[Show abstract][Hide abstract] ABSTRACT: Background
Epithelial-mesenchymal transition (EMT) played an important role in the progression of hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA). However, whether sorafenib could be used to suppress the EMT of HCC after insufficient RFA and further prevent the progression of residual HCC remains poorly unknown.
Insufficient RFA was simulated using a water bath (47 °C 5, 10, 15, 20 and 25 min gradually). MTT assay and transwell assay were used to evaluate the effects of sorafenib on viability, migration and invasion of HepG2 and SMMC7721 cells after insufficient RFA in vitro. After insufficient RFA, the molecular changes in HCC cells with the treatment of sorafeinb were evaluated using western blot and ELISAs. An ectopic nude mice model was used to evaluate the effect of sorafenib on the growth of HepG2 cells in vivo after insufficient RFA.
HepG2 and SMMC7721 cells after insufficient RFA (named as HepG2-H and SMMC7721-H) exhibited enhanced viability, migration and invasion in vitro. Sorafenib inhibited the enhanced viability, migration and invasion of HepG2 and SMMC7721 cells after insufficient RFA. Molecular changes of EMT were observed in HepG2-H and SMMC7721-H cells. Sorafenib inhibited the EMT of HepG2-H and SMMC7721-H cells. HepG2-H cells also exhibited larger tumor size in vivo. Higher expression of PCNA, Ki67, N-cadherin, MMP-2 and MMP-9, was also observed in HepG2-H tumors. Sorafenib blocked the enhanced growth of HepG2 cells in vivo after insufficient RFA.
Sorafenib inhibited the EMT of HCC cells after insufficient RFA, and may be used to prevent the progression of HCC after RFA.
Electronic supplementary material
The online version of this article (doi:10.1186/s12885-015-1949-7) contains supplementary material, which is available to authorized users.
[Show abstract][Hide abstract] ABSTRACT: Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) formation is a rare entity found microscopically in 1% to 9.2% of resected specimens. The ideal treatment for HCC is surgical resection. However, because of poor hepatic functional reserve in patients with HCC, most tumors are unresectable. Here, we report 2 cases of HCC with BDTT type III accompanied by hepatic dysfunction that were successfully treated with radiofrequency (RF) ablation. We used RF ablation as both a radical therapeutic method and an efficient way to control bleeding from the origin of BDTT after BDTT removal. At the time of writing, the 2 patients have been disease-free for 16 and 12 months, respectively.
Our results show that RF ablation may be used as a radical therapeutic alternative for HCC with BDTT in patients with liver cirrhosis and obstructive jaundice.
[Show abstract][Hide abstract] ABSTRACT: microRNAs (miRNAs) have been reported to modulate macrophage colony-stimulating factor (M-CSF) and macrophages. The aim of this study was to find whether miR-26a can suppress M-CSF expression and the recruitment of macrophages.
Hepatocellular carcinoma (HCC) cell lines with decreased or increased expression of miR-26a were established in a previous study. M-CSF expression by tumor cells was measured by enzyme-linked immunosorbent assay, and cell migration assays were used to explore the effect of HCC cell lines on macrophage recruitment in vitro. Real-time PCR measured a panel of mRNAs expressed by macrophages. Xenograft models were used to observe tumor growth. Immunohistochemistry was conducted to study the relation between miR-26a expression and M-CSF expression and macrophage recruitment in patients with HCC.
Ectopic expression of miR-26a reduced expression of M-CSF. The conditioned medium (CM) from HepG2 cells that overexpressed miR-26a reduced the migration ability of THP-1 cells stimulated by phorbol myristate acetate (PMA) increased expression of interleukin (IL)-12b or IL-23 mRNA and decreased expression of chemokine (C-C motif) ligand (CCL)22, CCL17, and IL-10 mRNA, in comparison to the medium from the parental HepG2 cells. These effects could be interrupted by the PI3K/Akt pathway inhibitor LY294002. Ectopic expression of miR-26a in HCC cells suppressed tumor growth, M-CSF expression, and infiltration of macrophages in tumors. Similar results were also found when using HCCLM3 cells. Furthermore, the expression of miR-26a was inversely correlated with M-CSF expression and macrophage infiltration in tumor tissues from patients with HCC.
miR-26a expression reduced M-CSF expression and recruitment of macrophages in HCC.
