Search tips
Search criteria

Results 1-25 (453)

Clipboard (0)
Year of Publication
1.  Autologous bone marrow stem cell transplantation for the treatment of postoperative hand infection with a skin defect in diabetes mellitus: A case report 
Oncology Letters  2014;7(6):1857-1862.
Among stem cells, autologous mesenchymal stem cells (MSCs) are ideal for transplantation by virtue of limited rejection reactions and marked proliferative ability. This study presents a novel method by which MSCs were harvested from the bone marrow of a patient who presented with severe post-traumatic infection and a non-healing skin defect in the hand, secondary to uncontrolled diabetes mellitus (DM). An autologous MSC suspension was injected into the persistent skin defect after stabilizing the blood glucose level and appropriate infection control. During the course of a regular 18-month postoperative follow-up, the patient exhibited immediate recovery with no transplant-associated complications, as well as no evidence of tumorigenicity. Thus, transplantation of autologous MSCs may play a role in the clinical application of stem cells, particularly for treatment of skin defects following surgery in cases of DM and for those caused by various other traumas.
PMCID: PMC4049741  PMID: 24932248
bone marrow mesenchymal stem cell; autotransplantation; diabetes mellitus; skin defect; tumorigenicity
2.  DCF intraperitoneal and intravenous dual chemotherapy regimen for advanced gastric cancer: A feasibility study 
Oncology Letters  2014;9(1):491-497.
Gastric cancer is the fourth most common type of cancer globally and accounts for the second highest cancer-associated mortality rate in the world. Current treatment strategies for gastric cancer include surgery, radiotherapy, chemotherapy and targeted therapy. Intraperitoneal (IP) chemotherapy may increase the IP concentrations of chemotherapy drugs and reduce the systemic toxicity. At present, IP chemotherapy is used to treat patients with advanced gastric cancer, which has a high rate of peritoneal recurrence. The present study evaluated the feasibility of using docetaxel, cisplatin and fluorouracil (DCF) in an IP and intravenous (IV) dual chemotherapy regimen for the treatment of advanced gastric cancer. The treatment-associated adverse reactions and preliminary efficacy were reported. The first dose level utilized the full dose of DCF: Docetaxel, day one, 45 mg/m2 (IP) and day eight, 30 mg/m2 (IV); cisplatin (DDP), day one, 75 mg/m2 (IP); and fluorouracil (FU), days one to five, 750 mg/m2 (continuous IV). A total of six patients were treated at this level and two patients withdrew due to serious adverse reactions. Taking into account that the the tolerated doses used in combination regimens for Eastern populations are lower than that of the corresponding doses for Western populations, the dosages of the three drugs were all reduced by 20% in the application of the second dose level: Docetaxel, day one, 30 mg/m2 (IP) and day eight, 30 mg/m2 (IV); DDP, day two, 60 mg/m2 (IP); and FU, days one to five, 600 mg/m2 (continuous IV). A total of 26 patients were treated at this level. The main adverse reaction was bone marrow suppression, with grade III/IV neutropenia, leukopenia and febrile neutropenia accounting for 61.5, 53.8 and 19.2% of reactions, respectively, and grade III/IV anemia and thrombocytopenia accounting for 19.2 and 15.4% of reactions, respectively. Gastrointestinal adverse reactions primarily consisted of abdominal pain, with grade III/IV abdominal pain accounting for 30.8% of reactions. Only 7.7% of the patients withdrew from the treatment. The median time to progression (TTP) was five months [95% confidence interval (CI), 1.0–9.0 months], and the median overall survival (OS) was nine months (95% CI, 7.4–10.6 months). It was concluded that the DCF regimen with reduced dosage should be applied. IP and IV dual chemotherapy for the treatment of unresectable advanced gastric cancer is tolerated and demonstrated a good initial efficacy. Strategies for mitigating and reducing the adverse gastrointestinal reactions, particularly abdominal pain, may be the focus of future studies.
PMCID: PMC4246631  PMID: 25436015
gastric cancer; intraperitoneal chemotherapy; dual chemotherapy; docetaxel; cisplatin; fluorouracil
3.  Human leukocyte antigen-haploidentical donor-derived cytokine-induced killer cells are safe and prolong the survival of patients with advanced non-small cell lung cancer 
Oncology Letters  2014;8(6):2727-2733.
