Non-small cell lung cancer (NSCLC) is one of the most prevalent and lethal types of cancers worldwide and its high incidence and mortality rates pose a significant public health challenge. Despite sig Show more
Non-small cell lung cancer (NSCLC) is one of the most prevalent and lethal types of cancers worldwide and its high incidence and mortality rates pose a significant public health challenge. Despite significant advances in targeted therapy and immunotherapy, the overall prognosis of patients with NSCLC remains poor. Hypoxia is a critical driving factor in tumor progression, influencing the biological behavior of tumor cells through complex molecular mechanisms. The present review systematically examined the role of the hypoxic microenvironment in NSCLC, demonstrating its crucial role in promoting tumor cell growth, invasion and metastasis. Additionally, it has been previously reported that the hypoxic microenvironment enhances tumor cell resistance by activating hypoxia-inducible factor and regulating exosome secretion. The hypoxic microenvironment also enables tumor cells to adapt to low oxygen and nutrient-deficient conditions by enhancing metabolic reprogramming, such as through upregulating glycolysis. Further studies have shown that the hypoxic microenvironment facilitates immune escape by modulating tumor-associated immune cells and suppressing the antitumor response of the immune system. Moreover, the hypoxic microenvironment increases tumor resistance to radiotherapy, chemotherapy and other types of targeted therapy through various pathways, significantly reducing the therapeutic efficacy of these treatments. Therefore, it could be suggested that early detection of cellular hypoxia and targeted therapy based on hypoxia may offer new therapeutic approaches for patients with NSCLC. The present review not only deepened the current understanding of the mechanisms of action and role of the hypoxic microenvironment in NSCLC but also provided a solid theoretical basis for the future development of precision treatments for patients with NSCLC. Show less
Colorectal cancer (CRC) is the third most common cancer worldwide, and the second most common cause of cancer-related death. In 2020, the estimated number of deaths due to CRC was approximately 930000 Show more
Colorectal cancer (CRC) is the third most common cancer worldwide, and the second most common cause of cancer-related death. In 2020, the estimated number of deaths due to CRC was approximately 930000, accounting for 10% of all cancer deaths worldwide. Accordingly, there is a vast amount of ongoing research aiming to find new and improved treatment modalities for CRC that can potentially increase survival and decrease overall morbidity and mortality. Current management strategies for CRC include surgical procedures for resectable cases, and radiotherapy, chemotherapy, and immunotherapy, in addition to their combination, for non-resectable tumors. Despite these options, CRC remains incurable in 50% of cases. Nonetheless, significant improvements in research techniques have allowed for treatment approaches for CRC to be frequently updated, leading to the availability of new drugs and therapeutic strategies. This review summarizes the most recent therapeutic approaches for CRC, with special emphasis on new strategies that are currently being studied and have great potential to improve the prognosis and lifespan of patients with CRC. Show less
Lung cancer is a common malignant tumor that occurs in the human body and poses a serious threat to human health and quality of life. The existing treatment methods mainly include surgical treatment, Show more
Lung cancer is a common malignant tumor that occurs in the human body and poses a serious threat to human health and quality of life. The existing treatment methods mainly include surgical treatment, chemotherapy, and radiotherapy. However, due to the strong metastatic characteristics of lung cancer and the emergence of related drug resistance and radiation resistance, the overall survival rate of lung cancer patients is not ideal. There is an urgent need to develop new treatment strategies or new effective drugs to treat lung cancer. Ferroptosis, a novel type of programmed cell death, is different from the traditional cell death pathways such as apoptosis, necrosis, pyroptosis and so on. It is caused by the increase of iron-dependent reactive oxygen species due to intracellular iron overload, which leads to the accumulation of lipid peroxides, thus inducing cell membrane oxidative damage, affecting the normal life process of cells, and finally promoting the process of ferroptosis. The regulation of ferroptosis is closely related to the normal physiological process of cells, and it involves iron metabolism, lipid metabolism, and the