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Simple Summary: In breast cancer (BC), the triple-negative breast cancer subtype, the upregulation of CDC20 is positively associated with cancer initiation, progression, metastasis, and chemotherapy resistance. The current functional enrichment analysis study demonstrated the significant association of CDC20 co-expressed genes with biological regulation and cellular processes. This study reveals a significant positive correlation between overexpressed CDC20 and tumor purity and many immune cells; the finding suggests that CDC20 plays a fundamental role in controlling tumor immunity and consequently influences BC prognosis. CDC20 deficiency led to decreased cell growth and metastasis, G2/M cell cycle arrest, and boosted the cytotoxic effects of paclitaxel treatment, which supports the current analysis. Developing natural and synthetic inhibitors of this oncogene is a promising approach to the therapeutic management of BC. Cell division cycle 20 homolog (CDC20) is a well-known regulator of cell cycle progression. Abnormal expression of CDC20 leads to mitotic defects, which play a significant role in cancer development. In breast cancer (BC), CDC20 has been identified as a biomarker that has been linked to poor patient outcomes. In this study, we investigated the association of CDC20 with BC prognosis and immune cell infiltration by using multiple online databases, including UALCAN, KM plotter, TIMER2.0, HPA, TNM-plot, bc-GenExMiner, LinkedOmics, STRING, and GEPIA. The results demonstrate that BC patients have an elevated CDC20 expression in tumor tissues compared with the adjacent normal tissue. In addition, BC patients with overexpressed CDC20 had a median survival of 63.6 months compared to 169.2 months in patients with low CDC20 expression. Prognostic analysis of the examined data indicated that elevated expression of CDC20 was associated with poor prognosis and a reduction of overall survival in BC patients. These findings were even more prevalent in chemoresistance triple-negative breast cancer (TNBC) patients. Furthermore, the Gene Set Enrichment Analysis tool indicated that CDC20 regulates BC cells' cell cycle and apoptosis. CDC20 also significantly correlates with increased infiltrating B cells, CD4+ T cells, neutrophils, and dendritic cells in BC. In conclusion, the findings of this study suggest that CDC20 may be involved in immunomodulating the tumor microenvironment and provide evidence that CDC20 inhibition may serve as a potential therapeutic approach for the treatment of BC patients. In addition, the data indicates that CDC20 can be a reliable prognostic biomarker for BC. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks specific targets such as estrogen, progesterone, and HER2 receptors. TNBC affects one in eight women in the United States, making up 15–20% of breast cancer cases. Patients with TNBC can develop resistance to chemotherapy over time, leading to treatment failure. Therefore, finding other options like natural products is necessary for treatment. The advantages of using natural products sourced from plants as anticancer agents are that they are less toxic, more affordable, and have fewer side effects. These products can modulate several cellular processes of the tumor microenvironment, such as proliferation, migration, angiogenesis, cell cycle arrest, and apoptosis. The phosphatidyl inositol 3-kinase (PI3K)-AKT signaling pathway is an important pathway that contributes to the survival and growth of the tumor microenvironment and is associated with these cellular processes. This current study examined the anticancer effects of fucoxanthin, a marine carotenoid isolated from brown seaweed, in the MDA-MB-231 and MDA-MB-468 TNBC cell lines. The methods used in this study include a cytotoxic assay, PI3K-AKT signaling pathway PCR arrays, and Wes analysis. Fucoxanthin (6.25 µM) + TNF-α (50 ng/mL) and TNF-α (50 ng/mL) showed no significant effect on cell viability compared to the control in both MDA-MB-231 and MDA-MB-468 cells after a 24 h treatment period. PI3K-AKT signaling pathway PCR array studies showed that in TNF-α-stimulated (50 ng/mL) MDA-MB-231 and MDA-MB-468 cells, fucoxanthin (6.25 µM) modulated the mRNA expression of 12 genes, including FOXO1, RASA1, HRAS, MAPK3, PDK2, IRS1, EIF4EBP1, EIF4B, PTK2, TIRAP, RHOA, and ELK1. Additionally, fucoxanthin significantly downregulated the protein expression of IRS1, EIF4B, and ELK1 in MDA-MB-231 cells, and no change in the protein expression of EIF4B and ELK1 was shown in MDA-MB-468 cells. Fucoxanthin upregulated the protein expression of RHOA in both cell lines. The modulation of the expression of genes and proteins of the PI3K-AKT signaling pathway may elucidate fucoxanthin's effects in cell cycle progression, apoptotic processes, migration, and proliferation, which shows that PI3K-AKT may be the possible molecular mechanism for fucoxanthin's effects. In conclusion, the results obtained in this study elucidate fucoxanthin's molecular mechanisms and indicate that fucoxanthin may be considered a promising candidate for breast cancer-targeted therapy. [ABSTRACT FROM AUTHOR]

