摘要:Background and purpose: Radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) is a big challenge in the management of thyroid cancer. Sorafenib and lenvatinib are the 2 tyrosine kinase inhibitors (TKIs) recently approved by FDA, which could not be affordable for most of the Chinese patients. This pilot study aimed to evaluate the short term efficacy and safety of apatinib, a Chinese domestic TKI targeted vascular endothelial growth factor receptor (VEGFR), in advanced RAIR-DTC. Methods: Ten patients who were identified as progressive RAIR-DTC were enrolled in this study. Patients received oral apatinib 750 mg once daily. Both thyroglobulin (Tg) and/or Tg antibody (TgAb) levels were monitored every 2 weeks after the treatment. Computed tomography (CT) was performed every 4 weeks after apatinib treatment to evaluate the response according to response evaluation criteria in solid tumor version 1.1 (RECIST 1.1). Within 8 weeks after apatinib treatment, therapeutic response was evaluated in terms of Tg, a sensitive biochemical tumor marker for DTC, and RECIST 1.1 assessment. Meanwhile, the adverse events (AE) were monitored during the therapy. Results: The Tg levels declined after the first 2 weeks of apatinib treatment, and a mean decline rate of 68% could be observed in 8 patients with Tg available for evaluation after 8 weeks, which repre-sented a biochemical partial response. Eighteen target lesions (TL) of 10 patients were evaluated and followed up. The diameter of TL began to decrease after 4 weeks, and a mean decline of 40% could be observed after 8 weeks’ apatinib treatment. A total of 9 patients (9/10) achieved partial response according to RECIST 1.1 criteria and 1 patient with stable disease, with 90% objective response rate and 100% disease control rate. The most common AE beyond grade 3 included hand-foot-skin reactions, hypertension and hypocalcemia, which accounted for 50%, 30% and 20% of the cases, respectively. No severe AE related to apatinib was observed during the treatment. Conclusion: A safe and rapid response and high partial response rate in terms of biochemistry, RECIST 1.1 could be observed in RAIR-DTC patients within 8 weeks of apatinib treatment.
关键词:Apatinib;Tyrosine kinase inhibitors;Radioactive iodine-refractory differentiated thyroid cancer
摘要:Background and purpose: There are few studies referring to population-based cancer survival of bladder cancer for more than forty years in China. This paper was to offer basis for assessing long-term survival trends of bladder cancer and the prognosis of this cancer through analysis of the survival rates based on cancer report documents from 1972 to 2011 in Qidong. Methods: The deadline of the last follow-up for survival status of the 1 619 registered cases was Apr. 2012. Cumulative observed survival rate (OS) and relative survival rate (RS) were calculated using Hakulinen’s method performed by the SURV3.01 Software which is developed by Finnish Cancer Registry. Results: The one-, three-, five-, ten-, fifteen-, twenty-, and thirty-year OS rates were 59.91%, 43.49%, 35.98%, 26.91%, 21.30%, 18.37% and 12.24%; and the one-, three-, five-, ten-, fifteen-, twenty-, and thirty-year RS rates were 64.07%, 53.02%, 50.06%, 52.42%, 59.59%, 76.39% and 115.75%, respectively. For males, these OS rates were 60.84%, 43.91%, 36.95%, 27.31%, 21.49%, 18.29% and 12.59%, and RS rates were 65.23%, 53.95%, 52.02%, 54.57%, 62.59%, 79.12% and 117.07%, respectively; For females, these OS rates were 56.61%, 42.03%, 32.44%, 25.65%, 20.78%, 18.80% and 0%, and RS rates, 59.99%, 49.91%, 43.37%, 45.86%, 51.21%, 69.02% and 0%, respectively. There were no statistical differences could be found between both sexes (P=0.256). Five-year RS rates of age groups 15-34, 35-44, 45-54, 55-64, 65-74, and more than 75 were 49.10%, 67.53%, 62.77%, 53.92%, 46.59% and 39.85%, and 10-year RS rates, 49.79%, 61.23%, 52.99%, 48.21%, 54.94% and 51.21%, respectively. Remarkable improvement could be seen for the five-, ten-, and fifteen-year RS rates in this setting since 1980’s. Conclusion: The survival outcome from Qidong registered cases with bladder cancer shows gradual progress during the past 2 decades. Early detection and improvement of therapies may be the factors affecting the prognosis of bladder cancer. Although the disparities in survival rates between Qidong and the developed countries are getting narrower, potential for survival improvement still exists.
