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Journal: Oncology letters

168

SOFT TISSUE TUMORS ARE CLASSIFIED ACCORDING TO THEIR HISTOLOGICAL RESEMBLANCE TO NORMAL ADULT TISSUES AND CAN BE GROUPED INTO THE FOLLOWING CATEGORIES BASED ON METASTATIC POTENTIAL: benign, intermediate (locally aggressive), intermediate (rarely metastasizing) and malignant. Over the past two decades, considerable progress has been made in our understanding of the genetic background of soft tissue tumors. Traditional laboratory techniques, such as cytogenetic analysis and fluorescence in situ hybridization (FISH), can be used for diagnostic purposes in soft tissue pathology practice. Moreover, cytogenetic and molecular studies are often necessary for prognostics and follow-up of soft tissue sarcoma patients. This review provides updated information on the applicability of laboratory genetic testing in the diagnosis of benign and intermediate soft tissue tumors. These tumors include nodular fasciitis, chondroid lipoma, collagenous fibroma (desmoplastic fibroblastoma), giant cell tumor of tendon sheath (GCTTS)/pigmented villonodular synovitis (PVNS), angiofibroma of soft tissue, myxoinflammatory fibroblastic sarcoma (MIFS) and ossifying fibromyxoid tumor (OFMT).

Concepts: Genetics, Cancer, Oncology, Extracellular matrix, Soft tissue sarcoma, Anatomical pathology, Fluorescent in situ hybridization, Cytogenetics

168

The current study sought to assess the role of paraaortic lymphadenectomy (LNE) in females with endometrial cancer. A retrospective analysis of patients diagnosed with endometrial cancer of stage IA to II preoperatively, between 2009 and 2011 was conducted. Patients were included who had suffered from endometrial cancer without preoperative adjuvant therapy and who underwent hysterectomy plus systematic pelvic LNE and paraaortic LNE by laparoscopy or laparotomy. A total of 54 patients who underwent surgery for preoperative endometrial cancer were selected. All patients underwent LNE. The incidences of pelvic and paraaortic lymph node metastases were 11.1% (6/54) and 7.4% (4/54), with a total positive lymph node rate of 14.8% (8/54). In addition, among the 8 positive cases, 5 patients underwent laparotomy and 3 underwent laparoscopy; 3 cases were classified as stage I and 5 as stage II preoperatively. Of these, 7 patients were identified with pathology-related risk factors, including low differentiation or clear cell adenocarcinoma postoperatively. Discordance of pathological differentiation between the pre- and postoperative stages reached 57.1% (4/7). The results revealed the high occurrence of positive lymph nodes in endometrial cancer which demonstrate the importance of systematic LNE. Additonally, no severe complications were caused by LNE besides lymph cysts. In summary, it is neccesary to perform LNE, particularly the removal of the paraaortic lymph node, in patients with endometrial cancers in order to improve postoperative therapy. Laparoscopy has similar surgical effects as laparotomy, but has a number of advantages.

Concepts: Cancer, Metastasis, Lung cancer, Cancer staging, Lymph node, Surgery, Endometrial cancer, Paraaortic lymph node

156

A 62-year-old female with neurofibromatosis type 1 (NF1; also von Recklinghausen’s disease) was diagnosed with a giant, thick-walled tubular mass, mainly located in the right abdominal area on computed tomography, following an examination for intermittent abdominal pain and increasing abdominal distension. According to the clinical manifestations and imaging features, the giant tubular mass was considered most likely to be a dilated fallopian tube associated with infection, while the possibility of obstructed bowel loops was excluded. However, the subsequent laparotomy revealed a giant appendix, caused by a large neurofibroma in the root region of the appendix, which occluded the lumen. Neurofibroma of the appendix is extremely rare, even in patients with NF1. To the best of our knowledge, only three such cases have previously been reported in the English literature to date.

Concepts: Neurology, Abdominal pain, Bowel obstruction, Neurofibromatosis type I, Neurofibromatosis, Abdominal distension, Friedrich Daniel von Recklinghausen, Café au lait spot

14

Damnacanthal, an anthraquinone compound, is isolated from the roots of Morinda citrifolia L. (noni), which has been used for traditional therapy in several chronic diseases, including cancer. Although noni has long been consumed in Asian and Polynesian countries, the molecular mechanisms by which it exerts several benefits are starting to emerge. In the present study, the effect of damnacanthal on MCF-7 cell growth regulation was investigated. Treatment of MCF-7 cells with damnacanthal for 72 h indicated an antiproliferative activity. The MTT method confirmed that damnacanthal inhibited the growth of MCF-7 cells at the concentration of 8.2 μg/ml for 72 h. In addition, the drug was found to induce cell cycle arrest at the G1 checkpoint in MCF-7 cells by cell cycle analysis. Damnacanthal induced apoptosis, determined by Annexin V-fluorescein isothiocyanate/propidium iodide (PI) dual-labeling, acridine-orange/PI dyeing and caspase-7 expression. Furthermore, damnacanthal-mediated apoptosis involves the sustained activation of p21, leading to the transcription of p53 and the Bax gene. Overall, the present study provided significant evidence demonstrating that p53-mediated damnacanthal induced apoptosis through the activation of p21 and caspase-7.

