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1.  Significantly increased expression of OCT4 and ABCG2 in spheroid body-forming cells of the human gastric cancer MKN-45 cell line 
Oncology Letters  2013;6(4):891-896.
The cancer stem cell (CSC) theory hypothesizes that CSCs are the cause of tumor formation, recurrence and metastasis. Key to the study of CSCs is their isolation and identification. The present study investigated whether spheroid body-forming cells in the human gastric cancer (GC) MKN-45 cell line are enriched for CSC properties, and also assessed the expression of the candidate CSC markers, octamer-binding transcription factor-4 (OCT4) and adenosine triphosphate-binding cassette transporter G2 (ABCG2) in the MKN-45 spheroid body cells. The MKN-45 cells were plated in a stem cell-conditioned culture system to allow for spheroid body formation. The expression levels of OCT4 and ABCG2 in the spheroid body cells were assessed by qPCR, western blot analysis and immunofluorescence staining, while the tumorigenicity of the spheroid body-forming cells was assessed by in vivo xenograft studies in nude mice. The MKN-45 cells were able to form spheroid bodies when cultured in stem cell-conditioned medium. The spheroid body-forming cells showed a significantly higher (P<0.01) expression of OCT4 and ABCG2 compared with the parental cells. These data suggest that the spheroid body cells from the MKN-45 GC cell line cultured in stem cell-conditioned medium possessed gastric CSC properties. The co-expression of OCT4 and ABCG2 by these cells may represent the presence of a subpopulation of gastric CSCs.
doi:10.3892/ol.2013.1506
PMCID: PMC3796425  PMID: 24137432
human gastric cancer; cancer stem cell; OCT4; ABCG2
2.  CCN3 (NOV) regulates proliferation, adhesion, migration and invasion in clear cell renal cell carcinoma 
Oncology Letters  2012;3(5):1099-1104.
The CCN3/nephroblastoma overexpressed gene belongs to the CCN family of genes that encode secreted proteins involved in a variety of processes including tumorigenesis. Altered expression of CCN3 has been observed in human nephroblastoma and renal cell carcinoma (RCC), suggesting that CCN3 plays a role in kidney tumorigenesis. The aim of the present study was to examine the role of CCN3 in clear cell RCC biology. In particular, we studied the expression of CCN3 in 32 pairs of RCC tissues and corresponding normal kidney tissues using immunohistochemistry. The CCN3 gene was transfected into the 786-O cell line and the behaviors of stably transfected clones were analyzed. Results showed the expression of CCN3 was lower in RCC tissues compared to corresponding normal kidney tissues and the expression of CCN3 was inversely correlated with the Ki67 index. CCN3-expressing clones exhibited significantly inhibited cell proliferation. Furthermore, CCN3-transfected 786-O cells exhibited increased adhesion to extracellular matrix proteins, migration and invasion in Matrigel. Our data indicated that CCN3 plays an anti-proliferative role in clear cell RCC cells and promotes the adhesion, migration and invasion of clear cell RCC cells.
doi:10.3892/ol.2012.607
PMCID: PMC3389651  PMID: 22783399
renal cell carcinoma; CCN3; migration; tumorigenicity
3.  Suppression effect of recombinant adenovirus vector containing hIL-24 on Hep-2 laryngeal carcinoma cells 
Oncology Letters  2014;7(3):771-777.
The melanoma differentiation-associated gene-7 [MDA-7; renamed interleukin (IL)-24] was isolated from human melanoma cells induced to terminally differentiate by treatment with interferon and mezerein. MDA-7/IL-24 functions as a multimodality anticancer agent, possessing proapoptotic, antiangiogenic and immunostimulatory properties. All these attributes make MDA-7/IL-24 an ideal candidate for cancer gene therapy. In the present study, the human MDA-7/IL-24 gene was transfected into the human laryngeal cancer Hep-2 cell line and human umbilical vein endothelial cells (HUVECs) with a replication-incompetent adenovirus vector. Reverse transcription polymerase chain reaction and western blot analysis confirmed that the Ad-hIL-24 was expressed in the two cells. The expression of the antiapoptotic gene, Bcl-2, was significantly decreased and the IL-24 receptor was markedly expressed in Hep-2 cells following infection with Ad-hIL-24, but not in HUVECs. In addition, the expression of the proapoptotic gene, Bax, was induced and the expression of caspase-3 was increased in the Hep-2 cells and HUVECs. Methyl thiazolyl tetrazolium assay indicated that Ad-hIL-24 may induce growth suppression in Hep-2 cells but not in HUVECs. In conclusion, Ad-hIL-24 selectively inhibits proliferation and induces apoptosis in Hep-2 cells. No visible damage was found in HUVECs. Therefore, the results of the current study indicated that Ad-hIL-24 may have a potent suppressive effect on human laryngeal carcinoma cell lines, but is safe for healthy cells.
doi:10.3892/ol.2014.1789
PMCID: PMC3919867  PMID: 24527085
human interleukin-24; adenovirus; Hep-2; apoptosis; human umbilical vein endothelial cell
4.  Local hyperthermia for esophageal cancer in a rabbit tumor model: Magnetic stent hyperthermia versus magnetic fluid hyperthermia 
Oncology Letters  2013;6(6):1550-1558.
