Measurement of depth-dose of linear accelerator and simulation by use of Geant4 computer code

AbstractRadiation therapy is an established method of cancer treatment. New technologies in cancer radiotherapy need a more accurate computation of the dose delivered in the radiotherapy treatment plan. This study presents some results of a Geant4-based application for simulation of the absorbed dose distribution given by a medical linear accelerator (LINAC). The LINAC geometry is accurately described in the Monte Carlo code with use of the accelerator manufacturer's specifications. The capability of the software for evaluating the dose distribution has been verified by comparisons with measurements in a water phantom; the comparisons were performed for percentage depth dose (PDD) and profiles for various field sizes and depths, for a 6-MV electron beam. Experimental and calculated dose values were in good agreement both in PDD and in transverse sections of the water phantom

Improved Refolding Efficacy of Recombinant Human Interferon α-2b via pH Modulation

Purpose: To increase the refolding yield of Recombinant Human Interferon α-2b in order to achieve a highly potent product.Methods: Interferon α-2b inclusion body was dissolved in tris-HCl buffer containing 6 M guanidine-HCl and CuSO4. Different refolding buffers were employed for refolding the target protein. The refolded proteins were then purified by affinity and gel filtration chromatography. The purified proteins were subjected to circular dichroism (CD) spectropolarimetry and assayed for biological activity in vitro.Results: Increment of pH to 8.5 improved refolding efficacies from 42.28 % to 71.22 %. However, the relative potency significantly increased up to pH 8.0 (from 19353546 to 28633902, p < 0.05) and then decreased to 21081305.00 at pH 8.5. The CD spectra demonstrated that by increasing pH to 8.5, the secondary structure of the protein was altered, probably due to increase in alpha-helix from 23.7 % at pH 7.0 to 28.1 %.Conclusion: Employing a low-cost and simple method, such as alteration of refolding buffer pH, results in higher refolding yield in downstream processing of rhIFN α-2b.Keywords: Recombinant human interferon α-2b, Refolding, Circular dichroism, Spectropolarimetry,Recombinant protein, pH effec

Effect of non-nutritional factors on nisin production

When attempting to improve production of nisin, understanding the effect of non-nutritional factors is essential owing to a lack of adequate information about these factors among various investigations. Inorder to assess some of non-nutritional factors and how they influence the nisin production in batch cultivation, a laboratory scale study was performed. Lactococcus lactis subsp. lactis ATCC 11454 produced nisin and Micrococcus luteus ATCC 10240 was used in bioassay measurement as the nisinsensitive strain. The age and size of inoculum, initial pH value of the medium and flask volume/medium volume (F/M) ratio, temperature as well as agitation were studied by changing one factor at a time whilekeeping others constant in de Man, Rogosa and Sharpe (MRS) medium. Our results implied that pH value was positively related to increase nisin production. Two other important factors for a maximum nisin production were found to be agitation and flask volume/medium volume (F/M) ratio. Inoculum size more than 2.5% (v/v) had no effect on nisin production. The most suitable condition for inoculum age was 32-hour-old culture (at the end of log phase) and 27°C temperature provided maximum nisinproduction

Glucose metabolism in cancer and the role of ketogenic diet

Department of Biochemistry and Clinical Biochemistry, Nicolae Testemitsanu State University of Medicine and Pharmacy, Chisinau, the Republic of MoldovaBackground: One of the fundamental metabolic characteristics of cancer tissues is high consumption of glucose by cancer cells. The purpose of this article is determination of the features in the energy metabolism of cancer cells, elucidation of energy metabolism due to the major nutritive substrates, such as glucose and glutamine, evaluation of lactate dehydrogenase (LDH) as a potential marker of malignancies, estimation of the ketogenic diet in the treatment of cancer. The cells with higher degree of proliferation have a lower level of reduced Nicotinamide Adenine Dinucleotide (NADH), confirming the hypothesis: anabolic processes are predominant in cancer. The preferred way of glucose utilization in cancer tissues is the conversion of pyruvate to lactate, a phenomenon known as aerobic glycolysis or Warburg effect. Tumors with a high level of aerobic glycolysis are the most aggressive. The fact that LDHA (which catalyzes the reversible reaction of pyruvate to lactate) reflects the aggressiveness of the tumor and demonstrates the importance of aerobic glycolytic metabolism (the Warburg effect) in the survival of tumor cells. Conclusions: Multiple studies have mentioned the possibility of using glutamine instead of glucose by the cancer cells. Use of glutamine is another way of generating energy contributing to tumor cell survival. It was established that on substitution of glucose with ketone bodies (ketogenic diet), cancer cells can not adapt and die. Modulation of energy metabolism represents a new stage in the treatment of cancer. The substitution of glucose with lipids in the feed ration (ketogenic diet) is a non-toxic method of cancer management, both in prevention and treatment

