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A 74-year-old man presented to our hospital with the chief complaint of epigastric pain; upper gastrointestinal endoscopy revealed a 7-cm-sized type 3 gastric cancer in the lesser curvature of the lower part of the stomach. Abdominal contrast computed tomography revealed a tumor embolus in the right gastric vein; the preoperative diagnosis was cT4a(SE) N3aH0P0M0, cStage ⅢC. Because the cancer could spread during surgical manipulation, performing a safe radical resection was difficult; therefore, we decided to initiate chemotherapy. The patient received 3 courses of trastuzumab plus CapeOX, which led to reduction of the primarylesion, peri-gastric lymph node, and right gastric vein tumor embolus. Partial remission was achieved after chemotherapy; therefore, distal gastrectomy, D2 lymph node dissection, and Roux-en-Y reconstruction were performed. Histopathological examination did not reveal viable tumor cells in the primarylesion, lymph nodes, or tumor embolus, and the histological effect was Grade 3. Currently, the patient is alive without relapse at 9 months post operation. Advanced gastric cancer accompanied with tumor embolism in the gastric vein is commonly observed in patients with liver metastasis and in those with severely progressed state of cancer; many of these patients have poor prognosis. Preoperative chemotherapymaybe effective in cases in which tumor embolism in the gastric vein is identified through preoperative diagnostic imaging.

Prognostic prediction has been reported to affect the decision of doctors and non-physician health care providers such as nurses, social workers, pastors, and hospice volunteers on the selection of appropriate medical interventions. This was a case of a 65-year-old woman who presented with a poor oral intake. The patient had a history of sigmoid colon cancer with abdominal wall metastasis and peritoneal dissemination. On the day of admission, nausea, anorexia, and malaise were noted, requiring immediate intervention. The patient’s prognosis was predicted using the Palliative Prognostic Index. The pharmacist suggested the use of dexamethasone tablets in order to alleviate the patient’s symptoms. Indeed, the administration of dexamethasone alleviated the symptoms of nausea, loss of appetite, and malaise. To the best of our knowledge, this is the first case report to demonstrate that prognosis prediction is important not only for other medical staff but also for pharmacists when deciding the need to initiate a treatment and continue such treatment, and when providing pharmacist interventions.

For the estimation of short-term prognosis in terminal cancer patients, it is important to establish a prognostic index that does not involve blood tests. We compared the prognostic ability of the Barthel Index (BI) with the Glasgow Prognostic Score (GPS). Ninety-seven inpatients with terminal cancer at Onomichi Municipal Hospital who died between 2018 and 2019 were retrospectively analyzed. The sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUROC) were compared between the BI and GPS. For predicting the 15 day prognosis, the BI showed higher specificity, accuracy, and AUROC than the GPS. For predicting the 30 day prognosis, the BI showed higher sensitivity, accuracy, and AUROC than the GPS. The BI can predict the 15 or 30 day prognosis in terminal cancer patients. As the BI does not require blood tests, it may be an option for prognostic prediction in terminal cancer patients.

A 72-year-old woman with a history of surgery for left breast cancer was found to have sigmoid colon cancer and solitary pulmonary tumor of left upper lobe. We diagnosed adenocarcinoma of the unknown origin by a transbronchial biopsy. We performed left upper segmentectomy and sigmoidectomy. Left pulmonary tumor was diagnosed metastatic lung tumor from breast cancer. A right pulmonary tumor was confirmed by chest computed tomography(CT) after sigmoidectomy. It was also considered to be metastasis from breast cancer and treated with vinorelbine ditartrate. Since no effect was observed by chemotherapy, tumor was surgically removed by wedge resection. Right pulmonary tumor was pathologically diagnosed as metastasis from sigmoid colon cancer. In suspicious case of pulmonary metastases from double cancer, the possibility of different lesions from different primary site should be kept in mind.