Magnetic-mediated hyperthermia (MMH) is a promising local thermotherapy approach for cancer treatment. The present study investigated the feasibility and effectiveness of MMH in esophageal cancer using a rabbit tumor model. The therapeutic effect of two hyperthermia approaches, magnetic stent hyperthermia (MSH), in which heat is induced by the clinical stent that is placed inside the esophagus, and magnetic fluid hyperthermia (MFH), where magnetic nanoparticles are applied as the agent, was systematically evaluated. A rabbit esophageal tumor model was established by injecting VX2 carcinoma cells into the esophageal submucosa. The esophageal stent was deployed perorally into the tumor segment of the esophagus. For the MFH, magnetic nanoparticles (MNPs) were administered to the rabbits by intratumoral injection. The rabbits were exposed under a benchtop applicator using an alternative magnetic field (AMF) with 300 kHz frequency for the hyperthermia treatment. The results demonstrated that esophageal stents and MNPs had ideal inductive heating properties upon exposure under an AMF of 300 kHz. MSH, using a thermal dose of 46°C with a 10-min treatment time, demonstrated antitumor effects on the rabbit esophageal cancer. However, the rabbit esophageal wall is not heat-resistant. Therefore, a higher temperature or longer treatment time may lead to necrosis of the rabbit esophagus. MFH has a significant antitumor effect by confining the heat within the tumor site without damaging the adjacent normal tissues. The present study indicates that the two hyperthermia procedures have therapeutic effects on esophageal cancer, and that MFH may be more specific than MSH in terms of temperature control during the treatment.
doi:10.3892/ol.2013.1618
PMCID: PMC3833863  PMID: 24260045
magnetic mediated hyperthermia; esophageal cancer; magnetic nanoparticles; esophageal stent; alternative magnetic field
5.  Cloning and expression analysis of the gastric carcinoma-related gene, ELCOX3 
Oncology Letters  2013;6(6):1744-1748.
Gastric cancer is a pathological process of an accumulation of multigene and multistage mutations. A new gene segment, MDSCBC11, has been previously obtained using a gene chip and is negatively associated with gastric cancer. The present study aimed to clone the full cDNA sequence of the MDSCBC11 segment and to detect its expression in gastric carcinomas and normal gastric mucosa. Multiple-tissue northern blots revealed that the new MDSCBC11-represented gene was expressed as two transcripts that were 0.8 kb and 1.5 kb in size. The cDNA sequence of the smaller transcript was 822 bp, created by 5′ rapid amplification of cDNA ends (RACE) and 3′ RACE methods. A bioinformatics analysis indicated that the deduced amino acid sequence of MDSCBC11 had a 99% homology with the cytochrome c oxidase III (COX3) gene in the mitochondria. A total of 46 cases of gastric carcinomas, adjacent gastric mucosa and normal gastric mucosa were individually collected, and the mRNA expression of the ELCOX3 gene was detected by RT-PCR. ELCOX3 mRNA was expressed in all 46 cases of the normal gastric mucosa. The expression levels of ELCOX3 mRNA in the gastric carcinomas were lower compared with that of the adjacent and normal gastric mucosa (P<0.05), with the percent of downregulation at 23.91% (11/46 cases). The downregulation of ELCOX3 gene expression was associated with the development of human gastric carcinomas.
doi:10.3892/ol.2013.1595
PMCID: PMC3834307  PMID: 24260070
gastric carcinoma; gene; cytochrome c oxidase; ELCOX3; MDSCBC11
6.  Anti-proliferative effects of anandamide in human hepatocellular carcinoma cells 
Oncology Letters  2012;4(3):403-407.
In our previous study, we reported that the cannabinoid receptors CB1 and CB2 are overexpressed in human hepatocellular carcinoma (HCC) tissues. Recently, the antitumor potential of the endogenous cannabinoid anandamide (AEA) has also been addressed. The present study was conducted to investigate the anti-proliferative effects of AEA in HCC cells. The human HCC cell line Huh7 was used. Cell proliferation was measured by MTT assay and flow cytometry. Apoptotic analysis was investigated by TUNEL assay. Real-time PCR and western blot analysis were used to analyze the expression of relevant molecules. The results of this study demonstrated that AEA inhibited the proliferation of Huh7 cells, resulted in G1 cell cycle arrest and induced apoptosis. Furthermore, downregulation of CDK4 and upregulation of p21 and Bak by AEA were observed. This study defines the anti-proliferative effects of anandamide in HCC cells and suggests that AEA has therapeutic potential in the management of HCC patients.
doi:10.3892/ol.2012.751
PMCID: PMC3439105  PMID: 22970038
hepatocellular carcinoma; anandamide; proliferation
7.  Composition and potential anticancer activities of essential oils obtained from myrrh and frankincense 
Oncology Letters  2013;6(4):1140-1146.