The aim of the present study was to evaluate the safety and efficacy of administering cytokine-induced killer cells (termed allogeneic CIKs), obtained from the blood of the offspring of patients, for the treatment of non-small cell lung cancer. Symptoms, signs and laboratory assessment results for 303 cancer patients were collected prior to and following treatment with autologous or allogeneic CIKs. In addition, 54 patients with advanced non-small cell lung cancer (NSCLC) were enrolled and divided into allogeneic CIK and optimal support groups (n=27 per group) according to gender, age, Karnofsky performance status score, TNM stage and histological type. In addition, overall survival (OS) was compared between the two groups. A total of 303 patients were treated with CIKs for 647 cycles, with 308 and 339 cycles in the autologous and allogeneic CIK groups, respectively. The mean number of CIKs in the autologous and allogeneic groups was 2.11±0.32×1010 and 2.29±0.36×1010, respectively, with no marked differences identified between the two groups (t=1.147; P>0.05). The predominant adverse events included insomnia, fever, nausea, vomiting and mild abdominal pain, which were found, respectively, in nine (6.8%), eight (6.0%), two (1.5%) and one (0.8%) patients receiving autologous CIKs and 11 (6.5%), 10 (5.9%), one (0.6%) and one (0.6%) patients receiving allogeneic CIKs, with no marked differences identified between the two groups (P>0.05). Adverse events were not associated with cell count, frequency or duration of treatment. Following CIK treatment, the outcomes of routine blood tests, and liver and kidney function tests, as well as immune function and electrocardiogram examinations remained unchanged (P>0.05). The median OS was 11.0 months (95% confidence interval (CI), 8.6–13.4 months) and 8.0 months (95% CI, 5.3–10.7 months) for NSCLC patients receiving allogeneic CIKs and optimal support, respectively; a statistically significant difference was identified (χ2=5.618; P=0.018). The present study demonstrated that CIKs from human leukocyte antigen haploidentical donors are safe and prolong the survival of NSCLC patients.
PMCID: PMC4214449  PMID: 25364456
cytokine-induced killer cells; immunotherapy; adoptive; allogeneic; malignant tumor; carcinoma; non-small cell lung
4.  Limb salvage surgery following resection of a melanoma: Foot and ankle reconstruction using cutaneous flaps 
Oncology Letters  2014;8(5):1966-1972.
Melanomas affect the foot and ankle region and are associated with a poor prognosis. The aim of the current study was to evaluate the functional and oncological outcomes of salvage surgery using cutaneous flaps for soft tissue reconstruction of the foot and ankle following the extended resection of a melanoma. A retrospective review was conducted to evaluate patients who presented with foot melanoma and underwent salvage surgery and defect reconstruction using three types of cutaneous flap (group S) or amputation (group A) between January 1999 and December 2010 at the First Hospital of Jilin University (Changchun, China). The postoperative mortality, surgical complications, functional outcomes and oncological outcomes were evaluated. Of the 21 patients, 11 were enrolled into group S and 10 were enrolled into group A. The median follow-up time of the patients was 58 months (range, 6–92 months). In group S, a reverse sural neurocutaneous island flap was used in six patients to perform the foot reconstruction, medial plantar flaps were used in four patients and lateral malleolus flaps were used in one patient. All 11 cutaneous flaps survived and provided satisfactory coverage. Only one cutaneous flap showed partial necrosis and required treatment comprising of debridement and regular changes to the wound dressing. The overall survival rate of patients was 65.0% and patients in the two groups experienced similar oncological outcomes. Salvage surgery with cutaneous flap reconstruction was found to be a reliable option for patients presenting with malignant melanoma of the foot and ankle.
PMCID: PMC4186625  PMID: 25295080
cutaneous flaps; foot and ankle; malignant melanoma; salvage surgery; soft tissue defects
5.  Interfering with CXCR4 expression inhibits proliferation, adhesion and migration of breast cancer MDA-MB-231 cells 
Oncology Letters  2014;8(4):1557-1562.
To investigate the effect and mechanism of the CXC chemokine receptor 4 (CXCR4) in the proliferation and migration of breast cancer, a short-hairpin RNA (shRNA) eukaryotic expression vector targeting CXCR4 was constructed, and the impact of such on the proliferation, adhesion and migration of human breast cancer MDA-MB-231 cells was observed. The fragments of CXCR4-shRNA were synthesized and cloned into a pGCsi-U6-Neo-green fluorescent protein vector. The recombinant plasmids were transfected into 293T cells and the most efficacious interfering vector was selected. MDA-MB-231 cells were transfected by liposome assay. The effects of silencing CXCR4 expression by shRNA on the growth, adhesion and migration of MDA-MB-231 cells were determined by Cell Counting Kit-8, cell-matrix adhesion and wound-healing assays. The shRNA eukaryotic expression vectors targeting CXCR4 (CXCR4-shRNA) were successfully constructed and transfected into 293T cells. Quantitative polymerase chain reaction and western blot analysis revealed that the maximum inhibitory rate of CXCR4 expression was 81.3%. CXCR4-shRNA transfection significantly inhibited the proliferation of MDA-MB-231 cells (P<0.05), as well as the adhesion between MDA-MB-231 cells and the extracellular matrix (P<0.05). Furthermore, wound-healing assays demonstrated that the migration distance of MDA-MB-231 cells in the CXCR4-shRNA transfection group was significantly smaller than that in the control plasmid and blank control groups (P<0.01). The CXCR4-shRNA interfering vector specifically inhibited CXCR4 expression, as well as the proliferation, adhesion and migration of MDA-MB-231 cells.
