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1.
J Exp Clin Cancer Res ; 39(1): 44, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111229

RESUMO

BACKGROUND: FK506-binding protein 9 (FKBP9) is amplified in high-grade gliomas (HGGs). However, the roles and mechanism(s) of FKBP9 in glioma are unknown. METHODS: The expression of FKBP9 in clinical glioma tissues was detected by immunohistochemistry (IHC). The correlation between FKBP9 expression levels and the clinical prognosis of glioma patients was examined by bioinformatic analysis. Glioblastoma (GBM) cell lines stably depleted of FKBP9 were established using lentiviruses expressing shRNAs against FKBP9. The effects of FKBP9 on GBM cells were determined by cell-based analyses, including anchorage-independent growth, spheroid formation, transwell invasion assay, confocal microscopy, immunoblot (IB) and coimmunoprecipitation assays. In vivo tumor growth was determined in both chick chorioallantoic membrane (CAM) and mouse xenograft models. RESULTS: High FKBP9 expression correlated with poor prognosis in glioma patients. Knockdown of FKBP9 markedly suppressed the malignant phenotype of GBM cells in vitro and inhibited tumor growth in vivo. Mechanistically, FKBP9 expression induced the activation of p38MAPK signaling via ASK1. Furthermore, ASK1-p38 signaling contributed to the FKBP9-mediated effects on GBM cell clonogenic growth. In addition, depletion of FKBP9 activated the IRE1α-XBP1 pathway, which played a role in the FKBP9-mediated oncogenic effects. Importantly, FKBP9 expression conferred GBM cell resistance to endoplasmic reticulum (ER) stress inducers that caused FKBP9 ubiquitination and degradation. CONCLUSIONS: Our findings suggest an oncogenic role for FKBP9 in GBM and reveal FKBP9 as a novel mediator in the IRE1α-XBP1 pathway.

2.
Onco Targets Ther ; 11: 1173-1182, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29535540

RESUMO

Background: Despite the breadth of understanding the noncoding RNAs' function in molecular biology, their functional roles in hepatocellular carcinoma (HCC) is poorly understood. In this study, we investigated the effect of hepatitis C virus (HCV) core upon the expression of noncoding RNAs. Methods: The lncRNAs, mRNAs, and circRNAs were employed for identification of HCV core protein gene expression in human Huh7 hepatoma (Huh7) cell line. In data analysis, we applied a threshold that eliminated all genes that were not increased or decreased by at least a 2-fold change in a comparison between transfected and control cells. Hierarchical Clustering and the Kyoto encyclopedia of genes and genome pathway analyses were performed to show the distinguishable lncRNA, mRNAs, and circRNAs expression pattern among samples. Results: The array data showed that 4,851 lncRNAs, 4,785 mRNAs, and 823 circRNAs were 2-fold up-regulated but 3,569 lncRNAs, 3,192 mRNAs, and 419 circRNAs were 2-fold down-regulated in Huh 7-core cells. The genes in the enriched set were associated with macromolecule and nucleic acid metabolic processes, DNA damage response and regulation of voltage-gated calcium channel. We identified 10 genes from the selected 14 genes that were higher or lower expression in Huh7-core cells than that of Huh7-vector cells by quantitative real-time polymerase chain reaction. Interestingly, overexpression of miR122 and miR204 partly abrogated the expression of TGFBRAP1 and HOTTIP, and increased the HPCAL1 expression in the predicted carcinogenic pathways. Conclusion: Our data suggests that the pathways of miR204-HPCAL1-lncRNAHOTTIP and miR122-TGFBRAP1 were likely involved in the carcinogenic progress due to the presence of HCV core, and that overexpression of miR122 and miR204 might inhibit the HCC progress by down-regulation of TGFBRAP1 and HOTTIP expression.

