors

    Directory of Open Access Journals (Sweden)

    Andrei G. Vlassenko

    2015-01-01

    Full Text Available Objectives. Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG, is a hallmark of active cancer cells that is not directly measured with standard 18F-fluorodeoxyglucose (FDG positron emission tomography (PET. In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism. Methods. Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF, oxygen (CMRO2 and glucose (CMRGlu metabolism, and AG, using 15O-labeled CO, O2 and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals. Results. Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2 and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures. Conclusions. Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET.

  4. Surgery for adrenal tumors

    International Nuclear Information System (INIS)

    Salamah, S.M.

    2002-01-01

    Objective: To analyze the presentation, localization, pathology, surgical management and outcome of surgery for adrenal gland tumors. Design: Prospective clinico epidemiological study. Place and Duration of Study: The study was conducted at the Department of General Surgery, University Unit, Riyadh medical Complex Kingdom of Saudi Rabia from June, 1991 to may, 2001. Subjects and Methods: A total of 21 cases with adrenal tumors were studied for demographic data, clinical presentation, diagnostic workup, localization, surgical management, pathology and outcome. The outcome of these patients was followed prospectively. Results: The study included 12 female and 9 male patients. The mean age at surgery was 36.7 years. Hypertension (69.%) was the commonest presentation in hypersecretory functional tumors. The localization accuracy for ultrasonography, computerized tomography, MRI and MIBG scan was 95.2%, 98.3% 87.8% and 83.6% respectively. Pheochromocytoma was the most common adrenal pathology observed in 14 (66.6%) cases. The overall morbidity was 19% with no hospital mortality. Complete follow-up of available 19 patients (90.5 %) revealed no tumor recurrence and persistent hypertension in 14.3% cases. Conclusion: surgery on adrenal glands is safe in experienced hands and is recommended in institutes with all backup facilities. (author)

  5. Understanding Brain Tumors

    Science.gov (United States)

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  6. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  7. Brain tumor - children

    Science.gov (United States)

    ... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

  8. Adrenal Gland Tumors: Statistics

    Science.gov (United States)

    ... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

  9. 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.)

  10. Diagnostic evaluatuin of gastrointestinal tumors

    International Nuclear Information System (INIS)

    Linke, R.; Tatsch, K.

    1998-01-01

    Prior to surgery of gastrointestinal tumors exact information about tumor localization, extent and possible infiltration in adjacent structures are important. The task for radiological and scintigraphic methods is predominantly the preoperative tumor staging. The upper (esophagus, stomach, duodenum) and the lower (colon, rectum) gastrointestinal tract should be routinely investigated by endoscopy and endosonography. CT or MRI imaging may add information about tumor extent, infiltration in adjacent structures and pathologically enlarged lymph nodes. The latter may be detected with similar or higher sensitivity by PET as well. Furthermore, with PET it is possible to differentiate a tumor recurrence from postoperative scar tissue earlier than with conventional morphological imaging techniques, for example in colorectal cancer. Liver tumors should primarily be inspected sonographically followed by an MRI scan if dignity is uncertain. The receptor scintigraphy with radioactive ligands allows to further characterize a detected tumor. Benigne liver lesions can be distinguished from malignant tumors (metastasis, hepatocellular carcinoma [HCC]) by the neogalactoalbumin-(NGA-)scintigraphy, because NGA binds exclusively to the liver galactose receptors of normally functioning hepatocytes. For the differentiation between liver metastasis and HCC insulin scintigraphy can be used, since insulin binds significantly in HCC due to an overexpression of insulin receptors in these tumors. If a malignant process is suspected, additionally CT-arterioportography may be recommended, because this newer radiological technique is capable to visualize lesions smaller than 1 cm. In such cases PET is sensitive as well and due to increased glucose metabolism even small foci can be detected with comparably high sepcificity. The method of choice for the detection of a pancreatic tumor is endoscopic sonography. In most cases the dignity of the tumor can be verified by ERCP, but sometimes it is very

  11. Testis tumors

    International Nuclear Information System (INIS)

    White, R.L.; Maier, J.G.

    1987-01-01

    Clinical trials are evaluating new combinations of drugs with the goal of diminishing the toxicity associated with the current regimens while not compromising the chance for cure. The evolution of information and staging studies such as tumor markers, CT scanning and MR scanning has made possible the detection of residual metastatic disease while obviating the need for surgical staging procedures. This has made less treatment possible for a large number of patients. The regularity of follow-up studies has made early detection of recurrences a possibility, so that effective and curative treatment is generally possible

  12. Antitumor action of 3-bromopyruvate implicates reorganized tumor growth regulatory components of tumor milieu, cell cycle arrest and induction of mitochondria-dependent tumor cell death.

    Science.gov (United States)

    Yadav, Saveg; Kujur, Praveen Kumar; Pandey, Shrish Kumar; Goel, Yugal; Maurya, Babu Nandan; Verma, Ashish; Kumar, Ajay; Singh, Rana Pratap; Singh, Sukh Mahendra

    2018-01-15

    Evidences demonstrate that metabolic inhibitor 3-bromopyruvate (3-BP) exerts a potent antitumor action against a wide range of malignancies. However, the effect of 3-BP on progression of the tumors of thymic origin remains unexplored. Although, constituents of tumor microenvironment (TME) plays a pivotal role in regulation of tumor progression, it remains unclear if 3-BP can alter the composition of the crucial tumor growth regulatory components of the external surrounding of tumor cells. Thus, the present investigation attempts to understand the effect of 3-BP administration to a host bearing a progressively growing tumor of thymic origin on tumor growth regulatory soluble, cellular and biophysical components of tumor milieu vis-à-vis understanding its association with tumor progression, accompanying cell cycle events and mode of cell death. Further, the expression of cell survival regulatory molecules and hemodynamic characteristics of the tumor milieu were analysed to decipher mechanisms underlying the antitumor action of 3-BP. Administration of 3-BP to tumor-bearing hosts retarded tumor progression accompanied by induction of tumor cell death, cell cycle arrest, declined metabolism, inhibited mitochondrial membrane potential, elevated release of cytochrome c and altered hemodynamics. Moreover, 3-BP reconstituted the external milieu, in concurrence with deregulated glucose and pH homeostasis and increased tumor infiltration by NK cells, macrophages, and T lymphocytes. Further, 3-BP administration altered the expression of key regulatory molecules involved in glucose uptake, intracellular pH and tumor cell survival. The outcomes of this study will help in optimizing the therapeutic application of 3-BP by targeting crucial tumor growth regulatory components of tumor milieu. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Antiproliferative and metabolic effects of metformin in a preoperative window clinical trial for endometrial cancer

    International Nuclear Information System (INIS)

    Schuler, Kevin M; Rambally, Brooke S; DiFurio, Megan J; Sampey, Brante P; Gehrig, Paola A; Makowski, Liza; Bae-Jump, Victoria L

    2015-01-01

    We conducted a preoperative window study of metformin in endometrial cancer (EC) patients and evaluated its antiproliferative, molecular and metabolic effects. Twenty obese women with endometrioid EC were treated with metformin (850 mg) daily for up to 4 weeks prior to surgical staging. Expression of the proliferation marker Ki-67, estrogen receptor (ER), progesterone receptor (PR), adenosine monophosphate-activated protein kinase (AMPK), and downstream targets of the mammalian target of rapamycin (mTOR) pathway were measured by immunohistochemistry. Global, untargeted metabolomics analysis of serum pre- and postmetformin treatment, and matched tumor, was performed. Metformin reduced proliferation by 11.75% (P = 0.008) based on the comparison of pre- and posttreatment endometrial tumors. A total of 65% of patients responded to metformin as defined by a decrease in Ki-67 staining in their endometrial tumors post-treatment. Metformin decreased expression of phosphorylated (p)-AMPK (P = 0.00001), p-Akt (P = 0.0002), p-S6 (51.2%, P = 0.0002), p-4E-BP-1 (P = 0.001), and ER (P = 0.0002) but not PR expression. Metabolomic profiling of serum indicated that responders versus nonresponders to treatment were more sensitive to metformin's effects on induction of lipolysis, which correlated with increased fatty acid oxidation and glycogen metabolism in matched tumors. In conclusion, metformin reduced tumor proliferation in a pre-operative window study in obese EC patients, with dramatic effects on inhibition of the mTOR pathway. Metformin induced a shift in lipid and glycogen metabolism that was more pronounced in the serum and tumors of responders versus nonresponders to treatment.This study provides support for therapeutic clinical trials of metformin in obese patients with EC

  14. Quantification of tumor extension in prostate biopsies: importance in the identification of confined tumors

    Directory of Open Access Journals (Sweden)

    Leite Kátia R.M.

    2003-01-01

    Full Text Available OBJECTIVE: To assess the importance of quantifying the adenocarcinoma in prostate biopsies when determining the tumor's final stage in patients who undergo radical prostatectomy. To identify the best methodology for obtaining such data. PATIENTS AND METHODS: Prostate biopsies from 132 patients were examined, with determination of Gleason histological grade and tumor volume in number of involved fragments, tumor extent of the fragment mostly affected by the tumor and the total percentage of tumor in the specimen. Theses parameters were statistically correlated with the neoplasia's final stage following the evaluation of radical prostatectomy specimens. RESULTS: An average of 12 and a median of 14 biopsy fragments were evaluated per patient. In the univariate analysis the Gleason histological grade, the largest tumor extent in one fragment and the total percentage of tumor in the specimen were correlated with tumor stage of the surgical specimen. In the multivariate analysis, the Gleason histological grade and the total percentage of tumor were strongly correlated with the neoplasia's final stage. The risk of the tumor not being confined was 3 for Gleason 7 tumors and 10.6 for Gleason 8 tumors or above. In cases where the tumor involved more than 60% of the specimen, the risk of non-confined disease was 4.4 times. Among 19 patients with unfavorable histological parameters, Gleason > 7 and extension greater than 60% the tumor final stage was pT3 in 95%. CONCLUSION: When associated to the Gleason histological grade, tumor quantification in prostate biopsies is an important factor for determining organ-confined disease, and among the methods, total percentage of tumor is the most informative one. Such data should be included in the pathological report and must be incorporated in future nomograms.

