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Yamazaki H.,Kitasato University | Chijiwa T.,Japan Self Defense Force Hospital Naha | Inoue Y.,Tokai University | Abe Y.,Tokorozawa PET Diagnostic Imaging Clinic | And 7 more authors.
Experimental and Therapeutic Medicine | Year: 2012

Malignant melanoma is the most aggressive neoplasm, with severe metastatic potential. microRNAs represent a class of endogenously expressed, small non-coding RNAs that regulate gene expression. As a consequence, the translation of these mRNAs is inhibited or they are destabilized resulting in downregulation of the encoded protein. The microRNA-34 (miR-34) family, which comprises three processed microRNAs (miR-34a/b/c) was identified as the mediator of tumor suppression by p53. Many reports suggest that the miR-34s contribute to the inhibition of invasion or metastasis in various tumor types. In this study, we evaluated the expression of the miR-34 family in four human melanoma cell lines (A375, G361, C32TG and SK-MEL-24) which have the wild-type p53 gene using real-time reverse transcription PCR. We also examined their generative and invasive characteristics using the cell proliferation assay and the invasion/migration assay, respectively. All four melanoma cell lines showed significant expression of miR-34s - A375: miR-34a 0.6176, miR-34b 0.7625, miR-34c 0.7877; G361: 7.6424, 16.4127, 22.0332; C32TG: 2.1630, 2.1091, 8.4425; SK-MEL-24: 0.3621, 2.5659, 8.5907. The cell doubling times of these cell lines in h:min were as follows: A375 23:23, G361 68:24, C32TG 47:22 and SK-MEL-24 67:03. The in vitro generation times of G361 and SK-MEL-24, which showed increased expression of miR-34c, were significantly shorter than A375 with decreased expression of miR-34c (p=0.0063, ANOVA). Invasion (%) of the four cell lines was as follows: A375 44.0%, G361 22.4%, C32TG 13.8% and SK-MEL-24 45.0%. In vitro invasiveness of G361 and C32TG, which showed increased expression of miR-34a, was significantly suppressed (p=0.005, ANOVA). These results suggest that overexpression of miR-34a and c suppresses invasive and generative potentials, respectively, in human malignant melanoma.


Abe Y.,Tokorozawa PET Diagnostic Imaging Clinic | Tamura K.,Tokorozawa PET Diagnostic Imaging Clinic | Sakata I.,Tokorozawa PET Diagnostic Imaging Clinic | Ishida J.,Tokorozawa PET Diagnostic Imaging Clinic | And 7 more authors.
Oncology Reports | Year: 2012

Malignant pleural mesothelioma (MPM) has a poor prognosis, and conventional imaging modalities do not reflect the prognosis of MPM. In this study, the clinical significance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging ( 18F-FDG PET/CT) was evaluated for the differential diagnosis, staging and prognosis in MPM patients. Ninety patients who underwent 18F-FDG PET/CT scanning due to a clinical diagnosis or suspicion of MPM prior to therapy were reviewed. Of 90 patients, 31 were pathologically diagnosed as MPM. Maximum standardized uptake values (SUVmax) were semi-quantitatively obtained from PET/CT 60 min (early phase) and 120 min (delayed phase) after injection of 18F-FDG, and the clinicopathological correlations with the level of SUVmax obtained from PET/CT were examined. The survival curves of MPM patients were plotted according to the methods of Kaplan-Meier. The prognostic implications of the level of SUVmax were estimated by t-test. PET/CT scan showed intense abnormal FDG uptake (SUVmax >2.0) in the pleural lesions of all 31 MPM patients at delayed phase, while it showed abnormal FDG uptake in 30 (97%) patients at early phase. In all 31 MPM patients, the values of SUVmax at delayed phase were higher than those at the early phase. PET/CT also indicated metastasis in the lymph node in 7 patients (23%) and in the systemic lesions in 8 patients (26%) with MPM. Twenty-three MPM patients with high SUVmax, whose prognosis was apparent, showed significantly poorer prognosis in both early and delayed phase (respectively, p=0.03 and p=0.01, t-test). The results showed that 18F-FDG PET/CT at delayed phase is very useful for the diagnosis of pleural diseases, and SUVmax on PET/CT in the delayed phase is a more reliable prognostic factor than that in the early phase. High uptake of 18F-FDG PET/CT may be a predictive factor of prognosis in MPM patients.


Ozeki Y.,National Defense Medical College | Abe Y.,Tokorozawa PET Diagnostic Imaging Clinic | Kita H.,Tokorozawa Chuoh Hospital | Tamura K.,Tokorozawa PET Diagnostic Imaging Clinic | And 3 more authors.
Oncology Letters | Year: 2011

