ABSTRACT
Cetuximab is widely used in patients with metastatic colon cancer expressing wildtype KRAS. However, acquired drug resistance limits its clinical efficacy. Exosomes are nanosized vesicles secreted by various cell types. Tumor cell-derived exosomes participate in many biological processes, including tumor invasion, metastasis, and drug resistance. In this study, exosomes derived from cetuximab-resistant RKO colon cancer cells induced cetuximab resistance in cetuximab-sensitive Caco-2 cells. Meanwhile, exosomes from RKO and Caco-2 cells showed different levels of phosphatase and tensin homolog (PTEN) and phosphor-Akt. Furthermore, reduced PTEN and increased phosphorylated Akt levels were found in Caco-2 cells after exposure to RKO cell-derived exosomes. Moreover, an Akt inhibitor prevented RKO cell-derived exosome-induced drug resistance in Caco-2 cells. These findings provide novel evidence that exosomes derived from cetuximab-resistant cells could induce cetuximab resistance in cetuximab-sensitive cells, by downregulating PTEN and increasing phosphorylated Akt levels.
Subject(s)
Humans , Colonic Neoplasms/drug therapy , PTEN Phosphohydrolase/drug effects , Proto-Oncogene Proteins c-akt/drug effects , Exosomes/drug effects , Cetuximab/pharmacology , Antineoplastic Agents, Immunological/pharmacology , Tetrazolium Salts , Time Factors , Blotting, Western , Analysis of Variance , Caco-2 Cells , Cell Line, TumorABSTRACT
As a mechanism compensating for obstructive coronary artery disease, coronary collateral circulation (CCC) has attracted cardiologists for a long time to explore its potential impact. In the present study, Chinese patients suffering from ≥95% coronary stenosis, as diagnosed by angiography, have been investigated for the correlation between CCC and lipoprotein(a) [Lp(a)] levels. A cohort of 654 patients was divided into four categories according to Rentrop grades 0, 1, 2, and 3. Lp(a) levels were divided into model 1, discretized with critical values of 33 and 66%, and model 2, discretized with a cutoff value of 30.0 mg/dL. Furthermore, we evaluated the correlation between CCC and serum Lp(a) levels. The four groups had significantly different Lp(a) levels (25.80±24.72, 18.99±17.83, 15.39±15.80, and 8.40±7.75 mg/dL; P<0.001). In model 1, concerning R0, the risk in the third Lp (a) tertile (OR=3.34, 95%CI=2.32-4.83) was greater than that in the first tertile. In model 2, concerning R0, the risk in Lp(a) >30.0 group (OR=6.77, 95%CI=4.44-10.4) was greater than that of Lp(a) <30.0 mg/dL. The worst condition of CCC can be predicted independently by Lp(a) levels. In addition to clinical usage, Lp(a) levels can also be utilized as biological markers.
Subject(s)
Humans , Male , Female , Middle Aged , Collateral Circulation/physiology , Coronary Artery Disease/blood , Coronary Artery Disease/diagnostic imaging , Coronary Circulation/physiology , Coronary Occlusion/blood , Lipoprotein(a)/blood , Biomarkers/blood , Cohort Studies , Coronary Angiography , Coronary Artery Disease/physiopathology , Coronary Occlusion/diagnostic imaging , Coronary Occlusion/physiopathology , Predictive Value of Tests , Risk FactorsABSTRACT
Seroreactivity to syphilis is high among Malaysian blood donors and expectant mothers indicating a high degree of treponemal infection. Further epidemiological studies are required to ascertain what proportion of these could be syphilis and what porportion yaws. Blood donors hava a higher reactivity rate than expectant mothers, the reasons probably being soical. The titres obtained in the VDRL test appear to have a relation to FTA-ABS reactivity although this is not to say treponematosis can be excluded on the basis of low titre VDRL results.