Monitoring twenty-six chronic myeloid leukemia patients by BCR-ABL mRNA level in bone marrow:a single hospital experience

Chronic myeloid leukemia (CML) is caused by the BCR-ABL oncogene. The Philadelphia chromosome (Ph) from a reciprocal translocation, t(9;22) (q34;q11) causes a fusion gene, BCR-ABL, that encodes a constitutively active tyrosine kinase. Treatment of CML by imatinib is effective to control the tyrosyl phosphorylation of the protein related to the cell signaling. BCR-ABL mRNA is overexpressed in the minimal residual disease (MRD), known as an early sign of relapse. Between December 2005 and June 2008, we measured BCR-ABL mRNA levels in the bone marrow (BM) from patients by quantitative real-time polymerase chain reaction (RQ-PCR) in Aomori Prefectural Central Hospital. Eighty-six samples from 26 patients were collected. Among the 26 CML patients, 11 patients (42%) were in the pretreatment group. Seven (64%) of the 11 patients achieved complete molecular response (CMR). In the post-treatment group consisting of the remaining 15 patients, 9 (60%) patients achieved CMR. The patients receiving imatinib at a dose over 300 mg per day required 13 (6-77) months [median (range)] to achieve CMR. On the other hand, the patients receiving a dose below 300 mg per day required 29.5 (11-84) months [median (range)]. When BCR-ABL mRNA was detected during the treatment course of patients with CMR, careful observation of BCR-ABL mRNA was useful for tracking the clinical course of patients. In conclusion, the BCR-ABL mRNA level was useful for monitoring the clinical course in 26 patients with CML.     

A human gastric choriocarcinoma cell line with human chorionic gonadotropin and placental alkaline phosphatase production.

A gastric choriocarcinoma cell line synthesizing human chorionic gonadotropin (HCG) was established in 1971 by Oboshi et al. and was found to possess human placental alkaline phosphatase. The present paper also deals with the relationship between the cell growth and HCG secretion and with cellular localization of HCG and human placental alkaline phosphatase by cytochemical and ultrastructural methods. This cell line was found to secrete HCG during cellular proliferation, with the maximum secretion in the stationary phase (about 1 muIU/cell/48 hr), and the hormone could be detected in a small proportion of mono- and/or multinuclear cells in both logarithmic and stationary phases. The organ-specific, heat-stable, L-phenylalanine-sensitive, immunoreactive human placental alkaline phosphatase was localized on the cell membrane of many cells. Ultrastructurally, the line consisted mainly of cytotrophoblastic and intermediate cells in the process of syncytial formation, with more or less squamous metaplasia. From these findings it was concluded that the cell line maintained the properties of trophoblastic cells from morphological and functional aspects, i.e., it was a cell line with two distinct marker substances.     

Clinical significance of immune cell infiltration within gallbladder cancer

To investigate the pathophysiological significance of infiltrating antitumour immune cells, we evaluated the quantity of immune cell intratumoral infiltration in 110 surgically resected gallbladder specimens by immunohistochemistry. We examined 45 cases of gallbladder cancer and 65 cases of benign gallbladder diseases for CD4(+) T cells, CD8(+) T cells, natural killer cells (NKCs), and dendritic cells (DCs). High levels of CD4(+) T cell, CD8(+) T cell, NKC, and DC infiltration were recognised in 51.1% (23 out of 45), 37.8% (17 out of 45), 33.3% (15 out of 45), and 48.9% (22 out of 45) of cancer specimens, respectively. High numbers of infiltrating CD4(+) and CD8(+) T cells correlated with decreasing tumour invasion, and high numbers of infiltrating DCs correlated with decreasing lymph-node tumour metastasis. Furthermore, increased infiltration of CD4(+) and CD8(+) T cells and DCs exhibited a significant correlation with prolonged survival. NKC infiltration, however, did not correlate with any of the clinicopathological factors examined. Additionally, high levels of infiltration were not identified in specimens from benign diseases, consistent with the cancer-specific activity of CD4(+) and CD8(+) T cells and DCs. In this study, we demonstrate that CD4(+) and CD8(+) tumour-infiltrating lymphocyte and DCs, but not NKCs, are important factors in the accurate prognosis of survival after surgical removal of gallbladder adenocarcinoma.     

RCAS1 as a tumour progression marker: an independent negative prognostic factor in gallbladder cancer.

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) induces apoptosis in immune cells bearing the RCAS1 receptor. We sought to determine RCAS1 involvement in the origin and progression of gallbladder cancer, and also implications of RCAS1 for patient survival. RCAS1 expression was examined immunohistochemically in 110 surgically resected gallbladder specimens. The gallbladders represented 20 cases of cholecystitis with no associated pancreaticobiliary maljunction; 23 cases of cholecystitis with pancreaticobiliary maljunction; 14 cases of adenomyomatosis; 7 adenomas; and 46 cancers. High expression of RCAS1 (immunoreactivity in over 25% of cells) was observed in 32 of the 46 cancers (70%), but not in other diseases, including pre-cancerous conditions. RCAS1 immunoreactivity was associated with depth of tumour invasion (P = 0.0180), lymph node metastasis (P = 0.0033), lymphatic involvement (P = 0.0104), venous involvement (P = 0.0224), perineural involvement (P = 0.0351) and stage by the tumour, nodes and metastases (TNM) classification (P = 0.0026). Thus, RCAS1 expression may be a relatively late event in gallbladder carcinogenesis, possibly promoting tumour progression. Cox regression multivariate analysis demonstrated RCAS1 positivity to be an independent negative predictor for survival (P = 0.0337; risk ratio, 12.690; 95% confidence interval, 1.216-132.423). High expression of RCAS1 significantly correlated with tumour progression and predicted poor outcome in gallbladder cancer.     

Ruptured aneurysm of the ductus diverticulum into the pulmonary artery in a man: a successful repair

Aneurysm of the ductus diverticulum in the adult is rare and its rupture is fatal. A 75-year-old man presented with congestive heart failure that suddenly occurred with a continuous murmur. Angiography showed a left-to-right shunt through a large thrombosed aneurysm of the ductus diverticulum (6 cm), and the pulmonary-to-systemic flow ratio was 2.6. Patch closure of the orifice (3x4 cm) of the aneurysm and repair of the perforated pulmonary artery were done emergently under hypothermic cardiopulmonary bypass with selective cerebral perfusion. He recovered uneventfully. Early recognition and early intervention should be indicated in this otherwise fatal condition.     

The prognostic significance of RCAS1 expression in squamous cell carcinoma of the oesophagus.

Overexpression of RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) protects cancer cells from immune attack and might be related to poor prognosis in several cancers. We investigated the immunoreactivity of RCAS1 and its correlation with clinicopathological features in 95 patients who underwent surgical resection for oesophageal squamous cell carcinoma. Thirty-two of the 95 (33.7%) cases were strongly positive for RCAS1. RCAS1 showed significant correlations with age and stage grouping. Expression of RCAS1 was associated with shorter postoperative survival. Multivariate analysis indicated that RCAS1 positivity was an independent negative prognostic factor. Our study establishes RCAS1 as a novel prognostic marker for surgically resected oesophageal squamous cell carcinoma.