Toshiyuki Nakasone

Regulation of chemokine production via oxidative pathway in HeLa cells.

Inflammation is associated with disease progression and, by largely unknown mechanisms, has been said to drive oncogenesis. At inflamed sites, neutrophils deploy a potent antimicrobial arsenal that includes proteinases, antimicrobial peptides, and ROS. Reactive oxygen species (ROSs) induce chemokines. In the present study, the concentrations of IL-8 in culture supernatants of HeLa cells treated with ROS were determined by enzyme-linked immunosorbent assay. We used o-phenanthroline to deplete Fe2+ in order to investigate the mechanisms through which ROSs induce IL-8 secretion in our system. The iron chelator o-phenanthroline effectively inhibited H2O2-induced ERK2 activation. Enzyme-linked immunosorbent assays showed that IL-8 protein secretion was elevated in ROS-treated HeLa cells. When Fe2+ was removed from these cells, IL-8 secretion was inhibited. Collectively, these results indicate that Fe2+-mediated Erk pathway activation is an important signal transduction pathway in ROS-induced IL-8 secretion in epithelial cells.

PDGF α receptor is a mediator for Cisplatin-induced Met expression.

For decades, platinum drugs have been the mainstay of cancer treatment. However, over time, drug resistance develops, leaving few treatment options. Here we show that platelet-derived growth factor α receptor (PDGF α receptor)-mediated signaling plays a key role in hepatocyte growth factor (HGF) receptor (c-Met) upregulation, which in turn is thought to play an important role in chemotherapy resistance. PDGF α receptor inhibition eliminates cisplatin-dependent Met expression in cervical cancer cell lines. PDGF α receptor inhibitors are widely used in clinical settings, suggesting that the clinical translation of our findings could reduce the suffering of people from drug resistance.

Mast Cell-Derived VEGF Enhances the Passage of IgE FE-3 through the Rat Aortic Endothelial Cell Monolayer

Background: It is well known that the IgE-mediated allergic reaction in various extravascular tissues is induced by the mutual interaction of IgE, target cells (mast cells, MCs) and allergens. However, so far little has been known about the detailed mechanism whereby IgE in the circulating blood is transferred to the extravascular tissue. To examine whether or not MCs are involved in the permeability of IgE across rat aortic endothelial cells (RAECs) in vitro, we determined the permeability constant (PC) of dinitrophenyl-specific rat IgE (IgE FE-3) using a dual chamber system. Methods: Isolated RAECs obtained by a primary explant technique were seeded on a collagen-coated membrane in the upper chamber. MCs were collected from the peritoneal cavity of Wistar rats and suspended in the lower chamber. The time-dependent changes in concentration of IgE FE-3 (IgE) in the upper and lower chambers were measured by IgE capture ELISA after addition of IgE (10 µg/ml) to the upper chamber. Results: The cultured medium of IgE-stimulated MCs significantly increased the PC of IgE (9.86 ± 0.46 × 10–6 cm/s), as compared to the value to which calcium ionophore A 23187-stimulated MCs increased the PC of IgE (7.97 ± 0.21 × 10–6 cm/s). The increase of PC by IgE-stimulated MCs was most strongly inhibited by suramin (92.3% ± 1.89), and was weakly inhibited by tranexamic acid, cimetidine and diphenhydramine. In addition, the PC of IgE was increased with the increase in the MC-derived vascular endothelial growth factor/permeability factor (VEGF). Conclusions: After IgE is transferred from the circulating blood to the extravascular tissue, it may bind to FcΕRI of the MC and the other FcΕRI-bearing cells. The MC is then activated through the interaction of IgE and FcΕRI. Release of VEGF from the activated MC increases, and the VEGF enhances the permeability of IgE.

Analysis of IgE turnover in non-sensitized and sensitized rats.

BACKGROUND: Although the levels of immunoglobulin E (IgE) in the circulating blood are often elevated in patients with allergic diseases, such levels cannot always be considered as pathognomonic signs of allergy. The induction of allergic reactions in the tissue was inferred to be related to the amount of IgE passing through the vascular wall. AIMS: We attempted to clarify which compartment, the intravascular or extravascular, plays an important role in the regulation of the turnover of rat IgE. METHODS: The level of DNP-specific rat IgE in the serum was estimated by IgE-capture enzyme-linked immunosorbent assay, and the turnover of IgE was analyzed from its pharmacokinetic parameters. RESULTS: The transfer rate constants from the central to tissue compartment (Kct) were larger than those from the tissue to central compartment (Ktc) irrespective of the sensitized state. The value of the distribution volume of the tissue compartment (Vt) was larger than that of the distribution volume of the central compartment (Vc) irrespective of the sensitized state. CONCLUSIONS: These Findings suggest that the short half-life of rat IgE in the circulation could be attributable to the distribution of IgE from the intravascular to the extravascular compartment.

Azelastine and suplatast shorten the distribution half-life of IgE in rats

We aim to clarify whether suplatast and azelastine (anti-allergic drugs) can shorten the half-life of imnunoglobulin E (IgE) in the circulating blood. Thirty Wistar rats were divided into six groups. Distilled water or anti-allergic drugs were given orally for 6 days after the first sensitization. Two milligrams of monoclonal dinitrophenyl (DNP)-specific rat IgE was administered to the rats, which had been given suplatast or azelastine orally. The level of DNP-specific rat IgE in the serum was estimated by IgE-capture enzyme-linked immunosorbent assay, and the turnover of IgE was analyzed from its pharmacokinetic parameters. The elimination half-life of rat IgE was about 12 h irrespective of the sensitized state. The intercompartmental rate constants (Kct and Ktc) in the suplatast-administered or azelastine-administered group were larger than those of the distilled water-administered group under non-sensitized conditions. These findings suggested that the anti-allergic drugs used in the present study facilitated the excretion of IgE from the circulation in rats.