  15. Whole tumor antigen vaccination using dendritic cells: Comparison of RNA electroporation and pulsing with UV-irradiated tumor cells

    Directory of Open Access Journals (Sweden)

    Benencia Fabian

    2008-04-01

    Full Text Available Abstract Because of the lack of full characterization of tumor associated antigens for solid tumors, whole antigen use is a convenient approach to tumor vaccination. Tumor RNA and apoptotic tumor cells have been used as a source of whole tumor antigen to prepare dendritic cell (DC based tumor vaccines, but their efficacy has not been directly compared. Here we compare directly RNA electroporation and pulsing of DCs with whole tumor cells killed by ultraviolet (UV B radiation using a convenient tumor model expressing human papilloma virus (HPV E6 and E7 oncogenes. Although both approaches led to DCs presenting tumor antigen, electroporation with tumor cell total RNA induced a significantly higher frequency of tumor-reactive IFN-gamma secreting T cells, and E7-specific CD8+ lymphocytes compared to pulsing with UV-irradiated tumor cells. DCs electroporated with tumor cell RNA induced a larger tumor infiltration by T cells and produced a significantly stronger delay in tumor growth compared to DCs pulsed with UV-irradiated tumor cells. We conclude that electroporation with whole tumor cell RNA and pulsing with UV-irradiated tumor cells are both effective in eliciting antitumor immune response, but RNA electroporation results in more potent tumor vaccination under the examined experimental conditions.

  16. Teratoid Wilms′ tumor - A rare renal tumor

    Directory of Open Access Journals (Sweden)

    Biswanath Mukhopadhyay

    2011-01-01

    Full Text Available Teratoid Wilms′ tumor is an extremely rare renal tumor. We report a case of unilateral teratoid Wilms′ tumor in a 4-year-old girl. The patient was admitted with a right-sided abdominal mass. The mass was arising from the right kidney. Radical nephrectomy was done and the patient had an uneventful recovery. Histopathology report showed teratoid Wilms′ tumor.

  17. What is Metabolic Syndrome?

    Science.gov (United States)

    ... Intramural Research Home / Metabolic Syndrome Metabolic Syndrome Also known as What Is Metabolic syndrome ... metabolic risk factors to be diagnosed with metabolic syndrome. Metabolic Risk Factors A Large Waistline Having a large ...

  18. Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor

    Energy Technology Data Exchange (ETDEWEB)

    Toyonaga, Takuya; Hirata, Kenji; Kobayashi, Kentaro; Manabe, Osamu; Watanabe, Shiro; Hattori, Naoya; Shiga, Tohru; Tamaki, Nagara [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo, Hokkaido (Japan); Yamaguchi, Shigeru [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo, Hokkaido (Japan); Hokkaido University Graduate School of Medicine, Department of Neurosurgery, Sapporo (Japan); Terasaka, Shunsuke; Kobayashi, Hiroyuki [Hokkaido University Graduate School of Medicine, Department of Neurosurgery, Sapporo (Japan); Kuge, Yuji [Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Tanaka, Shinya [Hokkaido University Graduate School of Medicine, Department of Cancer Pathology, Sapporo (Japan); Ito, Yoichi M. [Hokkaido University Graduate School of Medicine, Department of Biostatistics, Sapporo (Japan)

    2017-04-15

    Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV x FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV

  19. Brca1/p53 deficient mouse breast tumor hemodynamics during hyperoxic respiratory challenge monitored by a novel wide-field functional imaging (WiFI) system

    Science.gov (United States)

    Moy, Austin; Kim, Jae G.; Lee, Eva Y. H. P.; Tromberg, Bruce; Cerussi, Albert; Choi, Bernard

    2009-02-01

    Current imaging modalities allow precise visualization of tumors but do not enable quantitative characterization of the tumor metabolic state. Such quantitative information would enhance our understanding of tumor progression and response to treatment, and to our overall understanding of tumor biology. To address this problem, we have developed a wide-field functional imaging (WiFI) instrument which combines two optical imaging modalities, spatially modulated imaging (MI) and laser speckle imaging (LSI). Our current WiFI imaging protocol consists of multispectral imaging in the near infrared (650-980 nm) spectrum, over a wide (7 cm × 5 cm) field of view. Using MI, the spatially-resolved reflectance of sinusoidal patterns projected onto the tissue is assessed, and optical properties of the tissue are estimated using a Monte Carlo model. From the spatial maps of local absorption and reduced scattering coefficients, tissue composition information is extracted in the form of oxy-, deoxy-, and total hemoglobin concentrations, and percentage of lipid and water. Using LSI, the reflectance of a 785 nm laser speckle pattern on the tissue is acquired and analyzed to compute maps of blood perfusion in the tissue. Tissue metabolism state is estimated from the values of blood perfusion, volume and oxygenation state. We currently are employing the WiFI instrument to study tumor development in a BRCA1/p53 deficient mice breast tumor model. The animals are monitored with WiFI during hyperoxic respiratory challenge. At present, four tumors have been measured with WiFI, and preliminary data suggest that tumor metabolic changes during hyperoxic respiratory challenge can be determined.

  20. Rare incidence of tumor lysis syndrome in metastatic prostate cancer following treatment with docetaxel.

    Science.gov (United States)

    Bhardwaj, Sharonlin; Varma, Seema

    2018-03-01

    Tumor lysis syndrome is a serious and sometimes lethal complication of cancer treatment that is comprised of a set of metabolic disturbances along with clinical manifestations. Initiating chemotherapy in bulky, rapidly proliferating tumors causes rapid cell turnover that in turn releases metabolites into circulation that give rise to metabolic derangements that can be dangerous. This syndrome is usually seen in high-grade hematological malignancies. Less commonly, tumor lysis syndrome can present in solid tumors and even rarely in genitourinary tumors. In this report, the authors describe a specific case of tumor lysis syndrome in a patient with metastatic prostate cancer following treatment with docetaxel.

  1. Differential response of idiopathic sporadic tumoral calcinosis to bisphosphonates

    Directory of Open Access Journals (Sweden)

    Karthik Balachandran

    2014-01-01

    Full Text Available Context: Tumoral calcinosis is a disorder of phosphate metabolism characterized by ectopic calcification around major joints. Surgery is the current treatment of choice, but a suboptimal choice in recurrent and multicentric lesions. Aims: To evaluate the efficacy of bisphosphonates for the management of tumoral calcinosis on optimized medical treatment. Settings and Design: The study was done in the endocrine department of a tertiary care hospital in South India. We prospectively studied two patients with recurrent tumoral calcinosis who had failed therapy with phosphate lowering measures. Materials and Methods: After informed consent, we treated both patients with standard age adjusted doses of bisphosphonates for 18 months. The response was assessed by X ray and whole body 99mTc-methylene diphosphonate bone scan at the beginning of therapy and at the end of 1 year. We also estimated serum phosphate levels and urinary phosphate to document serial changes. Results: Two patients (aged 19 and 5 years with recurrent idiopathic hyperphosphatemic tumoral calcinosis, following surgery were studied. Both patients had failed therapy with conventional medical management − low phosphate diet and phosphate binders. They had restriction of joint mobility. Both were given standard doses of oral alendronate and parenteral pamidronate respectively for more than a year, along with phosphate lowering measures. At the end of 1 year, one of the patients had more than 95% and 90% reduction in the size of the lesions in right and left shoulder joints respectively with total improvement in range of motion. In contrast, the other patient (5-year-old had shown no improvement, despite continuing to maintain normophosphatemia following treatment. Conclusions: Bisphosphonate therapy in tumoral calcinosis is associated with lesion resolution and may be used as a viable alternative to surgery, especially in cases with multicentric recurrence or treatment failure to other

  2. Biomarkers of Pediatric Brain Tumors

    Directory of Open Access Journals (Sweden)

    Mark D Russell

    2013-03-01

    Full Text Available Background and Need for Novel Biomarkers: Brain tumors are the leading cause of death by solid tumors in children. Although improvements have been made in their radiological detection and treatment, our capacity to promptly diagnose pediatric brain tumors in their early stages remains limited. This contrasts several other cancers where serum biomarkers such as CA 19-9 and CA 125 facilitate early diagnosis and treatment. Aim: The aim of this article is to review the latest literature and highlight biomarkers which may be of clinical use in the common types of primary pediatric brain tumor. Methods: A PubMed search was performed to identify studies reporting biomarkers in the bodily fluids of pediatric patients with brain tumors. Details regarding the sample type (serum, cerebrospinal fluid or urine, biomarkers analyzed, methodology, tumor type and statistical significance were recorded. Results: A total of 12 manuscripts reporting 19 biomarkers in 367 patients vs. 397 controls were identified in the literature. Of the 19 biomarkers identified, 12 were isolated from cerebrospinal fluid, 2 from serum, 3 from urine, and 2 from multiple bodily fluids. All but one study reported statistically significant differences in biomarker expression between patient and control groups.Conclusions: This review identifies a panel of novel biomarkers for pediatric brain tumors. It provides a platform for the further studies necessary to validate these biomarkers and, in addition, highlights several techniques through which new biomarkers can be discovered.

