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Supplementary Figure 1 from Visible Drug Delivery by Supramolecular Nanocarriers Directing to Single-Platformed Diagnosis and Therapy of Pancreatic Tumor Model

Supplementary Table 2 from Visible Drug Delivery by Supramolecular Nanocarriers Directing to Single-Platformed Diagnosis and Therapy of Pancreatic Tumor Model

Nanoparticle therapeutics are promising platforms for cancer therapy. However, it remains a formidable challenge to assess their distribution and clinical efficacy for therapeutic applications. Here, by using multifunctional polymeric micellar nanocarriers incorporating clinically approved gadolinium (Gd)–based magnetic resonance imaging contrast agents and platinum (Pt) anticancer drugs through reversible metal chelation of Pt, simultaneous imaging and therapy of an orthotopic animal model of intractable human pancreatic tumor was successfully performed without any serious toxicity. The strong tumor contrast enhancement achieved by the micelles correlated with the 24 times increase of r1 of the Gd chelates, the highest for the formulations using clinically approved Gd chelates reported to date. From the micro-synchrotron radiation X-ray fluorescence spectrometry scanning of the lesions, we confirmed that both the Gd chelates and Pt drugs delivered by the micelles selectively colocalized in the tumor interior. Our study provides new insights for the design of theranostic micelles with high contrast enhancement and site-specific clinical potential. Cancer Res; 70(18); 7031–41. ©2010 AACR.

Supplementary Methods from Visible Drug Delivery by Supramolecular Nanocarriers Directing to Single-Platformed Diagnosis and Therapy of Pancreatic Tumor Model

Supplementary Figure 3 from Visible Drug Delivery by Supramolecular Nanocarriers Directing to Single-Platformed Diagnosis and Therapy of Pancreatic Tumor Model

Supplementary Table 1 from Visible Drug Delivery by Supramolecular Nanocarriers Directing to Single-Platformed Diagnosis and Therapy of Pancreatic Tumor Model

Supplementary Figure 2 from Visible Drug Delivery by Supramolecular Nanocarriers Directing to Single-Platformed Diagnosis and Therapy of Pancreatic Tumor Model

Western philosophy was rapidly introduced into East Asia from the second half of the nineteenth century, in a movement that began in Japan but quickly spread to China and Korea. When phenomenology appeared in Europe at the beginning of the twentieth century, the Japanese philosopher Nishida Kitaro was one of the first to realize its importance. In the 1920s, many Japanese scholars, including a number of Nishida’s students, traveled to Europe to study under Husserl and Heidegger in Freiburg. Korean philosophers also became interested in phenomenology in the 1920s, and Xiong Wei of China went to Freiburg in the 1930s and was greatly influenced by Heidegger. The reception of Western philosophy was impeded by the barrier of a different culture and intellectual tradition, in addition to the barrier of language, but phenomenology was felt to have many affinities to East Asian thinking. This was particularly true of Heidegger’s work. Both Husserl and Heidegger were criticized from the East Asian perspective on various points, but this criticism helped to develop the phenomenological movement as an intercultural project engaging both East and West. Japan, Korea and the countries that make up the Chinese cultural sphere have much in common, but differences in political and social climate affected the development of phenomenological research in each country. In Japan, existentialism became popular after the nation’s defeat in World War II (1939–45) and this led to a shift in interest from German phenomenology to French thinkers like Sartre and Merleau-Ponty. The Korean peninsula suffered a long period of chaos because of the same war and the Korean War that followed (1950–3), and the resulting devastation there also led to a heightened interest in existentialism. Marxism also became an important influence, especially in Japan, where various left-leaning thinkers attempted to integrate phenomenology with Marxist thought. In mainland China, the Communist Revolution and subsequent establishment of the People’s Republic of China (1949) and the Cultural Revolution of 1966–76 hampered the reception of Western philosophy, but the country has since produced many fine phenomenological researchers. The Chinese University of Hong Kong is a long-standing centre of phenomenological research and has maintained close ties with institutions on the mainland since Hong Kong’s reversion to China in 1997. Scholars in Taiwan continued to study phenomenology throughout the postwar period and now maintain active exchange with colleagues in Hong Kong and mainland China. Phenomenology is well established in East Asia, with research expanding in many directions. Scholars keep up with developments in the West and pursue research in similar directions; others focus on the connection between phenomenology and the intellectual traditions of East Asia; still others apply the methods of phenomenology to interdisciplinary studies. Other phenomenologists are working on original theories that are relatively free of cultural and disciplinary boundaries. Research is active at universities in all the countries in question. Each country has phenomenological organizations that are active domestically and which engage in academic exchange with organizations abroad. On the whole, East Asia may be said to be one of phenomenology’s most active venues.

