Cancer Research Challenges and Potential Solutions in Saudi Arabia: A Qualitative Discussion Group Study.

PURPOSE: Cancer incidence in Saudi Arabia has recently shown an upward trend. Research efforts within the different cancer continuum are pivotal to strengthening control measures. Since cancer research is evolving in the country, it is crucial to understand the current challenges and implement defined interventions to overcome them. The present qualitative study aimed to assess cancer research barriers among researchers and identify potential solutions from their perspectives. METHODS: We conducted a focus group discussion among 17 Saudi-based cancer researchers from diverse research backgrounds, provinces, and institutions. We used descriptive-interpretive thematic analysis following an open-ended approach to investigate the challenges in conducting cancer research. We also captured the solutions suggested based on the researchers' experiences. RESULTS: Six major themes emerged from the analysis: requirements of the data landscape, organizational support, national research roadmap, sustainable funding, clearer policies and regulations, and capacity building. To address challenges in these areas, researchers stressed the need for improved interinstitutional collaborations, immediate availability of research materials, and unlimited and easy access to research data. CONCLUSION: Improving health research is one of the primary goals of Saudi Vision 2030. It is, therefore, essential to overcome the current challenges in cancer research, enabling research findings to inform policies related to cancer control and care provision.

PD-L1 is highly expressed in ovarian cancer and associated with cancer stem cells populations expressing CD44 and other stem cell markers.

BACKGROUND: Immune checkpoint inhibitors, including PD-L1 (programmed death ligand-1) inhibitors have well documented anticancer therapeutic effect in most types of cancers but its use in the treatment of ovarian cancer is not yet proven. The aim of our study is to explore the predictive biomarkers in ovarian cancer and its association with the outcomes. We have investigated the role of PD-L1 expressions in the tumor microenvironment cells including immune cells and cancer stem cells in different types of ovarian cancer. METHODS: A total of 119 surgical archived ovarian cancer samples were collected from the pathology department at King Fahad Specialist Hospital, Dammam, Saudi Arabia that included serous carcinomas, clear cell carcinomas, mucinous carcinomas, endometrioid carcinomas, and granulosa cell tumors. Immunohistochemistry (IHC) staining was performed using (i) PD-L1 antibodies to detect PD-L1 expressions; (ii) CD8 and CD4 to detect Tumor Infiltrating Lymphocytes (TILs); and (iii) CD44, LGR5, and ALDH2 to detect stem cell markers. The clinicopathological data were collected from patients' medical record to investigate the association with PD-L1, TILs, and stem cells expressions. RESULTS: We report high PD-L1 expressions in 47.8% of ovarian cancer samples. PD-L1 expressions were detected in different types of epithelial ovarian cancer and were not associated with poor prognosis of ovarian cancer. However, determining the expression levels of TILs in the ovarian cancer tissues found that 81% (n = 97) of ovarian cancer samples have TILs that express both of CD8 and CD4 and significantly associated with high PD-L1 expressions. Interestingly, we have found that ovarian cancer tissues with high expressions of PD-L1 were associated with high expressions of stem cells expressing CD44 and LGR5. CONCLUSIONS: PD-L1 is highly expressed in the serous type of ovarian carcinomas and the overall expression of PD-L1 is not associated with poor survival rate. Furthermore, PD-L1 expressions are strongly associated with TILs and stem cell markers in ovarian cancer. Inhibiting the PD-L1 using immune checkpoint inhibitors might downregulate stem cell population that known to be associated with cancer recurrence.

PAX2 induces vascular-like structures in normal ovarian cells and ovarian cancer.

In adult tissue, the paired box 2 (PAX2) protein is expressed in healthy oviductal, but not normal ovarian surface epithelial cells. PAX2 is expressed in a subset of cases of serous ovarian carcinoma; however, the role of PAX2 in the initiation and progression of ovarian cancer remains unknown. The aim of the present study was to determine the biological effects of PAX2 expression in normal and cancerous epithelial cells. By culturing the normal and cancerous ovarian cells that express PAX2 in 3D culture and staining the cells with vasculogenic mimicry markers such as CD31 and PAS, it was shown that PAX2 overexpression in both normal and cancerous ovarian epithelial cells induced formation of vascular-like structures both in vitro and in vivo. These results indicated a potential role of PAX2 in ovarian cancer progression by increasing the presence of vascular-like structures to promote the supply of nutrients to tumor cells and facilitate cancer cell proliferation and invasion.

Synergistic anti-cancer effects of Nigella sativa seed oil and conventional cytotoxic agent against human breast cancer.

OBJECTIVES: Breast cancer is the most commonly diagnosed invasive non-skin malignancy in women worldwide, and it is the leading cause of cancer-related deaths in them. Nigella sativa Linn. seed oil has been found to be effective in cancer treatment as well as having anti-cancer properties in some other types of cancers. The study looked into the synergistic cytotoxic effects of N. sativa Linn. seed oil and doxorubicin in the treatment of human breast cancer cells (MCF-7). METHODS: Nigella sativa Linn. seed oil was used to evaluate its effect on human breast cancer cells, either alone or in conjunction with doxorubicin. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests were used to examine cell proliferation and cell viability, while phase-contrast inverted microscopy was used to examine cellular morphology. Furthermore, the role of N. sativa seed oil in decreasing cell tumorigenicity features was highlighted by testing the cancer cell migration using the wound healing assay. RESULTS: Results showed that higher concentrations (50 µg/mL) of N. sativa Linn. seed oil changed the breast cancer cell morphology and decreased the cell proliferation and viability. Breast cancer cells treated with black seed oil decreased cell movement after 24 hours compared to the untreated cell in the wound healing assay. Whereas, only the higher concentration of doxorubicin (0.5-2.5 µg/mL) reduced cell proliferation and cell viability. Moreover, the combination treatment of 50 µg/mL of black seed oil with different concentrations of doxorubicin caused a significant cell proliferation reduction and decreased cell viability. The activity was seen optimum at lower concentration (0.1 µg/mL) of doxorubicin. CONCLUSIONS: There was decreased cell proliferation and cell viability when N. sativa seed oil was used alone or in conjunction with doxorubicin in Breast cancer cells (MCF-7) revealing potential opportunities in the field of cancer treatment.

PAX2 maintains the differentiation of mouse oviductal epithelium and inhibits the transition to a stem cell-like state.

Recent studies have provided evidence that the secretory cells of the fallopian tube (oviduct) are a probable origin for high-grade serous ovarian carcinoma. In addition to secretory cells, the fallopian tube epithelium consists of ciliated cells and CD44+ undifferentiated stem-like cells. Loss of PAX2 expression is recognized as an early event in epithelial transformation, but the specific role of PAX2 in this transition is unknown. The aim of this study was to define the role of PAX2 in oviductal epithelial (OVE) cells and its response to transforming growth factor ß1 (TGFß), characterizing specifically its potential involvement in regulating stem cell-like behaviors that may contribute to formation of cancer-initiating cells. Treatment of primary cultures of mouse OVE cells with TGFß induced an epithelial-mesenchymal transition (EMT) associated with decreased expression of PAX2 and an increase in the fraction of cells expressing CD44. PAX2 knockdown in OVE cells and overexpression in ovarian epithelial cells confirmed that PAX2 inhibits stem cell characteristics and regulates the degree of epithelial differentiation of OVE cells. These results suggest that loss of PAX2, as occurs in serous tubal intraepithelial carcinomas, may shift secretory cells to a more mesenchymal phenotype associated with stem-like features.