Yukihisa Tamaki

Pifithrin-μ, an Inhibitor of Heat-Shock Protein 70, Can Increase the Antitumor Effects of Hyperthermia Against Human Prostate Cancer Cells

Hyperthermia (HT) improves the efficacy of anti-cancer radiotherapy and chemotherapy. However, HT also inevitably evokes stress responses and increases the expression of heat-shock proteins (HSPs) in cancer cells. Among the HSPs, HSP70 is known as a pro-survival protein. In this study, we investigated the sensitizing effect of pifithrin (PFT)-μ, a small molecule inhibitor of HSP70, when three human prostate cancer cell lines (LNCaP, PC-3, and DU-145) were treated with HT (43°C for 2 h). All cell lines constitutively expressed HSP70, and HT further increased its expression in LNCaP and DU-145. Knockdown of HSP70 with RNA interference decreased the viability and colony-forming ability of cancer cells. PFT-μ decreased the viabilities of all cell lines at one-tenth the dose of Quercetin, a well-known HSP inhibitor. The combination therapy with suboptimal doses of PFT-μ and HT decreased the viability of cancer cells most effectively when PFT-μ was added immediately before HT, and this combination effect was abolished by pre-knockdown of HSP70, suggesting that the effect was mediated via HSP70 inhibition. The combination therapy induced cell death, partially caspase-dependent, and decreased proliferating cancer cells, with decreased expression of c-Myc and cyclin D1 and increased expression of p21WAF1/Cip, indicating arrest of cell growth. Additionally, the combination therapy significantly decreased the colony-forming ability of cancer cells compared to therapy with either alone. Furthermore, in a xenograft mouse model, the combination therapy significantly inhibited PC-3 tumor growth. These findings suggest that PFT-μ can effectively enhance HT-induced antitumor effects via HSP70 inhibition by inducing cell death and arrest of cell growth, and that PFT-μ is a promising agent for use in combination with HT to treat prostate cancer.

Comparison of utility of tumor size and apparent diffusion coefficient for differentiation of low- and high-grade clear-cell renal cell carcinoma

Background: There is a significant correlation between tumor size and tumor grade for clear-cell renal cell carcinoma (RCC) in pathology. Thus, apparent diffusion coefficient (ADC) of clear-cell RCC might be influenced by tumor size. Purpose: To compare the utility of tumor size and ADC for distinguishing low-grade from high-grade clear-cell RCC. Material and Methods: Forty-nine patients undergoing preoperative magnetic resonance imaging were retrospectively assessed. ADC values were calculated using b-value combinations of 0 and 800 s/mm2 at 1.5 T. Two radiologists in consensus measured ADC values via small region of interest (ROI) (mean ROI area, 88.8 mm2; range, 80–108 mm2) placement on an area of solid tumor on a single slice. Maximum tumor diameter was measured at the maximum tumor area. A single pathologist reviewed all pathological slides to determine the nuclear grade according to the Fuhrman classification. The utility of ADC, tumor size, and ADC/size ratio for distinguishing low-grade from high-grade tumors was assessed. Receiver-operating characteristic (ROC) analysis and regression analysis of the each index were performed. The correlation between ADC and tumor size was also investigated. Results: The 49 clear-cell RCC included 34 low-grade and 15 high-grade tumors. The differences of ADC, tumor size, and ADC/size ratio between high-grade and low-grade tumors were statistically significant (P <0.05). The area under the ROC curve of ADC, tumor size, and ADC/size ratio were 0.802, 0.763, and 0.804 respectively. However, using regression analysis, only ADC (P <0.05) was statistically significant index as independent risk factors for high-grade clear-cell RCC. Moreover, weak significant correlation was observed between tumor size and ADC (R2 = 0.3865, P <0.01). Conclusion: There was a weak significant correlation between tumor size and ADC value of clear-cell RCC. Using ROC and regression analysis, ADC was statistically significant index for distinguishing low-grade from high-grade clear-cell RCC more than tumor size and ADC/size ratio.

Present and future roles of FDG-PET/CT imaging in the management of lung cancer

Integrated positron emission tomography/computed tomography (PET/CT) using 2-[18F]fluoro-2-deoxy-d-glucose (18F-FDG) has emerged as a powerful tool for combined metabolic and anatomic evaluation in clinical oncologic imaging. This review discusses the utility of 18F-FDG PET/CT as a tool for managing patients with lung cancer. We discuss different patient management stages, including diagnosis, initial staging, therapy planning, early treatment response assessment, re-staging, and prognosis.