摘要:Background and purpose: Previous studies have suggested Na+-Ca2+ exchanger isoform 1 (NCX1) as a key component of calcium homeostasis was involved in the tumorigenesis. However, the role of NCX1 and calcium signal in tumorigenesis of hepatocellular carcinoma (HCC) has not been explored. This study aimed to investigate the effect of NCX1 on cell proliferation and migration of HCC HepG2 cells in vitro and the possible mechanism. Methods: Both the real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) and Western blot were applied to assess the expression of NCX1 mRNA and protein in normal hepatic cells (LO2), HCC cell line (HepG2), human normal hepatic tissues and hepatocellular carcinoma tissues. The change of intracellular calcium signal in LO2 and HepG2 cells via activated NCX1 channel in the presence or absence of Na+ was examined by a confocal laser scanning microscope. The effects of NCX1 special inhibitor KB-R7943 on cell proliferation and migration of HepG2 cells were measured by MTT and cell scratch test. Results: Both mRNA and protein expression of NCX1 were higher in HCC tissues and cell line HepG2 than in the normal tissues and cell line LO2 (P<0.05). The activation of NCX1 channel induced a slight rise in cytoplasmic Ca2+ concentration ([Ca2+]cyt) in normal cells, but caused a marked increase in cancer cells. And the NCX1 activation induced intracellular calcium increase was significantly reversed by NCX1 inhibitor KB-R7943 (P<0.05). Both NCX1-mediated proliferation and migration of HepG2 were also significantly attenuated by the KB-R7943 (P<0.05). Conclusion: NCX1 is up-regulated in HCC cells and tissues. The activation of NCX1 mediates intracellular calcium homeostasis. The inhibition of NCX1 activity can suppress the proliferation and migration of HepG2 cells. It is suggested that NCX1 may be involved in the development and progression of HCC.
摘要:Background and purpose: A large number of studies have showed that retinoblastoma gene 1 (RB1) can inhibit the occurrence and development of many tumors, including neuroblastoma, small cell lung cancer, osteosarcoma, pancreatic cancer, breast cancer and so on. RB1 is also closely related to the regulation of cell cycle, differentiation, senescence, apoptosis, growth inhibition, etc. The goal of this article is to elucidate whether miR-222 promotes cell proliferation and invasion by targeting RB1, further to explore the molecular mechanism that miR-222 functions as an oncogene in retinoblastoma cells. Methods: miR-222 (miR-222 mimics) and RB1-wt, miR-NC and RB1-wt, miR-222 and RB1-mut, miR-NC (a controlled miR-222 mimics) and RB1-mut were co-transfected into Y79 cells, and luciferase activity was detected by single photon. Retinoblastoma cells were transfected with miR-222 mimics and miR-NC, and the expressions of RB1 protein were detected by Western blot. Retinoblastoma cell proliferation assays were performed by MTS assay when miR-222, miR-NC, RB1 (pcDNA3.1-RB1), vector (pcDNA3.1), miR-222+RB1 and miR-NC+vec- tor were transfected into Y79 cells. The growth and invasion ability of Y79 cells with ectopic expression of miR-222 were evaluated by MTS and Transwell invasion assays. Results: This study demonstrated that miR-222 could promote the luciferase activity of RB1-wt. The expression levels of luciferase reporter gene activity in Y79 cells after transfection with miR-222+RB1-wt were higher than those in the negative control cells (miR-NC+RB1-wt) (P<0.05). The protein expression levels of RB1 in Y79 cells after transfection with miR-222 were lower than those in miR-NC (P<0.05). Overexpression of RB1 inhibited the proliferation of retinoblastoma cells. miR-222 promoted the proliferation of retinoblastoma cells through targeting RB1 (P<0.05). Moreover, there was no significant difference between the cell survival rates of Y79 which were transfected with miR-222+pcDNA3.1-RB1 and miR-NC+pcDNA3.1 (P>0.05). After transfection with miR-222 mimics for 48 h, Transwell invasion assay showed that the number of cells through the basement membrane was (193±10). Compared with the control group (144±11), it could significantly accelerate the invasion of Y79 cells (P<0.01). There was no significant difference between the number of cells through the basement membrane which were transfected with miR-222+pcDNA3.1-RB1 and miR-NC+pcDNA3.1 (P>0.05). Conclusion: miR-222 promotes cell proliferation and invasion by targeting RB1 expression in retinoblastoma cells.
