CBCT-guided radiotherapy for locally advanced head and cancer: dosimetric impact of weight loss on VMAT and IMRT plans for selected organs at risk structures (OARs)

Purpose: It is common for head and neck patients to be affected by time trend errors as a result of weight loss during a course of radiation treatment. The objective of this planning study was to investigate the impact of weight loss on Volumetric Modulated Arc Therapy (VMAT) as well as Intensity modulated radiation therapy (IMRT) for locally advanced head and neck cancer using automatic co-registration of the CBCT. Methods and Materials: A retrospective analysis of previously treated IMRT plans for 10 patients with locally advanced head and neck cancer patients was done. A VMAT plan was also produced for all patients. We calculated the dose–volume histograms (DVH) indices for spinal cord planning at risk volumes (PRVs), the brainstem PRVs (SC+0.5cm and BS+0.5cm, respectively) as well as mean dose to the parotid glands. Results: The results show that the mean difference in dose to the SC+0.5cm was 1.03% and 1.27% for the IMRT and VMAT plans, respectively. As for dose to the BS+0.5, the percentage difference was 0.63% for the IMRT plans and 0.61% for the VMAT plans. The analysis of the parotid gland doses shows that the percentage change in mean dose to left parotid was -8.0% whereas that of the right parotid was -6.4% for the IMRT treatment plans. In the VMAT plans, the percentages change for the left and the right parotid glands were -6.6% and -6.7% respectively. Conclusions: This study shows a clinically significant impact of weight loss on DVH indices analysed in head and neck organs at risk. It highlights the importance of adaptive radiotherapy in head and neck patients if organ at risk sparing is to be maintained.

Magnesium/Copper Nanocomposite through Digestive Ripening

Composing nanocomposites: Co-digestive ripening of as-prepared Mg and Cu colloids prepared by the solvated metal atom dispersion method results in a highly monodisperse colloid of Mg/Cu nanocomposite with an average particle size of 3.0 +/- 0.5 nm. Annealing of these samples at 300 degrees C gives the Cu/MgO nanocomposite.

Effect of rabbit antiserum to ovine LH on reproductive organs in male hamsters and guinea-pigs

Administration of rabbit antiserum to ovine luteinizing hormone to immature hamsters and guinea-pigs resulted in a significant decrease in the weights of testes, seminal vesicle and ventral prostate. The author wishes to thank Prof. N.R. Moudgal for his interest and Family Planning Foundation for financial assistance.

GATA Transcription Factors in Tissue Homeostasis and Pathology of the Gastrointestinal Tract and Liver

Mammalian gastrointestinal tract and liver are self-renewing organs that are able to sustain themselves due to stem cells present in their tissues. In constant, inflammation-related epithelial damage, vigorous activation of stem cells may lead to their uncontrolled proliferation, and further, to cancer. GATA-4, GATA-5, and GATA-6 regulate cell proliferation and differentiation in many mammalian organs. Lack of GATA-4 or GATA-6 leads to defective endodermal development and cell differentiation. GATA-4 and GATA-5 are considered the ones with tumor suppressive functions, whereas GATA-6 is more related to tumor promotion. In the digestive system their roles in inflammation and tumor-related molecular pathways remain unclear. In this study, we examined the GATA-related molecular pathways involved in normal tissue organization and renewal and in inflammation-related epithelial repair in the gastrointestinal tract and liver. The overall purpose of this study was to elucidate the relation of GATA factors to gastrointestinal and hepatic disease pathology and to evaluate their possible clinical significance in tumor biology. The results indicated distinct expression patterns for GATA-4, GATA-5, and GATA-6 in the human and murine gastrointestinal tract and liver, and their involvement in the regulation of intestine-specific genes. GATA-5 was confined to the intestines of suckling mice, suggesting an association with postnatal enzymatic changes. GATA-4 was upregulated in bowel inflammation concomitantly with TGF-β signaling. In gastrointestinal tumors, GATA-4 was restricted to benign neoplasias of the stomach, while GATA-6 was detected especially at the invasive edges of malignant tumors throughout the gut. In the liver, GATA-4 was upregulated in pediatric tumors along with erythropoietin (Epo), which was detected also in the sera of tumor patients. Furthermore, GATA-4 was enhanced in areas of vigorous hepatic regeneration in patients with tyrosinemia type I. These results suggest a central role for GATA-4 in pediatric tumor biology of the liver. To conclude, GATA-4, GATA-5, and GATA-6 are associated with normal gastrointestinal and hepatic development and regeneration. The appearance of GATA-4 along with TGF-β-signaling in the inflammatory bowel suggests a protective role in the response to inflammation-related epithelial destruction. However, in extremely malignant pediatric liver tumors, GATA-4 function is unlikely to be tumor-suppressing, probably due to the nature of the very primitive multipotent tumor cells. GATA-4, along with its possible downstream factor Epo, could be utilized as novel hepatic tumor markers to supplement the present diagnostics. They could also serve a function in future biological therapies for aggressive pediatric tumors.

