Delayed HIV diagnosis in a cystic fibrosis patient: Not just another exacerbation.

Patients with cystic fibrosis (CF) are living longer due to advancements in treatment. We present a patient with CF in whom diagnoses of Human Immunodeficiency Virus (HIV) and severe pneumocystis pneumonia were delayed due to anchor bias. Our case highlights the importance of routine age-appropriate health screenings in patients with CF. In addition, we discuss the number of management challenges that may arise in patients with a dual diagnosis of CF and HIV.

Molecular mechanism of gossypol mediating CCL2 and IL­8 attenuation in triple­negative breast cancer cells.

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 triple­negative breast cancer (TNBC) cells, the most aggressive breast cancer type with poor prognosis. GOSS effects were examined in two TNBC cell lines: MDA­MB­231 (MM­231) and MDA­MB­468 (MM­468), 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 cancer­related cytokines in the two cell lines. Although GOSS did not alter CCL2 expression in MM­468 cells, it was able to cause 30% inhibition in TNF­α­stimulated MM­231 cells. Additionally, IL­8 was not altered by GOSS treatment in MM­231 cells, while its expression was inhibited by 60% in TNF­α­activated MM­468 cells. ELISA assays supported the microarray data and indicated that CCL2 expression was inhibited by 40% in MM­231 cells, and IL­8 expression was inhibited by 50% in MM­468 cells. Furthermore, in MM­231 cells, GOSS inhibited CCL2 release via the repression of IKBKE, CCL2 and MAPK1 gene expression. Additionally, in MM­468 cells, the compound downregulated the release of IL­8 through repressing IL­8, 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.

Effects of gossypol on apoptosis­related gene expression in racially distinct triple­negative breast cancer cells.

Apoptosis is a gene­directed mechanism that regulates cell proliferation and maintains homeostasis. Moreover, an aberrant apoptotic process can lead to several pathological conditions, such as tumorigenesis and cancer metastasis. In the present study, the apoptotic effect of the natural polyphenol compound gossypol GOSS) was investigated in triple­negative breast cancer TNBC) cells. The effect of GOSS was evaluated in two cell lines representative of a Caucasian­American and African­American origin, MDA­MB­231 MM­231) and MDA­MB­468 MM­468), respectively. A similar response to both cytotoxicity and proliferation was observed in the two cell lines. However, MM­468 cells were 2­fold more sensitive to the apoptotic effect of the compound, which was accompanied by a longer delay in colony formation. Furthermore, GOSS was found to alter the mRNA expression of many apoptosis­related genes. The compound significantly upregulated growth arrest and DNA damage­inducible 45 alpha protein (GADD45A), tumor necrosis factor receptor superfamily 9 (TNFRSF9) and BCL2 interacting protein 3 BNIP3) in MM­231 cells. Similarly, GADD45A and BNIP3 were upregulated in MM­468 cells. A significant finding in this study is the profound 159­fold increase in TNF gene expression that was observed in MM­468 cells. Moreover, the apoptosis­suppressor gene baculoviral IAP repeat containing 5 BIRC5) was significantly repressed (by more than 90%) in both cell lines, as well as death­associated protein kinase 1 (DAPK1) in MM­231 cells and tumor protein 73 (TP73) in MM­468 cells. In conclusion, the data obtained in this study provide a molecular understanding of the GOSS­induced apoptosis effect and suggest the importance of this polyphenol compound targeted towards TNBC treatment, particularly in African­American women.