Objective The aim of this study was to search for novel markers of visceral adiposity. Methods Visceral (omental) and subcutaneous adipose tissues were obtained from 43 Japanese men. Microarray analysis using total RNA from visceral and subcutaneous adipose tissues obtained from five men with abdominal obesity and five nonobese men was first conducted. Then the expression pattern of candidate genes identified in the human study in mouse models of adiposity was examined. Results Among 30,500 genes evaluated, the mRNA expression of CCDC3 (encoding coiled-coil domain-containing protein 3) was upregulated in omental adipose tissues from abdominally obese subjects (3.07-fold) but not in subcutaneous adipose tissues (0.89-fold). Similar expression patterns were found in two distinct mouse models of obesity. In the analysis of all 43 men, CCDC3 mRNA levels in omental, but not in subcutaneous adipose tissue, were positively correlated with waist circumference and body mass index. CCDC3 was predicted to be a secretory protein, which was confirmed by western blotting, as overexpressed CCDC3 was secreted into the culture media. Conclusions The expression of CCDC3 is specifically increased in visceral adipose tissues in abdominally obese subjects. These results suggest that CCDC3 is a potential biomarker for estimating visceral adiposity.

To identify new cancer biomarkers and therapeutic targets for colorectal cancers (CRCs), we performed immunohistochemical analysis using tissue microarrays covering archival tumor tissue samples from 434 CRC patients and antibodies to cell division cycle-associated protein 1 (CDCA1) that was originally identified as an oncoantigen by our gene expression profile database, and compared its expression with several clinicopathological factors. Strong CDCA1 positivity was associated with poorer prognosis for patients with CRC (P=0.019) and multivariate analysis confirmed its independent prognostic value. In addition, transfection of siRNAs against CDCA1 suppressed its expression and induced apoptosis of CRC cells. These results suggest that CDCA1 could be a prognostic biomarker and a potential therapeutic target for CRCs.

The number of bariatric procedures performed in Japan is increasing. There are isolated reports of bariatric surgery, but there have been no nationwide surveys including long-term data. We retrospectively reviewed data for patients who underwent bariatric and metabolic surgery throughout Japan and reviewed outcomes. Surveys were sent to ten institutions for number of procedures, preoperative patient weight and preoperative obesity-related comorbidities, and data at 1, 3, and 5 years postoperatively. Improvement of type 2 diabetes mellitus at 3 years after surgery was stratified by baseline ABCD score, based on age, body mass index, C-peptide level, and duration of diabetes. Replies were received from nine of the ten institutions. From August 2005 to June 2015, 831 patients, including 366 males and 465 females, underwent bariatric procedures. The mean age was 41 years, and mean BMI was 42 kg/m2. The most common procedure was laparoscopic sleeve gastrectomy (n = 501, 60 %) followed by laparoscopic sleeve gastrectomy with duodenojejunal bypass (n = 149, 18 %). Laparoscopic Roux-en-Y gastric bypass was performed in 100 patients (12 %), and laparoscopic adjustable gastric banding was performed in 81 (10 %). At 3 years postoperatively, the remission rate of obesity-related comorbidities was 78 % for diabetes, 60 % for hypertension, and 65 % for dyslipidemia. Patients with complete remission of diabetes at 3 years postoperatively had a higher ABCD score than those without (6.4 ± 1.6 vs 4.2 ± 2.0, P