PMCID: PMC4156168  PMID: 25202367
CXC chemokine receptor 4; RNA interference; breast cancer
6.  Synergistic killing of lung cancer cells by cisplatin and radiation via autophagy and apoptosis 
Oncology Letters  2014;7(6):1903-1910.
Cisplatin is a commonly used drug for chemotherapy, however, whether it may be used synergistically with radiotherapy remains unclear. The present study investigated the underlying mechanisms of synergistic killing by radiosensitization and cisplatin, with a focus on the growth inhibition, apoptosis and autophagy of non-small cell human lung cancer cells in vitro and in a tumor xenograft in vivo. A549 cells were used for the in vitro experiments and divided into the following four treatment groups: Sham-irradiated; conventional radiotherapy (CRT) of five doses of 2 Gy every day; hyperfractionated radiotherapy of five doses of 2 Gy (1 Gy twice a day at 4 h intervals) every day; and CRT plus cisplatin. A xenograft tumor-bearing C57BL/6 model was established for the in vivo experiments and the above-mentioned treatments were administered. MTT and colony formation assays were used to detect cell viability and western blotting was performed to detect the levels of protein expression. Monodansylcadaverine staining and the immunofluorescence technique were used to analyze the autophagy rate, while flow cytometry and immunohistochemistry were performed to detect the expression levels of the genes associated with apoptosis and autophagy, including microtubule-associated protein 1 light chain 3 (MAPLC3)-II, phosphoinositide 3-kinase (PI3K) III, Beclin1, phosphorylated protein kinase B (p-AKT), damage-regulated autophagy modulator (DRAM), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein, caspase-3 and p21. The MTT assay demonstrated that cisplatin exhibits a dose-dependent cytotoxicity in A549 cells and synergizes with radiation to promote the cell-killing effect of radiation. In the xenograft mouse model of Lewis cells, cisplatin plus ionizing radiation (IR) (five doses of 2 Gy) yielded the most significant tumor suppression. The autophagic vacuoles, the ratio of MAPLC3-II to MAPLC3-I (LC3-II/LC3-I) and the levels of Beclin1 were found to increase in all treatment groups, with the most marked upregulation observed in the CRT plus cisplatin treatment group. In addition, caspase-3 processing was enhanced in the group treated with the combination of cisplatin with radiation, compared with the group treated with radiation alone. Fractionated IR resulted in a significant increase in p21 expression, which was further enhanced when combined with cisplatin. Furthermore, treatment with cisplatin and fractionated IR resulted in a significant elevation of the expression of the autophagy-related genes, PI3KIII, Beclin1 and DRAM1. However, the levels of p-AKT were observed to decline following exposure to fractionated IR in the presence or absence of cisplatin. As for the apoptosis signaling genes, the combination of cisplatin and fractionated IR therapy resulted in a significant decrease in Bcl-2 expression and a marked upregulation of p21 expression. The current study offers strong evidence that the combination of cisplatin with radiation strengthens the killing effect of radiation via pro-apoptotic and pro-autophagic cell death.
PMCID: PMC4049698  PMID: 24932256
cisplatin; radiosensitivity; synergistic killing; lung cancer; autophagy; apoptosis
7.  Functionally active rat S100A4 from a polymerase chain reaction-synthesized gene expressed in soluble form in Escherichia coli 
Oncology Letters  2014;7(4):1179-1184.
S100A4 protein is associated with Ca2+-dependent regulation of intracellular activities and is significant in the invasion, growth and metastasis of cancer. In order to express rat S100A4 functionally and identify its biological activity following purification, an S100A4 gene fragment was optimized and fully synthesized via overlapping polymerase chain reaction. The gene was inserted into the prokaryotic expression vector, pBV220, with phage λ PRPL promoters following confirmation by DNA sequencing. The pBV220-S100A4 plasmid was constructed and transformed into Escherichia coli DH5α. Following temperature induction, rat S100A4 was overexpressed and the protein was observed to be located in the supernatant of the lysates, which was ~30–40% of the total protein within the host. The protein was isolated and purified by metal-chelate affinity chromatography. High purity protein (>98% purity) was obtained and in vitro western blot analysis identified that the recombinant S100A4 was able to bind to the antibody against wild-type S100A4. The bioactivity of the recombinant protein was detected via Transwell migration and invasion assays. The polyclonal antibody of rat S100A4 protein was prepared for rabbit immunization and exhibited similar efficacies when compared with commercial S100A4. Therefore, rat S100A4 was functionally expressed in E. coli; thus, the production of active recombinant S100A4 protein in E. coli may further aid with the investigation and application of S100A4.