Multidisciplinary therapy is necessary to prevent recurrence of advanced rectal cancer and advanced cancer with metastases. Here we report a case of long-term survival of a patient with advanced rectal cancer with multiple liver metastases. An 80's woman had previously undergone both Hartmann's operation and a partial hepatectomy for advanced rectal cancer with multiple liver metastases. A year after chemotherapy, a CT scan revealed multiple liver metastases. Thus, we performed partial liver resection. After another round of chemotherapy, a CT scan revealed lung metastases and local recurrence of the rectal cancer; therefore, we performed partial lung resection and a Miles operation. These procedures were conducted 4 years after her first operation. The following year, PET-CT revealed a mediastinum lymph node metastasis; consequently, we performed radiation therapy. New lung metastases and local recurrences of rectal cancer were identified after the radiation therapy; thus, we resumed the therapy, including a molecular targeting drug. Although the patient is in a tumor-bearing state, she is still alive 10 years after her first operation.

Fetal lung interstitial tumor (FLIT) is a recently reported type of congenital lung lesion comprising solid and cystic components. The pathological features include unique interstitial mesenchyme-based cell proliferation, and differ from other neoplasms represented by pleuropulmonary blastoma or congenital peribronchial myofibroblastic tumor. FLIT is extremely rare and its gene expression profile has not yet been reported. We provide the first report of a novel chromosomal rearrangement resulting in α-2-macroglobulin (A2M) and anaplastic lymphoma kinase (ALK) gene fusion in a patient with FLIT. The tumor cells contained a t(2;12)(p23;p13) and were mesenchymal in origin (e.g., inflammatory myofibroblastic tumors), suggesting the involvement of ALK in this case of FLIT. Break apart fluorescence in situ hybridization demonstrated chromosomal rearrangement at ALK 2p23. Using 5'-rapid amplification of cDNA ends, we further identified a novel transcript fusing exon 22 of A2M to exon 19 of ALK, which was confirmed by reverse-transcription polymerase chain reaction. The corresponding chimeric gene was subsequently confirmed by sequencing, including the genomic break point between intron 22 and 18 of A2M and ALK, respectively. Discovery of A2M as a novel ALK fusion partner, together with the involvement of ALK, provides new insights into the pathogenesis of FLIT, and suggests the potential for new therapeutic strategies based on ALK inhibitors.

IL-21 regulates certain functions of T cells, B cells, NK cells and dendritic cells. Although activated CD4(+) T cells produce IL-21, data identifying the specific CD4(+) T cell subsets that produce IL-21 are conflicting. In a previous study, mouse IL-21 message was detected in T(H)2, whereas human IL-21 (hIL-21) message was found in both T(H)1 and follicular helper T cells. To identify the IL-21-secreting cell populations in human, we established a hybridoma cell line producing an anti-hIL-21 mAb. Intracellular hIL-21-staining experiments showed that hIL-21 was mainly expressed in activated CD4(+) central memory T cells and in activated CD4(+) effector memory T cells, but not in activated CD4(+) naive T cells. Moreover, IL-21 was produced upon activation by some IFN-gamma-producing T(H)1-polarized cells and some IL-17-producing T(H)17-polarized cells, but not by IL-4-producing T(H)2-polarized cells. These results suggest that specific CD4(+) T cell populations produce IL-21. In the functional analysis, we found that IL-21 significantly enhanced the cytokine-driven proliferation of CD4(+) helper T cells synergistically with IL-7 and IL-15 without T cell activation stimuli. Taken together, IL-21 produced from CD4(+) memory T cells may have a supportive role in the maintenance of CD4(+) T cell subsets.

Interleukin-21 (IL-21) has pleiotropic functions on the cells, which play roles in both innate and acquired immunity, such as T cells, B cells, natural killer (NK) cells and dendritic cells. In this study we identified a novel isoform of IL-21, IL-21iso in human and mouse. IL-21iso might be an alternative splicing variant form and the C-terminal region of predicted IL-21iso amino acid sequences were different from original IL-21 in both human and mouse. In spite of the differences in C-terminal amino acid sequences, both human IL-21 and IL-21iso showed comparable proliferative effect on anti-CD40 Ab-activated primary B cells, anti-CD3 Ab-activated primary T cells and human NK cell line, NK0, and upregulated IFN-γ production from NK0. Furthermore IL-21 and IL-21iso similarly activated STAT1 and STAT3. IL-21iso mRNA was expressed in activated T cells as well as IL-21 mRNA. However, cycloheximide treatment partially blocked the upregulation of IL-21iso mRNA in activated T cells while little affected the IL-21 mRNA expression suggesting that de novo protein synthesis is required for the full expression of IL-21iso transcript. We also show that the secretion efficiency of hIL-21iso is much lower than that of hIL-21. These results may suggest there are some different regulatory mechanisms to produce IL-21 or IL-21iso in transcriptional and secretory steps.