A small number of robust studies have explored the association between cognitive tests and marital status levels of mild cognitive impairment (MCI) patients using the TADPOLE dataset. Rey Auditory Verbal Learning Test (RAVLT) cognition performance combined with marital status levels is associated with increased odds of MCI than either RAVLT in isolation. The cross-sectional association between RAVLT performance in immediate response, learning, forgetting, and perception of forgetting with marital status and MCI was evaluated using TADPOLE data. We included participants with MCI and normal cognition in our study. Based on our logistic regression model, four RAVLT subgroups are associated with MCI (low and high response performance, immediate response with learning, immediate response with learning and forgetting, immediate response with learning, forgetting, and perception of forgetting). We adjusted models for sex, age, race, marital status, education, ethnicity, APOE4 genotype, hippocampus, whole brain, ventricles, and ICV. A mean age of 77/67 years was observed in the sample (n = 6560), 44% of participants were females, and 58% had mild cognitive impairment. Subgroups whose ages are 61 to 70 (OR 0.26, 95% CI 0.15–0.45) and older (OR 0.07, 95% CI 0.04–0.12), as well as race: black/African American (OR 0.13, 95% CI 0.03–0.52), multiple races (OR 0.05, 95% CI 0.01–0.24), and never married (OR 0.2, 95% CI 0.12–0.34) were negatively associated with immediate response and forgetting subgroup tests. There is a need for studies that evaluate other cognitive tests in the TADPOLE dataset with missing data as a predictive tool that aligns with the factors associated with MCI. [ABSTRACT FROM AUTHOR]

Chronic inflammation associated with cancer is characterized by the production of different types of chemokines and cytokines. In cancer, numerous signaling pathways upregulate the expression levels of several cytokines and evolve cells to the neoplastic state. Therefore, targeting these signaling pathways through the inhibition of distinctive gene expression is a primary target for cancer therapy. The present study investigated the anticancer effects of the natural polyphenol gossypol (GOSS) in triple-negative breast cancer (TNBC) cells, the most aggressive breast cancer type with poor prognosis. GOSS effects were examined in two TNBC cell lines: MDA-MB-231 (MM-231) and MDA-MB-468 (MM-468), representing Caucasian Americans (CA) and African Americans (AA), respectively. The obtained IC50s revealed no significant difference between the two cell lines' response to the compound. However, the use of microarray assays for cytokine determination indicated the ability of GOSS to attenuate the expression levels of cancer-related cytokines in the two cell lines. Although GOSS did not alter CCL2 expression in MM-468 cells, it was able to cause 30% inhibition in TNF-α-stimulated MM-231 cells. Additionally, IL-8 was not altered by GOSS treatment in MM-231 cells, while its expression was inhibited by 60% in TNF-α-activated MM-468 cells. ELISA assays supported the microarray data and indicated that CCL2 expression was inhibited by 40% in MM-231 cells, and IL-8 expression was inhibited by 50% in MM-468 cells. Furthermore, in MM-231 cells, GOSS inhibited CCL2 release via the repression of IKBKE, CCL2 and MAPK1 gene expression. Additionally, in MM-468 cells, the compound downregulated the release of IL-8 through repressing IL-8, MAPK1, MAPK3, CCDC88A, STAT3 and PIK3CD gene expression. In conclusion, the data obtained in the present study indicate that the polyphenol compound GOSS may provide a valuable tool in TNBC therapy. [ABSTRACT FROM AUTHOR]

Background/aim: Chemotherapy resistance in triple-negative breast cancer (TNBC) cells is well documented. Therefore, it is necessary to develop safer and more effective therapeutic agents to enhance the outcomes of chemotherapeutic agents. The natural alkaloid sanguinarine (SANG) has demonstrated therapeutic synergy when coupled with chemotherapeutic agents. SANG can also induce cell cycle arrest and trigger apoptosis in various cancer cells., Materials and Methods: In this study, we investigated the molecular mechanism underlying SANG activity in MDA-MB-231 and MDA-MB-468 cells as two genetically different models of TNBC. We employed various assays including Alamar Blue to measure the effect of SANG on cell viability and proliferation rate, flow cytometry analysis to study the potential of the compound to induce apoptosis and cell cycle arrest, quantitative qRT PCR apoptosis array to measure the expression of different genes mediating apoptosis, and the western system was used to analyze the impact of the compound on AKT protein expression., Results: SANG lowered cell