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1.
Chao Li Jing Ruan Meng Yang Fei Pan Guo Gao Su Qu You-Lan Shen Yong-Jun Dang Kan Wang Wei-Lin Jin Da-Xiang Cui 《癌症生物学与医学(英文版)》2015,12(3):163-174
Objective
Human induced pluripotent stem (iPS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human iPS cells labeled with fluorescent magnetic nanoparticles (FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo.Methods
Human iPS cells were prepared and cultured for 72 h. The culture medium was collected, and then was co-incubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human iPS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly.Results
iPS cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iPS cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field.Conclusion
FMNP-labeled human iPS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer.KEYWORDS : Human induced pluripotent stem cell (human iPS cells), targeted imaging, hyperthermia therapy, fluorescent magnetic nanoparticles, gastric cancer, nude mice 相似文献2.
Siobhan P. Lynch Xiudong Lei Limin Hsu Funda Meric‐Bernstam Thomas A. Buchholz Hong Zhang Gabriel N. Hortobágyi Ana M. Gonzalez‐Angulo Vicente Valero 《The oncologist》2013,18(11):1167-1173
Background.
The impact of multifocal (MF) or multicentric (MC) breast cancer on locoregional (LR) control rates is unknown.Methods.
MF was defined as two or more separate invasive tumors in the same quadrant of the breast. MC was defined as two or more separate invasive tumors occupying more than one quadrant of the same breast. Patients were categorized by LR treatment: breast conservation therapy (BCT; n = 256), mastectomy (n = 466), or mastectomy plus postmastectomy radiation therapy (PMRT; n = 184). All patients with MC disease had mastectomy (10 patients treated with BCT for MC disease were excluded). The Kaplan-Meier product limit method was used to calculate 5-year LR control rate. Cox proportional hazards models were used to determine independent associations of multifocality or multicentricity with LR control.Results.
A total of 906 patients had either MF disease (n = 673) or MC disease (n = 233). With median follow-up of 52 months, the 5-year LR control rate was 99% for MF, 96% for MC, and 98% for unifocal tumors (p = .44). Subset analysis revealed no difference in LR control regardless of the LR treatment (p = .67 for BCT, p = .37 for mastectomy, p = .29 for mastectomy plus PMRT). There were five in-breast recurrences after BCT in the MF group. MF and MC did not have an independent impact on LR control rate on multivariate analysis.Conclusion.
MF and MC disease are not independent risk factors for LR recurrence. Patients with MF and MC breast cancer had rates of LR control similar to those of their unifocal counterparts. These data suggest that BCT is a safe option for patients with MF tumors and that MF or MC disease alone is not an indication for PMRT. 相似文献3.
Maxim A. Shevtsov Ludmila Y. Yakovleva Boris P. Nikolaev Yaroslav Y. Marchenko Anatolii V. Dobrodumov Kirill V. Onokhin Yana S. Onokhina Sergey A. Selkov Anastasiia L. Mikhrina Irina V. Guzhova Marina G. Martynova Olga A. Bystrova Alexander M. Ischenko Boris A. Margulis 《Neuro-oncology》2014,16(1):38-49
Background
Superparamagnetic iron oxide nanoparticles (SPIONs), due to their unique magnetic properties, have the ability to function both as magnetic resonance (MR) contrast agents, and can be used for thermotherapy. SPIONs conjugated to the heat shock protein Hsp70 that selectively binds to the CD40 receptor present on glioma cells, could be used for MR contrast enhancement of experimental C6 glioma.Methods
The magnetic properties of the Hsp70-SPIONs were measured by NMR relaxometry method. The uptake of nanoparticles was assessed on the C6 glioma cells by confocal and electron microscopes. The tumor selectivity of Hsp70-SPIONs being intravenously administered was analyzed in the experimental model of C6 glioma in the MRI scanner.Results
Hsp70-SPIONs relaxivity corresponded to the properties of negative contrast agents with a hypointensive change of resonance signal in MR imaging. A significant accumulation of the Hsp70-SPIONs but not the non-conjugated nanoparticles was observed by confocal microscopy within C6 cells. Negative contrast tumor enhancement in the T2-weighted MR images was higher in the case of Hsp70-SPIONs in comparison to non-modified SPIONs. Histological analysis of the brain sections confirmed the retention of the Hsp70-SPIONs in the glioma tumor but not in the adjacent normal brain tissues.Conclusion
The study demonstrated that Hsp70-SPION conjugate intravenously administered in C6 glioma model accumulated in the tumors and enhanced the contrast of their MR images. 相似文献4.