Reactive oxygen species are involved in the aging process and diseases. Despite the important role of Cu/Zn SOD (superoxide dismutase) encoded by SOD1, SOD1−/− mice appear to grow normally under conventional breeding conditions. In the present paper we report on a novel finding showing a distinct connection between oxidative stress in erythrocytes and the production of autoantibodies against erythrocytes in SOD1−/− mice. Evidence is presented to show that SOD1 is primarily required for maintaining erythrocyte lifespan by suppressing oxidative stress. A SOD1 deficiency led to an increased erythrocyte vulnerability by the oxidative modification of proteins and lipids, resulting in anaemia and compensatory activation of erythropoiesis. The continuous destruction of oxidized erythrocytes appears to induce the formation of autoantibodies against certain erythrocyte components, e.g. carbonic anhydrase II, and the immune complex is deposited in the glomeruli. The administration of an antioxidant, N-acetylcysteine, suppressed erythrocyte oxidation, ameliorated the anaemia, and inhibited the production of autoantibodies. These data imply that a high level of oxidative stress in erythrocytes increases the production of autoantibodies, possibly leading to an autoimmune response, and that the intake of antioxidants would prevent certain autoimmune responses by maintaining an appropriate redox balance in erythrocytes.

乳糜腹水は術後に比較的まれに認められる合併症とされているが, 蛋白・リンパ球漏出に伴う栄養・免疫面での問題を生じうる. 2001年4月から2004年3月までに当科において施行された肝膵切除術後に乳糜腹水を認めた症例を対象とし, その臨床的特徴および治療法について検討を行った. 乳糜腹水の合併は204例中7例 (3.4%) に認められ, 決してまれな合併症ではないと考えられた. また, 乳糜腹水量1日最多量と血中最低アルブミン値を2変数とした回帰分析では有意が認められ, 乳糜腹水量の減少が栄養状態の改善に必要であることが示唆された.治療法としては, オクトレオチドの投与が有効で, 投与を試みた6例全例において3日以内に著明な乳糜腹水量の減少を認めた. 栄養状態の改善のためにも, 早期からの積極的なオクトレオチドの投与が必要と考えられた.

1987～2002年の間に施行された乳房温存手術584例を対象に再発形式を検討した.対象例の切除断端陽性例は74例(12.7%)であり,乳房照射は370例(63.4%)に行われた.平均観察期間は58.5カ月であり,再発は52例(8.9%)に認められ,その内訳は乳房19例(36.5%),乳房・その他3例(5.8%),局所8例(15.4%),遠隔転移22例(42.3%)であった.乳房の無再発生存率は, 5年95.7%, 10年94.0%であった.再発後の5年生存率は,乳房94.7%,局所70.0%,遠隔転移52.2%であり,乳房・その他は100%であった.乳房再発の19例の約2/3に再度乳房温存手術が施行された.予後が良好な原因としてその約半数がDCISもしくはそれに準じたものであったためと考えられることより,乳房温存手術後には可能な限り乳房再発の早期発見に努める必要がある.

1994年から1999年までに術前評価にて根治度AあるいはBの手術が可能と判断された壁深達度MP'以深の下部直腸癌症例を対象に左右側D3郭清を伴う手術を施行した結果Stage I以上の下部直腸癌115例中18例(15.6%)に側方リンパ節転移を認めた. 18例の組織学的壁深達度は全例mp以深で,側方2群までの転移が3例, 3群までの転移が15例であった. 18例のうち中枢方向にリンパ節転移を認めなかった6例は中枢方向に転移を認めた5例および組織学的病期Stage IVの7例に比較しリンパ節転移個数が少なく,静脈侵襲も軽度で, 3年生存率は50%と比較的良好であったが,他の12例には3年生存例は認めなかった.下部直腸癌側方リンパ節転移陽性例の予後は総じて不良なものが多いが,外科的手術によりある程度制御可能な症例も存在し,他の代替療法がない以上側方郭清の意義はあるものと考えられた.