Introduction: In Japan, laparoscopic bariatric surgery has not been popular until recently because morbidly obese patients were infrequently encountered previous and Japanese health insurance does not cover this type of surgery. In 2010, the Japan Research Society for Endoscopic and Laparoscopic Treatments of Obesity undertook the first nationwide survey on laparoscopic bariatric surgery to evaluate its current status and outcomes. Methods: A mail survey was sent to the society's 64 member institutions, which included almost all institutions in Japan actively performing laparoscopic gastrointestinal surgery. Results: From 2000 to 2009, 340 laparoscopic bariatric procedures, in total, were performed in nine of the 64 institutions (14%). The most popular procedure was laparoscopic Roux-en-Y gastric bypass (LRYGB, n=147), second was laparoscopic sleeve gastrectomy (LSG, n=102), and third was laparoscopic adjustable gastric banding (LAGB, n=55). However, the number of LRYGB procedures has decreased while the number of LSG procedures has rapidly increased. Total morbidity rates were 12.2% for LRYGB, 10.9% for LAGB, and 7.8% for LSG. Percent excess weight loss was 78% at 5 years after LRYGB, 52% at 4 years after LAGB, and 68% at 2 years after LSG. Although the bariatric procedures frequently resolved or improved obesity-related comorbidities, LRYGB appears to be superior to LAGB, as was previously reported. Conclusion: The first nationwide survey of laparoscopic bariatric surgery in Japan clearly showed the current status and outcomes of this group of procedures. The Japanese results appear to be comparable to similarly undertaken surveys in Europe and the USA.

To examine the effect of laparoscopic sleeve gastrectomy (LSG) on glucose metabolism. LSG was performed in two patients with diabetes and one with impaired glucose tolerance. An oral glucose tolerance test (OGTT) was performed preoperatively and 3 months postoperatively. Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) levels were measured during the OGTT. Fasting ghrelin levels were also measured. Two diabetic patients discontinued oral hypoglycemic agents or insulin immediately post-surgery, and the HbA1c level was improved. The area under the curve for insulin and GLP-1 was increased after surgery. In contrast, GIP secretion did not change significantly. Fasting ghrelin levels were decreased in all patients. LSG can lead to a rapid improvement of glucose tolerance with enhanced insulin secretion. Increased GLP-1 secretion and decreased ghrelin levels may play a role in improvement of glucose tolerance and insulin secretion after LSG.

Nanoparticle therapeutics are promising platforms for cancer therapy. However, it remains a formidable challenge to assess their distribution and clinical efficacy for therapeutic applications. Here, by using multifunctional polymeric micellar nanocarriers incorporating clinically approved gadolinium (Gd)–based magnetic resonance imaging contrast agents and platinum (Pt) anticancer drugs through reversible metal chelation of Pt, simultaneous imaging and therapy of an orthotopic animal model of intractable human pancreatic tumor was successfully performed without any serious toxicity. The strong tumor contrast enhancement achieved by the micelles correlated with the 24 times increase of r1 of the Gd chelates, the highest for the formulations using clinically approved Gd chelates reported to date. From the micro-synchrotron radiation X-ray fluorescence spectrometry scanning of the lesions, we confirmed that both the Gd chelates and Pt drugs delivered by the micelles selectively colocalized in the tumor interior. Our study provides new insights for the design of theranostic micelles with high contrast enhancement and site-specific clinical potential. Cancer Res; 70(18); 7031–41. ©2010 AACR.

To determine the potential role of the transcriptional factor-activating enhancer-binding protein-2beta (TFAP2B) in the regulation of expression of adipokines, adiponectin, leptin, and interleukin-6 (IL-6) in vivo, we quantified the mRNA expression levels of these adipokines and TFAP2B in visceral (omental) and abdominal subcutaneous adipose tissues of 66 individuals with variable degree of adiposity and studied their correlations with BMI and their plasma concentrations. We found that BMI correlated negatively with plasma adiponectin levels and positively with those of leptin. Adiponection mRNA expression in subcutaneous fat correlated negatively with BMI, whereas leptin mRNA levels in the omentum correlated with plasma leptin levels and BMI. In contrast, IL-6 mRNA levels in subcutaneous and omental fat did not correlate with BMI. IL-6 mRNA levels in the omental fat correlated with plasma IL-6 levels. Whereas TFAP2B mRNA expression did not correlate with BMI, it correlated negatively with adiponectin expression in the subcutaneous adipose tissue. Furthermore, TFAP2B mRNA expression correlated negatively with leptin and positively with IL-6 expression in both subcutaneous and omental adipose tissues. These relationships are consistent with our in vitro observations and indicate that TFAP2B seems to regulate the expression of various adipokines in vivo.

