Wei Huang

Biological Effects of Calceolarioside A as a Natural Compound: Anti-Ovarian Cancer, Anti-Tyrosinase, and Anti-HMG-CoA Reductase Potentials with Molecular Docking and Dynamics Simulation Studies

One kind of hydroxycinnamic acid is calceolarioside A. Plantago coronopus, Cassinopsis madagascariensis, and other organisms for whom data are available are known to have this naturally occurring compound. IC50 values of Calceolarioside A for ovarian cell lines (NIH-OVCAR-3, ES-2, UACC-1598, Hs832.Tc, TOV-21G, UWB1.289) were 24.42, 13.50, 9.31, 14.90, 20.07, and 16.18 µM, respectively. IC50 values were 19.83 and 73.48 µM for tyrosinase and HMG-CoA reductase enzymes. The chemical activities of Calceolarioside A against HMG-CoA reductase and tyrosinase were assessed by conducting the molecular docking study, MM/GBSA calculation, and molecular dynamics (MD) simulation. The anticancer activities of this compound were evaluated against some ovarian cancer cells, such as NIH-OVCAR-3, ES-2, UACC-1598, Hs832.Tc, TOV-21G, and UWB1.289 cell lines. The chemical activities of Calceolarioside A against some of the expressed surface receptor proteins (folate receptor, CD44, EGFR, Formyl Peptide Receptor-Like 1, M2 muscarinic receptor, and estrogen receptors) were investigated using computational methods. The results exhibited the interplay among atoms. The compound formed robust associations with both the enzymes and receptors. Calceolarioside A can hinder the functioning of these enzymes and the proliferation of malignant cells.

Mutant PP2A Induces IGFBP2 Secretion to Promote Development of High-Grade Uterine Cancer

Abstract Uterine serous carcinoma (USC) and uterine carcinosarcoma (UCS) tumors are uniquely aggressive, suggesting that the primary tumor is intrinsically equipped to disseminate and metastasize. Previous work identified mutational hotspots within PPP2R1A, which encodes the Aα scaffolding subunit of protein phosphatase 2A (PP2A), a heterotrimeric serine/threonine phosphatase. Two recurrent heterozygous PPP2R1A mutations, P179R and S256F, occur exclusively within high-grade subtypes of uterine cancer and can drive tumorigenesis and metastasis. Elucidation of the mechanisms by which PP2A Aα mutants promote tumor development and progression could help identify therapeutic opportunities. Here, we showed that expression of these mutants in USC/UCS cell lines enhanced tumor-initiating capacity, drove a hybrid epithelial-to-mesenchymal plasticity phenotype, and elevated secretion of the tumorigenic cytokine insulin growth factor (IGF) binding protein 2 (IGFBP2). Therapeutic targeting of the IGFBP2/IGF receptor 1 signaling axis using small molecules and genetic approaches resulted in marked tumor growth inhibition. Mechanistically, PP2A regulated IGFBP2 expression through the transcription factor, NF-κB, which harbors a B56 recognition motif. Collectively, these results identify a role for PP2A in regulating paracrine cancer cell signaling that can be targeted to block the initiation and metastasis of high-grade uterine cancer. Significance: Elevated IGFBP2 secretion by uterine cancer cells with heterozygous PPP2R1A mutations supports tumor progression and confers a vulnerability to IGFBP2/IGF1R inhibition as a therapeutic approach for this highly aggressive cancer subtype.

Hybrid Membrane Camouflaged Chemodrug-Gene Nanoparticles for Enhanced Combination Therapy of Ovarian Cancer

