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PDF file - 23K, List of Primers

PDF file - 68K, Isolation of CSCs/CICs from human RCC cells

PDF file - 74K, RT-PCR analysis

PDF file - 91K, SP analysis of DNAJB8- transduced cells

PDF file - 67K, Western blot analysis

PDF file - 142K, Protein expression of DNAJB8 in SP and MP cells

PDF file - 92K, Serine-rich region of DNAJB8 has role for induction of SP cells

This study aims to evaluate the influence of myosteatosis on survival of patients after radical cystectomy (RC) for bladder cancer. We retrospectively identified 230 patients who underwent RC for bladder cancer at our three institutions between 2009 and 2018. Digitized free-hand outlines of the left and right psoas muscles were made on axial non-contrast computed tomography images at level L3. To assess myosteatosis, average total psoas density (ATPD) in Hounsfield Units (HU) was also calculated as an average of bilateral psoas muscle density. We compared cancer-specific survival (CSS) between high ATPD and low ATPD groups and performed cox regression hazard analyses to identify the predictors of CSS. Median ATPD was 44 HU (quartile: 39–47 Hounsfield Units). Two-year CSS rate in overall patients was 76.6%. Patients with low ATPD (P = 0.01) than patients with high ATPD (≥ 44 HU). According to multivariate analysis, significant independent predictors of poor CSS were: Eastern Cooperative Oncology Group performance status ≥ 1 (P = 0.03), decreasing ATPD (P = 0.03), non-urothelial carcinoma (P = 0.01), pT ≥ 3 (P P

Our objectives were to compare measurements of ureteral wall area, ureteral wall volume and ureteral wall thickness for their use in prediction of shock wave lithotripsy outcomes. We retrospectively identified 218 patients that underwent shock wave lithotripsy for ureteral calculi with pretreatment non-contrast computed tomography. We measured ureteral wall thickness, ureteral wall area and ureteral wall volume by high functional viewer. Ureteral wall thickness was defined as the maximum thickness of ureteral wall, and ureteral wall area as the area of ureteral wall around the stone in the maximal stone diameter on axial computed tomography image. Ureteral wall volume was defined as the volume of ureteral wall from the upper to lower edge of the stone. Treatment success was defined as absence of residual fragments within 3 months after the first session. We compared the outcome predictive power among these parameters and logistic regression analysis to identify factors contributing to treatment failure. The treatment success rate was 47.6%. Ureteral wall thickness, ureteral wall area and ureteral wall volume in successful cases were all significantly smaller than those in unsuccessful cases (all p

We herein present an innovative technique of laparoscopic posterior mesh rectopexy (LPMR) for full-thickness rectal prolapse and report the clinical outcomes in our institution. Ten consecutive patients who were treated with our latest LPMR technique using mesh with an anti-adhesion coating from June 2014 to May 2017 were retrospectively analyzed. All patients were women with a mean age of 63.6 years (range, 39 to 82 y). The median operative time and blood loss volume were 197.5 minutes (range, 156 to 285 min) and 0 mL (range, 0 to 152 mL), respectively. No perioperative complications occurred, including surgical site infection, pneumonia, urinary dysfunction, and intestinal obstruction. The median follow-up duration was 768 days (range, 396 to 1150 d). During the follow-up, the cumulative incidence of full-thickness rectal prolapse and any mesh-related complications was 0. It may be possible to eliminate retroperitoneal closure using a mesh with an anti-adhesion coating. Our LPMR technique appears safe and acceptable.

Objectives The objective of the present study was to investigate the usefulness of three-dimensional images of stones to measure mean stone density for predicting the outcome of shock wave lithotripsy. Methods We retrospectively identified 239 patients who underwent shock wave lithotripsy with pretreatment non-contrast computed tomography. We automatically measured the mean stone density of three-dimensional images of stones using a high-functional viewer. For comparison, mean stone density was also measured by two previously reported techniques using both the abdominal windows and the bone windows on the axial slice at the level of the largest diameter of the stone. We compared the outcome predictive power after the first treatment with outcomes according to measurement by four other methods. We also carried out logistic regression analysis, including mean stone density measured by three-dimensional images. Results The single treatment success rate was 48.5%. The effect size (14.148) of the mean stone density measured by three-dimensional images was higher than those of the other four manual methods. In addition, the area under the curve (0.6330) of the mean stone density measured by three-dimensional images was significantly higher than those of the other methods. Increasing stone volume (P = 0.002) and increasing mean stone density measured by three-dimensional images (P = 0.023) were significant independent predictors of the treatment outcome on multivariate analysis. Conclusions This is the first study to compare the predictive powers for shock wave lithotripsy outcome of various mean stone density measuring methods. There is an indication that mean stone density automatically measured by three-dimensional images of stones is more useful than other measuring methods for predicting outcomes of shock wave lithotripsy.