The present study aimed to investigate the composition and potential anticancer activities of essential oils obtained from two species, myrrh and frankincense, by hydrodistillation. Using gas chromatography-mass spectrometry (GC-MS), 76 and 99 components were identified in the myrrh and frankincense essential oils, respectively, with the most abundant components, 2-Cyclohexen-1-one, 4-ethynyl-4-hydroxy-3,5,5-trimethyl- and n-Octylacetate, accounting for 12.01 and 34.66%, respectively. The effects of the two essential oils, independently and as a mixture, on five tumor cell lines, MCF-7, HS-1, HepG2, HeLa and A549, were investigated using the MTT assay. The results indicated that the MCF-7 and HS-1 cell lines showed increased sensitivity to the myrrh and frankincense essential oils compared with the remaining cell lines. In addition, the anticancer effects of myrrh were markedly increased compared with those of frankincense, however, no significant synergistic effects were identified. The flow cytometry results indicated that apoptosis may be a major contributor to the biological efficacy of MCF-7 cells.
doi:10.3892/ol.2013.1520
PMCID: PMC3796379  PMID: 24137478
myrrh; frankincense; essential oil; gas chromatography mass spectrometry; antiproliferative activity; apoptosis
8.  Lentivirus-mediated LIGHT overexpression inhibits human colorectal carcinoma cell growth in vitro and in vivo 
Oncology Letters  2013;6(4):927-932.
Human LIGHT (lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells) is the 14th member of the tumor necrosis factor (TNF) superfamily and is therefore also known as TNFSF14. LIGHT has been proven to be a multifunctional molecule affecting cell proliferation, differentiation and a number of other biological processes, in particular, cell growth inhibition. However, the expression and molecular mechanisms of the LIGHT gene in human colorectal carcinoma cells remain largely unclear. In the present study, the LIGHT gene was overexpressed using a lentiviral expression vector in HCT116 human colorectal carcinoma cells in vitro and in vivo, in order to explore the mechanism by which the LIGHT gene inhibits cell growth and suppresses tumor formation. The results showed that the recombinant lentivirus with LIGHT overexpression inhibited the proliferative capacity of the HCT116 cells and significantly decreased the xenografted tumor volumes in nude mice. Furthermore, LIGHT treatment effectively initiated increased caspase-3 and decreased Bcl-2 activities in the HCT116 cells. This study provides a basis for the improved understanding of the role and molecular mechanisms of the LIGHT gene in human colorectal carcinoma cells and may facilitate further functional studies of LIGHT.
doi:10.3892/ol.2013.1505
PMCID: PMC3796404  PMID: 24137438
LIGHT/TNFSF14; lentiviral vector; colorectal carcinoma cell; xenografted tumor
9.  Microsurgical treatment for parasagittal meningioma in the central gyrus region 
Oncology Letters  2013;6(3):781-784.
The aim of the present study was to determine the efficacy of microsurgery treatment for parasagittal meningioma in the central gyrus region. A microsurgical technique was used to treat 26 patients with large parasagittal meningioma in the central gyrus region. The Rolandic and draining veins and the peritumoral normal brain tissue were retained, and the associated sagittal sinus was appropriately protected. A Simpson grade I, II or III resection was performed in 8 (30.8%), 12 (46.2%) and 6 (23.1%) patients, respectively, with no post-operative mortalities. Following treatment, 9 patients exhibited hemiparalysis. No tumor recurrence was found in 21 patients during the follow-up examination. The treatment protocol described in the current study included sufficient pre-operative imaging evaluations, a skilled microsurgical technique, improved protection of the Rolandic vein and treatment of the sagittal sinus, and was found to significantly increase the total tumor removal rate and decrease post-operative recurrence.
doi:10.3892/ol.2013.1429
PMCID: PMC3789089  PMID: 24137410
parasagittal meningioma; central gyrus region; microsurgery; Rolandic vein
10.  Role of the ROS/AMPK signaling pathway in tetramethylpyrazine-induced apoptosis in gastric cancer cells 
Oncology Letters  2013;6(2):583-589.
