Tissue engineering using Adipose Derived Stromal Cells (ADSCs) has emerged as a novel regenerativ... more Tissue engineering using Adipose Derived Stromal Cells (ADSCs) has emerged as a novel regenerative medicine approach to replace and reconstruct soft tissue damaged or lost as a result of disease process or therapeutic surgical resection. ADSCs are an attractive cell source for soft tissue regeneration due to the fact that they are easily accessible, multipotent, non-immunogenic and pro-angiogenic. ADSC based regenerative strategies have been successfully translated to the clinical setting for the treatment of Crohn's fistulae, musculoskeletal pathologies, wound healing, and cosmetic breast augmentation (fat grafting). ADSCs are particularly attractive as a source for adipose tissue engineering as they exhibit preferential differentiation to adipocytes and support maintenance of mature adipose graft volume. The potential for reconstruction with an autologous tissue sources and a natural appearance and texture is particularly appealing in the setting of breast cancer; up to 40% of patients require mastectomy for locoregional control and current approaches to post-mastectomy breast reconstruction (PMBR) are limited by the potential for complications at the donor and reconstruction sites. Despite their potential, the use of ADSCs in breast cancer patients is controversial due to concerns regarding oncological safety. These concerns relate to the regeneration of tissue at a site where a malignancy has been treated and the impact this may have on stimulating local disease recurrence or dissemination. Pre-clinical data suggest that ADSCs exhibit pro-oncogenic characteristics and are involved in stimulating progression, and growth of tumour cells. However, there have been conflicting reports on the oncologic outcome, in terms of locoregional recurrence, for breast cancer patients in whom ADSC enhanced fat grafting was utilised as an alternative to reconstruction for small volume defects. A further consideration which may impact the successful translation of ADSC based regenerative strategies for post cancer reconstruction is the potential effects of cancer therapy. This review aims to address the effect of malignant cells, adjuvant therapies and patient-specific factors that may influence the success of regenerative strategies using ADSCs for post cancer tissue regeneration.
Molecular modeling method has been used for modeling a new molecule for Breast and colorectal can... more Molecular modeling method has been used for modeling a new molecule for Breast and colorectal cancer using Topotecan, a drug that’s already designed. This drug is drawn using HYPERCHEM and its R group is modified by replacing different functional groups like OH, CCl2OH, CF2OH, CH2CH2CH3, CH2CH3, CH3, Cl, F, H, and NH2, etc in its place. Molecules designed as such are optimized using different algorithms and their affinity is checked with the protein. The binding free energy of the protein is calculated by performing docking process. The docking process is done with the help of GOLD software. The molecule with minimum binding energy will have the maximum binding affinity. From the results obtained it’s clear that ligand “2(CCl2OH)”has the maximum binding affinity and this molecule is determined as the best lead molecule targets computationally. The calculated binding affinities between inhibitors 1,2,3,4,5,6, 7,8,9,10 are compared. The calculated binding affinities of the inhibitors indicate that inhibitor “2” (CCl2OH) would be expected to be better inhibitor than lead inhibitor 1,3,4,5,6,7,8,9 and 10. Inhibitor “2’’ predicted to be the most potent inhibitor of TOPOTECAN inhibitor as compared to all the other inhibitors considered in this study. For all the cases the minimization results provided qualitative agreement with experimental results. Therefore, this approach could be very useful for screening a larger set of compounds prior to synthesis accordingly; there is a need for methods that enable rapid assessment of large number of structurally unrelated molecules in a reasonably accurate manner. Energy components calculated by performing molecular mechanics calculations both in explicit solvent and complex states are sufficient to estimate the relative binding free energy differences between inhibitors qualitatively.
A Simple, Fast, Precise reverse phase isocratic high performance liquid chromatographic (HPLC) te... more A Simple, Fast, Precise reverse phase isocratic high performance liquid chromatographic (HPLC) technique has been developed for the simultaneous estimation of Olmesartan medoxomil (OLM) and Hydrochlorothiazide (HCTZ) in marketed formulations. Estimation of these combined formulation was performed using Waters Symmetry C 18 column (150 x 4.6 mm, 5µm) using the mobile phase of composition Methanol , Acetonitrile and Ammonium acetate buffer (50:25:25 v/v/v, pH 3.5). The flow rate was 1.0ml/min and the seperation was observed at 240nm. The retention time of OLM and HCTZ was found to be 3.34 min and 1.69 min respectively. The method was found to be linear over a range of 30 µg/ml for OLM and 18.75 µg/ml for HCTZ. The method was validated according to the guidelines of International Conference on Harmonisation (ICH) and was successfully employed in the estimation of commercial formulations.