In a previous study, we found that DNAJB8, a heat shock protein (HSP) 40 family member is expressed in kidney cancer stem-like cells (CSC)/cancer-initiating cells (CIC) and that it has a role in the maintenance of kidney CSC/CIC. Heat shock factor (HSF) 1 is a key transcription factor for responses to stress including heat shock, and it induces HSP family expression through activation by phosphorylation. In the present study, we therefore examined whether heat shock (HS) induces CSC/CIC. We treated the human kidney cancer cell line ACHN with HS, and found that HS increased side population (SP) cells. Western blot analysis and qRT-PCR showed that HS increased the expression of DNAJB8 and SOX2. Gene knockdown experiments using siRNAs showed that the increase in SOX2 expression and SP cell ratio depends on DNAJB8 and that the increase in DNAJB8 and SOX2 depend on HSF1. Furthermore, treatment with a mammalian target of rapamycin (mTOR) inhibitor, temsirolimus, decreased the expression of DNAJB8 and SOX2 and the ratio of SP cells. Taken together, the results indicate that heat shock induces DNAJB8 by activation of HSF1 and induces cancer stem-like cells.

Objectives To identify antigenic peptides of cancer stem-like cells (CSCs) antigen, DNAJB8, and establish a mouse CSCs-targeting immunotherapy model. Materials and methods To induce DNAJB8-specific immune reaction, we stimulated human CD8+ lymphocytes with antigen-presenting cells pulsed with a cocktail of three candidate HLA-A*24:02 restricted peptides and assessed peptide specific human cytotoxic T lymphocytes (CTLs) induction. One of the antigenic peptides showed identical amino acid sequence as corresponding mouse DNAJB8. We evaluated CTL induction with the peptide immunization in mouse model. Results We confirmed peptide-specific interferon-γ secretions and cytotoxic activities of induced human CTLs. In vivo immunization with the peptide to mice, peptide-specific CTL response could be observed in mouse CD8+ T cells. Furthermore, immunization with the peptide showed significant anti-tumor effects compared with negative controls. Conclusion DNAJB8-derived peptide is a novel candidate for CSCs-targeting immunotherapy, and mouse models can be used to evaluate CSCs-targeting immunotherapy.

Objectives To identify biomarkers predicting prognosis in bladder cancer patients undergoing the gemcitabine and cisplatin regimen. Methods We studied 52 patients with metastatic bladder cancer treated with the gemcitabine and cisplatin regimen by evaluating the relationship between the expression of two biomarkers, ribonucleotide reductase subunit M1 and excision repair cross complementing 1, by immunohistochemistry and clinical outcomes. Results The patients with low expression of ribonucleotide reductase subunit M1 showed a higher objective response rate by the gemcitabine and cisplatin regimen than those with high expression of ribonucleotide reductase subunit M1 (80.0% and 45.5%, respectively). No differences were observed according to the expression level of excision repair cross complementing 1. Low expression of ribonucleotide reductase subunit M1 significantly prolonged overall survival and progression-free survival compared with the high expression group. Low expression of excision repair cross complementing 1 tended to prolong overall survival and progression-free survival, but there were no significant differences (P = 0.07 and 0.10, respectively). Multivariate analysis showed that the expression of ribonucleotide reductase subunit M1 was the only independent prognostic factor (P = 0.012). Conclusions The expressions of ribonucleotide reductase subunit M1 seem to be associated with clinical response and survival in patients with metastatic bladder cancer treated with gemcitabine and cisplatin-based chemotherapy.

A 51-year-old man visited our hospital since he had noticed remarkable increase in size of left scrotal contents. Computed tomography revealed left testicular swelling, retroperitoneal, pelvic and left inguinal lymph nodes. Serum testicular tumor markers (α fetoprotein, β-human chorionic gonadotropin, lactate dehydrogenase) were elevated. Low left orchiectomy was performed due to swelling of the left inguinal lymph node. The excised specimen weighed 3,400g. Pathological findings were non-seminoma. Although there was no operation history of scrotal groin, there was metastasis in the left inguinal lymph node ; therefore, the stage of disease was T2N3M1a. According to the postoperative values of tumor markers, his condition was judged as "good prognosis" in the International Germ Cell Consensus Classification (IGCCC), and he underwent 3 courses of bleomycin, etoposide and cis-platin (BEP) therapy. Although the tumor markers decreased to the normal limit and the size of lymph node was remarkably decreased after 2 courses of BEP therapy, one course of EP therapy was added for further reduction of tumor size. For the residual lymph node metastasis, retroperitoneal lymph node dissection (RPLND) was performed. Then pelvic and left inguinal lymph node dissection was performed at a later date. Pathological findings of excised lymph nodes were only necrotic tissue. He is alive without disease recurrence three years after treatment.

