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1.
IFI16 restoration in hepatocellular carcinoma induces tumour inhibition via activation of p53 signals and inflammasome 下载免费PDF全文
Objective
Interferon‐inducible 16 (IFI16) is known to involve in p53‐dependent tumour suppression and also the formation of inflammasome, which function, however, remains controversy during carcinogenesis as a pattern recognition receptor for tumour death‐derived free DNA. In this study, we investigated the anti‐tumour role of IFI16 in hepatocellular carcinoma (HCC).Materials and methods
Hepatocellular carcinoma tissues (n = 20) and corresponding non‐neoplastic tissues (n = 20) were collected to determine the expression of IFI16. After the transfection of pcDNA3.1‐IFI16 into Huh7 and SMMC7721 cells in vitro, the influence of IFI16 overexpression on cell vitality, colony formation, apoptosis and migration were analysed. The role effect of IFI16 in vivo was further investigated.Results
The expression of IFI16 was significantly decreased in tumour tissues and cell lines. Overexpression of IFI16 induced decrease of cell vitality, colony formation and increased apoptosis with impaired ability of migration. Mechanistically, IFI16 could activate p53 at Ser15 to up‐regulate the p21WAF1/CIP1 level to inhibit tumour growth and migration, which was restored by the p53 inhibitor Pifithrin‐α (20 μmol/L). Moreover, IFI16‐induced tumour cell death promoted the recruitment of inflammasome complex to enhance tumour inhibition, but the caspase‐1 inhibitor Ac‐YVAD‐CMK (50 μmol/L) could suppress this process in HCC. The results in vivo indicated that restored expression of IFI16 in tumour cells effectively promote tumour regression, which could be partly abrogated by the inhibition of activation of p53 signals or induced inflammasome.Conclusion
IFI16 is a tumour suppressor in HCC via activation of p53 signals and inflammasome.2.
Peter Hammarsten Mariateresa Cipriano Andreas Josefsson P?r Stattin Lars Egevad Torvald Granfors Christopher J. Fowler 《PloS one》2012,7(10)
Background
In the present study, we have investigated the prognostic usefulness of phosphorylated Akt immunoreactivity (pAkt-IR) in prostate cancer using a well-characterised tissue microarray from men who had undergone transurethral resection due to lower urinary tract symptoms.Methodology/Principal Findings
pAkt-IR in prostate epithelial and tumour cells was assessed using a monoclonal anti-pAkt (Ser473) antibody. Immunoreactive intensity was determined for 282 (tumour) and 240 (non-mlignant tissue) cases. Tumour pAkt-IR scores correlated with Gleason score, tumour Ki67-IR (a marker of cell proliferation) and tumour phosphorylated epidermal growth factor receptor (pEGFR)-IR. For cases followed with expectancy, a high tumour pAkt-IR was associated with a poor disease-specific survival, and the prognostic information provided by this biomarker was additive to that provided by either (but not both) tumour pEFGR-IR or Ki67-IR. Upon division of the cases with respect to their Gleason scores, the prognostic value of pAkt-IR was seen for patients with Gleason score 8–10, but not for patients with Gleason score 6–7.Conclusions/Significance
Tumour pAkt-IR is associated with both disease severity and disease-specific survival. However, its clinical use as a biomarker is limited, since it does not provide prognostic information in patients with Gleason scores 6–7. 相似文献3.
Regulation of quiescence and cell cycle entry is pivotal for the maintenance of stem cell populations. Regulatory mechanisms, however, are poorly understood. In particular, it is unclear how the activity of single stem cells is coordinated within the population or if cells divide in a purely random fashion. We addressed this issue by analyzing division events in an adult neural stem cell (NSC) population of the zebrafish telencephalon. Spatial statistics and mathematical modeling of over 80,000 NSCs in 36 brain hemispheres revealed weakly aggregated, nonrandom division patterns in space and time. Analyzing divisions at 2 time points allowed us to infer cell cycle and S-phase lengths computationally. Interestingly, we observed rapid cell cycle reentries in roughly 15% of newly born NSCs. In agent-based simulations of NSC populations, this redividing activity sufficed to induce aggregated spatiotemporal division patterns that matched the ones observed experimentally. In contrast, omitting redivisions leads to a random spatiotemporal distribution of dividing cells. Spatiotemporal aggregation of dividing stem cells can thus emerge solely from the cells’ history.An interdisciplinary study of the rules governing cell divisions in a population of neural stem cells in the zebrafish brain reveals the existence of aggregated spatio-temporal division patterns of rapid cell cycles in stem cells, and shows that these patterns can be explained by a simple agent-based model relying solely on the cells‘ division history. 相似文献
4.
