Successful treatment of c-kit-positive metastatic Adenoid Cystic Carcinoma (ACC) with a combination of curcumin plus imatinib: A case report.

Adenoid cystic carcinoma (ACC) is an aggressive malignant neoplasm of the secretory glands. Conventional chemotherapy has poor effectiveness against metastatic ACC. Thus, a novel effective therapy is needed against metastatic ACC. A majority of ACCs (up to 94%) express c-kit. Imatinib is monoclonal antibody with specific activity against c-kit but has not been found to be effective in treating patients with ACC in which c-kit is overexpressed and activated. The NF-κB and mTOR pathways have been shown that ubiquitously and concurrently activated, indicating that the inhibition of these pathways may represent a novel treatment approach for patients with ACC. Curcumin has been shown to inhibit NF-κB and NF-κB-related pathways. 43-year-old patient was diagnosed ACC from submandibular salivary gland. After complete resection of tumor adjuvant radiotherapy was initiated. Seven years later multiple lung metastases were detected and ACC was confirmed by re-biopsy. First-line chemotherapy failed. NF-κB and c-kit were overexpressed in the metastatic specimens. Therefore, we treated the patient with metastatic chemoresistant ACC with imatinib 400mg/day and intravenous curcumin 225mg/m(2) twice a week plus oral bioavailable curcumin Arantal(®) 2×84mg/day. At 24 months, we observed near complete anatomic and complete metabolic response. To our knowledge, this is the first report of a patient with a c-kit-positive ACC that is successfully treated with the combination of imatinib and curcumin in an integrative approach.

The effects of excess boron with niacin on Daucus carota L. (carrot) root callus.

Niacin (Nicotinic acid, B3 vitamin) may be involved in reduction of toxic effects of boron by regulating growth metabolism. This study was designed to examine whether external niacin treatment would improve the boron mobility in carrot callus cells or not. The results showed that excess boron caused tracheary inversions in meristematic root tissue, and also a shortage was seen in tracheary lengths with boric acid treatment. Boron excess induced the plant tolerance to water stress inverting the tracheary cells. This shortage converted nearly to normal size with niacin and boron treatment together. The results showed that boron mobility induced by niacin could reduce significantly the fresh and dry weight of carrot root cells, protein and ABA content was reduced also, in contrary, external boron and boron with niacin treatment considerable increased the two factors after one month stress. Fresh weight reduction and ABA content reduction indicated that niacin treatment caused water stress on the root cells of carrot, but boron treatment and boron with niacin treatment increased drought tolerance in carrot cells by increasing the both factors. In addition, turning the conversion of the length of the trachearies to their normal size proved that niacin treatment ended the polarizing effects of boron on cell walls.

Effect of static electric fields in root cells of Vicia faba (Fabaceae).

Serial electron microscopic sections were prepared from half-ripened meristematic root cells of Vicia faba (Fabaceae) which had been exposed gradually to 700, 1000, 2500, 3500, and 5000 V/m static electric fields during seven days with and without Zn and Cd electrodes. At the end of five weeks, wall loosenings and very small nuclei were observed in those root cells which were exposed to static electric currents from the lower side of the medium without electrodes, while abnormalities in cell formation, e.g., two cells with one nucleus, and GER occurrence were present in an electrolytic (Cd upward and Zn downward) medium. The cells exposed to a static current from the upper side of the medium had small nuclei and abnormal cell divisions in the electrolyte, but in a non-electrolyte very large nuclei and thicker cell walls were observed, the cytoplasm was dense with GER, pinocytosis was seen filled with mitochondria, and protoplast formation with big nuclei was seen in exocytosis.

The effect of shear stress on solitary waves in arteries.

In the present work, we study the propagation of solitary waves in a prestressed thick walled elastic tube filled with an incompressible inviscid fluid. In order to include the geometric dispersion in the analysis the wall inertia and shear deformation effects are taken into account for the inner pressure-cross-sectional area relation. Using the reductive perturbation technique, the propagation of weakly non-linear waves in the long-wave approximation is examined. It is shown that, contrary to thin tube theories, the present approach makes it possible to have solitary waves even for a Mooney-Rivlin (M-R) material. Due to dependence of the coefficients of the governing Korteweg-deVries equation on initial deformation, the solution profile changes with inner pressure and the axial stretch. The variation of wave profiles for a class of elastic materials are depicted in graphic forms. As might be seen from these illustrations, with increasing thickness ratio, the profile of solitary wave is steepened for a M-R material but it is broadened for biological tissue.

Waves in initially stressed fluid-filled thick tubes.

