Ovarian Cancer Patient-Derived Organoids Used as a Model for Replicating Genetic Characteristics and Testing Drug Responsiveness: A Preliminary Study.

This study aimed to explore the role of ovarian cancer patient-derived organoids (PDOs) in their replicating genetic characteristics and testing drug responsiveness. Ovarian cancer PDOs were cultured in Matrigel with a specialized medium. The successful rate and proliferation rate were calculated.

Bone Marrow Mesenchymal Stem Cells Promote Ovarian Cancer Cell Proliferation via Cytokine Interactions.

Bone marrow mesenchymal stem cells (BMSCs) are key players in promoting ovarian cancer cell proliferation, orchestrated by the dynamic interplay between cytokines and their interactions with immune cells; however, the intricate crosstalk among BMSCs and cytokines has not yet been elucidated. Here, we aimed to investigate interactions between BMSCs and ovarian cancer cells. We established BMSCs with a characterized morphology, surface marker expression, and tri-lineage differentiation potential.

Celecoxib attenuates interleukin 33-induced expression of vascular cell adhesion molecule-1 in human ovarian endometriotic stromal cells.

Objective: Endometriosis is an estrogen-dependent chronic inflammatory disease in women of reproductive age. A review of the literature revealed that cytokines and inflammatory factors are associated with endometriosis-associated infertility. Interleukin 33 (IL-33) is a strong inducer of other pro-inflammatory cytokines.

Effectiveness of Chinese Herbal Medicine as a Complementary Treatment for Neutropenia Prevention and Immunity Modulation During Chemotherapy in Patients With Breast Cancer: Protocol for a Real-World Pragmatic Clinical Trial.

Background: In recent years, advancements in cancer treatment have enabled cancer cell inhibition, leading to improved patient outcomes. However, the side effects of chemotherapy, especially leukopenia, impact patients' ability to tolerate their treatments and affect their quality of life. Traditional Chinese medicine is thought to provide complementary cancer treatment to improve the quality of life and prolong survival time among patients with cancer.

Assessment of Fallopian Tube Epithelium Features Derived from Induced Pluripotent Stem Cells of Both Fallopian Tube and Skin Origins.

Fallopian tube epithelial cells (FTECs) play a significant role in the development of high-grade serous ovarian cancer (HGSOC), but their utilization in in vitro experiments presents challenges. To address these limitations, induced pluripotent stem cells (iPSCs) have been employed as a potential solution, driven by the hypothesis that orthologous iPSCs may offer superior differentiation capabilities compared with their non-orthologous counterparts. Our objective was to generate iPSCs from FTECs, referred to as FTEC-iPSCs, and compare their differentiation potential with iPSCs derived from skin keratinocytes (NHEK).

Role of LRRN4 in promoting malignant behavior in a p53- and Rb-defective human fallopian tube epithelial cell line.

This study explored the role of leucine-rich repeat neuronal 4 (LRRN4) in ovarian carcinogenesis using the p53- and Rb-defective human fallopian tube epithelial cell line FE25. We evaluated the expression of LRRN4 in FE25 cells with and without LRRN4 knockdown by short hairpin RNA (shRNA) and studied its effects on cell proliferation, cell cycle, migration, invasion, chemotherapeutic sensitivity, apoptosis, and xenograft formation. The results showed that FE25 shRNA-LRRN4 cells exhibited more aggressive malignant behaviors than FE25 cells, including faster proliferation and increased cell distribution in the G2/M phase, Akt pathway activation, cell migration, and cell invasion, as well as decreased sensitivity to chemotherapeutic drugs.

The Role and Applications of Exosomes in Gynecological Cancer: A Review.

Exosomes are phospholipid bilayer vesicles that are released by all types of cells, containing proteins, lipids, and nucleic acids such as DNAs and RNAs. Exosomes can be transferred between cells and play a variety of physiological and pathological regulatory functions. Noncoding RNAs, including micro RNAs, long noncoding RNAs, and circular RNAs, are the most studied biomolecules from exosomes and more and more studies found that noncoding RNAs play an important role in the diagnosis, prognosis, and treatment of diseases, including various types of cancer.

Effects of the Overexpression of Progesterone Receptors on a Precancer p53 and Rb-Defective Human Fallopian Tube Epithelial Cell Line.

