scholarly journals PL1.2 Multiparametric assessment of factors influencing 2 HG accumulation in diffuse brain gliomas

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii1-iii2
Author(s):  
L Nichelli ◽  
F Branzoli ◽  
R Valabregue ◽  
L Capelle ◽  
C Ottolenghi ◽  
...  

Abstract BACKGROUND 2-hydroxyglutarate (2HG) can be detected non-invasively in IDH-mutant gliomas by in vivo magnetic resonance spectroscopy (MRS). We investigated factors affecting 2 HG accumulation and explored the prognostic value of 2 HG detection in IDH mutant gliomas and 2 HG variations during anti-cancer therapies. MATERIAL AND METHODS We prospectively scanned by MEGA-PRESS 70 glioma patients (24 before surgery and 46 IDH mutant operated glioma) and measured 2HG. CRLB cut-off was 50%. We followed up 9 IDH mutant patients during radiotherapy and chemotherapy.We analyzed radiological parameters (tumor and cystic/necrotic volumes, fractions of VOI filled with tumor, spectroscopic profile, “infiltrative” versus “expansive” morphology, contrast-enhancement) and genetic profile (IDH1, IDH2, 1p19q codeletion). 2HG concentrations in plasma, urine, and surgical obtained samples were measured by gas chromatography-mass spectrometry (GC-MS). RESULTS MEGA-PRESS sequence detected 2HG with a sensitivity of 95% in untreated patients, and of 69% in pre-treated patient. Positive predictive value was 100% in both groups. 2HG was lower in pre-treated IDH mutant gliomas (1.1 versus 2.3 mM, P=0.02) and decreased rapidly during radiotherapy and chemotherapy before any radiological change. 2HG detection was positively correlated with tumor volume (P=0.02), choline measurements (r=0.58 P<0.0001), cellular density (measured by restricted diffusivity, Pearson r -0.40 P=0.01), “expansive” presentation, mutated reads/total reads ratio by NGS and was inversely correlated with Myo-inositol (Pearson R -0.29 P=0.03) and cystic/necrotic areas (P=0.04). 2HG by MRS positively correlated with urine 2HG (r=0.80 P=0.003). 2 HG was higher in IDH2 mutant (4.7 versus 2.4 Mm, P=0.02) and lower in non R132H IDH1 mutant (1.12 mM P=0.004). Among IDH mutant glioma patients, 2 HG detection was associated with longer survival (HR 0.09; 95%CI 0.018–0.52). CONCLUSION Tumor volume, cellular density, previous radio- and chemotherapy and genetic features determine 2 HG detection in IDH mutant gliomas. 2 HG detection is associated with better outcome and can be reliably monitored during anti-cancer treatments.

2013 ◽  
Vol 54 (1) ◽  
pp. 121-126
Author(s):  
Paul Walker ◽  
Peggy Provent ◽  
Xavier Tizon ◽  
Gilles Créhange ◽  
Olivier Duchamp ◽  
...  

Background To assist the development of new anti-cancer drugs, it is important to identify biomarkers of treatment efficacy in the preclinical phases of drug development. In order to improve the predictivity of preclinical experiments, more realistic animal models are needed, for example, tumors xenografted directly on the prostate gland of rodents. Purpose To characterize the in-vivo metabolism of healthy rat prostate and of an orthotopic human prostate cancer model using proton magnetic resonance spectroscopy (MRS). Material and Methods The highly metastatic and hormone-independent PC3-MM2 human prostate cancer model was implanted into the ventral prostate lobe of three Nude rats. Healthy Nude (n = 6) and Sprague-Dawley (n = 6) rats were also studied for interspecies comparison of normal prostate metabolism. Magnetic resonance imaging and short echo-time (TE 11.2 ms) single voxel PRESS spectroscopy were performed on dorsal (DP) and ventral (VP) prostate as well as tumor at 4.7 T. The metabolic content and volume of dorsal and ventral lobes were characterized as a function of species and age. Results Slightly lower total creatine (tCr)/water (11.3±2.6 vs. 15.3±3.0, NS), but significantly higher Inositol (Ins)/water (18.9±1.9 vs. 6.6±3.3, P < 0.003) and total choline (tCho)/water (15.0±2.1 vs. 5.6±1.1, P< 0.00007) were observed within healthy DP lobes with respect to VP lobes. No significant variation in metabolic content was seen in healthy DP and VP lobes of Nude rats as a function of age, and no species dependence was observed in their metabolic content. For the orthotopic PC3-MM2 tumor, implanted in VP, the tCr/water ratio was significantly lower (3.1±0.9) than neighboring DP (12.8±1.8, P < 0.00003) and healthy VP (15.3±3.0, P < 0.00006). For Ins, the metabolite ratio in PC3-MM2 was close to that of healthy VP (4.3±2.8 vs. 6.6±3.3, p = NS), but much lower than in neighboring DP (19.1±1.3, P < 0.00005). A similar trend was also observed for tCho, where metabolite ratios in PC3-MM2, healthy VP and neighboring DP were 3.5±0.9, 5.6±1.1, and 15.9±0.8, respectively. Conclusion The in-vivo MRS study of healthy prostate and orthotopic prostate cancer is feasible in rats. Such baseline data could be important when following the modifications in metabolism, including during anti-cancer drug development protocols or following radiotherapy.


