Ketone ester supplementation of Atkins type diet prolongs survival in an orthotopic xenograft model of glioblastoma

Hassan Azari,Angela Poff,Dominic D’Agostino,Brent Reynolds 대한해부학회 2024 Anatomy & Cell Biology Vol.57 No.1

Heavy reliance on glucose metabolism and a reduced capacity to use ketone bodies makes glioblastoma (GBM) a promising candidate for ketone-based therapies. Ketogenic diet (KD) is well-known for its promising effects in controlling tumor growth in GBM. Moreover, synthetic ketone ester (KE) has demonstrated to increase blood ketone levels and enhance animal survival in a metastatic VM-M3 murine tumor model. Here, we compared the efficacy of a KE-supplemented Atkins-type diet (ATD-KE) to a classic KD in controlling tumor progression and enhancing survival in a clinically relevant orthotopic patient-derived xenograft GBM model. Our findings demonstrate that ATD-KE preserves body weight (percent change from the baseline; 112±2.99 vs. 116.9±2.52 and 104.8±3.67), decreases blood glucose (80.55±0.86 vs. 118.6±9.51 and 52.35±3.89 mg/dl), and increases ketone bodies in blood (1.15±0.03 mM vs. 0.55±0.04 and 2.66±0.21 mM) and brain tumor tissue (3.35±0.30 mM vs. 2.04±0.3 and 4.25±0.25 mM) comparable to the KD (results presented for ATD-KE vs. standard diet [STD] and KD, respectively). Importantly, the ATD-KE treatment significantly enhanced survival compared to the STD and was indistinguishable from the KD (47 days in STD vs. 56 days in KD and ATD-KE), suggesting that a nutritionally balanced low carbohydrate ATD combined with KE may be as effective as the KD alone in reducing brain tumor progression. Overall, these data support the rationale for clinical testing of KE-supplemented low-carb diet as an adjunct treatment for brain tumor patients.

A study on the effect of JNJ-10397049 on proliferation and differentiation of neural precursor cells

Neda Karami,Hassan Azari,Moosa Rahimi,Hadi Aligholi,Tahereh Kalantari 대한해부학회 2022 Anatomy & Cell Biology Vol.55 No.2

Coexistence of multiple anomalies in the hepatobiliary system

Seyed Hadi Anjamrooz,Hassan Azari 대한해부학회 2012 Anatomy & Cell Biology Vol.45 No.1

The co-occurrence of several anomalies in the hepatobiliary system is uncommon. In the present study, hepatic lobe anomalies occurring in combination with hepatic artery and biliary variations were observed in an adult male cadaver. There are no previous reports in the literature on the coexistence of such anatomical variations. Preoperative diagnosis of such coexisting anomalies is very difficult. Hence, a thorough knowledge of these variations will enable surgeons to select the most appropriate hepatobiliary surgical procedure and postoperative management.

Abnormal patterns of the renal veins

Seyed Hadi Anjamrooz,Hassan Azari,Mehdi Abedinzadeh 대한해부학회 2012 Anatomy & Cell Biology Vol.45 No.1

Knowledge of the renal vascular anatomy may greatly contribute to the success of surgical, invasive and radiological procedures of the retroperitoneal region. Here, morphometric and histological studies of a human cadaveric specimen presented a complex, anomalous pattern of renal veins. The left renal vein had an oblique retro-aortic course and received two lumbar veins. It bifurcated near its drainage point into the inferior vena cava. The right renal vein received the right testicular vein. In addition, the left kidney was located at a low position. The spleen was enlarged. The present case is unique and provides information that may help surgeons or angiologists to apply safer interventions.