Concepts: DNA, Gene, Gene expression, Cancer, Breast cancer, Apoptosis, Chemotherapy, Cell cycle

7

Altered glucose metabolism has been described as a cause of chemoresistance in multiple tumor types. The present study aimed to identify the expression profile of glucose metabolism in drug-resistant acute myeloid leukemia (AML) cells and provide potential strategies for the treatment of drug-resistant AML. Bone marrow and serum samples were obtained from patients with AML that were newly diagnosed or had relapsed. The messenger RNA expression of hypoxia inducible factor (HIF)-1α, glucose transporter (GLUT)1, and hexokinase-II was measured by quantitative polymerase chain reaction. The levels of LDH and β subunit of human F1-F0 adenosine triphosphate synthase (β-F1-ATPase) were detected by enzyme-linked immunosorbent and western blot assays. The HL-60 and HL-60/ADR cell lines were used to evaluate glycolytic activity and effect of glycolysis inhibition on cellular proliferation and apoptosis. Drug-resistant HL-60/ADR cells exhibited a significantly increased level of glycolysis compared with the drug-sensitive HL-60 cell line. The expression of HIF-1α, hexokinase-II, GLUT1 and LDH were increased in AML patients with no remission (NR), compared to healthy control individuals and patients with complete remission (CR) and partial remission. The expression of β-F1-ATPase in patients with NR was decreased compared with the expression in the CR group. Treatment of HL-60/ADR cells with 2-deoxy-D-glucose or 3-bromopyruvate increased in vitro sensitivity to Adriamycin (ADR), while treatment of HL-60 cells did not affect drug cytotoxicity. Subsequent to treatment for 24 h, apoptosis in these two cell lines showed no significant difference. However, glycolytic inhibitors in combination with ADR increased cellular necrosis. These findings indicate that increased glycolysis and low efficiency of oxidative phosphorylation may contribute to drug resistance. Targeting glycolysis is a viable strategy for modulating chemoresistance in AML.

Concepts: DNA, Gene expression, Cell, Adenosine triphosphate, Enzyme, Glucose, Oxidative phosphorylation, Glycolysis

4

The aim of the present population-based cohort study was to analyze the association between the prevalence of 32 types of human papilloma virus (HPV) in 615 female patients with abnormal cervical cytopathology findings. In total, 32 HPV types were screened by DNA array technology. HPV infection was detected in 470 women (76.42%), 419 of whom (89.15%) were infected with ≥1 high-risk (HR)-HPV type. HPV16, which is recognized as the main HR-HPV type responsible for the development of cervical cancer, was observed in 32.98% of HPV(+) participants, followed by HPV42 (18.09%), HPV31 (17.66%), HPV51 (13.83%), HPV56 (10.00%), HPV53 (8.72%) and HPV66 (8.72%). The prevalence of HR-HPV types, which may be suppressed directly (in the case of HPV16 and 18), or possibly via cross-protection (in the case of HPV31) following vaccination, was considerably lower in participants ≤22 years of age (HPV16, 28.57%; HPV18, 2.04%; HPV31, 6.12%), compared with participants 23-29 years of age (HPV16, 45.71%; HPV18, 7.86%; HPV31, 22.86%), who were less likely to be vaccinated. Consequently, the present study hypothesizes that there may be a continuous shift in the prevalence of HPV types as a result of vaccination. Furthermore, the percentage of non-vaccine HR-HPV types was higher than expected, considering that eight HPV types formerly classified as ‘low-risk’ or ‘probably high-risk’ are in fact HR-HPV types. Therefore, it may be important to monitor non-vaccine HPV types in future studies, and an investigation concerning several HR-HPV types as risk factors for the development of cervical cancer is required.

