Adipocytokines and squamous cell carcinoma of the esophagus

Purpose  

Adipocytokines are adipocyte-secreted hormones associated with some malignancies. It has been reported that the impaired response of adipocytokines to body weight loss may play a role in the pathogenesis of cancer-induced cachexia. We investigated the association between adipocytokines with squamous cell carcinoma of the esophagus (SCCE).     

Case report of rheumatoid arthritis associated with type A gastritis and Hashimoto thyroiditis

A 59-year-old woman was initially thought to have either type A gastritis, or autoimmune gastritis by upper-gastrointestinal-tract endoscopy and a serological examination. Furthermore, the patient was also suspected to have Hashimoto disease based on a positive antithyroid-antibody test. Rheumatoid arthritis was diagnosed 1 year later. Pernicious anemia, gastric-carcinoid and stomach cancer are the primary complications of A type gastritis. However, we hypothesized that the development of other autoimmune diseases, such as autoimmune thyroid disease, was the primary complication experienced in this case. Therefore, we report the findings of this case while taking into consideration the findings of several other previously published studies.     

Relationship between circulating levels of monocyte chemoattractant protein-1 and systolic dysfunction in patients with hypertrophic cardiomyopathy

BackgroundProgression of hypertrophic cardiomyopathy (HCM) to left ventricular dilatation and systolic dysfunction sometimes occurs. However, the mechanism of the transition from hypertrophy to dysfunction has not been elucidated. It has been reported that circulating levels of monocyte chemoattractant protein-1 (MCP-1), which is a major factor promoting the accumulation of macrophages, are increased in patients with congestive heart failure. We measured circulating levels of MCP-1 in patients with HCM and examined whether MCP-1 was expressed in the myocardium of HCM patients. We also examined whether circulating levels of MCP-1 were correlated with left ventricular dysfunction.MethodsCirculating levels of MCP-1 were measured by an enzyme immunoassay in 26 patients with HCM (60±2 years old) and 20 control subjects (57±2 years old). Cardiac function was evaluated by two-dimensional echocardiography and cardiac catheterization.ResultsHCM patients had significantly elevated levels of MCP-1 (HCM: 309±30 vs. control: 178±8 pg/ml, P<.001). MCP-1 levels in patients with systolic dysfunction were significantly higher than those in patients without systolic dysfunction (P<.05) and were also significantly higher than those in patients with outflow obstruction (P<.05). Immunohistochemical analysis revealed that MCP-1 was expressed in endomyocardial biopsy samples obtained from HCM patients with systolic dysfunction. Furthermore, MCP-1 levels were inversely correlated with fractional shortening (r=?.401, P<.05) and correlated with left ventricular end-diastolic pressure (r=?.579, P<.01).ConclusionThese results show that MCP-1 is associated with, and might be involved in the pathogenesis of, left ventricular systolic dysfunction in patients with HCM.     

Complications in the central nervous system during chemotherapy for childhood acute lymphoblastic leukemia: JACLS ALL-02 study

We evaluated central nervous system (CNS) complications treated under the ALL-02 protocol of the Japan Association of Childhood Leukemia Study (JACLS) from April 2002 to March 2005. According to NCI Toxicity Criteria, 17 events of grade 3 and 4 CNS complications were reported in 15 out of 541 patients. Out of these CNS complications, leukoencephalopathy was seen in 5 patients; seizure in 5; cerebrovascular disease in 3; conscious disturbance in 2; and hypertensive encephalopathy and reversible posterior leukoencephalopathy syndrome in one patient each. The complications were intensively observed during induction therapy and the last of the early phase chemotherapy. The protocol treatment was stopped or modified in most patients after CNS complications. MRI imaging demonstrated no improvement in one patient with leukoencephalopathy who developed an isolated CNS relapse, while other patients were alive and remain in their first complete remission without any neurological sequelae. Further studies will be required to analyze risk factors for CNS complications during chemotherapy not accompanied by irradiation and to establish alternative treatments after the appearance of such CNS complications.     

The benchmark analysis of gastric, colorectal and rectal cancer pathways: toward establishing standardized clinical pathway in the cancer care

Most clinical pathways in treating cancers in Japan are based on individual physician's personal experiences rather than on an empirical analysis of clinical data such as benchmark comparison with other hospitals. Therefore, these pathways are far from being standardized. By comparing detailed clinical data from five cancer centers, we have observed various differences among hospitals. By conducting benchmark analyses, providing detailed feedback to the participating hospitals and by repeating the benchmark a year later, we strive to develop more standardized clinical pathways for the treatment of cancers. The Cancer Quality Initiative was launched in 2007 by five cancer centers. Using diagnosis procedure combination data, the member hospitals benchmarked their pre-operative and post-operative length of stays, the duration of antibiotics administrations and the post-operative fasting duration for gastric, colon and rectal cancers. The benchmark was conducted by disclosing hospital identities and performed using 2007 and 2008 data. In the 2007 benchmark, substantial differences were shown among five hospitals in the treatment of gastric, colon and rectal cancers. After providing the 2007 results to the participating hospitals and organizing several brainstorming discussions, significant improvements were observed in the 2008 data study. The benchmark analysis of clinical data is extremely useful in promoting more standardized care and, thus in improving the quality of cancer treatment in Japan. By repeating the benchmark analyses, we can offer truly clinical evidence-based higher quality standardized cancer treatment to our patients.     