  3. Neurosurgical treatment of extracerebral tumors

    International Nuclear Information System (INIS)

    Antoniadis, G.; Kretschmer, T.; Braun, V.; Rath, S.; Richter, H.P.

    1998-01-01

    Extracerebral tumors represent 29-30% of the intracranial tumors. Meningiomas rank first in incidence with 13-19%, followed by neurinomas and pituitary adenomas, 6-8% each. Due to their slow growth rate, meningiomas in the initial stages do not produce symptoms. Complete recovery can be achieved by complete removal of the tumor, which in general is possible in case of tumor sites at the convexity. Meningiomas at the basis, or meningiomas spreading into the sinus sagittalis superior often cannot be totally removed, so that for treatment of remaining or recurrent tumors and anaplastic meningiomas, post-operative radiation therapy is recommended. Neurinomas of the nervus acusticus originate at the N. vestibularis and may spread from the Meatus acusticus internus into the brain stem. With the modern methods of microsurgery combined with intraoperative monitoring it is possible to preserve the Nn. facialis and cochlearis and their functions. As an alternative to surgery, radiosurgery techniques have been on trial in the last few years. Via transsphenoidal approach, intra- and suprasellar pituitary adenomas can be completely destroyed. Parasellar tumors can be resected by transcranial approach only. Remaining tumors in the Sinus cavernosus, or recurrent adenomas, should receive post-surgery radiation treatment. (orig./CB) [de

  4. Tumor suppressors: enhancers or suppressors of regeneration?

    Science.gov (United States)

    Pomerantz, Jason H.; Blau, Helen M.

    2013-01-01

    Tumor suppressors are so named because cancers occur in their absence, but these genes also have important functions in development, metabolism and tissue homeostasis. Here, we discuss known and potential functions of tumor suppressor genes during tissue regeneration, focusing on the evolutionarily conserved tumor suppressors pRb1, p53, Pten and Hippo. We propose that their activity is essential for tissue regeneration. This is in contrast to suggestions that tumor suppression is a trade-off for regenerative capacity. We also hypothesize that certain aspects of tumor suppressor pathways inhibit regenerative processes in mammals, and that transient targeted modification of these pathways could be fruitfully exploited to enhance processes that are important to regenerative medicine. PMID:23715544

  5. [Metabolic acidosis].

    Science.gov (United States)

    Regolisti, Giuseppe; Fani, Filippo; Antoniotti, Riccardo; Castellano, Giuseppe; Cremaschi, Elena; Greco, Paolo; Parenti, Elisabetta; Morabito, Santo; Sabatino, Alice; Fiaccadori, Enrico

    2016-01-01

    Metabolic acidosis is frequently observed in clinical practice, especially among critically ill patients and/or in the course of renal failure. Complex mechanisms are involved, in most cases identifiable by medical history, pathophysiology-based diagnostic reasoning and measure of some key acid-base parameters that are easily available or calculable. On this basis the bedside differential diagnosis of metabolic acidosis should be started from the identification of the two main subtypes of metabolic acidosis: the high anion gap metabolic acidosis and the normal anion gap (or hyperchloremic) metabolic acidosis. Metabolic acidosis, especially in its acute forms with elevated anion gap such as is the case of lactic acidosis, diabetic and acute intoxications, may significantly affect metabolic body homeostasis and patients hemodynamic status, setting the stage for true medical emergencies. The therapeutic approach should be first aimed at early correction of concurrent clinical problems (e.g. fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, hemodialysis for acute intoxications etc.), in parallel to the formulation of a diagnosis. In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy.

  6. Prevalence of bone and soft tissue tumors.

    Science.gov (United States)

    Yücetürk, Güven; Sabah, Dündar; Keçeci, Burçin; Kara, Ahmet Duran; Yalçinkaya, Selçuk

    2011-01-01

    Multidisciplinary approach is a necessity for the appropriate diagnosis and treatment of bone and soft tissue tumors. The Ege University Musculoskeletal Tumor Council offers consultation services to other hospitals in the Aegean region. Since 1988 the Council has met weekly and spent approximately 1,500 hours evaluating almost 6,000 patients with suspected skeletal system tumors. Our objective was to present the data obtained from this patient group. A total of 5,658 patients, suspected to have a musculoskeletal tumor, were evaluated retrospectively. Multiple records of the patients due to multiple attendance to the Council were excluded. The prevalance of the bone and soft tissue tumors in these patients were analysed. Malignant mesenchymal tumors accounted for 39.7% of the total patients, benign tumors for 17%, tumor-like lesions for 17.8% and metastatic carsinomas for 8.6%. Malignant bone tumors were 50.2% and malignant soft tissue tumors were 49.8% of all the sarcomas. Among the malignant bone tumors the most common was osteosarcomas at a rate of 33.6%, followed by Ewing-PNET at 25.5%, chondrosarcomas at 19.4% and haematopoietic tumors at 17.6%. Pleomorphic sarcomas (24.5%), liposarcoma (16.4%), synovial sarcoma (13%) and undifferential sarcomas (8.8%) were the most common types of malignant sof tissue tumors. Benign soft tissue tumors (48%), benign cartilage tumors (28%), giant cell tumor (15%) and osteogenic tumors (9%) were found among the benign tumors. Hemangioma, lipoma, agressive fibromatosis, enchondroma, solitary chondroma and osteoid osteoma were the most common tumors in their groups. Lung (27%), breast (24%), gastrointestinal system (10.5%) and kidney (8.2%) carcinomas were the most common primary sites of the bone metastasis. Turkey still lacks a comprehensive series indicating the incidence and diagnostic distribution of bone and soft tissue tumors. The presented data would add to our knowledge on the specific rates of the bone and soft tissue

  7. Effects of canrenone in patients with metabolic syndrome.

    Science.gov (United States)

    Derosa, Giuseppe; Bonaventura, Aldo; Bianchi, Lucio; Romano, Davide; D'Angelo, Angela; Fogari, Elena; Maffioli, Pamela

    2013-11-01

    Metabolic syndrome is becoming a common disease due to a rise in obesity rates among adults. The aim was to evaluate the effects of canrenone compared to placebo on metabolic and inflammatory parameters in patients affected by metabolic syndrome. A total of 145 patients were treated with placebo or canrenone, 50 mg/day, for 3 months and then 50 mg b.i.d. till the end of the study. Blood pressure, body weight, body mass index, fasting plasma glucose (FPG), fasting plasma insulin, HOMA-IR, lipid profile, plasma aldosterone, brain natriuretic peptide, high-sensitivity C-reactive protein (Hs-CRP), tumor necrosis factor-α (TNF-α) and M value were evaluated. A decrease of blood pressure was observed in canrenone group compared to baseline; moreover, systolic blood pressure value recorded after 6 months of canrenone therapy was lower than the one recorded with placebo. Canrenone gave a significant decrease of FPI and HOMA index, and an increase of M value both compared to baseline and to placebo. Canrenone also decreased triglycerides and FPG was not observed with placebo. Canrenone also decreased plasma aldosterone, Hs-CRP and TNF-α compared to baseline and to placebo. Canrenone seems to be effective in reducing some factors involved in metabolic syndrome and in improving insulin-resistance and the inflammatory state observed in these patients.

  8. Metabolic Profiles of Brain Metastases

    Directory of Open Access Journals (Sweden)

    Tone F. Bathen

    2013-01-01

    Full Text Available Metastasis to the brain is a feared complication of systemic cancer, associated with significant morbidity and poor prognosis. A better understanding of the tumor metabolism might help us meet the challenges in controlling brain metastases. The study aims to characterize the metabolic profile of brain metastases of different origin using high resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS to correlate the metabolic profiles to clinical and pathological information. Biopsy samples of human brain metastases (n = 49 were investigated. A significant correlation between lipid signals and necrosis in brain metastases was observed (p < 0.01, irrespective of their primary origin. The principal component analysis (PCA showed that brain metastases from malignant melanomas cluster together, while lung carcinomas were metabolically heterogeneous and overlap with other subtypes. Metastatic melanomas have higher amounts of glycerophosphocholine than other brain metastases. A significant correlation between microscopically visible lipid droplets estimated by Nile Red staining and MR visible lipid signals was observed in metastatic lung carcinomas (p = 0.01, indicating that the proton MR visible lipid signals arise from cytoplasmic lipid droplets. MRS-based metabolomic profiling is a useful tool for exploring the metabolic profiles of metastatic brain tumors.

  9. [Metabolic bone disease osteomalacia].

    Science.gov (United States)

    Reuss-Borst, M A

    2014-05-01

    Osteomalacia is a rare disorder of bone metabolism leading to reduced bone mineralization. Underlying vitamin D deficiency and a disturbed phosphate metabolism (so-called hypophosphatemic osteomalacia) can cause the disease. Leading symptoms are dull localized or generalized bone pain, muscle weakness and cramps as well as increased incidence of falls. Rheumatic diseases, such as polymyalgia rheumatica, rheumatoid arthritis, myositis and fibromyalgia must be considered in the differential diagnosis. Alkaline phosphatase (AP) is typically elevated in osteomalacia while serum phosphate and/or 25-OH vitamin D3 levels are reduced. The diagnosis of osteomalacia can be confirmed by an iliac crest bone biopsy. Histological correlate is reduced or deficient mineralization of the newly synthesized extracellular matrix. Treatment strategies comprise supplementation of vitamin D and calcium and for patients with intestinal malabsorption syndromes vitamin D and calcium are also given parenterally. In renal phosphate wasting syndromes substitution of phosphate is the treatment of choice, except for tumor-induced osteomalacia when removal of the tumor leads to a cure in most cases.