This study investigated the effects of progesterone receptors A (PRA) and B (PRB) on proliferation, migration, invasion, anchorage-independent growth (AIG), and apoptosis of FE25 cells, a precancer p53- and retinoblastoma-defective human fallopian tube epithelial cell line. We observed that the transfection of PRA (FE25-PRA) or PRB (FE25-PRB) into FE25 cells significantly increased the expression of PRA or PRB at both RNA and protein levels without affecting cell morphology. The FE25-PRA cells exhibited slower proliferation, whereas FE25-PRB showed faster cell proliferation than the control cells.

A non-genetic engineering platform for rapidly generating and expanding cancer-specific armed T cells.

Background: Cancer-specific adoptive T cell therapy has achieved successful milestones in multiple clinical treatments. However, the commercial production of cancer-specific T cells is often hampered by laborious cell culture procedures, the concern of retrovirus-based gene transfection, or insufficient T cell purity.

Methods: In this study, we developed a non-genetic engineering technology for rapidly manufacturing a large amount of cancer-specific T cells by utilizing a unique anti-cancer/anti-CD3 bispecific antibody (BsAb) to directly culture human peripheral blood mononuclear cells (PBMCs).

Role of cancer-associated mesenchymal stem cells in the tumor microenvironment: A review.

Mesenchymal stem cells (MSCs) were applied to the therapy for degenerative diseases, immune, and inflammation. In tumor microenvironments (TME), different sources of MSCs showed that tumor-promoting and -inhibiting effects were mediated by different signaling pathways. Cancer-associated MSCs (CaMSCs) could be recruited from bone marrow or local tissues and mainly showed tumor-promoting and immunosuppressive effects.

Oct-4 induces cisplatin resistance and tumor stem cell-like properties in endometrial carcinoma cells.

Objective: Research has suggested that tumor-initiating tumor stem cells are derived from normal stem cells and that tumor cells undergo progressive de-differentiation to achieve a stem cell-like state. Tumor stem cells are characterized by high proliferation ability, high plasticity, expression of multi-drug resistance proteins, and the ability to seed new tumors. Octamer-binding transcription factor 4 (Oct-4) and its activation targets are overexpressed in the tumor stem cells of various types of tumors, and this expression is associated with the pathogenesis, development, and poor prognosis of tumors.

Comparing the Therapeutic Mechanism and Immune Response of Human and Mouse Mesenchymal Stem Cells in Immunocompetent Mice With Acute Liver Failure.

Current mesenchymal stem cell (MSC) research is based on xenotransplantation of human MSCs (hMSCs) in immunodeficient mice and cannot comprehensively predict MSC repair mechanisms and immunomodulatory effects in damaged tissue. This study compared the therapeutic efficacy, mechanisms, and immune response of hMSCs and mouse MSCs (mMSCs) in immunocompetent mice with CCl4-induced acute liver failure. mMSCs maintained F4/80+ hepatic macrophage recruitment into the damaged liver region, increased IL-6-dependent hepatocyte proliferation, and reduced inflammatory TNF-α cytokine secretion.

Statins as Repurposed Drugs in Gynecological Cancer: A Review.

Discovering new drugs is an expensive and time-consuming process, including target identification, bioavailability, pharmacokinetic (PK) tests, pharmacodynamic (PD) tests, toxicity profiles, recommended dosage test, and observation of the side effects, etc. Repurposed drugs could bypass some steps, starting from phase II trials, and shorten the processes. Statins, also known as HMG-CoA inhibitors (HMGCR), are commonly used to manage and prevent various cardiovascular diseases and have been shown to improve the morbidity and mortality of patients.

Endometrial Cancer-Infiltrating Mesenchymal Stem Cells Exhibit Immunosuppressive Effects.

Endometrial cancer is the most common gynecologic cancer with high heterogeneity. However, there are limited treatment options for advanced endometrial carcinoma. In recent years, immunotherapy has broadly been used for the treatment of various cancers.

Novel FLT3/AURK multikinase inhibitor is efficacious against sorafenib-refractory and sorafenib-resistant hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is the sixth most common type of cancer and has a high mortality rate worldwide. Sorafenib is the only systemic treatment demonstrating a statistically significant but modest overall survival benefit. We previously have identified the aurora kinases (AURKs) and FMS-like tyrosine kinase 3 (FLT3) multikinase inhibitor DBPR114 exhibiting broad spectrum anti-tumor effects in both leukemia and solid tumors.

