- TGFB1-driven mesenchymal stem cell-mediated NIS gene transfer. [Journal Article]
- EREndocr Relat Cancer 2018 Aug 18
- Based on their excellent tumor-homing capacity, genetically engineered mesenchymal stem cells (MSCs) are under investigation as tumor-selective gene delivery vehicles. Transgenic expression of the so...
Based on their excellent tumor-homing capacity, genetically engineered mesenchymal stem cells (MSCs) are under investigation as tumor-selective gene delivery vehicles. Transgenic expression of the sodium iodide symporter (NIS) in genetically engineered MSCs allows noninvasive tracking of MSC homing by imaging of functional NIS expression as well as therapeutic application of 131I. The use of tumor-stroma activated promoters can improve tumor-specific MSC-mediated transgene delivery. The essential role of transforming growth factor B1 (TGFB1) and the SMAD downstream target in the signaling between tumor and the surrounding stroma makes the biology of this pathway a potential option to better control NIS expression within the tumor milieu. Bone marrow-derived MSCs were stably transfected with a NIS-expressing plasmid driven by a synthetic SMAD-responsive promoter (SMAD-NIS-MSCs). Radioiodide uptake assays revealed a 4.9-fold increase in NIS-mediated perchlorate-sensitive iodide uptake in SMAD-NIS MSCs after TGFB1 stimulation compared to unstimulated cells demonstrating the successful establishment of MSCs which induce NIS expression in response to activation of TGFB1 signaling using a SMAD-responsive promoter. 123I-scintigraphy revealed significant tumor-specific radioiodide accumulation and thus NIS expression after systemic application of SMAD-NIS-MSCs into mice harboring subcutaneous tumors derived from the human hepatocellular carcinoma (HCC) cell line HuH7, which express TGFB1. 131I therapy in SMAD-NIS-MSCs-treated mice demonstrated a significant delay in tumor growth and prolonged survival. Making use of the tumoral TGFB1 signaling network in the context of MSC-mediated NIS gene delivery is a promising approach to foster tumor stroma-selectivity of NIS transgene expression and tailor NIS-based gene therapy to TGFB1-rich tumor environments.
- Modified Fe3O4 Magnetic Nanoparticle Delivery of CpG Inhibits Tumor Growth and Spontaneous Pulmonary Metastases to Enhance Immunotherapy. [Journal Article]
- NRNanoscale Res Lett 2018 Aug 17; 13(1):240
- As a novel toll-like receptor 9 (TLR9) agonist, synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides can stimulate a Th1 immune response and potentially be used as therapeuti...
As a novel toll-like receptor 9 (TLR9) agonist, synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides can stimulate a Th1 immune response and potentially be used as therapeutic agents or vaccine adjuvants for the treatment of cancer. However, some drawbacks of CpG limit their applications, such as rapid elimination by nuclease-mediated degradation and poor cellular uptake. Therefore, repeat high-dose drug administration is required for treatment. In this work, a CpG delivery system based on 3-aminopropyltriethoxysilane (APTES)-modified Fe3O4 nanoparticles (FeNPs) was designed and studied for the first time to achieve better bioactivity of CpG. In our results, we designed FeNP-delivered CpG particles (FeNP/CpG) with a small average size of approximately 50 nm by loading CpG into FeNPs. The FeNP/CpG particle delivery system, with enhanced cell uptake of CpG in bone marrow-derived dendritic cells (BMDCs) in vitro and through intratumoral injection, showed significant antitumor ability by stimulating better humoral and cellular immune responses in C26 colon cancer and 4T1 breast cancer xenograft models in vivo over those of free CpG. Moreover, mice treated by FeNP/CpG particles had delayed tumor growth with an inhibitory rate as high as 94.4%. In addition, approximately 50% of the tumors in the C26 model appeared to regress completely. Similarly, there were lower pulmonary metastases and a 69% tumor inhibitory rate in the 4T1 breast cancer tumor model than those in the untreated controls. In addition to their effectiveness, the easy preparation, safety, and high stability of FeNP/CpG particles also make them an attractive antitumor immunotherapy.
- Long Non-Coding RNA HULC Promotes Progression of Bone Neoplasms. [Journal Article]
- MSMed Sci Monit 2018 Aug 18; 24:5754-5760
- CONCLUSIONS: LncRNA HULC can promote the tumorigenesis of bone neoplasms through increasing the proliferation, invasion, and migration abilities and the expression level of EMT-related factors.
