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metabolic tumor burden

Hanne A Eide, Ingerid Skjei Knudtsen, Vandana Sandhu, Ayca M Løndalen, Ann Rita Halvorsen, Azadeh Abravan, Elin H Kure, Trond V Bogsrud, Odd Terje Brustugun, Jon Amund Kyte, Eirik Malinen, Åslaug Helland
Purpose: Radiation therapy effectively kills cancer cells and elicits local effects in the irradiated tissue. The aim of this study was to investigate the kinetics of cytokines in the serum of patients with lung cancer undergoing radiation therapy and to identify associations with metabolic tumor burden as determined by 2-deoxy-2-fluoro-D-glucose (18 F-FDG) positron emission tomography (PET). Methods and materials: Forty-five patients with advanced non-small cell lung cancer were included in a phase 2 clinical trial and randomized between fractionated thoracic radiation therapy alone or concurrent with an epidermal growth factor receptor inhibitor...
April 2018: Advances in Radiation Oncology
David E Moulder, Diana Hatoum, Enoch Tay, Yiguang Lin, Eileen M McGowan
Cancer research has been heavily geared towards genomic events in the development and progression of cancer. In contrast, metabolic regulation, such as aberrant metabolism in cancer, is poorly understood. Alteration in cellular metabolism was once regarded simply as a consequence of cancer rather than as playing a primary role in cancer promotion and maintenance. Resurgence of cancer metabolism research has identified critical metabolic reprogramming events within biosynthetic and bioenergetic pathways needed to fulfill the requirements of cancer cell growth and maintenance...
June 8, 2018: Cancers
Maria J Forteza, Konstantinos A Polyzos, Roland Baumgartner, Bianca E Suur, Marion Mussbacher, Daniel K Johansson, Andreas Hermansson, Göran K Hansson, Daniel F J Ketelhuth
T-cell activation is characteristic during the development of atherosclerosis. While overall T-cell responses have been implicated in disease acceleration, regulatory T cells (Tregs) exhibit atheroprotective effects. The expression of the enzyme indoleamine 2,3-dioxygenase-1 (IDO1), which catalyzes the degradation of tryptophan (Trp) along the kynurenine pathway, has been implicated in the induction and expansion of Treg populations. Hence, Tregs can reciprocally promote IDO1 expression in dendritic cells (DCs) via reverse signaling mechanisms during antigen presentation...
2018: Frontiers in Immunology
Feng Ren, Jian Li, Yanglin Wang, Yongxia Wang, Sijia Feng, Zhiqing Yuan, Xinlai Qian
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...
May 25, 2018: Cellular Physiology and Biochemistry
Souleymane Abdoul-Azize, Catherine Buquet, Hong Li, Jean-Michel Picquenot, Jean-Pierre Vannier
Recent studies have suggested that the lipid-lowering agent simvastatin holds great promise as a cancer therapeutic; it inhibits the growth of multiple tumors, including triple-negative breast cancer. Doxorubicin- and simvastatin-induced cytotoxicity has been associated with the modulation of Ca2+ signaling, but the underlying mechanisms remain incompletely understood. Here we identify how Ca2+ signaling regulates the breast tumor cell response to doxorubicin and simvastatin. These two drugs inhibit cell survival while increasing apoptosis in two human breast cancer cell lines and five primary breast tumor specimens through the modulation of Ca2+ signaling...
May 23, 2018: Oncogene
Haifeng Duan
The accumulation of mutated somatic cells due to the incompetency of body's immune system may lead to tumor onset. Therefore, enhancing the ability of the system to eliminate such cells should be the core of tumor therapy. The intrinsic antitumor immunity is triggered by tumor-specific antigens (TSA) or TSA-sensitized dendritic cells (DC). Once initiated, specific anti-tumor antibodies are produced and tumor-specific killer immune cells, including cytotoxic T lymphocytes (CTL), NK cells, and macrophages, are raised or induced...
May 22, 2018: Cellular Physiology and Biochemistry
Lavinia Vija Racaru, Mathieu Sinigaglia, Salim Kanoun, Fayçal Ben Bouallègue, Ilan Tal, Sévérine Brillouet, Mathilde Bauriaud-Mallet, Slimane Zerdoud, Lawrence Dierickx, Delphine Vallot, Olivier Caselles, Erwan Gabiache, Pierre Pascal, Frederic Courbon
PURPOSE: This study aims to predict hematological toxicity induced by Ra therapy. We investigated the value of metabolically active bone tumor volume (MBTV) and total bone lesion activity (TLA) calculated on pretreatment fluorine-18-fluorocholine (F-FCH) PET/CT in castrate-resistant prostate cancer (CRPC) patients with bone metastases treated with Ra radionuclide therapy. PATIENTS AND METHODS: F-FCH PET/CT imaging was performed in 15 patients with CRPC before treatment with Ra...