3.
Biomed Chromatogr ; 32(6): e4190, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29334690

RESUMO

Rhizoma et Radix Polygoni Cuspidati (RRPC) is commonly prescribed for the treatment of amenorrhea, arthralgia, jaundice and abscess in traditional Chinese medicine. Previous pharmacological studies have indicated that polyphenols are the main pharmacological active ingredients in RRPC. Meanwhile, the poor bioavailability of polyphenols in RRPC implies that those components are probably metabolized by intestinal bacteria before absorption. However, there is rather limited information about RRPC''s metabolites produced by intestinal bacteria and the intestinal absorbed constituents. In the present study, the metabolites were characterized after the aqueous extract of RRPC was incubated with the crude enzyme of human intestinal bacteria in vitro. The metabolic characteristics of glycosides in RRPC were figured out by comparing the metabolic profiles of emodin-8-O-ß-d-glucopyranoside and polydatin between aqueous extract of RRPC and equivalent amounts of these two glycosides. The transitional constituents absorbed into blood were investigated in rats via intraduodental administration and portal vein intubation. A total of 38 prototype components and 43 metabolites were detected and characterized in vivo. The overall results demonstrated that the intestinal bacteria played an important role in the metabolism of RRPC, and the main metabolic pathways were hydrolysis in vitro, glucuronidation and sulfation in vivo.


Assuntos
Bactérias/metabolismo , Medicamentos de Ervas Chinesas/metabolismo , Fallopia japonica , Microbioma Gastrointestinal/fisiologia , Polifenóis/metabolismo , Animais , Antraquinonas/análise , Antraquinonas/metabolismo , Feminino , Humanos , Masculino , Polifenóis/análise , Veia Porta/fisiologia , Ratos , Ratos Sprague-Dawley
4.
Biomed Chromatogr ; 31(10)2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28342275

RESUMO

Emodin is the representative form of rhubarb, which is widely used in traditional Chinese medicine for the treatment of purgative, anti-inflammatory, antioxidative and antiviral, etc. Previous reports demonstrated that emodin glucuronide was the major metabolite in plasma. Owing to the extensive conjugation reactions of polyphenols, the aim of this study was to identify the metabolites of emodin in rat bile and urine. Neutral loss and precursor ion scan methods of triple-quadrupole mass spectrometer revealed 13 conjugated metabolites in rat bile and 22 metabolites in rat urine, which included four phase I and 18 phase II metabolites. The major metabolites in rat biosamples were emodin glucuronoconjugates. Moreover, rhein monoglucuronide, chrysophanol monoglucuronide and rhein sulfate were proposed for the first time after oral administration of emodin. Overall, liquid chromatography hybrid triple-quadrupole mass spectrometry analysis leads to the discovery of several novel emodin metabolites in rat bile and urine and underscores that conjugated with glucuronic acid is the main metabolic pathway.


Assuntos
Bile/química , Emodina/análise , Emodina/metabolismo , Glucuronídeos/análise , Glucuronídeos/metabolismo , Animais , Cromatografia Líquida de Alta Pressão/métodos , Emodina/urina , Glucuronídeos/urina , Masculino , Ratos , Ratos Sprague-Dawley , Rheum , Espectrometria de Massas em Tandem/métodos
5.
Biochem Pharmacol ; 132: 18-28, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28232025

