DNA vaccination with all-trans retinoic acid treatment induces long-term survival and elicits specific immune responses requiring CD4+ and CD8+ T-cell activation in an acute promyelocytic leukemia mouse model.

DNA vaccination and all-trans retinoic acid (ATRA) result in a survival advantage in a mouse model of acute promyelocytic leukemia (APL). Depletion of CD4(+) or CD8(+) cells abolished this effect. CD4(+) depletions of long-term survivors resulted in relapse and death within 3 months, thus demonstrating the need of both CD4(+) and CD8(+) subsets for the generation of DNA-driven antileukemic immune responses and underscoring a crucial role of CD4(+) cells in the maintenance of durable remissions. Degranulation and cytotoxic carboxyfluorescein diacetate succinimidyl ester-based assays showed major histocompatibility complex-restricted APL-specific T cell-mediated immune responses. Sorted APL-specific CD8(+)CD107a(+) T cells showed an increase of antileukemic activity. Effectors from ATRA + DNA-treated mice were shown to secrete interferon-gamma when stimulated with either APL cells or peptides from the promyelocytic leukemia-RARalpha vaccine-derived sequences as detected by ELISpot assays. Our results demonstrate that DNA vaccination with ATRA confers the effective boosting of interferon-gamma-producing and cytotoxic T cells in the leukemic mice.

[A case of drug-induced interstitial pneumonia due to phenytoin].

A 48-year-old woman had been given phenytoin for prevention of epilepsy for 30 years. She developed a dry cough and low grade fever from one year and half before admission to our hospital. During this interval, she was treated with various antibiotics, however, her condition did not improve. A chest radiograph and CT showed diffuse reticular ground glass opacities in bilateral lung fields. A drug lymphocyte stimulation test (DLST) for phenytoin showed positive results. Lung biopsy specimen by VATS revealed predominant lymphocytic infiltration of lung parenchyma, compatible with drug-induced pneumonitis. Administration of phenytoin was discontinued, oral administration of 30 mg prednisolone was initiated, and the symptoms and shadow on X-ray films improved. These observations strongly suggested the presence of drug-induced pneumonia due to phenytoin in this patient. In patients who develop pneumonia not associated with infection, the possibility of drug-induced pneumonia should be always considered even though the drug has been administered for a long period.

New Approach to Complete Video-assisted Thoracoscopic Lobectomy in T2 and T3 Non-Small Cell Lung Cancer.

Complete video-assisted thoracoscopic surgery (c-VATS) for lung cancer is minimally invasive because of the small incision required. c-VATS has recently become a standard procedure for treatment of stage IA/IB lung cancer. However, a long thoracic incision or extensive costal rib resection is required in patients with large lung tumors. We herein introduce an improved VATS lobectomy procedure for patients with T2 and T3 lung cancer. In this technique, resected tissue is removed through a small upper abdominal midline incision below the xiphoid through the retrosternal-extraperitoneal pathway. Five patients who underwent this new procedure were compared against 10 control patients who underwent hybrid VATS lobectomy. Significantly fewer patients who underwent c-VATS lobectomy complained of severe postoperative pain; however, there was no significant difference in the postoperative hospital stay between the two groups. The present study demonstrates that c-VATS lobectomy can be performed with minimal operative pain and without need for a long thoracic incision or extensive rib resection, even in patients with large lung tumors (T2 and T3). These results suggest that the indications for c-VATS lobectomy in patients with T2 and T3 non-small cell lung cancer can be expanded by implementation of our approach, which involves removal of the freed lobe through an abdominal incision.

Intraperitoneal administration of a tumor-associated antigen SART3, CD40L, and GM-CSF gene-loaded polyplex micelle elicits a vaccine effect in mouse tumor models.

Polyplex micelles have demonstrated biocompatibility and achieve efficient gene transfection in vivo. Here, we investigated a polyplex micelle encapsulating genes encoding the tumor-associated antigen squamous cell carcinoma antigen recognized by T cells-3 (SART3), adjuvant CD40L, and granulocyte macrophage colony-stimulating factor (GM-CSF) as a DNA vaccine platform in mouse tumor models with different types of major histocompatibility antigen complex (MHC). Intraperitoneally administrated polyplex micelles were predominantly found in the lymph nodes, spleen, and liver. Compared with mock controls, the triple gene vaccine significantly prolonged the survival of mice harboring peritoneal dissemination of CT26 colorectal cancer cells, of which long-term surviving mice showed complete rejection when re-challenged with CT26 tumors. Moreover, the DNA vaccine inhibited the growth and metastasis of subcutaneous CT26 and Lewis lung tumors in BALB/c and C57BL/6 mice, respectively, which represent different MHC haplotypes. The DNA vaccine highly stimulated both cytotoxic T lymphocyte and natural killer cell activities, and increased the infiltration of CD11c+ DCs and CD4+/CD8a+ T cells into tumors. Depletion of CD4+ or CD8a+ T cells by neutralizing antibodies deteriorated the anti-tumor efficacy of the DNA vaccine. In conclusion, a SART3/CD40L+GM-CSF gene-loaded polyplex micelle can be applied as a novel vaccine platform to elicit tumor rejection immunity regardless of the recipient MHC haplotype.

Esophageal ruptures: triage using the systemic inflammatory response syndrome score.

Esophageal rupture is a rare entity. Delay in the diagnosis and treatment may threaten the patient's life. The decision for surgical or nonsurgical treatment, however, remains controversial because advocates of both treatments have reported comparable results. To quantify the decision making, we suggest the systemic inflammatory response syndrome (SIRS) score for triage of an esophageal rupture. Using this criterion for 12 patients resulted in the survival of all of them. Therefore, we advocate use of the SIRS score for triage of an esophageal rupture.