Gene therapy for malignant mesothelioma: current prospects and challenges.

Malignant mesothelioma, developed in the thoracic cavity, is resistant to current treatments. Suppression of the local tumor growth is beneficial to the patients since mesothelioma infrequently metastasizes to extrapleural organs. A majority of the tumors have a homologous genetic deletion at the INK4A/ARF locus that includes the p14ARF and the p16INK4A genes, and the genetic defect results in an inactivation of the p53-mediated pathways and in progression of cell cycle through pRb phosphorylation. Preclinical studies targeting the genetic abnormality with adenoviruses showed that restoration of the p53 pathways induced pRb dephosphorylation and subsequently produced anti-tumor effects. A number of preclinical studies with different genes and vector systems demonstrated the therapeutic efficacy and raised the possibility of gene therapy in clinical settings. An intrapleural administration of vectors has several advantages in transducing pleural mesothelioma but activates rapid antibody production which impedes further gene expression. There have been several clinical studies conducted for mesothelioma and these trials showed the feasibility of intrapleural administrations of adenovirus vectors. In this review we summarize major preclinical and clinical gene therapy for mesothelioma, and discuss the advantages of gene therapy in the context of stimulating host immune systems. Accumulating clinical data suggest that an intrapleural administration of viral vectors has distinct aspects which are not observed in other administration routes.

Dynamics of airborne pollen particles from inhalation to allergic reaction in the nose.

BACKGROUND: Pollinosis is common worldwide, and has been frequently studied. However, the intranasal dynamics of pollen grains have not yet been documented. The purpose of this study is to elucidate for the first time the dynamics of Japanese cedar pollen (JCP) in the human nose at consecutive steps from inhalation to allergic reaction together with release of Cry j 1 (a major allergenic component of JCP) in the nose. METHODS: A personal sampler collected airborne pollens at head height outdoor on the street, while intranasal pollens after natural or experimental inhalation were collected by irrigation with 200ml saline. Cry j 1 in the supernatant after in vitro incubation with phosphate buffered saline or lavage was determined by enzyme-linked immunoassay. RESULTS: Head-height pollen was 183.0 +/- 43.1/300L/h, with 99% of the inhaled pollens deposited on the nasal surface. Eighty eight% of the inhaled pollen was transported to the out-side of the nose by ciliary function within 3 hours. During this process, considerable amounts of Cry j 1 were released in the nose reaching its plateau within 30 min. When the number of pollen deposited exceeded more than approximately 65 particles, symptoms may occur, leading presumably up to a 74% reduction of the intra-nasal pollen. CONCLUSION: The majority of inhaled airborne pollens was deposited on the nasal mucosal surface and moved out from the nose by mucociliary transportation. During this process, when allergenic substances are released up to a critical concentration, allergic reactions occur leading to expelling of pollen from the nose followed by subsiding of the symptoms.

Surgical resection combined with intrathoracic hyperthermic perfusion for thymic carcinoma with an intrathoracic disseminated lesion: a case report.

Thymic undifferentiated carcinoma has a poor prognosis. We encountered a patient with thymic carcinoma associated with an intrathoracic disseminated lesion, who underwent surgery combined with intrathoracic hyperthermic perfusion after systemic chemotherapy and showed good results. The 45-year-old man was diagnosed as having a thymoma with an intrathoracic disseminated lesion. After he underwent three courses of systemic chemotherapy, he was admitted to our hospital. An anterior mediastinal tumor and an intrathoracic disseminated lesion remained, and were treated by surgical resection combined with intrathoracic hyperthermic perfusion. The tumors were histopathologically diagnosed as thymic undifferentiated carcinomas with pleural dissemination. At present, approximately 16 months after surgery, the patient is alive without recurrence.

[Suitable and successful management in preoperative deposit of autologous blood transfusion in cases of orthopedic elective surgeries].

To reveal the suitable and successful management in preoperative deposit of autologous blood, the 307 cases who had autologous blood transfusion during orthopedic elective surgery were studied retrospectively. Light body weight(less than 43 kg), predonative anemic condition(less than 11.3 g/dl in Hb concentration), and the aged(older than 68 yrs) were the main factors causing less deposit than scheduled amount. Less deposit (< 766 ml in THA), when preoperative low Hb concentration and unexpectedly massive bleeding added to it, was responsible for necessity of homologous blood transfusion. Combination of 400 ml-donation with 200 ml-donation, and gradual increase of rhEPO administration, are effective to prevent from unexpectedly less deposit.