betadex and Hypoxia

Radiotherapy is an indispensable treatment for esophageal cancer (EC), but radioresistance is not uncommon. Curcumol, as an active extract from traditional Chinese medicines, has been reported to have antitumor activity in various types of human tumor cells. However, its reversal of radioresistance has been rarely reported.. In the present study, curcumol was prepared as an inclusion complex with β-cyclodextrin. EC cell lines were treated with radiation and curcumol β-cyclodextrin inclusion complex (CβC), and the effect of radiosensitization of CβC was investigated in vitro and in vivo. The in vitro experiments included cell proliferation assay, clonogenic survival assay, apoptosis assay, cell cycle assay, and western blot assay.. The in vitro data revealed that CβC and irradiation synergistically inhibited the proliferation, reduced the colony formation, promoted the apoptosis, increased the G2/M phase, inhibited DNA damage repair, and reversed the hypoxia-mediated radioresistance of EC cells to a greater extent than did CβC alone or irradiation alone. The sensitization enhancement ratios (SERs) were 1.39 for TE-1 and 1.48 for ECA109 under hypoxia. The SERs were 1.25 for TE-1 and 1.32 for ECA109 under normoxia. The in vivo data demonstrated that the combination of CβC and irradiation could inhibit tumor growth to the greatest extent compared with either monotherapy alone. The enhancement factor was 2.45.. This study demonstrated that CβC could enhance radiosensitivity of EC cells under hypoxic and normoxic condition. Thus, CβC can be used as an effective radiosensitizer for EC.

Topics: beta-Cyclodextrins; Esophageal Neoplasms; Humans; Hypoxia; Radiation Tolerance

Topics: beta-Cyclodextrins; Cell Line, Tumor; Humans; Hydrogen Peroxide; Hypoxia; Nanoparticles; Neoplasms; Photochemotherapy; Photosensitizing Agents; Photothermal Therapy; Tumor Microenvironment

Hypoxia is one of the critical features in solid tumors, and hypoxia-targeting contrast agents (CAs) could greatly enhance the magnetic resonance imaging (MRI) of tumors by increasing its specificity and providing more diagnosis information. In this article, an internally hydroxy dendrimer of high molecular weight was facilely synthesized by "epoxy-amine" and "thiol-ene" reactions with a β-cyclodextrin (β-CD) as the core, and a hypoxia-targeting dendritic contrast agent (DCA) was synthesized through conjugating Gd chelates onto the internal hydroxyl groups and grafting the hypoxia-targeting groups sulfonamides and zwitterionic groups onto the exterior groups of the dendrimer. The zwitterionic surface without disturbance from internally conjugated CAs could reduce unspecific cellular uptake by normal cells, while the hypoxia-targeting group mediate the cellular uptake by hypoxic tumor cells. The in vitro and in vivo study showed that the hypoxia-targeting DCA could be selectively uptake by hypoxic cancer cells and greatly enhance the MRI of orthotopic breast tumor in a mouse model.

Topics: Animals; beta-Cyclodextrins; Cell Line, Tumor; Chelating Agents; Contrast Media; Dendrimers; Drug Design; Female; Gadolinium; HeLa Cells; Humans; Hypoxia; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Microscopy, Confocal; Neoplasm Transplantation; Rhodamines

The hyper-activation of glutamate receptors is a key event in the degenerative processes triggered by ischemia in the brain. Several types of these receptors reside in cholesterol-sphingomyelin rich domains of post-synaptic plasma membranes and have been described to be sensitive to cholesterol depletion. Hence we investigated, by extracellular recordings, the effect of cholesterol depletion on population spikes (PS) during ischemia-like conditions in the CA1 region of rat hippocampal slices using the cholesterol-depleting agent methyl-beta-cyclodextrin (MbetaCD). Results obtained demonstrate that MbetaCD prevents the changes induced by anoxic insult, i.e., depression of the population spike amplitude and insurgence of ischemic long-term potentiation. Furthermore cholesterol depletion prevents the disappearance of population spike induced by anoxia/aglycemia during kainate perfusion. Our data suggest a possible role of MbetaCD in preventing the pathological changes in synaptic activity induced by ischemia and indicate that manipulation of lipid components of membrane rafts might provide a new approach for the treatment of ischemia.

Topics: Action Potentials; Analysis of Variance; Animals; beta-Cyclodextrins; CA1 Region, Hippocampal; Cholesterol; Electrophysiology; Excitatory Postsynaptic Potentials; Glucose; Hypoxia; Kainic Acid; Male; Membrane Potentials; N-Methylaspartate; Neurons; Organ Culture Techniques; Rats; Rats, Wistar; Time Factors