Annexin A10 (ANXA10) is a member of the annexin family and a calcium-dependent phospholipid-binding protein. The aim of this study was to clarify the clinical significance of ANXA10 expression in lung adenocarcinoma.

ANXA10 expression was immunohistochemically examined in surgical specimens of lung adenocarcinoma obtained from 74 consecutive patients who underwent complete resection from January 2014 to December 2014. Expression of ANXA10 was down-regulated in A549 cells via siRNA transfection and the effect of ANXA10 on cell migration was assessed by the wound healing assay. Expression of ANXA10 was examined by immunocytochemistry and polymerase chain reaction.

High ANXA10 expression was significantly correlated with poor overall survival (p=0.00705). Multivariate analysis with the Cox proportional hazard model demonstrated that ANXA10 expression was an independent prognostic factor. Cell migration was suppressed in ANXA10-down-regulated A549 cell lines.

ANXA10 has a role in cancer cell migration and high ANXA10 expression is a novel prognostic marker in lung adenocarcinoma.

ANXA10 has a role in cancer cell migration and high ANXA10 expression is a novel prognostic marker in lung adenocarcinoma.

The acquisition of resistance to apoptosis is one of the biggest problems in colorectal cancer (CRC) treatment. This study aimed to elucidate the mechanisms of resistance to apoptosis with a focus on interleukin (IL)-6 produced by the interaction between cancer cells and cancer-associated fibroblasts (CAFs).

DLD-1 and HCT116 cell lines were treated with IL-6 and furthermore co-cultured with CAFs. The expression levels of Bcl-xL, Mcl-1 and phosphorylation of STAT3 were evaluated by western blotting. We also performed immunostaining for CRC specimens and evaluated the correlation between CAFs invasion and Bcl-xL/Mcl-1 expression.

Both IL-6 and co-culturing enhanced Bcl-xL, Mcl-1 and the phosphorylation of STAT3. Immunohistochemistry showed a positive correlation between CAFs and Bcl-xL/Mcl-1. These results showed that the interaction between CAFs and cancer cells enhances Bcl-xL and Mcl-1 through the IL-6/STAT3 signaling pathway.

Our findings provide new potential therapeutic targets and strategies for CRC treatment.

Our findings provide new potential therapeutic targets and strategies for CRC treatment.

Drug resistance to molecular targeted agents, such as lenvatinib, is an important issue. The aim of this study was to explore the mechanism of lenvatinib resistance and to investigate potential drugs that may improve the treatment of lenvatinib-resistant (LR) hepatocellular carcinoma (HCC).

LR cells were developed by long-term culture under lenvatinib exposure. We analyzed the biological characteristics of LR cells in vitro, and investigated the antitumor effects and endogenous mechanisms of cisplatin in LR cells.

The proliferative potential of LR cells was enhanced by activation of ERK signaling and changes in several miRNAs. Cisplatin inhibited cell proliferation of LR cells and induced G2/M cell cycle arrest. Furthermore, cisplatin triggered the DNA damage response, via the ATM/ATR-Chk1/Chk2 signaling pathway.

Proliferation of LR cells was induced upon ERK signaling activation. Cisplatin exerted antitumor effects in LR cells and was involved in the regulation of miRNAs associated with drug resistance.

Proliferation of LR cells was induced upon ERK signaling activation. Cisplatin exerted antitumor effects in LR cells and was involved in the regulation of miRNAs associated with drug resistance.

The aim of the present investigation was to characterize the growth pattern and antigen profile of peripheral nerve sheath tumors (PNST) in a large series of tumors obtained from patients with Neurofibromatosis type 1 (NF1) focusing on morphological characteristics of diffuse plexiform neurofibroma (DPNF).

Tissue micro-array (TMA) analysis was applied to study 520 formalin-fixed, paraffin-embedded human PNST of 385 patients with confirmed NF1 diagnosis. PNST originated from all areas of the body and were classified as cutaneous neurofibroma (CNF, n=114), diffuse neurofibroma (DNF, n=109), DPNF (n=108), plexiform neurofibroma (PNF, n=110), and malignant peripheral nerve sheath tumor (MPNST, n=22). Histomorphology and antigen expression patterns of the tumors were determined [S100, epithelial membrane antigen (EMA), CD90, mast cell tryptase, and neurofilament].

Benign PNST showed significantly more S100-positive tumor cells than MPNST (p<0.001). EMA expression was most pronounced in perineurium of DPNFow some distinct cellular characteristics. A high number of EMA positive cells possibly indicates the dissemination of perineural cells to the surrounding tissue. Concerning mast cell density, DPNF resemble DNF and CNS rather than PNF. Close contact of tumor cells in DPNF, DNF and CNF with the immune system is a prerequisite for permanent immunological reactions in contrast to PNF in which tumor cells are partitioned from the immune system by the perineurium and blood-nerve barrier of blood vessels. It is assumed that these morphological distinctions may reflect in part the biological differences between the entities. While PNF is a known precancerous stage in NF1 patients, DPNF are not rated as such. Furthermore, the morphologic differences between benign nerve sheath tumors may be important for the efficacy of drugs to access tumor cells.

Low-grade gliomas (LGG) are heterogenous tumours, causing variable survivals in patients. Identifying molecular markers for a more accurate prognosis is, therefore, important. Since death receptor 6 (DR6) is up-regulated in gliomas and shows an aberrant signalling network, we tested its suitability as a prognostic marker.