摘要:Background and purpose: Breast cancer has the highest morbidity and mortality rate in women worldwide. Triple-negative breast cancer (TNBC) has no specific target and has low survival rate. Recent studies have verified BRD4 could promote tumor progression. This study aimed to detect the expression level of BRD4 in TNBC after treatment with gemcitabine, and to reveal the effect of BRD4 silencing plus gemcitabine as a treatment for TNBC. Methods: The expression of BRD4 in TNBC cell lines treated with gemcitabine was detected by reverse transcription PCR (RT-PCR) and Western blot. The effect of BRD4 silencing plus gemcitabine in TNBC was illustrated in vitro and in vivo. Results: The expression of BRD4 in TNBC was significantly increased after treatment with gemcitabine. In vitro, BRD4 knockdown significantly lowered the IC50 value. The apoptotic rate of TNBC was significantly increased in the BRD4 silencing plus gemcitabine group compared to the other. The growth rate of tumor in vivo was significantly lowered in the BRD4 silencing plus gemcitabine group. Conclusion: BRD4 may play an important role in the drug resistance to gemcitabine in TNBC. BRD4 silencing plus gemcitabine may be a novel treatment strategy for TNBC.
关键词:Triple-negative breast cancer;BRD4;Gemcitabine
摘要:Background and purpose: Cytotoxic T lymphocyte (CTL) plays a vital role in the process of antitumor immunology. The aim of this study was to investigate whether changes in concentration of IL-2 (50, 200 and 1 000 U/mL) would affect the sub-population and cytotoxic function of cells cultivated by peptide-specific CTL induction system in vitro and also observe whether using the concentration of IL-2 at a range of 50-1 000 U/mL is beneficial to regulatory cells (Tregs) enrichment. Methods: Peripheral blood from 10 healthy donors and 10 cancer patients that were HLA-A2 positive, were collected in the study. HLA-A2 restricted CTL epitope P321 (ILIGETIKI) derived from COX-2 pulsed with different concentrations of IL-2 were used to induce peptides-specific CTL in vitro. Flow cytometry was performed to analyze the proliferative capability, the proportion of different T-cell subsets, and secretion of perforin, granzyme B and IFN-γ. IFN-γ secretion was assessed by ELISpot assay. Results: High concentration of IL-2 increased the proliferative activity. The percentage of CD4+ T cells of cancer patient group was significantly higher than that of healthy donor group, while the percentage of CD8+ T cells of cancer patient group was significantly lower than that of healthy donor group. And there was no significant difference in the percentages of CD4+ T cells, CD8+ T cells and Tregs among groups with different IL-2 concentrations. No difference was seen in cytokine (perforin, granzyme B, IFN-γ) secretion capacity of CD8+ T cells. ELISpot study revealed that high-dose IL-2 resulted in the increasing of IFN-γ secretion. Conclusion: The sub-population and the function of cells cultured by peptide-specific CTL induction system in vitro are not affected by different concentrations of IL-2. Furthermore, high concentrations of IL-2 (50-1 000 U/mL) do not provide the enrichment for Tregs. Higher concentration of IL-2 is likely to cause high secretion of IFN-γ in ELISpot assay. In order to exclude the distraction of NK cells or NKT cells, the concentration of 50 U/mL is better choice.