BACKGROUND Recent large-scale randomized studies have demonstrated that 2 new hormone preparations (abiraterone and enzalutamide) prolong survival in docetaxel-treated or -naïve castration-resistant prostate cancer patients. However, no studies have directly compared antitumor effects between these 2 agents, and no clear guidelines are available for choosing between them. OBJECTIVE The objective of this clinical study is to compare antitumor effects and adverse events between abiraterone and enzalutamide by allocating castration-resistant prostate cancer patients deemed not indicated for docetaxel treatment to receive either of the 2 agents. METHODS This study is an open-label, comparative study allocating castration-resistant prostate cancer patients to abiraterone or enzalutamide treatment arms (allocation factors: age RESULTS Recruitment started in May 2016, and 13 patients have been recruited so far. We expect to complete enrollment by December 2020. CONCLUSIONS Recently, cross-resistance between abiraterone and enzalutamide has been an issue of focus. Urologists thus tend to prefer docetaxel rather than sequential therapies using 2 hormonal preparations after the progression of a first hormonal preparation. From that perspective, our clinical trial is rather out of fashion. Nevertheless, we assume that many patients receive hormonal sequential therapy in the actual clinical setting, since most such patients cannot receive chemotherapeutic agents due to old age or poor performance status. This is why we are attempting this randomized clinical trial comparing abiraterone versus enzalutamide. We will try to identify which drug is suitable for initial hormonal therapy among castration-resistant prostate cancer patients who do not meet the indications for docetaxel therapy in terms of not only antitumor effect, but also adverse events and quality of life. CLINICALTRIAL University Hospital Medical Information Network UMIN000022102; https://upload.umin.ac.jp /cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000025463 (Archived by WebCite at http://www.webcitation.org/70xaQfGlJ)

Kidney stones are a major public health concern with continuously increasing worldwide prevalence. Shock wave lithotripsy (SWL) is the first line treatment choice for upper urinary tract calculi with ureteroscopy and has advantages of safety and noninvasiveness, but the treatment success rate of SWL is lower than that of other therapies. It is therefore important to identify predictive factors for SWL outcome and select a suitable treatment choice for patients with upper urinary tract calculi. In recent years, computed tomography (CT) has become the gold standard for diagnosis of upper urinary tract calculi. Several factors based on CT images, including skin-to-stone distance, mean stone density, stone heterogeneity index, and variation coefficient of stone density, have been reported to be useful for predicting SWL outcome. In addition, a new method of analysis, CT texture analysis, is reportedly useful for predicting SWL outcomes. This review aims to summarize CT parameters for predicting the outcome of shock wave lithotripsy in stone cases in the upper urinary tract.

Background It remains controversial as to whether active stone removal should be performed in patients with poor performance status because of their short life expectancy and perioperative risks. Our objectives were to evaluate treatment outcomes of active stone removal in patients with poor performance status and to compare life prognosis with those managed conservatively. Methods We retrospectively reviewed 74 patients with Eastern Cooperative Oncology Group performance status 3 or 4 treated for upper urinary tract calculi at our four hospitals between January 2009 and March 2016. Patients were classified into either surgical treatment group or conservative management group based on the presence of active stone removal. Stone-free rate and perioperative complications in surgical treatment group were reviewed. In addition, we compared overall survival and stone-specific survival between the two groups. Cox proportional hazards analysis was performed to investigate predictors of overall survival and stone-specific survival. Results Fifty-two patients (70.3%) underwent active stone removal (surgical treatment group) by extracorporeal shock wave lithotripsy (n = 6), ureteroscopy (n = 39), percutaneous nephrolithotomy (n = 6) or nephrectomy (n = 1). The overall stone-free rate was 78.8% and perioperative complication was observed in nine patients (17.3%). Conservative treatment was undergone by 22 patients (29.7%) (conservative management group). Two-year overall survival rates in surgical treatment and conservative management groups were 88.0% and 38.4%, respectively (p

OBJECTIVES To compare various fat parameters based on computed tomography images between recurrent stone-forming patients and patients forming stones for the first time. METHODS Included in the present study were 300 patients with upper urinary tract calculi who had undergone active stone removal in our hospital. Using pretreatment computed tomography images, we measured visceral fat area and volume, subcutaneous fat area and volume, visceral fat area ratio and visceral fat volume ratio. We compared patient backgrounds and these fat parameters between those who recurrently formed stones and those who formed stones for the first time. We also performed logistic regression analysis to identify factors that contribute to severe stones. RESULTS A total of 148 (49.3%) patients were recurrent stone-forming patients. Recurrent stone-forming patients were statistically significantly younger (P < 0.01) and there were more male patients (P < 0.01). In addition, visceral fat area ratio and visceral fat volume ratio in recurrent stone-forming patients were significantly higher than those in first-time stone-forming patients (P = 0.03 and P = 0.01, respectively). On the other hand, there was no significant difference in visceral fat area (P = 0.32), subcutaneous fat area (P = 0.36), visceral fat volume (P = 0.38) or subcutaneous fat volume (P = 0.23). Receiver operating characteristics analysis showed that area under the curve of visceral fat volume ratio (0.583) for recurrent stones was larger than that of visceral fat area ratio (0.571). In multivariate analysis, increasing visceral fat volume ratio was an independent significant predictor of recurrent stones (P = 0.04). CONCLUSIONS Recurrent stone-forming patients have high visceral fat ratios compared to first-time stone-forming patients, shown here for the first time.