  10. Recent advances in cancer metabolism: a technological perspective.

    Science.gov (United States)

    Kang, Yun Pyo; Ward, Nathan P; DeNicola, Gina M

    2018-04-16

    Cancer cells are highly dependent on metabolic pathways to sustain both their proliferation and adaption to harsh microenvironments. Thus, understanding the metabolic reprogramming that occurs in tumors can provide critical insights for the development of therapies targeting metabolism. In this review, we will discuss recent advancements in metabolomics and other multidisciplinary techniques that have led to the discovery of novel metabolic pathways and mechanisms in diverse cancer types.

  11. Radiotherapy for pediatric brain stem tumors

    International Nuclear Information System (INIS)

    Shcherbenko, O.I.; Parkhomenko, R.A.; Govorina, E.V.; Zelinskaya, N.I.; Ardatova, G.V.; Nechaeva, V.N.

    2000-01-01

    The immediate and short-term results of gamma therapy of brain stem tumors in 24 children were evaluated. All the patients were able to sustain treatment due to adjuvant support with dehydrating and hormonal drugs, and beneficial clinical effect was recorded in 80%. However, magnetic resonance tomography showed no decrease in tumor size. Tumor growth relapsed 3-8 months after radiotherapy. Although total dose ranged 60-72 Gy in 19 patients, there was no clinical evidence of radiation injury [ru

  12. Drug Metabolism

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 3. Drug Metabolism: A Fascinating Link Between Chemistry and Biology. Nikhil Taxak Prasad V Bharatam. General Article Volume 19 Issue 3 March 2014 pp 259-282 ...

  13. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    behind metabolic reactions, importance, and consequences with several ... required for drug action. ... lism, which is catalyzed by enzymes present in the above-men- ... catalyze the transfer of one atom of oxygen to a substrate produc-.

  14. Modulators of arginine metabolism support cancer immunosurveillance

    Directory of Open Access Journals (Sweden)

    Freschi Massimo

    2009-01-01

    Full Text Available Abstract Background Tumor-associated accrual of myeloid derived suppressor cells (MDSC in the blood, lymphoid organs and tumor tissues may lead to perturbation of the arginine metabolism and impairment of the endogenous antitumor immunity. The objective of this study was to evaluate whether accumulation of MDSC occurred in Th2 prone BALB/c and Th1 biased C57BL/6 mice bearing the C26GM colon carcinoma and RMA T lymphoma, respectively, and to investigate whether N(G nitro-L-arginine methyl ester (L-NAME and sildenafil, both modulators of the arginine metabolism, restored antitumor immunity. Results We report here that MDSC accumulate in the spleen and blood of mice irrespective of the mouse and tumor model used. Treatment of tumor-bearing mice with either the phosphodiesterase-5 inhibitor sildenafil or the nitric-oxide synthase (NOS inhibitor L-NAME significantly restrained tumor growth and expanded the tumor-specific immune response. Conclusion Our data emphasize the role of MDSC in modulating the endogenous tumor-specific immune response and underline the anti-neoplastic therapeutic potential of arginine metabolism modulators.

  15. Malignant renal tumors in pediatrics

    International Nuclear Information System (INIS)

    Pena, C.; Torterolo, J.; Irigoyen, B.; Bel, M.; Elias, E.

    2004-01-01

    Introduction: Professionals who work in pediatric oncology, we see childhood cancer as a common disease, but in fact constitutes about 2% of all cancers diagnosed worldwide. Wilms tumor accounts for 6% of all childhood tumors and presentation bilateral accounts for 4-6% of all Wilms tumors diagnosed. Theoretical Framework: In the period between the year 1994-2003 period were attended in the Pediatric Hematology-Oncology Center, a total of 29 cases of malignant renal tumors, corresponding to 86% (25 cases) to Wilms tumor or nephroblastoma tumor. The Wilms is of embryonic origin, capable of metastatic spread, (85% lungs 15% liver). Very sensitive to chemotherapy and radiotherapy, which confers high cure rates (85%); having a multidisciplinary treatment model, combining surgery, chemotherapy, and radiotherapy. The role of nursing in comprehensive cancer care child is essential in the prevention and early detection of side effects or complications. Case report: S.D. currently 10 years old. In 10/1994, at 8 months of age, was diagnosed with bilateral Wilms tumor. On admission her weight was 8200gr with abdominal circumference 50cm. Conducted pre-operative MDT and 02/1995 nephrectomy of the left kidney and right kidney lumpectomy (tumor nodule 420gr. and a 250gr.). MDT begins in 03/1995 01/1996 ending. 09/2003 with abdominal pain and vomiting, and kidney failure. 10/2003 lumpectomy biopsy (sclerotic nodule associated with maturation nephroblastoma). Currently severe renal insufficiency plan enters dialysis. Nursing process: Objectives: 1) To prepare the child and family to the side effects and possible complications of chemotherapy and / or radiotherapy 2) Prevent and minimize related complications tumor and / or treatment. Care Plan comprises four stages: A) rating and customer income. B) Implement care chemotherapy C) post-operative Care D) Implement radiation care

  16. Metabolic Myopathies.

    Science.gov (United States)

    Tarnopolsky, Mark A

    2016-12-01

    Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal muscle. Impairments in glycolysis/glycogenolysis (glycogen-storage disease), fatty acid transport and oxidation (fatty acid oxidation defects), and the mitochondrial respiratory chain (mitochondrial myopathies) represent the majority of known defects. The purpose of this review is to develop a diagnostic and treatment algorithm for the metabolic myopathies. The metabolic myopathies can present in the neonatal and infant period as part of more systemic involvement with hypotonia, hypoglycemia, and encephalopathy; however, most cases present in childhood or in adulthood with exercise intolerance (often with rhabdomyolysis) and weakness. The glycogen-storage diseases present during brief bouts of high-intensity exercise, whereas fatty acid oxidation defects and mitochondrial myopathies present during a long-duration/low-intensity endurance-type activity or during fasting or another metabolically stressful event (eg, surgery, fever). The clinical examination is often normal between acute events, and evaluation involves exercise testing, blood testing (creatine kinase, acylcarnitine profile, lactate, amino acids), urine organic acids (ketones, dicarboxylic acids, 3-methylglutaconic acid), muscle biopsy (histology, ultrastructure, enzyme testing), MRI/spectroscopy, and targeted or untargeted genetic testing. Accurate and early identification of metabolic myopathies can lead to therapeutic interventions with lifestyle and nutritional modification, cofactor treatment, and rapid treatment of rhabdomyolysis.

  17. Animal metabolism

    International Nuclear Information System (INIS)

    Walburg, H.E.

    1977-01-01

    Studies on placental transport included the following: clearance of tritiated water as a baseline measurement for transport of materials across perfused placentas; transport of organic and inorganic mercury across the perfused placenta of the guinea pig in late gestation; and transport of cadmium across the perfused placenta of the guinea pig in late gestation. Studies on cadmium absorption and metabolism included the following: intestinal absorption and retention of cadmium in neonatal rats; uptake and distribution of an oral dose of cadmium in postweanling male and female, iron-deficient and normal rats; postnatal viability and growth in rat pups after oral cadmium administration during gestation; and the effect of calcium and phosphorus on the absorption and toxicity of cadmium. Studies on gastrointestinal absorption and mineral metabolism included: uptake and distribution of orally administered plutonium complex compounds in male mice; gastrointestinal absorption of 144 Ce in the newborn mouse, rat, and pig; and gastrointestinal absorption of 95 Nb by rats of different ages. Studies on iodine metabolism included the following: influence of thyroid status and thiocyanate on iodine metabolism in the bovine; effects of simulated fallout radiation on iodine metabolism in dairy cattle; and effects of feeding iodine binding agents on iodine metabolism in the calf

  18. Pathophysiological aspects of malignant brain tumors studied with positron emission tomography

    International Nuclear Information System (INIS)

    Jarden, J.O.

    1994-01-01

    To further understand the control of brain tumor fluid balance and pH, the following studies were undertaken. The transport of a water soluble molecule across the brain and tumor capillary endothelium was studied during glucocorticoid and radiation treatment. The brain and brain-tumor acidity (pH) was evaluated as a single measurement in patients receiving a low maintenance dose of glucocorticoid. Transport changes and pH were measured in 61 patients with cerebral tumors using 82 Rubidium ( 82 Rb) and 11 C-Dimethyloxa-zolidindione ( 11 C-DMO), respectively, and Positron Emission Tomography (PET). Supplementary studies of tumor and contralateral brain blood flow and blood volume using the C 15 O 2 /PET and C 15 O/PET technique, respectively, were included to validate the 82 Rb/PET model and obtain further information. A total of 125 PET scans were performed. Supplementary studies were undertaken to estimate delay of blood registration and form distribution of arterial blood isotope activity curves. Blood-to-tumor barrier transport was outlined at baseline and at 6 and 24 hours after the start of glucocorticoid treatment, finding a significant decrease in the transpfort. Radiation treatment (2-6 gray) did not alter the blood-to-tumor barrier transport when restudied within one hour in patients receiving glucocorticoid. The pH in brain tumors was as high as 6.88-7.26, suggesting that tumors are more alkalotic than the normal brain. The permeability surface area product and the permeability coefficient were determined form the 82 Rb/PET transport and C 15 O 2 /PET flow studies. Baseline permeability values were comparable to the literature values both for 82 Rb and potassium. No difference in tissue blood volume was seen between 82 Rb/PET and C 15 O/PET models and was of the same magnitude in the tumor and the contralateral tissue. Aspects of tumor alkalosis, tumor edema production, glucocorticoid edema clearance, and relationship between the anti-edema effect of

  19. Pediatric Brain Tumor Foundation

    Science.gov (United States)

    ... navigate their brain tumor diagnosis. WATCH AND SHARE Brain tumors and their treatment can be deadly so ... Pediatric Central Nervous System Cancers Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  20. Brain Tumors (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Brain Tumors KidsHealth / For Parents / Brain Tumors What's in ... radiation therapy or chemotherapy, or both. Types of Brain Tumors There are many different types of brain ...