摘要:Background and purpose: B cell-specific MLV integration site 1 (BMI-1) gene plays an important role in DNA damage after exposure to irradiation. The present study aimed to investigate the effect of BMI-1 on radiosensitivity of esophageal carcinoma cell after down-regulation of BMI-1 expression by silencing siRNA. Methods: Three pairs of siRNA based on the sequences of the BMI-1 mRNA were synthesized (siRNA1, siRNA2 and siRNA3) by compa-ny, and transfected into cultured TE13 cells as the BMI-1 siRNA groups, and a negative one was synthesized to be used as the negative control (NC) group. The untransfected group was named as the control group. BMI-1 mRNA and protein expression in esophageal cancer TE13 cells were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot in different groups. This study used flow cytometry assay to analyze cell cycle of transfected cells, and examined cellular growth and radiosensitivity in vitro by MTT and clone formation assay. mRNA and protein expression of p16 and CDK4 in esophageal cancer TE13 cells were detected by RT-PCR and Western blot. Results: The results of RTPCR and Western blot showed that the expressions of BMI-1 at gene and protein levels were inhibited after silencing the BMI-1 gene. The mRNA and protein expression of BMI-1 in BMI-1 siRNA3 group were both significantly lower than that in BMI-1 siRNA1 and 2 groups. There was no significant difference in the cell proliferation among control, NC and BMI-1 siRNA3 groups. The values of D0, Dq, and SF2 in BMI-1 siRNA3 group were 1.761, 2.122 and 0.6255, respectively, obviously lower than those in control group (2.514, 2.694 and 0.8268) and those in NC group (2.506, 2.664 and 0.8231), while the value of N in BMI-1 siRNA3 group (3.336) was higher than that in control group (2.92) and that in NC group (2.895), which showed higher radiosensitivity in BMI-1 siRNA3 group. In addition, the cell cycle was arrested at G2/M phase after irradiation in control and NC groups. The percentage of G0/G1 phase in BMI-1 siRNA3 group was higher than that of control group and NC group, while the percentage of G2/M phase was lower than those in the latter. The up-regulation of p16 and down-regulation of CDK4 at gene and protein levels were detected after knockdown of BMI-1 expression by siRNA (P<0.01). Conclusion: siRNA could inhibit BMI-1 gene expression in esophageal cancer TE13 cells and enhance radiosensitivity, followed by eliminating the cell cycle arrest at G2/M stage after irradiation in vitro, which is related to the regulation of the protein expression of p16 and CDK4.
摘要:Background and purpose: In preparation for using this tracer in humans, this study estimated the dosimetry of 18F-FES with the method established by MIRD based on whole-body PET imaging of mice. Methods: Three female mice received Ⅳ tail injections of 18F-FES and were scanned for 160 min in an Inveon dedicated PET/CT scanner. This study selected some important organs (brain, lung, liver, heart wall, small intestine, large intestine, kidney and urinary bladder), computed their residence times. Then, the residence times in mice organs were converted to human values using scale factors based on differences between organ and body weights. OLINDA/EXM 1.1 software was used to compute the absorbed human doses in multiple organs for both adult female and adult male body phantoms. Results: The highest absorbed doses in gallbladder wall, urinary bladder wall, small intestine, upper large intestine and liver are 0.072 5, 0.044 5, 0.043 0, 0.031 5 and 0.028 2 mGy/MBq, respectively. The organs which have the lowest absorbed doses were brain (0.005 2 mGy/MBq), followed by skin (0.001 1 mGy/MBq), breast (0.001 1 mGy/MBq), heart wall (0.001 2 mGy/MBq) and thyroid (0.001 2 mGy/MBq). The mean absorbed doses for the other major organs ranged from 0.009 5 to 0.023 5 mGy/MBq. The total mean effective dose is 0.019 0 mSv/MBq and the mean effective doses equivalent is 0.025 0 mGy/MBq. A 370-MBq injection of 18F-FES leads to an estimated effective dose of 7.03 mSv for the female. There was no statistical difference in the doses results obtained from direct measurement of 18F-FES absorption in normal people between previous publications by others and our work. Conclusion: The whole-body mouse imaging can be used as a preclinical tool for initial estimation of the absorbed doses of 18F-FES in humans. Furthermore, the potential radiation risk associated with 18F-FES imaging is well within the accepted limits.
摘要:Background and purpose: The third generation of aromatase inhibitors (AI) in postmenopausal hormone receptor-positive patients is the routine treatments in endocrine therapy. The 500 mg fulvestrant showed clinical benefits in patients with previous AI treatment. This study aimed to access the efficacy and safety of 500 mg fulvestrant in estrogen receptor (ER) positive postmenopausal patients who had previous AI treatments with locally advanced and metastatic breast cancer. Methods: This study retrospectively analyzed the clinical data from 188 post-AI ER positive and (or) progesterone receptor (PR)-positive locally advanced and metastatic breast cancer patients treated with 500 mg fulvestrant in Fudan University Shanghai Cancer Center from Jul. 2011 to Dec. 2015. Primary end point was progression-free survival (PFS). Secondary end points were objective response rate (ORR), clinical benefit rate (CBR) and safety profile. Results: After the median follow-up of 11.3 months, median PFS was 5.9 months (95%CI: 4.2-7.5), CBR was 40.0% and ORR was 3.4%. COX proportional hazards regression analysis indicated that PFS was correlated with the number of metastatic sites (HR=1.92, 95% CI: 1.2-2.9, P =0.002) and previous lines of chemotherapy (HR=1.52, 95%CI:1.0-2.1, P=0.022). Six patients stopped the treatment for intolerable adverse events. Conclusion: The treatment of 500 mg fulvestrant has a favorable efficacy and safety in treatment of post-AI ER positive postmenopausal patients with metastatic breast cancer.