Purpose To assess whether Gd-DTPA-Gel-Cis, a conjugate of gadolinium (Gd), cis diamminedichloroplatinum (Cis), diethylenetriaminepentaacetic acid (DTPA)-dianhydride, and bovine gelatin (Gel) can be used as an intravascular contrast agent at MRI and as an antitumor cell proliferation agent in vitro. Materials and Methods We injected Gd-DTPA-Gel-Cis (200 mg/mL) into the caudal vein of female HER-2/neu transgenic mice with spontaneous mammary tumors. The tumor signal intensity was measured with a 0.3 Tesla MRI scanner. HER-2/neu-expressing NT cells were treated with Gd-DTPA-Gel-Cis (5 μM cisplatin, 200 mg/mL Gel), Cis alone (5 μM cisplatin), or Gel alone (200 mg/mL gelatin). Differences of P < 0.05 were considered to be statistically significant. Results On T1-weighted MRI scans of mice injected with Gd-DTPA-Gel-Cis we observed a 23% increase in signal intensity. The survival rates of cells exposed to Gd-DTPA-Gel-Cis or Cis were 70.9% and 58.3%, respectively, of the survival rates observed after treatment with Gel alone. Gd-DTPA-Gel-Cis showed significant toxicity (P < 0.05). Conclusion Gd-DTPA-Gel-Cis shows promise for use as an MRI contrast medium and as an antitumor agent. J. Magn. Reson. Imaging 2009;30:907–910. © 2009 Wiley-Liss, Inc.

Japan has absorbed many western ideas since the late nineteenth century, but Japanese philosophers have often been reluctant to accept the western idea of the “I” in its entirety. The I transgresses to the Other more easily than western philosophies think and imports what belongs to the Other as his own. How is this possible? Husserl attempted to explain the constitution of the Other by the intentionality that goes from the I to the Other, mediated by the body. However, Husserl later discovered that the constitution of both the I and the Other is more of a two-way movement. This double-movement is essential for all constitutions and departs from a deep (primal) dimension that is not yet egological. Even in the self-reflection of the I, a similar double-movement between the primal and egological dimensions can be seen. The I is supported, but at the same time threatened, by this movement.

大腸癌に合併した陳旧性肝内血腫の1例を経験したので報告する. 症例は71歳, 女性. 検診での血液検査にて貧血を指摘され, 近医にて精査の結果, 上行結腸に亜全周性2型腫瘍と, 肝S7に腫瘤性病変を認めたため当院紹介となった. 転移性肝癌の可能性を否定できず, 開腹手術を施行した. 術式は結腸右半切除術, D3郭清, 肝部分切除術を施行した. 肝腫瘤の組織型は陳旧性肝内血腫であった. 陳旧性肝内血腫の文献報告例は本邦でも12例あるが, 悪性腫瘍との合併例は稀であり, 若干の文献的考察を加え, 報告する.

