Osteopontin-integrin α(v)β(3) axis is crucial for 5-fluorouracil resistance in oral squamous cell carcinoma.

Clinical applications of a chemotherapeutic agent, 5-fluorouracil (5-FU) in oral squamous cell carcinoma (OSCC) have been limited because of drug resistance. This study aimed to identify novel mechanisms of 5-FU resistance. Here we found increased osteopontin (OPN) gene expression in OSCC tissues with resistance to 5-FU-based chemoradiotherapy.

Stromal expression of neutrophil gelatinase-associated lipocalin correlates with poor differentiation and adverse prognosis in oral squamous cell carcinoma.

Aims: Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin superfamily. Although its overexpression in various cancers has been reported, little is known about its expression and clinical significance in oral squamous cell carcinoma (OSCC). This study aimed to elucidate the clinical significance of NGAL in OSCC.

Downregulation of midkine induces cisplatin resistance in human oral squamous cell carcinoma.

The presence of drug-resistant cancer cells has been associated with poor clinical outcomes. Cisplatin is one of the most effective chemotherapeutic agents commonly used for several malignancies including oral squamous cell carcinoma (OSCC). Although cisplatin resistance is a major obstacle in cancer treatment, mechanisms by which it develops are not well understood.

Selective inhibition of nuclear factor-κB by nuclear factor-κB essential modulator-binding domain peptide suppresses the metastasis of highly metastatic oral squamous cell carcinoma.

Nuclear factor-κB (NF-κB) activation contributes to the development of metastasis, thus leading to a poor prognosis in many cancers, including OSCC. However, little in vivo experimental data are available about the effects of NF-κB inhibition on OSCC metastasis. OSCC sublines were established from a GFP-expressing parental cell line, GSAS, and designated GSAS/N3 and N5 according to the in vivo passage number after cervical lymph node metastasis by a serial orthotopic transplantation model.

Therapeutic approaches targeting midkine suppress tumor growth and lung metastasis in osteosarcoma.

Midkine (MK) plays important roles in tumorigenesis, however, the biological function of MK and whether MK can be a therapeutic target in osteosarcoma are unclear. Here, we found that osteosarcoma tissues showed high MK expression. MK knockdown by small interfering RNA significantly induced apoptosis in osteosarcoma cells, whereas recombinant MK increased cell proliferation.

Interleukin-6 signalling regulates vascular endothelial growth factor-C synthesis and lymphangiogenesis in human oral squamous cell carcinoma.

Lymph node metastasis is associated with resistance to conventional therapy and poor survival of patients with oral squamous cell carcinoma (OSCC). Although lymphangiogenesis is well known to be associated with the occurrence of lymph node metastasis in various cancers, the precise mechanisms of lymphangiogenesis in OSCC are largely unknown. IL-6, a potent pro-inflammatory cytokine, has been shown to play active roles in various cancers, including OSCC.

Midkine expression is correlated with an adverse prognosis and is down-regulated by p53 in oral squamous cell carcinoma.

Midkine (MK) expression has been documented to be inversely correlated with the prognosis of patients with various tumors, but the mechanism of this relationship has not been well characterized. Recent studies have also correlated p53 expression with prognosis of patients with oral squamous cell carcinoma (OSCC). We evaluated the relationship between MK expression and clinicopathological features of patients with OSCC to clarify the influence of p53 status on MK expression in OSCC cells.

Midkine expression in malignant salivary gland tumors and its role in tumor angiogenesis.

The aims of this study were to investigate midkine (MK) expression patterns in salivary gland tumors (SGTs) and to evaluate the correlation between MK expression and the degree of malignancy. We performed immunohistochemistry to examine MK expression in specimens of adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC), and pleomorphic adenoma (PA). In addition, we performed immunohistochemistry for CD31 and measured microvessel density (MVD), which is an indicator of angiogenesis.

Humanized anti-interleukin-6 receptor antibody suppresses tumor angiogenesis and in vivo growth of human oral squamous cell carcinoma.

Purpose: The biological effect of interleukin-6 (IL-6) signaling in oral squamous cell carcinoma (OSCC) and whether IL-6 receptor (IL-6R)-mediated signaling can be a therapeutic target for OSCC are unclear. The aim of this study was to investigate the effects of inhibition of IL-6R-mediated signaling on OSCC progression and to evaluate the availability of tocilizumab, a humanized antihuman IL-6R antibody, as a therapeutic agent for OSCC.