The G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) facilitates tumor development by serving as an extracellular pH sensor

Tumors often are associated with a low extracellular pH, which induces a variety of cellular events. However, the mechanisms by which tumor cells recognize and react to the acidic environment have not been fully elucidated. T-cell death-associated gene 8 (TDAG8) is an extracellular pH-sensing G protein-coupled receptor that is overexpressed in various tumors and tumor cell lines. In this report, we show that TDAG8 on the surface of tumor cells facilitates tumor development by sensing the acidic environment. Overexpression of TDAG8 in mouse Lewis lung carcinoma (LLC) cells enhanced tumor development in animal models and rendered LLC cells resistant to acidic culture conditions by increasing activation of protein kinase A and extracellular signal-regulated kinase in vitro. Moreover, shRNA-mediated knockdown of endogenous TDAG8 in NCI-H460 human non-small cell lung cancer cells reduced cell survival in an acidic environment in vitro as well as tumor development in vivo. Microarray analyses of tumor-containing lung tissues of mice injected with TDAG8-expressing LLC cells revealed up-regulation of genes related to cell growth and glycolysis. These results support the hypothesis that TDAG8 enhances tumor development by promoting adaptation to the acidic environment to enhance cell survival/proliferation. TDAG8 may represent a therapeutic target for arresting tumor growth.     

Effectiveness of lidocaine infusion for status epilepticus in childhood: a retrospective multi-institutional study in Japan

We evaluated the usefulness of intravenous lidocaine therapy for managing of status epilepticus (SE) during childhood in a retrospective multi-institutional study. Questionnaires were sent to 28 hospitals concerning patients admitted for SE who were managed with lidocaine, assessing patient characteristics, treatment protocols and efficacy. In 279 treated patients, 261 SE occurrences at ages between 1 month and 15 years were analyzed. SE was classified as showing continuous, clustered, or frequently repeated seizures. Considering efficacy and side effects in combination, the usefulness of lidocaine was classified into six categories: extremely useful, useful, slightly useful, not useful, associated with deterioration, or unevaluated. In 148 SE cases (56.7%), lidocaine was rated as useful or extremely useful. Multivariate analysis indicated lidocaine was to be useful in SE with clustered and frequently repeated seizures, and SE attributable to certain acute illnesses, such as convulsions with mild gastroenteritis. Efficacy was poor when SE caused by central nervous system (CNS) infectious disease. Standard doses (approximately 2mg/kg as a bolus, 2mg/kg/h as maintenance) produced better outcomes than lower or higher doses. Poor responders to the initial bolus injection of lidocaine were less likely to respond to subsequent continuous infusion than good initial responders. We recommend lidocaine for use in SE with clustered or frequently repeated seizures, and in SE associated with benign infantile convulsion and convulsions with mild gastroenteritis. Lidocaine should be initiated with a bolus of 2mg/kg. If SE is arrested by the bolus, continuous maintenance infusion should follow; treatment should proceed to different measures when SE shows a poor response to the initial bolus of lidocaine.     

Genetic abnormalities involved in t(12;21) TEL-AML1 acute lymphoblastic leukemia: analysis by means of array-based comparative genomic hybridization

The TEL (ETV6)-AML1 (RUNX1) chimeric gene fusion is the most common genetic abnormality in childhood acute lymphoblastic leukemias. Evidence suggests that this chimeric gene fusion constitutes an initiating mutation that is necessary but insufficient for the development of leukemia. In a search for additional genetic events that could be linked to the development of leukemia, we applied a genome-wide array-comparative genomic hybridization technique to 24 TEL-AML1 leukemia samples and two cell lines. It was found that at least two chromosomal imbalances were involved in all samples. Recurrent regions of chromosomal imbalance (>10% of cases) and representative involved genes were gain of chromosomes 10 (17%) and 21q (25%; RUNX1) and loss of 12p13.2 (87%; TEL), 9p21.3 (29%; p16INK4a/ARF), 9p13.2 (25%; PAX5), 12q21.3 (25%; BTG1), 3p21 (21%; LIMD1), 6q21 (17%; AIM1 and BLIMP1), 4q31.23 (17%; NR3C2), 11q22-q23 (13%; ATM) and 19q13.11-q13.12 (13%; PDCD5). Enforced expression of TEL and to a lesser extent BTG1, both single genes known to be located in their respective minimum common region of loss, inhibited proliferation of the TEL-AML1 cell line Reh. Together, these findings suggest that some of the genes identified as lost by array-comparative genomic hybridization may partly account for the development of leukemia.