Free convection heat transfer and entropy generation analysis of water-Fe 3 O 4 /CNT hybrid nanofluid in a concentric annulus

© 2018, Emerald Publishing Limited. Purpose: This paper aims to numerically investigate the heat transfer and entropy generation characteristics of water-based hybrid nanofluid in natural convection flow inside a concentric horizontal annulus. Design/methodology/approach: The hybrid nanofluid is prepared by suspending tetramethylammonium hydroxide-coated Fe 3 O 4 (magnetite) nanoparticles and gum arabic (GA)-coated carbon nanotubes (CNTs) in water. The effects of nanoparticle volume concentration and Rayleigh number on the streamlines, isotherms, average Nusselt number and the thermal, frictional and total entropy generation rates are investigated comprehensively. Findings: Results show the advantageous effect of hybrid nanofluid on the average Nusselt number. Furthermore, the study of entropy generation shows the increment of both frictional and thermal entropy generation rates by increasing Fe 3 O 4 and CNT concentrations at various Rayleigh numbers. Increasing Rayleigh number from 103 to 105, at Fe 3 O 4 concentration of 0.9 per cent and CNT concentration of 1.35 per cent, increases the average Nusselt number, thermal entropy generation rate and frictional entropy generation rate by 224.95, 224.65 and 155.25 per cent, respectively. Moreover, increasing the Fe 3 O 4 concentration from 0.5 to 0.9 per cent, at Rayleigh number of 105 and CNT concentration of 1.35 per cent, intensifies the average Nusselt number, thermal entropy generation rate and frictional entropy generation rate by 18.36, 22.78 and 72.7 per cent, respectively. Originality/value: To the best knowledge of the authors, there are not any archival publications considering the detailed behaviour of the natural convective heat transfer and entropy generation of hybrid nanofluid in a concentric annulus

Measurement of depth-dose of linear accelerator and simulation by use of Geant4 computer code

Radiation therapy is an established method of cancer treatment. New technologies in cancer radiotherapy need a more accurate computation of the dose delivered in the radiotherapy treatment plan. This study presents some results of a Geant4-based application for simulation of the absorbed dose distribution given by a medical linear accelerator (LINAC). The LINAC geometry is accurately described in the Monte Carlo code with use of the accelerator manufacturer's specifications. The capability of the software for evaluating the dose distribution has been verified by comparisons with measurements in a water phantom; the comparisons were performed for percentage depth dose (PDD) and profiles for various field sizes and depths, for a 6-MV electron beam. Experimental and calculated dose values were in good agreement both in PDD and in transverse sections of the water phantom

Razvoj radiomarkiranog β-humanog koriogonadotropina

-human chorionic gonadotropin (-hCG) was successively labeled with [67Ga] gallium chloride after conjugation with freshly prepared diethylenetriaminepentaacetic acid dianhydride (ccDTPA). After solid phase purification of the radiolabeled hormone, high performance liquid chromatography showed radiochemical purity higher than 95 % under optimized conditions (specific activity = 2223 TBq mM1, labeling efficiency 80 %). Preliminary in vivo studies (ID g1, %) in male wild-type rats showed marked gonadal uptake of the tracer after 240 minutes in agreement with the biodistribution studies and reported -hCG receptors. Target to blood ratios were 5.1 and 15.2 after 3 and 24 hours, respectively, while target to muscle ratios were 35 and 40 after 3 and 24 hours, respectively.Beta-humani korionski gonadotropin (beta-hCG) uspješno je markiran s [67Ga] galijevim kloridom nakon konjugacije sa svježe priređenim dianhidridom dietilentriaminpentaoctene kiseline (ccDTPA). Nakon čišćenja radiomarkiranog hormona na čvrstoj fazi, radiokemijska čistoća bila je prema HPLC veća od 95 % (specifična aktivnost = 22-23 TBq mM-1, učinkovitost markiranja 80 %). Preliminarni in vivo pokusi (ID g-1, %) na mužjacima divljeg tipa štakora pokazali su da obilježeni hormon značajno ulazi u gonade nakon 240 minuta, što je u suglasnosti s ispitivanjima biodistribucije i podacima o receptorima za beta-hCG. Omjer koncentracija u gonadama i krvi bio je 5,1, odnosno 15,2 nakon 3, odnosno 24 sata, dok je omjer koncentracija u gonadama i mišićima bio 35, odnosno 40 nakon 3, odnosno 24 sata

Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs

Tumor treating fields (TTFields) are low intensity, intermediate frequency, alternating electric fields used to treat cancerous tumors. This novel treatment modality effectively inhibits the growth of solid tumors in vivo and has shown promise in pilot clinical trials in patients with advanced stage solid tumors. TTFields were tested for their potential to inhibit metastatic spread of solid tumors to the lungs in two animal models: (1) Mice injected with malignant melanoma cells (B16F10) into the tail vein, (2) New Zealand White rabbits implanted with VX-2 tumors within the kidney capsule. Mice and rabbits were treated using two-directional TTFields at 100–200 kHz. Animals were either monitored for survival, or sacrificed for pathological and histological analysis of the lungs. The total number of lung surface metastases and the absolute weight of the lungs were both significantly lower in TTFields treated mice then in sham control mice. TTFields treated rabbits survived longer than sham control animals. This extension in survival was found to be due to an inhibition of metastatic spread, seeding or growth in the lungs of TTFields treated rabbits compared to controls. Histologically, extensive peri- and intra-tumoral immune cell infiltration was seen in TTFields treated rabbits only. These results raise the possibility that in addition to their proven inhibitory effect on the growth of solid tumors, TTFields may also have clinical benefit in the prevention of metastatic spread from primary tumors

Breast adenocarcinoma liver metastases, in contrast to colorectal cancer liver metastases, display a non-angiogenic growth pattern that preserves the stroma and lacks hypoxia

Although angiogenesis is a prerequisite for the growth of most human solid tumours, alternative mechanisms of vascularisation can be adopted. We have previously described a non-angiogenic growth pattern in liver metastases of colorectal adenocarcinomas (CRC) in which tumour cells replace hepatocytes at the tumour-liver interface, preserving the liver architecture and co-opting the sinusoidal blood vessels. The aim of this study was to determine whether this replacement pattern occurs during liver metastasis of breast adenocarcinomas (BC) and whether the lack of an angiogenic switch in such metastases is due to the absence of hypoxia and subsequent vascular fibrinogen leakage. The growth pattern of 45 BC liver metastases and 28 CRC liver metastases (73 consecutive patients) was assessed on haematoxylin- and eosin-stained tissue sections. The majority of the BC liver metastases had a replacement growth pattern (96%), in contrast to only 32% of the CRC metastases (P<0.0001). The median carbonic anhydrase 9 (CA9) expression (M75 antibody), as a marker of hypoxia, (intensity x % of stained tumour cells) was 0 in the BC metastases and 53 in the CRC metastases (P<0.0001). There was CA9 expression at the tumour-liver interface in only 16% of the BC liver metastases vs 54% of the CRC metastases (P=0.002). There was fibrin (T2G1 antibody) at the tumour-liver interface in only 21% of the BC metastases vs 56% of the CRC metastases (P=0.04). The median macrophage count (Chalkley morphometry; KP-1 anti-CD68 antibody) at the interface was 4.3 and 7.5, respectively (P<0.0001). Carbonic anhydrase 9 score and macrophage count were positively correlated (r=0.42; P=0.002) in all metastases. Glandular differentiation was less in the BC liver metastases: 80% had less than 10% gland formation vs only 7% of the CRC metastases (P<0.0001). The liver is a densely vascularised organ and can host metastases that exploit this environment by replacing the hepatocytes and co-opting the vasculature. Our findings confirm that a non-angiogenic pattern of liver metastasis indeed occurs in BC, that this pattern of replacement growth is even more prevalent than in CRC, and that the process induces neither hypoxia nor vascular leakage