PMCID: PMC3961442  PMID: 24944689
rat S100A4; functional expression; gene recombination
8.  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.
PMCID: PMC3796425  PMID: 24137432
human gastric cancer; cancer stem cell; OCT4; ABCG2
9.  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.
PMCID: PMC3389651  PMID: 22783399
renal cell carcinoma; CCN3; migration; tumorigenicity
10.  Effect of hypoxia on hypoxia inducible factor-1α, insulin-like growth factor I and vascular endothelial growth factor expression in hepatocellular carcinoma HepG2 cells 
Oncology Letters  2015;9(3):1142-1148.
Hypoxic microenvironments and angiogenesis have been a focus of tumor research in previous years. The aim of the the present study was to create a hypoxic model and observe the effect of hypoxia on the expression of hypoxia inducible factor-1α (HIF-1α), insulin-like growth factor I (IGF-1) and vascular endothelial growth factor expression. The hypoxia model was generated using cobalt chloride (CoCl2) and an MTT assay was used to observe the influence of hypoxia on HepG2 cells. Reverse transcription-polymerase chain reaction, western blotting, ELISA and confocal immunofluorescence microscopy were used to detect the expression of HIF-1α, IGF-1 and VEGF in HepG2 cells, in which hypoxia was induced by various concentrations of CoCl2 and for various incubation times. The cell viability worsened with increasing concentrations of CoCl2. The expression of HIF-1α and IGF-1R was observed in hypoxic HepG2 cells, with the exception of HIF-1α mRNA. The expression of IGF-1R and VEGF mRNA and protein was correlated with the concentration of CoCl2 and the time that hypoxia was induced for. The expression of HIF-1α mRNA and protein was positively correlated with the expression of the VEGF mRNA and protein in a dose- and time-dependent manner under hypoxic conditions. Using immunofluorescence, it was observed that IGF-1R and HIF-1α were secreted from the hypoxic HepG2 cells. It was concluded that hypoxia induces the accumulation of IGF-1R and HIF-1α mRNA and protein, which regulates the expression of VEGF mRNA and protein in hypoxic HepG2 cells.
PMCID: PMC4315007  PMID: 25663870
hepatocellular carcinoma; hypoxia; hypoxia inducible factor-1α; insulin-like growth factor I; vascular endothelial growth factor
11.  Impact of obesity upon prostate cancer-associated mortality: A meta-analysis of 17 cohort studies 
Oncology Letters  2014;9(3):1307-1312.
A number of epidemiological studies have suggested that obesity is associated, albeit inconsistently, with the incidence of prostate cancer (PCa). In order to provide a quantitative assessment of this association, the present study examined the correlation between obesity and the incidence and associated mortalities of PCa in an updated meta-analysis of cohort studies. The cohort studies were identified by searching the EMBASE and MEDLINE databases on January 1, 2014. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models. In total, 17 studies, which included 3,569,926 individuals overall, were selected according to predefined inclusion criteria. Based upon the results of the random-effects models, obesity was not significantly correlated with the incidence of PCa (RR, 1.00; 95% CI, 0.95–1.06). However, further analysis revealed that obesity was significantly correlated with an increased risk of aggressive PCa (RR, 1.14; 95% CI, 1.04–1.25). Furthermore, an increased risk of PCa-associated mortality was significantly associated with obesity (RR, 1.24; 95% CI, 1.15–2.33), without any heterogeneity between the studies (I2=0.0%; P=0.847). The present study provides preliminary evidence to demonstrate that obesity is a significant risk factor for aggressive PCa and PCa-specific mortality. The low survival rates observed among obese males with PCa may be a likely explanation for this association.
PMCID: PMC4315023  PMID: 25663903
prostate cancer; obesity; prospective cohort studies; incidence; mortality; meta-analysis
12.  T-cell acute lymphoid leukemia resembling Burkitt leukemia cell morphology: A case report 
Oncology Letters  2014;9(3):1236-1238.
Biphenotypic acute leukemia (BAL) is an uncommon type of cancer, which accounts for <5% of all adult ALs. Based upon a previously described scoring system, the European Group for the Immunological Classification of Leukemias (EGIL) proposed a set of diagnostic criteria for BAL. This scoring system is based upon the number and degree of specificity of several markers for myeloid or T/B-lymphoid blasts. The present study describes a case of T-cell acute lymphoblastic leukemia (T-ALL) with Burkitt-like cytology, which according to the French-American-British classification, corresponded to a diagnosis of Burkitt type L3 ALL. Flow cytometry analysis demonstrated that the blasts were positive for T-lymphoid markers, cytoplasmic cluster of differentiation (CD)3, CD7 and CD56, and myeloid markers, CD13, CD33 and CD15. At first, a diagnosis of BAL was suggested by the EGIL score, however, according to the 2008 World Health Organization criteria, a case of T-ALL with aberrant myeloid markers was established. The study also reviewed the literature and discussed the limitations of the EGIL scoring system in clinical decision making, to aid in the selection of an appropriate therapeutic regimen.