  1. Childhood Brain Tumors

    Science.gov (United States)

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  2. Malignant bone tumors

    International Nuclear Information System (INIS)

    Zedgenidze, G.A.; Kishkovskij, A.N.; Elashov, Yu.G.

    1984-01-01

    Clinicoroentgenologic semiotics of malignant bone tumors as well as metastatic bone tumors are presented. Diagnosis of malignant and metastatic bone tumors should be always complex, representing a result of cooperation of a physician, roentgenologist, pathoanatomist

  3. Tumors and Pregnancy

    Science.gov (United States)

    Tumors during pregnancy are rare, but they can happen. Tumors can be either benign or malignant. Benign tumors aren't cancer. Malignant ones are. The most common cancers in pregnancy are breast cancer, cervical cancer, lymphoma, and melanoma. ...

  4. Neuroendocrine Tumor: Statistics

    Science.gov (United States)

    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 01/ ... the body. It is important to remember that statistics on the survival rates for people with a ...

  5. Real-time PCR analysis of genes encoding tumor antigens in esophageal tumors and a cancer vaccine

    DEFF Research Database (Denmark)

    Weinert, Brian T; Krishnadath, Kausilia K; Milano, Francesca

    2009-01-01

    Tumor antigens are the primary target of therapeutic cancer vaccines. We set out to define and compare the expression pattern of tumor antigen genes in esophagus carcinoma biopsies and in an allogeneic tumor lysate-based cancer vaccine, MelCancerVac. Cells used for vaccine production were treated...... in the production of the vaccine. Quantitative PCR was used to assay 74 tumor antigen genes in patients with squamous cell carcinoma of the esophagus. 81% (13/16) of tumors expressed more than five cancer/testis (CT) antigens. A total of 96 genes were assayed in the tumor cell clone (DDM1.7) used to make tumor cell...

  6. Tumor segmentation of whole-body magnetic resonance imaging in neurofibromatosis type 1 patients: tumor burden correlates

    Energy Technology Data Exchange (ETDEWEB)

    Heffler, Michael A.; Xi, Yin; Chhabra, Avneesh [University of Texas Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); Le, Lu Q. [University of Texas Southwestern Medical Center, Department of Dermatology, Dallas, TX (United States)

    2017-01-15

    Segmentation of whole-body MRI (WBMRI) to assess the feasibility, quantitate the total tumor volume (tumor burden) in patients with neurofibromatosis type 1 (NF1) and examine associations with demographic, disease-related and anthropomorphic features. A consecutive series of patients with NF1 underwent WBMRI and were reviewed for tumors. Tumors were segmented using a semiautomated software-based tool. Tumors were classified as superficial or deep and discrete or plexiform. Segmentation times were recorded. Segmentation yielded the quantity and tumor burden of superficial, internal and plexiform tumors. Correlations between segmentation data and demographic, disease-related and anthropomorphic features were examined. Fifteen patients were evaluated (42.3 ± 13.6 years, 10 female, 5 male). Segmentation times were a median of 30 min and yielded 2,328 tumors (1,582 superficial, 746 internal and 23 plexiform). One tumor was malignant. Tumor counts ranged from 14 to 397. Tumor burden ranged from 6.95 cm3 to 571 cm3. Individual tumor volume ranged from 0.0120 cm3 to 298 cm3. Significant correlation was found between the total volume of superficial tumors and height (ρ = 0.5966, p < 0.02). Male patients had higher overall tumor burdens (p < 0.05) and higher superficial tumor burden (p < 0.03). Patients with negative family history had more tumors (p < 0.05). Segmentation of WBMRI in patients with NF1 is feasible and elucidates meaningful relationships among disease phenotype, anthropomorphic and demographic features. (orig.)

  7. Tumor segmentation of whole-body magnetic resonance imaging in neurofibromatosis type 1 patients: tumor burden correlates

    International Nuclear Information System (INIS)

    Heffler, Michael A.; Xi, Yin; Chhabra, Avneesh; Le, Lu Q.

    2017-01-01

    Segmentation of whole-body MRI (WBMRI) to assess the feasibility, quantitate the total tumor volume (tumor burden) in patients with neurofibromatosis type 1 (NF1) and examine associations with demographic, disease-related and anthropomorphic features. A consecutive series of patients with NF1 underwent WBMRI and were reviewed for tumors. Tumors were segmented using a semiautomated software-based tool. Tumors were classified as superficial or deep and discrete or plexiform. Segmentation times were recorded. Segmentation yielded the quantity and tumor burden of superficial, internal and plexiform tumors. Correlations between segmentation data and demographic, disease-related and anthropomorphic features were examined. Fifteen patients were evaluated (42.3 ± 13.6 years, 10 female, 5 male). Segmentation times were a median of 30 min and yielded 2,328 tumors (1,582 superficial, 746 internal and 23 plexiform). One tumor was malignant. Tumor counts ranged from 14 to 397. Tumor burden ranged from 6.95 cm3 to 571 cm3. Individual tumor volume ranged from 0.0120 cm3 to 298 cm3. Significant correlation was found between the total volume of superficial tumors and height (ρ = 0.5966, p < 0.02). Male patients had higher overall tumor burdens (p < 0.05) and higher superficial tumor burden (p < 0.03). Patients with negative family history had more tumors (p < 0.05). Segmentation of WBMRI in patients with NF1 is feasible and elucidates meaningful relationships among disease phenotype, anthropomorphic and demographic features. (orig.)

  8. Peripheral epithelial odontogenic tumor

    International Nuclear Information System (INIS)

    Carzoglio, J.; Tancredi, N.; Capurro, S.; Ravecca, T.; Scarrone, P.

    2006-01-01

    A new case of peripheral epithelial odontogenic tumor (Pindborg tumor) is reported. It is localized in the superior right gingival region, a less frequent site, and has the histopathological features previously reported. Immunochemical studies were performed, revealing a differential positive stain to cytokeratins in tumor cells deeply seated in the tumor mass, probably related to tumoral cell heterogeneity.Interestingly, in this particular case S-100 protein positive reactivity was also detected in arborescent cells intermingled with tumoral cells, resembling Langerhans cells. Even though referred in the literature in central Pindborg tumors, no references were found about their presence in peripheral tumors, like the one that is presented here

  9. Pretreatment tumor SUV{sub max} predicts disease-specific and overall survival in patients with head and neck soft tissue sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Seung Cheol; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon [University of Ulsan College of Medicine, Departments of Otolaryngology, Asan Medical Center, Songpa-gu, Seoul (Korea, Republic of); Oh, Jungsu S.; Moon, Hyojeong; Kim, Jae Seung [University of Ulsan College of Medicine, Departments of Nuclear Medicine, Asan Medical Center, Seoul (Korea, Republic of); Cho, Kyung-Ja [University of Ulsan College of Medicine, Departments of Pathology, Asan Medical Center, Seoul (Korea, Republic of)

    2017-01-15

    Head and neck soft tissue sarcoma (HNSTS) is a rare type of tumor with various histological presentations and clinical behaviors. {sup 18}F-FDG PET/CT is being increasingly used for staging, grading, and predicting treatment outcomes in various types of human cancers, although this modality has been rarely studied in the survival prediction of HNSTS. Here we examined the prognostic value of tumor metabolic parameters measured using {sup 18}F-FDG PET/CT in patients with HNSTS. This study included 36 consecutive patients with HNSTS who underwent {sup 18}F-FDG PET/CT scanning prior to treatment at our institution. Tumor gross total volume (GTV) was measured from pretreatment contrast-enhanced CT scans, and maximum standardized uptake value (SUV{sub max}), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured using pretreatment {sup 18}F-FDG PET/CT scans. Univariate and multivariate Cox proportional hazard regression analyses were used to identify associations between imaging parameters and disease-specific survival (DSS) or overall survival (OS). Univariate analyses showed that SUV{sub max}, MTV, and TLG, but not GTV, were significantly associated with DSS and OS (all P < 0.05). After controlling for clinicopathological factors, SUV{sub max}, MTV, and TLG were significantly associated with DSS and OS (all P < 0.05). Patients with a tumor SUV{sub max} value of >7.0 experienced an approximately fivefold increase in mortality in terms of DSS and OS relative to those with a tumor SUV{sub max} <7.0. Quantitative metabolic measurements on pretreatment {sup 18}F-FDG PET/CT can yield values that are significantly predictive of survival after treatment for HNSTS. (orig.)

  10. [Metabolic myopathies].

