Izumi Yoshitomi

Nagasaki University, Nagasaki-shi, Nagasaki-ken, Japan

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Publications (34)40.64 Total impact

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    ABSTRACT: OBJECTIVES: Toxins, such as PCBs, dramatically affect patients even decades after exposure. Although 40 years have passed since the accidental poisoning with polychlorinated biphenyl (PCB) in Western Japan in 1968, high concentrations of PCBs are still detected in the serum of the "Yusho" (oil disease) patients. In this study, an epidemiological examination was carried out to reveal the prevalence of the oral pigmentation and blood concentrations of PCBs and polychlorinated quaterphenyl (PCQ) in Yusho victims. DESIGN: We performed a group examination of patients (Yusho victims) from 2004 to 2006, including 72 Yusho victims and 15 control subjects. The oral examination was performed by two oral and maxillofacial surgeons. The serum concentrations of PCB and PCQ were determined using gas chromatography; blood samples from Yusho victims were analyzed for PCB and PCQ by saponification in 1M NaOH ethanol solution, extraction with n-hexane column chromatography on silica gel, and then gas chromatography with electron capture detection. RESULTS: The mean Yusho victim's serum PCB and PCQ concentrations were 3.3ppb and 0.9ppb, respectively. In controls, these were 0.7ppb and 0ppb, respectively. Oral pigmentation was observed in 24 out of 72 Yusho patients. In controls, oral pigmentation was observed in one out of 15 persons. Oral pigmentation was most frequently observed in the buccal mucosa, followed by gingival mucosa. The blood concentration of PCB in Yusho patients with oral pigmentations was significantly higher than that in Yusho patients without oral pigmentation. CONCLUSION: These results indicated that PCB-related compounds may be responsible for the higher prevalence of oral pigmentation in Yusho victims, even though a long time has passed since the Yusho poisoning accident.
    Archives of oral biology 05/2013; · 1.65 Impact Factor
  • Goro Kawasaki, Izumi Yoshitomi, Masahiro Umeda
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    ABSTRACT: In the present study, we clarified the TMJ symptoms of Yusho patients. An epidemiologic examination was carried out to identify TMJ arthrosis in patients with Yusho. The patients were collected during annual Yusho examinations in 2012. Nine of 187 patients had TMJ symptoms. The symptoms were pain, trismus, and a clicking sound of the TMJ. We diagnosed these patients with TMJ arthrosis. The rate of TMJ arthrosis in Yusho patients was 4.8%, being similar to the rate of TMJ arthrosis in general. The PCB concentration in the blood of these 9 patients was 2.76 ppb, and the average blood PCB concentration of all patients was 2.98 ppb. We identified no relationship between the blood PCB concentration and TMJ arthrosis.
    Fukuoka igaku zasshi = Hukuoka acta medica 04/2013; 104(4):100-3.
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    ABSTRACT: Small cell carcinoma (SmCC) in the oral and maxillofacial region is extremely rare high-grade malignant tumor. We report a case of a SmCC occurring in the maxillary gingiva. A 39-year-old man exhibited upper left gingival swelling that rapidly increased in size. Histopathological examination revealed proliferation of round cells with scant cytoplasm. Immunohistochemically, the tumor cells were positive for cytokeratin AE1/AE3, chromogranin A, synaptophysin, neuron-specific enorase (NSE), CD56, Leu 7, neurofilament and bcl-2, but negative for CD20, CD79a, S-100 and cyclin D1. Surgical resection and radical neck dissection were performed, and adjuvant chemotherapy combining CDDP and irinotecan (CPT11) was administered. Ten months after the operation, buccal lymph node metastasis and distant metastasis to the liver were found. Although irradiation therapy was performed, the liver lesion was unaffected by irradiation. Therefore, a further chemotherapy including etoposide was performed. The mass of the liver remained resistant to additional chemotherapy, and he subsequently died because of cachexia in spite of the partial hepatectomy.
    Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology. 04/2013; 25(2):179–182.
