Lung cancer is one of the leading causes of cancer-related deaths worldwide with a 5-year survival rate of less than 18%. Current treatment modalities include surgery, chemotherapy, radiation therapy, targeted therapy, and immunotherapy. Despite advances in therapeutic options, resistance to therapy remains a major obstacle to the effectiveness of long-term treatment, eventually leading to therapeutic insensitivity, poor progression-free survival, and disease relapse. Resistance mechanisms stem from genetic mutations and/or epigenetic changes, unregulated drug efflux, tumor hypoxia, alterations in the tumor microenvironment, and several other cellular and molecular alterations. A better understanding of these mechanisms is crucial for targeting factors involved in therapeutic resistance, establishing novel antitumor targets, and developing therapeutic strategies to resensitize cancer cells towards treatment. In this review, we summarize diverse mechanisms driving resistance to chemotherapy, radiotherapy, targeted therapy, and immunotherapy, and promising strategies to help overcome this therapeutic resistance.
Background: : Thymoquinone is a promising anticancer molecule of which chemopreventive role is well-known at least in vitro and in animal model. In this review article, we have focused on the anti-inflammatory activities of thymoquionone in cancer cells. Method:: Research data on inflammation, cancer and thymoquinone was acquired from pubmed, scopus, web of science and google scholar. We have reviewed paper from the middle of last century, but mostly cited papers from last ten years. Results:: In addition to chemopreventive role, studies indicated that thymoquinone also have potential immunotherapeutic role, as thymoquinone can target and modulate inflammatory modulators, like nuclear factor kappa B (NF-κβ), interleukins, tumor necrosis factor-α (TNF-α), and certain growth factors. As chronic inflammation plays role in cancer development, controlling inflammatory pathways is an important mechanism of immunotherapeutic action of anticancer molecule. Conclusion: : This article reviewed the role of inflammation on cancer development, and the action of thymoquinone on inflammatory molecules, which have been proved in vitro and in vivo. Much more attention is required for studying the immunotherapeutic role of thymoquinone and developing this molecule as future immunotherapeutic drug.
Cancer immunotherapy shows durable treatment responses and therapeutic benefits compared to other cancer treatment modalities, but many cancer patients display primary and acquired resistance to immunotherapeutics. Immunosuppressive tumor microenvironment (TME) is a major barrier to cancer immunotherapy. Notably, cancer cells depend on high mitochondrial bioenergetics accompanied with the supply of heme for their growth, proliferation, progression, and metastasis. This excessive mitochondrial respiration increases tumor cells oxygen consumption, which triggers hypoxia and irregular blood vessels formation in various regions of TME, resulting in an immunosuppressive TME, evasion of anti-tumor immunity, and resistance to immunotherapeutic agents. In this review, we discuss the role of heme, heme catabolism, and mitochondrial respiration on mediating immunosuppressive TME by promoting hypoxia, angiogenesis, and leaky tumor vasculature. Moreover, we discuss the therapeutic prospects of targeting heme and mitochondrial respiration in alleviating tumor hypoxia, normalizing tumor vasculature, and TME to restore anti-tumor immunity and resensitize cancer cells to immunotherapy.
Background: SARS-CoV-2 is a coronavirus, of which infection causing COVID-19 was first reported in Wuhan, China at the end of 2019, and the outbreak became pandemic in February of 2020. Till now there is no effective drug or vaccine against this virus that can make complete cure; however, a number of drugs are in trials. Objectives: In this review, we have focused on an alternative therapeutic approach using natural products utilizing host anti-viral responses for resolving COVID-19 pathogenesis. Methods: We have searched databases like PubMed, Scopus, Web of Science and Google Scholar for articles related to natural products and viral diseases, with a specific focus on coronaviruses, as well as other RNA viruses and recent updates on COVID-19 pandemic, and collected articles and reviewed comprehensively. Results: Scientific studies clarified the viral pathogenesis that involved viral entrance into host cells, and antiviral response inside the cells, which can be effectively targeted by numerous natural compounds from different sources. Many of these compounds can potentially target viral genomic material or protein machinery. Natural products which were found effective against other coronaviruses, especially SARS-CoV or MERS-CoV (which emerged in 2002 and 2012, respectively) might be effective against SARS-CoV-2 due to their structural similarities; however, it needs time to establish the clinical success of these drugs. Conclusion: COVID-19 pandemic is a global emergency problem and urgent drug development is necessary. Natural products can be the biggest source of drugs, as they have been found effective in other coronaviruses previously; however, it needs time to establish these drugs for clinical application.
