To study the effect of IL-18 and nitric oxide(NO) on the growth and metastasis of non-small cell lung cancer (NSCLC).Methods Serum IL-18 and nitrate and nitrite levels in 82 patients with NSCLC and 20 healthy control ...To study the effect of IL-18 and nitric oxide(NO) on the growth and metastasis of non-small cell lung cancer (NSCLC).Methods Serum IL-18 and nitrate and nitrite levels in 82 patients with NSCLC and 20 healthy control subjects were measured by using ELISA and Griess.Results The levels of serum IL-18 were (334.2±31.0)ng/L in NSCLC patients and (151.3±22.0)ng/L in control subjects,respectively.The levels of nitrate and nitrite were (237.1±21.0)μmol/L in NSCLC patients and (44.2±15.0)μmol/L in control subjects.The levels of serum IL-18 and nitrate and nitrite were not related with age,gender,histological types in patients with NSCLC.The levels of serum IL-18 was closely associated with TNM stage,lymph node metastasis and distal metastasis,but not with its degree and organ types of metastasis.There was a negative correlation between the levels of serum IL-18 and nitrate and nitrite.Conclusion Serum IL-18 and nitrate and nitrite levels may be useful to evaluate the prognosis of the patients with NSCLC.16 refs,2 tabs.展开更多
The tumor suppressor protein p53 is central to cancer biology,with its pathway reactivation emerging as a promising therapeutic strategy in oncology.This study introduced LZ22,a novel compound that selectively inhibit...The tumor suppressor protein p53 is central to cancer biology,with its pathway reactivation emerging as a promising therapeutic strategy in oncology.This study introduced LZ22,a novel compound that selectively inhibits the growth,migration,and metastasis of tumor cells expressing wild-type p53,demonstrating ineffectiveness in cells devoid of p53 or those expressing mutant p53.LZ22’s mechanism of action involves a high-affinity interaction with the histidine-96 pocket of the MDM2 protein.This interaction disrupted the MDM2-p53 binding,consequently stabilizing p53 by shielding it from proteasomal degradation.LZ22 impeded cell cycle progression and diminished cell proliferation by reinstating the p53-dependent suppression of the CDK2/Rb signaling pathway.Moreover,LZ22 alleviated the p53-dependent repression of Snail transcription factor expression and its consequent EMT,effectively reducing tumor cell migration and distal metastasis.Importantly,LZ22 administration in tumor-bearing mice did not manifest notable side effects.The findings position LZ22 as a structurally unique reactivator of p53,offering therapeutic promise for the management of human cancers with wild-type TP53.展开更多
文摘To study the effect of IL-18 and nitric oxide(NO) on the growth and metastasis of non-small cell lung cancer (NSCLC).Methods Serum IL-18 and nitrate and nitrite levels in 82 patients with NSCLC and 20 healthy control subjects were measured by using ELISA and Griess.Results The levels of serum IL-18 were (334.2±31.0)ng/L in NSCLC patients and (151.3±22.0)ng/L in control subjects,respectively.The levels of nitrate and nitrite were (237.1±21.0)μmol/L in NSCLC patients and (44.2±15.0)μmol/L in control subjects.The levels of serum IL-18 and nitrate and nitrite were not related with age,gender,histological types in patients with NSCLC.The levels of serum IL-18 was closely associated with TNM stage,lymph node metastasis and distal metastasis,but not with its degree and organ types of metastasis.There was a negative correlation between the levels of serum IL-18 and nitrate and nitrite.Conclusion Serum IL-18 and nitrate and nitrite levels may be useful to evaluate the prognosis of the patients with NSCLC.16 refs,2 tabs.
基金supported by the National Natural Science Foundation of China(Nos.82125036,82273964,81973363,82304538,81973188)the State Key Laboratory of Natural Medicines of CPU(No.SKLNMZZ202207)+3 种基金the“Double-First Class”Program of CPU,the National Key Research and Development Program of China(No.2017YFA0503900)the Jiangsu Provincial Natural Science Fund for Distinguished Young Scholar(No.BK20230042)the Jiangsu Funding Program for Excellent Postdoctoral Talent(No.2023ZB171)the Shenzhen Fundamental Research Program(No.JCYJ20200109114225087).
文摘The tumor suppressor protein p53 is central to cancer biology,with its pathway reactivation emerging as a promising therapeutic strategy in oncology.This study introduced LZ22,a novel compound that selectively inhibits the growth,migration,and metastasis of tumor cells expressing wild-type p53,demonstrating ineffectiveness in cells devoid of p53 or those expressing mutant p53.LZ22’s mechanism of action involves a high-affinity interaction with the histidine-96 pocket of the MDM2 protein.This interaction disrupted the MDM2-p53 binding,consequently stabilizing p53 by shielding it from proteasomal degradation.LZ22 impeded cell cycle progression and diminished cell proliferation by reinstating the p53-dependent suppression of the CDK2/Rb signaling pathway.Moreover,LZ22 alleviated the p53-dependent repression of Snail transcription factor expression and its consequent EMT,effectively reducing tumor cell migration and distal metastasis.Importantly,LZ22 administration in tumor-bearing mice did not manifest notable side effects.The findings position LZ22 as a structurally unique reactivator of p53,offering therapeutic promise for the management of human cancers with wild-type TP53.