fosbretabulin and Uterine-Cervical-Neoplasms

In this study, we investigated the nanocharacteristics of CB-NPs, focusing on active pharmaceutical ingredients (API), as well as lyophilized samples combining API with protective agents (PAs). The in vivo efficacy of final sample (API + PAs) was evaluated.. The assembled sphere of API with complex core and thin-shell structure was confirmed. PAs were found to significantly influence in vivo efficacy. Collaborative efforts between API and PAs, namely mannitol and lactose, resulted in the most promising lyophilized sample, ie, the final sample (FS2) for CC therapy. Impressively, FS2 demonstrated an exceptional 100% cure rate on the CC U14-bearing mice model.. FS2 has provided significant insights for cervical cancer therapy. It is also crucial to develop a comprehensive evaluation strategy for the formulation of nanomedicine, which has the potential to serve as a guideline for future clinical trials.

Topics: Animals; Antineoplastic Agents; Female; Glutamic Acid; Humans; Mice; Nanoparticles; Polyethylene Glycols; Uterine Cervical Neoplasms

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Drug Design; Female; HEK293 Cells; HeLa Cells; Humans; Indoles; Mice, Nude; Mitosis; Models, Molecular; Neoplasms; Pyrazoles; Tubulin Modulators; Uterine Cervical Neoplasms

In the synergistic treatment with cytotoxic drug and vascular disrupting agent, the order of drug release shows great importance to enhance the antitumor efficacy. When vascular disrupting agent is firstly administrated, the reduced blood supply and overexpressed hypoxia-inducible factor-1α greatly limit the efficiency of chemotherapy. In this work, an injectable thermo-sensitive polypeptide hydrogel was firstly developed for the locally sequential delivery of hydrophilic doxorubicin (DOX, a cytotoxic agent) and hydrophobic combretastatin A4 (CA4, a vascular disrupting drug). The aqueous solution of polypeptide at low temperature transformed into hydrogel under the body temperature after subcutaneous injection and completely degraded after four weeks with excellent biocompatibility. DOX and CA4 were co-loaded into the hydrogel, and the release of DOX showed much faster than that of CA4 due to their difference in water solubility. The superior inhibition of tumor volume after treatment with DOX and CA4 co-loaded hydrogel occurred in the treatment of grafted mouse U14 cervical tumor compared with both free drugs and single drug-loaded hydrogels. In addition, the co-loaded hydrogel obtained enhanced apoptosis of tumor cells, significant shutdown of blood vessels, and wholly regional tumor apoptosis, which indicated the eradication of solid tumor. Moreover, treatments with the drug-loaded hydrogels showed negligible damage to normal tissues, suggesting their low systemic toxicity. The locally sequential delivery system had great potential for in situ synergistic chemotherapy.. The release order makes great difference in the synergistic efficacies of cytotoxic drug and vascular disrupting agent. When cytotoxic drug is administrated before vascular disrupting agent, an eradication of tumor might be obtained. On the contrary, the antitumor efficiency will be greatly hindered by limited penetration of later cytotoxic drug and drug resistant induced by vascular disrupting agent. Therefore, the adjustment of the delivery behaviors of such two-pronged agents in one platform was significant for their efficiently synergistic chemotherapy. The present study originally provides a convenient strategy and an advanced sample for sequential administration of cytotoxic drug and vascular disrupting agent in one platform based on their water solubility to achieve upregulated efficacy and safety.

Topics: Animals; Doxorubicin; Drug Carriers; Drug Screening Assays, Antitumor; Female; Hydrogels; Mice; Mice, Inbred BALB C; Neoplasms, Experimental; Stilbenes; Uterine Cervical Neoplasms

Microtubules are dynamic structures that play a crucial role in cellular division and are recognized as an important target for cancer therapy. In search of new compounds with strong antiproliferative activity and simple molecular structure, a new series of 2-amino-3-(3',4',5'-trimethoxybenzoyl)-5-(hetero)aryl ethynyl thiophene derivatives was prepared by the Sonogashira coupling reaction of the corresponding 5-bromothiophenes with several (hetero)aryl acetylenes. When these compounds were analyzed in vitro for their inhibition of cell proliferation, the 2- and 3-thiophenyl acetylene derivatives were the most powerful compounds, both of which exerted cytostatic effects at submicromolar concentrations. In contrast, the presence of a more flexible ethyl chain between the (hetero)aryl and the 5-position of the thiophene ring resulted in significant reduction in activity relative to the 5-(hetero)aryl acetylene substituted derivatives. The effects of a selected series of compounds on cell cycle progression correlated well with their strong antiproliferative activity and inhibition of tubulin polymerization. We found that the antiproliferative effects of the most active compounds were associated with increase of the proportion of cells in the G(2)/M and sub-G(1) phases of the cell cycle.

Topics: Animals; Antimitotic Agents; Cell Line, Tumor; Cell Proliferation; Female; Humans; Leukemia; Mice; Molecular Structure; Structure-Activity Relationship; Thiophenes; Uterine Cervical Neoplasms