Artificial Cells, Nanomedicine, and Biotechnology

Identification of stemness subtypes and features to improve endometrial cancer treatment using machine learning

Endometrial cancer is one of the most common malignant tumours in women, and cancer stem cells are known to play an important role in its growth, invasion, metastasis, and drug resistance. Immunotherapy for endometrial cancer is still under research. In this study, a total of 547 endometrial cancer cases were randomly divided into training set (351 cases) set and test set (196 cases). The stemness index of patients was calculated using the One-Class Logistic Regression (OCLR) machine learning algorithm to explore the clinicopathological differences between index levels. Stemness subtypes were determined according to the characteristics of cancer stemness and their clinicopathological characteristics, immune features, and therapeutic effects were described. Our study suggests that endometrial cancer is classified into two stemness subtypes. Stemness subtypes, which are associated with its clinical features, may be independent prognostic factors for endometrial cancer. The stemness subtypes differed significantly in immune activity, immune cell infiltration, and the immune microenvironment, including sensitivity to chemotherapeutic drugs and potential therapeutic compounds. Algorithms were utilised to construct a stemness subtype prediction model and predictor. These findings will provide guidance for the clinical diagnosis, treatment, and prognosis of endometrial cancer.

RDM1 plays an oncogenic role in human ovarian carcinoma cells

Ovarian cancer is one of the deadliest gynecological cancer, with a low overall 5-year survival rate. RDM1, RAD52 motif-containing protein 1, is sensitive to cisplatin, a common chemotherapy drug and it has an important role inDNA damage repair pathway. Until now, the effect of RDM1 in ovarian cancer is undiscovered. Here, clinical data shows that the tumour tissues of ovarian carcinoma patients with higher mRNA and protein expression of RDM1. Knockdown of

LncRNA PTENP1 inhibits cervical cancer progression by suppressing miR-106b

LncRNA PTENP1 is a competitive endogenous RNA (ceRNA) involved in decoying miR-106b in multiple diseases. This study investigates the interaction of PTENP1 and miR-106b in cell proliferation, apoptosis and epithelial-mesenchymal transition (EMT) in cervical cancer. The expressions of PTENP1, miR-106b and PTEN were determined in cervical cancer tissues, adjacent normal tissues, cervical cancer cells (HeLa, SiHa, C33A and CasKi) and normal cervical epithelial H8 cells. Up-regulation of PTENP1 and down-regulation of miR-106b were conducted in HeLa and CasKi cells by transfecting cells with corresponding miRNA mimics and inhibitors. Bioinformatics analysis, luciferase reporter assay and RNA-pull down assay were performed to verify the association of miR-106b, PTEN, and PTENP1. Cell growth and cell apoptosis were determined by CCK-8 and flow cytometry analysis. It was found that the expressions of PTENP1 and PTEN were up-regulated and that of miR-106b were down-regulated in cervical cancer tissues and cells. PTENP1 localized in cytoplasm and competitively bound to miR-106b. Up-regulation of PTENP1 and down-regulation of miR-106b contributed to increased expressions of PTEN and E-cadherin. Decreased expression of miR-106b, ZEB1, Snail and Vimentin, resulted in inhibiting cell proliferation and promoting cell apoptosis. Over-expression of PTENP1 and miR-106b accelerated cell proliferation and slowed down cell apoptosis. miR-106b inhibited the expression of PTEN. Our results suggest that LncRNA PTENP1 inhibits cervical cancer progression by competitively binding to miR-106b, leading to promote PTEN expression, inhibit cell proliferation and EMT and induce cell apoptosis in cervical cancer cells.

Inhibition of Wnt signalling pathway by XAV939 enhances radiosensitivity in human cervical cancer HeLa cells

Cervical cancer is the second most common malignant tumour threatening women's health. In recent years, heavy-ion beam therapy is becoming a newly emerging therapeutic mean of cancer; however, radio-resistance and radiation-induced damage constitute the main obstacles for curative treatment of cervical cancer. Therefore, to identify the radiosensitizers is essential. Here, we investigated the effects of Wnt signalling pathway on the response of

Anti-tumour activity of zinc ionophore pyrithione in human ovarian cancer cells through inhibition of proliferation and migration and promotion of lysosome-mitochondrial apoptosis

Zinc pyrithione (ZPT) is widely used as an antimicrobial. Zinc is a necessary trace element of the human whose homeostasis associated with several cancers. However, the anticancer effect of increased Zinc in ovarian cancer is still unclear. This study focussed on the anti-tumour effects of ZPT combined with Zinc in SKOV3 and SKOV3/DDP cells. The cell viability, apoptosis, migration, and invasion assays were detected by CCK-8, flow cytometry, wound healing and transwell assay, respectively. The distribution of Zinc in cells was monitored by staining of Zinc fluorescent dye and lysosome tracker. The changes in lysosomal membrane stability were reflected by acridine orange fluorescence and cathepsin D reposition. Expression of the proteins about invasion and apoptosis was evaluated by western blot. The results indicated that ZPT combined with Zinc could notably reduce cell viability, inhibit migration and invasion in SKOV3 and SKOV3/DDP cells. Besides, ZPT performed as a Zinc carrier targeted lysosomes, caused the increase of its membrane permeability and the release of cathepsin D accompanied by mitochondrial apoptosis in SKOV3/DDP cells. In conclusion, our work suggests that ZPT combined with Zinc could inhibit proliferation, migration, invasion, and promote apoptosis by trigger the lysosome-mitochondrial apoptosis pathway in ovarian carcinoma.