Hemorrhagic shock followed by resuscitation (HSR) induces oxidative stress, which leads to acute lung injury. Heme oxygenase (HO)-1 (EC 1.14.99.3), the rate-limiting enzyme in heme catabolism, is inducible by oxidative stress and is thought to play an important role in the protection from oxidative tissue injuries. In this study, we examined expression of HO-1 as well as tissue injuries in the lung, liver, and kidney after HSR in rats. We also pretreated animals with heme arginate (HA), a strong inducer of HO-1, and examined its effect on the HSR-induced lung injury. HO-1 expression significantly increased in the liver and kidney following HSR, while its expression in the lung was very low and unchanged after HSR. In contrast to HO-1 expression, tissue injury and tumor necrosis factor-alpha (TNF-alpha) gene expression was more prominent in the lung compared with those in the liver and kidney. HA pretreatment markedly induced HO-1 in pulmonary epithelial cells, and ameliorated the lung injury induced by HSR as judged by the improvement of histological changes, while it decreased TNF-alpha and inducible nitric oxide synthase gene expression, lung wet weight to dry weight ratio, and myeloperoxidase activity. In contrast, inhibition of HO-1 by tin-mesoporphyrin administration abolished the beneficial effect of HA pretreatment. These findings suggest that tissues with higher HO-1 may be better protected than those with lower HO-1 from oxidative tissue injury induced by HSR. Our findings also indicate that HA pretreatment can significantly suppress the HSR-induced lung injury by virtue of its ability to induce HO-1.

経仙骨的直腸切除術後に瘢痕ヘルニアをきたした症例を経験した.症例は57歳男性で主訴は仙骨部腫瘤であった.直腸癌に対し経腹仙骨的直腸切除術を施行した8カ月後より右臀部仙骨右縁下端の手術創部の皮下に腫瘤を自覚するようになり, 2004年10月には8cm×6cmにまで増大した.骨盤部CTにて仙骨右側下方の臀部皮下に腸管が入り込んでいることを認め,瘢痕ヘルニアと診断し手術を施行した.ヘルニア門は仙骨右縁下端の尾骨切除部近傍で,ヘルニア嚢は後腹膜,ヘルニア内容は小腸であった.ヘルニア嚢を骨盤腔側へ内翻後ヘルニア門をメッシュプラグで修復し,さらに大殿筋回転皮弁を作成してメッシュ部を被覆した.仙骨的直腸切除後の瘢痕ヘルニアは文献的には前例がなく修復法を熟考したが,メッシュを使用したtension freeのヘルニア門閉鎖方法に加え大殿筋皮弁の使用を付加することが最良であるという印象であった.

Adenovirus-mediated wild-type p53 gene transfer induces apoptosis in a variety of human cancer cells. Although clinical trials have demonstrated that a replication-deficient recombinant adenovirus expressing the wild-type p53 gene (Ad-p53) is effective in suppressing growth of non-small cell lung cancer (NSCLC), we often experienced late resistance to this treatment. To elucidate the mechanism of late resistance to Ad-p53 in human lung cancer cells, we generated 5 different resistant variants from p53-susceptible H1299 NSCLC cells by repeated infections with Ad-p53. We first examined the transduction efficiency of adenoviral vector by Ad-LacZ transduction followed by X-gal staining in parental and 5 resistant H1299 cell lines. Their sensitivity to viral infection decreased in correlation with the magnitude of resistance, and Ad-p53-mediated tumor suppression could be restored by dose escalation of Ad-p53 in the resistant variants. The expression of Coxsackie and adenovirus receptor (CAR) and alphaV integrins, which are cellular receptors for attachment and internalization of the virus, respectively, was next investigated in these cell lines. Flow cytometry revealed that alphaVbeta3 and alphaVbeta5 integrin expression was consistent, while p53-resistant cell lines showed that diminished CAR expression correlated with the magnitude of the resistance. Our results demonstrated that decreased CAR expression could be one of the mechanisms of late resistance to Ad-p53, which may have a significant impact on the outcome of adenovirus-based cancer gene therapy.

傍十二指腸ヘルニアはTreitz靱帯周囲の腹部窩に腸管が入り込む内ヘルニアの一つで,本邦では約100例が報告されているにすぎない.症例は14歳の男性で, 1年前より4回の腹痛発作を繰り返していた. 4度目の腹痛発作時,腸閉塞の診断のもとイレウス管を挿入した.腸閉塞は解除されたが,腹痛発作を繰り返すため,診断治療目的で腹腔鏡補助下に手術を行った.左傍十二指腸ヘルニアが認められたため開腹し,ヘルニア内容を還納した後ヘルニア門を閉鎖した.ヘルニア門は脈管環によって締め付けられていた.術前には確定診断できなかったが,腹部CTにて下腸間膜静脈が上方に圧排され,その背側に小腸が嵌入しているなど,特徴的な小腸および血管系の走行異常が確認できた.比較的若年者で,開腹手術の既往がなく,腹痛を繰り返す症例では傍十二指腸ヘルニアの可能性を考慮する必要があり,その診断に造影CTが有効である.