Interaction of alcohol and smoking in the pathogenesis of upper digestive tract cancers - possible chemoprevention with cysteine

Background: Alcohol consumption and smoking are the main causes of upper digestive tract cancers. These risk factors account for over 75% of all cases in developed countries. Epidemiological studies have shown that alcohol and tobacco interact in a multiplicative way to the cancer risk, but the pathogenetic mechanism behind this is poorly understood. Strong experimental and human genetic linkage data suggest that acetaldehyde is one of the major factors behind the carcinogenic effect. In the digestive tract, acetaldehyde is mainly formed by microbial metabolism of ethanol. Acetaldehyde is also a major constituent of tobacco smoke. Thus, acetaldehyde from both of these sources may have an interacting carcinogenic effect in the human upper digestive tract. Aims: The first aim of this thesis was to investigate acetaldehyde production and exposure in the human mouth resulting from alcohol ingestion and tobacco smoking in vivo. Secondly, specific L-cysteine products were prepared to examine their efficacy in the binding of salivary acetaldehyde in order to reduce the exposure of the upper digestive tract to acetaldehyde. Methods: Acetaldehyde levels in saliva were measured from human volunteers during alcohol metabolism, during tobacco smoking and during the combined use of alcohol and tobacco. The ability of L-cysteine to eliminate acetaldehyde during alcohol metabolism and tobacco smoking was also investigated with specifically developed tablets. Also the acetaldehyde production of Escherichia coli - an important member of the human microbiota - was measured in different conditions prevailing in the digestive tract. Results and conclusions: These studies established that smokers have significantly increased acetaldehyde exposure during ethanol consumption even when not actively smoking. Acetaldehyde exposure was dramatically further increased during active tobacco smoking. Thus, the elevated aerodigestive tract cancer risk observed in smokers and drinkers may be the result of the increased acetaldehyde exposure. Acetaldehyde produced in the oral cavity during ethanol challenge was significantly decreased by a buccal L-cysteine -releasing tablet. Also smoking-derived acetaldehyde could be totally removed by using a tablet containing L-cysteine. In conclusion, this thesis confirms the essential role of acetaldehyde in the pathogenesis of alcohol- and smoking-induced cancers. This thesis presents a novel experimental approach to decrease the local acetaldehyde exposure of the upper digestive tract with L-cysteine, with the eventual goal of reducting the prevalence of upper digestive tract cancers.

Synthesis of Cu@ZnO Core−Shell Nanocomposite through Digestive Ripening of Cu and Zn Nanoparticles

The synthesis of colloids of copper and zinc nanoparticles by solvated metal atom dispersion (SMAD) is described. The as-prepared colloids with a large size distribution of the particles are transformed into colloidal nanoparticles of a narrow size distribution by the digestive ripening process which involves refluxing the colloid at or near the boiling point of the solvent in the presence of a passivating ligand. The copper nanoparticles of 2.1 ± 0.3 nm and zinc nanoparticles of 3.9 ± 0.3 nm diameters have thus been obtained. Digestive ripening of the as-prepared copper and zinc colloids together in the presence of a passivating agent gave Cu@ZnO core−shell nanoparticles, with an average diameter of 3.0 ± 0.7 nm. Particles synthesized in this manner were characterized by UV−visible spectroscopy, high-resolution electron microscopy, energy-filtered electron microscopy, and powder X-ray diffraction methods which confirm the core−shell structure.