Experimental Design: We evaluated expression levels of IL-6 and IL-6R in 58 OSCC tissues and 4 OSCC cell lines by real-time quantitative reverse transcription-PCR and/or immunohistochemstry.

Phase II study of preoperative concurrent chemoradiation therapy with S-1 in patients with T4 oral squamous cell carcinoma.

Purpose: To determine the feasibility and efficacy of preoperative concurrent chemoradiation therapy (CCRT) with S-1, an oral fluoropyrimidine derivative, in patients with T4 oral squamous cell carcinoma (SCC).

Methods And Materials: Only patients with histologically proven T4 oral SCC were included. Radiotherapy (total dose, 30 Gy) was delivered in 2-Gy daily fractions over a period of 3 weeks.

Midkine in plasma as a novel breast cancer marker.

Midkine, a heparin-binding growth factor, is up-regulated in many types of cancer. The aim of this study was to measure plasma midkine levels in patients with breast cancer and to assess its clinical significance. We examined plasma midkine levels in 95 healthy volunteers, 11 patients with ductal carcinoma in situ (DCIS), 111 patients with primary invasive breast cancer without distant metastasis (PIBC), and 25 patients with distant metastatic breast cancer (MBC), using an automatic immunoasssay analyzer (TOSOH AIA system).

Aberrant expression of serum amyloid A in head and neck squamous cell carcinoma.

Serum amyloid A (SAA) is an acute-phase reactant, the blood level of which is often elevated in response to some types of neoplasia. Here, we investigated expression of the gene SAA1 and the protein SAA in head and neck squamous cell carcinoma (HNSCC) and normal oral mucosal tissues as well as blood SAA levels in HNSCC patients. Also, we investigated the effects of inhibiting signal transducer and activator of transcription 3 (STAT3) signaling on SAA1 expression in the HNSCC cell line SAS.

SELDI-TOF mass spectrometry evaluation of variant transthyretins for diagnosis and pathogenesis of familial amyloidotic polyneuropathy.

Background: Mass spectrometric analyses are valuable for detection of transthyretin (TTR) variants, which cause familial amyloidotic polyneuropathy (FAP). However, those methods require an immunoprecipitation step with an anti-TTR antibody and are not suitable for quantitative detection. We investigated the usefulness of SELDI-TOF mass spectrometry (MS) without an immunoprecipitation step.

Antitumor effect of humanized anti-interleukin-6 receptor antibody (tocilizumab) on glioma cell proliferation. Laboratory investigation.

Object: Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates diverse physiological functions, including cell proliferation and survival. Recent studies have shown that IL-6 expression is often elevated in response to several types of glioma. Although IL-6 is said to play an important role in glioma, the involvement of IL-6 signaling has been quite controversial.

Role of conformational change in the C-terminus of beta2-microglobulin in dialysis-related amyloidosis.

Background: Beta(2)-microglobulin (beta(2)m) has been identified as the precursor protein of dialysis-related amyloidosis (DRA), which is a serious complication for haemodialysis (HD) patients. However, mechanisms underlying beta(2)m amyloid fibril formation remains to be elucidated. We previously demonstrated, in amyloid deposits from HD patients, a conformational isoform of beta(2)m with an unfolded C-terminus.

Impact of FDG-PET/CT imaging on nodal staging for head-and-neck squamous cell carcinoma.

Purpose: To evaluate the impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging on nodal staging for head-and-neck squamous cell carcinoma (SCC).

Methods And Materials: The study population consisted of 23 patients with head-and-neck SCC who were evaluated with FDG-PET/CT and went on to neck dissection. Two observers consensually determined the lesion size and maximum standardized uptake value (SUVmax) and compared the results with pathologic findings on nodal-level involvement.

ADAM-17 associated with CD44 cleavage and metastasis in oral squamous cell carcinoma.

ADAM-17 (a disintegrin and metalloproteinase 17) is a membrane-anchored protein, which can cleave the ectodomain in a variety of transmembrane proteins. In the in vitro experiments with tumor cells, ADAM-17 is reported to cleave CD44, an adhesion molecule that interacts with hyaluronic acid, to promote tumor cell migration. In the present study, we examined ADAM-17 expression and CD44 cleavage in specimens from 50 patients diagnosed to have oral squamous cell carcinoma (SCC).