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Several previous studies have revealed that the expression of zinc finger E-box binding homeobox 1 (ZEB1) in solid malignancies has an important significance on the clinical outcome of patients. However, the association between ZEB1 expression and survival in patients with epithelial ovarian carcinoma (EOC) remains unclear. The objective of the present study was to examine the extent of ZEB1 expression in EOC using immunohistochemical staining and investigate its association with patient outcome. A total of 40 patients with EOC initially treated with cytoreductive surgery and systematic chemotherapy were enrolled. ZEB1 expression was immunohistochemically categorized as negative, weak, moderate and strong according to the size of the staining area, and intensity. Subsequently, the associations between ZEB1 expression and recurrence/progression-free survival (RFS) rate were examined. The median age of patients in the current study was 54 years old (range, 22-72 years old). Among these patients, 15 (37.5%) exhibited International Federation of Gynecology and Obstetrics stage I disease, and 10 (25.0%), 13 (32.5%), and 2 (5%) had stage II, III, and IV disease, respectively. No patients with negative expression of ZEB1 experienced recurrence. In addition, ZEB1 expression was identified to be a significant predictor of a poorer RFS rate compared with negative expression (negative vs. weak, moderate and strong, P=0.0126). Furthermore, multivariate analyses revealed that moderate and strong ZEB1 expression levels were significant prognostic indicators of a poorer RFS rate in patients with EOC (hazard ratio, 2.265; 95% confidence interval, 1.072-8.021; P=0.0349). Confining analysis to patients with the clear-cell/mucinous histological type, those with moderate/strong ZEB1 expression demonstrated a significantly poorer RFS rate (P=0.0025). Positive ZEB1 expression may be an indicator to predict unfavorable RFS in patients with EOC. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract. It is well known that activating mutations in the receptor tyrosine kinases KIT and platelet-derived growth factor receptor-a have essential roles in the pathogenesis of GISTs. The activation of these receptor protein kinases triggers multiple signaling pathways that promote cell proliferation and survival; however, the exact mechanism by which the activation of these kinases promotes the progression of GISTs remains uncertain. The aim of the present was to search for genes that are associated with the progression of GIST. The present study used reverse transcription-quantitative polymerase chain reaction to demonstrate that adenosine monophosphate deaminase 3 (AMPD3) was highly expressed in GISTs. Furthermore, transfection of GIST-T1 cells with KIT-specific small interfering RNA (siRNA) demonstrated that the expression of AMPD3 was dependent on KIT expression, while the depletion of AMPD3 in human GIST-T1 cells using AMPD3-specific siRNA resulted in the suppression of cell migration and invasion. In addition, AMPD3 depletion sensitized GIST-T1 cells to the tyrosine kinase inhibitor imatinib. The results of the present suggested that the combined inhibition of tyrosine kinases and AMPD3 may be effective for the treatment of GISTs. [ABSTRACT FROM AUTHOR]

Interleukin-1β (IL-1b) is a pleiotropic cytokine that is important in tumor progression and invasion. Matrix metalloproteinase-9 (MMP-9), which is a secreted matrix-degrading enzyme, is one of the key regulators of tumor invasion and metastasis. The current report indicated that IL-1b promotes MMP-9 production and cell invasion in non-metastatic MCF-7 breast cancer cells. IL-1b activated focal adhesion kinase (FAK) and proto-oncogene tyrosine-protein kinase Src (Src). Moreover, inhibiting the Src/FAK pathway reduced the IL-1b-induced production of MMP-9 and cell invasion. To investigate the functional role of FAK in MMP-9 production cell lines expressing mutant FAK in FAK knock-out mouse fibroblasts were generated. In wild-type FAK-expressing cells, MMP-9 production was induced by IL-1b stimulation. By contrast, IL-1b-induced MMP-9 production was abrogated in FAK knock-out, FAK Y397F, FAK Y925F, and kinase dead mutant-expressing cells. Therefore the results of the current study indicate that FAK and Src kinases are activated by IL-1b and play a critical role in MMP-9 production and tumor cell invasion. [ABSTRACT FROM AUTHOR]

Thyroid hormone receptor interactor 13 (TRIP13) is a member of the ATPases associated with various cellular activities family of proteins and is highly conserved in a wide range of species. Recent studies have demonstrated that TRIP13 is critical for the inactivation of the spindle assembly checkpoint and is associated with the progression of certain cancers. In the present study, the role of TRIP13 in colorectal cancer (CRC) was examined. Reverse transcription-quantitative polymerase chain reaction analysis revealed that TRIP13 messenger RNA was highly expressed in multiple CRC tissues. The depletion of TRIP13 in CRC cells suppressed cell proliferation, migration and invasion. To determine whether the catalytic activity of TRIP13 was critical for cancer progression, an inactive mutant of TRIP13 was expressed in CRC cells. The invasion of cancer cells that expressed the mutant TRIP13 was significantly reduced compared with that of the wild type TRIP13-expressing cancer cells. These results indicate that TRIP13 could be a potential target for CRC treatment. [ABSTRACT FROM AUTHOR]