Preview · Article · May 2015 · Journal of Hematology & Oncology
[Show abstract][Hide abstract] ABSTRACT: To compare safety and therapeutic efficacy of laparoscopic radiofrequency (RF) ablation vs computed tomography (CT)-guided RF ablation for large hepatic hemangiomas abutting the diaphragm.
We retrospectively reviewed our sequential experience of treating 51 large hepatic hemangiomas abutting the diaphragm in 51 patients by CT-guided or laparoscopic RF ablation due to either the presence of symptoms and/or the enlargement of hemangioma. Altogether, 24 hemangiomas were ablated via a CT-guided percutaneous approach (CT-guided ablation group), and 27 hemangiomas were treated via a laparoscopic approach (laparoscopic ablation group).
The mean diameter of the 51 hemangiomas was 9.6 ± 1.8 cm (range, 6.0-12.0 cm). There was no difference in the diameter of hemangiomas between the two groups (P > 0.05). RF ablation was performed successfully in all patients. There was no difference in ablation times between groups (P > 0.05). There were 23 thoracic complications in 17 patients: 15 (62.5%, 15/24) in the CT-guided ablation group and 2 (7.4%, 2/27) in the laparoscopic ablation group (P < 0.05). According to the Dindo-Clavien classification, two complications (pleural effusion and diaphragmatic rupture grade III) were major in two patients. All others were minor (grade I). Both major complications occurred in the CT-guided ablation group. The minor complications were treated successfully with conservative measures, and the two major complications underwent treatment by chest tube drainage and thoracoscopic surgery, respectively. Complete ablation was achieved in 91.7% (22/24) and 96.3% (26/27) in the CT-guided and the laparoscopic ablation groups, respectively (P > 0.05).
Laparoscopic RF ablation therapy should be used as the first-line treatment option for large hepatic hemangiomas abutting the diaphragm. It avoids thermal injury to the diaphragm and reduces thoracic complications.
[Show abstract][Hide abstract] ABSTRACT: Alternative splicing of VEGF-A gives rise to two families - the pro-angiogenic VEGFxxx family and the anti-angiogenic VEGFxxxb family that differ by only six amino acids at their C-terminal end. The first verified and widely reported VEGFxxxb family member is VEGF165b, and here VEGF165b is a positive control.
VEGF111b mRNA was detected in ovarian cancer cell lines SKOV3 and OVCAR3 by RT-PCR. Western blot was used to detect VEGF111b and VEGF165b protein in the CMs and lysates of OVCAR3 cells. MTT and colony formation assay were used to detect the short-term and long-term proliferation inhibition ability of ovarian cancer cells with VEGF111b overexpression. Cell-cycle analysis was performed to further characterize VEGF111b inhibition effects. VEGF111b signaling on ovarian cancer cells were determined by western blot. The expression levels of Ki67, PCNA, CD31 and VEGF in VEGF111b overexpression xenograft model were detected by immunohistochemistry.
Under the effect of mitomycin C, we identify a new member of VEGFxxxb family-VEGF111b in ovarian cancer cell lines. SKOV3 and OVCAR cells were transfected with empty lentivirus, VEGF111b or VEGF165b lentivirus. VEGF111b and VEGF165b overexpression inhibits proliferation of the ovarian cancer cells, but inhibition effect of VEGF111b is slightly less efficient than VEGF165b. Cell cycle analysis was further used to elucidate the mechanism involved in the inhibition effect. Further, we detected the expression of VEGF-R2 in SKOV3 and OVCAR3 cells, and shown that VEGF111b might bind to conventional VEGF-R2 with the results of reducing VEGF-R2 tyrosine phosphorylation and downstream signaling to have anti-tumor effects. In vivo VEGF111b overexpression inhibits ovarian cancer growth in xenograft mice.