Boyd M Mairs SC Stevenson K Livingstone A Clark AM Ross SC Mairs RJ 《The journal of gene medicine》2002,4(5):567-576
Background
We describe an in vitro tumour model for targeted radiotherapy and gene therapy that incorporates cell population heterogeneity.Materials and methods
Transfectant mosaic spheroids (TMS) and transfected mosaic monolayers (TMM) are composed of two cell populations derived from a single cell line. The cells of one population were transfected with the noradrenaline transporter gene (NAT), allowing active uptake of a radiolabelled targeting agent meta‐[131I]iodobenzylguanidine ([131I]MIBG); the other population of cells was derived from the same parent line and transfected with a marker gene – green fluorescent protein (GFP). After treatment with [131I]MIBG, cell kill was determined in TMM by clonogenic assay and in TMS by clonogenic assay and spheroid growth delay.Results
We have used the TMS model to assess the ‘radiological bystander effect’ (radiation cross‐fire) conferred by the β‐emitting radiopharmaceutical [131I] MIBG whose cellular uptake is facilitated by the transfected gene encoding NAT. We show that cell killing by [131I]MIBG in both TMS and TMM cultures increased in direct proportion to the fraction of NAT‐transfected cells and that the degree of cell killing against fraction transfected was greater in TMS, suggestive of a greater bystander effect in the three‐dimensional culture system.Conclusions
TMS provide a useful model for assessment of the effectiveness of targeted radiotherapy in combination with gene therapy when less than 100% of the target cell population is expressing the NAT transgene. Further, this novel model offers the unique opportunity to investigate radiation‐induced bystander effects and their contribution to cell cytotoxicity in radiotherapy and other gene therapy applications. Copyright © 2002 John Wiley & Sons, Ltd.5.
Kouichi Kobayashi Yuriko Tanaka Shigetoshi Horiguchi Shouji Yamamoto Nakayama Toshinori Akira Sugimoto Yoshitaka Okamoto 《Cancer immunology, immunotherapy : CII》2010,59(10):1503-1509
Background
Cancer immunotherapy with NKT cells is a potential new treatment strategy for advanced head and neck cancer. NKT cell therapy is promising due to its unique anti-tumor activity and higher degree of safety compared to current therapies. Radiotherapy is indispensable as a standard treatment for advanced head and neck cancer. To elucidate the possibility of using NKT cells as an adjuvant immunotherapy with radiotherapy, we examined the effect of radiotherapy on NKT cells in patients with head and neck cancer.Methods
The number, IFN-γ production and proliferation capacity of NKT cells were analyzed before and after 50 Gy radiation therapy in 12 patients with stage IV head and neck squamous cell carcinoma. The cytotoxic activity of NKT cells was examined in vitro.Results
The number of NKT cells in the blood varied widely between patients. After radiation therapy, the population of CD3 T cells decreased significantly, while the NKT cell population remained stable. The number of NKT cells was the same after radiation therapy as before. IFN-γ production from NKT cells collected just after radiotherapy was impaired after stimulation with exogenous ligand, but the proliferative responses of these NKT cells was enhanced in comparison to those collected before radiation therapy. Furthermore, the proliferated NKT cells displayed a significant level of anti-tumor activity.Conclusion
NKT cells are relatively resistant to radiation and might therefore be suitable for adjuvant immunotherapy to eradicate remnant cancer cells in patients who have undergone radiation therapy. 相似文献6.