PMCID: PMC4314994  PMID: 25663889
biphenotypic acute leukemia; acute lymphoblastic leukemia; Burkitt leukemia
13.  Extraskeletal Ewing’s sarcoma/primitive neuroectodermal tumor of the mediastinum: Significant response to chemoradiotherapy 
Oncology Letters  2014;9(2):626-628.
Primary mediastinal extraskeletal Ewing’s sarcoma (EES) is quite rare. To the best of our knowledge, only five cases have been reported. Given the paucity of data, there is consequently no optimal treatment strategy available. The current study presents the case of a 51-year-old female with unresectable EES of the posterior mediastinum. Chemoradiotherapy achieved near complete remission without severe side-effects. The literature associated with EES is also reviewed. The present case highlights the possibility of the diagnosis of EES for a mediastinal mass. Chemoradiotherapy may be a good option for unresectable cases. In the future, large-scale collaborative clinical trials should be initiated to provide an improved understanding of the characteristics of EES and the best treatment strategy.
PMCID: PMC4301504  PMID: 25621030
extraskeletal Ewing’s sarcoma; mediastinum; chemoradiotherapy
14.  MicroRNA-133a suppresses colorectal cancer cell invasion by targeting Fascin1 
Oncology Letters  2014;9(2):869-874.
MicroRNAs (miRs) are a type of small non-coding RNA molecule that are involved in gene silencing and the regulation of cancer progression; miR-133a in particular has been implicated in colorectal cancer, although its specific role and underlying mechanism have yet to be determined. In the present study, the expression level of miR-133a was significantly downregulated in a number of colorectal cancer cell lines, as well as in colorectal cancer tissues compared with the normal adjacent tissues. Furthermore, the Fascin1 (FSCN1) gene was identified as a direct target of miR-133a, and the protein expression level of FSCN1 was negatively regulated by miR-133a in colorectal cancer cells. Additionally, restoration of miR-133a expression and downregulation of FSCN1 protein expression suppressed colorectal cancer cell invasion, while overexpression of FSCN1 reversed the inhibitory effect of miR-133a upregulation on colorectal cancer cell invasion. Thus, the present data indicates that miR-133a may at least partially suppress colorectal cancer cell invasion, possibly via the inhibition of FSCN1 expression. The present study highlights the important role of miR-133a in the progression of colorectal cancer.
PMCID: PMC4301513  PMID: 25621061
colorectal cancer; microRNA-133a; Fascin1; invasion
15.  Role of antiviral therapy in reducing recurrence and improving survival in hepatitis B virus-associated hepatocellular carcinoma following curative resection (Review) 
Oncology Letters  2014;9(2):527-534.
Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related mortality worldwide, with the majority of cases associated with persistent hepatitis B virus (HBV) or hepatitis C virus infection. In particular, chronic HBV infection is a predominant risk factor for the development of HCC in Asian and African populations. Hepatic resection, liver transplantion and radiofrequency ablation are increasingly used for the curative treatment of HCC, however, the survival rate of HCC patients who have undergone curative resection remains unsatisfactory due to the high recurrence rate. HCC is a complex disease that is typically resistant to the most commonly used types of chemotherapy and radiotherapy; therefore, the development of novel treatment strategies is required to improve the survival rate of this disease. A high viral load of HBV DNA is the most important correctable risk factor for HCC recurrence, for example nucleos(t)ide analogs improve the outcome following curative resection of HBV-associated HCC, and interferon-α exhibits antitumor activity against various types of cancer via direct inhibitory effects on tumor cells, anti-angiogenesis, enhanced immunogenicity of tumors, immunomodulatory effects and liver dysfunction. In the present review, antiviral treatment for HBV-associated HCC is described as a strategy to reduce recurrence and improve survival.
PMCID: PMC4301553  PMID: 25624883
hepatocellular carcinoma; hepatitis B virus; recurrence; interferon-α; survival rates; curative resection; sorafenib; transatheter arterial chemoembolization
16.  Subcellular location and photodynamic therapeutic effect of chlorin e6 in the human tongue squamous cell cancer Tca8113 cell line 
Oncology Letters  2014;9(2):551-556.