Effects of high-fat diet on the numerical density and number of neuronal cells and the volume of the mouse hypothalamus : a stereological study

Mohammad Reza Namavar,Samira Raminfard,Zahra Vojdani Jahromi,Hassan Azari 대한해부학회 2012 Anatomy & Cell Biology Vol.45 No.3

It has been demonstrated that the type of diet affects the brain structure and function. Consumption of fat-rich food is one of the most important factors that lead to increase in the prevalence of cardiovascular and neurological diseases. High-fat diet may change the volume and neuronal number or density in the hypothalamus, which is the center of energy control. Therefore, this study was designed to study the effect of high-fat diet on the density and number of neurons, and also the volume of hypothalamus in adult male mice. Forty male mice were divided into the control and experimental groups. The control group were fed with standard and the experimental groups, with high-fat diet for 4 (short-term) or 8 (long-term) weeks. The animals were perfused and brains were immediately removed, post-fixed and cut coronally and serially using cryostat at 30-㎛ thickness. Every 6th sections were stained by cresyl violet. The numerical density and number of neuron and the volume of hypothalamus were estimated by using unbiased stereological methods. Data analysis showed that both short and long time consumption of high-fat diet decreased the neuronal cell density of the hypothalamus. Interestingly, despite a decrease in the neuronal cell density, long time consumption of high-fat diet could significantly increase the volume of hypothalamus (P<0.05). High fat diet decreased the neuronal cell density and increased the volume of the hypothalamus, but it did not significantly change its total neurons. These changes might be due to an increase in the extracellular space through inflammation or gliosis in the hypothalamus.

Ibrutinib reduces neutrophil infiltration, preserves neural tissue and enhances locomotor recovery in mouse contusion model of spinal cord injury

Somayyeh Torabi,Seyed Hadi Anjamrooz,Zahra Zeraatpisheh,Hadi Aligholi,Hassan Azari 대한해부학회 2021 Anatomy & Cell Biology Vol.54 No.3

Following acute spinal cord injury (SCI), excessive recruitment of neutrophils can result in inflammation, neural tissue loss and exacerbation of neurological outcomes. Ibrutinib is a bruton’s tyrosine kinase inhibitor in innate immune cells such as the neutrophils that diminishes their activation and influx to the site of injury. The present study evaluated the efficacy of ibrutinib administration in the acute phase of SCI on neural tissue preservation and locomotor recovery. Ibrutinib was delivered intravenously at 3.125 mg/kg either immediately, 12 hours after, or both immediately and 12 hours after SCI induction in adult male C57BL/6 mice. Neutrophil influx into the lesion area was evaluated 24 hours following SCI using light microscopy and immunohistochemistry methods. Animals’ body weight changes were recorded, and their functional motor recovery was assessed based on the Basso mouse scale during 28 days after treatment. Finally, spinal cord lesion volume was estimated by an unbiased stereological method. While animals’ weight in the control group started to increase one week after injury, it stayed unchanged in treatment groups. However, the double injection of ibrutinib led to a significantly lower body weight compared to the control group at 4 weeks post-injury. Mean neutrophil counts per visual field and the lesion volume were significantly decreased in all ibrutinib-treated groups. In addition, ibrutinib significantly improved locomotor functional recovery in all treated groups, especially in immediate and double-injection groups. Neural tissue protection and locomotor functional recovery suggest ibrutinib treatment as a potent immunotherapeutic intervention for traumatic SCI that warrants clinical testing.

Effects of radiofrequency exposure emitted from a GSM mobile phone on proliferation, differentiation, and apoptosis of neural stem cells

Mahsa Eghlidospour,Amir Ghanbari,Seyyed Mohammad Javad Mortazavi,Hassan Azari 대한해부학회 2017 Anatomy & Cell Biology Vol.50 No.2

Due to the importance of neural stem cells (NSCs) in plasticity of the nervous system and treating neurodegenerative diseases, the main goal of this study was to evaluate the effects of radiofrequency radiation emitted from a GSM 900-MHz mobile phone with different exposure duration on proliferation, differentiation and apoptosis of adult murine NSCs in vitro. We used neurosphere assay to evaluate NSCs proliferation, and immunofluorescence assay of neural cell markers to examine NSCs differentiation. We also employed alamarBlue and caspase 3 apoptosis assays to assess harmful effects of mobile phone on NSCs. Our results showed that the number and size of resulting neurospheres and also the percentage of cells differentiated into neurons decreased significantly with increasing exposure duration to GSM 900-MHz radiofrequency (RF)-electromagnetic field (EMF). In contrast, exposure to GSM 900-MHz RF-EMF at different durations did not influence cell viability and apoptosis of NSCs and also their astrocytic differentiation. It is concluded that accumulating dose of GSM 900-MHz RF-EMF might have devastating effects on NSCs proliferation and neurogenesis requiring more causations in terms of using mobile devices.