Fetal lung interstitial tumor (FLIT) is a recently reported type of congenital lung lesion comprising solid and cystic components. The pathological features include unique interstitial mesenchyme-based cell proliferation, and differ from other neoplasms represented by pleuropulmonary blastoma or congenital peribronchial myofibroblastic tumor. FLIT is extremely rare and its gene expression profile has not yet been reported. We provide the first report of a novel chromosomal rearrangement resulting in α-2-macroglobulin (A2M) and anaplastic lymphoma kinase (ALK) gene fusion in a patient with FLIT. The tumor cells contained a t(2;12)(p23;p13) and were mesenchymal in origin (e.g., inflammatory myofibroblastic tumors), suggesting the involvement of ALK in this case of FLIT. Break apart fluorescence in situ hybridization demonstrated chromosomal rearrangement at ALK 2p23. Using 5'-rapid amplification of cDNA ends, we further identified a novel transcript fusing exon 22 of A2M to exon 19 of ALK, which was confirmed by reverse-transcription polymerase chain reaction. The corresponding chimeric gene was subsequently confirmed by sequencing, including the genomic break point between intron 22 and 18 of A2M and ALK, respectively. Discovery of A2M as a novel ALK fusion partner, together with the involvement of ALK, provides new insights into the pathogenesis of FLIT, and suggests the potential for new therapeutic strategies based on ALK inhibitors.

Day surgery was performed under local anesthesia on 88 cases of relatively early breast cancer. Evaluation was therefore made on the safety, operative results, economy, and level of patient's satisfaction of day surgery to elucidate the present status and problematic points of day surgery for breast cancer. Postoperative complications were observed in 5 patients (5.7%) and one patient underwent a repeated surgery due to postoperative bleeding. On the premise that the unit has prompt ability to cope with emergency, day surgery can be performed. The postoperative results were satisfactory when indications for day surgery were strictly observed. In terms of economic aspect, the economic effect was found to be great, because by decreasing the average period of hospitalization, the medical expenses borne by the individual patient could be saved to be about 1/7 of those involved in hospitalization. However, though the level of patient's satisfaction was high, few patients highly evaluated that reduction of their medical expenses. Despite the decrease in revenue of the hospital, the burden on physicians has on the contrary increased. For the promotion of day surgery, every effort should be made to lesser these unbalances and discrepancies.

Complications and/or sequelae following breast cancer surgery such as arm edema on the affected side have serious deleterious effects on QOL. Methods of therapy were classified into lumpectomy with or without axillary dissection and breast irradiation, lumpectomy+axillary dissection+breast irradiation, and modified mastectomy. A questionnaire survey was conducted on level of functional disorder of the arm. Results indicated that the present standard breast conservation therapy in which axillary dissection is followed by breast irradiation unfavorably affects QOL with respect to movement, numbness, pain and edema of the affected arm. Efforts should therefore be made after selection of indications to avoid either axillary dissection or breast irradiation.

In total, 573 lesions were resected from 518 patients with primary gastric mucosal cancer in Hiroshima City Hospital over the last 20 years, and the patients with ly(+) or v(+) lesions were analyzed from the clinicopathological point of view. The results were as follows. 1) 17 patients (3.0%) had ly(+) lesions, 3 (0.6%) had v(+) lesions. 2) In all but one case the lesions were located in the M or A area. 3) In all cases except two the lesions were depressed or mixed type. 4) Although one lesion was pap, the others were sig or tub 1, 2. However, there were no significant differences between the differentiated and undifferentiated types. 5) The maximal tumor diameter ranged from 1.5cm in the n(+) cases, but in the ly(+) cases from 0.7cm less than those cases. 6) 12 patients had n(+). Although 7 of the latter had ly(+), there were 3 n(+) cases even among the ly(-) cases. Furthermore, the 10 cases had depressive compartment. 7) Two patients died of another disease and one died of bone metastasis. The other patients are all alive. These results indicate that gastrectomy with node dissection should be done for the depressed or mixed type of lesion which has the possibility of being not only n(+) but also ly(+), v(+) even in the case of mucosal cancer.