    Science.gov (United States)

    Papazian, Óscar; Rivas-Chacón, Rafael

    2013-09-06

    To review the metabolic myopathies manifested only by crisis of myalgias, cramps and rigidity of the muscles with decreased voluntary contractions and normal inter crisis neurologic examination in children and adolescents. These metabolic myopathies are autosomic recessive inherited enzymatic deficiencies of the carbohydrates and lipids metabolisms. The end result is a reduction of intra muscle adenosine triphosphate, mainly through mitochondrial oxidative phosphorylation, with decrease of available energy for muscle contraction. The one secondary to carbohydrates intra muscle metabolism disorders are triggered by high intensity brief (fatty acids metabolism disorders are triggered by low intensity prolonged (> 10 min) exercises. The conditions in the first group in order of decreasing frequency are the deficiencies of myophosforilase (GSD V), muscle phosphofructokinase (GSD VII), phosphoglycerate mutase 1 (GSD X) and beta enolase (GSD XIII). The conditions in the second group in order of decreasing frequency are the deficiencies of carnitine palmitoyl transferase II and very long chain acyl CoA dehydrogenase. The differential characteristics of patients in each group and within each group will allow to make the initial presumptive clinical diagnosis in the majority and then to order only the necessary tests to achieve the final diagnosis. Treatment during the crisis includes hydration, glucose and alkalinization of urine if myoglobin in blood and urine are elevated. Prevention includes avoiding exercise which may induce the crisis and fasting. The prognosis is good with the exception of rare cases of acute renal failure due to hipermyoglobinemia because of severe rabdomyolisis.

  11. The expression and regulation of glucose transporters in tumor cells

    Directory of Open Access Journals (Sweden)

    Pengfei Zhao

    2016-12-01

    Full Text Available Glucose transporter proteins are involved in many physiological and biochemical processes. In particular, the high expressions of sodium-glucose cotransporter and glucose transporter proteins in tumor cells show that these two transporters play a key role in tumor cell metabolism. Studying the crystal structure and conformation of human glucose transporter proteins has enabled the development of drugs based on specific binding sites, opening up a new path towards more effective cancer treatments. This mini review serves to summarize our existing understanding of the metabolic pathways of tumor cells, focusing on the roles of glucose transporter proteins.

  12. DNA Damage, Repair, and Cancer Metabolism

    Science.gov (United States)

    Turgeon, Marc-Olivier; Perry, Nicholas J. S.; Poulogiannis, George

    2018-01-01

    Although there has been a renewed interest in the field of cancer metabolism in the last decade, the link between metabolism and DNA damage/DNA repair in cancer has yet to be appreciably explored. In this review, we examine the evidence connecting DNA damage and repair mechanisms with cell metabolism through three principal links. (1) Regulation of methyl- and acetyl-group donors through different metabolic pathways can impact DNA folding and remodeling, an essential part of accurate double strand break repair. (2) Glutamine, aspartate, and other nutrients are essential for de novo nucleotide synthesis, which dictates the availability of the nucleotide pool, and thereby influences DNA repair and replication. (3) Reactive oxygen species, which can increase oxidative DNA damage and hence the load of the DNA-repair machinery, are regulated through different metabolic pathways. Interestingly, while metabolism affects DNA repair, DNA damage can also induce metabolic rewiring. Activation of the DNA damage response (DDR) triggers an increase in nucleotide synthesis and anabolic glucose metabolism, while also reducing glutamine anaplerosis. Furthermore, mutations in genes involved in the DDR and DNA repair also lead to metabolic rewiring. Links between cancer metabolism and DNA damage/DNA repair are increasingly apparent, yielding opportunities to investigate the mechanistic basis behind potential metabolic vulnerabilities of a substantial fraction of tumors. PMID:29459886

  13. Effects of Synchronization of Carbohydrate and Protein Supply in Total Mixed Ration with Korean Rice Wine Residue on Ruminal Fermentation, Nitrogen Metabolism and Microbial Protein Synthesis in Holstein Steers

    Directory of Open Access Journals (Sweden)

    Min Yu Piao

    2012-11-01

    Full Text Available Three Holstein steers in the growing phase, each with a ruminal cannula, were used to test the hypothesis that the synchronization of the hourly rate of carbohydrate and nitrogen (N released in the rumen would increase the amount of retained nitrogen for growth and thus improve the efficiency of microbial protein synthesis (EMPS. In Experiment 1, in situ degradability coefficients of carbohydrate and N in feeds including Korean rice wine residue (RWR were determined. In Experiment 2, three total mixed ration (TMR diets having different rates of carbohydrate and N release in the rumen were formulated using the in situ degradability of the feeds. All diets were made to contain similar contents of crude protein (CP and neutral detergent fiber (NDF but varied in their hourly pattern of nutrient release. The synchrony index of the three TMRs was 0.51 (LS, 0.77 (MS and 0.95 (HS, respectively. The diets were fed at a restricted level (2% of the animal’s body weight in a 3×3 Latin-square design. Synchronizing the hourly supply of energy and N in the rumen did not significantly alter the digestibility of dry matter, organic matter, crude protein, NDF or acid detergent fiber (ADF (p>0.05. The ruminal NH3-N content of the LS group at three hours after feeding was significantly higher (p0.05. In addition, the purine derivative (PD excretion in urine and microbial-N production (MN among the three groups were not significantly different (p>0.05. In conclusion, synchronizing dietary energy and N supply to the rumen did not have a major effect on nutrient digestion or microbial protein synthesis (MPS in Holstein steers.

  14. Quantification of patterns of regional cardiac metabolism

    International Nuclear Information System (INIS)

    Lear, J.L.; Ackermann, R.F.

    1990-01-01

    To quantitatively map and compare patterns of regional cardiac metabolism with greater spatial resolution than is possible with positron emission tomography (PET), the authors developed autoradiographic techniques for use with combinations of radiolabeled fluorodeoxyglucose (FDG), glucose (GLU), and acetate (ACE) and applied the techniques to normal rats. Kinetic models were developed to compare GLU-based oxidative glucose metabolism with FDG-based total glucose metabolism (oxidative plus anaerobic) and to compare ACE-based overall oxidative metabolism with FDG-based total glucose metabolism. GLU-based metabolism generally paralleled FDG-based metabolism, but divergence occurred in certain structures such as the papillary muscles, where FDG-based metabolism was much greater. ACE-based metabolism also generally paralleled FDG-based metabolism, but again, the papillary muscles had relatively greater FDG-based metabolism. These discrepancies between FDG-based metabolism and GLU- or ACE-based metabolism suggest the presence of high levels of anaerobic glycolysis. Thus, the study indicates that anaerobic glycolysis, in addition to occurring in ischemic or stunned myocardium (as has been shown in recent PET studies), occurs normally in specific cardiac regions, despite the presence of abundant oxygen

  15. Radiological diagnostics of skeletal tumors

    International Nuclear Information System (INIS)

    Uhl, M.; Herget, G.W.

    2008-01-01

    The book contains contributions concerning the following topics: 1. introduction and fundamentals: WHO classification of bone tumors, imaging diagnostics and their function; localization, typical clinical and radiological criteria, TNM classification and status classification, invasive tumor diagnostics; 2. specific tumor diagnostics: chondrogenic bone tumors, osseous tumors, connective tissue bony tumors, osteoclastoma, osteomyelogenic bone tumors, vascular bone tumors, neurogenic bone tumors, chordoma; adamantinoma of the long tubular bone; tumor-like lesions, bony metastases, bone granulomas, differential diagnostics: tumor-like lesions

  16. Total knee arthroplasty in ochronosis

    Directory of Open Access Journals (Sweden)

    Vaibhav G. Patel, MBBS

    2015-09-01

    Full Text Available Alkaptonuria is disorder of tyrosine metabolism due to deficiency of homogentisic oxidase characterized by excretion of homogentisic acid in urine, deposition of oxidized homogensitate pigments in connective tissues and articular cartilages (ochronosis. The result is dark pigmentation and weakening of the tissues resulting in chronic inflammation and osteoarthritis. Management of alkaptonuric ochronic osteoarthritis is usually symptomatic and replacements have comparable outcomes to osteoarthritis in patients without ochronosis. I report a case of a patient with ochronosis of knee treated with total knee replacement and report operative pearls for surgery in this rare disorder.

  17. Bone scintigraphic patterns in patients of tumor induced osteomalacia

    International Nuclear Information System (INIS)

    Sood, Ashwani; Agarwal, Kanhaiyalal; Shukla, Jaya; Goel, Reema; Dhir, Varun; Bhattacharya, Anish; Rai Mittal, Bhagwant

    2013-01-01

    Tumor induced osteomalacia (TIO) or oncogenic osteomalacia is a rare condition associated with small tumor that secretes one of the phosphaturic hormones, i.e., fibroblast growth factor 23, resulting in abnormal phosphate metabolism. Patients may present with non-specific symptoms leading to delay in the diagnosis. Extensive skeletal involvement is frequently seen due to delay in the diagnosis and treatment. The small sized tumor and unexpected location make the identification of tumor difficult even after diagnosis of osteogenic osteomalacia. The bone scan done for the skeletal involvement may show the presence of metabolic features and the scan findings are a sensitive indicator of metabolic bone disorders. We present the bone scan findings in three patients diagnosed to have TIO

  18. Front instabilities and invasiveness of simulated 3D avascular tumors.

    Directory of Open Access Journals (Sweden)

    Nikodem J Poplawski

    2010-05-01

    Full Text Available We use the Glazier-Graner-Hogeweg model to simulate three-dimensional (3D, single-phenotype, avascular tumors growing in an homogeneous tissue matrix (TM supplying a single limiting nutrient. We study the effects of two parameters on tumor morphology: a diffusion-limitation parameter defined as the ratio of the tumor-substrate consumption rate to the substrate-transport rate, and the tumor-TM surface tension. This initial model omits necrosis and oxidative/hypoxic metabolism effects, which can further influence tumor morphology, but our simplified model still shows significant parameter dependencies. The diffusion-limitation parameter determines whether the growing solid tumor develops a smooth (noninvasive or fingered (invasive interface, as in our earlier two-dimensional (2D simulations. The sensitivity of 3D tumor morphology to tumor-TM surface tension increases with the size of the diffusion-limitation parameter, as in 2D. The 3D results are unexpectedly close to those in 2D. Our results therefore may justify using simpler 2D simulations of tumor growth, instead of more realistic but more computationally expensive 3D simulations. While geometrical artifacts mean that 2D sections of connected 3D tumors may be disconnected, the morphologies of 3D simulated tumors nevertheless correlate with the morphologies of their 2D sections, especially for low-surface-tension tumors, allowing the use of 2D sections to partially reconstruct medically-important 3D-tumor structures.

