摘要:Background and purpose: Senescent cancer-associated fibroblasts (CAFs) in tumor microenvironment are known to mediate the invasion and radio- or chemo-resistance of epithelial cancers. The inflammatory cytokine IL-6 derived from CAFs may promote the invasion and radio-resistance of epithelial cervical cancer. However, the detailed mechanism is not clear. This study aimed to investigate the effects of IL-6 on CAFs senescence, cervical cancer cell invasiveness and radio-resistance. Methods: CAFs from cervical cancer, normal fibroblasts (NFs) from normal cervical tissues, and cervical cancer cell lines including HeLa, Siha and ME180 were used in this study. Different treatments of cells with IL-6 and inhibitors of STAT3 and Notch were conducted to investigate the alterations of cellular senescence, STAT3/Notch signaling, cell invasiveness, and radiotherapy-induced apoptosis by using cell staining, immunofluorescence, Western blot, and flow cytometery. Results: This study found that the conditioned medium (CM) of CAFs or IL-6 could activate the STAT3 and Notch signaling to promote cellular senescence and cervical cancer cell invasiveness. Co-culture of cervical cancer cells HeLa or Siha along with CAFs also increased the invasiveness of cancer cells, but further treatments of cells by addition of an IL-6 antibody or the inhibitors of STAT3 (S31-201) or Notch (DAPT) blocked the cancer cell invasion. Meanwhile, this study also found that STAT3 functions at the upstream of the Notch signaling to up-regulate Jagged-1, one of the key ligands of Notch in fibroblasts or epithelial cancer cells through IL-6-mediated autocrine or paracrine pathways, which eventually confers the radio-resistance of cervical cancer cells/tissues. Conclusion: CAFs in tumor microenvironment could induce cervical cancer cell invasiveness and radio-resistance through IL-6/STAT3-mediated Notch activation, and that targeting of the STAT3/Notch signaling-associated molecules may improve the efficacy of radiotherapy for cervical cancer.
摘要:Background and purpose: Human epidermal growth factor receptor-2 (HER-2), a member of epidermal growth factor receptor family, initiates a diverse set of signaling pathways that ultimately affect such fundamental processes as cell proliferation, cell motility and cell apoptosis. It is reported that HER-2 was associated with epithelial-mesenchymal transition (EMT) process. However, the mechanism needs further investigation. The purpose of this study was to investigate the mechanism of HER-2 on regulating EMT process. Methods: Transwell assay was used to determine the motility of breast cancer cells; Real-time fluorescence quantitative polymerase chain reaction (RTFQ- PCR) was employed to determine the expression of genes of interest, and reactive oxygen species production was measured by reactive oxygen species detection kit. Results: HER-2 overexpression in breast cancer cells could promote cell migration and invasion. Mechanistic study showed that HER-2 overexpression could upregulate ZEB1 expression. ZEB1 silencing by siRNA reduced cell motility of HER-2-overexpressing breast cancer cells. Furthermore, reactive oxygen species produced in HER-2-overexpressing breast cancer cells were less than those produced in corresponding control cells. Conclusion: Our study demonstrated that HER-2 overexpression endowed breast cancer cells with EMT related properties by upregulating ZEB1 expression. ZEB1 could be a candidate target for further study of the relationship between HER-2 and EMT.
摘要:Background and purpose: Metabolism change is one of the main characteristics of the tumor development. Many studies have confirmed that cytosolic acetyl-CoA synthetase 2 (ACSS2) plays a critical role in hydrocarbon metabolism of cancer cells. This study aimed to explore the effect of ACSS2 on cellular proliferation, apoptosis and migration of A549 cells by RNA interference. Methods: The ACSS2 interference fragment ACSS2-siRNA and negative control were designed and synthesized for RNA interference followed by the transient transfection in non-small cell lung cancer (NSCLC) cell line A549. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect ACSS2 mRNA expression. Methyl thiazolyl tetrazolium (MTT), flow cytometry and wound healing assay were used to detect cell proliferation, apoptosis rate and migration. Results: The expression of ACSS2 mRNA was significantly decreased after transfection with the interference fragment ACSS2-siRNA in NSCLC cell line A549. The proliferation and migration activity of ACSS2-siRNA treated cells were decreased significantly compared with the control group. The apoptosis rate, especially the early apoptosis, was increased.. Conclusion: Knockdown of the ACSS2 expression in NSCLC cell line A549 can significantly inhibit the cell proliferation, migration ability and pro- mote the apoptosis rate, especially early apoptosis. This study indicates that ACSS2 may contribute to the progression of human lung adenocarcinoma and may have the potential to serve as a novel therapeutic target.