2017 ◽  
Vol 59 (4) ◽  
pp. 497-505 ◽  
Author(s):  
Sigmund Ytre-Hauge ◽  
Morteza Esmaeili ◽  
Torill E Sjøbakk ◽  
Renate Grüner ◽  
Kathrine Woie ◽  
...  

Background In vivo magnetic resonance spectroscopy (MRS) enables non-invasive measurements of tumor metabolites. Choline-containing metabolites play a key role in tumor metabolism. Purpose To explore whether preoperative MRS-derived tumor choline levels are associated with clinical and histological features in endometrial carcinomas. Material and Methods Preoperative pelvic magnetic resonance imaging (MRI) (1.5T), including structural and diffusion-weighted imaging and localized multivoxel proton MR (1H-MR) spectroscopy, was performed in 77 prospectively included patients with histologically confirmed endometrial carcinomas. Relative levels of total choline-containing metabolites (tCho) in tumor and myometrium were measured using the ratios: tCho/Creatine; tCho/Water; and tCho/Noise. MRS parameters were analyzed in relation to histological subtype and grade, surgicopathological staging parameters, MRI-measured tumor volume, and tumor apparent diffusion coefficient (ADC) value and clinical outcome. Results Tumor tissue had significantly higher ratios for tCho/Creatine, tCho/Water, and tCho/Noise than normal myometrial tissue ( P < 0.001 for all). High tumor tCho/Water ratio was significantly associated with high tumor grade in endometrioid tumors ( P = 0.02). Tumor tCho/Creatine ratio was positively correlated to MRI-measured tumor volume (rs = 0.25; P = 0.03). Conclusion High choline levels in tumor are associated with high-risk features. In vivo MRS may potentially aid in the preoperative risk stratification in endometrial cancer.


Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3313 ◽  
Author(s):  
El-Saied ◽  
El-Aarag ◽  
Salem ◽  
Said ◽  
Khalifa ◽  
...  

The current study aimed to synthesize new metal coordination complexes with potential biomedical applications. Metal complexes were prepared via the reaction of isatin-N(4)anti- pyrinethiosemicarbazone ligand 1 with Cu(II), Ni(II), Co(II), Zn(II), and Fe(III) ions. The obtained metal complexes 2−12 were characterized using elemental, spectral (1H-NMR, EPR, Mass, IR, UV-Vis) and thermal (TGA) techniques, as well as magnetic moment and molar conductance measurements. In addition, their geometries were studied using EPR and UV−Vis spectroscopy. To evaluate the in vivo anti-cancer activities of these complexes, the ligand 1 and its metal complexes 2, 7 and 9 were tested against solid tumors. The solid tumors were induced by subcutaneous (SC) injection of Ehrlich ascites carcinoma (EAC) cells in mice. The impact of the selected complexes on the reduction of tumor volume was determined. Also, the expression levels of vascular endothelial growth factor (VEGF) and cysteine aspartyl-specific protease-7 (caspase-7) in tumor and liver tissues of mice bearing EAC tumor were determined. Moreover, their effects on alanine transaminase (ALT), aspartate transaminase (AST), albumin, and glucose levels were measured. The results revealed that the tested compounds, especially complex 9, reduced tumor volume, inhibited the expression of VEGF, and induced the expression of caspase-7. Additionally, they restored the levels of ALT, AST, albumin, and glucose close to their normal levels. Taken together, our newly synthesized metal complexes are promising anti-cancer agents against solid tumors induced by EAC cells as supported by the inhibition of VEGF and induction of caspase-7.