癌に対する根治性を保持しつつ術後消化吸収機能の向上をめざして, MおよびA領域の早期胃癌に対してD2郭清を伴う自律神経温存幽門保存胃切除術を施行した. 1993年12月から1995年12月までの2年間に41例に本術式を行った. 縫合不全, ダンピング症候群や逆流性食道炎などの合併症は1例も認めなかった. 術後6か月目のX線造影検査や内視鏡検査で幽門機能や蠕動運動が良好に保たれている様子が観察された. また内視鏡検査にて半数以上の症例に食物残渣の貯留所見を認めたが残胃粘膜には軽度の胃炎所見以外の器質的変化を認めなかった. 残胃のうっ滞症状を12例 (29.3%) の例に認めたが多くは一過性であった. 術後胆石症の発症は1例も認めなかった. 本術式群では幽門側胃切除術群と比較して術後3か月目以降の体重回復傾向が有意に良好であった. 本術式は根治性と術後QOLの改善をともにめざせる合理的な機能温存手術と考えられた.

Ataxia telangiectasia (AT) is a rare autosomal recessive multisystem disorder characterised by cerebellar degeneration, immunodeficiency and cancer predisposition. Around 10% of AT patients develop lymphoid malignancies, but the development of myeloid leukaemia with AT (AT-AML) is extremely rare, and there have been no previous publications regarding suitable therapies. Here, we first describe a successful therapeutic experience in a patient with AT-AML (FAB-M1) who attained remission after induction therapy and maintained stable disease for a year. To minimise therapy-induced toxicity, low-dose induction was applied first, though this was obviously insufficient and the patient subsequently responded well to dose-intensified short-term chemotherapy. In this report, we suggest a curative therapeutic approach for AT-AML, though the issue of how best to manage patients with cancer complicated by immunodeficiency remains undecided.

Chest wall resection with reconstruction is regarded to be the most effective therapeutic method for solitary chest wall necurrence of breast cancer and radiotherapy is rarely employed as therapy of first choice. For the purpose of observing the effectiveness of radiotherapy, six patients though with operative indication were followed with only radiotherapy and their prognoses were compared with those of 10 patients who underwent only chest wall resection during the same period. Accroding to the results of this comparson, among the patients with chest wall recurrence of breast cancer, those without distant metastasis, with disease-free interval of more than 3 years and with the infiltration not reaching into the pleura showed a 5-ear survival rate of 80%, indicating that chest wall resection is therapy of first choice. However, effective cases were also observed among those undergoing radiotherapy. Furthermore, for patients who did not satisfy the foregoing three conditions, no difference in effective rate was observed between the therapeutic methods. It is suggested that the indications of radiotherapy for chest wall recurrence of breast cancer can be further expanded.

An 88-year-old woman was referred to the hospital because of an abdominal pain. By simple X-ray examination of the chest and abdomen in addition to CT, perforation of the transverse colon associating with Morgagni hernia was suggested. Laparotomy was immediately performed. After the resection of the transverse colon, the hilus of the hernia was closed by knotted sutures. A 3×3 cm ulcer was found in the resected colon and the perforation was formed in the center of it, through which about 100 ml of content of the transverse colon flew out to the hernial sac causing local peritonitis. Histopathologically, strangulated change was also confirmed.

A case of lymphoepithelial cyst of the pancreas is reported. A 64-year-old man complaining of fatique was admitted to the hospital because of an increase in serum amylase value, which was pointed out at a medical checkup. He was found to have a cystic tumor in the upper border of the pancreatic body, as revealed by abdominal computed tomography. This unilocular cyst, measuring 2.0cm and containing keratin material, was dissected easily from the pancreas. Histologically, the cyst wall was lined by mature squamous epithelium with sebaceus glands and surrounded by lymphoid tissue. It was diagnosed as a lymphoepithelial cyst of the pancreas. Lymphoepith-elial cysts are occasionally observed in the lateral cervical lesion or palotid gland, and are called branchial cyst. However, lymphoepithelial cyst of the pancreas is a rare lesion, with 28 cases having been reported since it was first recognized in 1985.

