Comparison of Natural Killer Cells Differentiated from Various Pluripotent Stem Cells.

Allogeneic natural killer (NK) cell therapy has been effective in treating cancer. Many studies have tested NK cell therapy using human pluripotent stem cells (hPSCs). However, the impacts of the origin of PSC-NK cells on competence are unclear.

Implementation of learning by design in a synchronized online environment to teach educational robotics to inservice teachers.

Teaching educational robotics is of growing interest in K-12 settings. Yet, immense efforts are needed to move the field forward by framing the teaching of robotics with pedagogically sound theories as well as appropriate instructional design models and strategies. To meet this need, the authors designed and implemented an online educational robotics course for inservice teachers who had little or no prior experience in teaching robotics, by applying instructional design factors as well as teaching and facilitation strategies derived from the learning by design (LBD) framework.

Hands-on, Minds-on, Hearts-on, Social-on: A Collaborative Maker Project Integrating Arts in a Synchronous Online Environment for Teachers.

This article presents a collaborative maker project integrating the arts in a synchronous online environment. Based on the Thinkering, Making, Sharing, and Reflecting (TMSR) model, the four components of hands-on, minds-on, hearts-on, and social-on learning were integrated into an online collaborative maker project involving arts, music, and coding. The authors first describe the theoretical framework of the TMSR model and the design and implementation of the maker project, and then report on the experiences and reflections of the participating teachers, who were enrolled in an online graduate course.

Cationic Nanoparticle-Mediated Activation of Natural Killer Cells for Effective Cancer Immunotherapy.

Natural killer (NK) cells have been recognized as a next-generation therapy for cancer as they are less likely to trigger adverse events (., cytokine storm or graft-versus-host disease) than T cell-based therapeutics. Although NK cell activation strategies through genetic engineering and cytokine treatment have been actively studied for successful cancer treatment, the approaches are inefficient, expensive, and involve complex processing.

Combined CDK2 and CDK4/6 Inhibition Overcomes Palbociclib Resistance in Breast Cancer by Enhancing Senescence.

Breast cancer represents the number one global cancer burden in women and the hormone receptor (HR)-positive subtype comprises approximately 70% of breast cancers. Unfortunately, acquired resistance ultimately occurs in almost all cases, even though cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are a highly effective therapy for HR-positive/human epidermal growth factor receptor 2-negative subtype. Here, we investigated mechanisms of resistance to CDK4/6 inhibitor and potential therapeutic strategies using our palbociclib-resistant preclinical model.

Potential of Cell-Free Supernatant from NIBR97, Including Novel Bacteriocins, as a Natural Alternative to Chemical Disinfectants.

The recent pandemic of coronavirus disease 2019 (COVID-19) has increased demand for chemical disinfectants, which can be potentially hazardous to users. Here, we suggest that the cell-free supernatant from NIBR97, including novel bacteriocins, has potential as a natural alternative to chemical disinfectants. It exhibits significant antibacterial activities against a broad range of pathogens, and was observed by scanning electron microscopy (SEM) to cause cellular lysis through pore formation in bacterial membranes, implying that its antibacterial activity may be mediated by peptides or proteins and supported by proteinase K treatment.

IL-27 enhances IL-15/IL-18-mediated activation of human natural killer cells.

Background: Natural killer (NK) cells are an emerging new tool for cancer immunotherapy. To develop NK cell therapeutics from peripheral blood mononuclear cells (PBMCs) of healthy donors, substantial expansion of primary NK cells is necessary because of the very low number of these cells in peripheral blood. In this study, we aimed to investigate the effect of various cytokine alone or combinations, in expanded NK cells and to analyze the synergetic effect of cytokine combinations.

Serum exosomal miRNA-145 and miRNA-200c as promising biomarkers for preoperative diagnosis of ovarian carcinomas.

: Exosomes are extracellular microvesicles that are released by most cells and widely distributed in various body fluids. Malignant cells secrete large amounts of exosomes containing various molecular constituents reflecting the originating tumor. We investigated the difference in microRNA (miRNA) expression in serum exosomes from the patients with benign, borderline and malignant ovarian masses to assess the diagnostic relevance of serum exosomal miRNAs as biomarkers for preoperative diagnosis of ovarian carcinoma.

Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review.