  19. Clinical Characteristics and Metabolic Features of Patients with Adrenal Incidentalomas with or without Subclinical Cushing's Syndrome

    Directory of Open Access Journals (Sweden)

    Bo-Yeon Kim

    2014-12-01

    Full Text Available BackgroundThe aim of this study was to examine the clinical characteristics of adrenal incidentalomas discovered by computed tomography (CT and to investigate metabolic features of subclinical Cushing's syndrome (SCS in patients with adrenal incidentalomas in a tertiary hospital in Korea.MethodsThis retrospective study examined the clinical aspects of 268 patients with adrenal incidentalomas discovered by CT at Soonchunhyang University Bucheon Hospital. Clinical data and endocrine function of the patients as well as histological findings were obtained from medical records, while anatomic characteristics were analyzed by reviewing imaging studies. Hormonal tests for pheochromocytoma, Cushing's syndrome, and aldosterone-secreting adenoma were performed.ResultsMost (n=218, 81.3% cases were nonfunctioning tumors. Of the 50 patients with functioning tumors (18.7%, 19 (7.1% were diagnosed with SCS, nine (3.4% with overt Cushing's syndrome, 12 (4.5% with primary aldosteronism, and 10 (3.7% with pheochromocytoma. Malignant tumors (both primary and metastatic were rare (n=2, 0.7%. Body mass index, fasting glucose, hemoglobin A1c, and total cholesterol were significantly higher in patients with SCS in comparison with those with nonfunctioning tumors. The prevalence of type 2 diabetes mellitus and hypertension were significantly higher in patients with SCS compared with those with nonfunctioning tumors.ConclusionFunctioning tumors, especially those with subclinical cortisol excess, are commonly found in patients with adrenal incidentalomas, although malignancy is rare. In addition, patients with SCS in adrenal incidentalomas have adverse metabolic and cardiovascular profiles.

  20. RNA-Sequencing of Primary Retinoblastoma Tumors Provides New Insights and Challenges Into Tumor Development

    Directory of Open Access Journals (Sweden)

    Sailaja V. Elchuri

    2018-05-01

    Full Text Available Retinoblastoma is rare tumor of the retina caused by the homozygous loss of the Retinoblastoma 1 tumor suppressor gene (RB1. Loss of the RB1 protein, pRB, results in de-regulated activity of the E2F transcription factors, chromatin changes and developmental defects leading to tumor development. Extensive microarray profiles of these tumors have enabled the identification of genes sensitive to pRB disruption, however, this technology has a number of limitations in the RNA profiles that they generate. The advent of RNA-sequencing has enabled the global profiling of all of the RNA within the cell including both coding and non-coding features and the detection of aberrant RNA processing events. In this perspective, we focus on discussing how RNA-sequencing of rare Retinoblastoma tumors will build on existing data and open up new area’s to improve our understanding of the biology of these tumors. In particular, we discuss how the RB-research field may be to use this data to determine how RB1 loss results in the expression of; non-coding RNAs, causes aberrant RNA processing events and how a deeper analysis of metabolic RNA changes can be utilized to model tumor specific shifts in metabolism. Each section discusses new opportunities and challenges associated with these types of analyses and aims to provide an honest assessment of how understanding these different processes may contribute to the treatment of Retinoblastoma.

  1. Organ-Tumor-on-a-Chip for Chemosensitivity Assay: A Critical Review

    Directory of Open Access Journals (Sweden)

    Navid Kashaninejad

    2016-07-01

    Full Text Available With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death worldwide. However, the emerging field of microfluidics can potentially shed light on this puzzling disease. Unique characteristics of microfluidic chips (also known as micro-total analysis system make them excellent candidates for biological applications. The ex vivo approach of tumor-on-a-chip is becoming an indispensable part of personalized medicine and can replace in vivo animal testing as well as conventional in vitro methods. In tumor-on-a-chip, the complex three-dimensional (3D nature of malignant tumor is co-cultured on a microfluidic chip and high throughput screening tools to evaluate the efficacy of anticancer drugs are integrated on the same chip. In this article, we critically review the cutting edge advances in this field and mainly categorize each tumor-on-a-chip work based on its primary organ. Specifically, design, fabrication and characterization of tumor microenvironment; cell culture technique; transferring mechanism of cultured cells into the microchip; concentration gradient generators for drug delivery; in vitro screening assays of drug efficacy; and pros and cons of each microfluidic platform used in the recent literature will be discussed separately for the tumor of following organs: (1 Lung; (2 Bone marrow; (3 Brain; (4 Breast; (5 Urinary system (kidney, bladder and prostate; (6 Intestine; and (7 Liver. By comparing these microchips, we intend to demonstrate the unique design considerations of each tumor-on-a-chip based on primary organ, e.g., how microfluidic platform of lung-tumor-on-a-chip may differ from liver-tumor-on-a-chip. In addition, the importance of heart–liver–intestine co-culture with microvasculature in tumor-on-a-chip devices for in vitro chemosensitivity assay will be discussed. Such system would be able to completely evaluate the absorption, distribution, metabolism, excretion and toxicity (ADMET of

  2. Liver Tumors (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Liver Tumors KidsHealth / For Parents / Liver Tumors What's in this article? Types of Tumors ... Cancerous) Tumors Symptoms Diagnosis Treatment Coping Print The liver is the body's largest solid organ. Lying next ...

  3. Nucleotide Metabolism

    DEFF Research Database (Denmark)

    Martinussen, Jan; Willemoës, M.; Kilstrup, Mogens

    2011-01-01

    Metabolic pathways are connected through their utilization of nucleotides as supplier of energy, allosteric effectors, and their role in activation of intermediates. Therefore, any attempt to exploit a given living organism in a biotechnological process will have an impact on nucleotide metabolis...

  4. Endocrine tumors other than thyroid tumors

    International Nuclear Information System (INIS)

    Takeichi, Norio; Dohi, Kiyohiko

    1992-01-01

    This paper discusses the tendency for the occurrence of tumors in the endocrine glands, other than the thyroid gland, in A-bomb survivors using both autopsy and clinical data. ABCC-RERF sample data using 4136 autopsy cases (1961-1977) revealed parathyroid tumors in 13 A-bomb survivors, including 3 with the associated hyperparathyroidism, with the suggestion of dose-dependent increase in the occurrence of tumors. Based on clinical data from Hiroshima University, 7 (46.7%) of 15 parathyroid tumors cases were A-bomb survivors. Data (1974-1987) from the Tumor Registry Committee (TRC) in Hiroshima Prefecture revealed that a relative risk of parathyroid tumors was 5.6 times higher in the entire group of A-bomb survivors and 16.2 times higher in the group of heavily exposed A-bomb survivors, suggesting the dose-dependent increase in their occurrence. Adrenal tumors were detected in 47 of 123 cases from the TRC data, and 15 (31.5%) of these 47 were A-bomb survivors. Particularly, 11 cases of adrenal tumors associated with Cushing syndrome included 6 A-bomb survivors (54.5%). The incidence of multiple endocrine gonadial tumors (MEGT) tended to be higher with increasing exposure doses; and the 1-9 rad group, the 10-99 rad group, and the 100 or more rad group had a risk of developing MEGT of 4.1, 5.7, and 7.1, respectively, relative to both the not-in the city group and the 0 rad group. These findings suggested that there is a correlation between A-bomb radiation and the occurrence of parathyroid tumors (including hyperparathyroidism), adrenal tumors associated with Cushing syndrome and MEGT (especially, the combined thyroid and ovarian tumors and the combined thyroid and parathyroid tumors). (N.K.)

  5. Development of {sup 18}F-FDG ([F-18]-2-fluoro-2-deoxy-D-glucose) injection for imaging of tumor reflecting glucose metabolism. Results of preclinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Ino, Sento; Shimada, Takayuki; Kanagawa, Masaru; Suzuki, Noriaki; Kondo, Susumu; Shirakami, Yoshifumi; Ito, Osamu; Kato-Azuma, Makoto [Nihon Medi-Physics Co., Ltd., Sodegaura, Chiba (Japan). Research Center

    1999-07-01

    Fluorine-18-2-fluoro-2-deoxy-D-glucose ({sup 18}F-FDG) injection was prepared by a modification of a method originally developed by Hamacher et al. The dosage form is the injectable solution (2 ml) containing 185 MBq of {sup 18}F-FDG at a calibration time. Preclinical studies of the agent were performed. Its radiochemical purity is more than 95% and expiration time is 4 hours after the calibration time at ambient temperature. No toxicity was observed with up to 200 mg/kg and 100 mg/kg of non-radioactive FDG intravenously injected to rats and dogs in single dose toxicity tests, respectively. Biodistribution studies demonstrated that the radioactivity was mainly distributed into brain (3.0 to 3.3% I.D./Organ at 30 minutes) and heart (4.2 to 5.8% I.D./Organ at 1 to 3 hours) after intravenous injection of the agent to normal rats. In a tumor transplanted mouse model (colon 26), tumor uptake was 10.9{+-}3.5% I.D./g at 1 hr after intravenous injection of the agent, the radioactivity was retained until 3 hours. The radiation absorbed dose was estimated according to the MIRD Pamphlet based on the biodistribution data both in humans reported by Mejia et al. and rats described in this report. The radiation absorbed dose was not higher than those of commercially available radiopharmaceuticals. In conclusion, the {sup 18}F-FDG injection is expected to be useful for further clinical application. (author)

  6. Investigating mechanisms of alkalinization for reducing primary breast tumor invasion.

    Science.gov (United States)

    Robey, Ian F; Nesbit, Lance A

    2013-01-01

    The extracellular pH (pHe) of many solid tumors is acidic as a result of glycolytic metabolism and poor perfusion. Acidity promotes invasion and enhances metastatic potential. Tumor acidity can be buffered by systemic administration of an alkaline agent such as sodium bicarbonate. Tumor-bearing mice maintained on sodium bicarbonate drinking water exhibit fewer metastases and survive longer than untreated controls. We predict this effect is due to inhibition of tumor invasion. Reducing tumor invasion should result in fewer circulating tumor cells (CTCs). We report that bicarbonate-treated MDA-MB-231 tumor-bearing mice exhibited significantly lower numbers of CTCs than untreated mice (P cancer where systemic alkalinization slows the rate of invasion.