Clinicopathological study was made on 111 thoracic esophageal cancers experienced in the 1st department of Surgery of the Shiga University of Medical Science from 1979 to 1998. Cancers positioned in the middle part of the esophagus accounted for 68.2% of all cases. Stage 3 and 4 advanced cancers accounted for 61.7% of all lesions, and the frequency of early cancer was 22%. The lymph node metastasis to the upper mediastinum, especially along the recurrent nerves, was observed with a high frequency (60%) in the Ut cases. The lymph node metastasis in the neck was observed frequently in the Ut (20%) and Mt cases (19.4%), and the lymph node metastasis to the abdominal region was observed frequently in Lt cases (47.8%). In cases of superficial esophageal cancer, the lymph node metastasis was observed as a tumor invaded the depth of middle layer of submucosa (sm2). No cancer death occurred in cases of mucosal (m) and sml superficial cancer, however, the 5-year survival rates of sm2 and sm3 cases decreased remarkably. If the lymph node dissection along the recurrent nerves is reliable, significant difference in the survival rate was not recognized between the 2-field lymph node dissection and 3-field lymph node dissection.

Ninty nine cases with severe infection were evaluated their endotoxin levels with two different methods during endotoxin adsobing therapy (Toraymyxin®) .84 patients out of 99 had multiple organ failure. Survival rate at 2 weeks after direct hemoperfusion (DHP) with Toraymyxin was 63%. The endotoxin was measured in 45 cases by PCA method, and in 52 cases by Toxikolor method.The endotoxin levels measured by PCA showed 27% decrease after DHP in survived group but no changes in died group. But measured values by Toxikolor showed a decrease in both groups.The result of two methods showed the similar tendency that the plasma endotoxin changes by DHP correlated with the changes of blood pressure (BP) and PaO2/FiO2 (P/F) ratio. The cases with BP under 100 mmHg showed a significant increase over 100 mmHg after DHP in the group whose endotoxin level decreased with DHP. The same tendency was shown in P/F ratio. But in the group whose endotoxin levels did not decreased with DHP, both BP and P/F ratio could not improved significantly by DHP.

We report a case of advanced rectal cancer with bladder carcinoma. The patient was a 81-year-old man who complained of abdominal bloating. A colonoscopy showed that he had advanced lower rectal cancer. CT scan revealed many lymph node metastases around the tumor, and also a bladder tumor. He experienced myocardial infarction during the operation but was relieved by PCI. During the operation, sigmoid colostomy was performed. The curative operation was declined and chemotherapy was selected. Capecitabine(2, 000mg/m / 2, biweekly)plus oxaliplatin(130mg/m2, day 1)was selected. At first, he complained of peripheral vein pain. The speed of oxaliplatin infusion was slowed and the pain was relieved. He had Grade 3 platelet decrease, but the number improved after 3 weeks. The tumor marker decreased after 3 courses, 6 courses after CT scan revealed that the tumor and lymph node metastases had evidently decreased. Capecitabine plus oxaliplatin(XELOX)was considered to be a useful chemotherapy against advanced rectal cancer, even for older patients or high risk groups.