Advances in screening and diagnostic lab-on-chip tools for gynaecological cancers – a review

Gynaecological cancers are a major global health concern due to the lack of effective screening programmes for ovarian and endometrial cancer, for example, and variable access to vaccination and screening tests for cervical cancer in many countries. Recent research on portable and cost-effective lab-on-a-chip (LoC) technologies show promise for mass screening and diagnostic procedures for gynaecological cancers. However, most LoCs for gynaecological cancer are still in development, with a need to establish and clinically validate factors such as the type of biomarker, sample and method of detection, before patient use. Multiplex approaches, detecting a panel of gynaecological biomarkers in a single LoC, offer potential for more reliable diagnosis. This review highlights the current research on LoCs for gynaecological cancer screening and diagnosis, emphasizing the need for further research and validation prior to their widespread adoption in clinical practice.

Folate receptor-targeted PLGA-PEG nanoparticles for enhancing the activity of genistein in ovarian cancer

Genistein (GEN), a natural isoflavone possesses a wide range of pharmacological properties and nutraceutical applications. GEN has been studied for its anticancer activity against different types of cancers, but its use in clinical practice is limited due to its low water solubility, rapid metabolism and excretion, lack of cancer cell targeting and poor bioavailability. In the present study, we investigated folate receptor-targeted and PEGylated poly(lactide-co-glycolide) nanoparticles (PLGA-PEG-FA NPs) containing GEN for targeted delivery to ovarian cancer cells. PLGA-PEG and PLGA-PEG-FA polymer conjugates were synthesized and characterized. Nano-precipitation method was employed for the fabrication of NPs of PLGA, PLGA-PEG and PLGA-PEG-FA containing GEN. GEN containing PLGA-PEG and PLGA-PEG-FA NPs prepared were small (104.17 ± 1.61 and 125.41 ± 3.11 nm, respectively) and exhibited sustained release of GEN for around six days. Folate-decorated PLGA-PEG NPs showed increased cellular uptake in comparison to non-targeted PLGA-PEG NPs. The GEN containing PLGA-PEG-FA NPs showed superior anticancer activity than non-targeted PLGA and PLGA-PEG NPs in folate receptor-overexpressing ovarian cancer cell line, SKOV-3. The IC

Antiviral activity of curcumin-nanoemulsion associated with photodynamic therapy in vulvar cell lines transducing different variants of HPV-16

Vulvar intraepithelial neoplasia (VIN) is associated with human papillomavirus (HPV) infection. Curcumin is a natural bioactive compound with antineoplastic properties. The use of nanoparticles containing curcumin could allow a better performance of this compound in therapies. So, VIN biopsies were collected and HPV DNA detection was performed by PCR, positive samples were genotyped by Restriction Fragment Length Polymorphism (RFLP) and HPV-16 variants were determined by sequencing. HPV-16 positive vulva carcinoma cells (A431) were transduced with E-P and E-350G HPV-16 E6 variants. The viability of the transduced cells treated with nanoemulsions was determined by MTT assay. Besides, apoptosis was evaluated by enzymatic activity of Caspase-3/7. The cell viability assay showed that both the empty nanoemulsion (NE-V) and the nanoemulsion of curcumin (NE-CUR) had little effect on cell viability as compared to control cells. Additionally, we observed that cells irradiated in the presence of NE-CUR presented 90% of cell death. The apoptosis assay further revealed a significant increase in the activity of caspases 3 and 7 in A431 cells expressing both HPV-16 E6 variants after treatment with NE-CUR. Finally, we submitted the HPV transduced A431 cells to organotypic cultures and observed that the combination of treatments affected tissue architecture with evident signals of tissue damage. We concluded that nanoemulsions attain good biocompatibility, since no cytotoxicity was observed and NE-CUR associated with photoactivation showed promising results, leading to death only in cells subjected to irradiation. This drug delivery system associated with photodynamic therapy may become promising in the treatment of vulva lesions.

Inhibiting the PI3K/AKT/mTOR signalling pathway with copper oxide nanoparticles from Houttuynia cordata plant: attenuating the proliferation of cervical cancer cells

Cervical cancer is the most important female genital cancer that develops from the cervix, a lower part of uterus.