Contrast-enhanced ultrasound of abdominal organs in cats

The primary aim of this thesis was the evaluation of the perfusion of normal organs in cats using contrast-enhanced ultrasound (CEUS), to serve as a reference for later clinical studies. Little is known of the use of CEUS in cats, especially regarding its safety and the effects of anesthesia on the procedure, thus, secondary aims here were to validate the quantitative analyzing method, to investigate the biological effects of CEUS on feline kidneys, and to assess the effect of anesthesia on splenic perfusion in cats undergoing CEUS. -- The studies were conducted on healthy, young, purpose-bred cats. CEUS of the liver, left kidney, spleen, pancreas, small intestine, and mesenteric lymph nodes was performed to characterize the normal perfusion of these organs on ten anesthetized, male cats. To validate the quantification method, the effects of placement and size of the region of interest (ROI) on perfusion parameters were investigated using CEUS: Three separate sets of ROIs were placed in the kidney cortex, varying in location, size, or depth. The biological effects of CEUS on feline kidneys were estimated by measuring urinary enzymatic activities, analyzing urinary specific gravity, pH, protein, creatinine, albumin, and sediment, and measuring plasma urea and creatinine concentrations before and after CEUS. Finally, the impact of anesthesia on contrast enhancement of the spleen was investigated by imaging cats with CEUS first awake and later under anesthesia on separate days. -- Typical perfusion patterns were found for each of the studied organs. The liver had a gradual and more heterogeneous perfusion pattern due to its dual blood flow and close proximity to the diaphragm. An obvious and statistically significant difference emerged in the perfusion between the kidney cortex and medulla. Enhancement in the spleen was very heterogeneous at the beginning of imaging, indicating focal dissimilarities in perfusion. No significant differences emerged in the perfusion parameters between the pancreas, small intestine, and mesenteric lymph nodes. -- The ROI placement and size were found to have an influence on the quantitative measurements of CEUS. Increasing the depth or the size of the ROI decreased the peak intensity value significantly, suggesting that where and how the ROI is placed does matter in quantitative analyses. --- A significant increase occurred in the urinary N-acetyl-β-D-glucosaminidase (NAG) to creatinine ratio after CEUS. No changes were noted in the serum biochemistry profile after CEUS, with the exception of a small decrease in blood urea concentration. The magnitude of the rise in the NAG/creatinine ratio was, however, less than the circadian variation reported earlier in healthy cats. Thus, the changes observed in the laboratory values after CEUS of the left kidney did not indicate any detrimental effects in kidneys. Heterogeneity of the spleen was observed to be less and time of first contrast appearance earlier in nonanesthetized cats than in anesthetized ones, suggesting that anesthesia increases heterogeneity of the feline spleen in CEUS. ---- In conclusion, the results suggest that CEUS can be used also in feline veterinary patients as an additional diagnostics aid. The perfusion patterns found in the imaged organs were typical and similar to those seen earlier in other species, with the exception of the heterogeneous perfusion pattern in the cat spleen. Differences in the perfusion between organs corresponded with physiology. Based on the results, estimation of focal perfusion defects of the spleen in cats should be performed with caution and after the disappearance of the initial heterogeneity, especially in anesthetized or sedated cats. Finally, these results indicate that CEUS can be used safely to analyze kidney perfusion also in cats. Future clinical studies are needed to evaluate the full potential of CEUS in feline medicine as a tool for diagnosing lesions in various organ systems.

A Procedure for the 3D Reconstruction of Biological Organs from 2D Image Sequences

In this work, a procedure is presented for the reconstruction of biological organs from image sequences obtained through CT-scan. Although commercial software, which can accomplish this task, are readily available, the procedure presented here needs only free software. The procedure has been applied to reconstruct a liver from the scan data available in literature. 3D biological organs obtained this way can be used for the finite element analysis of biological organs and this has been demonstrated by carrying out an FE analysis on the reconstructed liver.

Reconstructing Solid Model from 2D Scanned Images of Biological Organs for Finite Element Simulation

This work presents a methodology to reconstruct 3D biological organs from image sequences or other scan data using readily available free softwares with the final goal of using the organs (3D solids) for finite element analysis. The methodology deals with issues such as segmentation, conversion to polygonal surface meshes, and finally conversion of these meshes to 3D solids. The user is able to control the detail or the level of complexity of the solid constructed. The methodology is illustrated using 3D reconstruction of a porcine liver as an example. Finally, the reconstructed liver is imported into the commercial software ANSYS, and together with a cyst inside the liver, a nonlinear analysis performed. The results confirm that the methodology can be used for obtaining 3D geometry of biological organs. The results also demonstrate that the geometry obtained by following this methodology can be used for the nonlinear finite element analysis of organs. The methodology (or the procedure) would be of use in surgery planning and surgery simulation since both of these extensively use finite elements for numerical simulations and it is better if these simulations are carried out on patient specific organ geometries. Instead of following the present methodology, it would cost a lot to buy a commercial software which can reconstruct 3D biological organs from scanned image sequences.

Colloidal calcium nanoparticles: digestive ripening in the presence of a capping agent and coalescence of particles under an electron beam

The nanochemistry of calcium remains unexplored, which is largely due to the inaccessibility of calcium nanoparticles in an easy to handle form by conventional methods of synthesis as well as its highly reactive and pyrophoric nature. The synthesis of colloidal Ca nanoparticles by the solvated metal atom dispersion (SMAD) method is described. The as-prepared Ca-THF nanoparticles, which are polydisperse, undergo digestive ripening in the presence of a capping agent, hexadecyl amine (HDA) to afford highly monodisperse colloids consisting of 2-3 nm sized Ca-HDA nanoparticles. These are quite stable towards precipitation for long periods of time, thereby providing access to the study of the nanochemistry of Ca. Particles synthesized in this manner were characterized by UV-visible spectroscopy, high resolution electron microscopy, and powder X-ray diffraction methods. Under an electron beam, two adjacent Ca nanoparticles undergo coalescence to form a larger particle.