RESUMO

BACKGROUND: Although multiple myeloma (MM) treatment has improved in the last decade, it remains largely incurable. One of main reasons is that there are cancer stem cells (CSCs) in MM, which are responsible for MM's drug resistance and relapse. In this study, we used the targeting microbubbles (MBs) conjugated with anti-ABCG2 monoclonal antibody (mAb) for ultrasound mediated epirubicin (EPI) delivery to evaluate the therapeutic effectiveness of the novel agent in MM CSC xenograft model. METHODS: MM CSCs, marked by CD138-CD34- cell phenotypes were isolated from human MM RPMI8226 cell line using immune magnetic activated cell sorting system, and inoculated into nonobese diabetic/severe combined immunodeficient mice by subcutaneous or intravenous injection. After the mice developed MM, they were intravenous injection treated with EPI, EPI-MBs+mAb, and EPI-MBs+mAb with ultrasound exposure, respectively. RESULTS: All treated mice showed inhibited tumor sizes or bone lesions, decreased renal damages and anemia, and increased MM bearing mice' survival. In particular, the EPI-MBs+mAb plus ultrasound exhibited significantly enhanced therapeutic MM effectiveness by inducing apoptosis compared with other biologic agents. CONCLUSION: The data provide evidence that EPI-MBs+mAb with ultrasound exposure might be available for treatment MM patients in clinic.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/imunologia , Antibióticos Antineoplásicos/administração & dosagem , Epirubicina/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Animais , Anticorpos Monoclonais/imunologia , Imunoconjugados/administração & dosagem , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Exp Biol Med (Maywood) ; 242(9): 996-1004, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28056549

RESUMO

The goal of this investigation was to evaluate the inhibiting effect of high proportion polyethyleneglycol of long-circulating homoharringtonine liposomes on RPMI8226 multiple myeloma cancer stem cells. The CD138-CD34- multiple myeloma cancer stem cells isolated from RPMI8226 cell line using magnetic activated cell sorting system were, respectively, incubated with the optimized formulation of polyethyleneglycol of long-circulating homoharringtonine liposomes and the homoharringtonine in vitro, and the multiple myeloma cancer stem cell proliferation, colony formation, and cell cycle were analyzed. The inhibition of the multiple myeloma CD138-CD34- cancer stem cell growth was investigated in non-obese-diabetic/severe-combined-immunodeficiency mice that were implanted with multiple myeloma RPMI 8226 cancer stem cells and treated with the LCL-HHT-H-PEG. The results showed that the polyethyleneglycol of long-circulating homoharringtonine liposomes significantly inhibited MM cancer stem cell proliferation, colony formation, and induced cancer stem cell apoptosis in vitro as well as MM cancer stem cell growth in non-obese-diabetic/severe-combined-immunodeficiency mice compared with the homoharringtonine. In addition, the mouse bone mineral density and the red blood cell count were significantly increased in polyethyleneglycol of long-circulating homoharringtonine liposomes group. In conclusion, the data demonstrated that the developed polyethyleneglycol of long-circulating homoharringtonine liposomes formulation may serve as an efficient therapeutic drug for suppressing CD138-CD34- multiple myeloma cancer stem cell growth by inducing cancer stem cell apoptosis in non-obese-diabetic/severe-combined-immunodeficiency mouse model. Impact statement Multiple myeloma (MM) remains largely incurable until now. One of the main reasons is that there are cancer stem cells (CSCs) in MM, which are responsible for MM's drug resistance and relapse. In this study, we wanted to extend our previous investigation22 that whether we developed the LCL-HHT-H-PEG formulation have an inhibitory effect on MM CD138-CD34-CSCs in MM CSC engrafted NOD/SCID mouse model. Our data from the present study have demonstrated the therapeutic effect of LCL-HHT-H-PEG on MM-bearing mouse model. The study represents the first attempt to demonstrate that the LCL-HHT-H-PEG formulation is available for treatment MM patients in clinic. Therefore, this finding is important and deserves publication in Experimental Biology and Medicine.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Portadores de Fármacos/administração & dosagem , Harringtoninas/farmacologia , Lipossomos/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Mepesuccinato de Omacetaxina , Humanos , Camundongos , Camundongos SCID , Resultado do Tratamento
7.
Am J Transl Res ; 8(3): 1355-68, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27186264

