siRNA-mediated silencing of CD44 delivered by Jet Pei enhanced Doxorubicin chemo sensitivity and altered miRNA expression in human breast cancer cell line (MDA-MB468)

Molecular Biology Reports - CD44, as a superficial cellular glycoprotein, is an essential factor in cell–cell and cell–matrix interaction. The CD44 expression level has been...     

CD133: An emerging prognostic factor and therapeutic target in colorectal cancer

Colorectal cancer (CRC) is one of the leading causes of death worldwide. Recently, the role of cancer stem cells (CSCs) has been highlighted as a crucial emerging factor in chemoresistance, cancer relapse, and metastasis. CD133 is a surface marker of CSCs and has been argued to have prognostic and therapeutic values in CRC along with its related pathways such as Wnt, Notch, and hedgehog. Several studies have successfully applied targeted therapies against CD133 in CRC models namely bispecific antibodies (BiAbs) and anti‐Wnt and notch pathways agents. These studies have yielded initial promising results in this regard. However, none of the therapeutics have been used in the clinical setting and their efficacy and adverse effects profile are yet to be elucidated. This review aims to gather the old and most recent data on the prognostic and therapeutic values of CD133 and CD133‐targeted therapies in CRC.     

Prostate cancer cells modulate the differentiation of THP‐1 cells in response to etoposide and TLR agonists treatments

The aim of this study was to determine the polarization of macrophages in the tumor microenvironment, as well as the effect of soluble factors secreted from these polarized macrophages on etoposide‐induced cancer cell apoptosis. We investigated the effect of soluble factors secreted from the supernatant of PC3 cells treated with TLR4 and TLR8 agonists, and etoposide on macrophage polarization at the protein level through flow cytometry and enzyme‐linked immunosorbent assay. We further explored the cell cycle distribution and phagocytic activity of THP‐1 cells by flow cytometry. To imitate the relationship between cancer cells and tumor‐associated macrophages (TAMs), we cocultured macrophages with etoposide‐treated PC3 cells. After the incubation, the apoptosis in cancer cells was assessed through FACS analysis and by annexin V and PI staining. Our results demonstrate that protein expression of M1 and M2 markers confirmed the upregulation of M1 markers upon etoposide treatment, and mixed M1/M2 phenotype upon treatment with TLR agonists‐treated PC3 supernatant. In coculture methods, our results demonstrate that the apoptosis of etoposide‐treated cancer cells increases in the presence of M0 macrophages and THP‐1 cells incubated with the supernatant of TLR4 agonists‐treated PC3 cells. These results indicate clear protective effects of M0 macrophages and THP‐1 cells incubated with the supernatant of PC3 cells treated with TLR4 agonists (THP‐1 + SUP + TLR4a) on etoposide‐induced cancer cell apoptosis.     

High frequency of microsatellite instability in sporadic colorectal cancer patients in Iran

Microsatellite instability in sporadic colorectal cancer patients was assessed, and the clinicopathological associations were evaluated in northeastern Iran, which is a high-risk region for gastrointestinal malignancies. Microsatellite instability (MSI) status of tumoral tissue, compared to normal tissue, was assessed with a standard panel of MSI markers on paraffin-embedded surgically resected tissues from 67 consecutive sporadic colorectal cancer patients. Eleven of the patients were under 40 years old. Female patients were significantly younger than male patients (mean age 54.2 vs 62.1 years, P = 0.020). MSI analysis revealed 18 cases of MSI-H (26.9%), 11 MSI-L (16.4%) and 38 MSS (microsatellite stable tumors; 56.7%). While a greater proportion of patients consisted of males, 56.7 vs 43.3% females, MSI-H was more frequent in females (34.5 vs 21.5%). MSI was associated with proximal location of tumor (P = 0.003) and lower stages of tumor (P = 0.002), while MSS tumors were associated with node metastasis. MSI has a higher frequency in sporadic colorectal cancer patients, suggesting that molecular epidemiology of the genetic alterations involved in colorectal cancer carcinogenesis has a different pattern in the Iranian population, which deserves further epidemiological attention. The high frequency of MSI-H in this population suggests that we should look at microsatellite instability prior to chemotherapy to determine the most appropriate chemotherapeutic strategy in our population.     

Cloning and in silico characterization of two signal peptides from Pediococcus pentosaceus and their function for the secretion of heterologous protein in Lactococcus lactis

Fifty signal peptides of Pediococcus pentosaceus were characterized by in silico analysis and, based on the physicochemical analysis, (two potential signal peptides Spk1 and Spk3 were identified). The coding sequences of SP were amplified and fused to the gene coding for green fluorescent protein (GFP) and cloned into Lactococcus lactis pNZ8048 and pMG36e vectors, respectively. Western blot analysis indicated that the GFP proteins were secreted using both heterologous SPs. ELISA showed that the secretion efficiency of GFP using Spk1 (0.64 μg/ml) was similar to using Usp45 (0.62 μg/ml) and Spk3 (0.58 μg/ml).     

