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Biomedical subjects

Ali Khan

Publications and source records attributed to Ali Khan.

8 recordsLinked to original sources
PubMed2026

Targeting of tripartite neuron-cancer-immune cell crosstalk augments response to chemotherapy and immunotherapy.

We report presence of cholinergic nerve fibers in the periphery and stroma of colon cancer tissues and their correlation with poor T cell and increased macrophage infiltration. We employed hydrogel-mediated localized delivery of an FDA-approved local anesthetic, bupivacaine (BUP), to target acetylcholine (ACh)-mediated crosstalk of cholinergic neurons with cancer and immune cells. Localized BUP-Gel therapy promotes T cell-mediated tumor inhibition and enhances the antitumor response of systemic chemotherapy and immunotherapy. Further, blockade of cancer- and immune cell-specific ACh receptors inhibits tumor growth, alters the TME, and augments the impact of chemotherapy and immunotherapy. Finally, we demonstrate that ACh receptor antagonists polarize macrophages toward an M1-like phenotype and activate T cell immunity in tumor explants of patients. Therefore, targeting cholinergic signals through localized delivery of anesthetics, as well as direct immune reprogramming via cholinergic receptor antagonists, may provide a means to modulate this tripartite crosstalk, with potential implications for therapeutic strategies.

Humans↗
PubMed2005

Solubilization and location of phenethylalcohol, benzaldehyde, and limonene in lamellar liquid crystal formed with block copolymer and water.

Three fragrances, phenethylalcohol, benzaldehyde, and limonene (that differ in their polarity), were solubilized in lamellar liquid crystal using the polyethylene oxide-polypropylene oxide-polyethylene oxide, (EO27PO61EO27), P104 triblock copolymer, and water. The interlayer spacing of the lamellar liquid crystal were established using small angle X-ray scattering (SAXS). The SAXS data are used to calculate the interfacial area per polyethylene oxide (PEO) block and to determine the location of each fragrance in the association structure. The results show the presence of phenethylalcohol at the interface while part of benzaldehyde contributing to the interface and the other part being located inside the polar/apolar domains. The third fragrance, limonene, did not participate in the formation of the interface and is located inside the apolar domain.

Journal Article↗
PubMed2005

Semi-automated basal ganglia segmentation using large deformation diffeomorphic metric mapping.

This paper investigates the techniques required to produce accurate and reliable segmentations via grayscale image matching. Finding a large deformation, dense, non-rigid transformation from a template image to a target image allows us to map a template segmentation to the target image space, and therefore compute the target image segmentation and labeling. We outline a semi-automated procedure involving landmark and image intensity-based matching via the large deformation diffeomorphic mapping metric (LDDMM) algorithm. Our method is applied specifically to the segmentation of the caudate nucleus in pre- and post-symptomatic Huntington's Disease (HD) patients. Our accuracy is compared against gold-standard manual segmentations and various automated segmentation tools through the use of several error metrics.

Algorithms↗
PubMed2004

Temperature and concentration effects on supramolecular aggregation and phase behavior for poly(propylene oxide)-b-poly(ethylene oxide)- b-poly(propylene oxide) copolymers of different composition in aqueous mixtures, 1.

The phase behavior (temperature vs composition) and microstructure for the two binary systems Pluronic 25R4 [(PO)19(EO)33(PO)19]-water and Pluronic 25R2 [(PO)21(EO)14(PO)21]-water have been studied by a combined experimental approach in the whole concentration range and from 5 to 80 degrees C. The general phase behavior has been identified by inspection under polarized light. Precise phase boundaries have been determined by analyzing 2H NMR line shape. The identification and microstructural characterization of the liquid crystalline phases have been achieved using small-angle X-ray scattering (SAXS). The isotropic liquid solution phases have been investigated by self-diffusion measurements (PGSE-NMR method). 25R2 does not form liquid crystals and is miscible with water in the whole concentration range; with increasing temperature, the mixtures split into water-rich and a copolymer-rich solutions in equilibrium. 25R4 shows rich phase behavior, passing, with increasing copolymer concentration, from a water-rich solution to a lamellar and copolymer-rich solution. A small hexagonal phase, completely encircled in the stability region of the water-rich solution, is also present. In water-rich solutions, at low temperatures and low copolymer concentrations, the copolymers are dissolved as independent macromolecules. With increasing copolymer concentrations an interconnected network of micelles is formed in which micellar cores of hydrophobic poly(propylene oxide) are interconnected by poly(ethylene oxide) strands. In copolymer-rich solutions water is molecularly dissolved in the copolymer. The factors influencing the self-aggregation of Pluronic R copolymers (PPO-PEO-PPO sequence) are discussed, and their behavior in water is compared to that of Pluronic copolymers (PEO-PPO-PEO sequence).

Macromolecular Substances↗
PubMed2004

Lysozyme in catanionic surfactant mixtures.