Role of diffusion weighted imaging and contrast-enhanced MRI in the evaluation of intrapelvic recurrence of gynecological malignant tumor.

Background and Purpose To investigate the diagnostic performance of diffusion-weighted imaging (DWI) and contrast-enhanced imaging in combination with T2-weighted imaging (T2WI) for magnetic resonance imaging (MRI) evaluation of intrapelvic recurrence of gynecological malignancies. Materials and Methods Sixty-two patients with suspected intrapelvic recurrence of gynecological malignancies underwent pelvic MRI including T2WI DWI, and contrast-enhanced imaging. Diagnostic performance for detection of local recurrence, pelvic lymph node and bone metastases, and peritoneal lesions was evaluated by consensus reading of two experienced radiologists using a 5-point scoring system, and compared among T2WI with unenhanced T1-weighted imaging (T1WI) (protocol A), a combination of protocol A and DWI (protocol B), and a combination of protocol B and contrast-enhanced imaging (protocol C). Final diagnoses were obtained by histopathological examinations, radiological imaging and clinical follow-up for at least 6 months. Receiver operating characteristic (ROC) analysis and McNemar test were employed for statistical analysis. Results Locally recurrent disease, lymph node recurrence, peritoneal dissemination and bone metastases were present in 48.4%, 29.0%, 16.1%, and 6.5% of the patients, respectively. The patient-based sensitivity, specificity, accuracy, and area under the ROC curve (AUC) for detection of intrapelvic recurrence were 55.0, 81.8, 64.5% and 0.753 for protocol A, 80.0, 77.3, 79.0% and 0.838 for protocol B, and 80.0, 90.9, 83.9% and 0.862 for protocol C, respectively. The sensitivity, accuracy, and AUC were significantly better for protocols B and C than for protocol A (p<0.001). There was no significant difference between protocols B and C. Conclusion MRI using a combination of DWI and T2WI gives comparatively acceptable results for assessment of intrapelvic recurrence of gynecological malignancies.

Computed diffusion-weighted imaging using 1.5-T magnetic resonance imaging for prostate cancer diagnosis.

Computed diffusion-weighted magnetic resonance imaging (cDWI) is gradually being known to be useful to detect prostate cancer. We found that cDWIs (b=2000 s/mm2) were easily generated from measured DWIs (mDWIs) with image processing using Image J and that the contrast ratio (CR) of cDWIs-2000 appeared to be higher than the CR of mDWIs-1000 and mDWIs-2000. The diagnostic ability of cDWI-2000 for prostate cancer detection was equivalent to that of mDWI-2000. There is a possibility that cDWIs-2000 can replace mDWIs-2000.

The relation between apparent diffusion coefficient and clinical stage of clear-cell renal cell carcinoma.

PURPOSE The utility of the apparent diffusion coefficient (ADC) in patients with clear-cell renal cell carcinoma (RCC) for distinguishing between the four clinical stages was assessed. METHODS Forty-nine patients with pathologically proven RCCs (I, II, III, IV; 27, 5, 10, 7) were included. The ADC was compared between each stage. RESULTS The difference of ADC between stage I and the more advanced stages (III and IV) was statistically significant. CONCLUSIONS When ADC in primary tumor site of clear-cell RCC would be higher than the cutoff level, the stage might not be an advanced stage (III or IV).

Present and future roles of FDG-PET/CT imaging in the management of gastrointestinal cancer : an update

ABSTRACT Positron emission tomography/computed tomography (PET/CT) integrated with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) is a useful tool for acquisition of both glucose metabolism and anatomic imaging data, as only a single device and one diagnostic session is required, thus opening a new field in clinical oncologic imaging. FDG-PET/CT has been successfully used for initial staging, restaging, assessment of early treatment response, evaluation of metastatic disease response, and prognostication of intestinal cancer as well as various malignant tumors. We reviewed the current status and role of FDG-PET/CT for management of patients with esophageal cancer, gastric cancer, and colorectal cancer, with focus on both its usefulness and limitations.