The present study aimed to investigate the distribution and photodynamic therapeutic effect of chlorin e6 (Ce6) in the human tongue squamous cell carcinoma Tca8113 cell line in vitro. The distribution of Ce6 in the Tca8113 cells was observed in situ combined with mitochondrial and lysosomal fluorescent probes. Next, 630-nm semiconductor laser irradiation was performed. The MTS colorimetric method was used to determine cell survival. Annexin V fluorescein isothiocyanate/propidium iodide (PI) double staining was used to detect early apoptosis following photodynamic therapy (PDT). The flow cytometer was used to analyze the DNA content subsequent to PI-staining. It was observed that Ce6 could combine with the cellular membrane following 30 min of incubation with the Tca8113 cells. As the length of incubation increased, Ce6 gradually entered the cells in a particular distribution and reached saturation by 3 h. Co-localization analysis demonstrated that Ce6 was more likely to be present in the mitochondria than in the lysosomes. The cells incubated with 5 μg/ml Ce6 for 24 h exhibited a low toxicity of 5%, however, following light irradiation, Ce6-PDT was able to kill the Tca8113 cells in vitro. The cell toxicity was positively correlated with Ce6 concentration and light dose, therefore, the effect of Ce6 was concentration/dose-dependent (P<0.01). The lower Ce6 concentrations and light doses could significantly induce apoptosis in the Tca8113 cells, while higher doses increased necrosis/percentage of dead cells. In summary, Ce6 saturated the Tca8113 cells following 3 h of incubation. Furthermore, Ce6-PDT effectively killed the cultured Tca8113 cells in vitro at a safe concentration. At a low concentration and light dose, Ce6 is more likely to induce cell apoptosis via the mitochondria than the lysosomes.
PMCID: PMC4301477  PMID: 25621023
photodynamic therapy; chlorin; mitochondria; human tongue squamous cell carcinoma; cell death
17.  Small cell carcinoma of the uterine cervix in pregnancy: A case report and review of the literature 
Oncology Letters  2014;9(1):91-95.
The occurrence of cervical cancer during pregnancy is extremely rare, particularly small cell carcinoma. Small cell cervical carcinoma (SCCC) is a neuroendocrine tumor with a poor prognosis. This study presents the case of an 18-year-old female with stage IB2 SCCC complicated by pregnancy, who was treated with chemotherapy and radiotherapy. The patient was diagnosed shortly after giving birth, and is the youngest female case to be reported in the world. The patient was treated with cisplatin and etoposide chemotherapy and radiotherapy. Complete remission was achieved following neoadjuvant chemotherapy and radiotherapy, and the patient remains in clinical remission eight months following treatment. Cytological screening, colposcopy and if necessary, biopsy, and selective conization at 14–20 weeks should be considered in the patient evaluation.
PMCID: PMC4246688  PMID: 25435939
cervix; neoadjustchemotherapy; pregnancy; radiotherapy; small cell carcinoma
18.  Ki67 as a predictor of poor prognosis in patients with triple-negative breast cancer 
Oncology Letters  2014;9(1):149-152.
The aim of the current study was to investigate the expression of the proliferation antigen, Ki67, in triple-negative breast cancer (TNBC) and its correlation with clinicopathological factors. The expression of Ki67 and other biological indicators in 24 cases of TNBC tissues and 178 cases of non-TNBC tissues were detected using immunohistochemistry. Their correlation with the clinicopathological factors were also analyzed using the χ2 test. The positive rate of Ki67 expression in TNBC tissues was 83.3%, exhibiting a statistically significant difference when compared with that in non-TNBC tissues (73.0%) (P<0.05). The expression of Ki67 in breast cancer tissue significantly correlated with the tumor size and lymph node metastases; however, no correlation was observed with the age and the clinical stage. Ki67 may be an indicator of poor prognosis in TNBC patients.
PMCID: PMC4246616  PMID: 25435949
breast cancer; estrogen receptor; progesterone receptor; human epidermal growth factor receptor 2; Ki67
19.  Unusual presentation of duodenal plasmablastic lymphoma in an immunocompetent patient: A case report and literature review 
Oncology Letters  2014;8(6):2539-2542.
Plasmablastic lymphoma (PBL) is a rare and recently described entity of large B-cell lymphoma. It predominantly occurs in the oral cavity of human immunodeficiency virus (HIV)-positive patients and exhibits a highly aggressive clinical behavior without effective treatment. Recently, sporadic cases describing PBL in extraoral locations of HIV-negative patients have been reported; frequently in patients with underlying immunosuppressive states. To develop the understanding of PBL, the current study reports the unusual presentation of duodenal PBL and reviews the pathogenesis, immunohistochemical features, clinical and differential diagnoses, as well as the treatment of PBL as described in previous studies. The case of a 75-year-old female with duodenal PBL without definite immunosuppression is presented in the current report. The tumor was composed of large B-cell-like cells, and was positive for cluster of differentiation 138 and melanoma ubiquitous mutated-1, with ~80% of the tumor cells positive for Ki-67. The features of the tumor were as follows: Extraoral location, HIV-negative, immunoglobulin M λ-type M protein expression, light chain restriction (monoclonal) and Epstein-Barr virus-encoded small RNA-negative, which are considered to be unusual for PBL. These unusual features complicate the differentiation of PBL from other plasma cell diseases. To the best of our knowledge, this is the first study to report a case of duodenal PBL in an immunocompetent patient. To date, the standard treatment of PBL remains elusive, however, the most commonly administered chemotherapy treatments are CHOP [intravenous cyclophosphamide (750 mg/m2, day 1), intravenous doxorubicin (50 mg/m2, day 1), intravenous vincristine (1.4 mg/m2, day 1) and prednisone (100 mg, days 1–50)]-like regimens. The patient was administered two cycles of CHOP chemotherapy for 56 days, however, ultimately succumbed as a result of disease progression. Therefore, PBL represents a diagnostic and therapeutic challenge. PBL must be considered in the differential diagnosis of gastrointestinal tumors in daily practice, even in immunocompetent patients. Furthermore, CHOP does not appear to be an optimal treatment regimen and more intensive regimens are required.