Our results show that VEGF111b, as a new member of VEGFxxxb family, with similar properties to VEGF165b, plays potent anti-tumor effect in vitro and in vivo that can target the VEGF-R2 and its signaling pathway to inhibit ovarian tumor growth. This also opens a new avenue for treating ovarian cancer.
Full-text · Article · May 2015 · Journal of Translational Medicine
[Show abstract][Hide abstract] ABSTRACT: Dextran-coated superparamagnetic iron oxide nanoparticles (DSPIONs) have gained considerable interest, because of their biocompatibility and biosafety in clinics. Doxorubicin (Dox), a widely used chemotherapeutic drug, always has limited applications in clinical therapy due to its serious side effects of dose-limiting irreversible cardiotoxicity and myelo suppression. Herein, DSPIONs were synthesized and developed as magnetic carriers for doxorubicin. The Dox-DSPIONs conjugates were evaluated in in vitro test of Dox release, which showed pH-dependence with the highest release percentage of 50.3% at pH 5.0 and lowest release percentage of 11.8% in physiological environment. The cytotoxicity of DSPIONs and Dox-DSPIONs evaluated by MTT assay indicated that DSPIONs had no cytotoxicity and the conjugates had significantly reduced the toxicity (IC50=1.36 μg mL-1) compared to free Dox (IC50=0.533 μg mL-1). Furthermore, confocal microscopic data of cell uptake suggest that the less cytotoxicity of Dox-DSPIONs may be attributed by the cellular internalization of the conjugates and sustainable release of DOX from the formulation in the cytoplasm. More importantly, the results from rabbit VX2 liver tumor model test under the external magnetic field showed that the conjugates had approximately twice anti-tumor activity and two and half folds of animal survival rate, respectively, compared to free Dox. Collectively, our data have demonstrated that Dox-DSPIONs have the less toxicity with better antitumor effectiveness in in vitro and in vivo application, suggesting that the conjugates have potentials to be developed into chemo-therapeutic formulations.
[Show abstract][Hide abstract] ABSTRACT: Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft-tissue sarcoma for which there is no standardized treatment regimen available. The current treatment options for SEF are resection, radiation and chemotherapy. Surgical resection remains the mainstay of therapy for SEF. However, SEF is an aggressive tumor that is prone to repeated local recurrence if not widely excised. Radiation and chemotherapy are less commonly used due to the insensitivity of SEF to these therapies. The treatment of recurrent SEF is even more challenging. The present study describes a patient who presented with a giant recurrent SEF arising from the chest wall that was accompanied by emergent bleeding. The patient was a 70-year-old male who had multiple comorbid diseases, including hypertension and chronic cardiac dysfunction. A computed tomography (CT) scan indicated the involvement of the sternum and anterior mediastinum. However, the patient refused any further surgery. Subsequent to careful discussion and consideration, radiofrequency (RF) ablation and percutaneous iodine-125 implantation was administered. The emergent bleeding was successfully stopped and the tumor was eliminated using RF ablation. Percutaneous iodine-125 implantation under CT guidance established effective control on the growth of the tumor involving the mediastinum. Despite this, the tumor recurred 6 months after treatment. The patient refused any further treatment and was discharged. In conclusion, RF ablation and percutaneous permanent iodine-125 implantation is a feasible and safe salvage therapy for patients with recurrent SEF of the chest wall.