Proper bioriented attachment of microtubules and kinetochores is essential for the precise distribution of duplicated chromosomes to each daughter cell. An aberrant kinetochore-microtubule attachment results in chromosome instability, which leads to cellular transformation or apoptosis. In this article, we show that ubiquitin-associated protein 2-like (UBAP2L) is necessary for correct kinetochore-microtubule attachment. Depletion of UBAP2L inhibited chromosome alignment in metaphase and delayed progression to anaphase by activating spindle assembly checkpoint signaling. In addition, UBAP2L knockdown increased side-on attachment of kinetochores along the microtubules and suppressed stable kinetochore fiber formation. A proteomics analysis identified protein arginine methyltransferase (PRMT)1 as a direct interaction partner of UBAP2L. UBAP2L has an arginine- and glycine-rich motif called the RGG/RG or GAR motif in the N terminus. Biochemical analysis confirmed that arginine residues in the RGG/RG motif of UBAP2L were directly methylated by PRMT1. Finally, we demonstrated that the RGG/RG motif of UBAP2L is essential for the proper alignment of chromosomes in metaphase for the accurate distribution of chromosomes. Our results show a possible role for arginine methylation in UBAP2L for the progression of mitosis.--Maeda, M., Hasegawa, H., Sugiyama, M., Hyodo, T., Ito, S., Chen, D., Asano, E., Masuda, A., Hasegawa, Y., Hamaguchi, M., Senga, T. Arginine methylation of ubiquitin-associated protein 2-like is required for the accurate distribution of chromosomes. [ABSTRACT FROM AUTHOR]

Cancer remains one of the leading causes of human mortality worldwide. Radiation and chemotherapy are commonly used for cancer treatment; however, the combination of these therapies and surgery do not completely eradicate cancer cells. Near-infrared radiation (NIR) is a low-energy form of radiation that exerts multiple effects on mammalian cells. Previous studies have reported that NIR induces DNA double-strand breaks and apoptosis of cancer cells. In the present study, a 915-nm laser was used to examine the effects of NIR on pancreatic cancer cells. Irradiation of pancreatic cancer cells using a 915-nm laser significantly induced caspase-3 activation and apoptosis. In addition, the combination of gemcitabine treatment and a 915-nm laser synergistically increased the number of apoptotic cells. The results of the present study indicate the use of infrared irradiation and chemotherapy may be a possible therapy for the treatment of cancer. [ABSTRACT FROM AUTHOR]

Cervical cancer is a major global public health care concern and the second most commonly diagnosed malignancy among females worldwide. B7-H4 is an immunoregulatory protein that has been shown to be overexpressed in several types of cancer and is often associated with more advanced disease and poor prognosis. We investigated whether B7-H4 is a prognostic maker for cervical cancer by detecting its expression in cervical cancer specimens. Formalin-fixed, paraffin-embedded tissue blocks from cervical cancer were evaluated for B7-H4 expression by immunohistochemistry with free R software analysis. The intensity of B7-H4 immunoexpression was evaluated according to age, histological type, International Federation of Gynecology and Obstetrics (FIGO) stage, lymphovascular space invasion (LVSI) and lymph node status. We investigated the distribution and expression of B7-H4 in 102 cervical cancer specimens and determined the association between its expression and clinicopathological characteristics, including patient outcomes. Of the 102 specimens, 31 were found to be negative for B7-H4 immunoexpression, whereas 71 were B7-H4-positive. When classified by negative vs. positive expression, B7-H4 was not found to be associated with any of the clinicopathological parameters investigated. A positive B7-H4 expression significantly predicted poor overall survival (OS) when compared to negative expression (P<0.05). In the multivariate analysis, positive B7-H4 expression was identified as an independent prognostic factor for OS (P<0.05). Our data suggested that positive B7-H4 expression may be a useful biomarker in patients with cervical cancer likely to have an unfavorable clinical outcome. [ABSTRACT FROM AUTHOR]

Polo-like kinase 1 (PLK1) is a wiΔely conserveΔ serine/threonine kinase that regulates progression of multiple stages of mitosis. Although extensive stuΔies about PLK1 functions Δuring cell Δivision have been performeΔ, it is still not known how PLK1 regulates myosin II activation at the equatorial cortex anΔ ingression of the cleavage furrow. In this report, we show that an actin/myosin-IIbinΔing protein, supervillin (SVIL), is a substrate of PLK1. PLK1 phosphorylates Ser238 of SVIL, which can promote the localization of SVIL to the central spinΔle anΔ association with PRC1. Expression of a PLK1 phosphorylation site mutant, S238A-SVIL, inhibiteΔ myosin II activation at the equatorial cortex anΔ inΔuceΔ aberrant furrowing. SVIL has both actin- anΔ myosin-II-binΔing regions in the N-terminus. Expression of ΔMyo-SVIL (ΔeleteΔ of the myosin-II-binΔing region), but not of ΔAct-SVIL (ΔeleteΔ of actin-binΔing region), reΔuceΔ myosin II activation anΔ causeΔ Δefects in furrowing. Our stuΔy inΔicates a possible role of phosphorylateΔ SVIL as a molecular link between the central spinΔle anΔ the contractile ring to coorΔinate the activation of myosin II for the ingression of the cleavage furrow. [ABSTRACT FROM AUTHOR]

A three-dimensional (3D) cell culture system has been fabricated using a magnetic force based cell patterning method, demonstrating a facile approach for the analysis of invasive capacity of BALB/3T3/v-srcusing an magnetic force and magnetite nanoparticles. The 3D cell patterning was performed using an external magnetic force and a pin holder, which enables the assembly of the magnetically labeled cells on the collagen gel-coated surface as array-like cell patterns, resulting in the development of a 3D in vitroculture model. The cells embedded in type I collagen showed a compacted, spheroid like configuration at each spot, and distinct, accelerated cell growth was observed in cancer model cells compared with the control cells. The developed 3D cell culture array was applied to the susceptibility assay of the GM6001 matrix metalloproteinase (MMP) inhibitor, a collagenase inhibitor; a distinct suppression of cell proliferation was observed, while little change was observed in 2D. The developed 3D cell culture array system is useful to assess the effects of pharmacologic and/or microenvironmental influences on tumor cell invasion. [ABSTRACT FROM AUTHOR]