Colorectal cancer (CRC) constitutes one of the most aggressive malignancies worldwide and in Malaysia. Due to high recurrence rate and toxic side effects associated with radiation and chemotherapies, new agents are urgently needed. CARP-1 is a peri-nuclear phospho-protein which plays a dynamic role in regulating cell growth and apoptosis. CARP-1 functional mimetics (CFMs) are a class of compounds that stimulate CARP-1. CFM-4, a lead compound, was shown to suppress growth and metastasis of various cancers, other than CRC. We hypothesized that CFM-4 inhibits proliferation and metastasis in CRC. Materials and method: CFM-4 anti-cancer effects of on CRC cells were investigated using MTT assay, Annexin V/Propidium iodide (PI) apoptosis assay, cell cycle analysis, quantitative real-time PCR (qRT-PCR) and Western blotting. Antimetastatic activities were assessed by migration, colony formation and invasion assays. Results: CFM-4 inhibited CRC cell proliferation and was much more potent than the classical anti-CRC 5-fluorouracil. These effects were shown to be mediated at least in part by stimulating apoptosis, as indicated in our Annexin V/PI assay results. Cell cycle analysis showed that CFM-4 induced G2/M phase arrest. Molecularly, qRT-PCR results revealed that CFM-4 promoted intrinsic apoptosis by upregulating expression of caspase-8 and -9 , p53, PUMA and Noxa, and stimulated extrinsic apoptosis by enhancing expression of death receptors (DR4 and DR5). CFM-4 upregulated NF- k B signaling inhibitor A20-binding inhibitor protein and the PI3K negative regulator PTEN. Western blot analysis results revealed that CFM-4 enhanced expression of CARP1, caspase-8 and executioner caspase-3. Metastatic properties of the CRC cells were reduced by CFM-4 through blocking their capabilities to form colonies, migrate and invade through the matrix-coated membranes. Conclusion: The potent antitumor and anti-metastatic properties of CFM-4 against CRC are due to collective pro-apoptotic, anti-proliferative and anti-metastatic activities. Together our data warrants further investigations of CFM-4 as potential anti-tumor agent for CRC malignancy and metastasis.
The rapid thermal cracking technology of biomass can convert biomass into bio-oil and is beneficial for industrial applications. Agricultural and forestry wastes are important parts of China's energy, and their high-grade utilization is useful to solve the problem of energy shortages and environmental pollution. To the best of our knowledge, the impact of nanocatalysts on converting biowastes for bio-oil has not been studied. Consequently, we examined the production of bio-oil by pyrolysis of Aesculus chinensis Bunge Seed (ACBS) using nanocatalysts (Fe2O3 and NiO catalysts) for the first time. The pyrolysis products of ACBS include 1-hydroxy-2-propanone (3.97%), acetic acid (5.42%), and furfural (0.66%). These chemical components can be recovered for use as chemical feedstock in the form of bio-oil, thus indicating the potential of ACBS as a feedstock to be converted by pyrolysis to produce value-added bio-oil. The Fe2O3 and NiO catalysts enhanced the pyrolysis process, which accelerated the precipitation of gaseous products. The pyrolysis rates of the samples gradually increased at DTGmax, effectively promoting the catalytic cracking of ACBS, which is beneficial to the development and utilization of ACBS to produce high valorization products. Combining ACBS and nanocatalysts can change the development direction of high valorization agricultural and forestry wastes in the future.
Dihydropyrimidines are widely recognized for their diverse biological properties and are often synthesized by the Biginelli reactions. In this backdrop, a novel series of Biginelli dihydropyrimidines were designed, synthesized, purified, and analyzed by FT-IR, 1H NMR, 13C NMR, and mass spectrometry. Anticancer activity against MCF-7 breast cancer cells was evaluated as part of their cytotoxicity in comparison with the normal Vero cells. The cytotoxicity of dihydropyrimidines ranges from moderate to significant. Among the 38 dihydropyrimidines screened, compounds 16, 21, and 39 exhibited significant cytotoxicity. These 3 compounds were subjected to flow cytometry studies and EGFRwt Kinase inhibition assay using lapatinib as a standard. The study included evaluation for the inhibition of EGFR and HER2 expression at five different concentrations. At a concentration of 1000 nM compound 21 showed 98.51 % and 96.79 % inhibition of EGFR and HER2 expression. Moreover, compounds 16, 21 and 39 significantly inhibited EGFRwt activity with IC50 = 69.83, 37.21 and 76.79 nM, respectively. In addition, 3D-QSAR experiments were conducted to elucidate Structure activity relationships in a 3D grid space by comparing the experimental and predicted cytotoxic activities. Molecular docking studies were performed to validate the results by in silico method. All together, we developed a new series of Biginelli dihydropyrimidines as dual EGFR/HER2 inhibitors.
In low-middle income countries (LMICs) and the Middle East and North Africa (MENA) region, there is an unmet need to establish and improve breast cancer (BC) awareness, early diagnosis and risk reduction programs. During the 12th Breast, Gynecological & Immuno-oncology International Cancer Conference - Egypt 2020, 26 experts from 7 countries worldwide voted to establish the first consensus for BC awareness, early detection and risk reduction in LMICs/MENA region. The panel advised that there is an extreme necessity for a well-developed BC data registries and prospective clinical studies that address alternative modalities/modified BC screening programs in areas of limited resources. The most important recommendations of the panel were: (a) BC awareness campaigns should be promoted to public and all adult age groups; (b) early detection programs should combine geographically distributed mammographic facilities with clinical breast examination (CBE); (c) breast awareness should be encouraged; and (d) intensive surveillance and chemoprevention strategies should be fostered for high-risk women. The panel defined some areas for future clinical research, which included the role of CBE and breast self-examination as an alternative to radiological screening in areas of limited resources, the interval and methodology of BC surveillance in women with increased risk of BC and the use of low dose tamoxifen in BC risk reduction. In LMICs/MENA region, BC awareness and early detection campaigns should take into consideration the specific disease criteria and the socioeconomic status of the target population. The statements with no consensus reached should serve as potential catalyst for future clinical research.
Background: The management of patients with triple-negative breast cancer (TNBC) is challenging with several controversies and unmet needs. During the 12th Breast-Gynaecological & Immuno-oncology International Cancer Conference (BGICC) Egypt, 2020, a panel of 35 breast cancer experts from 13 countries voted on consensus guidelines for the clinical management of TNBC. The consensus was subsequently updated based on the most recent data evolved lately. Methods: A consensus conference approach adapted from the American Society of Clinical Oncology (ASCO) was utilized. The panellists voted anonymously on each question, and a consensus was achieved when ≥75% of voters selected an answer. The final consensus was later circulated to the panellists for critical revision of important intellectual content. Results and conclusion: These recommendations represent the available clinical evidence and expert opinion when evidence is scarce. The percentage of the consensus votes, levels of evidence and grades of recommendation are presented for each statement. The consensus covered all the aspects of TNBC management starting from defining TNBC to the management of metastatic disease and highlighted the rapidly evolving landscape in this field. Consensus was reached in 70% of the statements (35/50). In addition, areas of warranted research were identified to guide future prospective clinical trials.