Although previous studies have indicated that stone heterogeneity can affect extracorporeal shockwave lithotripsy (SWL) outcomes, there is no established measurement of stone heterogeneity on CT imagery. We investigated whether variation coefficient of stone density (VCSD) can predict shockwave success.We conducted a retrospective review of 245 patients with urinary calculi who had undergone SWL. We compared the predictive powers of treatment success between VCSD and other parameters associated with CT attenuation. In addition, we performed logistic regression analysis to identify the factors contributing to treatment success. Treatment success was determined within 3 months after first treatment using noncontrast CT.The treatment success rate was 47.8% (117/245 cases). From receiver operating characteristic curves for treatment success, area under curve of VCSD (0.7181) was larger than that of mean stone density (MSD) (0.6384, p = 0.09) and standard deviation of stone density (0.5412, p 0.01). Multivariate analysis revealed that MSD (p = 0.028) and VCSD (p 0.001) independently predicted the outcome. Categorized by stone location, VCSD was the independent significant predictor for SWL outcomes in both kidney (p = 0.047) and ureteral calculi (p 0.001).We found that VCSD can be a novel predictor of SWL success. The development of nomograms or scoring systems, including VCSD, can assist in the decision process for patients and minimize unnecessary delay in treatment of urolithiasis.

Objective To validate two prediction models (European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment) for recurrence and progression of non-muscle invasive bladder cancer in Japanese patients who underwent bacillus Calmette–Guerin instillation therapy. Methods From March 1985 to April 2007, data were analyzed from 366 patients who underwent transurethral resection of bladder tumor followed by bacillus Calmette–Guerin instillation therapy. The ability of two scoring models to predict recurrence and progression was assessed by concordance index. Results For recurrence probability, the concordance index of the European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment models was 0.514 and 0.576, respectively, which was lower than that (0.604) of a selected single prognostic factor (age) by our multivariate analysis. For progression probability, the concordance index of European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment models was 0.693 and 0.764, respectively, which was higher than that (0.633) of a selected single factor (T stage) by our multivariate analysis. The Spanish Urological Club for Oncological Treatment scoring system resulted in better stratification of tumor recurrence and progression when compared with the European Organization for Research and Treatment of Cancer model, probably because more patients underwent bacillus Calmette–Guerin treatment in the Spanish Urological Club for Oncological Treatment cohort than in the European Organization for Research and Treatment of Cancer cohort. Conclusions The Spanish Urological Club for Oncological Treatment scoring system is a good predictor of tumor recurrence and progression in Japanese patients who underwent bacillus Calmette–Guerin immunotherapy. A large prospective study is warranted to confirm the efficacy of this system.

A 63-year-old man was admitted to our hospital owing to weight loss and vertigo. Endoscopic examination revealed advanced gastric cancer type 2. Abdominal CT showed a 62mm liver tumor in segment 4 and a 26mm tumor in segment 8. Distal gastrectomy and D2 lymph node dissection were performed. After surgery, he was administered chemotherapy with S- 1. After 2 courses of treatment, the tumors' in segments 4 and 8 were reduced to 52mm and 16mm, respectively. No other metastases were detected. Left lobectomy and partial resection of segment 8 were performed. The pathological therapeutic effects were rated as Grade 1b for the tumor in segment 4 and Grade 3 for the tumor in segment 8. After hepatectomy, he was administered adjuvant chemotherapy with S-1 for 1 year. No recurrence has been detected for 4 years and 6months after hepatectomy.

Cancer stem–like cells (CSC) are a small population of cancer cells with superior tumor initiating, self-renewal, and differentiation properties. In this study, we show that the cancer-testis antigen and HSP40 family member DNAJB8 contributes to the CSC phenotype in renal cell carcinoma (RCC). DNAJB8 overexpression increased the percentage of side population (SP) cells representing CSCs in RCC cells, enhancing their tumor-initiating ability. Conversely, attenuation of DNAJB8 decreased SP cells and reduced tumor-initiating ability. The utility of DNAJB8 as an immunologic target was established in DNA vaccination experiments. Compared with immunization with the tumor-associated antigen survivin, which was expressed in both CSCs and non-CSCs in RCC, immunization with Dnajb8 expression plasmids yielded stronger antitumor effects. Together, our findings suggest that DNAJB8 plays a role in CSC maintenance and that it offers a candidate for CSC-targeting immunotherapy in RCC. Cancer Res; 72(11); 2844–54. ©2012 AACR.

症例は60歳代，男性．8年前に肝細胞癌に対し肝部分切除術が施行された．平成23年2月の精査で肝S4/8とS6に再発が認められたため手術予定となった．糖尿病のコントロールが悪くHbA1cが8％台と長期間高値であったため術前にdi-peptidyl peptidase-IV（以下DPP-4）阻害薬内服によりコントロールを行った．DPP-4阻害薬内服前の腫瘍最大径はダイナミックCTでS4/8が5.0 cm，S6が2.5 cmであったが，内服開始3週間後のダイナミックCTでは腫瘍最大径はS4/8が2.5 cm，S6が2.0 cmと縮小した．AFPとPIVKA-IIはDPP-4阻害薬内服後に著明に低下した．病理組織学検査で肝細胞癌内に著明なリンパ球浸潤を認め，免疫組織化学染色で浸潤リンパ球はCD8陽性T細胞であった．免疫応答が強く関与していると考えられる肝細胞癌自然退縮の1例を経験した．