viability and disrupted cell cycle progression in both cell lines. Furthermore, S-phase cell cycle arrest-mediated apoptosis was found to be the primary contributor to cell growth inhibition in MDA-MB-231 cells. SANG-treated TNBC cells showed significantly up-regulated mRNA expression of 18 genes associated with apoptosis, including eight TNF receptor superfamily (TNFRSF), three members of the BCL2 family, and two members of the caspase (CASP) family in MDA-MB-468 cells. In MDA-MB-231 cells, two members of the TNF superfamily and four members of the BCL2 family were affected. The western study data showed the inhibition of AKT protein expression in both cell lines concurrent with up-regulated BCL2L11 gene. Our results point to the AKT/PI3K signaling pathway as one of the key mechanisms behind SANG-induced cell cycle arrest and death., Conclusion: SANG shows anticancer properties and apoptosis-related gene expression changes in the two TNBC cell lines and suggests AKT/PI3K pathway implication in apoptosis induction and cell cycle arrest. Thus, we propose SANG's potential as a solitary or supplementary treatment agent against TNBC., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Activating mutations of the epidermal growth factor receptor (EGFR) gene have been utilized to predict the effectiveness of EGFR tyrosine kinase inhibitor (TKI) therapy. The most common EGFR mutations are exon 19 deletion and exon 21-point mutation, which are sensitive to EGFR TKI. However, rare/complex EGFR mutations still exist, data of which are scarce and controversial. Hence, their role in response to standard therapy remains uncertain., Case Report: We present the case of a patient diagnosed with stage IV lung adenocarcinoma for whom standard chemotherapies, including platinum agents, had failed. The patient was found to have an EGFR exon 19 (L747P) mutation, as evident in her liquid biopsy. This alteration has not been described before in the literature on non-Asian females. Data from the current case study highlight the aggressive nature of this type of EGFR mutation as indicated by the complete resistance to erlotinib. Using standard first-generation EGFR inhibitors in treating this point mutation was considered inadequate. However, this patient showed a substantial response when treated with erlotinib combined with epigenetic therapies, consisting of DNA methyltransferase and histone deacetylase inhibitors. For more than 8 years, the patient has been responding to combination therapy with a normal quality of life., Conclusion: This case represents a possible novel approach to reducing resistance in patients harboring this rare EGFR mutation which may translate to better outcomes., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aims: Monoamine oxidase-B inhibitors (MAO-BIs) are used for the initial therapy of Parkinson's disease. Also, MAO-BIs have shown to be effective neuroprotective agents in several neurodegenerative diseases. However, some concerns exist regarding the long-term use of these compounds. Meanwhile, natural compounds showed potential MAO-B selective inhibitions. To date, few selective natural MAO-BIs have been identified. Therefore, the current study is designed to identify plants with potent and specific MAO-B inhibition., Study Design: In this work, we utilized high throughput screening to evaluate the different plants ethanolic extract for their effectiveness to inhibit recombinant human ( h )MAO-A and h MAO-B and to determine the relative selectivity of the top MAO-BI., Methodology: Recombinant human isozymes were verified by Western blotting, and the 155 plants were screened. A continuous fluorometric screening assay was performed followed by two separate h MAO-A and h MAO-B microtiter screenings and IC 50 determinations for the top extracts., Results: In the screened plants, 9% of the extracts showed more than 1.5-fold relative inhibition of h MAO-B (RI B ) and another 9% showed more than 1.5-fold relative inhibition of h MAO-A. The top extracts with the most potent RI B s were Psoralea corylifolia seeds, Phellodendron amurense bark, Glycyrrhiza uralensis roots, and Ferula assafoetida roots, with the highest RI B of 5.9-fold. Furthermore, extensive maceration of the promising extracts led to increase inhibitory effects with a preserved RI B as confirmed with luminescence assay. The top four extracts h MAO-BIs were equally potent (IC 50 = 1.3 to 3.8 μg/mL) with highly significant relative selectivities to inhibit h MAO-B (4.1- to 13.4-fold)., Conclusion: The obtained results indicate that Psoralea corylifolia seeds, Ferula assafoetida, Glycyrrhiza uralensis roots, and Phellodendron amurense ethanolic extracts have selective inhibitions for human MAO-B. Investigating these plant extracts as natural resources for novel selective MAO-BIs may lead to the development of molecules that can be used in the therapeutic management of neurodegenerative diseases including Parkinson's disease.