balance between oxygen-free radical reaction and lipid peroxidation. A large number of studies have confirmed that ferroptosis is a result of the combined action of the cellular oxidation/antioxidant system and cell membrane damage/repair, which has great potential application in tumor therapy. Therefore, this review aims to explore potential therapeutic targets for ferroptosis in lung cancer by clarifying the regulatory pathway of ferroptosis. Based on the study of ferroptosis, the regulation mechanism of ferroptosis in lung cancer was understood and the existing chemical drugs and natural compounds targeting ferroptosis in lung cancer were summarized, with the aim of providing new ideas for the treatment of lung cancer. In addition, it also provides the basis for the discovery and clinical application of chemical drugs and natural compounds targeting ferroptosis to effectively treat lung cancer. Show less
In this work, we have synthesized a series of novel C,N-cyclometalated 2H-indazole-ruthenium(II) and -iridium(III) complexes with varying substituents (H, CH3, isopropyl, and CFShow more
In this work, we have synthesized a series of novel C,N-cyclometalated 2H-indazole-ruthenium(II) and -iridium(III) complexes with varying substituents (H, CH3, isopropyl, and CF3) in the R4 position of the phenyl ring of the 2H-indazole chelating ligand. All of the complexes were characterized by 1H, 13C, high-resolution mass spectrometry, and elemental analysis. The methyl-substituted 2H-indazole-Ir(III) complex was further characterized by single-crystal X-ray analysis. The cytotoxic activity of new ruthenium(II) and iridium(III) compounds has been evaluated in a panel of triple negative breast cancer (TNBC) cell lines (MDA-MB-231 and MDA-MB-468) and colon cancer cell line HCT-116 to investigate their structure-activity relationships. Most of these new complexes have shown appreciable activity, comparable to or significantly better than that of cisplatin in TNBC cell lines. R4 substitution of the phenyl ring of the 2H-indazole ligand with methyl and isopropyl substituents showed increased potency in ruthenium(II) and iridium(III) complexes compared to that of their parent compounds in all cell lines. These novel transition metal-based complexes exhibited high specificity toward cancer cells by inducing alterations in the metabolism and proliferation of cancer cells. In general, iridium complexes are more active than the corresponding ruthenium complexes. The new Ir(III)-2H-indazole complex with an isopropyl substituent induced mitochondrial damage by generating large amounts of reactive oxygen species (ROS), which triggered mitochondrion-mediated apoptosis in TNBC cell line MDA-MB-468. Moreover, this complex also induced G2/M phase cell cycle arrest and inhibited cellular migration of TNBC cells. Our findings reveal the key roles of the novel C-N-cyclometalated 2H-indazole-Ir(III) complex to specifically induce toxicity in cancer cell lines through contributing effects of ROS-induced mitochondrial disruption along with chromosomal and mitochondrial DNA target inhibition. Show less
Abstract2â(1HâTetrazolâ5âyl)pyridine (L) has been reacted separately with Me2NCH2CH2Clâ HCl and ClCH2CH2OH to yield two regioisomers in each case,N,Nâdimethylâ2â[5â(pyridinâ2âyl)â1Hâtetrazolâ1âyl]ethan Show more
Abstract2â(1HâTetrazolâ5âyl)pyridine (L) has been reacted separately with Me2NCH2CH2Clâ HCl and ClCH2CH2OH to yield two regioisomers in each case,N,Nâdimethylâ2â[5â(pyridinâ2âyl)â1Hâtetrazolâ1âyl]ethanamine (L1)/N,Nâdimethylâ2â[5â(pyridinâ2âyl)â2Hâtetrazolâ2âyl]ethanamine (L2) and 2â[5â(pyridinâ2âyl)â1Hâtetrazolâ1âyl]ethanol (L3)/2â[5â(pyridinâ2âyl)â2Hâtetrazolâ2âyl]ethanol (L4), respectively. These ligands,L1âL4, have been coordinated with CuCl2â H2O in 1 : 1 composition to furnish the corresponding complexes1â4. EPR Spectra of Cu complexes1and3were characteristic of square planar geometry, with nuclear hyperfine spin 3/2. Single Xâray crystallographic studies of3revealed that the Cu center has a square planar structure. DNA binding studies were carried out by UV/VIS absorption; viscosity and thermal denaturation studies revealed that each of these complexes are avid binders of calf thymus DNA. Investigation of nucleolytic cleavage activities of the complexes was carried out on doubleâstranded pBR322 circular plasmid DNA by using a gel electrophoresis experiment under various conditions, where cleavage of DNA takes place by oxidative freeâradical mechanism (OHâ ).In vitroanticancer activities of the complexes against MCFâ7 (human breast adenocarcinoma) cells revealed that the complexes inhibit the growth of cancer cells. TheIC50values of the complexes showed that Cu complexes exhibit comparable cytotoxic activities compared to the standard drug cisplatin. Show less