Author(s):  
D.J. Meyerhoff

Magnetic Resonance Imaging (MRI) observes tissue water in the presence of a magnetic field gradient to study morphological changes such as tissue volume loss and signal hyperintensities in human disease. These changes are mostly non-specific and do not appear to be correlated with the range of severity of a certain disease. In contrast, Magnetic Resonance Spectroscopy (MRS), which measures many different chemicals and tissue metabolites in the millimolar concentration range in the absence of a magnetic field gradient, has been shown to reveal characteristic metabolite patterns which are often correlated with the severity of a disease. In-vivo MRS studies are performed on widely available MRI scanners without any “sample preparation” or invasive procedures and are therefore widely used in clinical research. Hydrogen (H) MRS and MR Spectroscopic Imaging (MRSI, conceptionally a combination of MRI and MRS) measure N-acetylaspartate (a putative marker of neurons), creatine-containing metabolites (involved in energy processes in the cell), choline-containing metabolites (involved in membrane metabolism and, possibly, inflammatory processes),


2018 ◽  
Author(s):  
Danila Barskiy ◽  
Lucia Ke ◽  
Xingyang Li ◽  
Vincent Stevenson ◽  
Nevin Widarman ◽  
...  

<p>Hyperpolarization techniques based on the use of parahydrogen provide orders of magnitude signal enhancement for magnetic resonance spectroscopy and imaging. The main drawback limiting widespread applicability of parahydrogen-based techniques in biomedicine is the presence of organometallic compounds (the polarization transfer catalysts) in solution with hyperpolarized contrast agents. These catalysts are typically complexes of platinum-group metals and their administration in vivo should be avoided.</p> <p><br></p><p>Herein, we show how extraction of a hyperpolarized compound from an organic phase to an aqueous phase combined with a rapid (less than 10 seconds) Ir-based catalyst capture by metal scavenging agents can produce pure parahydrogen-based hyperpolarized contrast agents as demonstrated by high-resolution nuclear magnetic resonance (NMR) spectroscopy and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The presented methodology enables fast and efficient means of producing pure hyperpolarized aqueous solutions for biomedical and other uses.</p>


2018 ◽  
Author(s):  
Danila Barskiy ◽  
Lucia Ke ◽  
Xingyang Li ◽  
Vincent Stevenson ◽  
Nevin Widarman ◽  
...  

<p>Hyperpolarization techniques based on the use of parahydrogen provide orders of magnitude signal enhancement for magnetic resonance spectroscopy and imaging. The main drawback limiting widespread applicability of parahydrogen-based techniques in biomedicine is the presence of organometallic compounds (the polarization transfer catalysts) in solution with hyperpolarized contrast agents. These catalysts are typically complexes of platinum-group metals and their administration in vivo should be avoided.</p> <p><br></p><p>Herein, we show how extraction of a hyperpolarized compound from an organic phase to an aqueous phase combined with a rapid (less than 10 seconds) Ir-based catalyst capture by metal scavenging agents can produce pure parahydrogen-based hyperpolarized contrast agents as demonstrated by high-resolution nuclear magnetic resonance (NMR) spectroscopy and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The presented methodology enables fast and efficient means of producing pure hyperpolarized aqueous solutions for biomedical and other uses.</p>


Author(s):  
Bhavani J ◽  
Sunil Kumar Prajapati ◽  
Ravichandran S

Cancer is assemblage diseases involving abnormal cell growth amid the potential of spread to other parts of the body due to tobacco use are the cause of about of cancer deaths. Another 10% is due to obesity, poor diet & drinking alcohol. In 2012 about 14.1 million new cases of cancer occurred globally. In females, the most common type is breast cancer. Cisplatin also known as cytophosphane is a nitrogen mustard alkylating agent from the oxazophosphinans groups were used to treat cancers & autoimmune disorders. Based on the above reasons I will fix the aim Preparation characterization of Cisplatin- nano particles  &  its anticancer activity. Solid tumor volume examination report showed that the assessment of different day indication 15,20,25 & 30th variations of different groups of tumor volumes were decreased CPG Nanoparticles (100 mg/kg)+ DAL(15th day 4.97±0.24↓), (20th day 0.6±0.13↓), (25th day 1.35±0.30↓) & (30th day 1.89±0.13↓).


2018 ◽  
Vol 69 (8) ◽  
pp. 2295-2299
Author(s):  
Elena Ionescu ◽  
Tanta Verona Iordache ◽  
Carmen Elena Tebrencu ◽  
Ruxandra Mihaela Cretu ◽  
Ana Mihaela Florea ◽  
...  

St. John s Wort (SJW) or Hypericum perforatum L. is a therapeutic plant highly used in pharmacology. Recent in vivo anti-cancer action of naphtodianthrones (NTs) has extended the research related to enrichment methodologies of SJW phyto-extracts. Therefore, the presented study pursuits the optimization of single-step extraction methodologies to obtain NTs-rich extracts from SJW.


Sign in / Sign up

Export Citation Format

Share Document