摘要:Background and purpose: Breast cancer is one of the most common malignant diseases in women and its malignant proliferation is the major cause of death. To investigate the effects of N-myc downstream regulated gene 2 (NDRG2) on proliferation of breast cancer cells by using two parallel cell lines (MCF-7 and LM-MCF-7) with different metastatic abilities. Methods: The expression level of NDRG2 in breast cancer cells was detected by Western blot. The effects of overexpressing (or down-regulating) NDRG2 on proliferation of breast cancer cells were investigated by flow cytometry. The expression and location of β-catenin were detected by Western blot and immunofluorescence respectively. NDRG2 blocking the transcription activity of β-catenin was investigated via co-transfecting MCF-7 cells with NDRG2 siRNA and pCMV-Tcfδ (lacking the portion responsible for the protein binding to DNA). Results: The expression level of NDRG2 was negatively related to the proliferation ability of breast cancer cells. Over-expressing NDRG2 (or down-regulating) via transfecting LM-MCF-7 (or MCF-7) cells with pCMV-NDRG2 (or NDRG2 siRNA) could inhibit (or promote) cell proliferation. Interestingly, the results of Western blot, immunofluorescence and flow cytometry revealed that down-regulation of NDRG2 resulted from the down-regulation of β-catenin and blocking its nuclear translocation, which led to losing control of the proliferation of breast cancer cells. Conclusion: NDRG2 inhibit the proliferation of breast cancer cells via down-regulating the expression of β-catenin and blocking its nuclear translocation, which is significant for exploring the molecular mechanism of proliferation of breast cancer cells.
摘要:Background and purpose: Selenium is one of the essential trace elements for human activities, and plays an incomparable role in maintaining human health. It was reported that selenium compound 1,4-bis[2-(benzylselanyl) ethoxy] (BSEA) anthracene has antiseptic and antiphlogistic effects. However, the mechanisms underlying anticancer effects of BSEA are rarely reported. BSEA-induced apoptosis in human laryngeal carcinoma Hep-2 cells and its mechanisms were studied. Methods: Methyl thiazolyl tetrazolium (MTT) assay was used to determine inhibition ratio of Hep-2 cells 24 hours after Hep-2 cells were treated with different concentrations of BSEA. Fluorescence microscope was used to observe the morphology change of apoptosis in Hep-2 cells. The apoptosis was detected by Annexin Ⅴ-FITC. Mitochondrial membrane potential was assayed by JC-1. Microplate reader detected the activity of caspase-3 and caspase-8. The mRNA and protein levels of Bax and XIAP were measured by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) and Western blot. Results: The results showed that BSEA caused a dose-dependent inhibition of the growth of human laryngeal carcinoma cell line Hep-2 in vitro, and IC50 was 35.74 μmol/L. The apoptotic bodies were distinctly observed at a concentration of 80 μmol/L of BSEA by AO fluorescence staining. This study found that the eversion of phosphatidyl serine intensified, and mitochondrial membrane potential also began to decline. The activity of caspase-3 appeared the tendency of dependence on dosage, while the activity of caspase-8 did not change significantly. The mRNA and protein expression level of Bax increased, whereas the mRNA and protein expression level of XIAP decreased. Conclusion: Therefore, BSEA could obviously inhibit human laryngeal carcinoma Hep-2 cells proliferation and induce apoptosis via the mitochondrial pathway.
摘要:Background and purpose: As one of the most fatal malignant tumors in China, the morbidity and mortality of lung cancer remain high. Early diagnosis and normative treatment is the key to improve the prognosis of lung cancer. The aim of this study was to explore the practice of early lung cancer screening with low-dose spiral computed tomography (CT) based on the current situation in community health service, with integration of superior resources of medical institutions at all levels in Shanghai. Methods: From Aug. 2013 to Aug. 2014, we screened high-risk population in selected communities of Minhang District, Shanghai, for early diagnosis of lung cancer with low-dose spiral CT combined with multidisciplinary comprehensive treatment models including minimally invasive surgery, exploring the medical service network covering prevention, diagnosis, treatment, rehabilitation and follow-up. Results: Screening population is 11 332 (male 7 144, female 4 188); Twenty-nine cases with pathological diagnosis of malignant tumor, including 27 cases of primary lung cancer, 1 case of lung metastasis, 1 case of breast cancer. The morbidity of primary lung cancer is 238.26×10-5. There were 22 cases of Stage 0-Ⅰ lung cancer accounting for 81.48% of all diagnosed primary lung cancer. Conclusion: Based on community health service, screening with low-dose spiral CT could improve the early diagnosis rate of lung cancer with feasibility and validity, which could be applicable in qualified eligible medical center and community in China.