Cancer stem-like cells (CSCs) and tumor-initiating cells (TICs) are a small population of cancer cells that share three properties: tumor initiating ability, self-renewal, and differentiation. These properties suggest that CSCs/TICs are essential for tumor maintenance, recurrence, and distant metastasis. Here, we show that cytotoxic T lymphocytes (CTLs) specific for the tumor-associated antigen CEP55 can efficiently recognize colon CSCs/TICs both in vitro and in vivo. Using Hoechst 33342 dye staining, we isolated CSCs/TICs as side population (SP) cells from colon cancer cell lines SW480, HT29, and HCT15. The SP cells expressed high levels of the stem cell markers SOX2, POU5F1, LGR5, and ALDH1A1 and showed resistance to chemotherapeutic agents such as irinotecan or etoposide.To evaluate the susceptibility of SP cells to CTLs, we used CTL clone 41, which is specific for the CEP55-derived antigenic peptide Cep55/c10orf3_193 (10) (VYVKGLLAKI). The SP cells expressed HLA class I and CEP55 at the same level as the main population cells. The SP cells were susceptible to CTL clone 41 at the same level as main population cells. Furthermore, adoptive transfer of CTL clone 41 inhibited tumor growth of SW480 SP cells in vivo. These observations suggest that Cep55/c10orf3_193(10) peptide-based cancer vaccine therapy or adoptive cell transfer of the CTL clone is a possible approach for targeting chemotherapy-resistant colon CSCs/TICs.

症例は45歳，男性．平成21年3月上腹部痛を主訴に受診した．腹部ダイナミックCT像上，左横隔膜脚部に接する後縦隔に濃染されない径5cmの腫瘤を認めた．神経原性腫瘍やリンパ嚢胞を疑い同年6月開腹下に摘出術を行った．摘出の際一部開胸となったが，腫瘍と肺との交通はみられなかった．腫瘍は黄白色の粘液を伴う嚢胞であった．病理組織上，嚢胞内面には多列線毛円柱上皮が被覆し，壁には平滑筋や気管支腺と思われる腺組織や軟骨組織がみられ，気管支嚢胞と診断された．気管支嚢胞は先天性の気管，気管支の異常分枝により生じ，肺内や中縦隔に発生することが多い．気管支との交通がある場合には感染症状を呈することもあるが，多くは無症状で経過することが多い．本症例は発生部位より気管支嚢胞との術前診断が困難で，大きさより悪性腫瘍も否定できず，摘出術の適応であったと考えられる．

Background: Recent large-scale randomized studies have demonstrated that 2 new hormone preparations (abiraterone and enzalutamide) prolong survival in docetaxel-treated or -naive castration-resistant prostate cancer patients. However, no studies have directly compared antitumor effects between these 2 agents, and no clear guidelines are available for choosing between them. Objective: The objective of this clinical study is to compare antitumor effects and adverse events between abiraterone and enzalutamide by allocating castration-resistant prostate cancer patients deemed not indicated for docetaxel treatment to receive either of the 2 agents. Methods: This study is an open-label, comparative study allocating castration-resistant prostate cancer patients to abiraterone or enzalutamide treatment arms (allocation factors: age

OBJECTIVE To investigate the association between metabolic syndrome and urinary stone disease, and whether insulin resistance associated with adiposity affects the risk of urinary stone formation, using a rat model of metabolic syndrome. MATERIALS AND METHODS Four-week-old male Otsuka Long-Evans Tokushima 'Fatty' (OLETF, a model of human type 2 diabetes and metabolic syndrome) rats, and Long-Evans Tokushima (LETO, a non-diabetic control) rats (10 each) were given a standardized diet and free access to water. Body weight and serum and urinary biochemistry were determined every 4 weeks. Ten-week-old male OLETF and LETO rats were divided into three groups of nine each and treated with vehicle or oral administration of 3 or 10 mg/kg/day pioglitazone, an agent that improves insulin resistance. After 4 weeks, body weight and serum and urinary biochemistry were determined. RESULTS The OLETF rats had significantly lower urinary pH and citrate excretion, and higher urinary uric acid and calcium excretion, than the LETO rats, with increases in body weight, serum triglyceride, glucose and insulin. The administration of pioglitazone to the OLETF rats for 4 weeks significantly increased urinary pH dose-dependently. There was no change in the urinary excretion of citrate, uric acid, calcium, oxalate or magnesium. CONCLUSION These results indicate that metabolic syndrome causes the changes in urinary constituents, leading to increased risk of both uric acid and calcium stone formation. Improvement in insulin resistance, a central cause of metabolic syndrome, might prevent uric acid stone formation by raising urinary pH.