PMCID: PMC4214469  PMID: 25364423
plasmablastic lymphoma; immunocompetent; duodenum; Epstein-Barr virus-encoded small RNA-negative
20.  Gastric wall implantation metastasis of retroperitoneal extraskeletal osteosarcoma: A case report and review of the literature 
Oncology Letters  2014;8(6):2431-2435.
Retroperitoneal extraskeletal osteosarcoma (ESOS) is a rare and highly invasive tumor that is usually diagnosed at an advanced stage due to the insidious onset. The present study analyses a case of retroperitoneal ESOS and its clinical, radiological and therapeutic conditions, and also provides a review of the literature. A 52-year-old male was diagnosed with retroperitoneal ESOS. The patient succumbed to the condition one year after the initial surgery. During treatment, the patient underwent two additional surgeries and two courses of chemotherapy. In the present case, a peritoneal metastatic lesion of ESOS was shed from the peritoneum and implanted into the outer membrane of the stomach and metastasis was identified, this has rarely been reported in the literature. Retroperitoneal ESOS should be considered in the differential diagnosis of a retroperitoneal mass in order to facilitate the management of surgery and help determine the appropriate treatment of the disease.
PMCID: PMC4214496  PMID: 25364404
retroperitoneal extraskeletal osteosarcoma; implantation metastasis; therapy
21.  MicroRNA-7 sensitizes non-small cell lung cancer cells to paclitaxel 
Oncology Letters  2014;8(5):2193-2200.
Paclitaxel (PTX) is the front-line chemotherapeutic agent against human non-small cell lung cancer (NSCLC). However, its therapeutic efficacy is restricted by the increasing frequency of chemotherapeutic resistance in NSCLC. Accumulating evidence has shown the potential role of microRNAs (miRNAs) in the chemotherapeutic sensitivity of cancer cells. Previously it was reported that microRNA-7 (miR-7) acts as an important tumor suppressor in NSCLC. Therefore, the present study was conducted to determine the regulatory role of miR-7 in PTX chemotherapy for NSCLC. Four NSCLC cell lines were used to analyze the correlation of the PTX-sensitivity and endogenoaus miR-7 expression. miR-7 expression was up- and downregulated using miR-7 mimics and inhibitors respectively, and the role of miR-7 in sensitizing NSCLC cells to PTX was assessed by cell viability and apoptosis assays. The molecular mechanism of PTX sensitivity was determined by quantitative polymerase chain reaction and western blotting. It was found that the sensitivity of NSCLC cells to PTX was dependent on endogenous miR-7. Upregulation of miR-7 enhanced the PTX-sensitivity of NSCLC cells by suppressing cell proliferation and promoting cell apoptosis, while the inhibition of miR-7 abrogated the antiproliferative proapoptotic effects of PTX. Pretreatment of miR-7 mimics enhanced the PTX-mediated downregulation of epidermal growth factor receptor (EGFR) in NSCLC cells. These results have identified miR-7 as a potential EGFR-targeting sensitizer in PTX therapy. These data may facilitate the development of novel chemotherapeutic approaches for NSCLC.
PMCID: PMC4186567  PMID: 25289099
microRNA; chemotherapy; drug resistance; lung cancer; EGFR
22.  PKM2 regulates Gli1 expression in hepatocellular carcinoma 
Oncology Letters  2014;8(5):1973-1979.
Hedgehog (Hh) signaling and the pyruvate kinase isoenzyme M2 (PKM2 or M2-PK) are often involved in tumorigenesis and growth. Aberrant activation of Hh signaling is found in a variety of malignancies. In tumor cells, PKM2 determines whether glucose is used for the synthesis of cellular building blocks or the production of lactate for energy regeneration; it associated with the Warburg effect. Gli1 is a downstream molecule of the Hh signaling pathway; however, the association between Hh signaling and PKM2 is not well understood. In the present study, it was identified that PKM2 and Gli1 expression levels were significantly elevated in hepatocellular carcinoma (HCC) compared with para-carcinoma. In vitro study revealed that overexpression of PKM2 in HepG2 cells upregulated the transcription of Gli1, while the ablation of PKM2 by shRNA caused the downregulation of Gli1 gene expression. Gli1 transcription could be rescued by PKM2. Overall, these findings suggest that PKM2 is a regulator of Gli1 gene expression in HCC, and may contribute to tumorigenesis through Gli1.