Tetramethylpyrazine (TMPZ) is one of the active compounds extracted from the traditional Chinese medicinal herb Chuanxiong and several studies have shown it to possess anticancer properties. However, its effectiveness in gastric cancer and its cellular mechanisms are relatively unknown. The present study aimed to investigate the effect of TMPZ on SGC7901 cells, and it was demonstrated that a high dose of TMPZ inhibited cell viability and induced apoptosis by stimulating AMP-activated protein kinase (AMPK) through the generation of reactive oxygen species (ROS). Furthermore, TMPZ-induced apoptosis resulted in the sequential events beginning with the translocation of Bax, the collapse of mitochondrial membrane potential (ΔΨm), the release of cytochrome c and the activation of caspase-9 and -3. Each of these events was inhibited by compound C, a pharmacological inhibitor of AMPK. To the best of our knowledge, these results demonstrate for the first time that the induction of apoptosis by TMPZ in gastric cancer cells is associated with the activation of the ROS/AMPK pathway. AMPK activation induces apoptosis through the mitochondrial apoptotic pathway. In addition, these results raise the possibility that TMPZ may have a future therapeutic role in gastric cancer.
doi:10.3892/ol.2013.1403
PMCID: PMC3789019  PMID: 24137375
AMP-activated protein kinase; reactive oxygen species; tetramethylpyrazine; apoptosis; mitochondria; gastric cancer cell
11.  Detection of intravenous leiomyomatosis with intracardiac extension by ultrasonography: A case report 
Oncology Letters  2013;6(2):336-338.
Intravenous leiomyomatosis (IVL) is characterized by histologically benign tumors that exhibit aggressive clinical behavior. On rare occasions, the tumors may extend into the regional and systemic veins, thus reaching the heart. This may subsequently cause intracardiac leiomyomatosis (ICL), which may lead to congestive heart failure and occasionally, sudden fatalities. Due to its rarity and diffuse symptoms, the misdiagnosis of ICL is common and as a result, the condition may be under-reported. The present study reports a 33-year-old female who was admitted to Shandong Provincial Hospital Affiliated to Shandong University for myomectomy due to a rapidly growing myoma of the uterus. In routine pre-operative abdominal ultrasonography, a moderately sized echoic mass in the right internal iliac vein was observed, which extended to the common iliac vein, the inferior vena cava and the orifice of the right atrium. A presumptive diagnosis of ICL was made. The patient underwent a well-prepared one-stage thoraco-abdominal surgical procedure and the pathological report confirmed ICL. This case illustrates that the early detection of ICL may prevent a potential emergency situation and abdominal ultrasonography may be considered a useful tool in the diagnosis of ICL.
doi:10.3892/ol.2013.1387
PMCID: PMC3788829  PMID: 24137326
intravascular growth; intracardiac leiomyomatosis; ultrasonography; diagnostic imaging
12.  α-linolenic acid inhibits human renal cell carcinoma cell proliferation through PPAR-γ activation and COX-2 inhibition 
Oncology Letters  2013;6(1):197-202.
ω-3 fatty acids have potential anticancer effects, and consuming food rich in ω-3 fatty acids reduces the human renal cell carcinoma (RCC) risk. However, the direct effect of ω-3 fatty acids on RCC in vitro is unknown. In the present study, the effects of α-linolenic acid (ALA), an ω-3 fatty acid, were observed on cell proliferation in the RCC cell line OS-RC-2. The activity and gene expression levels of peroxisome proliferator-activated receptor-γ (PPAR-γ) and cyclooxygenase-2 (COX-2) in the OS-RC-2 cells were measured by ELISA and real-time RT-PCR, respectively, following ALA treatment. ALA (20–80 μM) dose-dependently suppressed the proliferation of the OS-RC-2 cells. PPAR-γ activity and gene expression were significantly increased by ALA at 20 and 40 μM. COX-2 activity and gene expression levels were significantly decreased by ALA from 20 μM. Use of purely the PPAR-γ agonist, rosiglitazone, decreased the proliferation of the OS-RC-2 cells, while ALA induced further suppression of cell proliferation in the presence of rosiglitazone. The COX-2 inhibitor N-(3-Pyridyl)indomethacinamide induced further suppression of cell proliferation in the presence of rosiglitazone. N-(3-Pyridyl)indomethacinamide also suppressed the proliferation of the OS-RC-2 cells. In the presence of N-(3-Pyridyl)indomethacinamide, ALA and rosiglitazone further inhibited OS-RC-2 cell proliferation. In conclusion, ALA inhibits the cell proliferation of the OS-RC-2 human RCC cell line. PPAR-γ activation and COX-2 inhibition serve as two signaling pathways for the inhibitory effects of ALA on RCC cell proliferation.
doi:10.3892/ol.2013.1336
PMCID: PMC3742629  PMID: 23946803
renal cell carcinoma; α-linolenic acid; peroxisome proliferator-activated receptor-γ; cyclooxygenase-2; cell proliferation
13.  Ethanol extract of Chaenomeles speciosa Nakai induces apoptosis in cancer cells and suppresses tumor growth in mice 
Oncology Letters  2013;6(1):256-260.