A 6-year-old boy was diagnosed with FLT3-ITD+acute monoblastic leukemia (AMoL). He showed resistance to 2 cycles of induction chemotherapy with etoposide, cytarabine, and mitoxantrone or idarubicin performed according to the Japan Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 protocol. His condition was also refractory to salvage FLAI-GO (fludarabine, cytarabine, idarubicin, and gemtuzumab ozogamicin) chemotherapy. Sequential administration of sorafenib at doses of up to 300 mg/day resulted in the first remission. He underwent bone marrow transplantation from his HLA 2-locus mismatched father. Recurrence was observed on post-transplantation day 71. A sustained partial response was observed after alternate-day readministration of sorafenib 150mg/day. In spite of a donor lymphocyte infusion, his blast cell count increased on day 245. Chemotherapy with an increased dose of sorafenib reduced the blast cell count. Although a second HLA-mismatched allogeneic peripheral blood stem cell transfusion was performed, the patient died of regimen-related toxicity. Herein, we report a pediatric case of primary refractory FLT3-ITD+ AMoL. Further prospective studies are necessary to validate the efficacy of sorafenib treatment.

Interleukin-21 (IL-21) is overproduced in human intestines affected by inflammatory bowel disease (IBD) and in the gut of mice with DSS-induced colitis. IL-21-deficient mice are largely protected against DSS-induced colitis, indicating that IL-21 plays a key role in the development of IBD. We previously identified a novel IL-21 isoform named IL-21iso. In this study, we found that in addition to the conventional IL-21, IL-21iso mRNA was also expressed in the colon with DSS-induced colitis. To investigate whether IL-21iso plays a role in DSS-induced colitis, we established transgenic mice (mIL-21iso-Tg mice) that expressed mouse IL-21iso under the control of the lck proximal promoter. Although mIL-21iso-Tg mice did not have any gross physical abnormalities, their peripheral lymphocytes counts were higher than those in wild-type littermates. Notably, their CD8 + T cell and CD4 + effector memory T-cell populations were elevated. DSS-induced colitis was far more severe in the mIL-21iso-Tg mice than in wild-type mice, and was accompanied by a marked loss of body weight and by colon inflammation with increased cellular infiltration. In DSS-treated mice, colon tissues from mIL-21iso-Tg mice had significantly higher gene activation levels for cytokines such as IL-17A, TNF-α, IL-6, IL-10, and IL-4, and for transcription factors such as T-bet, GATA-3, RORγt, and Foxp3, than were found in wild-type mice. These results indicate that besides IL-21, IL-21iso may be another regulator of gut inflammation.

IL-21 is a pleiotropic cytokine that regulates T-cell and B-cell differentiation, NK-cell activation, and dendritic cell functions. IL-21 activates the JAK-STAT, ERK, and PI3K pathways. We report here that Ape1/Ref-1 has an essential role in IL-21-induced cell growth signal transduction. Overexpression of Ape1/Ref-1 enhances IL-21-induced cell proliferation, but it is suppressed by overexpressing an N-terminal deletion mutant of Ape1/Ref-1 that lacks the redox domain. Furthermore, knockdown of the Ape1/Ref-1 mRNA dramatically compromises IL-21-induced ERK1/2 activation and cell proliferation with increasing cell death. These impaired activities are recovered by the re-expression of Ape1/Ref-1 in the knockdown cells. Our findings are the first demonstration that Ape1/Ref-1 is an indispensable molecule for the IL-21-mediated signal transduction through ERK1/2 activation.

We experienced a case of von Recklinghausen disease (R-disease) associating with a rectal cancer. A 55-year-old man was pointed out having a rectal tumor at complete physical examination. There was no family history of R-disease, but he had a several-year history of multiple small soft tumors in the trunk. With various examinations the patient was diagnosed as having a rectal cancer of Rb. Excision of the rectum and biopsy of the cutaneous tumors were carried out. Histologically the rectal tumor was well differentiated adenocarcinoma and cutaneous tumors were neurofibroma. R-disease is an autosomal dominant inheritant disease which is characterized by cafe-au-lait-spots and multiple neurofibromas in the skin and peripheral nerves. It is often associated with nonepithelial tumors. Sometimes the association of nonepithelial tumors of nerve origin in the gastrointestinal organs has been reported, but that of gastrointestinal epithelial tumor has been rarely seen in the Japanese literature. This is the 7th case which was associated with rectal cancer. However, there has been no opinion declaring the existence of some causative relation between R-disease and gastrointestinal cancer, in that further studies are demanded.