[Show abstract][Hide abstract] ABSTRACT: Accumulating evidences have reported that caffeine has anticancer effectsat high blood concentrations. However, whether caffeine hasanticancer effectson human hepatocellular carcinoma (HCC)cells at low concentration,especially at physiologically applicableconcentration (< 412 μM)is still not well understood.In this study, HCCcell linesHepG2and Huh7 were used.The cells were incubatedwith varying concentrations of caffeine (0, 50,100,200,400 or 600μM). MTT assay was used to investigatethe proliferation ability in vitro. Migration and invasionabilitieswere determined by wound healing assay and transwell assay. The molecular changeswere detected by westernblot. An ectopic nude mice model which the mice were gavaged with caffeine wasused to reveal the anticancereffectsof caffeine on HepG2 cells in vivo. Results showed that caffeine could inhibit the proliferation, migration and invasion significantly at physiologically applicable concentrationin vitro. Also the associated molecular changes of cancerprogression were observed. In animal experiment, the mice gavaged with caffeine also performanced reduced tumor burden in vivo.Moreover, the interrelated protein expression was also observed in vivowhich was coincident with the results in vitro.All in all, this observation indicated that caffeine may suppress the progression of HCC through Akt signaling pathway. This makes caffeine a potential candidate for treating HCC which will be a safer and more effective treatment by giving for a long time at physiologically applicableconcentration.
Full-text · Article · Feb 2015 · Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents)
[Show abstract][Hide abstract] ABSTRACT: Traditional systemic chemotherapy does not provide survival benefits in patients with hepatocellular carcinoma (HCC). Molecular targeted therapy shows promise for HCC treatment, however, the duration of effectiveness for targeted therapies is finite and combination therapies offer the potential for improved effectiveness.
Sorafenib, a multikinase inhibitor, and YC-1, a soluble guanylyl cyclase (sGC) activator, were tested in HCC by proliferation assay, cell cycle analysis and western blot in vitro and orthotopic and ectopic HCC models in vivo.
In vitro, combination of sorafenib and YC-1 synergistically inhibited proliferation and colony formation of HepG2, BEL-7402 and HCCLM3 cells. The combination also induced S cell cycle arrest and apoptosis, as observed by activated PARP and caspase 8. Sorafenib and YC-1 respectively suppressed the expression of phosphorylated STAT3 (p-STAT3) (Y705) in a dose- and time-dependent manner. Combination of sorafenib and YC-1 significantly inhibited the expression of p-STAT3 (Y705) (S727), p-ERK1/2, cyclin D1 and survivin and SHP-1 activity compared with sorafenib or YC-1 used alone in all tested HCC cell lines. In vivo, sorafenib-YC-1 combination significantly suppressed the growth of HepG2 tumor xenografts with decreased cell proliferation and increased apoptosis observed by PCNA and PARP. Similar results were also confirmed in a HCCLM3 orthotopic model. There was a reduction in CD31-positive blood vessels and reduced VEGF expression, which suggested a combinational effect of sorafenib and YC-1 on angiogenesis. The reduced expression of p-STAT3, cyclin D1 and survivin was also observed with the combination of sorafenib and YC-1.
Our data show that sorafenib-YC-1 combination is a novel potent therapeutic agent that can target the STAT3 signaling pathway to inhibit HCC tumor growth.
[Show abstract][Hide abstract] ABSTRACT: Residual tumor progression after insufficient radiofrequency ablation (RFA) has been recently reported. However, whether epithelial-mesenchymal transition (EMT), which is a key process that drives cancer metastasis, is involved in the tumor progression after insufficient RFA is not well understood.
Human hepatocellular carcinoma (HCC) cell lines SMMC7721 and Huh7 were used. Insufficient RFA was simulated using a water bath (47[degree sign]C 5 min, 10 min, 15 min, 20 min and 25 min gradually). MTT assay was used to evaluate the proliferation of HCC cells in vitro. Migration and invasion of HCC cells were determined by transwell assay. The molecular changes in HCC cells after insufficient RFA were evaluated by western blot. LY294002 and PD98059 were used to treat HCC cells. An ectopic nude mice model and a tail vein metastatic assay were used to evaluate the growth and metastatic potential of SMMC7721 cells in vivo after insufficient RFA.