Loredana Marcu Eva Bezak 《Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)》2010,26(4):177-183
Advanced head and neck cancers are one of the most challenging cancers facing the oncologists due to their aggressiveness attributable to the high hypoxic content and the tumour's ability to repopulate during radiotherapy. Alterations of radiotherapy fractionation schedules are possible ways to improve tumour control. Clinical trials have shown that both hyperfractionated radiotherapy (multiple fractions a day, over the same treatment time), and accelerated radiotherapy (higher doses per fraction, six days a week, over 5 weeks or less) are more effective than conventional radiotherapy in the management of head and neck cancer. However, the treatment choice between hyperfractionated and accelerated radiotherapy is still debated, due to very similar results obtained regarding tumour control. Furthermore, while radiotherapy alone has an impact on the short-term prognosis of advanced head and neck cancer, the long-term benefits have been moderate. Cisplatin is a chemotherapeutic agent which combined with conventional radiotherapy has shown to improve patient survival. The present paper employs a Monte Carlo modelling approach in assessing the effect of combined cisplatin-altered fractionation schedule on tumour response. The growth of a head and neck carcinoma has been modelled using probabilistic functions sampled by computer generated random number sequences, maintaining the biological constitution of a tumour. The tumour growth model has been built to simulate the in vivo processes taking place before and after radiotherapy/chemotherapy. The model has shown that adding cisplatin to radiotherapy improves tumour control in both hyperfractionated and accelerated radiotherapy. 相似文献
7.
8.
Somers P Robyns L Nollet E De Somer F Cornelissen M Thierens H Van Nooten G 《Cell proliferation》2012,45(4):378-385
Objective
The aim of this study was to repopulate decellularized heart valve matrices with ovine mesenchymal stem cells (oMSCs) by the use of platelet gel (PG) supernatant, a storage vehicle for growth factors.Methods
oMSCs were exposed to different concentrations of PG‐released supernatant and cell proliferation was evaluated using the MTS assay. oMSC motility and invasiveness were assayed using a Boyden chamber. A quantitative sandwich enzyme immunoassay was used to examine amounts of bFGF and TGF‐β1 in the PG supernatant. Repopulation of acellular heart valve matrices was stimulated by seeding matrices with oMSCs supplemented with the PG supernatant.Results
The most significant increase in proliferation induced by PG supernatant appeared at 1 × 105 plts/ml concentration. Higher concentrations evoked reduction of the stimulatory process. oMSC motility was most significantly stimulated at 1 × 106 plts/ml. Stimulating invasiveness of oMSCs needed the much higher concentration of 2 × 106 plts/ml. Immunoassays revealed that sheep PG supernatant contains 184.8 pg/ml bFGF and 60.5 ng/ml TGF‐β1. Moreover, repopulation of acellular heart valve matrices was significantly enhanced by PG supernatant addition and resulted in upregulation of the myofibroblast marker alpha‐smooth muscle actin.Conclusions
Growth factors released from platelets had the potential to induce cell repopulation in a heart valve tissue engineering procedure, through stimulation of mesenchymal stem‐cell migration and invasion. 相似文献9.
10.
E. Cortés‐Barberena I. Ceballos‐Olvera H. González‐Márquez R. Ortiz‐Muñiz 《Cell proliferation》2013,46(2):164-171
Objectives
Previous studies have shown alterations in bone marrow cell proliferation in malnourished rats, during lactation. The objective of this study was to determine in vivo effects of moderate and severe malnutrition on spleen cell proliferation in 21‐day‐old rat pups.Materials and methods
Spleen cell proliferation was determined following administration of bromodeoxyuridine (BrdUrd) over a time course of 2, 4, 6 and 8 h. Incorporation of BrdUrd was detected using FITC‐conjugated anti‐BrdUrd monoclonal antibodies and total DNA content was detected and evaluated using propidium iodide using flow cytometry.Results
Proportions of cells in S and G2/M were reduced in the rats with moderate (MN2nd) and severe (MN3rd) malnutrition. BrdUrd incorporation was lower in both groups of malnourished rat. In cells of MN2nd individuals, length of G1 became shorter, while length of S‐phase increased. In contrast, fraction of cells in proliferation was significantly lower in both groups of malnourished rat, with MN3rd group having lowest percentage of cell population growth. In this study, severe malnutrition did not significantly affect duration of phases of the cell cycle, although fractions of proliferating cells were dramatically reduced.Conclusion
Moderate malnutrition increased time of cells in DNA synthesis and time of total cell cycle and severe malnutrition reduced growth fraction of spleen cells in malnourished rats during lactation.11.