Interleukin-21 (IL-21) is a pleiotropic cytokine that regulates T-cell, B-cell, NK-cell, and myeloid-cell functions. IL-21 binds with its cognate receptor complex, which consists of the IL-21 receptor (IL-21R) and the common gamma chain. We identified a novel IL-21R-binding molecule, WSB-1, which contains WD-40 repeats and a SOCS-box domain. WSB-1 associates with the middle part of intracytoplasmic region of IL-21R and enhances the maturation of IL-21R from N-linked glycosylated form to fully glycosylated mature form. Furthermore, WSB-1 moderates IL-21R degradation. Taken together, our present study suggests that WSB-1 has a role in the tuning of the maturation and degradation of IL-21R.

Interleukin-21 (IL-21) is a pleiotropic cytokine that regulates T-cell, B-cell, NK-cell, and myeloid-cell functions. IL-21 binds with its cognate receptor complex, which consists of the IL-21 receptor (IL-21R) and the common gamma chain (γc) receptor subunit. We identified novel IL-21R-binding molecule, WD-40 repeats containing SOCS-box-2, WSB-2. WSB-2 associated with the membrane-proximal intracytoplasmic region of IL-21R, including box1 and box2. Overexpression study of WSB-2 showed the reduction of IL-21R expression and IL-21-induced signal transduction. On the other hand, small interfering RNA for WSB-2 enhanced the expression level of IL-21R and IL-21-induced STAT3 activation, indicating that WSB-2 negatively controls the receptor expression. This report provides the first evidence that WSB-2 is a regulator of IL-21R expression and IL-21-induced signal transduction.

A 54-year-old male visited our hospital with the chief complaint of anorexia. Based on various tests, a diagnosis of scirrhous gastric carcinoma accompanied by bone metastasis and liver metastasis was made. As DIC developed following hospital admission, 5-FU and PTX therapy (5-FU at 600 mg/m(2), 24-hour continuous infusion, day 1-5 and PTX at 80 mg/m(2), iv, day 8, 15, 22) were administered. Although primary foci, bone metastasis, and liver metastasis were observed by image diagnostic procedures, recovery from DIC was achieved. 5-FU+PTX therapy is considered to be effective for DIC due to bone metastasis of gastric carcinoma.

Eighteen subjects with cases of HCC who underwent endoscopic local coagulation therapy at Hiroshima City Hospital between 1998 and 2004 were studied and compared with 6 cases of HCC patients who underwent laparoscopic partial hepatectomy during the same period. The subjects composed of 10 cases of laparoscopic microwave coagulation therapy (L-MCT), 5 cases of laparoscopic radio frequency ablation therapy (L-RFA), and 3 cases of thoracoscopic microwave coagulation therapy (T-MCT). The operation time was 114 minutes for L-MCT and 92 minutes for L-RFA, both of which were significantly shorter than 208 minutes for resection cases. No complications were developed in any of the cases and the postoperative hospitalization period of the cases was 13.1 days, 8.2 days, and 13.0 days, respectively. Although each case of local recurrence was observed both in L-MCT and L-RFA groups, one case displayed observation difficulty from the liver surface and the other required a daughter nodule. The three-year survival rate was 71.4%, while the five-year survival rate was 53.6%. Endoscopic local coagulation therapy is not too invasive and useful for hepatocellular carcinoma in which percutaneous RFA is difficult. However, it is well indicated when the scope is evident with observation being feasible from the liver surface.

We evaluated the significance of multimodality therapy for cases of liver metastases of gastric cancer. Accumulated survival rate and median survival time were analyzed for twenty cases of such gastric cancer. Survival rates of H1+H2 group and hepatic resection (HR) group were higher than that of H3 group and non-HR group. MST of HR group and hepatic arterial infusion (HAI) group were longer than that of non-HR group and non-HAI group. Survival rate of HAI group was higher than that of non-HAI group among eleven cases of HR group. On the other hand, survival rate of HR group was higher than that of non-HR group among eleven cases of HAI group. These results suggested that HAI chemotherapy after hepatic resection for gastric cancer patients with synchronous liver metastasis would improve prognosis.