Deregulation of the cyclin D-CDK4/6-INK4-RB pathway leading to uncontrolled cell proliferation, is frequently observed in breast cancer. Currently, three selective CDK4/6 inhibitors have been FDA approved: palbociclib, ribociclib and abemaciclib. Despite promising clinical outcomes, intrinsic or acquired resistance to CDK4/6 inhibitors has limited the success of these treatments; therefore, the development of various strategies to overcome this resistance is of great importance.

Organizing pneumonia resembling disease progression in a non-small-cell lung cancer patient receiving ceritinib: A case report.

Rationale: Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), a distinct molecular entity, is highly sensitive to ALK tyrosine kinase inhibitors (TKIs) such as crizotinib or ceritinib. Interstitial lung disease is a rare (1.2%) pulmonary toxicity that can result from ALK TKIs, however, organizing pneumonia has not been reported to date.

CD44/CD24 and aldehyde dehydrogenase 1 in estrogen receptor-positive early breast cancer treated with tamoxifen: CD24 positivity is a poor prognosticator.

CD44/CD24 or aldehyde dehydrogenase 1 (ALDH1) has been suggested as a potential marker for breast cancer stem cells. In the cohort of 819 patients with resected ER-positive breast cancer, the '5-year relapse group' within 5 years postsurgery during adjuvant tamoxifen treatment and the 'non-relapse group' longer than 9 years postsurgery were defined. Paraffin-embedded tumor tissues were available in 31 patients from 5-year relapse group and 68 from the non-relapse group.

Correlation of Expression: Clinical implication in Ovarian Carcinomas.

: ALDH1 is a putative cancer stem cell marker, while the Notch signaling pathway is involved in regulation of cancer stem cell (CSC)s. This study aims to determine the expression of Notch signaling genes in ovarian CSCs, and to assess the clinical impact of expression of and Notch signaling genes in ovarian cancers. : We examined expression of Notch signaling genes in FACS-sorted ALDH1(+) putative ovarian CSCs and expression of and Notch signaling genes in 86 ovarian epithelial tumors and various ovarian cancer cell lines by real-time RT-PCR, including Notch receptors (), Notch ligands (), and the downstream molecule, .

MicroRNA-136 inhibits cancer stem cell activity and enhances the anti-tumor effect of paclitaxel against chemoresistant ovarian cancer cells by targeting Notch3.

To identify microRNAs (miRNAs) regulating Notch3 expression in association with paclitaxel resistance, candidate miRNAs targeting Notch3 were predicted using TargetScan. We found that miR-136 directly targets Notch3, and miR-136 was significantly downregulated in OSC tissues relative to normal control tissues, and low expression of miR-136 correlated with poor overall in ovarian cancer patients. Artificial miR-136 overexpression significantly reduced cell viability, proliferation, Cancer stem cell (CSC) spheroid formation, and angiogenesis, and increased apoptosis in paclitaxel-resistant SKpac cells compared with the effects of paclitaxel alone.

Hsa-miR-1246 and hsa-miR-1290 are associated with stemness and invasiveness of non-small cell lung cancer.

Objectives: Cancer stem cells (CSCs) are considered to play a pivotal role in the process of invasion, metastasis and chemotherapy resistance. Diverse aberrantly expressed microRNAs (miRNAs) have been reported in lung cancer cells. However, there have been few reports about miRNAs that were associated with stemness and invasion of lung cancer.

HPV genotyping 9G membrane test: a point-of-care diagnostic platform.

The results of HPV detection in 550 cervical samples by cervical cytology were compared with the sequencing analysis and HPV genotyping 9G membrane test. The HPV genotyping 9G membrane test can efficiently identify and discriminate five HR-HPV genotypes. The 100% identical results of HPV genotyping 9G membrane tests with the sequencing results in 550 clinical samples ensure its wide clinical applicability.

HPV genotyping 9G membrane test.

The results of the genital human papillomavirus (HPV) detection in 439 cervical samples by cervical cytology were compared with sequencing analysis and a newly developed HPV genotyping 9G membrane test. The excellent sensitivity and specificity of the HPV genotyping 9G membrane test was assured by a signal to noise ratio of more than 300 and a target hybridization to non-target hybridization ratio of 300 ~ 400 at 25 °C. The final results can be obtained in 29 min by simple loading of the hybridization and washing solutions and scanning the membranes without any drying steps or special handling.

MicroRNAs overexpressed in ovarian ALDH1-positive cells are associated with chemoresistance.