Tissue engineering using Adipose Derived Stromal Cells (ADSCs) has emerged as a novel regenerativ... more Tissue engineering using Adipose Derived Stromal Cells (ADSCs) has emerged as a novel regenerative medicine approach to replace and reconstruct soft tissue damaged or lost as a result of disease process or therapeutic surgical resection. ADSCs are an attractive cell source for soft tissue regeneration due to the fact that they are easily accessible, multipotent, non-immunogenic and pro-angiogenic. ADSC based regenerative strategies have been successfully translated to the clinical setting for the treatment of Crohn's fistulae, musculoskeletal pathologies, wound healing, and cosmetic breast augmentation (fat grafting). ADSCs are particularly attractive as a source for adipose tissue engineering as they exhibit preferential differentiation to adipocytes and support maintenance of mature adipose graft volume. The potential for reconstruction with an autologous tissue sources and a natural appearance and texture is particularly appealing in the setting of breast cancer; up to 40% of patients require mastectomy for locoregional control and current approaches to post-mastectomy breast reconstruction (PMBR) are limited by the potential for complications at the donor and reconstruction sites. Despite their potential, the use of ADSCs in breast cancer patients is controversial due to concerns regarding oncological safety. These concerns relate to the regeneration of tissue at a site where a malignancy has been treated and the impact this may have on stimulating local disease recurrence or dissemination. Pre-clinical data suggest that ADSCs exhibit pro-oncogenic characteristics and are involved in stimulating progression, and growth of tumour cells. However, there have been conflicting reports on the oncologic outcome, in terms of locoregional recurrence, for breast cancer patients in whom ADSC enhanced fat grafting was utilised as an alternative to reconstruction for small volume defects. A further consideration which may impact the successful translation of ADSC based regenerative strategies for post cancer reconstruction is the potential effects of cancer therapy. This review aims to address the effect of malignant cells, adjuvant therapies and patient-specific factors that may influence the success of regenerative strategies using ADSCs for post cancer tissue regeneration.
Molecular modeling method has been used for modeling a new molecule for Breast and colorectal can... more Molecular modeling method has been used for modeling a new molecule for Breast and colorectal cancer using Topotecan, a drug that’s already designed. This drug is drawn using HYPERCHEM and its R group is modified by replacing different functional groups like OH, CCl2OH, CF2OH, CH2CH2CH3, CH2CH3, CH3, Cl, F, H, and NH2, etc in its place. Molecules designed as such are optimized using different algorithms and their affinity is checked with the protein. The binding free energy of the protein is calculated by performing docking process. The docking process is done with the help of GOLD software. The molecule with minimum binding energy will have the maximum binding affinity. From the results obtained it’s clear that ligand “2(CCl2OH)”has the maximum binding affinity and this molecule is determined as the best lead molecule targets computationally. The calculated binding affinities between inhibitors 1,2,3,4,5,6, 7,8,9,10 are compared. The calculated binding affinities of the inhibitors indicate that inhibitor “2” (CCl2OH) would be expected to be better inhibitor than lead inhibitor 1,3,4,5,6,7,8,9 and 10. Inhibitor “2’’ predicted to be the most potent inhibitor of TOPOTECAN inhibitor as compared to all the other inhibitors considered in this study. For all the cases the minimization results provided qualitative agreement with experimental results. Therefore, this approach could be very useful for screening a larger set of compounds prior to synthesis accordingly; there is a need for methods that enable rapid assessment of large number of structurally unrelated molecules in a reasonably accurate manner. Energy components calculated by performing molecular mechanics calculations both in explicit solvent and complex states are sufficient to estimate the relative binding free energy differences between inhibitors qualitatively.
A Simple, Fast, Precise reverse phase isocratic high performance liquid chromatographic (HPLC) te... more A Simple, Fast, Precise reverse phase isocratic high performance liquid chromatographic (HPLC) technique has been developed for the simultaneous estimation of Olmesartan medoxomil (OLM) and Hydrochlorothiazide (HCTZ) in marketed formulations. Estimation of these combined formulation was performed using Waters Symmetry C 18 column (150 x 4.6 mm, 5µm) using the mobile phase of composition Methanol , Acetonitrile and Ammonium acetate buffer (50:25:25 v/v/v, pH 3.5). The flow rate was 1.0ml/min and the seperation was observed at 240nm. The retention time of OLM and HCTZ was found to be 3.34 min and 1.69 min respectively. The method was found to be linear over a range of 30 µg/ml for OLM and 18.75 µg/ml for HCTZ. The method was validated according to the guidelines of International Conference on Harmonisation (ICH) and was successfully employed in the estimation of commercial formulations.
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Papers by Ritihaas Surya Challapalli