We studied the significance of repeated intraperitoneal CDDP administration, as adjuvant chemotherapy, for the prevention of T3 and T4 gastric cancer. Fifty-two patients who had been operated as Curability B were divided into the following two groups, and the data on survival rate, median survival time and interval of "free of recurrence" were accumulated and analyzed. Group A consisted of nineteen patients treated with intraperitoneal CDDP administration and oral anticancer drugs. Group B were treated with systemic chemotherapy. Group A was superior to Group B in comparing the analyzed data. These results suggested that repeated intraperitoneal CDDP chemotherapy for the prevention of T3 and T4 advanced gastric cancer would improve survival rate.

We examined the significance of low-dose cisplatinum (CDDP) intraperitoneal administration for cases of peritoneal dissemination of gastric cancer. Sixty-eight cases of gastric cancer, diagnosed as P1 or CY1 in the gastrectomy operation that was carried out during the period between January 1994 and December 2001, were studied based on accumulated survival rate and mean survival time (MST). Ten milligram of CDDP was weekly administrated intraperitoneally through an infusion port. A two-week interval was taken after the eight-week administration. This group, the CDDP intraperitoneal administration group, was statistically superior both in the accumulated survival rate and MST. These results suggested that the low-dose CDDP intraperitoneal administration would contribute to improved prognosis of such gastric cancers as P1 or CY1.

The patient was a seventy-seven-year old woman, who was diagnosed with advanced gastric cancer with stenosis of the esophagocardiac junction. Her cancer was diagnosed as Stage IV (T3N3H0P3M0). As there was no indication for surgery, radiation therapy (Linac electron beam, 1.8 Gy/day, total 50.4 Gy) was selected to improve the stenosis, after which she was able to eat food. Subjective complaints such as nausea and vomiting were also decreased, promoting her QOL. We conclude that radiation therapy treatment can be a treatment option for far advanced cardiac cancer.

We evaluated the antitumor effect of an interleukin 2 (IL-2) slow delivery system, the IL-2 mini-pellet, in two murine solid tumor models, and also investigated the enhancement of its therapeutic effect by serial administration. The IL-2 mini-pellet contains 1 x 10(6) units of IL-2 and releases it slowly in vivo. In our experiment, the IL-2 mini-pellet was administered subcutaneously near the tumor site in combination with the intravenous injection of lymphokine-activated killer (LAK) cells. When this regimen was given on days 8 and 11 after the subcutaneous inoculation of Meth A fibrosarcoma into BALB/c mice, tumor growth was significantly inhibited (p less than 0.05) compared to tumor growth in untreated controls. Moreover, the IL-2 mini-pellet alone was also effective in inhibiting tumor growth. In another experiment, MH134 hepatoma was inoculated into C3H/He mice. Both administration of the IL-2 mini-pellet alone and in combination with LAK cells resulted in complete tumor regression in four of five mice. In a third experiment, serial administration of the IL-2 mini-pellet at 3- or 5-day intervals prolonged the suppression of Meth A fibrosarcoma growth in BALB/c mice. These results suggested that the IL-2 mini-pellet could be applied to cancer immunotherapy and that its antitumor effect could be prolonged by serial administration.

1. Die Wasserstoffuberspannung an Elektroden aus Gold, Platin, Kupfer, Nickel und Quecksilber wurde aus der Stromspannungskurve ermittelt.

1. Es wurde die Uberspannung festgestellt, welche auftritt, wenn ein elektrischer Strom von 1-1,3 A. durch eine Goldelektrode von 0,6 cm Durchmesser und 1 cm Lange hindurchgeht.

Versuche mit Platin-, Gold-, Kupfer- und Nickelelektroden wurden unter verschiedenen Versuchsbedingungen ausgefuhrt, um zu zeigen, das die Wasserstoff-Uberspannung sich erheblich mit der Geschichte der Elektrodenoberflache verandert.

1. Unter Anwendung von Elektroden aus Platin, Gold, Kupfer oder Nickel, die man in verschiedener Weise behandelte, lies der Versuch erkennen, das die Sauerstoffuberspannung sich nur sehr wenig mit der Geschichte der Elektrodenoberflache andert und beinahe als konstant betrachtet werden kann.