OBJECTIVE To determine whether dendritic cells (DC) transduced with the prostate-specific antigen (PSA) gene can induce PSA-specific cytotoxic lymphocytes (CTL) against prostate cancer cells, and whether bacillus Calmette-Guerin (BCG) cell-wall skeleton (CWS) can enhance the maturation of DC-PSA and the killing activity of subsequently induced PSA-specific CTL. MATERIALS AND METHODS We generated an adenovirus encoding the PSA gene (AxCA-PSA) using the cosmid-terminal protein complex method. DC were infected with AxCA-PSA using the centrifugal method. The ability of CTL to lyse target cells expressing PSA, i.e the PSA-positive prostate cancer cell line, LNCap, and PSA-transduced autologous phytohaemagglutinin (PHA) blasts expressing PSA, was assessed using the 51Cr-release assay. The maturation of DC-PSA stimulated by BCG-CWS was assayed by flow cytometry. The cytotoxic activity enhanced by BCG-CWS was assessed by the 51Cr-release assay. RESULTS DC-PSA induced PSA-specific CTL with 85% cytotoxic activity against LNCaP (effector: target ratio, E:T, of 50:1). However, the cytotoxic activity against PSA-negative cells was very low. Anti-CD8 and anti-major histocompatibility (MHC) class I antibodies blocked PSA-specific cytotoxicity. The PSA-specific killing was reproducible against autologous PHA blast cells expressing PSA, independently of human leukocyte antigen haplotype. Furthermore, the combination of DC-PSA with BCG-CWS remarkably enhanced the PSA-specific cytotoxicity against PHA blasts expressing PSA (15–30% at an E:T ratio of 50:1). CONCLUSION These findings suggest that DC-PSA can induce MHC class I-restricted PSA-specific CD8+ CTL responses and that DC-PSA matured by BCG-CWS enhance PSA-specific cytotoxicity. The combination of DC-PSA with BCG-CWS might be a useful approach for treating advanced prostate cancer.

無平線植毛技術を用いた歯ブラシは植毛台が薄く, 口腔内の操作性がより高まると考えられる。以前我々は, ブラシの性状と植毛台の厚さが若干異なる2種類の無平線植毛歯ブラシにおけるプラーク除去効果について報告した。そこで, 本研究において歯ブラシの植毛台の厚さがプラーク除去効果に与える影響について検索するため, 刷毛の性状は同じであるが植毛技術の異なる2種類の歯ブラシ(歯ブラシS : 無平線歯ブラシ, 植毛台の厚さ2.5mm, 毛丈9.0mm, 毛先テーパード加工歯ブラシN : 平線歯ブラシ, 植毛台の厚さ5.0mm, 毛丈9.0mm, 毛先テーパード加工)と, 刷毛の性状が異なる無平線歯ブラシ(歯ブラシM : 植毛台の厚さ2.9mm, 毛丈9.5mm, 毛先ラウンド加工)を用い, プラーク除去効果について測定を行った。被験者は, ブラッシング技術が標準化された歯科衛生士学校の第2学年生徒(26名)とし, Ramfjord の代表6歯(16,21,24,36,41,44)に17,26,27,37,46,47の大臼歯を加えた12 歯を対象とし検討した。その結果, 全ての部位においてプラーク除去率は歯ブラシSが最も高く, 次いで歯ブラシN, 歯ブラシMの順であった。大臼歯部における歯ブラシSのプラーク除去率(46.9%)は他の歯ブラシ(歯ブラシM : 32.4%, 歯ブラシN : 33.2%)に比べ高く, 歯ブラシMに対しては統計学的に有意(p < 0.05)に高かった。歯ブラシSのプラーク除去率が歯ブラシNに比べて高かったのは, 植毛台の厚さが影響していることが示唆され, その効果は大臼歯部において顕著であった。日本歯周病学会会誌(日誌周誌)50(2) : 104-111, 2008

症例は82歳，男性．2005年7月頃より右腰背部の膨隆を自覚していた．腹部CT施行されたところ広背筋の腹側にて腰方形筋と内腹斜筋の間より脱出する後腹膜脂肪織を認め上腰ヘルニアと診断され手術目的にて当科紹介受診となった．右第12肋骨下縁三横指尾側，脊柱の右側に鶏卵大の柔らかな腹圧により膨隆する腫瘤を触知した．2006年3月に硬膜外麻酔下に左側臥位にて手術を施行した．ヘルニア門周囲を構成している筋群が比較的健常であったため直接縫合・閉鎖が可能であった．術後合併症なく13病日に退院した．以後の再発は認めていない．腰ヘルニアは稀な疾患であり，直接縫合閉鎖により修復可能であった上腰ヘルニア1例を経験したので報告する．