Background: Ovarian carcinoma is the leading cause of cancer death worldwide among gynecological malignancies, and the majority of cases are related with recurrence and chemoresistance. Cancer stem cells (CSCs) are believed to be one of the causes of recurrent or chemoresistant ovarian cancer, and microRNAs are regulatory molecules newly implicated to control a variety of cellular processes, including CSCs. Therefore, we identified ovarian CSC-specific microRNAs and investigated their clinicopathological implication in ovarian carcinomas.

Targeted inhibition of phosphatidyl inositol-3-kinase p110β, but not p110α, enhances apoptosis and sensitivity to paclitaxel in chemoresistant ovarian cancers.

The phosphatidylinositol 3-kinase (PI3K) pathway is one of the critical signaling cascades playing important roles in the chemoresistance of human cancer cells, including ovarian cancer. In this study, we investigated the potential of targeting the PI3K p110β-isoform as a novel approach to overcome the chemoresistance in ovarian cancer. The effects on apoptosis, cell viability, proliferation and migration in chemoresistant ovarian cancer cell were determined following targeted p110β inhibition by small interfering RNA (siRNA).

Notch3 and Jagged2 contribute to gastric cancer development and to glandular differentiation associated with MUC2 and MUC5AC expression.

Aims: Notch signalling plays diverse roles in malignant tumours as well as in normal tissue development. In this study we investigated the expression of Notch signalling pathway genes and their clinicopathological significance in gastric carcinomas.

Methods And Results: Notch1, Notch3, Jagged1, Jagged2 and Hes1 expression were analysed by quantitative real-time polymerase chain reaction (qRT-PCR) (n = 81) and immunohistochemistry (n = 103) in gastric carcinomas.

HPV 9G DNAChip: Based on the 9G DNAChip technology.

The novel HPV 9G DNAChips were developed for the detection and discrimination of the HPV genotypes in the clinical samples. The HPV 9G DNAChip established high SBR of 50-70 and 100% target-specific hybridization after 30min hybridization and 2×2min washing at 25°C. We compared the genotyping results of the 959 HPV positive and 82 HPV negative clinical samples by the HPV 9G DNAChip and the sequencing; the results are in 100% agreement.

HPV 9G DNA chip: 100% clinical sensitivity and specificity.

We describe a novel HPV 9G DNA chip test for the accurate and reliable genotyping of human papillomavirus (HPV). The HPV 9G DNA chip test established its efficiency in terms of a signal-to-background ratio (SBR) of 200, which is 50 times superior to commercial HPV DNA chips, and 100% target-specific hybridization at 25°C. We compared the genotyping results for the 439 clinical samples by the HPV 9G DNA chip test with the sequencing results for the MY11/GP6+ (M2) primer set-mediated PCR products.

Proteomic molecular portrait of interface zone in breast cancer.

Surgical tumor margins are intended to encompass residual tumor cells but may not always accurately delineate the boundary between tumor and normal tissue. Efforts to define tumor margins based on molecular analysis have achieved limited success. Furthermore, no clinical trials have addressed the scope of the tumor microenvironment.

Glassy cell carcinoma predominantly commits to a squamous lineage and is strongly associated with high-risk type human papillomavirus infection.

Glassy cell carcinoma (GCC) has been believed to have originated from reserve or uncommitted cells as a poorly differentiated adenosquamous carcinoma. This study includes immunoprofiles of p63, cytokeratin 17 (CK17), and CD44 to clarify which lineage of GCC is committed to human papillomavirus (HPV) detection, and to verify whether or not HPV plays a role in GCC. Nine uterine GCCs showing overwhelmingly glassy features were evaluated by an HPV genotyping chip and by immunohistochemistry for E-cadherin, CD44, p63, CEA, erb-B2, cytokeratin 17, and p16.

Molecular characterization of uterine clear cell carcinoma.

Clinicopathological studies support a broad classification of endometrial carcinoma into two major types, designated as type I and type II, which correlate with their biological behavior. More recently, molecular studies have provided further insights into this classification scheme by elucidating the genetic events involved in the development and progression of endometrial carcinoma. Microsatellite instability and mutations in the PTEN gene have been widely associated with type I (endometrioid) endometrial carcinoma, while p53 mutations have been identified in the majority of type II endometrial carcinoma, of which uterine serous carcinoma is the prototype.