RESUMO

Multiple myeloma (MM) remains an incurable disease in most patients. Homoharringtonine (HHT) is a natural alkaloid produced by various Cephalotaxus species, and is approved by the United States of America Food and Drug Administration to treat patients with acute and chronic myeloid lymphoma. The aim of this study was to develop the high proportion polyethyleneglycol (PEG) of long-circulating HHT liposomes (LCL-HHT-H-PEG) and investigate its therapeutic applicability in vitro and in vivo against RPMI8226 MM. The optimized formulation of LCL-HHT-H-PEG showed a higher association with cytotoxicity against MM RPMI8226 cells than those of low proportion PEG of long-circulating HHT liposomes, liposome-encapsulated-HHT, micelle-HHT, and HHT in vitro. Therapeutic experiments in severe combined immunodeficient mice implanted with MM RPMI8226 cells by the subcutaeous route showed the significant inhibition of tumor growth in LCL-HHT-H-PEG group compared with the HHT group, and other control groups. The analysis of flow cytometry and transmission electron microscopy indicated that LCL-HHT-H-PEG exerted the cytotoxicity against MM by inducing the MM apoptosis in vitro and in vivo. This study suggests that our developed LCL-HHT-H-PEG may be regarded as a promising nano-device to deliver anti-MM drug HHT for treatment of MM patients.

8.
Am J Transl Res ; 8(1): 98-108, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27069543

RESUMO

Research on the relationship between aberrant long non-coding RNA (lncRNA) and cancer stem cell (CSC) biology in cancer patients has been recently gaining attention. The goal of this study was to investigate whether the decreasing lncRNA HOTAIR expression would inhibit human colorectal cancer (CRC) stem cells. CD133(+)CSCs were isolated from human CRC LoVo cell line by using a magnetic-activated cell sorting system, and were transfected with the expression vector-based small hairpin RNA targeting HOTAIR (shHOTAIR). The ability of cellular proliferation, migration, invasion, colony-forming, and the epithelial-mesenchymal transition (EMT)-associated molecule expression as well as the tumorigenicity of CD133(+)-shHOTAIR were evaluated by the MTT, wound-healing, cellular invasion, colony formation and Western blot assays, respectively. This study found that, when compared with control cells in vitro, CD133(+)-shHOTAIR exhibited the decreased HOTAIR expression, suppressed cellular proliferation, migration, invasion, colony-forming, and inhibited the Vimentin expression with increased E-cadherin expression. In particular, the down-regulation of the HOTAIR expression in CD133(+)CSCs markedly attenuated the tumor growth and lung metastasis in xenograft nude mice. Taken together, this study found that down-regulating the HOTAIR expression in CD133(+)CSCs could serve as a potential anti-cancer regimen to inhibit the invasiveness and metastasis of CRC CSCs.

9.
Am J Transl Res ; 8(12): 5433-5443, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28078014

RESUMO

Hematological malignancy originated from B-cell line, multiple myeloma (MM), is a kind of plasma cells in bone marrow hyperplasia and cause of osteoclast-mediated skeletal destruction disease. MiR-34a plays an important epigenetic regulating role in malignant tumors and presents a therapeutic potential. In this study, we investigated the effects of overexpression of miR-34a in MM cancer stem cells (CSCs) on tumor growth and bone lesions. Here we showed that miR-34a overexpression inhibited cell proliferation, colony formation, and increased CSC apoptosis in vitro. The apparent epigenetic modulation induced by miR-34a overexpression was found no only in MM RPMI8226 cells but also in CSC xenograft MM. Both bioinformatics prediction and dual-luciferase reporter assay showed that transforming growth interaction factor 2 (TGIF2) was sufficient to confer miR-34a regulation. The results of qRT-PCR and Western blot assays demonstrated that the expression of TGIF2 was significant decreased in tumor tissues from NOD/SCID mice injected with miR-34a-MM CSCs. We conclude that miR-34a overexpression in MM CSCs significantly suppressed the tumorigenicity and lytic bone lesions in mouse model by inducing apoptosis and inhibiting TGIF2 expression.