We experienced a case of recurrent breast cancer to the chest wall 12 years after the first operation. The patient was a 52-year-old woman. There was a previous history of undergoing a radical mastectomy for a right breast cancer (t2n1βM0, Stage II) in October, 1982. The histologic type was solid tubular carcinoma and the tumor was estrogen and progesterone receptor positive. In July, 1984, bilateral oophorectomy was carried out, followed by administration of tegafur and tamoxifen. The drug regimen was discontiuned in March, 1993, because she had no signs of recurrence. Two years later (in January, 1995), erosion associating with hemorrhage developed in the right anterior thoracic region. Close examination indicated a recurrence in the chest wall involving the right 4 and 5th ribs. After one course of CAF regimen excision of the chest wall with associated excision of the 3, 4 and 5th ribs ranging about 15 cm was carried out. A 15×8 cm defect in the chest wall was reconstructed with Marex mesh and latissimus dorsi muscle and skin flap. Postoperative course was uneventful. After two courses of CAF regimen, the patient was idscharged from the hospital. There has been no sign of recurrence, as of August, 1995, while tegafur and tagafur are still continued.

The clinical significance of preoperative chemotherapy, including trastuzumab for HER2-positive breast cancer, was examined based on hormone receptors(HR)to clarify future issues.104 HER2-positive breast cancer patients who completed preoperative chemotherapy and underwent surgery from May 2005 to August 2010. All patients received sequential treatment with taxane±trastuzumab for FEC(5-FU+epirubicin+cyclophosphamide)therapy, and from 2008 they received trastuzumab postoperatively for one year.Concerning the histological effects, the rate of comprehensive pCR(CpCR)in the 104 patients(31 HR-negative administered trastuzumab, 15 HR-negative not administered trastuzumab, 28 HR-positive administered trastuzumab, 30 HR-positive not administered trastuzumab)was 65%, 47%, 21% and 23% for each group, respectively CpCR was a significant factor(p0. 05)in prolonged distant disease-free survival(DDFS)in the HR-negative group. Distant metastasis occurred in 14 patients, namely, brain metastasis in 7 patients(4 HR-negative administered trastuzumab, 1 HR-negative not administered trastuzumab, 2 HR-positive administered trastuzumab). The therapeutic efficacy was pINV in 5 of these 7 patients(3HR-negative administered trastuzumab, 1 HR-negative not administered trastuzumab, 1 HR-positive administered trastuzumab), and 4 of those 5 patients received trastuzumab postoperatively.The responsiveness to preoperative chemotherapy including trastuzumab for HER2-positive breast cancer differs between HR-positive and HR-negative. pINV patients seem to be at a high risk for brain metastasis regardless of HR, and it may be difficult to suppress its occurrence only with trastuzumab adjuvant therapy.

We report a male case of beta-catenin-activated hepatocellular adenoma (HCA) focusing on findings of gadoxetic-acid-enhanced magnetic resonance imaging (EOB-MRI) and discussing the molecular background and possible clinical significance. The patient was a 31-year-old man in whom computed tomography (CT) showed a large nodule of 14 cm in diameter in the right liver lobe. On dynamic contrast-enhanced CT, heterogeneous and slight to moderate enhancement was observed during the early phase, with washout in the late phase. Focal fat deposits and a scar-like portion in the lesion were also seen. Most of the lesion was slightly hyperintense compared with the background liver on the hepatobiliary phase of EOB-MRI. After operation, this patient was confirmed pathologically as having beta-catenin-activated HCA with a portion suggestive of malignant transformation. In addition, intense organic anion transporter polypeptide 8 expression was observed throughout the tumor by immunohistochemical staining.

Postoperative adjuvant chemotherapy with S-1 is a standard treatment for several digestive cancers. We conducted alter- nate-day oral therapy as postoperative adjuvant chemotherapy with S-1, for 31 patients with pathological stage II / IIIgastric cancer for whom radical resection had been performed. We examined the effects, the rate of compliance with all of the dosing instructions, cancer recurrence, and the survival rate with S-1 by the administration method for 31 cases. Twenty-eight patients(90. 3%)could be administered S-1 for one year. Those with side effects were admitted in 4 cases(13%). Those with side effects of grade 3 or more were not admitted. The 3-year survival rate was obtained; stage II 91%, and stage III 67% in gastric cancer. Four patients had recurrences at; the rate of 13%. In conclusion, the number of side effects was decreased, and a high rate of compliance with all dosing instructions was achieved in alternate-day oral therapy with S-1, compared with the daily oral method. This method can be a safe and useful way to administer S-1 oral therapy.