Background: Cellular senescence has been perceived as a barrier against carcinogenesis. However, the senescence-associated secretory phenotype (SASP) of senescent cells can promote tumorigenesis. Our previous researches revealed that the secretary cytokines from senescent cancer cells induced by bleomycin promoted migration and invasion of associated non-senescent cells, while the impact of hydrogen peroxide (H 2 O 2 )-induced senescent epithelial originated tumor cells on associated non-senescent tumor cells was rarely reported and the underlying mechanisms has not been discerned. Method: Senescence was induced in human lung adenocarcinoma cancer cells (A549 and NCI-H1299) by Oxidative DNA damage chemical, hydrogen peroxide (H 2 O 2 ), and verified by senescence-associated b-galactosidase (SA-b gal) staining and flow cytometry. A549 and NCI-H1299 cells were treated with condition medium of senescent/nonsenescent A549 and NCI-H1299 (senescent vs. non-senescent group), and their protumorigenic roles were tested by cell viability assay, colony formation assay and cell invasion and migration assay. Labelfree quantitative proteomics was performed to detect the expression of cytokines in culture medium of senescent/non-senescent A549 and NCI-H1299. To determine whether the YAP and programmed cell death ligand 1 (PD-L1) were involved in the tumorigenic roles, the protein and mRNA expression levels of PD-L1, YAP, CYR61, c-Myc and CTGF in A549 and NCI-H1299 were assessed by Western blot (WB) and quantitative reverse transcriptase PCR (qRT-PCR). To characterize senescent cells in lung cancer patients, we performed SA-b-Gal staining using fresh-frozen tissue sections from 20 normal lung samples and 40 lung adenocarcinoma cancer samples. To elucidate the relationship between YAP and PD-L1 in the same tumor tissue, immunohistochemistry detected the expression of both YAP and PD-L1. Result: A549 and NCI-H1299 could be steadily induced senescence with an induced rate of more than 90% at a dose of 200uM and 100uM of H 2 O 2 , respectively. The proliferation and migration ability of cells was significantly higher in senescent than in non-senescent group. Senescent condition medium significantly promoted cell proliferation and migration in both PD-L1 high-expressing NCI-H1299 and PD-L1 lowexpressing A549. However, the presence of senescent condition medium increased the proliferation and invasion of co-cultured cells was significantly less in PD-L1 low-expression A549 than that seen in PD-L1 high-expressing NCI-1299. The secrete proteins identified following H 2 O 2 treatment included extracellular matrix protein, inflammatory cytokines, growth factors, chemokines etc. Further mechanistic investigations revealed that mRNA level of target genes of YAP (CYR61, c-Myc, CTGF) and PD-L1 were increased after H 2 O 2 treatment and their expression were positively correlated. Besides, in senescent lung adenocarcinoma cancer tissue, PD-L1 positive lung adenocarcinoma cancer samples showed significantly higher nuclear YAP positive ratios co...
Ureteric carcinoma is the rarest of all urothelial malignancies, and little attention has been given to it. Palliation in these groups of patients is a dilemma in the clinics. Use of chemotherapeutic agents in ureteric carcinoma is a double edged sword, as these patients had already impaired renal function due to post-renal failure and nephrotoxic nature of most of the chemotherapeutic agents can further deteriorate the renal function, making the management approach, a relatively visionary task. Here, we present a case of a 77-year-old female with metastatic ureteric carcinoma locally complicated with hydroureteronephrosis, coming to us with gross haematuria, lower abdominal pain along with cough. Apart from age factor of the lady, presence of hydroureteronephrosis and pulmonary metastases was another challenge for us. Paclitaxel remains the mainstay of our treatment.
Genetic alteration of tumor suppressor and oncogene plays important role in development and progression of cancer. Tumor suppressor gene, Tp53 also knows as ‘guardian of genome’ has very important role in head and neck squamous cell carcinoma (HNSCC). Mutation of Tp53 has been commonly observed in other carcinomas including HNSCC, comprising of 75-85% of head and neck cancer, with highest in larynx and hypopharynx followed by oral cavity. Tp53 mutation is more commonly seen in Human Papilloma Virus (HPV)-ve and wild type Tp53 in HPV+ve carcinomas. Role of Tp53 mutation help us to know about the prognostic state, molecular stage and chance of local recurrence. Different studies have highlighted the importance of assessing Tp53 mutation in the negative surgical margin, which showed mutation of Tp53 in the negative surgical margin resulted increase in chance of local recurrence. These studies provide significance of moving conventional method of histopathological assessment to molecular assessment, that gives advantage of proper management decision as well as prognosis of tumor. Regarding techniques of these assessments, molecular technique has been always superior to immunohistochemistry (IHC) but is somewhat tedious, so more clinical analysis on the alternatives of IHC combined with Next generation sequencing (NGS) gives the platform to perform more Tp53 mutation test in the surgical margin. This is the need of time to incorporate molecular staging in the conventional staging for proper treatment and outcome in the management of head and neck cancers.
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