10.
J Drug Target ; 24(1): 34-46, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26204324

RESUMO

Ultrasound-targeted microbubble destruction (UTMD) technique is thought to improve the chemotherapeutic agent delivery from microbubbles (MBs) in tumor tissues and reduce the side effects in non-tumor tissues. Multiple myeloma (MM) is a bone marrow cancer and remains to be an incurable disease. In this study, we used the UTMD technique to investigate the inhibitory effect of our developed novel reagent on MM cancer stem cells (CD138(-)CD34(-)MM CSCs) that are MM cells with CD138(-)CD34(-) phenotypes, responsible for MM-initiating potential, drug resistance and eventual relapse. The preparatory steps of novel reagent was first epirubicin (EPI)-loaded in the lipid MBs that was consisted of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]-biotin, dipalmitoyl-phosphatidylglycerol and 25-NBD-cholesterol, then anti-ABCG2 monoclonal antibody (mAb) was conjugated onto the MB surface to form EPI-MBs+mAb. CD138(-)CD34(-)MM CSCs were isolated from human MM RPMI 8226 cell line by the magnetic associated cell sorting method. The results showed that the attenuated proliferation, migration and invasion ability, and increased apoptosis were observed when MM CSCs were incubated with a various agents. EPI-MBs+mAb combined with therapeutic ultrasound significantly promoted the MM CSC apoptosis compared with EPI, EPI-MBs alone or EPI-MBs+mAb without ultrasound exposure. These results suggest that the developed EPI-MBs+mAb combined with therapeutic ultrasound remarkably induced MM CSC apoptosis in vitro.


Assuntos
Transportadores de Cassetes de Ligação de ATP/imunologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Epirubicina/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Proteínas de Neoplasias/imunologia , Terapia por Ultrassom/métodos , 4-Cloro-7-nitrobenzofurazano/análogos & derivados , 4-Cloro-7-nitrobenzofurazano/química , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Apoptose , Movimento Celular , Sobrevivência Celular , Colesterol/análogos & derivados , Colesterol/química , Portadores de Fármacos/química , Resistencia a Medicamentos Antineoplásicos , Epirubicina/administração & dosagem , Epirubicina/farmacologia , Humanos , Microbolhas , Células-Tronco Neoplásicas , Fenótipo
11.
Am J Transl Res ; 7(10): 1870-82, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26692931

RESUMO

Tumor vaccines may induce antitumor efficacy, however, weak immunogenicity of tumor antigens is one of the prime obstacles for excitation of the antitumor immune responses. Therefore, strategies that enhance immunogenicity of tumor vaccines are of particular interest. In this study, a novel melanoma B16F10 CD133(+)CD44(+) cancer stem cell (CSC) vaccine expressing 6 kDa early secreted antigenic target (ESAT-6) in the glycosylphosphatidylinositol (GPI)-anchored form and secreting interleukin (IL)-21 was developed. Its anti-melanoma efficacy and mechanisms were investigated in mice. The results demonstrated that the B16F10-ESAT-6-gpi/IL-21 CD133(+)CD44(+) CSC vaccine exhibited enhanced anti-melanoma efficacy as determined by inhibited melanoma growth, prolonged survival of melanoma bearing mice. The anti-melanoma immunity was associated with elevated levels of serum anti-ESAT-6 and interferon (IFN)-γ as well as increased cytotoxic activities of natural killer cells, splenocytes, and complement dependent cytotoxicity. Furthermore, this CSC-based vaccine apparently inhibited melanoma lung metastasis by decreasing the level of Vimentin while increasing the level of E-cadherin expression, suggesting an inhibited epithelial mesenchymal transition. Thus, the B16F10-ESAT-6-gpi/IL-21 CD133(+)CD44(+) CSC vaccine may be used to reactivate the anti-tumor immunity and for treatment of melanoma.