DR6 was investigated in patient samples via PCR and western blot. Clinical data were analysed and compared to The Cancer Genome Atlas (TCGA) 'brain lower grade glioma’ dataset.

DR6 was found to be enhanced in LGG and its expression increased in recurrent LGG. The receptor showed a protective effect in primary LGG with a significantly elongated progression-free survival that was confirmed in the TCGA study. This effect was reversed in relapsed LGG in which cases with high DR6 expression reveal a shorter overall survival.

DR6 is an interesting candidate for further studies regarding its effect as a prognostic marker, playing an opposing role in primary and relapsed LGG.

DR6 is an interesting candidate for further studies regarding its effect as a prognostic marker, playing an opposing role in primary and relapsed LGG.

Chronic inflammation is believed to play a critical role in the pathogenesis of lung cancer. Interleukin-8 (IL-8) is an inflammatory cytokine and plays an important role in cancer development. Few studies have investigated the association between interleukin-8 – 251T/A (rs4073) genotype and lung cancer risk in various populations.

In the current study, genotypes of interleukin-8 rs4073 were analyzed in 358 lung cancer patients and 716 healthy controls in Taiwan, by the PCR-RFLP methodology.

The distribution frequencies of interleukin-8 rs4073 genotypes between control and case groups were compared, and the homozygous variant AA genotypes showed a lower percentage in the case group compared to the control group (OR=0.57, 95%CI=0.39-0.85, p=0.0059). The distributions of alleles frequencies also exhibited statistical difference (p=0.0066). There was an interaction between interleukin-8 rs4073 and smoking habits (p=0.0051).

Interleukin-8 rs4073 genotypes were associated with lung cancer susceptibility, especially for smokers.

Interleukin-8 rs4073 genotypes were associated with lung cancer susceptibility, especially for smokers.

γ-Glutamyl cyclotransferase (GGCT) is up-regulated in various cancer types, including lung cancer. In this study, we evaluated efficacy of gapmer-type antisense oligonucleotides (ASOs) targeting GGCT in an A549 lung cancer xenograft mouse model and studied their mechanisms of action.

GGCT was inhibited using GGCT-ASOs and cell proliferation was evaluated by dye exclusion test. Western blot analysis was conducted to measure expression of GGCT, p21, p16 and p27, phosphorylation of AMP-activated protein kinase, and caspase activation in A549 cells. Induction of apoptosis and up-regulation of reactive oxygen species were assessed by flow cytometry using annexin V staining and 2′,7′-dichlorodihydrofluorescein diacetate dye, respectively.

GGCT-ASOs suppressed GGCT expression in A549 cells, inhibited proliferation, and induced apoptosis with activation of caspases. GGCT-ASOs also increased expression of cell-cycle regulating proteins, phospho-AMPK and ROS levels. Systemic administration of GGCT-ASOs to animals bearing A549 lung cancer xenografts showed significant antitumor effects without evident toxicity.

GGCT-ASOs appear to be promising as novel cancer therapeutic agents.

GGCT-ASOs appear to be promising as novel cancer therapeutic agents.

Kindlins are essential integrin activators. Kindlin-1 and kindlin-2 are often concomitantly expressed in epithelial tumor cells and participate in regulating tumor malignancy. However, it remains unclear whether kindlin-3, the one expressed in immune cells, also plays a role in regulating tumor malignancy.

To examine the role of kindlin-3 in different immune cells in regulating solid tumor growth, a xenograft model of prostate cancer tumor growth in genetically modified kindlin-3 mice was employed.

Disruption of crosstalk between kindlin-3 and integrins significantly promoted subcutaneous prostate cancer tumor growth in mice. Furthermore, deficiency of kindlin-3 in T cells and NK cells, but not myeloid cells and B cells, significantly enhanced prostate cancer tumor growth.

Tumor-killing leukocytes require Kindlin-3 for suppressing cancerous tumor growth, thus providing a novel anticancer mechanism.

Tumor-killing leukocytes require Kindlin-3 for suppressing cancerous tumor growth, thus providing a novel anticancer mechanism.

We aimed to clarify the role of complement C3a and its receptor C3aR in progression of pancreatic ductal adenocarcinoma (PDAC).

We evaluated the serum levels of C3 and C3a in patients with PDAC. C3aR expression in tissue was assessed using a tissue microarray. To confirm the protumoral effects of C3a in PDAC, we conducted in vitro experiments using PDAC cell lines (Panc-1 and MiaPaca-2) that exhibit high C3aR expression.

Serum levels of both C3 and C3a were higher in 26 patients with PDAC than in 28 nontumor-bearing controls. In the tissue microarray, we observed increased expression of C3aR in PDAC cells, especially in cases with metastatic lesions. In vitro experiments showed that C3a facilitated tumor cell proliferation, migration and invasion by activating the extracellular-regulated kinase signaling pathway and inducing epithelial-to-mesenchymal transition. Inhibition of the C3a-C3aR axis by pharmacological blockade and short-hairpin RNA-mediated knockdown of C3aR alleviated its protumoral effect.

These findings provide a new approach for the development of treatments targeting the C3a-C3aR axis.

These findings provide a new approach for the development of treatments targeting the C3a-C3aR axis.