Effect of microgravity on proliferation and differentiation of embryonic stem cells in an automated culturing system during the TZ‐1 space mission 下载免费PDF全文
Xiaohua Lei Yujing Cao Ying Zhang Jingjing Qian Qian Zhao Fangwu Liu Tao Zhang Jiaxi Zhou Ying Gu Guoliang Xia Enkui Duan 《Cell proliferation》2018,51(5)
Objective
Despite a great number of studies analysing the effects of microgravity on stem cell proliferation and differentiation, few of them have focused on real‐time imaging estimates in space. Herein, we utilized the TZ‐1 cargo spacecraft, automatic cell culture equipment and live cell imaging techniques to examine the effects of real microgravity on the proliferation and differentiation of mouse embryonic stem cells (mESCs).Materials and methods
Oct4‐GFP, Brachyury‐GFP mESC and Oct4‐GFP mESC‐derived EBs were used as experimental samples in the TZ‐1 spaceflight mission. These samples were seeded into chambers, cultured in an automatic cell culture device and were transported into space during the TZ‐1 mission. Over 15 days of spaceflight, bright field and fluorescent images of cell growth were taken in micrography, and the medium was changed every day. Real‐time image data were transferred to the ground for analysis.Results
Space microgravity maintains stemness and long‐term survival of mESCs, promising 3D aggregate formation. Although microgravity did not significantly prevent the migration of EBs on the ECM substrate, it did prevent terminal differentiation of cells.Conclusions
This study demonstrates that space microgravity might play a potential role in supporting 3D cell growth and maintenance of stemness in embryonic stem cells, while it may negatively affect terminal differentiation.12.
Tirino V Desiderio V d'Aquino R De Francesco F Pirozzi G Graziano A Galderisi U Cavaliere C De Rosa A Papaccio G Giordano A 《PloS one》2008,3(10):e3469
Background
Osteosarcoma is the most common primary tumour of bone. Solid tumours are made of heterogeneous cell populations, which display different goals and roles in tumour economy. A rather small cell subset can hold or acquire stem potentials, gaining aggressiveness and increasing expectancy of recurrence. The CD133 antigen is a pentaspan membrane glycoprotein, which has been proposed as a cancer stem cell marker, since it has been previously demonstrated to be capable of identifying a cancer initiating subpopulation in brain, colon, melanoma and other solid tumours. Therefore, our aim was to observe the possible presence of cells expressing the CD133 antigen within solid tumour cell lines of osteosarcoma and, then, understand their biological characteristics and performances.Methodology and Principal Findings
In this study, using SAOS2, MG63 and U2OS, three human sarcoma cell lines isolated from young Caucasian subjects, we were able to identify and characterize, among them, CD133+ cells showing the following features: high proliferation rate, cell cycle detection in a G2\M phase, positivity for Ki-67, and expression of ABCG2 transporters. In addition, at the FACS, we were able to observe the CD133+ cell fraction showing side population profile and forming sphere-clusters in serum-free medium with a high clonogenic efficiency.Conclusions
Taken together, our findings lead to the thought that we can assume that we have identified, for the first time, CD133+ cells within osteosarcoma cell lines, showing many features of cancer stem cells. This can be of rather interest in order to design new therapies against the bone cancer. 相似文献13.
Liene Daukste Britta Basse Bruce C. Baguley David J.N. Wall 《Journal of theoretical biology》2009,260(4):563-571
There is increasing evidence that the growth of human tumours is driven by a small proportion of tumour stem cells with self-renewal properties. Multiplication of these cells leads to loss of self-renewal and after division for a finite number of times the cells undergo programmed cell death. Cell cycle times of human cancers have been measured in vivo and shown to vary in the range from two days to several weeks, depending on the individual. Cells cultured directly from tumours removed at surgery initially grow at a rate comparable to the in vivo rate but continued culture leads to the generation of cell lines that have shorter cycle times (1–3 days). It has been postulated that the more rapidly growing sub-population exhibits some of the properties of tumour stem cells and are the precursors of a slower growing sub-population that comprise the bulk of the tumour. We have previously developed a mathematical model to describe the behaviour of cell lines and we extend this model here to describe the behaviour of a system with two cell populations with different kinetic characteristics and a precursor–product relationship. The aim is to provide a framework for understanding the behaviour of cancer tissue that is sustained by a minor population of proliferating stem cells. 相似文献
14.