Muhammad Gul Bahar Ashiq Mohammad Mam Saeed Bashir Ahmad Tahir Noorddin Ibrahim Muhammad Nadeem 《中国癌症研究》2013,25(6):756-761
Objective: Laser-induced Coulomb explosion of gold nanoparticles for breast cancer has been studied by nanophotolysis technique. This study aimed to investigate whether laser-induced bubble formation due to Coulomb explosion can provide an effective approach for selective damage of breast cancer with gold nanoparticles. Method: Numerical method involves laser-induced Coulomb explosion of gold nanoparticles. Different parameters related to nanophotolysis such as laser fluence, tumor depth, cluster radius, laser pulse duration, and bubble formation is studied numerically. Numerical simulation was performed using Mat lab. Results: The gold nanopartieles of 10, 20, 30, 40, and 50 nm in radius could penetrate into tumor 1.14, 1.155, 1.189, 1.20 and 1.22 cm in depth respectively. The maximum penetration depth in tumor could be obtained with nanoparticles of 50 nm radius. Short laser pulse of 40 ns with nanoparticles of 10 nm radius could penetrate into tumor 1.14 cm in depth. Bubbles with a radius of 9 pm could effectively kill breast cancer cells without damaging healthy ones. The bubble radius increased from 4 to 9 lam with an increase in pulse duration in the range of 10 to 30 ns. Conclusions: Gold nanoparticles with increasing radius and bubble formation for selective damage of breast cancer cells are successfully probed. The present calculated results are compared with other experimental findings, and good correlation is found between the present work and previous experimental values. It was demonstrated that bubble formation in tumor may further increase the efficacy of breast cancer treatment. 相似文献
5.
Olivier Facy Fran?ois Radais Sylvain Ladoire Delphine Delroeux Hervé Tixier Fran?ois Ghiringhelli Patrick Rat Bruno Chauffert Pablo Ortega-Deballon 《Journal of experimental & clinical cancer research : CR》2011,30(1):4
Background
The best method to deliver intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis from ovarian cancer is not well defined. The aim of this study was to assess the ability of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a rat model of peritoneal carcinomatosis.Methods
Four groups of 5 BDIX rats with ovarian peritoneal carcinomatosis underwent IPC with 30 mg/l of cisplatin according to the following conditions: normothermia at 37° for 1 or 2 hours, hyperthermia at 42°C for 1 hour or normothermia at 37°C for 2 hours with 2 mg/l adrenaline. Tissue platinum content was measured by atomic absorption spectroscopy. The effect of hyperthermia, adrenaline and the duration of exposure to the drug was measured in vivo (tissue concentration of platinum in tumor, abdominal and extra abdominal tissues) and in vitro (cytotoxicity on human ovarian cancer cells).Results
In vitro, hyperthermia and longer exposure enhanced the accumulation and the cytotoxic effect of cisplatin on cancer cells. In vivo, only the 2 hours treatment with adrenaline resulted in increased platinum concentrations. The rats treated with adrenaline showed significantly lower concentrations of cisplatin in extra peritoneal tissues than those treated with hyperthermia.Conclusion
Adrenaline is more effective than hyperthermia in order to enhance the intratumoral concentration of cisplatin in rats with peritoneal carcinomatosis from ovarian origin. It may also decrease the systemic absorption of the drug. 相似文献6.