- Sorafenib in patients with progressed and refractory bone tumors. [Journal Article]
- MOMed Oncol 2018 Aug 16; 35(10):126
- Patients with metastatic, progressive, or recurrent bone tumors have a dismal outcome. Sorafenib has been proposed as an effective salvage regimen for some malignancies. Thus, we sought to evaluate t...
Patients with metastatic, progressive, or recurrent bone tumors have a dismal outcome. Sorafenib has been proposed as an effective salvage regimen for some malignancies. Thus, we sought to evaluate this approach for young patients with relapsed or refractory bone tumors. Twelve patients with refractory bone tumors (two with Ewing sarcoma, two with chondrosarcoma, and eight with osteosarcoma) received salvage treatment with sorafenib. All patients had standard tumor imaging and laboratory evaluation. All toxicities were documented. At the time of the beginning of sorafenib treatment median age among 12 patients was 18 years (range 4.1-27.9 years), eight were male, and eight had osteosarcoma. All received sorafenib because of relapse. Seven patients were treated parallel to other standard chemotherapy. Overall response rate was 75%. Median time to sorafenib time to progression for patients with osteosarcoma was 4 months (range 1.8-7.9 months). Four patients (33%) are alive, in that two with no evidence of disease with a median follow-up of 41 months (range 26.5-60.9 months). The estimated 5 year overall survival (OS) for the whole group was 64.49%. There were no serious toxicities. Sorafenib is well-tolerated in young patients with bone tumors, and particularly could be an option for patients with metastatic disease and refractory osteosarcoma. Sorafenib only allows to extend OS and different procedures are needed to achieve permanent remission. This regimen deserves further investigation in the upfront management of patients with high-risk bone tumors.
- Real-Time Monitoring of Cancer Cells in Live Mouse Bone Marrow. [Journal Article]
- FIFront Immunol 2018; 9:1681
- Disseminated tumor cells in the bone marrow environment are the main cause of systemic metastasis after curative treatment for major solid tumors. However, the detailed biological processes of tumor ...
Disseminated tumor cells in the bone marrow environment are the main cause of systemic metastasis after curative treatment for major solid tumors. However, the detailed biological processes of tumor biology in bone marrow have not been well defined in a real-time manner, because of a lack of a proper in vivo experimental model thereof. In this study, we established intravital imaging models of the bone marrow environment to enable real-time observation of cancer cells in the bone marrow. Using these novel imaging models of intact bone marrow and transplanted bone marrow of mice, respectively, via two-photon microscopy, we could first successfully track and analyze both the distribution and the phenotype of cancer cells in bone marrow of live mouse. Therefore, these novel in vivo imaging models for the bone marrow would provide a valuable tool to identify the biologic processes of cancer cells in a real-time manner in a live animal model.
- Graft-versus-leukaemia effect post fludarabine, melphalan and alemtuzumab reduced intensity allogeneic stem cell transplantat in HIV-infected patient with acute myeloid leukaemia. [Journal Article]
- BMBone Marrow Transplant 2018 Aug 16
- Allogeneic stem cell transplantation (Allo-HSCT) is sine qua non to cure high-risk acute myeloid leukaemia (AML). In spite the advent of highly active antiretroviral treatment, HIV-infected patients ...
Allogeneic stem cell transplantation (Allo-HSCT) is sine qua non to cure high-risk acute myeloid leukaemia (AML). In spite the advent of highly active antiretroviral treatment, HIV-infected patients display a remarkable risk for haematological neoplasms such as non-Hodgkin lymphomas, Hodgkin lymphoma and acute leukaemia. Several case series have confirmed the efficacy of the autologous stem cell transplantation for the treatment of non-Hodgkin lymphomas in the HIV setting. Nonetheless, there is a paucity of data for the role of the Allo-HSCT in HIV-infected individuals with haematological malignancies. Herein, we presented the successful long-term outcome of a HIV-infected patient who received reduced intensity conditioned, matched unrelated donor transplant with alemtuzumab as graft-versus-host disease prophylaxis for therapy-related acute myeloid leukaemia. We propose that Allo-HSCT in HIV patients is safe and that alemtuzumab-based conditioning could further work to eradicate HIV in those whose donor is not CCR5 homozygous.