May 21, 2018: Nuclear Medicine Communications
Angelo Castello, H A Macapinlac, E Lopci, E B Santos
PURPOSE: Prostate-specific antigen (PSA) flare is a well-known phenomenon in patients with prostate cancer, but its impact during radium-223 dichloride (223 RaCl2 ) therapy is still unclear. This radioisotope has shown to improve overall survival in metastatic castration-resistant prostate cancer (mCRPC). We sought to evaluate the impact of PSA flare on survival and its relation with metabolic parameters on 18 F-labeled sodium fluoride PET/CT. METHODS: We conducted a retrospective study of 168 patients with mCRPC (median age 69; median PSA 29...
May 21, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Alexander L Chin, Kiran A Kumar, Haiwei H Guo, Peter G Maxim, Heather Wakelee, Joel W Neal, Maximillian Diehn, Billy W Loo, Michael F Gensheimer
BACKGROUND: Emerging data support aggressive local treatment of oligometastatic non-small-cell lung cancer (NSCLC) patients. We sought to determine whether the metabolic burden of disease found by fluorodeoxyglucose positron emission tomography at the time of high-dose radiotherapy (RT) for oligometastatic NSCLC can serve as a prognostic biomarker. MATERIALS AND METHODS: We conducted a retrospective cohort study of 67 RT treatment courses in 55 patients with oligometastatic NSCLC who had undergone high-dose RT to all sites of active disease at our institution...
April 19, 2018: Clinical Lung Cancer
Dorottya Bányai, Dániel Végh, Mihály Vaszilkó, Ádám Végh, Lili Ács, Noémi Rózsa, Péter Hermann, Zsolt Németh, Márta Ujpál
INTRODUCTION: Data proves that Hungary has a leading role in the statistics of oral cancer and patients living with type 2 diabetes. AIM: Our aim was to understand the statistical correlation between oral cancer and metabolic disorder (diabetes mellitus and impaired fasting glucose) due to the valuable data from the Semmelweis University. METHOD: We analyzed the data of 835 patients diagnosed with malignant oral cancer and 587 tumor-free control patients...
May 2018: Orvosi Hetilap
Christian Schmidkonz, Michael Cordes, Daniela Schmidt, Tobias Bäuerle, Theresa Ida Goetz, Michael Beck, Olaf Prante, Alexander Cavallaro, Michael Uder, Bernd Wullich, Peter Goebell, Torsten Kuwert, Philipp Ritt
PURPOSE: 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. METHODS: 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...
May 3, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Muhannad Abu-Remaileh, Abed Khalaileh, Eli Pikarsky, Rami I Aqeilan
Liver cancer is one of the most lethal malignancies with very poor prognosis once diagnosed. The most common form of liver cancer is hepatocellular carcinoma (HCC). The WW domain-containing oxidoreductase (WWOX) is a large gene that is often perturbed in a wide variety of tumors, including HCC. WWOX has been shown to act as a tumor suppressor modulating cellular metabolism via regulating hypoxia-inducible factor 1α (HIF-1α) levels and function. Given that WWOX is commonly inactivated in HCC, we set to determine whether specific targeted deletion of murine Wwox affects liver biology and HCC development...
May 3, 2018: Cell Death & Disease
Inga B Fricke, Raquel De Souza, Lais Costa Ayub, Giulio Francia, Robert Kerbel, David A Jaffray, Jinzi Zheng
BACKGROUND: Preclinical breast cancer models recapitulating the clinical course of metastatic disease are crucial for drug development. Highly metastatic cell lines forming spontaneous metastasis following orthotopic implantation were previously developed and characterized regarding their biological and histological characteristics. This study aimed to non-invasively and longitudinally characterize the spatiotemporal pattern of metastasis formation and progression in the MDA-MB-231-derived triple negative LM2-4 and HER2+ LM2-4H2N cell lines, using bioluminescence imaging (BLI), contrast enhanced computed tomography (CT), fluorescence imaging, and 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography ([18F]FDG-PET)...
2018: PloS One
Sonia Rosa Veiga, Xuemei Ge, Carol A Mercer, María Isabel Hernández-Alvarez, Hala Elnakat Thomas, Javier Hernández-Losa, Santiago Ramón Y Cajal, Antonio Zorzano, George Thomas, Sara C Kozma
PURPOSE: Hepatocellular carcinoma (HCC) ranks second in cancer mortality and has limited therapeutic options. We recently described the synergistic effect of allosteric and ATP-site competitive inhibitors against the mammalian target of rapamycin (mTOR) for the treatment of HCC. However, such inhibitors induce glycemia and increase mitochondrial efficiency. Here we determined whether the mitochondrial complex I inhibitor Phenformin could reverse both side effects, impose an energetic-stress on cancer cells and suppress the growth of HCC...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Ronald B Brown, Mohammed S Razzaque
In this article, we briefly summarized evidence that cellular phosphate burden from phosphate toxicity is a pathophysiological determinant of cancer cell growth. Tumor cells express more phosphate cotransporters and store more inorganic phosphate than normal cells, and dysregulated phosphate homeostasis is associated with the genesis of various human tumors. High dietary phosphate consumption causes the growth of lung and skin tumors in experimental animal models. Additional studies show that excessive phosphate burden induces growth-promoting cell signaling, stimulates neovascularization, and is associated with chromosome instability and metastasis...