Hong Wu Ruhui Li XiaoDong Hang Ming Yan Feng Niu Lidi Liu Wei Liu Song Zhao Shaokun Zhang 《JOURNAL OF BREAST CANCER》2011,14(3):175-180
Purpose
To investigate the distribution of CD44+/CD24- cells in breast cancers in relation to tumor size before and after the administration of neoadjuvant chemotherapy.Methods
CD44+/CD24- tumor cells obtained from breast cancer specimens were characterized in vivo and in vitro using tumor formation assays and mammosphere generation assays, respectively. The distribution of CD44+/CD24- tumor cells in 78 breast cancer specimens following administration of neoadjuvant chemotherapy was also evaluated using immunofluorescence assays, and this distribution was compared with the extent of tumor invasion predicted by Response Evaluation Criteria in Solid Tumours (RECIST).Results
In 27/78 cases, complete remission (CR) was identified using RECIST. However, 18 of these CR cases were associated with a scattered distribution of tumor stem cells in the outline of the original tumor prior to neoadjuvant chemotherapy. After neoadjuvant chemotherapy, 24 cases involved cancer cells that were confined to the tumor outline, and 21 cases had tumor cells or tumor stem cells overlapping the tumor outline. In addition, there were 6 patients who were insensitive to chemotherapy, and in these cases, both cancer cells and stem cells were detected outside the contours of the tumor volume imaged prior to chemotherapy.Conclusion
CD44+/CD24- tumor cells may be an additional parameter to evaluate when determining the extent of breast cancer invasion. 相似文献7.
Objective:Estimation of activity accumulated in tumor and organs is very important in predicting the response of radiopharmaceuticals treatment.In this study,we synthesized 177Lutetium(177Lu)-trastuzumabiron oxide nanoparticles as a double radiopharmaceutical agent for treatment and better estimation of organ activity in a new way by magnetic resonance imaging(MRI).Methods:177Lu-trastuzumab-iron oxide nanoparticles were synthesized and all the quality control tests such as labeling yield,nanoparticle size determination,stability in buffer and blood serum up to 4 d,immunoreactivity and biodistribution in normal mice were determined.In mice bearing breast tumor,liver and tumor activities were calculated with three methods:single photon emission computed tomography(SPECT),MRI and organ extraction,which were compared with each other.Results:The good results of quality control tests(labeling yield:61%±2%,mean nanoparticle hydrodynamic size:41±15 nm,stability in buffer:86%±5%,stability in blood serum:80%±3%,immunoreactivity:80%±2%) indicated that 177Lu-trastuzumab-iron oxide nanoparticles could be used as a double radiopharmaceutical agent in mice bearing tumor.Results showed that 177Lu-trastuzumab-iron oxide nanoparticles with MRI had the ability to measure organ activities more accurate than SPECT.Conclusions:Co-conjugating radiopharmaceutical to MRI contrast agents such as iron oxide nanoparticles may be a good way for better dosimetry in nuclear medicine treatment. 相似文献
8.
Han Shi Yuchao Gu Jing Yang Liang Xu Wenyi Mi Wengong Yu 《Journal of experimental & clinical cancer research : CR》2008,27(1):83
Background
Lipocalin 2, an iron binding protein, is abnormally expressed in some malignant human cancers and may play an important role in tumor metastasis. However, the roles of lipocalin 2 in breast cancer formation and metastasis have not been clearly shown. This study aimed to investigate the roles of lipocalin 2 in breast tumor metastasis.Methods
Lipocalin 2 was overexpressed in the metastatic 4T1 murine mammary cancer cells. The effects of lipocalin 2 overexpression on the malignancy of breast cancer cells were examined using cell proliferation assay, migration assay, invasion assay, and soft agar assay in vitro. Tumor formation and metastasis abilities were examined using a well established mouse mammary tumor model in vivo.Results
Lipocalin 2 overexpression significantly enhanced the migration and invasion abilities of 4T1 cells in vitro, and lung metastasis in vivo. But overexpression of lipocalin 2 in 4T1 cells didn''t affect cell proliferation and anchorage-independent growth in vitro, and primary tumor weight in vivo. Further studies demonstrated that the inhibition of the PI3K/Akt pathway could be a causative mechanism for the promotion of breast cancer migration/invasion induced by lipocalin 2 overexpression.Conclusion
These results clarified that lipocalin 2 could promote lung metastasis of 4T1 cells through the inhibition of the PI3K/Akt pathway, suggesting that lipocalin 2 was a potential target for therapy of breast cancer. 相似文献9.
10.
11.