  7. Application of tumor markers in the immunodiagnosis of cancer

    International Nuclear Information System (INIS)

    Gelder, F.B.; Barr, L.H.; Goldman, L.I.

    1983-01-01

    Recently, research directed toward the detection of both tumor-specific and tumor-related products has intensified for several reasons. 1. The growing knowledge of tumor metabolism has lead some investigators to hypothesize that most, if not all, malignant tumors produce these substances. 2. The use of multiple tumor markers appears more valuable than application of single markers. 3. The availability of highly sensitive and specific immunological methods provides the tools to measure substances which previously could not be assayed. 4. As additional information evolves, the events associated with malignant transformation and tumor behaviour may become clear. Tumor-related products include immune markers, altered cell surface membranes, as well as fetal and/or ectopic proteins, to name but a few. The synthesis of fetal and/or ectopic proteins occurs in several cancers. These have served as the basis for most immunodiagnostic tests and comprise the major thrust of this review

  8. Should direct measurements of tumor oxygenation relate to the radiobiological hypoxic fraction of a tumor?

    International Nuclear Information System (INIS)

    Fenton, Bruce M.; Kiani, Mohammad F.; Siemann, Dietmar W.

    1995-01-01

    Purpose: Numerous previous studies have attempted to relate the radiobiological hypoxic fraction (HF) to direct measures of tumor oxygenation such as HbO 2 saturations, tumor pO 2 levels, or hypoxic cell labeling. Although correlations have been found within tumor lines, no overall relationships were seen across tumor lines. The current objective was to examine the effect on HF of changes in the fractions of the oxygenated and anoxic tumor cells that remain clonogenic. Methods and Materials: A mathematical model was developed that relates the HF to direct measures of tumor oxygenation. The primary assumptions were that: (a) the tumor is divided into distinct compartments of either fully oxygenated or fully anoxic cells, and (b) the survival of the oxygenated cells is negligible compared to that of the anoxic cells. Based on these assumptions, the HF is plotted as a function of the fractions of clonogenic or nonclonogenic, and oxygenated or anoxic cells. Results: If all cells are clonogenic, then the HF equals the fraction of anoxic cells. If a higher fraction of anoxic than oxygenated cells are nonclonogenic, then the HF will be overestimated by the fraction of the tumor measured to be anoxic using direct measuring techniques. If a higher fraction of the oxygenated than anoxic cells are nonclonogenic, the HF will be underestimated by the fraction of anoxic cells. Conclusion: Correlations between the HF and direct measures of tumor oxygenation have been described within tumor lines evaluated under different physiological condition. However, such relationships can be totally unpredictable between different tumors if the fraction of the anoxic cells that is clonogenic varies substantially. Clearly, if tumor anoxia cannot be detected using direct measures, this is an accurate indication that the tumor is well oxygenated. When tumor anoxia is present, however, the conclusions are ambiguous. Even when a small fraction of the tumor is measured as anoxic, direct measures

  9. CT of abdominal tumor

    International Nuclear Information System (INIS)

    Endo, Satoshi; Yamada, Kenji; Ito, Masatoshi; Ito, Hisao; Yamaura, Harutsugu

    1981-01-01

    CT findings in 33 patients who had an abdominal tumor were evaluated. CT revealed a tumor in 31 cases. The organ from which the tumor originated was correctly diagnosed in 18 patients. Whether the tumor was solid or cystic was correctly predicted in 28 patients. The diagnosis malignant or benign nature of tumor was correct, incorrect and impossible, in 23, 3, and five patiens, respectively. (Kondo, M.)

  10. Recurrent desmoid tumor of the abdominal wall | Toughrai | Pan ...

    African Journals Online (AJOL)

    Desmoid tumors most often occur in abdominal wall. Their tendency to recur lead to repeated operations which can make the abdominal wall reconstruction difficult. We report a 28-year-old female history. The patient was referred to our hospital for a recurrent desmoid tumor of the abdominal wall. The tumor was totally ...

  11. Prognostic significance of total lesion glycolysis in patients with advanced non-small cell lung cancer receiving chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zaizen, Yoshiaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Azuma, Koichi, E-mail: azuma@med.kurume-u.ac.jp [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kurata, Seiji [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Sadashima, Eiji; Hattori, Satoshi [Biostatistics Center, Kurume University, Kurume (Japan); Sasada, Tetsuro [Department of Immunology and Immunotherapy, Kurume University School of Medicine, Kurume (Japan); Imamura, Yohei [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kaida, Hayato [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Kawahara, Akihiko [Department of Pathology, Kurume University School of Medicine, Kurume (Japan); Kinoshita, Takashi [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Ishibashi, Masatoshi [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Hoshino, Tomoaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan)

    2012-12-15

    Background: [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) imaging has been employed as a non-invasive diagnostic tool for malignant tumors. Total lesion glycolysis (TLG) on FDG-PET is calculated by multiplying the mean standardized uptake value (SUVmean) by the tumor volume. Unlike the maximum standardized uptake value (SUVmax), which represents the point of greatest metabolic activity within tumors, TLG has been suggested to reflect global metabolic activity in whole tumors. Methods: We retrospectively examined whether or not FDG-PET measurements, including SUVmean, SUVmax, and TLG, could predict progression-free survival (PFS) or overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving chemotherapy. Results: This study involved 81 consecutive patients with NSCLC who received chemotherapy. All of the patients underwent FDG-PET examination before treatment. SUVmean, SUVmax, and TLG on FDG-PET were significantly associated with gender, smoking status, and tumor histology. With adjustment for several other variables, Cox regression analysis showed that TLG was significantly prognostic for both PFS [hazard ratio = 2.34; 95% confidence interval, 1.18–4.64; P = 0.015] and OS (hazard ratio = 2.80; 95% confidence interval, 1.12–6.96; P = 0.003), whereas SUVmean and SUVmax had no significant association with PFS (P = 0.693 and P = 0.322, respectively) or OS (P = 0.587 and P = 0.214, respectively). Conclusions: Our findings suggest that TLG may be more useful than SUVmean and SUVmax for predicting PFS and OS in NSCLC patients receiving chemotherapy. The TLG measurement on FDG-PET imaging could be routinely recommended to advanced NSCLC patients.

  12. The role of (18)F-FDG positron emission tomography in the follow-up of liver tumors treated with (90)Yttrium radioembolization.

    Science.gov (United States)

    Bagni, Oreste; Filippi, Luca; Schillaci, Orazio

    2015-01-01

    In the last years, radioembolization (RE) has emerged as a novel technique for the treatment of malignant hepatic lesions using (90)Y embedded in spheres, which are infused directly into the hepatic arterial circulation. (90)Y-spheres, once implanted in liver, can release a significant radiation burden to neoplastic cells with a relative low dose to normal parenchyma. (90)Y RE results as a combination of embolization and radiation therapy, thus the standard radiologic follow up modalities may be not sufficiently accurate to assess tumor response to treatment. (18)Fluoro-deoxyglucose Positron Emission Tomography ((18)F-FDG PET) detects glucose uptake and metabolic activity in tumor cells. (18)F-FDG PET has become a well established diagnostic tool in many oncological scenarios. Furthermore, PET response criteria (PERCIST) have been recently introduced to categorize the metabolic response to therapy of cancer patients. Several semiquantitative parameters, such as SUVmax and its changes, the Functional Tumor Volume and the Total Lesion Glycolysis can be useful to accurately assess tumor changes after therapy. The purpose of this article is to present the literature on the role of (18)F-FDG PET in the evaluation of patients with primary and secondary liver tumors treated with (90)Y RE.

  13. Anti-tumor effect of low dose radiation in mice

    International Nuclear Information System (INIS)

    Fan Zhengping; Lu Jiaben; Zhu Bingchai

    1997-01-01

    The author reports the effects of the total body irradiation of low dose radiation (LDR) and/or the local irradiation of large dose on average tumor weights and tumor inhibitory rates in 170 mice inoculated S 180 sarcoma cell, and the influence of LDR on average longevity in 40 tumor-bearing animals. Results show (1) LDR in the range of 75∼250 mGy can inhibit tumor growth to some extent; (2) fractionated irradiation of 75 mGy and local irradiation of 10 Gy may produce a synergism in tumor growth inhibition; and (3)LDR may enhance average longevity in ascitic tumor-bearing mice