Neurosphere and adherent culture conditions are equivalent for malignant glioma stem cell lines

Maryam Rahman,Karina Reyner,Loic Deleyrolle,Sebastien Millette,Hassan Azari,Bryan W. Day,Brett W. Stringer,Andrew W. Boyd,Terrance G. Johns,Vincent Blot,Rohit Duggal,Brent A. Reynolds 대한해부학회 2015 Anatomy & Cell Biology Vol.48 No.1

Certain limitations of the neurosphere assay (NSA) have resulted in a search for alternative culture techniques forbrain tumor-initiating cells (TICs). Recently, reports have described growing glioblastoma (GBM) TICs as a monolayer usinglaminin. We performed a side-by-side analysis of the NSA and laminin (adherent) culture conditions to compare the growthand expansion of GBM TICs. GBM cells were grown using the NSA and adherent culture conditions. Comparisons weremade using growth in culture, apoptosis assays, protein expression, limiting dilution clonal frequency assay, genetic affymetrixanalysis, and tumorigenicity in vivo. In vitro expansion curves for the NSA and adherent culture conditions were virtuallyidentical (P=0.24) and the clonogenic frequencies (5.2% for NSA vs. 5.0% for laminin, P=0.9) were similar as well. Likewise,markers of differentiation (glial fibrillary acidic protein and beta tubulin III) and proliferation (Ki67 and MCM2) revealedno statistical difference between the sphere and attachment methods. Several different methods were used to determine thenumbers of dead or dying cells (trypan blue, DiIC, caspase-3, and annexin V) with none of the assays noting a meaningfulvariance between the two methods. In addition, genetic expression analysis with microarrays revealed no significant differencesbetween the two groups. Finally, glioma cells derived from both methods of expansion formed large invasive tumors exhibitingGBM features when implanted in immune-compromised animals. A detailed functional, protein and genetic characterization ofhuman GBM cells cultured in serum-free defined conditions demonstrated no statistically meaningful differences when grownusing sphere (NSA) or adherent conditions. Hence, both methods are functionally equivalent and remain suitable options forexpanding primary high-grade gliomas in tissue culture.

A simple technique for morphological measurement of cerebral arterial circle variations using public domain software (Osiris)

Saeed Ansari,Majid Dadmehr,Behzad Eftekhar,Douglas J. McConnell,Sarah Ganji,Hassan Azari,Shahab Kamali-Ardakani,Brian L. Hoh,J. Mocco 대한해부학회 2011 Anatomy & Cell Biology Vol.44 No.4

This article describes a straightforward method to measure the dimensions and identify morphological variations in the cerebral arterial circle using the general-purpose software program Osiris. This user-friendly and portable program displays, manipulates, and analyzes medical digital images, and it has the capability to determine morphometric properties of selected blood vessels (or other anatomical structures) in humans and animals. To ascertain morphometric variations in the cerebral arterial circle, 132 brains of recently deceased fetuses, infants, and adults were dissected. The dissection procedure was first digitized, and then the dimensions were measured with Osiris software. Measurements of each vessel’s length and external diameters were used to identify and classify morphological variations in the cerebral arterial circle. The most commonly observed anatomical variations were uni- and bilateral hypoplasia of the posterior communicating artery. This study demonstrates that public domain soft ware can be used to measure and classify cerebral arterial circle vessels. This method could be extended to examine other anatomical regions or to study other animals. Additionally, knowledge of variations within the circle could be applied clinically to enhance diagnostic and treatment specificity.