Recently, cell membrane camouflaged nanoparticles (NPs) endowed with natural cellular functions have been extensively studied in various biomedical fields. However, there are few reports about such biomimetic NPs used to codeliver chemodrug and genes for synergistic cancer treatment up to now. Herein, we first prepare chemodrug-gene nanoparticles (Mito-Her2 NPs) by the electrostatic interaction coself-assembly of mitoxantrone hydrochloride (Mito) and human epidermal growth factor receptor-2 antisense oligonucleotide (Her2 ASO). Then, Mito-Her2 NPs are coated by a hybrid membrane (RSHM), consisting of the red blood cell membrane (RBCM) and the SKOV3 ovarian cancer cell membrane (SCM), to produce biomimetic chemodrug-gene nanoparticles (Mito-Her2@RSHM NPs) for combination therapy of ovarian cancer. Mito-Her2@RSHM NPs integrate the advantages of RBCM (e.g., good immune evasion capability and long circulation lifetime in the blood) and SCM (e.g., highly specific cognate recognition) together and improve the anticancer efficacy of Mito-Her2 NPs. The results show that Mito-Her2@RSHM NPs can be devoured by SKOV3 ovarian cancer cells and effectively degraded to release Her2 ASOs and Mito simultaneously. Her2 ASOs can inhibit the expression of endogenous Her2 genes and recover cancer cells' sensitivity to Mito, which ultimately led to a high apoptosis rate of 75.7% in vitro. Mito-Her2@RSHM NPs also show a high tumor suppression rate of 83.33 ± 4.16% in vivo without significant damage to normal tissues. In summary, Mito-Her2@RSHM NPs would be expected as a versatile and safe nanodrug delivery platform with high efficiency for chemo-gene combined cancer treatment.

Floxuridine-chlorambucil conjugate nanodrugs for ovarian cancer combination chemotherapy

Due to no specific symptoms and lack of early diagnosis for ovarian cancer, most diagnosed patients are often in the terminal stage resulting that tumor tissue is unable to be resected completely by operation. So postoperative chemotherapy has become an important and indispensable treatment procedure for them. Up to date, it remains a challenge to treat ovarian cancer by an effective chemotherapy strategy. Recently, the strategy of ADDC has been regarded as a highly effective chemotherapy strategy to treat various cancers without any drug carriers. Here a novel ADDC is synthesized by linking a water-soluble antitumor drug floxuridine (Fud) and a water-insoluble antitumor drug chlorambucil (Cb) through the esterification. Then the Fud-Cb conjugate can form stable nanodrugs in water with an average size around 103.0 nm through molecular self-assembly. After internalization of cells, the ester bonds in nanodrugs can be degraded to release free Fud and Cb at a fixed ratio under the intracellular acid conditions, which exhibits the high synergistic effect on ovarian cancer cells. The cytotoxicity test results show that Fud-Cb nanodrugs can efficiently inhibit the growth of ovarian cancer cells. The apoptosis data exhibit that the cell necrotic and apoptotic rate treated with Fud-Cb nanodrugs is about 73.7 % and 18.76 % within 24 h. These results suggest that Fud-Cb nanodrugs based on ADDC strategy can effectively enhance synergistic anticancer efficacy to ovarian cancer.

Endometrial polyps effect on pregnancy outcomes in infertile women with minimal/mild endometriosis: A retrospective study

AbstractObjectiveTo assess the pregnancy outcomes and associated influencing factors of pregnancy after hysteroscopy combined with laparoscopy treatment in infertile patients with minimal/mild endometriosis.DesignA retrospective study.SettingWest China Second University Hospital of Sichuan University.PatientsWe enrolled 898 infertile women who had their minimal/mild endometriosis lesions removed by laparoscopy, including 271 patients additionally diagnosed with endometrial polyps who also underwent hysteroscopic polypectomy.MethodsBased on the existence of endometrial polyps, patients with minimal/mild endometriosis were enrolled and divided into polyps group and non‐polyps group.Main Outcome MeasuresPregnancy outcomes.ResultsA total of 271 women with minimal/mild endometriosis were included in polyps group while 491 women with minimal/mild endometriosis were included in non‐polyps group. The pregnancy rate of polyps group was not statistically significant compared with non‐polyp group (60.15% vs. 58.25%). The pregnancy rate was higher among patients with polyps ≥1 cm (76.06%, 54/71) than patients with polyps <1 cm (54.50%, 109/200) or patients without polyps (58.25%, 286/491) (p = 0.006). The pregnancy rate was higher for patients with multiple polyps (67.86%, 95/140) than for patients with single polyp (51.91%, 68/131) or without polyps (p = 0.025).ConclusionsAmong women with minimal/mild endometriosis, hysteroscopic polypectomy did significantly increase fertility in infertile patients with multiple polyps or size of polyp ≥1 cm compared with those without endometrial polyps, single polyp, and size of polyp <1 cm. The size and number of polyps were independently associated with the reproductive ability of women with minimal/mild endometriosis.