- Dedifferentiated parosteal osteosarcoma of the maxilla: a case report and review of the literature. [Journal Article]
- JMJ Med Case Rep 2018 Aug 17; 12(1):235
- CONCLUSIONS: Dedifferentiated parosteal osteosarcoma can occur in the head and neck region. Chemotherapy including anthracycline anticancer agent could be effective for high-grade component of dedifferentiated parosteal osteosarcoma.
- Clinicopathological study of 9 cases of megakaryocytes in pleural and peritoneal fluids. [Journal Article]
- MMedicine (Baltimore) 2018; 97(33):e11923
- To systemically analyze megakaryocytes in pleural and peritoneal fluids and their clinical significance. We retrospectively examined 10,846 pleural, peritoneal, and pericardial fluid samples obtained...
To systemically analyze megakaryocytes in pleural and peritoneal fluids and their clinical significance. We retrospectively examined 10,846 pleural, peritoneal, and pericardial fluid samples obtained from 3 hospitals over a 20-year period. Megakaryocytes were observed in the pleural fluid samples from 7 patients and peritoneal fluid samples from 2 patients, and the incidence was 0.83%. The clinical diagnoses of these 9 patients included myeloproliferative disorders, trauma, and tumors. The serous effusions in all 9 patients were bloody, and the megakaryocytes could be associated with trauma, bone marrow pollution, extramedullary hematopoiesis, or cancer. Additionally, differentiating between megakaryocytes and tumor cells or nuclear mesothelial cells in the pleural fluid is difficult. Therefore, megakaryocytes should be carefully observed and differentiated in pleural and peritoneal fluids because they can be confused with other cells in the clinic. Altogether, the megakaryocytes in the pleural and peritoneal fluids were mainly associated with contamination in the bone marrow or extramedullary hematopoiesis.
- Brown tumor of multiple facial bones associated with primary hyperparathyroidism: A clinical case report. [Journal Article]
- MMedicine (Baltimore) 2018; 97(33):e11877
- CONCLUSIONS: As multiple osteolytic lesions of facial bones can be caused by primary HPT, serum calcium and parathyroid hormone assays should be performed routinely when investigating these lesions.
New Search Next
- A novel cross-talk between CXCR4 and PI4KIIIα in prostate cancer cells. [Journal Article]
- OOncogene 2018 Aug 15
- Chemokine signaling regulates cell migration and tumor metastasis. CXCL12, a member of the chemokine family, and its receptor, CXCR4, a G protein coupled receptor (GPCR), are key mediators of prostat...
Chemokine signaling regulates cell migration and tumor metastasis. CXCL12, a member of the chemokine family, and its receptor, CXCR4, a G protein coupled receptor (GPCR), are key mediators of prostate-cancer (PC) bone metastasis. In PC cells androgens activate CXCR4 gene expression and receptor signaling on lipid rafts, which induces protease expression and cancer cell invasion. To identify novel lipid-raft-associated CXCR4 regulators supporting invasion/metastasis, we performed a SILAC-based quantitative proteomic analysis of lipid-rafts derived from PC3 stable cell lines with overexpression or knockdown of CXCR4. This analysis identified the evolutionarily conserved phosphatidylinositol 4-kinase IIIα (PI4KIIIα), and SAC1 phosphatase that dephosphorylates phosphatidylinositol-4-phosphate as potential candidate CXCR4 regulators. CXCR4 interacted with PI4KIIIα membrane targeting machinery recruiting them to the plasma membrane for PI4P production. Consistent with this interaction, PI4KIIIα was found tightly linked to the CXCR4 induced PC cell invasion. Thus, ablation of PI4KIIIα in CXCR4-expressing PC3 cells reduced cellular invasion in response to a variety of chemokines. Immunofluorescence microscopy in CXCR4-expressing cells revealed localized production of PI4P on the invasive projections. Human tumor studies documented increased PI4KIIIα expression in metastatic tumors vs. the primary tumor counterparts, further supporting the PI4KIIIα role in tumor metastasis. Furthermore, we also identified an unexpected function of PI4KIIIα in GPCR signaling where CXCR4 regulates PI4KIIIα activity and mediate tumor metastasis. Altogether, our study identifies a novel cross-talk between PI4KIIIα and CXCR4 in promoting tumor metastasis and suggests that PI4KIIIα pharmacological targeting may have therapeutic benefit for advanced prostate cancer patients.