In this paper, treating the artery as a thick walled cylindrical shell made of an incompressible, elastic and isotropic material and the blood as an incompressible inviscid fluid, by taking the inertia of the wall into account, the propagation of harmonic waves in an initially stressed tube, filled with an inviscid fluid, is studied. Utilizing inner-pressure-inner-cross-sectional-area relation in the linear momentum equation of the fluid, together with the continuity equation, we obtained two nonlinear equation governing the axial velocity and the cross-sectional area of the tube. Assuming that the dynamical motion superposed on large initial static deformation is small, a harmonic wave type of solution to incremental equations is sought and the dispersion relation is obtained as a function of transmural pressure, axial stretch, thickness ratio and the wave number. The wave speed is evaluated numerically for various materials and thickness/radius, and the results are depicted in graphical forms. The result indicates that, due to the inertial component of pressure, the wave is dispersive. The present formulation is compared with some previously published works.

A quasi-linear constitutive relation for arterial wall materials.

In this work, considering that under physiological conditions the arteries are subjected to a large initial static deformation and additional small dynamical displacements are superimposed on this initial field, a Boltzman type of constitutive relation is presented for arterial wall materials. For its simplicity in the analysis, the material under investigation is assumed to be isotropic, incompressible and constitutionally nonlinear in Green deformation tensor but linear in the history of deformation tensor. The numerical values of elastic coefficients are obtained by comparing the analytical results with experiments by Simon et al. [Circ. Res. 30, 491-500 (1972)]. For the determination of viscoelastic coefficients we studied the propagation of torsional waves in a prestressed thin cylindrical tube and proposed a method of determining the viscoelastic coefficients.

An evolution of pulse speed in arteries.

In this work, treating the artery as a thick-walled cylindrical shell made of an incompressible, isotropic and elastic solid, utilizing the large deformation theory and the stress-strain relation proposed by Demiray (1976b, Trans. ASME Ser. E, J. Appl. Mech., 98, 194-197), an explicit expression for the pulse speed is obtained and the effect of lumen pressure and the axial stretch on wave speed is discussed. Numerical results indicate that the wave speed increases with lumen pressure but decreases with the axial stretch. The results of the present model are compared with our previous work (Demiray, 1988, J. Biomech. 21, 55-58) on the same subject.

Pulse velocities in initially stressed arteries.

In this short paper, treating the artery as a thick walled cylindrical shell and employing the large deformation theory, an analytical expression for the pulse wave speed is obtained and the effect of lumen pressure and the axial stretch on the wave speed is discussed. Numerical results indicate that although the wave speed increases with inner pressure, it decreases with increasing axial stretch.

A stress-strain relation for a rat abdominal aorta.

Assuming the arterial wall is homogeneous, incompressible, isotropic and elastic, a stress-strain relation has been presented for a rat's abdominal aorta. As an illustrating example, the problem of simultaneous inflation and the axial stretch of a cylindrical artery under physiological loading has been solved and then the material coefficients are determined by comparing theoretical results with the existing experiments. The result indicates that the maximum deviation between the theory and experiment for various pressure levels is 3.7% which seems to be a good approximation of theory to the experiments. The variation of circumferential stress and the incremental pressure modulus with inner pressure are also depicted in the work.

Incremental elastic modulus for ventricles in diastole.

Utilizing the formulation of so-called 'small deformations superimposed on a large initial deformation' the incremental pressure modulus of a ventricle in diastole is studied and the explicit expression of it is obtained as a function of intraventricular pressure. In the analysis the ventricular wall material is assumed to be homogeneous, incompressible, isotropic and the stress-strain relation is exponential. The numerical results for a dog left ventricle indicate that above a critical value of inner pressure the incremental pressure modulus increases with increasing intra-ventricular pressure. Furthermore, the relationship between the stiffness and pressure is seen to be curvilinear (particularly for low pressure level), but for large values of inner pressure the behavior of the curve may be approximated by a set of straight lines.

On large periodic motions of arteries.

The large, radial periodic motion of an artery subjected to a dynamic inner pressure is studied through the use of finite deformation theory of elastic materials. The artery is assumed to behave as an isotropic, homogeneous and incompressible elastic material. Expressions for intramural pressure and wall stresses are obtained as a function of the large periodic motion. Dynamic effects are shown to both increase the diastolic pressure and decrease the systolic pressure. It is also shown that, under certain conditions, the artery may experience a negative intramural pressure, in which case the artery may collapse. The present study predicts very large circumferential stress and stress gradients which might lead the artery to arteriosclerosis.

Large deformation analysis of some soft biological tissues.

Due to physiological structure of most of the soft biological tissues, measurable stresses develop after the specimen has been stretched to many hundreds of percent of its relaxed length. Therefore, the nonlinear stress-strain relations developed for vulcanized rubber cannot be applied to soft tissues, which are constitutionally much more nonlinear than other engineering materials. In this article, using two different elastic models proposed for elastic soft tissues, simple elongation of a cylindrical bar and the inflation of a spherical thick shell, which is deemed to be a model for a left ventricle, are studied and the material coefficients characterizing the elastic model are obtained via comparing theoretical results with existing experiments on tissues. Furthermore, the elastic stiffnesses which are very important for physiologists and cardiologists are discussed and the consistency of the result with experiments are indicated.