Concepts: Immune system, Human papillomavirus, Cervical cancer, Papillomavirus, HPV vaccine, Gardasil, Anal cancer, Cervarix

2

Growing evidence indicates that the presence of extensive oxidative stress plays an essential role in the initiation and progression of Alzheimer’s disease (AD). Amyloid-β (Aβ) aggregation is involved in the elevation of oxidative stress, contributing to mitochondrial dysfunction and lipid peroxidation. In the present study, human placenta amniotic membrane-derived mesenchymal stem cells (hAMMSCs) were intravenously injected into C57BL/6J-APP transgenic mice. hAMMSCs significantly ameliorated spatial learning and memory function, and were associated with a decreased amount of amyloid plaques of the brain. The correlation of oxidative stress with Aβ levels was lower in the hAMMSCs-injected group than in the phosphate-buffered saline (PBS)-injected group, as indicated by the increased level of antioxidative enzymes and the decreased level of lipid peroxidation product. The glutathione (GSH) level and ratio of GSH to glutathione disulfide were higher in the hAMMSC group than in the PBS group. The superoxide dismutase activity and malonaldehyde level were improved significantly as the level of Aβ decreased, but there was no such trend in the PBS group. As a result, our findings represent evidence that hAMMSC treatment might improve the pathology of AD and memory function through the regulation of oxidative stress.

Concepts: Alzheimer's disease, Antioxidant, Stem cell, Mesenchymal stem cell, Oxidative stress, Reactive oxygen species, Superoxide dismutase, Glutathione

2

The therapeutic activity of drugs can be optimized by establishing an individualized dosage, based on the measurement of the drug concentration in the serum, particularly if the drugs are characterized by an inter-individual variation in pharmacokinetics that results in an under- or overexposure to treatment. In recent years, several tyrosine kinase inhibitors (TKIs) have been developed to block intracellular signaling pathways in tumor cells. These oral drugs are candidates for therapeutic drug monitoring (TDM) due to their high inter-individual variability for therapeutic and toxic effects. Following a literature search on PubMed, studies on TKIs and their pharmacokinetic characteristics, plasma quantification and inter-individual variability was studied. TDM is commonly used in various medical fields, including cardiology and psychiatry, but is not often applied in oncology. Plasma concentration monitoring has been thoroughly studied for imatinib, in order to evaluate the usefulness of TDM. The measurement of plasma concentration can be performed by various analytical techniques, with liquid chromatography-mass spectrometry being the reference method. This method is currently used to monitor the efficacy and tolerability of imatinib treatments. Although TDM is already being used for imatinib, additional studies are required in order to improve this practice with the inclusion of other TKIs.

Concepts: Pharmacology, Medicine, Cancer, Oncology, Signal transduction, Protein kinase, Pharmacokinetics, Pharmacodynamics

1

Although numerous long non-coding RNAs (lncRNAs) have been identified to be important in human cancer, their potential regulatory roles in epithelial tumorigenesis and tumor progression in ovarian cancer remain unclear. The purpose of the present study was to investigate lncRNAs that were differentially expressed (DE) in epithelial ovarian cancer and to explore their potential functions. The lncRNA profiles in five pairs of human epithelial ovarian cancer tissues and their adjacent normal tissues were described using microarrays. The results of the microarray analysis revealed that 672 upregulated and 549 downregulated (fold-change ≥2.0) lncRNAs were DE between the cancerous and normal tissues. Reverse transcription-quantitative polymerase chain reaction was used to validate the microarray results using four upregulated (RP11-1C1.7, XLOC_003286, growth arrest-specific 5 and ZNF295-AS1) and four downregulated (protein tyrosine kinase 7, maternally expressed gene 3, AC079776.2 and ribosomal protein lateral stalk subunit P0 pseudogene 2) lncRNAs. Furthermore, gene ontology and pathway analyses were used to carry out functional analyses of the candidate genes of DE lncRNAs. The results identified lncRNAs with significantly altered expression profiles in human epithelial ovarian cancer cells compared with those in adjacent normal cells. These data offer new insights into the occurrence and development of epithelial ovarian cancer, and these lncRNAs may provide novel molecular biomarkers for further research on epithelial ovarian cancer.

Concepts: DNA, Protein, Gene, Gene expression, Cancer, Molecular biology, RNA, Tyrosine kinase

1

Gliomas are the most common primary brain tumor, the diagnosis of which is challenging. In this respect, the use of immunohistochemical proliferation markers may aid diagnosis; survivin, also known as Baculoviral IAP Repeat Containing 5, is one such marker. Survivin is a unique member of the inhibitors of apoptosis protein gene family, and is known for its dual function as an apoptosis inhibitor and mitosis regulator. Furthermore, survivin has been demonstrated to be overexpressed in a number of malignancies. The purpose of the present literature review was to gain an overview of studies published on the diagnostic and/or prognostic use of survivin in gliomas. Using PubMed, 19 studies matching the inclusion criteria were ultimately included in the present review. The majority of the studies identified revealed that survivin was significantly associated with other proliferation markers, histological malignancy grade, and inversely associated with prognosis. However, there were a number of inconsistencies between studies, which suggests a requirement for standardization of immunohistochemical procedures.

Concepts: Cancer, Oncology, Lung cancer, Medical terms, Brain tumor, Medical diagnosis, Prognosis, Baculoviral IAP repeat-containing protein 3