  • Oral surgery, oral medicine, oral pathology and oral radiology. 02/2013;
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    ABSTRACT: INTRODUCTION: In this study, we investigated whether such a discontinuation of oral bisphosphonate (BP) for 3 months might influence the incidence of BP-related osteonecrosis of the jaw (BRONJ) and wound healing after tooth extraction in patients receiving oral BP therapy. MATERIAL AND METHODS: There were a total of 434 teeth in 201 patients (18 males and 183 females). The patients were divided into two groups depending on whether or not they underwent a 3-month discontinuation of BP therapy (BP- and BP+) before tooth extraction. In this observational study investigated delayed wound healing after tooth extraction in patients receiving oral BP therapy. RESULTS: In all cases of the BP- group, there were no BRONJ although there was delayed wound healing in two cases. However, in one case of the BP+ group, oral BP was continued because it was deemed high risk to discontinue treatment by the patient's physician. In this case, an intraoral fistula was still present with bone exposure at 120 weeks after extraction (BRONJ stage 1). CONCLUSION: This study supports the idea of a drug holiday and encourages further clinical research on this topic of tooth extraction in patients receiving oral BP therapy.
    Journal of cranio-maxillo-facial surgery: official publication of the European Association for Cranio-Maxillo-Facial Surgery 01/2013; · 1.25 Impact Factor
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    ABSTRACT: Intramuscular lipoma (IML) is an uncommon tumor in the oral cavity, and characterized by infiltrating adipose tissue and muscle atrophy. Although oral IMLs are almost always solitary, we reported a rare case of IML of the tongue complicated with diffuse lipomatosis of the forearm. A 58-year-old woman was referred to our department with a painless swelling of the left tongue that had been present for 6 months. Clinical examination revealed a 35 mm × 30 mm × 20 mm well-defined, elastic soft mass in the anterior left region of the tongue border. The lesion was removed under general anesthesia via the left margin of the tongue. No signs of recurrence have been observed 15 months after surgery.
    Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology. 11/2012; 24(4):237–240.
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    ABSTRACT: Local recurrence of oral squamous cell carcinoma (OSCC) after primary surgery has been considered to be a poor prognostic entity in terms of survival rate. The purpose of this study is to evaluate the incidence of local recurrence and to identify significant risk factors for the local recurrence in OSCC. The authors retrospectively reviewed records for 187 patients who underwent radical surgery for OSCC. The local recurrence rate was 16.0% (30/187 patients) in this study. The survival rate of patients with local recurrence was 33.3%, which was significantly lower than that (94.3%) of patients without local recurrence. Pattern of invasion (POI), neoadjuvant chemotherapy (NAC), and the status of the surgical margin were identified as factors influencing local recurrence. In particular, NAC and the status of the surgical margin were independent risk factors by multivariate analysis. The deep margin was resected at a close site in many NAC-treated patients, suggesting that NAC may lead to local recurrence and poor outcomes. No efficacy of NAC was observed, suggesting that the standard treatment of oral cancers is surgery alone.
    International Journal of Oral and Maxillofacial Surgery 08/2012; 41(10):1195-200. · 1.52 Impact Factor
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    ABSTRACT: Distant metastasis of malignant neoplasm to the oral soft tissue is extremely rare. We report a case of renal cell carcinoma (RCC) metastasizing to the tongue. A 47-year-old man visited our hospital with chief complaint of a lump on the middle third of the dorsum of his tongue and the lesion fell off from the tongue. Although histopathological diagnosis of the mass was granuloma teleangiectaticum, similar nodule reappeared in the same area 2 weeks later. The second lesion was composed of granuloma teleangiectaticum and aggregation of neoplastic clear cells in ductal arrangement. The clear cells were immunohistochemically positive for EMA and CD10. The abdominal CT scan revealed a 5.5 cm mass in the left kidney, suggesting RCC. Thus, the lingual lesion was consistent with metastatic RCC. There has been no recurrence for 2 years after the radical nephrectomy and local excision of the tongue.