SMMC7721 and Huh7 cells after insufficient RFA (named as SMMC7721-H and Huh7-H respectively) exhibited enhanced proliferation, migration and invasion (6.4% and 23.6%, 33.2% and 66.1%, and 44.1% and 57.4% increase respectively) in vitro. Molecular changes of EMT were observed in SMMC7721-H and Huh7-H cells. LY294002 and PD98059 inhibited the EMT of SMMC7721-H and Huh7-H cells. SMMC7721-H cells also exhibited larger tumor size (1440.8 +/- 250.3 mm3 versus 1048.56 +/- 227.6 mm3) and more lung metastasis (97.4% increase) than SMMC7721 cells in vivo. Higher expression of PCNA, N-cadherin and MMP-2 and MMP-9, was also observed in SMMC7721-H tumors.
Insufficient RFA could directly promote the invasiveness and metastasis of HCC cells. Insufficient RFA may promote the EMT of HCC cells through Akt and ERK signaling pathways.
Full-text · Article · Oct 2013 · Journal of Translational Medicine
[Show abstract][Hide abstract] ABSTRACT: microRNAs (miRNAs) have been reported to regulate angiogenesis by down-regulating the expression of pro-angiogenic or anti-angiogenic factors. The aims of this study were to investigate whether miR-26a inhibited angiogenesis by down-regulating vascular endothelial growth factor A (VEGFA) and its clinical relevance in hepatocellular carcinoma (HCC).
The expression of miR-26a was modified in HepG2 and HCCLM3 cell lines respectively, and a panel of angiogenic factors was measured by real-time PCR in the cells. A luciferase reporter assay was used to validate the target gene of miR-26a. Specific inhibitors of signal transduction pathway and siRNA approaches were used to explore the regulatory mechanism of miR-26a. Migration and tube forming assays were conducted to show the changes of angiogenesis induced by miR-26a and its target genes. Finally animal studies were used to further validate those findings.
Ectopic expression of miR-26a exhibited decreased levels of VEGFA in HepG2 cells. Migration and tube forming of human umbilical vein endothelial cells (HUVECs) were decreased in the conditioned medium from ectopic expression of miR-26a in HepG2 cells compared to control HepG2 cells. The pro-angiogenic effects of the conditioned medium of HepG2 cells on HUVECs were specifically decreased by LY294002, YC-1, and bevacizumab. Integrated analysis disclosed PIK3C2α as a downstream target gene of miR-26a. Ectopic expression of miR-26a suppressed ectopic and orthotopic tumor growth and vascularity in nude mice. The results in HCCLM3 were consistent with those in HepG2. miR-26a expression was inversely correlated with VEGFA expression in HCC patients.
miR-26a modulated angiogenesis of HCC through the PIK3C2α/Akt/HIF-1α/VEGFA pathway. The expression of VEGFA was inversely correlated with miR-26a expression in HCC tumors.
[Show abstract][Hide abstract] ABSTRACT: Vascular endothelial growth factor (VEGF-A) stimulating angiogenesis is required for tumor growth and progression. The conventional VEGF-A isoforms have been considered as pro-angiogenic factors. Another family of VEGF-A isoforms generated by alternative splicing, termed VEGFxxxb isoforms, has anti-angiogenic property, exemplified by VEGF165b. Here, we identify a new number of VEGFxxx family-VEGF111b induced by mitomycin C, although not detected in mitomycin C-unexposed ovarian cancer cells. SKOV3 cells were transfected with pcDNA3.1 empty vector, pcDNA3.1-VEGF111b or pcDNA3.1-VEGF165b to collect conditioned mediums respectively. VEGF111b overexpression inhibits proliferation, migration and tube formation of endothelial cell by inhibiting VEGF-R2 phosphorylation and its downstream signaling, similar to VEGF165b but slightly lower than VEGF165b. The anti-angiogenic property depends on the six amino acids of exon 8b of the VEGFxxxb isoforms. Our results show that VEGF111b is a novel potent anti-angiogenic agent that can target the VEGF-R2 and its signaling pathway to inhibit ovarian tumor growth.