摘要:Background and purpose: Hepatic epithelioid hemangioendothelioma (HEHE) is an extremely rare, vascularly original tumor, and would be misdiagnosed easily in the clinical and imaging characteristics. This study aimed to investigate the imaging features of HEHE and our experience in clinical diagnosis and treatment, and to provide important reference for the diagnosis and treatment of HEHE in the future. Methods: This study retrospectively analyzed clinical manifestations, imaging features, pathological characteristics and treatment effects of 5 HEHE cases confirmed by pathology at Department of Integrative Cancer, Fudan University Shanghai Cancer Center. Results: The ratio of male to female patients was 2 to 3. HEHE predominantly occurred in middle-aged female patients whose ages range from 26 to 65 (mean=45.6). Imaging features of HEHE included multifocal hepatic disease (n=2), systemic multi-center multi-tissue occurrence (n=3). The ultrasound images showed isoechoic or hypoechoic lesions with no obvious blood flow signal in the lesions. CT plain scan showed isointensity or hypointensity, while MR unenhanced with hypointense T1 signal and hyperintense T2 signal. The density or signal was uneven. Contrast-enhanced CT and MR images showed “slow in slow out”, obvious and variable degrees of peripheral rim enhancement. High FDG uptake showed delayed imaging characteristics (PET/CT). DSA angiography showed the tumor blood vessels were slim. After transcatheter arterial chemoembolization (TACE) surgery, lipiodol deposition within the lesion was not ideal. Under the microscope, tumor cells showed epithelial differentiation; angiogenesis was also visible. Immunohistochemistry staining showed CD31 and CD34 positive in all the 5 cases. Two cases treated with TACE combined with high intensity focused ultrasound (HIFU) and/or radiofrequency ablation (RFA) had good result. Conclusion: The clinical and radiological characteristics of HEHE are distinctive. Currently, for patients with systemic multi-organizational multi-center lesions, TACE combined with HIFU and/or RFA might be the most effective treatment method.
摘要:Background and purpose: The application of intensity-modulated radiotherapy (IMRT) has improved the local control rate of nasopharyngeal carcinoma greatly, which changed the predictive value of T classifications of TNM staging system. This study aimed to validate the predictive effect of T classifications in the 7th Union for International Cancer Control (UICC) staging system and discuss the simplification of T classifications. Methods: We retrospectively reviewed the clinical data of 641 primary nasopharyngeal carcinoma patients at our center from January 2007 to June 2011. We evaluated the predictive effect of T classifications by Kaplan-Meier method and Cox regression model. Results: The 5-year overall survival (OS), local relapse-free survival (LRFS), progression-free survival (PFS) and distant metastasis free survival (DMFS) were 85.4%, 88.5%, 78% and 87.1%, respectively. The 5-year OS of T1, T2, T3 and T4 categories were 91.6%, 85.3%, 90.1% and 76.5%, respectively; LRFS were 93%, 85.3%, 91.5% and 84.4%; PFS were 88.2%, 77.3%, 80.8% and 70.9%; DMFS were 95.1%, 88.9%, 88.2% and 81.3%, respectively. The difference in survival curves between T1, T2 and T3 were not significant (P>0.05). However, several prognostic indexes were significantly different between T4 and T1, T2, T3. We merged the T1, T2 and T3 classifications as new T1, and the T4 classification as new T2. The 5-year OS of new T1 and T2 were 89.1% and 76.5% (P=0.001); LRFS were 90.1% and 84.4% (P=0.028); PFS were 81% and 70.9% (P=0.001); DMFS were 90.8% and 81.2% (P=0.002). The survival curves were substantially separated. The simplified T classifications had obvious advantages when separately analyzed in different N stages. Conclusion: In the era of IMRT, the predictive effect of T classifications of the 7th UICC staging system has diminished. The simplification of T classifications can fit with the new treatment and provide a better survival prediction.