关键词:Fulvestrant;Metastatic breast cancer;Estrogen receptor positive;Aromatase inhibitor
摘要:Background and purpose: Although bortezomib has become one of the major therapeutic agents against newly diagnosed or relapsed multiple myeloma (MM), there are some patients who become resistant to bortezomib and then relapse, emerging as a major obstacle to long-term survival of MM patients. It has been found that elevation of intracellular cyclic adenosine monophosphate (cAMP) levels could induce cell cycle arrest and apoptosis in MM cells,which has become an interesting approach to MM therapy. This study aimed to investigate possible effects of forskolin combined with bortezomib on bortezomib-resistant myeloma cells and further explore its mechanisms. Methods: The bortezomib-resistant MM cell lines H929-R and primary cells from patients who do not respond to bortezomib were used as in vitro models. The influences of bortezomib and/or forskolin on MM cells were evaluated through cellular morphology, changes of cell distribution and apoptotic rate. Meanwhile, flow cytometry analysis was used to detect mitochondrial transmembrane potential (ΔΨm) and the expression levels of apoptosis regulators in these cells before and after the treatment were detected by Western blot. Results: Bortezomib (20 nmol/L) synergized with forskolin (50 nmol/L) to induce apoptosis of H929-R cells and bortezomib-resistant primary cells. In addition, bortezomib synergized with forskolin to induce collapse of mitochondrial transmembrane and facilitate the degradation of anti-apoptosis proteins including Bcl-2 and Mcl-1. Conclusion: Bortezomib could synergize with forskolin to induce apoptosis in bortezomib-resistant MM cells.
摘要:Background and purpose: Primary thyroid lymphoma (PTL) is uncommon in clinic with quite different treatment from that of other malignant thyroid tumors. Therefore, to achieve complete understanding of PTL has crucial significance. This study aimed to investigate the clinical and computed tomography (CT) characteristics of PTL. Methods: The clinical and imaging data from 22 patients with PTLs confirmed by pathology were collected. The clinical symptoms of patients, the site, size, shape, margin, CT value and enhancement pattern, relation with surrounding tissues of PTLs and cervical lymph nodes were summarized retrospectively. Results: All the 22 patients including 8 males and 14 females had an average age of 60 years (range: 39-77 years). Twelve PTLs rapidly progressed in short term and the rest expanded slowly. The tumors involved bilateral thyroid in 11 cases, unilateral thyroid in 8 cases and both right lobe and isthmus in the remaining 3 cases. The long and short ranges were (12-104) mm and (11-71) mm. The solitary, multiple and diffuse nodules distributed in 5, 5 and 12 patients, respectively. In axial plain CT scans, low density appeared in 15 patients, isodensity in 7 patients, calcification inside the lesion in 0 patient, and necrosis in 5 patients. Nineteen PTLs manifested slight or moderate enhancement, and 3 marked enhancement in contrast-enhanced axial CT images. Homogeneous density and mixed density were demonstrated in 13 and 9 cases, respectively. Trachea and esophagus was pushed in 17 and 5 cases, tumors were involved into superior mediastinum in 12 cases and enlarged lymph nodes were demonstrated in 8 cases. Conclusion: If a solid thyroidal mass in an old female patient rapidly progresses in short term and CT scans show homogeneous and low density, slight or moderate enhancement, and diffusive swelling with compression and invasion of surrounding tissues, it has a high possibility of PTL.
摘要:Colorectal cancer is one of the most common cancers in the world with high morbidity and mortality. Clinicians spare no effort to look for effective prevention and treatment strategies for colorectal cancer. Research shows that aspirin plays a unique role in colorectal cancer prevention and treatment. However, the effect is associated with the course of treatment, users’ genetic backgrounds and some other factors. This review aimed to summarize the prevention and treatment effects of aspirin on colorectal cancer, the possible molecular markers for predicting aspirin efficacy and related mechanisms.