Non-small cell lung cancer patients with ex19del or exon 21 L858R mutation: distinct mechanisms, different efficacies to treatments.

With the development of antitumor therapies, different treatment methods including monotherapy and combined therapy have achieved clinical efficacy in advanced epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients. Exon 19 deletion (ex19del) and exon 21 L858R mutation are common sensitive subtypes of EGFR mutation. However, potential distinct mechanisms are found from several dimensions including molecular structures, biological behaviors, concomitant mutations, resistance mechanisms and tumor mutation burdens. More evidence indicates the prognostic difference of EGFR subgroups. This review focused on the progress of potential distinct mechanisms and outcomes in clinical trials of advanced NSCLC patients with ex19del or exon 21 L858R mutation.

Effects of low-dose radiation on adaptive response in colon cancer stem cells

Purpose. Biological effects of low-dose radiation (LDR) are distinguishable from those of high-dose radiation. Adaptive response is an important biological effect following low-dose radiation. Cancer stem cells (CSCs) have self-renewal and multidirectional differentiation potency which results in relapse and metastasis of cancer. In this study, we aimed to examine whether adaptive response could be induced in CSCs by LDR. Methods. Parental cells of three colon cancer cell lines (HRT18, HT29, and HCT116) and CSCs of these three cell lines were irradiated with LDR (i.e., D1) and then high-dose radiation (HDR) of X-rays (i.e., D1 + D2) or only HDR (D2 alone), followed by examination of adaptive response. Results. Adaptive response was not observed either in the three tumor parental cells lines or in three CSCs lines following LDR, due to the lack of resistance to subsequent D2-induced cell growth inhibition. Conclusion. These results suggested that LDR may not induce adaptive response in colon cancer cells or colon CSCs under in vitro conditions. Our study provided experimental and clinical foundations for the application of LDR in the treatment of colon cancers (AU)

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Finite element analysis on tooth and periodontal stress under simulated occlusal loads.

The tooth stress elicited by occluding contact represents critical biomechanical information about dental health during chewing. Effects of occlusal contact on tooth stress remain obscure. In this study, a mandibular first molar finite element model was built from CT images. The effects of area size, location and direction of occlusal loading on both tooth and periodontal stresses were analysed. Results showed tooth and periodontal stress had drastically different patterns. Tooth stress value was much higher than periodontal stress value under the same task. Tooth stress concentration area and its value decreased from outside to inside. The Maximum Tooth Stress (MTS) always occurred at the loading site and a larger loading area elicited a smaller MTS value. The variation of MTS was larger when the fossa bottoms were inclined loaded than when the cusp tips were inclined loaded, larger when lingually loaded than when buccally loaded and larger when mesially loaded than when distally loaded. Distal loadings generally induced smaller Maximum Periodontal Stress (MPS) variations than the mesial loadings. These findings indicated exposure of the rational site(s) to occlusal contact should be helpful to achieve proper tooth and periodontal stress, thus to diminish loading associated structure problems.

Effects of low-dose radiation on adaptive response in colon cancer stem cells.

PURPOSE: Biological effects of low-dose radiation (LDR) are distinguishable from those of high-dose radiation. Adaptive response is an important biological effect following low-dose radiation. Cancer stem cells (CSCs) have self-renewal and multidirectional differentiation potency which results in relapse and metastasis of cancer. In this study, we aimed to examine whether adaptive response could be induced in CSCs by LDR. METHODS: Parental cells of three colon cancer cell lines (HRT18, HT29, and HCT116) and CSCs of these three cell lines were irradiated with LDR (i.e., D1) and then high-dose radiation (HDR) of X-rays (i.e., D1 + D2) or only HDR (D2 alone), followed by examination of adaptive response. RESULTS: Adaptive response was not observed either in the three tumor parental cells lines or in three CSCs lines following LDR, due to the lack of resistance to subsequent D2-induced cell growth inhibition. CONCLUSION: These results suggested that LDR may not induce adaptive response in colon cancer cells or colon CSCs under in vitro conditions. Our study provided experimental and clinical foundations for the application of LDR in the treatment of colon cancers.

Continuous Fli-1 expression plays an essential role in the proliferation and survival of F-MuLV-induced erythroleukemia and human erythroleukemia.

Erythroleukemia induced by Friend Murine Leukemia Virus (F-MuLV) serves as a powerful tool for the study of multistage carcinogenesis and hematological malignancies in mice. Fli-1, a proto-oncogene and member of the Ets family, is activated through viral integration in F-MuLV-induced erythroleukemia, and is the most critical event in the induction of this disease. Fli-1 aberrant regulation is also observed in human malignancies, including Ewing's sarcoma, which is often linked to expression of the EWS/Fli-1 fusion oncoprotein. Here we examined the effects of Fli-1 inhibition to further elucidate its role in these pathological occurrences. The constitutive suppression of Fli-1, through RNA interference (RNAi), inhibits growth and induces death in F-MuLV-induced erythroleukemia cells. Expression of a dominant negative protein Engrailed (En)/Fli-1 reduces proliferation of EWS/Fli-1-transformed NIH-3T3 cells, and both F-MuLV-induced and human erythroleukemia cells. F-MuLV-induced erythroleukemia cells also display increased apoptosis, associated with reduced expression of bcl-2, a known fli-1 target gene. Introduction of En/Fli-1 into an F-MuLV-infected erythroblastic cell line induces differentiation, as shown by increased alpha-globin expression. These results suggest, for the first time, an essential role for continuous Fli-1 overexpression in the maintenance and survival of the malignant phenotype in murine and human erythroleukemias.