Full-text · Article · Oct 2013 · Biochemical and Biophysical Research Communications
[Show abstract][Hide abstract] ABSTRACT: Background
The mechanism regarding rapid progression of residual hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA) has been preliminarily discussed. However, most studies have mainly focused on RFA-induced changes in the tumor cells. The present study was designed to determine whether tumor-associated endothelial cells (TAECs) could contribute to the invasiveness of HCC after insufficient RFA.
TAECs were isolated from fresh HCC tissue and characterized. Morphological changes were observed in TAECs after heat treatment for 10 min. TAEC proliferation, migration and tube formation after heat treatment for 10 min at 37°C (control group), and 42 and 47°C (insufficient RFA groups) were examined. The differences in TAECs interactions with HepG2-GFP or HCCLM3-GFP cells among the two insufficient RFA groups and control group were evaluated. The expression of E-selectin, ICAM-1 and VCAM-1 in TAECs was measured. The effects of TAECs on the invasiveness of HepG2-GFP or HCCLM3-GFP cells after insufficient RFA were analyzed. The IL-6, IL-8, MCP-1 and GRO-α concentrations in conditioned medium from TAECs were measured after insufficient RFA. The associated signaling pathways of Akt, ERK1/2, STAT3 and NF-κB were analyzed in TAECs after insufficient RFA.
TAECs expressed the EC-specific markers and took up complexes of Dil-Ac-LDL. Relative to the control group, the proliferation of TAECs was significantly inhibited and their migration and tube formation were significantly enhanced in the insufficient RFA groups. Significantly more HepG2-GFP or HCCLM3-GFP cells adhered to TACEs in these groups than in the control group (all P<0.001), via up-regulated expression of E-selectin, ICAM-1 and VCAM-1. TAECs promoted the invasiveness of HepG2-GFP or HCCLM3-GFP cells after insufficient RFA via the up-regulation of IL-6, IL-8, MCP-1 and GRO-α in conditioned medium (all P<0.05). Insufficient RFA enhanced the activities of Akt, ERK1/2 and NF-κB signaling pathways and inhibited STAT3 signaling pathways.
Insufficient RFA enhanced TAEC migration and tube formation, and this may play a key role in the rapid growth of residual HCC. Increased expression of metastasis-related molecules in TAECs after insufficient RFA may be a potential mechanism for the metastasis of residual HCC.
Full-text · Article · Nov 2012 · Journal of Translational Medicine
[Show abstract][Hide abstract] ABSTRACT: The mechanism of rapid growth of the residual tumor after radiofrequency (RF) ablation is poorly understood. In this study, we investigated the effect of hyperthermia on HepG2 cells and generated a subline with enhanced viability and dys-regulated angiogenesis in vivo, which was used as a model to further determine the molecular mechanism of the rapid growth of residual HCC after RF ablation.
Heat treatment was used to establish sublines of HepG2 cells. A subline (HepG2 k) with a relatively higher viability and significant heat tolerance was selected. The cellular protein levels of VEGFA, HIF-1α and p-Akt, VEGFA mRNA and secreted VEGFA were measured, and all of these were up-regulated in this subline compared to parental HepG2 cells. HIF-1α inhibitor YC-1 and VEGFA siRNA inhibited the high viability of the subline. The conditioned media from the subline exerted stronger pro-angiogenic effects. Bevacizumab, VEGFA siRNA and YC-1 inhibited proangiogenic effects of the conditioned media of HepG2 k cells and abolished the difference between parental HepG2 cells and HepG2 k cells. For in vivo studies, a nude mouse model was used, and the efficacy of bavacizumab was determined. HepG2 k tumor had stronger pro-angiogenic effects than parental HepG2 tumor. Bevacizumab could inhibit the tumor growth and angiogenesis, and also eliminate the difference in tumor growth and angiogenesis between parental HepG2 tumor and HepG2 k tumor in vivo.
