An alternative convenient synthesis of piperidazine-3-carboxylic acid derivatives.

The short-step synthesis of the unsubstituted, 5-hydroxy- and 5-chloropiperidazine-3-carboxylic acids using an aza Diels-Alder reaction between the 1,3-diene and azodicarboxylate was described. This synthetic methodology could be used for the preparation of the optically active piperazic acid in a 35% overall yield.

Tailor-made approach to photodynamic therapy in the treatment of cancer based on Bcl-2 photodamage.

It is very important to elucidate the mechanism of action and identify the molecular determinant of photodynamic medicine, in order to increase the number of clinical applications of photodynamic therapy (PDT) and perform personalized medicine. We have previously reported that PDT using some photosensitizers, such as phthalocyanine 4 (Pc 4) damages the anti-apoptotic protein Bcl-2, and that Bcl-2 is a molecular PDT target using a mitochondrion-targeting photosensitizer. In this study, we examined the molecular targets of Photofrin-PDT and NPe6-PDT, which are approved for early stage lung cancers by the Japanese Ministry of Health Labor and Welfare, by evaluating the photodamage to Bcl-2 using Western blot analysis. Our results showed that Photofrin-PDT damaged Bcl-2, induced morphologically typical apoptosis, and demonstrated equal sensitivity between MCF-7c3 cells (human breast cancer cells expressing stably transfected procaspase-3) and Bcl-2 overexpressing cells, MCF-7c3-GFP-Bcl-2 cells, with a clonogenic assay. However, NPe6-PDT did not damage Bcl-2 and took longer to induce typical apoptosis compared with Photofrin-PDT. MCF-7c3-GFP-Bcl-2 cells were considerably more resistant to the lethal effects of NPe6-PDT than parental MCF-7c3 cells. In conclusion, Photofrin-PDT damages different molecular targets, and our data indicate that the extent of Bcl-2 photodamage can determine the sensitivity of cancer cells to apoptosis and to overall cell killing caused by PDT using Photofrin, but not the lysosomal targeting NPe6. The application of these findings to clinical PDT may depend on the levels of the Bcl-2 proteins in the tumor being treated, and the tailor-made medicine based on the Bcl-2 photodamage may overcome any resistance afforded by elevated amounts of Bcl-2.

Airway stenting for the treatment of laryngotracheal stenosis secondary to thyroid cancer.

BACKGROUND AND OBJECTIVE: Airway stenting can be a valuable therapeutic option for symptomatic airway stenosis, but its role in the palliation of advanced thyroid cancers invading the upper airway is unclear. This study examined the hypothesis that durable and replaceable silicone stents would give better results than self-expanding metallic stents. METHODS: A retrospective analysis was conducted of consecutive patients stented for laryngotracheal obstruction due to thyroid cancer. Stenting was performed via a rigid bronchoscope when airway patency after dilatation was

Endoscopic tumor ablation for laryngotracheal intraluminal invasion secondary to advanced thyroid cancer.

CONCLUSIONS: Endoscopic tumor ablation is a valuable option for inoperable postoperative laryngotracheal intraluminal invasion of well-differentiated thyroid carcinoma (DTC). OBJECTIVES: To investigate whether DTC invasion to the laryngotracheal mucosa can be controlled by 'simple' tumor ablation considering its relatively slow-growing nature. PATIENTS AND METHODS: Twenty-two consecutive patients underwent endoscopic tumor ablation caused by DTC for local control of intraluminal lesions with no significant extrinsic laryngotracheal compression in symptomatic or asymptomatic patients in whom radical operations were contraindicated. Debulking by Nd:YAG laser was followed by electrocoagulation and microwave coagulation for the residual tumor base. RESULTS: The critical complication, post-treatment supraglottic stenosis, was managed by prophylactic minitracheotomy. During the follow-up period of up to 125 months, 6 of 22 patients died (median survival 50 months), mainly of lung metastases, but all had a patent airway at death. Post-surgical extraluminal lesion growth is indolent and since relapse of the intraluminal lesion is the main cause of symptoms, satisfactory local control could be obtained by re-ablation of the mucosal lesion every few years. Lesions requiring retreatment within 1 year after initial treatment usually have high-grade malignancy, causing extrinsic compression, and prognosis is unfavorable.