Radovan Vojtí?ek Ji?í Ferda Jind?ich Fínek 《Reports of Practical Oncology and Radiotherapy》2015,20(3):210-216
Aim
The aim of our study was to compare the staging of the disease declared before anticancer treatment was begun with the staging that was found after the planning PET/CT scanning with 18F-FLT was performed.Background
PET/CT in radiotherapy planning of head and neck cancers can facilitate the contouring of the primary tumour and the definition of metastatic lymph nodes.Materials and methods
Between November 2010 and November 2013, 26 patients suffering from head and neck carcinomas underwent planning PET/CT examination with 18F-FLT. We compared the staging of the disease and the treatment strategy declared before and after 18F-FLT-PET/CT was performed.Results
The findings from 18FLT-PET/CT led in 22 patients to a change of staging: in 19 patients it led to upstaging of the disease and in 3 patients it led to downstaging of the disease. In one patient, a secondary malignancy was found.Conclusions
We have confirmed in this study that the use of 18F-FLT-PET/CT scanning in radiotherapy planning of squamous cell head and neck carcinomas has a great potential in the precise evaluation of disease staging and consequently in the precise determination of target volumes. 相似文献15.
Berberine inhibits the chemotherapy‐induced repopulation by suppressing the arachidonic acid metabolic pathway and phosphorylation of FAK in ovarian cancer 下载免费PDF全文
Yawei Zhao Lianzhi Cui Yue Pan Dan Shao Xiao Zheng Fan Zhang Hansi Zhang Kan He Li Chen 《Cell proliferation》2017,50(6)
Objectives
Cytotoxic chemotherapy is an effective and traditional treatment of ovarian cancer. However, chemotherapy‐induced apoptosis may also trigger and ultimately accelerate the repopulation of the small number of adjacent surviving cells. This study mainly focused on the tumour cell repopulation caused by chemotherapy in ovarian cancer and the adjunctive/synergistic effect of Berberine on the prevention of tumour repopulation.Materials and methods
The transwell system was used to mimic the co‐culture of surviving ovarian cancer cells in the microenvironment of cytotoxic chemotherapy‐treated dying cells. Tumour cell proliferation was observed by crystal violet staining. AA and PGE2 levels were measured by ELISA, and changes of protein expression were analysed by Western blot.Results
Chemotherapy drug VP16 treatment triggered AA pathway, leading to the elevated PGE2 level, and ultimately enhanced the repopulation of ovarian cancer cells. Berberine can block the caspase 3‐iPLA2‐AA‐COX‐2‐PGE2 pathway by inhibiting the expression of iPLA2 and COX‐2. Berberine can also reverse the increased phosphorylation of FAK caused by abnormal PGE2 level and thus reverse the repopulation of ovarian cancer cells after VP16 treatment.Conclusions
Our observation suggested that Berberine could inhibit the chemotherapy‐induced repopulation of ovarian cancer cells by suppressing the AA pathway and phosphorylation of FAK. And these findings implicated a novel combined use of Berberine and chemotherapeutics, which might prevent ovarian cancer recurrence by abrogating early tumour repopulation.16.