食道癌術後には凝固異常が発症することが知られている。この凝固異常に対しては，現在までステロイドなどさまざまな薬剤投与が試みられてきた。今回われわれは，好中球エラスターゼの特異的阻害剤（シベレスタットナトリウム，以下SN）投与の食道癌術後の凝固能におよぼす影響について検討した。対象は食道癌切除再建を一期的に行った41例で，これら症例を術後SNを投与した21例（SN+群）と，SNを投与しなかった20例（SN-群）に分けた。SN+群でSNを，術直後より0.2mg/kg/hrで術5病日まで持続的に投与した。全例で術直前にメチルプレドニゾロン（500mg）を投与し，術7病日まで血小板数・FBG·FDP·D-Dimer·AT3·TAT·APTT·Protein C・α2PIを経時的に測定した。血小板数・FBG·FDP·D-Dimer·TATの変動には両群に差がなかった。AT3とProtein Cは術2·3病日でSN+群が有意に高値で，α2PIは術3病日でSN+群が有意に高値であった。APTTは，術3病日にSN-群で有意に高かった。食道癌術後管理におけるエラスターゼ阻害剤投与は食道癌術後の凝固異常状態を制御し，早期に回復させることが可能である。

INTRODUCTION AND OBJECTIVES: Cancer stem-like cells (CSCs) are small population of cancer cells with superior tumor initating, seilf-renewel, and differentiation properties. In the previous study, we found that HSP40 family member DNAJB8 contributes to the CSC phenotype in renal cell carcinoma(RCC). HSF1 has been described to induce heat shock proteins by heat shock stress and be related to initiation and progression of cancer. In this study, we investigated the relations of HSF1 and CSC phenotype including DNAJB8. METHODS: RCC cell lines ACHN was given heat shock by incubating in 45 degrees for 60 minutes. HSF1 and DNAJB8 expression was evaluated by RT-PCR and Western blot analysis. CSCs were isolated by side population method by flowcytometry. SP(side population) cells mean CSCs, MP(main population) cells mean non-CSCs. As an inhibitor of HSF1, temsirolimus (mTOR inhibitor) was used. The cell viability was assessed by MTT assay. RESULTS: Heat shock stress enhanced the expression of DNAJB8 as well as SOX2. The expression of these molecules reached maximum 24 hours after heat shock, and the SP population increased at the same time. When MP cells sorted by flowcytometry were stimulated by heat shock, SP population could be newly detected. This fact implies that heat shock stress could induce the reversion from MP cells to SP cells. Concerning the mechanism of the reversion from MP cells to SP cells by heat shock, HSF1 seems to play an important role. We found that the expression of phosphorylated HSF1 increased by heat shock, although the expression level of HSF1 itself did not change. Interestingly, when HSF1 was knocked down by siRNA, DNAJB8 could not be induced even after heat shock stress. This suggests that the stress-inducible expression of DNAJB8 is regulated by HSF1, which bind to the heat shock element(HSE) in the promoter of DNAJB8 gene and stimulate its transcription. Treatment with temsirolimus to ACHN cells could inhibit phosphorylation of HSF1, followed by down regulation of DNAJB8, resulting in the decrease of SP population. SP cells were more susceptible by temsilolimus treatment than MP cells. CONCLUSIONS: Stress including heat shock such as hyperthermia might induce DNAJB8 expression, which is related to CSC phenotype. Phosphorylation of HSF1 is required in this process. mTOR inhibitor could inhibit CSC specifically by inhibiting phosphorylation of HSF1.

成因の異なる良性食道気道瘻3例を経験した。症例1: 63歳，男性。食道癌に対し，60Gy照射した1年後に咳嗽と胸痛が出現した。内視鏡で食道と左主気管支間に瘻孔を認めたが，ステントにて瘻孔を遮断できず，右開胸下に瘻孔辺縁の食道壁によるパッチ閉鎖および食道癌根治術を行った。瘻孔部に癌遺残はなく，放射線傷害による食道気管支瘻と診断した。症例2: 56歳，男性。胆嚢摘出術後に左肺炎を繰り返した。胸部X線で左下肺野の肺炎像を，食道造影で中部食道の憩室から左下気管支へ造影剤の流入を認めた。左開胸下に憩室と左主気管支間に索状物，また左肺下葉の器質化を認めた。Braimbridge I型の先天性食道気管支瘻と診断し，憩室切除と左肺下葉切除を行った。症例3: 31歳，男性。交通事故での胸部外傷後，摂食時に咳嗽が出現した。内視鏡で膜様部欠損による食道気管瘻を認めた。外傷性食道気管瘻と診断し，右開胸下に瘻孔辺縁の食道壁によるパッチ閉鎖を行い，食道壁はGambee縫合で閉鎖した。良性食道気道瘻では食道や気道の狭窄を伴うことが少なく，ステントによる瘻孔遮断は無効なことが多い。手術による瘻孔閉鎖が有効である。

Sixteen infants were analyzed longitudinally from the onset of independent walking to 3 years of age using time parameters, speed and energy recovery. Considerable variation and irregularities were observed in many parameters of infant walking, especially until 13 months of age when infants had difficulty in walking steadily step by step. Infant walking until 3 years of age was characterized by a small braking duration, caused mainly by the forward inclination of the trunk, a large relative stance phase duration, which maintained static balance, short stride length, due to the small range of the lower limb joint angle, and a small recovery of external energy. These characteristics were also predominantly evident until 13 months of age. The small recovery characteristic of infants was caused by flexed lower limb joints, pronounced irregularities in energy output, and in younger infants, slow speed. The maximum recovery up until 2 years of age, though smaller than in adults, appeared at about 0.45 dimensionless speed, which is about the same speed that adults in particular naturally and at which their maximum recovery appeared. The forward inclination of the trunk and the lower limb joint angle, influenced the development of many characteristics of bipedal walking.

