scholarly journals Offset of apparent hyperpolarized 13 C lactate flux by the use of adjuvant metformin in ionizing radiation therapy in vivo

2021 ◽  
Author(s):  
Young‐Suk Choi ◽  
Joonsung Lee ◽  
Han‐Sol Lee ◽  
Jae Eun Song ◽  
Dong‐Hyun Kim ◽  
...  
2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i19-i19
Author(s):  
Aarooran Durairaj ◽  
Melanie McReynolds ◽  
Congcong Wang ◽  
Joy He ◽  
Joshua Rabinowitz ◽  
...  

Abstract Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, originates in astrocytes and oligodendrocytes and yields a median survival time of less than 2 years and a 5-year survival of 2.5%. There has been little in the way of treatments and novel approaches are needed to combat the poor prognosis of GBM. Recent studies have established that GBM cells exhibit metabolic reprogramming to adapt to diverse metabolic gradients within heterogenous tumor microenvironments. Using an unbiased metabolomics approach, we investigated metabolic changes both pre- and post-ionizing radiation across several patient-derived GBM cell lines. Surprisingly, acute high dosage of ionizing radiation resulted in significant changes in the synthesis of aminolevulinic acid (ALA), a non-proteinogenic amino acid. Fractionation of radiation therapy resulted in dose-dependent changes in the heme synthesis pathway within these cells. Using an orthotopic xenograft mouse model of GBM, we identify several enzymatic vulnerabilities in vivo and discuss a novel combinatorial therapeutic approach of radiation and targeted pharmacological intervention. Our findings reveal the fundamental biosynthetic changes that GBMs adopt when exposed to ionizing irradiation as well as the benefits of a combinatorial approach.


Author(s):  
ADEEB SHEHZAD ◽  
HIRA ZAHID ◽  
WAZIR MUHAMMAD ◽  
RIZWAN AHMAD ◽  
EBTESAM A AL-SUHAIMI

Objective: Radiation therapy has gained significant attention for the treatment and prevention of solid and malignant human tumors. However, after periodical exposures, radiation therapy losses its efficacy against cancer cells displaying radio-resistant phenotypes. Therefore, decursin might improve the efficiency of radiotherapy against a variety of human cancers. Methods: The chemopreventive efficacy of decursin was evaluated against B16F10 cancer cell lines and DMBA/croton oil-induced skin carcinogenesis in BALB/c mice. Decursin was administered intraperitoneal at the dose of 20 mg/kg/day for 8 weeks following exposure to 5 Gy of ionizing radiation (IR) after 1 month of DMBA application. Western blot was performed for underlying mechanism of radioresistance. Results: Decursin suppressed the proliferation and viability of melanoma cancer cell lines in a concentration- and time-dependent manner. The in vivo data collected from mice model revealed that decursin reduced the precancerous skin lesions and the incidence of tumor bearing in radiation-exposed mice. Decursin also enhanced the effect of IR by downregulation of Akt/NFκB pathway through activation of IκBα. Conclusion: Our results suggest that the activation of Akt/NFκB establishes a pro-survival response to radiation that may account for the development of radioresistance. Decursin blocks the abnormal expression of these proteins and potentiates the radiotherapeutic effect.


10.37206/88 ◽  
2005 ◽  
Author(s):  
Ellen Yorke ◽  
Rodica Alecu ◽  
Li Ding ◽  
Doracy Fontenla ◽  
Andre Kalend ◽  
...  

2012 ◽  
Vol 135 (2) ◽  
pp. 391-401 ◽  
Author(s):  
Victor C. K. Lo ◽  
Margarete K. Akens ◽  
Sara Moore ◽  
Albert J. M. Yee ◽  
Brian C. Wilson ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1614
Author(s):  
Ken-ichiro Matsumoto ◽  
James B. Mitchell ◽  
Murali C. Krishna

Radiation therapy is one of the main modalities to treat cancer/tumor. The response to radiation therapy, however, can be influenced by physiological and/or pathological conditions in the target tissues, especially by the low partial oxygen pressure and altered redox status in cancer/tumor tissues. Visualizing such cancer/tumor patho-physiological microenvironment would be a useful not only for planning radiotherapy but also to detect cancer/tumor in an earlier stage. Tumor hypoxia could be sensed by positron emission tomography (PET), electron paramagnetic resonance (EPR) oxygen mapping, and in vivo dynamic nuclear polarization (DNP) MRI. Tissue oxygenation could be visualized on a real-time basis by blood oxygen level dependent (BOLD) and/or tissue oxygen level dependent (TOLD) MRI signal. EPR imaging (EPRI) and/or T1-weighted MRI techniques can visualize tissue redox status non-invasively based on paramagnetic and diamagnetic conversions of nitroxyl radical contrast agent. 13C-DNP MRI can visualize glycometabolism of tumor/cancer tissues. Accurate co-registration of those multimodal images could make mechanisms of drug and/or relation of resulted biological effects clear. A multimodal instrument, such as PET-MRI, may have another possibility to link multiple functions. Functional imaging techniques individually developed to date have been converged on the concept of theranostics.


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