Deferoxamine promotes mesenchymal stem cell homing in noise‐induced injured cochlea through PI3K/AKT pathway 下载免费PDF全文
A.A. Peyvandi H.‐A. Abbaszadeh N. Ahmady Roozbahany A. Pourbakht S. Khoshsirat H. Haddadzade Niri H. Peyvandi S. Niknazar 《Cell proliferation》2018,51(2)
Objective
Over 5% of the world's population suffers from disabling hearing loss. Stem cell homing in target tissue is an important aspect of cell‐based therapy, which its augmentation increases cell therapy efficiency. Deferoxamine (DFO) can induce the Akt activation, and phosphorylation status of AKT (p‐AKT) upregulates CXC chemokine receptor‐4 (CXCR4) expression. We examined whether DFO can enhance mesenchymal stem cells (MSCs) homing in noise‐induced damaged cochlea by PI3K/AKT dependent mechanism.Materials and Methods
Mesenchymal stem cells were treated with DFO. AKT, p‐AKT protein and hypoxia inducible factor 1‐ α (HIF‐1α) and CXCR4 gene and protein expression was evaluated by RT‐ PCR and Western blot analysis. For in vivo assay, rats were assigned to control, sham, noise exposure groups without any treatment or receiving normal, DFO‐treated and DFO +LY294002 (The PI3K inhibitor)‐treated MSCs. Following chronic exposure to 115 dB white noise, MSCs were injected into the rat cochlea through the round window. Number of Hoechst‐ labelled cells was determined in the endolymph after 24 hours.Results
Deferoxamine increased P‐AKT, HIF‐1α and CXCR4 expression in MSCs compared to non‐treated cells. DFO pre‐conditioning significantly increased the homing ability of MSCs into injured ear compared to normal MSCs. These effects of DFO were blocked by LY294002.Conclusions
Pre‐conditioning of MSCs by DFO before transplantation can improve stem cell homing in the damaged cochlea through PI3K/AKT pathway activation.17.
18.
Y. Carmazzi M. Iorio C. Armani S. Cianchetti F. Raggi T. Neri C. Cordazzo S. Petrini R. Vanacore F. Bogazzi P. Paggiaro A. Celi 《Cell proliferation》2012,45(6):545-556
Objectives
Clinical data suggest that heparin treatment improves survival of lung cancer patients, but the mechanisms involved are not fully understood. We investigated whether low molecular weight heparin nadroparin, directly affects lung cancer cell population growth in conventionally cultured cell lines.Materials and methods
A549 and CALU1 cells’ viability was assessed by MTT and trypan blue exclusion assays. Cell proliferation was assessed using 5‐bromo‐2‐deoxyuridine incorporation. Apoptosis and cell‐cycle distribution were analysed by flow cytometry; cyclin B1, Cdk1, p‐Cdk1 Cdc25C, p‐Cdc25C and p21 expressions were analysed by western blotting. mRNA levels were analysed by real time RT‐PCR.Results
Nadroparin inhibited cell proliferation by 30% in both cell lines; it affected the cell cycle in A549, but not in CALU‐1 cells, inducing arrest in the G2/M phase. Nadroparin in A549 culture inhibited cyclin B1, Cdk1, Cdc25C and p‐Cdc25C, while levels of p‐Cdk1 were elevated; p21 expression was not altered. Dalteparin caused a similar reduction in A549 cell population growth; however, it did not alter cyclin B1 expression as expected, based on previous reports. Fondaparinux caused minimal inhibition of A549 cell population growth and no effect on either cell cycle or cyclin B1 expression.Conclusions
Nadroparin inhibited proliferation of A549 cells by inducing G2/M phase cell‐cycle arrest that was dependent on the Cdc25C pathway, whereas CALU‐1 cell proliferation was halted by as yet not elucidated modes. 相似文献19.
Background
Mucosal melanoma of the head and neck is a rare malignant tumor associated with a poor prognosis. Surgery, chemotherapy, radiotherapy, and biotherapy are common strategies for treating mucosal melanoma of the head and neck. Episcleritis is an idiopathic, immune-mediated disease, and is classified into two types: simple episcleritis and nodular episcleritis.Case presentation
In this case report we describe ocular changes involving simple episcleritis in a 65-year-old Chinese man with mucosal melanoma of the head and neck after treatment with interferon alfa-2b and radiotherapy. On the third day of interferon alfa-2b treatment, he began to develop simple episcleritis in his left eye. Moreover, the percentage of CD3+ T cells in lymphocytes from blood was increased after interferon alfa-2b treatment. After approximately 6 days, the symptoms of eye pain, hyperemia, and edema disappeared gradually. Then, after radiotherapy was performed three times, he again developed episcleritis in his left eye. The same symptoms of hyperemia and edema occurred again; CD3+ T cell frequency was also at a higher level. After approximately a week, all the symptoms disappeared completely. Simple treatment involving topical ofloxacin and phenylephrine was administered during the two periods of episcleritis.Conclusion
Episcleritis in this patient might have been due to the treatment with interferon alfa-2b and radiotherapy, leading to an increase in the level of CD3+ T cells and activation of immune system cells, which provides the guide for clinical clinicians.20.