    Medical Oncology 12/2011; 28(4):1389-94. · 2.14 Impact Factor
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    ABSTRACT: Amelanotic melanoma of the oral mucosa is extremely rare. We describe herein our experience of amelanotic melanoma arising in the mandibular mucosa. An 85-year-old woman was referred to our clinic with swelling of the left lower gingival mucosa. The histopathological diagnosis was amelanotic melanoma, as determined by immunohistochemical examination. The tumor cells were positive for S-100, Melan-A, HMB-45, and vimentin. The patient declined surgical treatment, so she received irradiation therapy. At a total dose of 10 Gy, the patient exhibited lassitude, so we terminated radiotherapy. Bleeding from the tumor persisted, and the patient developed anemia and hypouresis. She also contracted pneumonia. The patient's general condition worsened, and she died.
    International Journal of Oral Science 11/2011; 8(2):60–63. · 2.72 Impact Factor
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    ABSTRACT: Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are 5-fluorouracil (5-FU) metabolizing enzymes and are involved in the sensitivity of carcinoma patients to 5-FU. Although 5-FU is often used for the treatment of oral carcinoma, there has not been any investigation into the expression of these enzymes in metastatic lymph nodes or of their roles in the effectiveness of 5-FU in treating lymph node-metastatic cancer. Oral squamous cell carcinoma (OSCC) often metastasizes to the lymph nodes, and these enzymes may be significant in the survival of patients with this disease. This study investigated the expression of TS and DPD in cervical lymph node metastases and its relationship with primary OSCC, as well as the interaction between these enzymes and Kangai 1(KAI1/CD82) which is a metastasis suppressor protein. Surgical specimens from 20 cases of OSCC with lymph node metastasis, 20 cases of OSCC without lymph node metastasis, and 10 cases of normal mucosa were examined by immunohistochemistry. The relationship between TS and DPD expression and clinicopathological data was analyzed. TS and DPD proteins were overexpressed in primary OSCC compared to that in normal mucosa. TS expression of the primary oral cancer cells in the group with lymph node metastasis was higher than that of those without. DPD expression did not significantly correlate with the occurrence of lymph node metastasis, nor was it different between primary oral cancer cells and cervical metastases. CD82 expression was significantly reduced in lymph node metastases. These findings indicate that TS and CD82 may be of great value in assessing lymph node metastasis of OSCC, and could be taken as new targets for therapy of metastatic OSCC.
    Anticancer research 10/2011; 31(10):3521-6. · 1.71 Impact Factor
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    ABSTRACT: The aim of this study was to examine the effectiveness of covering wounds to the tongue with a polyglycolic acid (PGA) sheet and fibrin glue. Eighteen mature male Japanese white rabbits had a unilateral glossectomy involving an area 10mm×10mm×2mm. After glossectomy the tongues were covered with PGA sheets 8mm×8mm in size and fibrin glue (mucosal defect covered with fibrin glue and polyglycolic acid sheet=MCFP) 1 week after the operation (n=3), after 2 weeks (n=3), and after 4 weeks (n=3). In control groups, after 1, 2, and 4 weeks (n=3 in each group), the partially resected tongues were closed with absorbable sutures (polyglactin 910). One week (experimental and control groups 1), 2 weeks (experimental and control groups 2) and 4 weeks (experimental and control groups 3) after operation the tongues were harvested and stained for microscopic examination. Histological examination showed that the covered wound surface had not epithelialised and the basal layer had yet to form in experimental group 1, but had formed in experimental group 2. However, in control group 1, epithelialisation of the sutured wound had begun. Immunohistochemical examination showed that, in experimental group 1, the non-uniform epithelial layer of the covered wound surface expressed cytokeratin AE1/AE3, and the epithelial and connective tissue layers stained strongly for FGF-2. Similar results were obtained in experimental group 2, whereas in experimental group 3, FGF-2 was expressed only in the connective tissue layer, and epithelialisation was complete. However, in control group 1, AE1/AE3 was expressed in the epithelial layer, and FGF was expressed in the connective tissue layer beneath the basal layer. In control groups 2 and 3, AE1/AE3 and FGF-2 were expressed in patterns similar to those in experimental groups 2 and 3. We suggest that this method is useful and the operation is simple. However, further testing of the method is needed and it should be widely used clinically before it is recommended.