Chaenomeles speciosa Nakai is commonly used in traditional Chinese medicine for a variety of health-promoting effects. The present study aimed to investigate the antitumor effects of Chaenomeles speciosa Nakai. The tumor-inhibitory activity of the ethanol extract of Chaenomeles speciosa Nakai (EEC) was evaluated by in vitro growth assays of tumor cells and in vivo H22 tumor formation assays in mice. Mitochondrial membrane potential and DNA ladder assays were used to detect tumor cell apoptosis in the presence of EEC. To investigate the cellular targets of EEC, the immunomodulatory genes PD-L1, Foxp3 and TGF-β were detected in the tumor tissue using reverse transcription polymerase chain reaction (RT-PCR). Immune responses were determined by hemolysis and lymphocyte proliferation assays. EEC markedly inhibited the proliferation of the H22 cells in a dose-dependent manner. Moreover, it induced DNA fragmentation and decreased the mitochondrial membrane potential. In vivo, EEC inhibited tumor growth and enhanced the immune responses in mice, while the expression of PD-L1, Foxp3 and TGF-β was inhibited in the tumor tissue. These results provide the first evidence that EEC may inhibit tumor growth by directly killing tumor cells and enhancing immune function. Thus, it is a natural source for safe anticancer medicine.
doi:10.3892/ol.2013.1340
PMCID: PMC3742774  PMID: 23946814
Chaenomeles speciosa Nakai; immune; apoptosis; cancer; mitochondrial membrane potential
14.  Overexpression of S100A4 is closely associated with the progression and prognosis of gastric cancer in young patients 
Oncology Letters  2013;5(5):1485-1490.
The aim of this study was to determine the correlation of S100A4 expression with the progression, prognosis and clinical pathology of gastric cancer (GC) in young pateints. A total of 85 tumor tissues with corresponding adjacent normal tissues and 62 non-metastatic lymph nodes (LNs) with corresponding metastatic LNs were obtained from young GC patients (<40 years old) who underwent surgery between January 2001 and December 2006. The expression of S100A4 was detected by RT-PCR and immunohistochemistry. Differences in the expression of S100A4 mRNA or protein were observed among the GC tissues, matched normal gastric mucosa, non-metastatic LNs and metastatic LNs. The expression of S100A4 mRNA and protein in GC tissues and metastatic LNs was significantly higher compared with that in the matched normal gastric mucosa and non-metastatic LNs, respectively (P<0.05). The overexpression of S100A4 was significantly associated with parameters involved in tumor progression and poor prognosis, including tumor size (P=0.017), Lauren classification (P=0.002), histological classification (P= 0.010), histological differentiation (P= 0.000), Borrmann classification (P=0.020), tumor-node-metastasis (TNM) stage (P=0.000), LN metastasis (P=0.000) and distant metastasis (P=0.024). Multivariate analysis suggested that patient age (P=0.035), tumor size (P=0.002), TNM stage (P=0.001) and S100A4 upregulation (P=0.000) were independent prognostic indicators for the disease. The overexpression of S100A4 in young GC patients is significantly associated with the clinicopathological characteristics. S100A4 may be used as a biomarker to predict the progression and poor prognosis of GC in young patients.
doi:10.3892/ol.2013.1220
PMCID: PMC3678874  PMID: 23760193
S100A4; gastric cancer; young patients; progression; prognosis; immunohistochemistry
15.  Polymorphisms in thymidylate synthase and reduced folate carrier (SLC19A1) genes predict survival outcome in advanced non-small cell lung cancer patients treated with pemetrexed-based chemotherapy 
Oncology Letters  2013;5(4):1165-1170.
The aim of this study was to evaluate the association between thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR) and reduced folate carrier (SLC19A1) gene polymorphisms and the treatment efficacy of pemetrexed-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Advanced NSCLC patients received pemetrexed and cisplatin every three weeks. Polymorphisms in the TS, MTHFR and SLC19A1 genes were detected in peripheral blood samples using DNA sequencing and Taqman PCR. An analysis of gene polymorphisms was performed with respect to the progression-free survival (PFS), response rate (RR) and overall survival (OS) of patients treated with pemetrexed. The median PFS times for patients with the TS 2R/2R, 2R/3C or 3C/3C genotypes were significantly longer than those of patients with the 2R/3G, 3C/3G or 3G/3G genotypes (P=0.036). Patients with the SLC19A1 CC genotype had a significantly longer median OS compared with individuals with the homozygous and heterozygous genotypes (12.2 vs. 8.9 and 7.3 months, respectively; P=0.022). The PFS and OS did not differ for the three genotypes of MTHFR assessed. The RR was higher in patients with the TS 2R/2R, 2R/3C or 3C/3C genotypes than in the other groups (P=0.044). The polymorphisms of the 5′-UTR of the TS gene and exon 6 (2522) C/T of the SLC19A1 gene predict the survival of advanced NSCLC patients treated with pemetrexed. However, a large scale clinical trial is required to validate these findings.
doi:10.3892/ol.2013.1175
PMCID: PMC3629022  PMID: 23599757
pemetrexed; methylenetetrahydrofolate reductase; thymidylate synthase; SLC19A1; single nucleotide polymorphism; advanced non-small cell lung cancer
16.  Effect of autophagy inhibition on chemotherapy-induced apoptosis in A549 lung cancer cells 
Oncology Letters  2013;5(4):1261-1265.