Self-expandable metallic stent (EMS) placement has been the first choice for dysphagia because of the certainty over its safety, low invasiveness, and immediate efficacy. However, there still remain some problems in relation to the EMS placement site and anticancer therapies before and after EMS placement. Methods: Consecutive 78 patients in whom EMS was placed due to the unresectable malignant stricture in the esophagus or cardia from July 1995 to August 2003 in our department were studied. Results: Gastroesophageal reflux was found in 5 of 8 patients after placement of conventional EMS for the stricture in the gastroesophageal junction. Meanwhile, acid and bile reflux into the esophagus were not detected by pH and bilirubin monitoring, respectively, in 6 patients after placement of the EMS with an anti-reflux mechanism for the stricture in the gastroesophageal junction. The median survival period of all patients after EMS placement was 123 days. The median survival period of 7 patients with radiotherapy only after EMS placement was 138 days and that of 17 patients with radiotherapy before EMS placement was 60 days, which was shorter than that of the former (p

症例は,64歳,女性.高度大動脈弁狭窄症(AS)に対して自己心膜を用いた弁輪拡大術と機械弁による大動脈弁置換術を行ったが,約8ヵ月目に発熱と心不全をきたした.心臓超音波検査では,大動脈人工弁に疣贅の付着,人工弁周囲逆流とIII度の僧帽弁逆流を認め,平成11年7月26日に血行動態の悪化のため手術を施行した.感染した大動脈人工弁と自己心膜および僧帽弁の除去と,デブリドメンを行い感染巣を可及的に除去したのち,馬心膜を用いた大動脈弁輪拡大術と,大動脈弁,僧帽弁の2弁置換術を行った.大動脈人工弁は左冠尖部で弁輪から遊離し,その部には疣贅の付着を認めた.病理鏡検検査で真菌との混合感染症と診断し,術後2日目から抗真菌剤の投与を開始した.術後37日目に炎症反応が陰性化したため退院し,現在も抗真菌剤の投与を継続している.人工弁の真菌性心内膜炎に対する手術報告例は少ないが,弁輪拡大を伴った大動脈弁置換術後の感染性心内膜炎に対しては,2弁置換によるaortoatrioplastyは有効な術式であった.患者は現在まで術後約5年間を良好に経過しているが,今後も感染の再燃に対する注意が必要である.

Background A population-based prospective cohort study was undertaken to examine the predictors of functional decline in instrumental activities of daily living (I-ADL) among non-disabled older Japanese subjects living in a rural community during a five-year interval from 1992 to 1997. Methods The subjects consisted of 624 men and women aged from 65–89 years and independent in I-ADL at baseline, who could be completely followed for five years. Independent variables were various physical factors potentially associated with higher level of functional capacity obtained from an interview survey and medical examinations at baseline. Dependent variables were functional status in I-ADL obtained at the time of the 5-year follow-up. Results Significant predictors of functional decline in I-ADL during a 5-year follow-up period included: (1) older age; (2) higher blood pressure; and (3) lower maximum walking speed at baseline. Among these predictor, the maximum walking speed is likely to the strongest predictor for the decline in I-ADL. Conclusion The ability to walk faster in the old age is strongly associated with independence in the other I-ADL, and walking speed should be modified by the lifestyle to strengthen muscles of the lower extremities in daily life.

In this study, we examined the factorial structure of the physical performance measures and the longitudinal invariance of elderly people in the community. The subjects were investigated in Akita as part of TMG-LISA. Data used in this study were from 463 older adults who participated in all the physical performance tests, both in the baseline (1992) and the 4-year follow-up (1996) investigation. The test battery consisted of six items (hand power, walking, and balance). There were longitudinal aging changes in gender and age in all of the measurements between the baseline research and the follow-up research, except for the one-leg standing with eyes closed test. The factorial invariance of the structure in these measures taken in 1992 and 1996 was confirmed through the confirmatory factor analysis (CFA) of the structural equation modeling, controlled for gender and age. As a preliminary step for analysis of factorial invariance, we analyzed the fitting basic motor ability model to cross-sectional data of the baseline and follow-up. As a result of the analysis, the fitness levels of each data of the models were good. Then, we applied simultaneous analysis and analyzed longitudinal changes in the factorial structure of measurements. The results were that there were the same factors in the factorial structure model of physical performance measured in both the baseline and follow-up investigation, and that their arrangements were identical. Furthermore, we find that there was no difference in all factor-loading in both models being investigated. These results statistically indicated that there were no signs of aging changes in factorial structure of the measures between the baseline investigations and the follow-up 4 years later in spite of the longitudinal decline of the values of physical performance tests. Moreover, it was indicated that the simultaneous analysis, which this research used, was applicable for statistical analysis procedure of factorial invariance of various repeated measures on studies of aging, as a longitudinal study.