We investigate the competition between the associations of oppositely charged protein-surfactant complexes and oppositely charged surfactant complexes. In all systems examined, the most favorable complexation is the one between the two oppositely charged surfactant ions, despite the strong binding known, for example, dodecyl sulfate, DS-, to lysozyme. Thus, the phase behavior of the catanionic system is dominating the features observed also in the presence of protein. The phase behavior of the dilute protein-free dodecyltrimethylammonium chloride-sodium dodecyl sulfate-water system is presented and used as a basis for the discussion on the different solubilization mechanisms. Our results show that the mechanism for resolubilization of a protein-surfactant salt is fundamentally different when it is caused by addition of a second surfactant than when it is accomplished by an excess of the first surfactant. The competition between lysozyme and cationic amphiphiles as hosts for the anionic surfactants was studied experimentally and analyzed quantitatively. Aggregates with C12 cationic surfactants are clearly preferred by the anionic surfactants, while for C10 and particularly C8 a clear excess of cationic surfactant has to be added to completely dissolve the complex salt lysozyme-anionic surfactant.

Cations↗
PubMed2004

Perfusion of 99Tcm-labeled CD105 Mab into kidneys from patients with renal carcinoma suggests that CD105 is a promising vascular target.

There is strong published and unpublished evidence that our CD105 Mab E9, which is highly reactive with angiogenic endothelial cells, could be a useful reagent to target the vasculature of solid tumors in man. Since Mab E9 does not cross-react with animal tissues, we undertook here to evaluate its localization using human kidney as an ex vivo model. Perfusion was performed through the renal artery of 99Tcm-labeled purified CD105 Mab in freshly excised kidneys from 7 patients with renal carcinoma. In all 7 cases, immunoscintigraphs showed the presence of well-defined radioactive hot spots, which matched the positions of the tumors as identified by presurgery MRI scans and subsequent histopathologic examination. Importantly, in one instance, where a presurgery MRI scan had identified only one tumor, immunoscintigraphs showed 2 distinct hot spots of radioactivity. The pathology report confirmed that the additional hot spot corresponded to a small secondary well-vascularized tumor. The implication of this finding is that the radiolabeled Mab, E9, may be of use in the detection of metastatic disease. That the labeling of tumors was specific was confirmed when prior perfusion of unlabeled mab E9 in 2 kidneys completely blocked the localization of 99Tcm-conjugated Mab E9. Radioactivity in samples of tumor and normal tissue taken from 7 kidneys was counted in a gamma counter. In all cases, there was a greater uptake of radioactivity in tumors compared with the corresponding normal kidneys. The median values, adjusted per gram wet weight, for 99Tcm were 14.8 times (range, 4.8-113.0) greater in kidney tumors than in normal kidney tissue (p < 0.007). Immunofluorescent staining of cryostat sections of tumor tissues in each of the 7 cases showed strong and uniform localization of Mab E9 in tumor microvessels. Interestingly, chimeric staining of endothelial cells (ECs) was seen in an occasional microvessel segment. That is, while most of the ECs lining a microvessel were strongly stained, an occasional EC was negative. This was not an artifact of staining. Unstained ECs may be nonangiogenic or apoptotic since CD105 is a proliferation/activation-associated antigen. Further investigations are warranted to establish the pharmacokinetics of 99Tcm-labeled CD105 antibody in vivo. This would enable us to determine whether an apparently highly successful ex vivo study has the potential for tumor imaging/therapeutic vascular targeting in patients with cancer.

Antibodies, Monoclonal↗
PubMed2003

Vesicle formation and other structures in aqueous dispersions of monoolein and sodium oleate.

The macroscopic appearance and microstructure in the dilute corner of the ternary monoolein (MO)-sodium oleate (NaO)-water (2H2O) system have been investigated by visual inspection and by using direct structural imaging with light microscopy and cryogenic transmission electron microscopy. The microstructural transformations that take place between the micellar phase (binary NaO2H2O axis) and the dispersed cubic phase (binary MO2H2O axis) upon increasing the ratio of MO to NaO are micelles, ruptured multilamellar vesicles together with flexible threads, various vesicle structures, vesicles in equilibrium with densely packed layers that either represent bilayers or domains of H(II) tubes visible from the side, and finally a pattern that may be either a cubic phase or domains of H(II) tubes visible in a cross section. Spontaneously formed uni- and multilamellar vesicles that show long-term stability are found to be the dominant structure for mixed dispersions over almost the entire concentration range. The addition of NaOH to the non-bilayer-forming system, the ternary MOOA (oleic acid)-2H2O system, leads to the formation of vesicles. Vesicles were also observed in other ternary MO-aqueous-based systems with potassium oleate, cetyltrimethylammonium bromide, sodium taurodeoxycholate, or dipalmitoylphosphatidylcholine instead of NaO.

Cetrimonium↗