The Japan Lung Cancer Society–Japanese Society for Radiation Oncology consensus-based computed tomographic atlas for defining regional lymph node stations in radiotherapy for lung cancer

The purpose of this study was to develop a consensus-based computed tomographic (CT) atlas that defines lymph node stations in radiotherapy for lung cancer based on the lymph node map of the International Association for the Study of Lung Cancer (IASLC). A project group in the Japanese Radiation Oncology Study Group (JROSG) initially prepared a draft of the atlas in which lymph node Stations 1–11 were illustrated on axial CT images. Subsequently, a joint committee of the Japan Lung Cancer Society (JLCS) and the Japanese Society for Radiation Oncology (JASTRO) was formulated to revise this draft. The committee consisted of four radiation oncologists, four thoracic surgeons and three thoracic radiologists. The draft prepared by the JROSG project group was intensively reviewed and discussed at four meetings of the committee over several months. Finally, we proposed definitions for the regional lymph node stations and the consensus-based CT atlas. This atlas was approved by the Board of Directors of JLCS and JASTRO. This resulted in the first official CT atlas for defining regional lymph node stations in radiotherapy for lung cancer authorized by the JLCS and JASTRO. In conclusion, the JLCS–JASTRO consensus-based CT atlas, which conforms to the IASLC lymph node map, was established.

Reply to 'Addressing the challenge of proper delineation of lymph node stations in modern radiotherapy for lung cancer'

Japanese Society for Radiation Oncology, 1-4-14, Kyobashi, Chuo-ku, Tokyo 104-0031, Japan Department of Radiation Oncology, Shimane University, Faculty of Medicine, 89-1, Enya-cho, Izumo, Shimane 693-8501, Japan Department of Radiation Oncology, St Luke’s International Hospital, 9-1, Akashi-cho, Chuo-ku, Tokyo 104-8560, Japan Department of Radiology, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi 409-3898, Japan Department of Radiation Oncology, Kindai University, Faculty of Medicine, 377-2, Ohno-higashi, Osaka-sayama, Osaka 589-8511, Japan Department of Radiation Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan The Japan Lung Cancer Society, 3-8-16, Nihonbashi, Chuo-ku, Tokyo 103-0027, Japan Department of Thoracic Surgery, Kanagawa Cancer Center, 2-3-2, Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan Division of Thoracic Surgery, Shizuoka Cancer Center, 1007, Shimonagakubo, Nagaizumi, Sunto, Shizuoka 411-8777, Japan Department of Diagnostic Radiology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women’s Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan Department of General Thoracic Surgery, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan Department of Diagnostic Radiology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan Division of Thoracic Surgery, Keio University School of Medicine, 35, Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan *Corresponding author. Department of Radiation Oncology, Shimane University, Faculty of Medicine, 89-1, Enya-cho, Izumo, Shimane 693-8501, Japan. Tel: +81-853-20-2582; Fax: +81-853-20-2582; Email: ytamaki@med.shimane-u.ac.jp (Received 19 February 2018; revised 9 April 2018; editorial decision 15 April 2018)

The value of CT findings for prognostic prediction of spontaneous superior mesenteric artery dissection

Background Spontaneous superior mesenteric artery (SMA) dissection is rare cause of acute abdomen. Time-dependent change of SMA dissection has not been established. Purpose To determine Sakamoto classification (SC) type of acute and chronic SMA dissection (aSMAD and cSMAD) to predict the treatment methods and outcome. Material and Methods From April 2003 to March 2017, unenhanced and contrast-enhanced CT were used to diagnose acute symptomatic or chronic asymptomatic SMA dissection in 25 consecutive patients without aortic dissection. Correlations between SCs and treatment methods and outcomes were investigated. Results All 13 patients with aSMAD initially received conservative treatment. Initial SCs in aSMAD were type I = 1, type III = 9, and type IV = 3. Three of nine initial type III and two of three initial type IV changed to type I at follow-up. One of nine type III changed to type II at follow-up. Ohers did not change. One with initial type III required vascular repair, so the final SC was not available. Three patients required bowel resection. In cSMAD of 12 patients, the initial/final SC were type I and IV in ten and two patients, respectively, without change during follow-up. cSMAD was significantly older than aSMAD. The initial length of dissection of aSMAD was longer than in the cSMAD group. In aSMAD, the final length of dissection was significantly shorter than in the initial computed tomography scan. Conclusion Initial SC differed significantly between aSMAD and cSMAD. Initial SC types in aSMAD were type III and IV mainly, and changed during the observation period. In cSMAD, SC types were I and IV without change.