Indolent growth of low-grade myofibroblastic sarcoma of the cheek mimics benign lesions: A case report and literature review

Low-grade myofibroblastic sarcoma (LGMS) is a neoplasm of the soft tissue characterized by myofibroblastic differentiation. This type of tumor has been observed in various sites in the whole body, but frequently occurs in the head and neck region. It typically presents as a slow-growing painless mass, which is often mistaken for a benign lesion due to its indolent growth; however, LGMS is a malignant neoplasm. In the present study, a 43-year-old female presented with a 14-mm LGMS lesion in the buccal subcutaneous tissues of the buccinator muscle. The patient had initially noticed the lesion 2-months prior to presenting at the hospital. Following biopsy, the tumor was surgically resected and no recurrence or metastasis was observed during a follow-up time of 2 years. To the best of our knowledge, this case is the first report of LGMS located in the buccal subcutaneous tissue of the buccinator muscle. The present study a literature review of 55 cases of this tumor type in the head and neck region was conducted, revealing that the indolent growth of these lesions may contribute to a delay in diagnosis. The average time between the onset of clinical symptoms and hospital admission is 3.9 months, and this form of tumor is frequently misdiagnosed as a benign lesion. Therefore, the present study suggests that an incisional biopsy may be performed to rule out LGMS when clinicians encounter patients with the aforementioned indolent lesions anywhere in the body. In addition, the avoidance of radiotherapy is recommended following resection of the LGMS tumor, as it may induce LGMS recurrence.

Malignant Pheochromocytoma with Mandibular Metastasis

Abstract Malignant pheochromocytoma of the mandible is an extremely uncommon tumour. This report describes a 59-year-old woman with pheochromocytoma metastatic to the mandible. The patient was referred with a painless mandibular swelling on the right side. She had undergone dual tumour ablation for a pheochromocytoma of the adrenal medulla 7 years and 6 months previously, and for a pheochromocytoma metastatic lesion on the pelvis 2 years and 8 months previously. Radiographic examinations revealed a well-circumscribed radiolucent lesion of the mandibular ramus. A definitive diagnosis of malignant pheochromocytoma was made following a partial mandibulectomy. The patient died of disseminated intravascular coagulation and multiple bone metastases of pheochromocytoma about 10 years after the initial diagnosis of disease.

Triple primary malignancies of surface osteosarcoma of jaw, myelodysplastic syndrome and colorectal cancer as a second primary cancer detected by PET2‑[18F]‑fluoro‑2‑deoxy‑D‑glucose positron emission tomography: A case report

Second primary malignancy (SPM) is a severe issue for cancer survivors, particularly for osteosarcoma (OS) survivors. To date, the associations between subsequent SPM and OS have been well reported. Hematogenic and solid malignancies tend to occur following OS treatment. Reportedly, 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is mainly used in OS patients for initial cancer staging, to evaluate the response of neoadjuvant chemotherapy, and when recurrence or metastasis is clinically suspected. The present case report describes a 70-year-old man diagnosed with three primary malignancies: jaw OS, myelodysplastic syndrome and colorectal adenocarcinoma. To the best of our knowledge, this combination of malignancies has not been reported previously. Until now, there is no specific protocol of postoperative FDG-PET for OS patients. Few studies have described OS follow-up methods; therefore, there is no consensus on proper follow-up methods. In the present case report, the colorectal early-stage SPM was observed, without any symptoms, by FDG-PET/computed tomography. To avoid overlooking solid SPMs, it is suggested that FDG-PET should be performed in the long-term follow-up of OS patients.

Triple primary cancer of the head and neck, skin and prostate: A case report and literature review

Second primary cancer (SPC) is an important prognostic factor for patients with head and neck cancer (HNC); therefore, the association between the prognosis and development of SPC has been well-reported. The use of 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) is valuable to examine cancer stage, evaluate treatment responses and investigate suspected relapses or metastases. In the present study, the case of a male patient who was diagnosed with three primary cancer types, including well to moderately differentiated squamous cell carcinoma (SCC) of the mandible, axillary cutaneous poorly differentiated SCC and prostate adenocarcinoma, was described. Among these, mandible cancer was the first diagnosed when the patient was 70 years of age. Synchronous skin and prostate cancer (PRC) types then developed 3 years later. To the best of our knowledge, this is the first report of the aforementioned combination of cancer types. Postoperative FDG-PET was not performed as no lesions of recurrence or metastases of mandible cancer were found. Three years later, the PRC was asymptomatic and was incidentally detected by FDG-PET performed for a preoperative evaluation of skin cancer. It was indicated that FDG-PET could be utilized in patients with HNC due to there being no accurate FDG-PET protocol to detect SPC over a long-term follow-up.

Dedifferentiated liposarcoma of the oral floor: A case study and literature review of 50 cases of head and neck neoplasm

Dedifferentiated liposarcoma (DDLS) has a relatively poor prognosis, however this neoplasm rarely occurs in the head and neck. To date, no definite protocol has been established for the diagnosis and treatment of head and neck DDLS. The present study reports the case of a 69-year-old male patient with DDLS of the oral floor. To the best of our knowledge, this is the first documented case of oral floor DDLS. In addition, this is the first reported case with the development of a second primary malignancy following the treatment of head and neck DDLS. A literature review of 50 cases of head and neck DDLS revealed that preoperative biopsy is not reliable for the diagnosis of these tumors and an accurate pathological diagnosis with total resection is preferred.