Introducing Bacillus licheniformis as the causal agent of pistachio dieback in Iran

During 2004 and 2006 growing seasons some pistachio trees in Kerman province of Iran showed dieback symptoms. Initial symptoms were observed at the beginning of the growing season and they developed during two weeks after green tip stage, as shoot tips turned black and dieback occurred. During the growing season, the symptoms developed and vessel destruction was observed. If these stems were not pruned during winter, dieback developed in the spring. During the growing season affected pistachio samples were collected and surface disinfected with 0.01% mercury chloride. Pieces of affected vessels were grown on nutrient agar (NA) and incubated at 25°C for three-to-four days. Bacterial colonies with Bacillus characteristics were isolated and 15 representative strains were selected for further characterisation. The pathogenicity of selected strains was verified on 2–3 year-old pistachio seedlings using injection of bacterial suspension (10⁷ cfu p/ml) and control plants inoculated with distilled water; vessel destruction developed after 20 days, and bacterial causal agent was isolated from seedlings. No symptoms were observed in control plants. The strains were Gram positive, motile, with central spores and caused a hypersensitivity reaction (HR) on tobacco and geranium; they were positive for anaerobic growth, nitrate reduction, utilisation of citrate, VP test, urease, catalase, growth at pH 5.7, 7% NaCl and 45°C, acid production from arabinose, xylose, glucose and mannitol, and anaerobic fermentation of glucose. They could hydrolyze starch, aesculin, Tween 80 and gelatin but indole production was negative. Based on the characteristics of the isolated strains, they were identified as Bacillus licheniformis. This is the first report of Bacillus licheniformis as a causal agent of pistachio dieback.     

Identification of fungal diseases of Rosa damascena in Kerman province of Iran

The oil rose, Rosa damascena Mill. (Rosaceae) is an agricultural crop cultivated in various countries of the northern hemisphere, such as Turkey, Bulgaria, Morocco, Iran, Egypt, France, China and India. Iran, presently, is the largest producer of rose water in world. The major production areas in Iran are Kashan, Fars, Kerman and Azerbaijan. Kerman province with 2297 hectares ha of rose gardens and 6198 tons of flower production is one of the important rose production regions. The productions of this region are organic and do not use anychemical compounds such as pesticides and fertilisers. The major fungal pathogens were studied during 2008–2010 in oil rose production areas in Kerman province, Iran. Verticillium dahlias, Rosellinia necatrix, Alternaria alternata, Seimatosporium fusisporum and Podosphaera pannosa have been detected in the oil rose from different regions in Kerman province. A. alternata has the most isolates and infected plants per cent in the oil rose. This is the first report fromVerticillium dahliae, R. necatrix, A. alternata, S. fusisporum on oil roses (R.damascena) in the world.     

New emerging roles of CD133 in cancer stem cell: Signaling pathway and miRNA regulation

Cancer stem cells (CSC) are rare immortal cells within a tumor that are able to initiate tumor progression, development, and resistance. Advances studies show that, like normal stem cells, CSCs can be both self-renewed and given rise to many cell types, therefore form tumors. A number of cell surface markers, such as CD44, CD24, and CD133 are frequently used to identify CSCs. CD133, a transmembrane glycoprotein, either alone or in collaboration with other markers, has been mainly considered to identify CSCs from different solid tumors. However, the exactness of CD133 as a cancer stem cell biomarker has not been approved yet. The clinical importance of CD133 is as a CSC marker in many cancers. Also, it contributes to shorter survival, tumor progression, and tumor recurrence. The expression of CD133 is controlled by many extracellular or intracellular factors, such as tumor microenvironment, epigenetic factors, signaling pathways, and miRNAs. In this study, it was attempted to determine: 1) CD133 function; 2) the role of CD133 in cancer; 3) CD133 regulation; 4) the therapeutic role of CD133 in cancers.     

The combined restoration of miR-424-5p and miR-142-3p effectively inhibits MCF-7 breast cancer cell line via modulating apoptosis,proliferation, colony formation,cell cycle and autophagy

Background

The combined restoration of tumor-suppressive microRNAs (miRs) has been identified as a promising approach for inhibiting breast cancer development. This study investigated the effect of the combined restoration of miR-424-5p and miR-142-3p on MCF-7 cells and compared the efficacy of the combined therapy with the monotherapies with miR-424-5p and miR-142-3p.

Methods

After transfection of miR-424-5p and miR-142-3p mimics into MCF-7 cells in the combined and separated manner, the proliferation of tumoral cells was assessed by the MTT assay. Also, the apoptosis, autophagy, and cell cycle of the cells were analyzed by flow cytometry. Western blot and qRT-PCR were used to study the expression levels of c-Myc, Bcl-2, Bax, STAT-3, Oct-3, and Beclin-1.

Results

Our results have demonstrated that the combined restoration of miR-424-5p and miR-142-3p is more effective in inhibiting tumor proliferation via upregulating Bax and Beclin-1 and downregulating Bcl-2 and c-Myc. Besides, the combined therapy has arrested the cell cycle in the sub-G1 and G2 phases and has suppressed the clonogenicity via downregulating STAT-3 and Oct-3, respectively.

Conclusion

The combined restoration of miR-424-5p and miR-142-3p is more effective in inhibiting MCF-7 breast cancer development than monotherapies with miR-424-5p and miR-142-3p.