April 2018: Biochimica et Biophysica Acta
Sardar Zakariya Imam, Mohammad Faizan Zahid, Muhammad Asad Maqbool
Tumor lysis syndrome is a potentially lethal complication of chemotherapy, usually associated with aggressive hematologic malignancies. We describe the case of a young patient with metastatic hepatocellular cancer who developed rapid and fatal tumor lysis syndrome following initiation of sorafenib therapy. Although rare with sorafenib therapy for hepatocellular carcinoma, tumor lysis syndrome is serious complication. Patients with a high burden of disease at therapy initiation should have their metabolic parameters measured prior to starting therapy and closely followed for the first 1-2 weeks while being treated...
April 17, 2018: Hematology/oncology and Stem Cell Therapy
Krishna B Singh, Su-Hyeong Kim, Eun-Ryeong Hahm, Subrata K Pore, Bruce L Jacobs, Shivendra V Singh
Increased de novo synthesis of fatty acids is a rather unique and targetable mechanism of human prostate cancer. We have shown previously that oral administration of sulforaphane (SFN) significantly inhibits the incidence and/or burden of prostatic intraepithelial neoplasia and well-differentiated adenocarcinoma in TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice. The present study used cellular models of prostate cancer and archived plasma/adenocarcinoma tissues and sections from the TRAMP study to demonstrate inhibition of fatty acid synthesis by SFN treatment in vitro and in vivo...
May 28, 2018: Carcinogenesis
He Xu, Min-Sik Lee, Pei-Yun Tsai, Ashley S Adler, Natasha L Curry, Saketh Challa, Elizaveta Freinkman, Daniel S Hitchcock, Kyle D Copps, Morris F White, Roderick T Bronson, Michael Marcotrigiano, Yaotang Wu, Clary B Clish, Nada Y Kalaany
Non-small-cell lung cancer (NSCLC) is a leading cause of cancer death worldwide, with 25% of cases harboring oncogenic Kirsten rat sarcoma ( KRAS ). Although KRAS direct binding to and activation of PI3K is required for KRAS -driven lung tumorigenesis, the contribution of insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) in the context of mutant KRAS remains controversial. Here, we provide genetic evidence that lung-specific dual ablation of insulin receptor substrates 1/2 ( Irs1 / Irs2 ), which mediate insulin and IGF1 signaling, strongly suppresses tumor initiation and dramatically extends the survival of a mouse model of lung cancer with Kras activation and p53 loss...
April 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
Anne Ségolène Cottereau, Annibale Versari, Stefano Luminari, Jehan Dupuis, Loïc Chartier, René-Olivier Casasnovas, Alina Berriolo-Riedinger, Massimo Menga, Corinne Haioun, Hervé Tilly, Vittoria Tarantino, Massimo Federico, Gilles Salles, Judith Trotman, Michel Meignan
Both total metabolic tumor volume (TMTV), computed on baseline PET, and end of induction PET (EOI PET) are imaging biomarkers showing promise for early risk stratification in patients with high tumor burden follicular lymphoma. A model was built incorporating these two factors in 159 patients from three prospective trials. Median follow up was 64 months. High TMTV (>510cm3 ) and positive EOI PET were independent, significant risk factors for progression. Their combination stratified the population into three risk groups: patients with no risk factors (n = 102;64%) had a 5-year PFS of 67%, versus 33% (HR = 2...
March 20, 2018: Blood
Benjamin L Viglianti, Daniel J Wale, Ka Kit Wong, Timothy D Johnson, Christy Ky, Kirk A Frey, Milton D Gross
Purpose To examine the effect metabolic burden (tumor and/or cardiac myocyte uptake) has on fluorine 18 fluorodeoxyglucose (FDG) distribution in organs and tissues of interest. Materials and Methods Positron emission tomographic (PET)/computed tomographic (CT) scans at the Ann Arbor Veterans Affairs hospital from January to July 2015 were reviewed. A total of 107 scans (50 patients; mean age, 64.3 years ± 13.2 [standard deviation]) had metabolic tissue burden assessed by using total lesion glycolysis (TLG) obtained from autosegmentation of the tumor and/or cardiac tissue...
June 2018: Radiology
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