    British Journal of Oral and Maxillofacial Surgery 08/2011; 50(5):459-63. · 2.72 Impact Factor
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    ABSTRACT: Recent studies suggest that cancer stem cells may be responsible for tumorigenesis and contribute to some individuals' resistance to cancer therapy. Some studies demonstrate that side population (SP) cells isolated from diverse cancer cell lines harbor stem cell-like properties; however, there are few reports examining the role of SP cells in human oral cancer. To determine whether human oral cancer cell lines contain a SP cell fraction, we first isolated SP cells by fluorescence activated cell sorting, followed by culturing in serum-free medium (SFM) using the SCC25 tongue cancer cell line, so that SP cells were able to be propagated to maintain the CSC property. Differential expression profile of stem cell markers (ABCG2, Oct-4 and EpCAM) was examined by RT-PCR in either SP cells or non-SP cells. Growth inhibition by 5-FU was determined by the MTT assay. Clonogenic ability was evaluated by colony formation assay. SCC25 cells contained 0.23% SP cells. The fraction of SP cells was available to grow in SFM cultures. SP cells showed higher mRNA expression of stem cell markers (ABCG2, Oct-4 and EpCAM) as compared with non-SP cells. Moreover, SP cells demonstrated more drug resistance to 5-FU, as compared with non-SP cells. The clone formation efficiency of SP cells was significantly higher than non-SP cells at an equal cell number (P<0.01). We isolated cancer stem-like SP cells from an oral cancer cell line. SP cells possessed the characteristics of cancer stem cells, chemoresistance, and high proliferation ability. Further characterization of cancer stem-like SP cells may provide new insights for novel therapeutic targets.
    Oral Oncology 07/2011; 47(9):855-60. · 2.70 Impact Factor
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    ABSTRACT: S-1 is a newly developed oral fluoropyrimidine derivative that is now widely used as a chemotherapeutic agent in the treatment of various carcinomas. This study was performed to assess the efficacy and safety profile of the combination of S-1 and cisplatin(S-1/CDDP)in patients with oral cancer as neo-adjuvant chemotherapy. We reviewed our experience of 12 patients diagnosed with oral carcinoma, who were treated with S-1/CDDP. S-1 was administered orally at a dose of 50mg twice a day for 21 consecutive days, followed by a 14-day rest period. CDDP(60mg/m2)in 500 mL physiological saline was administered by intravenous drip as a 120-min infusion on day 8, together with standard premedications and hydration. Seven partial responders were obtained. The median follow-up duration was 54. 8 months, and all patients were alive excluding one case. This regimen was well tolerated, with only one case of grade 3 thrombocytopenia, and no grade 4 patient. No treatment-related death was observed. Moreover, we evaluated immunohistochemical expressions of thymidylate synthase (TS), dihydropyrimidine dehydrogenase(DPD), and orotate phosphoribosyl transferase(OPRT)which are associated with chemosensitivity to 5-FU-based therapies. We investigated the relation between the immunohistochemical score and clinicopathological factors, however we could not clarify the relationship between the efficacy of chemotherapy and results of immunohistochemistry.
    Gan to kagaku ryoho. Cancer & chemotherapy 06/2011; 38(6):951-7.