Sonia ávila-Arroyo Gema Santamaría Nu?ez Luis Francisco García-Fernández Carlos M. Galmarini 《JOURNAL OF BREAST CANCER》2015,18(4):329-338
Purpose
Trabectedin induces synthetic lethality in tumor cells carrying defects in homologous recombinant DNA repair. We evaluated the effect of concomitant inhibition of nucleotide-excision repair and poly (ADP-ribose) polymerase (PARP) activity with trabectedin and PARP inhibitors, respectively, and whether the synthetic lethality effect had the potential for a synergistic effect in breast cancer cell lines. Additionally, we investigated if this approach remained effective in BRCA1-positive breast tumor cells.Methods
We have evaluated the in vitro synergistic effect of combinations of trabectedin and three different PARP inhibitors (veliparib, olaparib, and iniparib) in four breast cancer cell lines, each presenting a different BRCA1 genetic background. Antiproliferative activity, DNA damage, cell cycle perturbations and poly(ADP-ribosyl)ation were assessed by MTT assay, comet assay, flow cytometry and western blot, respectively.Results
The combination of trabectedin and olaparib was synergistic in all the breast cancer cell lines tested. Our data indicated that the synergy persisted regardless of the BRCA1 status of the tumor cells. Combination treatment was associated with a strong accumulation of double-stranded DNA breaks, G2/M arrest, and apoptotic cell death. Synergistic effects were not observed when trabectedin was combined with veliparib or iniparib.Conclusion
Collectively, our results indicate that the combination of trabectedin and olaparib induces an artificial synthetic lethality effect that can be used to kill breast cancer cells, independent of BRCA1 status. 相似文献12.
Feng Ye Yan Qiu Li Li Libo Yang Fei Cheng Hongying Zhang Bing Wei Zhang Zhang Linyong Sun Hong Bu 《JOURNAL OF BREAST CANCER》2015,18(3):242-248
Purpose
It is well established that breast cancer stem cells (BCSCs) play an essential role in tumor invasion for both local and distant metastasis. The aim of this study was to establish whether BCSCs could act as a prognostic and clinical marker.Methods
We analyzed tumor tissues from 161 breast cancer patients. Dual immunohistochemistry and immunofluorescence were performed on all the slides, and we analyzed the relationship between EpCAM-/CD49f+ tumor cells and key clinical and prognostic factors.Results
Univariate survival analysis using the Kaplan-Meier method showed that the presence of EpCAM-/CD49f+ tumor cells in breast cancer was significantly associated with shorter disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed that the presence of EpCAM-/CD49f+ cells was associated with shorter DFS (p=0.010; hazard ratio [HR], 2.070) and OS (p=0.002; HR, 3.235). Tumors containing EpCAM-/CD49f+ cells were also more likely to metastasize after initial surgery (p=0.048).Conclusion
Our study suggests that breast tumors containing EpCAM-/CD49f+ cells are more likely to undergo distant metastasis after initial surgery and are associated with a shorter DFS and OS. 相似文献13.
14.
Background:
Alpha-1-syntrophin (SNTA1) has been implicated in the activation of Rac1. However, the underlying mechanism has not yet been explored. Here, we show that a novel complex, involving SNTA1, P66shc, and Grb2 proteins, is involved in Rac1 activation.Methods:
Co-immunoprecipitation assays were used to show the complex formation, while siRNAs and shRNAs were used to downregulate expression of these proteins. Various Rac1 activation assays and functional assays, such as migration assays, in vitro wound healing assays, cell proliferation assays, and ROS generation assays, were also performed.Results:
The results showed a significant increase in activation of Rac1 when SNTA1 and P66shc were overexpressed, whereas depletion of SNTA1 and P66shc expression effectively reduced the levels of active Rac1. The results indicated a significant displacement of Sos1 protein from Grb2 when SNTA1 and P66shc are overexpressed in breast cancer cell lines, resulting in Sos1 predominantly forming a complex with Eps8 and E3b1. In addition, the SNTA1/P66shc-mediated Rac1 activation resulted in an increase in reactive oxygen species (ROS) production and migratory potential in human breast cancer cells.Conclusion:
Together, our results present a possible mechanism of Rac1 activation involving SNTA1 and emphasise its role in ROS generation, cell migration, and acquisition of malignancy. 相似文献15.