Chemotherapy is one of the main methods of cancer treatment and is known to induce autophagy in cancer cells. The main mechanism of chemotherapeutic agents is to promote apoptosis. In the process of chemotherapy, there is a unique association between autophagy and apoptosis. In this study, MDC staining, Hoechst 33342 staining and flow cytometry were used to explore the effects of autophagy on chemotherapy-induced apoptosis in A549 lung cancer cells and the association between autophagy and apoptosis was investigated via the addition of an autophagic inhibitor (3-methyladenine, 3-MA). This study demonstrated that cisplatin and paclitaxel were able to induce autophagy and apoptosis in A549 lung cancer cells and the inhibition of autophagy promoted cisplatin and paclitaxel-induced apoptosis. Furthermore, autophagy may play a protective role in the processes of cisplatin and paclitaxel-induced apoptosis.
doi:10.3892/ol.2013.1154
PMCID: PMC3628963  PMID: 23599776
autophagy; chemotherapy; apoptosis
17.  Digestive tract hemorrhage due to complications with gastrointestinal stromal tumor treated with sunitinib: A case report 
Oncology Letters  2012;5(2):699-701.
Gastrointestinal stromal tumors (GISTs) are rare, and account for 1% of all gastrointestinal neoplasms. GISTs are the most frequent mesenchymal tumors of the gastrointestinal tract. However, the clinical and pathological characteristics of these neoplasms are not adequately understood. The best treatment approach for GISTs remains unclear. In the present study, we report a case of a GIST originating from the stomach. A digestive tract hemorrhage occurred as a complication of sunitinib treatment. This is the first report of a digestive tract hemorrhage due to sunitinib treatment.
doi:10.3892/ol.2012.1050
PMCID: PMC3572955  PMID: 23420084
gastrointestinal stromal tumor; sunitinib; hemorrhage
18.  Expression of C-X-C chemokine receptor types 1/2 in patients with gastric carcinoma: Clinicopathological correlations and significance 
Oncology Letters  2012;5(2):574-582.
C-X-C chemokine receptor types 1/2 (CXCR1/2) may play multiple roles in the development and progression of a number of types of tumor. The abnormal expression of CXCR1/2 in various types of malignant tumors has been reported, but less is known with regard to gastric carcinoma. The present study was preliminarily conducted to elucidate the correlation between clinicopathological factors and the immunohistochemical expression of CXCR1/2 in patients with gastric carcinoma. The expression of CXCR1/2 in 69 specimens of sporadic gastric carcinoma and their corresponding non-neoplastic mucosa obtained by gastrectomy was assayed by immunohistochemistry (IHC) using a polyclonal anti-CXCR1/2 antibody. ERK1/2 and AKT phosphorylation and the expression of indicators of proliferation, growth and apoptosis (Bcl-2 and Bax, Cyclin D1, EGFR and Ki-67), angiogenesis (VEGF and CD34), invasion and metastasis (MMP-9, MMP-2, TIMP-2 and E-cadherin) were also detected by IHC. A total of 68 (98.6%) of the 69 patients with gastric carcinoma were found to have positive CXCR1/2 expression, which appeared to be significantly higher in gastric carcinoma compared with corresponding non-neoplastic mucosa tissues. The expression of CXCR1/2 in gastric carcinoma was significantly associated with invasion, metastasis and TNM staging (P<0.001). Correlation analysis between CXCR1/2 and pAKT (P=0.032), pERK (P<0.001), Cyclin D1 (P=0.049), EGFR (P=0.013), Bcl-2 (P=0.003), microvessel density (P=0.001), MMP-9 (P=0.013) and MMP-2 (P=0.027) expression using the Spearman test showed significant correlation in gastric carcinoma. Univariate and multivariate logistic regression analysis showed that, compared with negative or weak expression, overexpression of CXCR1/2 protein was a significant risk factor for TNM stage (P<0.001). These results preliminarily suggest that CXCR1/2 may be a useful maker for progression of the tumors and a promising target for gastric carcinoma therapy.
doi:10.3892/ol.2012.1043
PMCID: PMC3573142  PMID: 23420470
chemokine; C-X-C chemokine receptor types 1/2; gastric carcinoma; tumor
19.  Retrospective analysis of 264 multiple myeloma patients 
Oncology Letters  2012;5(2):707-713.
