Sarcoidosis-associated hepatocellular carcinoma

Sarcoidosis is a systemic granulomatous inflammation of unknown etiology, and seems to involve the liver parenchyma in most cases. However, sarcoidosis-associated hepatocellular carcinoma is rare. We report here a case in which a hepatocellular carcinoma occurred within the liver, which was probably involved as a result of systemic sarcoidosis. A 57-year-old Japanese man had been followed up for 2 years because of diabetic nephropathy and sarcoidosis. On admission for pneumonia, imaging studies revealed an unexpected hepatic tumor. Histology revealed a hepatocellular carcinoma accompanied by T-lymphocytic infiltration and marked granulomatous inflammation, which was surrounding some tumor nodules. The background liver parenchyma exhibited a moderate degree of fibrosis with granulomatous inflammation. The patient had no other apparent liver disease such as viral hepatitis, steatohepatitis, or primary biliary cirrhosis. Therefore, in the present case, sarcoidosis may be considered the probable background etiology for hepatocarcinogenesis.     

OSU-03012, a novel celecoxib derivative, induces cell swelling and shortens action potential duration in mouse ventricular cells

OSU03012, a novel celecoxib derivative, has been shown to inhibit proliferation and induce apoptosis in numerous cancer cell lines. However, not much is known about its influence on cell volume regulation and cardiac function in the mammalian heart. We examined the effects of OSU-03012 on cell volume and action potentials in mouse ventricular cells. Video image analysis showed that cell volume increased on application of OSU-03012 in a dose-dependent manner. The action potential duration (APD) at 50% and 90% repolarization (APD(50) and APD(90) respectively) as well as the resting membrane potential (RMP) were measured in current-clamp experiments. OSU-03012 had little effect on APD(50) and RMP but induced approximately 30% shortening of APD(90). These results for cell volume and AP are similar to those in cells under ischaemia/hypoxia, and we confirmed that the shortening of APD(90) was almost completely recovered by glibenclamide, a potent inhibitor of ATP-sensitive potassium channels.We concluded that OSU-03012 may lead to cell swelling and shortening of AP via reduced ATP production in mouse ventricular cells.     

Androgens in human breast carcinoma

Sex steroids play important roles in the development of human breast carcinoma. Androgen receptor (AR) is expressed in a majority of breast carcinoma tissues. However, the significance of androgen actions remains largely unclear in breast carcinoma, differing from estrogen actions. Therefore, in this review, we summarized recent studies on androgens in breast carcinoma. Concentration of a potent androgen, 5α-dihydrotestosterone (DHT), was significantly higher in breast carcinoma tissue than in plasma, and DHT is considered to be locally produced from circulating androstenedione by 17β-hydroxysteroid dehydrogenase type 5 and 5α-reductase. On the other hand, aromatase was recently reported as a negative regulator for intratumoral DHT production by possibly reducing the precursor testosterone. Androgens predominantly show antiproliferative effects in breast carcinoma cells, but association between AR status and the clinical outcome of the patient remains controversial, perhaps partly because AR status does not necessarily reflect androgenic action in breast carcinoma. Recently, molecular apocrine breast carcinoma was identified by microarray analysis. Molecular apocrine carcinoma was characterized by being estrogen receptor (ER) negative and AR positive and by being associated with increased androgen signaling and apocrine features. Therefore, androgenic actions may also be involved in apocrine features in breast carcinoma.     

Prompt diagnosis of ectopic pregnancy with the human chorionic gonadotropin test using exuded extract from endometrial curettings

Using saline solution including exuded extract from uterine curettings, hCG tests were performed in 63 women in whom there was a suspicion of ectopic pregnancy, and their results correlated highly with the microscopic existence of chorionic villi and trophoblasts. Ectopic pregnancy can be mostly excluded when the test is positive, and either ectopic pregnancy or complete abortion is probable when it is negative.     

Detection of EML4-ALK fusion genes in a few cancer cells from transbronchial cytological specimens utilizing immediate cytology during bronchoscopy

The presence of fusion genes between the anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4) genes is useful for determining appropriate molecular-targeted therapies in patients with non-small cell lung cancer (NSCLC). The diagnosis of NSCLC is often judged from transbronchial cytological specimens. The efficacy of RT-PCR for detection of EML4-ALK fusion genes in transbronchial cytological specimens has not been studied. Here, we evaluated the detection rate of EML4-ALK fusion genes in transbronchial cytological specimens positive for NSCLC by immediate cytology during bronchoscopic examination. Various numbers of H2228 cells carrying EML4-ALK variant 3 were combined with 1×10(6) wild-type WBCs. The RNA was extracted and the sensitivity of detection of the EML4-ALK fusion gene was determined using a nested RT-PCR. A total of 161 cell samples, from cases without available tissue samples, obtained by bronchoscopic examinations utilized for immediate cytology in patients with NSCLC were subsequently analyzed for EML4-ALK fusion genes using a nested multiplex RT-PCR. EML4-ALK variant 3 was detected in a small number of H2228 cells (10 cells), even in the presence of 1×10(6) WBCs (sensitivity: 0.001%). In the patient cytological samples, EML4-ALK fusion genes were detected in five of 161 NSCLCs (3.1%) and four of 88 adenocarcinomas (4.5%). Sequencing confirmed that these samples included three variant 1 genes, one variant 2 gene and one variant 3 gene. Using the same cytological samples, EGFR mutations were detected in 39 of 161 NSCLCs (24.2%) and 36 of 88 adenocarcinomas (40.9%). There was no case in which both EML4-ALK fusion and EGFR mutation were simultaneously detected. Rapid diagnosis during bronchoscopy utilizing immediate cytology contributed to the selection of the best samples for genetic analysis. EML4-ALK fusion genes as well as EGFR mutations were successfully detected in a small number of cancer cells from transbronchial cytological specimens using a nested multiplex RT-PCR. Our present strategy can be integrated into the clinical process without additional invasive examination of patients. In the era of molecular-targeted treatments for NSCLC, the combination of rapid diagnosis during bronchoscopic examination and stocking samples as cDNA could further correspond to genetic analyses of accumulating driver genes in NSCLC.     

Docetaxel plus S-1 as a second-line chemotherapy for metastasis or recurrence of esophageal cancer

Although chemotherapy consisting of cisplatin and 5-fluorouracil(CF)has been a standard regimen for esophageal cancer, it might be difficult to use continuously. This study evaluated the response and safety of docetaxel plus S-1 used as a second line therapy. We reviewed 21 patients(postoperatively, 11; after definitive chemoradiotherapy, 8; after chemotherapy, 2) who received chemotherapy between 2006 and 2010. Metastatic or recurrent disease was detected in the organs(n=8), lymph nodes(n=8), main tumors(n=3), mediastinum(n=1), and pleura(n=1). Docetaxel 30mg/m2 was infused every 2 weeks, and S-1 80mg/m2 was taken for 2 weeks, then with 2 weeks rest until progression. Almost all of the patients received docetaxel in the outpatient chemotherapy room. The median number of treatment cycles was 3, ranging from 1-12. Among the 14 patients with a therapeutic response, three(21%)achieved PR, 8 showed SD, and 3 had PD. Toxicity which included grade 3/4 was neutropenia in 6 patients, and anemia in one patient. After a follow-up of over one year, the median overall survival was 10 months, and the one-year survival rate was 38%. Docetaxel plus S-1 might be a feasible regimen as a second-line chemotherapy for metastasis or recurrence of esophageal cancer.