The angiogenesis induced by HIF1α/VEGFA produced by altered cells after hyperthermia treatment may play an important role in the rapid growth of residual HCC after RF ablation. Bevacizumab may be a good candidate drug for preventing and treating the process.
[Show abstract][Hide abstract] ABSTRACT: Epidemiologic studies suggested complicated associations between type 2 diabetes mellitus and breast cancer. High-density lipoprotein (HDL) is inversely associated with the risk and mortality of breast cancer. Our study is to determine the different effects of normal and diabetic HDL on breast cancer cell metastasis.
MDA-MB-231 and MCF7 cells were treated with N-HDL, D-HDL, G-HDL, and Ox-HDL. Cell metastasis potency was examined using a tail-vein injection model, and cell adhesion abilities to human umbilical vein endothelial cells (HUVEC) and extracellular matrix (ECM) were determined in vitro. Integrin expression and protein kinase C (PKC) activity were evaluated, and PKC inhibitor was applied.
D-HDL dramatically promoted cell pulmonary metastasis (103.6% increase at P < 0.001 for MDA-MB-231 with 1 × 10(5) cell injection; 157.1% increase at P < 0.05 for MCF7 with 4 × 10(5) cell injection) and hepatic metastasis (18.1-fold increase at P < 0.001 for MCF7 with 4 × 10(5) cell injection), and stimulated higher TC-HUVECs adhesion (21.9% increase at P < 0.001 for MDA-MB-231; 23.6% increase at P < 0.05 for MCF7) and TC-ECM attachment (59.9% and 47.9% increase, respectively, for MDA-MB-231 and MCF7, both at P < 0.01) compared with N-HDL. D-HDL stimulated higher integrin (β1, β2, β3, and αν) expression on cell surface and induced higher PKC activity. Increased TC-HUVECs and TC-ECM adhesion induced by D-HDL, G-HDL, and Ox-HDL could be inhibited by staurosporine.
Our study showed that glycation and oxidation of HDL in diabetic patients could lead to abnormal actions on breast cancer cell adhesion to HUVECs and ECM, thereby promoting metastasis progression of breast cancer. This will largely draw the attention of HDL-based treatments in the diabetes patients with breast cancer.
Full-text · Article · Mar 2012 · Clinical Cancer Research
[Show abstract][Hide abstract] ABSTRACT: Rapid progression of residual tumor after radiofrequency ablation (RFA) of hepatocellular carcinoma has been observed increasingly. However, its underlying mechanisms remain to be clarified. The present study was designed to determine whether low temperature of RFA at the target sites facilitates rapid progression of residual hepatic VX2 carcinoma and to clarify the possible underlying mechanisms.
The residual VX2 hepatoma model in rabbits was established by using RFA at 55, 70 and 85 degrees C. Rabbits that were implanted with VX2 hepatoma but did not receive RFA acted as a control group. The relationship between rapid progression of residual hepatic VX2 carcinoma and low temperature of RFA at the target sites was carefully evaluated. A number of potential contributing molecular factors, such as proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and Interleukin-6 (IL-6) were measured.
The focal tumor volume and lung metastases of RFA-treated rabbits increased significantly compared with the control group (P < 0.05), and the greatest changes were seen in the 55 degrees C group (P < 0.05). Expression of PCNA, MMP-9, VEGF, HGF and IL-6 in tumor tissues increased significantly in the RFA-treated groups compared with the control group, and of the increases were greatest in the 55 degrees C group (P < 0.05). These results were consistent with gross pathological observation. Tumor re-inoculation experiments confirmed that low temperature of RFA at the target sites facilitated rapid progression of residual hepatic VX2 carcinoma.
Insufficient RFA that is caused by low temperature at the target sites could be an important cause of rapid progression of residual hepatic VX2 carcinoma. Residual hepatic VX2 carcinoma could facilitate its rapid progression through inducing overexpression of several molecular factors, such as PCNA, MMP-9, VEGF, HGF and IL-6.
Preview · Article · Jul 2010 · Journal of Translational Medicine