Cancer of unknown primary origin (CUP) is an aggressive disease with a poor prognosis. Metastatic brain tumors occur in approximately 15% of all cancer patients. F-18 2'-deoxy-2fluoro-D-glucose (FDG) positron emission tomography (PET) combined with computed tomography (PET/CT) contributes to the evaluation of cancer staging, although the benefits of PET/CT for detection of CUP origins has yet to be determined. In this study, we present a 37-year-old man with a brain tumor detected by magnetic resonance imaging. Surgical biopsy indicated a metastatic undifferentiated carcinoma, while clinical examination and a CT scan did not detect any abnormalities, with the exception of brain metastases. PET/CT did not reveal abnormal FDG uptake. PET/CT revealed abnormal intense FDG uptake in a small nodular lesion in the right lung 1 year following the detection of brain metastasis, and no other abnormal FDG uptake was observed elsewhere in the body. Right upper lobectomy and dissection of mediastinal lymph nodes were performed. The pathological diagnosis was poorly differentiated adenocarcinoma, which was similar to the brain metastatic lesion, and there was no lymph node metastasis. This case revealed an extremely rare lung cancer with primary lesions demonstrated by PET/CT 1 year after the detection of brain metastasis. This case reveals that F-18 FDG PET/CT imaging of CUP origin is capable of positively impacting on the identification of small primary tumor foci.


Kawai K.,Central Institute for Experimental Animals | Tamura K.,Tokorozawa PET Diagnostic Imaging Clinic | Sakata I.,Tokorozawa PET Diagnostic Imaging Clinic | Ishida J.,Tokorozawa PET Diagnostic Imaging Clinic | And 7 more authors.
Oncology Reports | Year: 2013

Clinically, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) is useful in the evaluation of various types of human cancers. While PET analysis has been established to evaluate subcutaneous lesions of human cancers in mice, its applications for internal lesions are still being developed. We are currently evaluating new PET approaches for the effective evaluation of in vivo metastatic lesions in the internal organs of small experimental animals. In this study, we analyzed in vivo hepatic metastases of human colonic cancer in immunodeficient mice (NOD/Shi-scid/IL-2Rγnull, NOG) using PET imaging. This new PET approach has been proposed for the evaluation of in vivo metastatic lesions in internal organs. The human colon cancer line HCT116 (1.0×10 5 and 1.0×106 cells/mouse) was transplanted by intrasplenic injection. 18F-FDG-PET/CT scans were performed 2 weeks after transplantation. After PET/CT scans, histopathological examinations were performed. PET/CT analysis disclosed multiple metastatic foci and increased standardized uptake values (SUV) of FDG in the livers of NOG mice (control, SUVmean 0.450±0.033, SUVmax 0.635±0.017; 1.0×105 cells, 0.853±0.087, 1.254±0.237; 1.0×106 cells, 1.211±0.108, 1.701±0.158). There were significant differences in FDG uptakes between the three groups (ANOVA, P=0.017 in SUVmean; P = 0.0 44 in SU Vma x, n=2). We clea rly a nd qua n-titatively detected images of hepatic metastasis in the livers of NOG mice by 18F-FDG-PET/CT in vivo. PET/CT analysis of internal organ lesions of human cancerous xenografts is a new reliable experimental system to simulate metastases. This model system is useful for analyzing metastatic mechanisms and for developing new novel drugs targeting hepatic metastases of cancer.


Abe Y.,Tokorozawa PET Diagnostic Imaging Clinic | Tamura K.,Tokorozawa PET Diagnostic Imaging Clinic | Sakata I.,Tokorozawa PET Diagnostic Imaging Clinic | Ishida J.,Tokorozawa PET Diagnostic Imaging Clinic | And 5 more authors.
Oncology Letters | Year: 2010

Pyothorax-associated lymphoma (PAL) is a unique and rare non-Hodgkin's lymphoma developing in the pleural cavity following a long-standing history of chronic pyothorax (CP). The development of F-18 2'-deoxy-2fluoro-D-glucose (FDG) positron emission tomography combined with computed tomography (PET/CT) has contributed to the evaluation of lymphoma staging. However, only a few studies describing FDG-PET/CT findings in PAL have been published. This study reported three cases of PAL; all 3 patients had previously undergone artificial collapse therapy for pulmonary tuberculosis. Both the first case (an 84-year-old male) and second case (an 83-year-old male) complained of abdominal pain. An ultrasound scan revealed a mass shadow in the left chest wall without abnormal findings in the abdomen, and the CT and magnetic resonance imaging scans suggested malignant lymphoma of the left chest. FDG-PET/CT imaging showed extremely intense FDG uptake only in the left pleura and chest wall. Diagnosis was CP in the two patients, showing a high maximum standardized uptake value (SUVmax: early, 14.8 and delayed, 19.4 in the first case; early, 20.8 and delayed, 27.3 in the second case, respectively). Histopathological analysis of the specimens obtained by biopsy of the PET/CT-positive pleural mass showed non-Hodgkin's, diffuse large B cell lymphoma in the two cases. The third case was a 79-year-old male with relapse after right pleuropneumonectomy for PAL (diffuse large B cell lymphoma) 4 years earlier. PET/CT showed intense FDG uptake (SUVmax: early, 19.9 and delayed, 35.7) in the right pleura and chest wall. Diagnosis was CP, suggesting the recurrence of PAL. Furthermore, abnormal intense FDG uptake was noted in the hilar, mediastinal and supraclavicular lymph nodes, as well as in the spleen. In conclusion, FDG-PET/CT imaging is useful in the evaluation of the area of invasion in PAL.

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