Keunhee Oh Ok-Young Lee Suh Youn Shon Onyou Nam Po Mee Ryu Myung Won Seo Dong-Sup Lee 《Breast cancer research : BCR》2013,15(5):R79
Introduction
Tumor cell interactions with the microenvironment, especially those of bone-marrow-derived myeloid cells, are important in various aspects of tumor metastasis. Myeloid-derived suppressor cells (MDSCs) have been suggested to constitute tumor-favoring microenvironments. In this study, we elucidated a novel mechanism by which the MDSCs can mediate spontaneous distant metastasis of breast cancer cells.Methods
Murine breast cancer cells, 4T1 and EMT6, were orthotopically grafted into the mammary fat pads of syngeneic BALB/c mice. CD11b+Gr-1+ MDSCs in the spleen, liver, lung and primary tumor mass were analyzed. To evaluate the role of MDSCs in the distant metastasis, MDSCs were depleted or reconstituted in tumor-bearing mice. To evaluate whether MDSCs in the metastasizing tumor microenvironment affect breast cancer cell behavior, MDSCs and cancer cells were co-cultivated. To investigate the role of MDSCs in in vivo metastasis, we blocked the interactions between MDSCs and cancer cells.Results
Using a murine breast cancer cell model, we showed that murine breast cancer cells with high IL-6 expression recruited more MDSCs and that the metastasizing capacity of cancer cells paralleled MDSC recruitment in tumor-bearing mice. Metastasizing, but not non-metastasizing, tumor-derived factors induced MDSCs to increase IL-6 production and full activation of recruited MDSCs occurred in the primary tumor site and metastatic organ in the vicinity of metastasizing cancer cells, but not in lymphoid organs. In addition, tumor-expanded MDSCs expressed Adam-family proteases, which facilitated shedding of IL-6 receptor, thereby contributing to breast cancer cell invasiveness and distant metastasis through IL-6 trans-signaling. The critical role of IL-6 trans-signaling was confirmed in both the afferent and efferent pathways of metastasis.Conclusion
In this study, we showed that metastasizing cancer cells induced higher MDSCs infiltration and prompted them to secret exaggerated IL-6 as well as soluble IL-6Rα, which, in turn, triggered a persistent increase of pSTAT3 in tumor cells. This potential tumor-MDSC axis involving IL-6 trans-signaling directly affected breast cancer cell aggressiveness, leading to spontaneous metastasis. 相似文献16.
Xiu-Rong Ren Jiangbo Wang Takuya Osada Robert A Mook Jr Michael A Morse Larry S Barak Herbert Kim Lyerly Wei Chen 《Breast cancer research : BCR》2015,17(1)
Introduction
Human epidermal growth factor receptor HER3 has been implicated in promoting the aggressiveness and metastatic potential of breast cancer. Upregulation of HER3 has been found to be a major mechanism underlying drug resistance to EGFR and HER2 tyrosine kinase inhibitors and to endocrine therapy in the treatment of breast cancer. Thus, agents that reduce HER3 expression at the plasma membrane may synergize with current therapies and offer a novel therapeutic strategy to improve treatment.Methods
We devised an image-based screening platform using membrane localized HER3-YFP to identify small molecules that promote HER3 internalization and degradation. In vitro and in vivo tumor models were used to characterize the signaling effects of perhexiline, an anti-anginal drug, identified by the screening platform.Results
We found perhexiline, an anti-anginal drug, selectively internalized HER3, decreased HER3 expression, and subsequently inhibited signaling downstream of HER3. Consistent with these results, perhexiline inhibited breast cancer cell proliferation in vitro and tumor growth in vivo.Conclusions
This is the first demonstration that HER3 can be targeted with small molecules by eliminating it from the cell membrane. The novel approach used here led to the discovery that perhexiline ablates HER3 expression, and offers an opportunity to identify HER3 ablation modulators as innovative therapeutics to improve survival in breast cancer patients.Electronic supplementary material
The online version of this article (doi:10.1186/s13058-015-0528-9) contains supplementary material, which is available to authorized users. 相似文献17.
Riad Akoum Albert Ghaoui Emile Brihi Maroun Ghabash Nicolas Hajjar 《Hereditary cancer in clinical practice》2009,7(1):10
Background
There are still controversies about the integration of breast cancer as a part of the disease spectrum in Lynch syndrome.Methods
A regular follow-up of a Lebanese pedigree with Lynch syndrome due to a point mutation of MSH2 gene at the splice donor site of intron 3 started in 1996.Results
A 26-year-old pregnant woman, mutation carrier, developed an aggressive breast cancer, refractory to standard chemotherapy regimens. The microsatellite analysis of the tumor showed an unstable pattern for markers BAT25 and BAT26. The immunohistochemical staining was negative for MSH2 and MSH6 and normal for MLH1 and PMS6 enzymes.Conclusion
The segregation of the mutation with the disease phenotype and these results suggest that MSH2 inactivation may be involved in the accelerated breast carcinogenesis and might be considered in the cancer screening program. 相似文献18.