PMCID: PMC4186579  PMID: 25289083
hepatocellular carcinoma; PKM2; Gli1
23.  Expression of tumor-associated calcium signal transducer 2 in patients with salivary adenoid cystic carcinoma: Correlation with clinicopathological features and prognosis 
Oncology Letters  2014;8(4):1670-1674.
Salivary adenoid cystic carcinoma (SACC) is a common salivary malignancy. The current treatment option for SACC is complete surgical excision with postoperative radiotherapy. The prognosis remains unsatisfactory, due to frequent local recurrence and distant metastases that directly reduce the overall survival time. Previous studies have shown that overexpression of tumor-associated calcium signal transducer 2 (TACSTD2) is associated with poor prognosis in various human epithelial cancers. The expression of TACSTD2 in SACC is currently unknown. The present study therefore aimed to retrospectively investigate TACSTD2 protein expression by immunohistochemistry on paraffin-embedded primary tumor tissue samples from a series of consecutive SACC patients (n=81). The correlation of TACSTD2 expression with clinicopathological variables was evaluated using either the Kruskal-Wallis or Mann-Whitney statistical tests. The survival curves were plotted using the Kaplan-Meier method. The parameters of prognostic significance found by univariate analysis were verified in a multivariate Cox regression model. Overexpression of TACSTD2 was detected in 35/81 (44%) SACC patients and was significantly associated with a decreased overall survival (P<0.01). Univariate analysis showed that TACSTD2 overexpression was correlated with TNM stage (P=0.020), local recurrence (P=0.002) and distant metastasis (P=0.001). Multivariate analyses further revealed that TACSTD2 may be an independent prognostic indicator. In conclusion, TACTSD2 could be recognized as an independent prognostic indicator for SACC. Gene therapy targeting TACSTD2 may be a possible treatment approach for patients with SACC overexpressing this cell-surface marker.
PMCID: PMC4156178  PMID: 25202389
salivary adenoid cystic carcinoma; TACSTD2; prognosis; clinicopathological feature
24.  Immune reconstitution from peripheral blood mononuclear cells inhibits lung carcinoma growth in NOD/SCID mice 
Oncology Letters  2014;8(4):1638-1644.
Drug resistance and immune deficiency are important factors for the poor prognosis of lung carcinoma. The present study explored the possible protective effect of immune reconstitution from peripheral blood mononuclear cells (PBMCs) on multi-drug-resistant human lung carcinoma Am1010 cells in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. The inoculated tumor fragments grew rapidly in the NOD/SCID mice. The growth was significantly inhibited by intraperitoneal injection of PBMCs. In the mice injected with PBMCs, numerous CD3+ and CD8+ cells, but less CD4+ cells, were found in spleen and tumor tissues. These data suggest that PBMC transplantation inhibits lung carcinoma progression via the reconstitution of the immune system, particularly of cytotoxic T lymphocytes.
PMCID: PMC4156269  PMID: 25202383
NOD/SCID; T lymphocytes; peripheral blood mononuclear cells; lung carcinoma; Am1010
25.  Dihydromyricetin induces apoptosis and inhibits proliferation in hepatocellular carcinoma cells 
Oncology Letters  2014;8(4):1645-1651.
Hepatocellular carcinoma (HCC) is a life-threatening disease that is known to exhibit a poor prognosis. Therefore, it is important to identify an effective drug therapy for the treatment of HCC. Dihydromyricetin (DHM) is a flavonoid compound, isolated from the classical Chinese herb Ampelopsis grossedentata, which exhibits multiple pharmacological activities, including anticancer effects. In this study, the anticancer effect of DHM was investigated in nine different types of HCC cell lines via cell proliferation and immunoassays, as well as apoptosis detection. Two immortalized normal human liver cell lines were utilized to determine hepatotoxicity. The results revealed that DHM significantly inhibited cell proliferation and induced cell apoptosis in the HCC cell lines. However, DHM exhibited no cytotoxicity to normal human hepatic cell lines. Furthermore, it was found that DHM induced cell apoptosis in a p53-dependent manner. DHM upregulated p53 expression, and the upregulation of p53 increased the levels of the cleaved caspase-3 protein, directly inducing cell apoptosis. These results indicate that DHM is a promising candidate for the treatment of HCC.
PMCID: PMC4156277  PMID: 25202384
dihydromyricetin; hepatocellular carcinoma; p53; apoptosis; caspase-3

Results 1-25 (453)