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    ABSTRACT: Thymidylate synthase(TS), dihydropyrimidine dehydrogenase(DPD), and orotate phosphoribosyl transferase(OPRT)are initial key enzymes in the 5-fluorouracil(5-FU)metabolic pathway. In this study, we investigated clinicopathological and immunohistochemical expressions of TS, DPD, and OPRT in oral cancer patients who showed a complete response(CR)to UFT. We also evaluated patients showing a partial response(PR)and stable disease(SD)following UFT. The numbers of CR, PR, and SD cases were 3, 5, and 10, respectively. Pathologically, all CR and PR cases were the well-differentiated type, and 5 out of 10 SD cases were of the moderately or poorly-differentiated type. Three out of the 5 cases of moderately or poorlydifferentiated type were DPD-negative. Most cases of CR and PR were DPD-positive. OPRT expression showed no difference with the UFT response. We suggest that UFT affects high DPD patients with the well-differentiated type, but may not influence low DPD patients with the moderately or poorly-differentiated type.
    Gan to kagaku ryoho. Cancer & chemotherapy 06/2010; 37(6):1035-9.
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    Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 01/2010; 68(1):212-7. · 1.58 Impact Factor
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    ABSTRACT: alpha-actinin-4, originally identified as an actin-binding protein associated with cell motility, invasion, and metastasis of cancer cells, appears to be overexpressed in various human epithelial carcinomas, including colorectal, breast, esophageal, ovarian, and non-small cell lung carcinomas. The authors evaluated whether alpha-actinin-4 might be appropriate as a molecular target for cancer gene therapy. In 64 primary oral squamous cell carcinomas (OSCCs) and 10 normal oral mucosal specimens, and in seven human OSCC cell lines, alpha-actinin-4 expression was evaluated immunologically and correlations with clinicopathologic factors were examined. Overexpression of alpha-actinin-4 was detected in 38 of 64 oral squamous cell carcinomas (70%); significantly more frequently than in normal oral mucosa. The expression of alpha-actinin-4 was significantly associated with invasion potential defined by the Matrigel invasion assay. Cancer cell lines with higher alpha-actinin-4 expression had greater invasive potential. An RNAi-mediated decrease in alpha-actinin-4 expression reduced the invasion potential. These results indicated that the overexpression of alpha-actinin-4 was associated with an aggressive phenotype of OSCC. The study indicated that alpha-actinin-4 could be a potential molecular target for gene therapy by RNAi targeting for OSCC.
    International Journal of Oral and Maxillofacial Surgery 11/2009; 39(1):61-7. · 1.52 Impact Factor
  • Oral Oncology Supplement 01/2009; 3(1):191-191.
  • International Journal of Oral and Maxillofacial Surgery - INT J ORAL MAXILLOFAC SURG. 01/2009; 38(5):568-568.
  • International Journal of Oral and Maxillofacial Surgery - INT J ORAL MAXILLOFAC SURG. 01/2009; 38(5):533-533.
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    ABSTRACT: Metastasis-associated protein 1 (MTA1) is physiologically expressed at low levels in human tissues. Its expression is associated with progression of solid cancers and is common in cancer cell lines. This study investigated whether MTA1 was expressed in squamous cell carcinoma (SCC) and would be a useful metastatic marker. Specimens from 38 patients with oral SCC were stained using the avidin-biotin-peroxidase technique with polyclonal antibodies against MTA1. Human SCC cell lines SAS, HSC2, OSC19 and OSC20 were analysed for MTA1 mRNA expression. MTA1 expression in control tissues was significantly lower than in carcinomas. MTA1 protein expression was detected in 33 of 38 SCC tissues from patients. Histologically, MTA1 protein production was strongly associated with cancer cell invasion, and clinically there was a correlation between lymph node metastasis and MTA1 protein production. Among the cancer cell lines, HSC2 showed the lowest mRNA expression, and OSC20 showed the highest MTA1 mRNA expression. In the Matrigel invasion assay, the HSC2 cell line showed the lowest invasion and the OSC20 cell line showed the highest invasion. RNAi-mediated MTA1 silencing in the OSC20 cells decreased the invasion index. MTA1 expression in oral SCC may be associated with increased invasive ability, which may cause lymph node metastasis.
    International Journal of Oral and Maxillofacial Surgery 11/2008; 37(11):1039-46. · 1.52 Impact Factor