Background: Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer with enhanced metastasis and poor survival. Though chemotherapy, radiotherapy, photothermal therapy (PTT), photodynamic therapy (PDT), and gene delivery are used to treat TNBC, various side effects limit these therapeutics against TNBC. In this review article, we have focused on the mechanism of action of gold nanoparticles (AuNPs) to enhance the efficacy of therapeutics with targeted delivery on TNBC cells. Methods: Research data were accumulated from PubMed, Scopus, Web of Science, and Google Scholar using searching criteria “gold nanoparticles and triple-negative breast cancer” and “gold nanoparticles and cancer”. Though we reviewed many old papers, most cited papers were from the last ten years. Results: Various studies indicate that AuNPs can enhance bioavailability, site-specific drug delivery, and efficacy of chemotherapy, radiotherapy, PTT, and PDT as well as modulate gene expression. The role of AuNPs in the modulation of TNBC therapeutics through the inhibition of cell proliferation, progression, and metastasis has been proved in vitro and in vivo studies. As these mechanistic actions of AuNPs are most desirable to develop drugs with enhanced therapeutic efficacy against TNBC, it might be a promising approach to apply AuNPs for TNBC therapeutics. Conclusion: This article reviewed the mechanism of action of AuNPs and their application in the enhancement of therapeutics against TNBC. Much more attention is required for studying the role of AuNPs in developing them either as a single or synergistic anti-cancer agent against TNBC.
In this study, we estimate the proximate compositions, phytochemicals (polyphenol, flavonoids, flavonol, tannin, protein, carbohydrate, reducing sugar, and β carotene), antioxidant activities, vitamins, minerals, and heavy metals of the four pulses (mung, anchor, chickpea, lentils) and compare among them to find out more nutritious pulse samples. Mung was found to contain the highest amount of polyphenol (98.02 ± 1.74 mg GAE/100 g) and tannin (447.98 ± 9.96 mg TE/100 g) and anchor (771.35 ± 3.76 mg CE/100 g) was rich in flavonoids as compared to other two pulse samples. Mung was also rich in ash, carbohydrate, vitamin B 1 , copper and anchor was rich in crude fiber, protein, reducing sugar, and vitamin B 2 content. The highest amount of phytochemicals contained in mung and anchor corresponded to its highest antioxidant activity in analyzed antioxidant assays respectively. Other two pulses included in this study were found to contain good source of vitamins, minerals and other nutrients.
Background: Cholera, a diarrheal illness causes millions of deaths worldwide due to large outbreaks. Monoclonal antibody used as therapeutic purposes of cholera are prone to be unstable due to various factors including self-aggregation. Objectives: In this bioinformatic analysis, we identified the aggregation prone regions (APRs) of different immunogens of antibody sequences (i.e., CTB, ZnM-CTB, ZnP-CTB, TcpA-CT-CTB, ZnM-TcpA-CT-CTB, ZnP-TcpA-CT-CTB, ZnM-TcpA, ZnP-TcpA, TcpA-CT-TcpA, ZnM-TcpA-CT-TcpA, ZnP-TcpA-CT-TcpA, Ogawa, Inaba and ZnM-Inaba) raised against Vibrio cholerae. Methods: To determine APRs in antibody sequences that were generated after immunizing Vibrio cholerae immunogens on Mus musculus, a total of 94 sequences were downloaded as FASTA format from a protein database and the algorithms such as Tango, Waltz, PASTA 2.0, and AGGRESCAN were followed to analyze probable APRs in all of the sequences. Results: A remarkably high number of regions in the monoclonal antibodies were identified to be APRs which could explain a cause of instability/short term protection of anticholera vaccine. Conclusion: To increase the stability, it would be interesting to eliminate the APR residues from the therapeutic antibodies in a such way that the antigen binding sites or the complementarity determining region loops involved in antigen recognition are not disrupted.
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