Dual targeting of TAM receptors Tyro3, Axl, and MerTK: Role in tumors and the tumor immune microenvironment.

In both normal and tumor tissues, receptor tyrosine kinases (RTKs) may be pleiotropically expressed. The RTKs not only regulate ordinary cellular processes, including proliferation, survival, adhesion, and migration, but also have a critical role in the development of many types of cancer. The Tyro3, Axl, and MerTK (TAM) family of RTKs (Tyro3, Axl, and MerTK) plays a pleiotropic role in phagocytosis, inflammation, and normal cellular processes.

Interleukin-33 promotes invasiveness of human ovarian endometriotic stromal cells through the ST2/MAPK/MMP-9 pathway activated by 17β-estradiol.

Objective: Endometriosis is an estrogen-dependent, benign, and chronic gynecological disorder occurring in women of reproductive age. Although the pathogenesis of endometriosis is poorly understood, implantation theory indicates that viable endometrial cells shed from the endometrium into the pelvic peritoneum or ovaries, possibly through retrograde menstruation, and then reattach, invade, and damage other tissues. Interleukin (IL)-33, a new member of the IL-1 superfamily, is mainly upregulated by stromal cells following proinflammatory stimulation.

Downregulation of gap junctional intercellular communication and connexin 43 expression by bisphenol A in human granulosa cells.

Gap junctional intercellular communication (GJIC) is the transfer of ions, metabolites, and second messengers between neighboring cells through intercellular junctions. Connexin 43 (Cx43) was found to be the type of gap junction protein responsible for human granulosa cells (GCs) and oocyte communication, which is required for folliculogenesis and oocyte maturation. Bisphenol A (BPA), an estrogenic-like endocrine-disrupting chemical, is one of the most widely produced chemicals around the world.

Modulation of tumor stem cell characteristics by 17β-estradiol in human mesenchymal stem cells derived from ovarian endometrioma.

Objective: Ovarian endometrioma is a cyst composed of endometrial tissue and is present in 20%-40% of patients with endometriosis. Endometriosis is an estrogen-dependent benign and chronic gynecological disease that affects women of reproductive age. Studies have reported that tumor stem cells can be isolated from numerous tumor types.

Development of a highly sensitive enzyme-linked immunosorbent assay (ELISA) through use of poly-protein G-expressing cell-based microplates.

The sensitivity of traditional enzyme-linked immunosorbent assays (ELISAs) is limited by the low binding avidity and heterogeneous orientation of capture antibodies coated on polystyrene-based microplates. Here, we developed a highly sensitive ELISA strategy by fixing poly-protein G-expressing cells on microplates to improve the coating amount and displayed orientation of capture antibodies. One or eight repeated fragment crystallisable (Fc) binding domains of protein G are stably expressed on the surface of BALB/c 3T3 cells (termed 1pG cells or 8pG cells), which then act as highly antibody-trapping microparticles.

Pueraria mirifica inhibits 17β-estradiol-induced cell proliferation of human endometrial mesenchymal stem cells.

Objective: The notion that the human endometrium may contain a population of stem cells has recently been proposed. The mesenchymal stem cells (MSCs) in the endometrium are believed to be responsible for the remarkable regenerative ability of endometrial cells. Estrogens influence the physiological and pathological processes of several hormone-dependent tissues, such as the endometrium.

Loss of calponin h1 confers anoikis resistance and tumor progression in the development of high-grade serous carcinoma originating from the fallopian tube epithelium.

Increasing evidence indicates that ovarian high-grade serous carcinoma (HGSC) originates from the fallopian tube epithelium and metastasizes to the ovary as the secondary site. A working hypothesis is that detached tubal HGSC cells survive anoikis and implant on the ovary. In this study, we found that downregulation of calponin h1 (CNN1) is necessary for the anoikis survival and cell transformation.

Lifespan Extension and Sustained Expression of Stem Cell Phenotype of Human Breast Epithelial Stem Cells in a Medium with Antioxidants.

We have previously reported the isolation and culture of a human breast epithelial cell type with stem cell characteristics (Type I HBEC) from reduction mammoplasty using the MSU-1 medium. Subsequently, we have developed several different normal human adult stem cell types from different tissues using the K-NAC medium. In this study, we determined whether this low calcium K-NAC medium with antioxidants (N-acetyl-L-cysteine and L-ascorbic acid-2-phosphate) is a better medium to grow human breast epithelial cells.