Efficient synthesis of carbon-14 labeled metabolites of the strobilurin fungicide mandestrobin using biomimetic iron-porphyrin catalyzed oxidation.

Biomimetic oxidation using synthetic iron-porphyrin (F20 TPPFeCl) as a catalyst eliminated a xylene moiety of the fungicide mandestrobin, uniformly labeled with carbon-14 at the benzyl ring, to produce the corresponding radiolabeled metabolite 1. This reaction mechanism was investigated by identifying chemical structures of intermediate 5 and p-xyloquinone derivatives 6 and 7, as by-products. Optimization of reaction factors based on the mechanism improved the yield of 1 from mandestrobin up to 87%. Finally, various carbon-14 labeled metabolites of mandestrobin were prepared from 1.

Four cases of invasive anterior mediastinal tumors definitively diagnosed by the chamberlain procedure.

Percutaneous needle biopsy, commonly used for a definitive diagnosis of anterior mediastinal tumors, is sometimes inconclusive because of the small size of the biopsy specimens and the histologic heterogeneity of the tumors. We herein report 4 cases of invasive anterior mediastinal tumors, in which the definitive diagnosis was made using the Chamberlain procedure. [Case 1] A 33-year-old man was found to have an anterior mediastinal tumor on chest X-ray and computed tomography (CT). The tumor was histologically diagnosed as thymic carcinoma (squamous cell carcinoma) using the Chamberlain procedure. After 3 courses of preoperative chemotherapy, the patient underwent surgery and postoperative radiotherapy. He remains well, 35 months after the biopsy. [Case 2] A 17-year-old boy was found to have a tumor in the anterior mediastinum on chest CT. His serum alpha-fetoprotein level was elevated to 2,461 ng/mL. Histological diagnosis of yolk sac tumor was confirmed using the Chamberlain procedure. He was treated with one course of chemotherapy, followed by surgery; he remains well 57 months after the biopsy. [Case 3] A 72-year-old man was found, on chest X-ray and CT, to have a left upper anterior mediastinal tumor with invasion of the subclavian vessels. The tumor was confirmed histologically as thymic (sarcomatoid) carcinoma using the Chamberlain procedure. Despite 2 courses of chemotherapy, the tumor continued to enlarge and metastasized to the lung and bone. The patient died 7 months after the biopsy. [Case 4] A 62-year-old woman under treatment for rheumatoid arthritis (RA) was found, on a chest X-ray, to have a right anterior mediastinal tumor. Histological diagnosis using the Chamberlain procedure suggested lymphoproliferative disorder, and the RA medication was discontinued. This was followed by a decrease in the tumor size and avoidance of invasive surgery. The patient remains well, 15 months after the biopsy. [Conclusion] The Chamberlain procedure proved useful for definitive diagnosis in all 4 cases of invasive anterior mediastinal tumors. We recommend the Chamberlain procedure for biopsy since it enables safe, rapid, and successful collection of tissue samples.

[A case of recurrence after resection of gastric cancer successfully treated by combination chemotherapy with CPT-11 and CDDP].

A 62-year-old man received total gastrectomy and splenectomy for gastric cancer in April 2008. The pathological diagnosis was stage IIIA(pT3N2M0). After the surgery, he was treated with oral administration of S-1 as postoperative adjuvant chemotherapy, but stopped after five months because of a drug eruption and general fatigue. He visited our hospital with complaints of abdominal pain and appetite loss in January 2010. Tumor marker(CEA)was elevated, and he was diagnosed as local recurrence with metastasis to the mediastinal/Virchow lymph node and thoracic vertebra after several examinations. He started to undergo combination chemotherapy with CPT-11 and CDDP. After three courses of treatment, local recurrence had almost disappeared and CEA level was normalized. After five courses of treatment, FDG-PET showed that all recurrent tumors had decreased in size and FDG uptake. We finished this combination chemotherapy after ten courses. After the treatment, PET-CT detected a slowly-growing right lung tumor. He received S6 segmentectomy of the right lung in May 2012. The pathological diagnosis was squamous cell carcinoma, and he was diagnosed as primary lung cancer(pT1aN0M0, stage I A). He was followed without showing any recurrence of gastric cancer in October 2012.

Detection of the JC virus genome in lung cancers: possible role of the T-antigen in lung oncogenesis.

The JC virus (JCV) infects a large proportion of the population worldwide and 80% to 90% of adults are seropositive and it may be activated in immunodeficient patients, resulting in progressive multifocal leukoencephalopathy. Recent reports described the possibility of its oncogenetic role in several malignancies. To clarify whether JCV might have a potential role in the genesis of lung cancers, we investigated the presence of its genome in 62 tumors, along with 23 samples of normal lung tissue, targeting the T-antigen, VP, and Agnoprotein by nested polymerase chain reaction/Southern blotting followed by direct DNA sequencing. Immunohistochemistry was performed to assess links between p53 and beta-catenin in lung cancers and the presence of T-antigen. The T-antigen was detected in 25 of 62 lung cancers but only 4 of 23 normal lung samples (P=0.048). In total, the JCV genome was present in 33 of the lung cancers and 10 of the normal samples. Furthermore, T-antigen was found in cancer cells in metastatic lymph nodes in 3 of 4 cases (P=0.042) and was more frequently detected in adenocarcinomas than in squamous cell carcinomas (P=0.038). Immunohistochemistry showed significant correlations between T-antigen and p53 (P=0.022) and also nuclear detection of beta-catenin (P=0.021). It is concluded that the JCV genome might be present in cancer cells in approximately half of all Japanese lung cancer cases, and that the T-antigen may play a role in oncogenesis of lung cancers through inactivation of p53 and dysregulation of the Wnt signaling pathway.