Multiple myeloma (MM) is the second most common hematological malignancy in China. However, there are only a small number of large cohort studies demonstrating the clinical features of newly diagnosed MM. In the present study, 264 newly diagnosed MM patients from the Beijing Chaoyang Hospital were retrospectively analyzed. The median patient age was 59 years (range, 28–84) and the most common monoclonal protein (42%) was the IgG subtype. Of the 49 patients detected by FISH, 10.2, 2.0 and 12.2% demonstrated del(17p), t(14;16) and t(4;14), respectively. In total, 228 (86%) patients achieved either a complete response (CR), a very good partial response (VGPR) or a partial response (PR). The overall response rate (ORR) in non-autologous stem cell transplantation (non-ASCT) patients was 83.0%, with 48 (18.2%), 7 (2.7%) and 121 (45.8%) patients achieving CR, VGPR and PR, respectively. ASCT patients achieved at least a PR prior to ASCT, and ASCT was not able to increase the ORR (P=0.55). Non-ASCT patients who received bortezomib-based regimens demonstrated an improved ORR compared with those who received regimens that did not contain bortezomib (92.3% vs. 75.8%; P<0.05). With a median follow-up time of 20 months, the estimated median progression-free survival (PFS) and overall survival (OS) times were 27.6 and 61.0 months, respectively. The OS time of patients with high-risk cytogenetic abnormality, del(17p), t(14;16) and t(4;14), was shorter compared with that of other patients (30.2 months vs. not reached, P=0.029). Patients who achieved a CR/VGPR in the ASCT group demonstrated a greater OS time compared with non-ASCT patients (P=0.031). Relapsed patients who received bortezomib-based regimens did not demonstrate a longer survival time post-relapse compared with those who received non-bortezomib-based regimens (26.5 months vs. 10.5 months; P=0.271). The current study presented the clinical characteristics of MM patients who were initially treated at the Beijing Chaoyang Hospital. Bortezomib-based regimens and ASCT were able to improve the OS of MM patients.
doi:10.3892/ol.2012.1018
PMCID: PMC3573013  PMID: 23420708
multiple myeloma; autologous stem cell transplantation; bortezomib; survival
20.  Sphere-forming tumor cells possess stem-like properties in human fibrosarcoma primary tumors and cell lines 
Oncology Letters  2012;4(6):1315-1320.
Fibrosarcoma is a malignant soft tissue tumor of mesenchymal origin. Despite advances in medical and surgical treatment, patient survival rates have remained poor. According to the cancer stem cell hypothesis, tumors are comprised of heterogeneous cell populations that have different roles in tumor formation and growth. Cancer stem cells are a small cell subpopulation that exhibits stem-like properties to gain aggressiveness and recurrence. These cells have been identified in a variety of cancerous tumors, but not in human fibrosarcoma. In this study, we observed that HT1080 cells and primary fibrosarcoma cells formed spheres and showed higher self-renewal capacity, invasiveness and drug resistance compared with their adherent counterparts. Moreover, we demonstrated that the cells showed higher expression of the embryonic stem cell-related genes Nanog, Oct3/4, Sox2, Sox10 and their encoding proteins, as well as greater tumorigenic capacity in nude mice. In conclusion, our data suggest the presence of a stem-like cell population in human fibrosarcoma tumors, which provides more evidence for the cancer stem cell hypothesis and assistance in designing new therapeutic strategies against human fibrosarcoma.
doi:10.3892/ol.2012.940
PMCID: PMC3506720  PMID: 23205129
human fibrosarcoma; cancer stem cell; drug resistance; aggressiveness; tumorigenicity
21.  Efficacy assessment of pemetrexed treatment of an NSCLC case with brain metastasis 
Oncology Letters  2012;4(5):1119-1121.
Non-small cell lung cancers (NSCLCs) are among the most common malignancies. Although pemetrexed is often used clinically to cure cancers, its efficacy in NSCLC patients with progressive brain metastases remains unclear. Here, we report a successful NSCLC (adenocarcinoma) case treated with pemetrexed. The detected tumors were treated with 900 mg of pemetrexed disodium (500 mg/m2) was administered to the patient on day 1, and 40 mg of cisplatin (25mg/m2) was administered on days 1–3, at the interval of 3 weeks. After two cycles of chemotherapy, the brain metastases were reduced. The lesion in the lung was reduced as determined by chest CT-scan. Our results suggest that pemetrexed is an effective therapy for patients with NSCLC and progressive brain metastases.
doi:10.3892/ol.2012.888
PMCID: PMC3499519  PMID: 23162663
pemetrexed; non-small cell lung cancer; efficacy; brain metastasis
22.  Primary giant lymphoma of the right thigh: A case report and brief review of the literature 
Oncology Letters  2012;4(5):1023-1026.
Primary soft tissue non-Hodgkin lymphoma (NHL) of the extremities is very rare. The clinical features of NHL mimic those of other soft tissue tumors, particularly sarcoma; however, they should be differentiated, as the treatment and prognosis are completely different. In this study, the case of a 68-year-old female with a giant mass, movement disorder, numbness and painful sensations in the right thigh is presented. Magnetic resonance (MR) imaging revealed a huge circle-shaped mass. Fine needle aspiration cytology (FNAC) of the tumor demonstrated neoplastic small, round cells. The tentative diagnosis was of a mesenchymal sarcoma. The right thigh was amputated. On histological examination of the amputated extremity, the diagnosis was found to be large B cell lymphoma. Primary soft tissue NHL of the extremities is a systemic malignant disease and is sensitive to chemo-therapy and radiotherapy. The histological diagnosis should be identified as far as possible before the tumor is widely excised.
doi:10.3892/ol.2012.848
PMCID: PMC3499538  PMID: 23162644
non-Hodgkin lymphoma; soft tissue; amputation; extremity
23.  Intra- and postoperative complications in 137 cases of giant thyroid gland tumor 
Oncology Letters  2012;4(5):965-969.