12.
Biosci Trends ; 9(5): 325-34, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26559025

RESUMO

Increasing evidence supports that cancer stem cells (CSCs) are responsible for driving tumor initiation and maintenance. Zinc-finger E-box binding homeobox 1 (ZEB1) is a transcription factor for regulating tumor progression, and contributes to maintenance of CSC-like properties. The goal of the present study is to investigate the effect of decreasing ZEB1 expression on the B16F10 CSC-like properties. The recombinant shRNA targeting ZEB1 were transfected into melanoma B16F10 cells, and shZEB1-CD133(+)CD44(+) CSCs were isolated from the stable transfected cells using the magnetic-associated cell sorting method. The shZEB1-CD133(+)CD44(+) CSC-like properties were systematically analyzed. The results show the B16F10 shZEB1-CD133(+)CD44(+) CSCs significantly decreased the ability of clonogenicity, cellular proliferation, migration, and invasion. Importantly, tumorigenicity and tumor lung metastasis was significantly inhibited in B16F10 shZEB1-CD133(+)CD44(+) CSCs compared with B16F10 scramble-CD133(+)CD44(+) CSCs. The decrease of ZEB1 expression markedly resulted in down-regulation of vimentin and N-cadherin expression as well as up-regulation of E-cadherin expression in tumor tissues from the mice injected with B16F10 shZEB1-CD44(+)CD133(+) CSCs. These findings contribute to understanding the maintenance of B16F10 CD133(+)CD44(+) CSC-like properties that was closely associated with ZEB1 expression. ZEB1 may serve as a new therapeutic target for treatment of malignant melanoma.


Assuntos
Proteínas de Homeodomínio/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Melanoma Experimental/metabolismo , Células-Tronco Neoplásicas/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Camundongos , Camundongos Endogâmicos C57BL , Invasividade Neoplásica , Metástase Neoplásica , Homeobox 1 de Ligação a E-box em Dedo de Zinco
13.
Oncotarget ; 6(29): 27714-24, 2015 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-26314844

RESUMO

Multiple myeloma (MM) remains to be an incurable disease. The purpose of this study was to evaluate the effect of ABCG2 monoclonal antibody (McAb) combined with paclitaxel (PTX) conjugated with Fe3O4 nanoparticles (NPs) on MM progressed from cancer stem cells (CSCs) in non-obese-diabetic/severe-combined-immunodeficiency (NOD/SCID) mouse model. Mice were injected with MM CSCs as marked by CD138-CD34- phenotypes through tail veins. The developed MM mice were examined by micro-computer tomography scanning, ultrasonography and enzyme-linked immunosorbent analysis. These mice were then intravenously treated with different combinations of NPs, PTX, McAb, PTX-NPs and melphalan/prednisone once a week for four weeks. The injected mice developed characteristic MM-associated syndromes, including lytic bone lesions, renal damages and proteinuria. All the treated mice showed decrease in bone lesions, renal damages and anemia but increase in apoptosis compared with the mice treated with NPs only. In particular, the treatment with ABCG2 McAb plus PTX-NPs induced the strongest therapeutic response and had an efficacy even better than that of melphalan/prednisone, a conventional regimen for MM patients. These data suggest that PTX-NPs with ABCG2 McAb can be developed into potential treatment regimens for patients with relapsed/refractory MM.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Nanopartículas Metálicas/química , Mieloma Múltiplo/tratamento farmacológico , Proteínas de Neoplasias/metabolismo , Paclitaxel/administração & dosagem , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/imunologia , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/química , Antígenos CD34/metabolismo , Apoptose , Osso e Ossos/patologia , Linhagem Celular Tumoral , Portadores de Fármacos/química , Ensaio de Imunoadsorção Enzimática , Eritrócitos/metabolismo , Humanos , Interleucina-6/metabolismo , Melfalan/administração & dosagem , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Pessoa de Meia-Idade , Proteínas de Neoplasias/imunologia , Células-Tronco Neoplásicas/citologia , Fenótipo , Prednisona/administração & dosagem , Sindecana-1/metabolismo , Microtomografia por Raio-X , Ensaios Antitumorais Modelo de Xenoenxerto
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