Sun Hyun Bae Won Park Seung Jae Huh Doo Ho Choi Seok Jin Nam Young-Hyuck Im Jin Seok Ahn 《JOURNAL OF BREAST CANCER》2012,15(3):329-336
Purpose
This study evaluated the treatment results and the necessity to irradiate the supraclavicular lymph node (SCN) region in pathological N0-N1 (pN0-N1) patients with locally advanced breast cancer treated with neoadjuvant chemotherapy (NAC) followed by surgery and radiotherapy (RT).Methods
Between 1996 and 2008, 184 patients with initial tumor size >5 cm or clinically positive lymph nodes were treated with NAC followed by surgery and RT. Among these patients, we retrospectively reviewed 98 patients with pN0-N1. Mastectomy was performed in 55%. The pathological lymph node stage was N0 in 49% and N1 in 51%. All patients received adjuvant RT to chest wall or breast and 56 patients (57%) also received RT to the SCN region (SCNRT).Results
At 5 years, locoregional recurrence (LRR)-free survival, distant metastasis-free survival, disease-free survival (DFS), and overall survival rates were 93%, 83%, 81%, and 91%, respectively. In pN0 patients, LRR was 7% in SCNRT- group and 5% in SCNRT+ group. In pN1 patients, LRR was 7% in SCNRT- group and 6% in SCNRT+ group. There was no significant difference of LRR, regardless of SCNRT. However, in pN1 patients, there were more patients with poor prognostic factors in the SCNRT+ group compared to SCNRT- group. These factors might be associated with worse DFS in the SCNRT+ group, even though RT was administered to the SCN region.Conclusion
Our study showed the similar LRR, regardless of SCNRT in pN0-pN1 breast cancer patients after NAC followed by surgery. Prospective randomized trial is called for to validate the role of SCNRT. 相似文献19.
Miranda A Hallett Bin Teng Hisashi Hasegawa Luciana P Schwab Tiffany N Seagroves Tayebeh Pourmotabbed 《Breast cancer research : BCR》2013,15(1):R12
Introduction
Despite continued improvements in diagnosis, surgical techniques, and chemotherapy, breast cancer patients are still overcome by cancer metastasis. Tumor cell proliferation, invasion and metastasis are mediated, at least in part, through degradation of basement membrane by neutral matrix metalloproteinases (MMP) produced by tumor and stromal cells. Evidence suggests that MMP-9 plays a significant role in breast tumor cell invasion and metastasis. DNAzymes or catalytic oligonucleotides are new classes of gene targeting molecules that bind and cleave a specific mRNA, resulting in decreased protein expression.Methods
The application of anti-MMP-9 DNAzyme (AM9D) for the treatment of primary and metastatic breast cancer was evaluated in vitro and in vivo using MDA-MB-231 cells and the MMTV-PyMT transgenic breast cancer mouse model. Spontaneously developed mammary tumors in MMTV-PyMT transgenic mice were treated intratumorally with naked AM9D, once a week for 4 weeks. The stability of DNAzyme was determined in vitro and in vivo using fluorescently labeled DNAzyme.Results
AM9D specifically inhibited expression of MMP-9 in MDA-MB-231 cells resulting in reduced invasive property of these cells by 43%. Weekly intratumoral treatment of spontaneously developed mammary tumors in MMTV-PyMT transgenic mice was sufficient to significantly reduce the rate of tumor growth and final tumor load in a dose dependent and statistically significant manner (P < 0.05). This decrease in tumor growth was correlated with decreased MMP-9 protein production within the treated tumor tissues. Tumors treated with AM9D were also less vascularized and contained more apoptotic cells compared to control and untreated tumors.Conclusions
These results show that targeting and down regulation of MMP-9 by AM9D could prove useful as a therapy against breast carcinoma tumor growth and invasion. 相似文献20.
Jongmin Sim Hyein Ahn Rehman Abdul Hyunsung Kim Ki-jong Yi Yu-min Chung Min Sung Chung Seung Sam Paik Young Soo Song Kiseok Jang 《JOURNAL OF BREAST CANCER》2015,18(4):323-328