Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions

USA Disease Area. Cancer Biological Target. TLR7 Summary. Although immune checkpoint inhibitors have change the treatment landscape of many tumors, durable responses are limited. Immunological treatment of cold tumors is a great challenge, as no adaptive immune response has been set up or maintained. Cold tumors can, however, contain a substantial number of myeloid cells, including macrophages, different subsets of dendritic cells, and myeloid-derived suppressor cells.Toll-like receptors (TLRs) detect highly conserved, pathogenic danger signals, resulting in a strong inflammatory response. TLRs detect a wide range of conserved pathogen-associated molecular patterns (PAMPs). There are 10 known members of the TLT family in humans. Within this family, TLR3, TLR7, TLR8, and TLR9 are located within endosomes. Systemic administration of TLR agonists leads to strong systemic activation of different immune cells, and eventually immune cells within the tumor microenvironment are activated to achieve an antitumor effect.The present application describes a series of novel phosphorylpurinone compounds as TLR7 inhibitors for the treatment of cancer. Further, the application discloses compounds, their preparation, use, and pharmaceutical composition, and treatment.Definitions. R 1 = C 1−6 alkyl; R 2 = C 1−6 alkyl; and R 3 = pyridinyl substituted by ((C 1−6 alkyl) 2 amino)C 1−6 alkoxy, ((C 1−6 alkyl) 2 amino)C 1−6 alkylamino, ((C 1−6 alkyl) 2 amino)-C 1−6 alkylpyrrolidinyl, (C 1−6 alkyl) 2 piperazinyl, (C 1−6 alkylamino) C 1−6 alkylamino, (C 1−6 alkylpyrrolidinyl)amino, 2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrolyl, 2,5-diazabicyclo[2.2.2]octanyl, aminopyrrolidinyl, C 1−6 alkyl-1-oxa-4,9-diazaspiro[5.

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Preparation and evaluation of curcumin nanoemulsion to inhibit TC-1 cell growth

Karimi,

Qomi,

Jahromy

et al. 2024

Preprint

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Curcumin (Cur), a substance originating from Curcuma longa, has been comprehensively examined for its anticancer properties. Nonetheless, its clinical application has been restricted by its inadequate solubility, bioavailability, and stability. TC-1 cells have been impressive in understanding HPV biology and developing therapeutic approaches for HPV infection and related cancers, like cervical cancer, offering a close mimicry of HPV-induced carcinogenesis. This study's primary goal is to formulate and optimize curcumin nanoemulsions (Cur-NE) to address these challenges and, secondarily, evaluate their impact on TC-1 cell growth. Characterization of the nanoemulsions was conducted using dynamic light scattering (DLS), transmission electron microscopy (TEM) and High-performance liquid chromatography (HPLC) revealing an average particle size of 52.5 nm, a zeta potential of -13.1 mV, and a drug content of 94.6%. Through the dialysis diffusion technique, drug release profiles demonstrated a sustained, slower release of Cur from Cur-NE compared to free curcumin. According to an MTT assay, Cur-Ne with an IC50 35 µg/ml exhibited an increased inhibitory effect of Cur on TC-1 cancer cells, while showing no inhibitory effects on MC3T3 normal cells at concentrations up to 100 µg/ml. In summary, this study underscores the potential of nanoemulsions as efficient carriers for Cur, with demonstrated safety in both cancer and normal cells. Moreover, Cur-NE displayed substantial inhibitory activity against TC-1 cancer cells, suggesting its promise in treating HPV-associated cancers, particularly cervical cancer. Further research is warranted to evaluate the long-term safety of this nanoemulsion for clinical trials and its efficacy against other cancer cell lines.

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Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions

Cited by 4 publications

References 396 publications

Cervical Cancer Natural History, Diagnosis, and Treatment: From Molecular Events to Clinical Management

Cervical Cancer Natural History, Diagnosis, and Treatment: From Molecular Events to Clinical Management

Novel Phosphorylpurinone Compounds for Treating Cancer

Preparation and evaluation of curcumin nanoemulsion to inhibit TC-1 cell growth

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