摘要:Background and purpose: The effect of TPF (docetaxel, cisplatin and 5-fluorouracil) induction chemotherapy plus concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. This study aimed to compare the outcomes and tolerance of neoadjuvant chemotherapy with TPF versus cisplatin and 5-fluorouracil (PF) followed by concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma patients. Methods: Patients with locoregionally advanced nasopharyngeal carcinoma were randomly divided into 2 groups: Group TPF and Group PF. Group TPF: One hundred and sixteen nasopharyngeal carcinoma patients received TPF consisting of docetaxel at 60 mg/m2 on day 1, cisplatin at 60 mg/m2 on day 1, and 5-fluorouracil at a dose of 750 mg/m2 by 24 h continuous infusion for 5 days for 3 cycles with a 21 day interval; Group PF: One hundred and sixteen nasopharyngeal carcinoma patients received PF consisting of cisplatin at 80 mg/m2 on day 1, and 5-fluorouracil at a dose of 750 mg/m2 by 24 h continuous infusion for 5 days for 3 cycles with a 21 day interval. After the completion of neoadjuvant chemotherapy, all the patients received intensity modulated radiation therapy (IMRT) with concomitant chemotherapy consisting of 2 cycles of cisplatin at 80 mg/m2 on day 1 and day 22. The prescribed doses were 6 810 cGy at 2.27 Gy/fraction to the gross tumor volume (GTV) with 5 daily fractions per week for 6 weeks. The acute toxicity and tumor response rate (RR), including complete response (CR) and partial response (PR), were evaluated. Additionally, the 5-year progress-free survival (PFS) rates and overall survival (OS) rates were further evaluated. Results: RR of Group TPF was higher than that of group PF at the end of neoadjuvant chemotherapy and within 13 weeks of the completion of concurrent chemoradiotherapy. The median recurrence time of TPF group was 2.98 years, and the 5-year PFS was 84.48%. The median recurrence time of PF group was 2.32 years, and the 5-year PFS was 82.75%. There was no statistically significant difference between the 2 groups (P=0.458). The 5-year OS of TPF group was 87.06%, and for the PF group was 85.34%. There was no statistically significant difference between the 2 groups (P=0.274). The incidence of leukopenia, thrombocyte penia, liver and kidney damage, diarrhea and mucosa necrosis in TPF group were significantly higher than those in PF group (P<0.001). The Ⅲ and Ⅳ degrees adverse reactions in TPF group were significantly higher than those in PF group (P<0.001). Conclusion: TPF induction chemotherapy was not superior to the PF regimen for locoregionally advanced nasopharyngeal carcinoma patients. It should not be recommended in terms of more acute toxicity.
摘要:Background and purpose: Cancer-related pain is one of the most important symptoms of patients with advanced cancer. Chemotherapy sometimes induces peripheral neuropathy and pain. These symptoms seriously affect patients’ quality of life. Cancer pain assessment is now achieved by the subjective scales of patients, but lacking objective measurement. In this study, we used the neurotic electrophysiological method by way of PainVision system (PV system) to evaluate cancer pain quantitatively to detect and analyze degree of chemotherapy-induced neuropathy. Methods: We obtained numerical rating scale (NRS) scores from patients receiving analgesics and calculated the PainRatio from PV system at the same time. Then we analyzed the relationship between NRS and PainRatio scores. We detected current perception threshold (CPT) levels of patients receiving chemotherapy to find the correlation between chemotherapy and CPT level, and attempt to evaluate chemotherapy-induced neuropathy. Results: PainRatio scores were linearly associated with NRS scores (Pearson correlation coefficient=0.849, P<0.001). Patients with neuropathy symptoms got higher CPTs. However, no statistically significant difference was observed between patients treated with oxaliplatin, paclitaxel and other agents. Conclusion: PainVision system can be used in cancer pain assessment quantitatively, and be helpful in cancer pain assessment objectively. Patients with defined neuropathy showed higher CPTs, indicating the potential clinical value of PV system in detecting and evaluating chemotherapy-induced neuropathy.
摘要:Sentinel lymph node biopsy has been proved to be the standard treatment for early breast cancer patients with negative axillary lymph node. The study related to the tracer has become one of the hottest topics in breast cancer research. At present, the biopsy is often performed using the tracer of isotope, blue dye or both of them. However, some deficiencies of the 2 tracers restrained their applications, which resulted that the rate of the procedure is limited to only about 60% of patients in developed countries and less than 5% of patients in China and other developing countries. In recent years, a variety of new tracers have emerged, such as indocyanine green, contrast-enhanced ultrasound using microbubbles, superparamagnetic iron oxide nanoparticles. In this article, we introduced the characteristics of these 3 substances and reviewed the related research on the new tracers. In conclusion, the new tracers are still in the preliminary stage of research, and further research is needed for clinical application.
摘要:Thyroid papillary carcinoma harbors higher rate of lymph node metastasis, so neck dissection is an important part of the treatment. Due to better prognosis, attention to postoperative function and appearance of the patients increased. Low-collar incision with cervical sensory nerve plexus preservation modified neck dissection can improve appearance and function in postoperative patients and is gradually applied in clinic. This review mainly examines the thoroughness and safety of this new neck dissection in thyroid papillary carcinoma patients.