The intra- and postoperative complications resulting from surgery for giant thyroid gland tumors (diameter greater than 10 cm) present serious challenges to patient recovery. Although there are a number of methods, all have limitations. In this study, we present our experience with several complications of surgical treatment of giant thyroid gland tumors to increase the awareness and aid the prevention of these complications. A total of 137 consecutive patients who underwent surgical treatment in Henan Tumor Hospital were retrospectively analyzed. Statistics pertaining to the patients’ clinical factors were gathered. We found that the most common surgical complications were recurrent laryngeal nerve (RLN) injury and symptomatic hypoparathyroidism. Other complications included incision site infections, bleeding, infection and chyle fistula, the incidence of which increased significantly with increasing extent of surgery from group I (near-total thyroidectomy) to group V (total thyroidectomy plus lateral neck dissection). Low complication rates may be achieved with more accurate knowledge of the surgical anatomy, skilled surgical treatment and experience. More extensive surgery results in a greater number of complications.
doi:10.3892/ol.2012.847
PMCID: PMC3499596  PMID: 23162632
complications; giant thyroid gland; recurrent laryngeal nerve; hypoparathyroidism
24.  The expression and clinical significance of PI3K, pAkt and VEGF in colon cancer 
Oncology Letters  2012;4(4):763-766.
Background PI3K/Akt signaling has been shown to be activated in a variety of cancers. However, the correlation between Akt activation and VEGF expression is unclear in colon cancer tissues. This study aimed to investigate the expression and predictive value of phosphorylated Akt (pAkt) and VEGF in colon cancer tissues. The expression of PI3K, pAkt and VEGF was detected by immunohistochemical staining in 60 samples of colon cancer tissues and their corresponding adjacent normal colon tissues. In addition, the correlations between the expression levels of the 3 proteins and the clinicopathological parameters of the colon cancer cases were analyzed. The positive rates of PI3K, pAkt and VEGF expression were 71.7% (43/60), 68.3% (41/60) and 61.7% (37/60) in colon cancer, respectively, which were significantly higher than in adjacent normal colon tissues (P<0.001). Correlation analyses showed that PI3K expression was not significantly associated with the gender or age of the patients, tumor size or differentiation (P>0.05), but was closely associated with serous coat infiltration and lymphatic metastasis of colon cancer (P<0.05). Neither pAkt nor VEGF expression were significantly associated with the gender or age of the patients, or tumor differentiation (P>0.05), but were closely associated with tumor size, serous coat infiltration and lymphatic metastasis of colon cancer (P<0.05). In addition, the expression levels of Pl3K and pAkt were positively correlated with that of VEGF in colon cancer tissues (P<0.05). Our data show a positive correlation between PI3K/Akt activation and VEGF expression in colon cancer tissues and indicate that pAkt is an independent prognostic marker for colon cancer patients.
doi:10.3892/ol.2012.822
PMCID: PMC3506699  PMID: 23205098
colon cancer; PI3K/Akt; VEGF; angiogenesis; prognosis
25.  Contrast-enhanced ultrasonography of the rabbit VX2 tumor model: Analysis of vascular pathology 
Oncology Letters  2012;4(4):685-690.
The accuracy of diagnosing tumors may be improved significantly by detecting the microvascular distribution. Indeed, contrast-enhanced ultrasonography (CEUS) has shown a distinct advantage in detecting microvasculature. This study aimed to determine the angiogenic characteristics of VX2 tumors in rabbits using CEUS. A total of 17 rabbits were injected with 0.5 ml VX2 cell suspension into the muscles of both hind legs to prepare the VX2 tumor models. At 14, 21, 28 and 35 days after tumor inoculation, CEUS was performed on the rabbits with 0.3 ml SonoVue following a local anesthesia. The pathological findings of the tumors were compared. A total of 12 rabbits survived after being inoculated with the tumor cells and developed a total of 38 tumors. The size of the tumors ranged from 1.12 to 10.85 cm. Using CEUS, all tumors demonstrated rim enhancement with some unenhanced regions. Enhancement began from the peripheral region and quickly showed internal reticular vessels. Regardless of the tumor size or the presence of necrosis, no complete enhancement of the tumors was observed. On microscopic examination, VX2 tumor cells were detected in striated muscles, immature blood capillaries and fibrosis tissues scattered in tumor nests. Immunohistochemical examination revealed that CD34+ cells appeared mainly in the muscles adjacent to vessels. In conclusion, CEUS may be an efficient method to evaluate angiogenesis and blood perfusion in VX2 tumors.
doi:10.3892/ol.2012.819
PMCID: PMC3506667  PMID: 23205083
contrast-enhanced ultrasonography; VX2 tumor; rabbit; animal model

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