Activiteit

Radiotherapy is widely used in the management of lung cancer, and physicians are aware that the effect of radiotherapy is dependent on radiosensitivity. Although a series of blockers and activators targeting molecules related to radioresistance have been developed as radiation sensitizers, compensatory mechanisms or drug resistance limits their clinical efficacy. The identification of a key molecule related to lung cancer cell radioresistance or an effective molecular target is a challenging but important problem in radiation oncology. A previous study found that neuropilin 1 (NRP1) is related to radioresistance in A549 cells and is associated with VEGF, PI3K-Akt, MAPK-ERK, P38, NF-κβ and TGF-β. Inhibition of NRP1 can increase the radiosensitivity of A549 cells. Therefore, NRP1 may be a molecular target for radiotherapy-sensitizing drugs in lung cancer. The present study investigated the key downstream genes of NRP1, verified their regulation and clarified their roles in regulating lung cancer radioresistance. NRP1 positively regulated the downstream homeobox genes (HOXs) HOXA6, HOXA9 and mixed lineage leukaemia 5 (MLL5) in addition to MLL5-regulated HOXA6 and HOXA9, but these genes did not regulate NRP1. MLL5, HOXA6 and HOXA9 levels were decreased in tumour tissues and positively correlated with NRP1. All of these genes were induced by ionizing radiation in vivo and in vitro. NRP1 expression was significantly lower in squamous cell carcinoma compared with that in adenocarcinoma, and lymph node metastasis occurred more often in patients with lung cancer with high MLL5 and NRP1 expression compared with patients with low MLL5 and NRP1 expression. Collectively, these data confirmed that NRP1 is associated with MLL5 and regulates radioresistance through HOXA6 and HOXA9.Recognized as a group I carcinogen for gastric cancer (GC) and a factor involved in the development of GC, Helicobacter pylori serves a major part in GC research. However, most studies have focused on H. pylori itself, ignoring the complicated pathogenic microbiological environment of GC and neglecting the synergistic or antagonistic effects of H. pylori with other pathogenic microorganisms. Increasing evidence has revealed that the human cytomegalovirus (HCMV) is present in several types of tumors and serves an important role in the neoplastic process of certain human malignant tumors, including GC. The aim of the present study was to explore the role of HCMV and H. pylori co-infection in GC. HCMV and H. pylori infection was analyzed in paired gastric tumor and peri-tumoral tissues from 134 (98 male and 36 female) patients using PCR. The results revealed that a total of 74 (55.2%) patients had H. pylori infection, 58 patients (43.3%) had HCMV infection, and 34 (25.4%) patients had both HCMV and H. pylori infection. Univariate and multivariate analyses demonstrated that H. pylori infection was independently associated with advanced lymphatic metastasis [P=0.007; odds ratio (OR)=3.51]. Furthermore, compared with HCMV-/H. pylori -, neither HCMV+/H. pylori – nor HCMV+/H. pylori + were associated with metastasis, but HCMV-/H. pylori + co-infection status was an independent risk factor for advanced lymphatic metastasis (P=0.005; OR=6.00). In conclusion, GC co-infected with HCMV and H. pylori exhibited a low tendency of lymph node metastasis. HCMV may interact with H. pylori to inhibit the process of lymphatic metastasis, and the mechanism requires further investigation.Cervical cancer is one of the most malignant tumors in women. miR-1298 was reported to be abnormally expressed and serve crucial role in tumorigenesis of several types of cancer; however, the role of miR-1298 in cervical cancer remains unknown. The present study aimed to evaluate the clinical and biological significance of miR-1298 in cervical cancer. To do so, the expression level of miR-1298 in cervical cancer tissues and cells was evaluated by reverse transcription quantitative PCR. Kaplan-Meier survival analysis and Cox regression analysis were used to explore the prognostic significance of miR-1298 in patients with cervical cancer. Cell Counting Kit-8 and Transwell migration and invasion assays were used to evaluate the effect of miR-1298 on the proliferative, migratory and invasive abilities of cervical cancer cells, respectively. The expression of miR-1298 was lower in cancer tissues and cells compared with normal tissues and cells. Furthermore, miR-1298 expression was associated with lymph node metastasis, tumor diameter and staging from the International Federation of Gynecology and Obstetrics. In addition, patients with low miR-1298 expression had poorer overall survival. These findings suggested that miR-1298 may be considered as an independent prognostic factor for patients with cervical cancer. Furthermore, the results demonstrated that miR-1298 knockdown could promote tumor cell proliferation and migratory and invasive abilities. In addition, nucleus accumbens-associated 1 (NACC1) was demonstrated to be a direct target of miR-1298. Taken together, these findings indicated that miR-1298 overexpression may be considered as a prognostic biomarker for cervical cancer and that miR-1298 may play an inhibitor role in cervical cancer by targeting NACC1.Trastuzumab resistance is a severe problem in the treatment of ErbB2-amplified cancer. Lanifibranor Although trastuzumab plus pertuzumab is able to partly overcome trastuzumab resistance in ErbB2-overexpressing cancer, its antitumor efficacy remains limited. The present study investigated the antitumor activity of the combination of trastuzumab with H2-18, which is an antibody targetinsg ErbB2 domain I. Cell proliferation and inhibition experiments indicated that H2-18 and trastuzumab synergistically inhibited the proliferation of both the trastuzumab-sensitive gastric cancer cell line, NCI-N87 and the trastuzumab-resistant gastric cancer cell line, NCI-N87-TraRT. Furthermore, H2-18 plus trastuzumab inhibited the growth of NCI-N87-TraRT cells more effectively than trastuzumab plus pertuzumab, both in vitro and in vivo. Compared with trastuzumab plus pertuzumab, H2-18 plus trastuzumab had a potent ability to inhibit NCI-N87-TraRT cells to form colonies. Notably, H2-18 plus trastuzumab was more effective in inducing cell death than trastuzumab plus pertuzumab.