Concurrent intra-arterial chemotherapy and radiotherapy for advanced laryngeal cancer.

OBJECTIVES: An intra-arterial chemoradiotherapy regimen (RADPLAT) provides remarkable local control for head and neck cancer. This study evaluates the efficacy of a reduced RADPLAT protocol in patients who are candidates for total laryngectomy. METHODS: Forty-three patients with advanced laryngeal cancer were treated with 2 courses of intra-arterial cisplatin infusion (100 mg per body) during 40-Gy irradiation. The patients who showed a greatly diminished tumor received sequential irradiation. The patients with obvious residual disease received chemotherapy during the sequential irradiation. Poor responders, with less than 50% tumor reduction, underwent total laryngectomy. RESULTS: Forty-two patients completed the protocol. All surviving patients were followed for at least 3 years. Thirty-four patients were alive (80% of the supraglottic cases and 87.5% of the glottic cases). Local control was achieved in 27 patients (67.5% of the 11 glottic cases and 64.0% of the supraglottic cases). The glottic cohort showed better progression-free survival rates than did the supraglottic cohort (68.8% and 45.0%, respectively; p = 0.019). There were 2 cases of grade 3 neutropenia and 3 cases of grade 3 mucositis. No patients required tube feeding. One patient required tracheostomy 3 months after the completion of the treatment protocol. CONCLUSIONS: Concurrent chemoradiotherapy with a reduced dose of intra-arterial cisplatin is feasible for patients with advanced glottic cancer.

Impact of MDM2 single nucleotide polymorphism on tumor onset in head and neck squamous cell carcinoma.

CONCLUSIONS: The GG genotype of MDM2 SNP309 is associated with an earlier onset of head and neck squamous cell carcinoma (HNSCC) in the Japanese population. SNP309 may be a key factor in the tumorigenesis of HNSCC as well as other hereditary or sporadic tumors. OBJECTIVE: This study was designed to evaluate the association between the single nucleotide polymorphism (SNP) 309 in the MDM2 gene with HNSCC. An MDM2 protein down-regulates the p53 pathway. Recently, an important SNP was discovered in the MDM2 promoter region, which could affect the tumorigenesis of HNSCC by attenuation of the p53 pathway. PATIENTS AND METHODS: Patients with 103 HNSCCs were genotyped using direct sequencing and real-time PCR. The relationship between the SNP309 genotypes and the clinicopathological features was statistically analyzed. RESULTS: The number of patients genotyped to TT, TG, and GG was 29 (28%), 46 (44.7%), and 28 (27.2%), respectively. The average age at tumor onset was 65.6 years for TT, 62.9 years for TG, and 56.7 years for GG. The patients with the GG genotype had a significantly earlier tumor onset in comparison to those with the TT genotype (p=0.032).

Treatment of locally recurrent Epstein-Barr virus-associated nasopharyngeal carcinoma using the anti-viral agent cidofovir.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) associated malignant tumor. Recently, cidofovir, an anti-viral drug which is an acyclic nucleoside analogue, has been reported to have an anti-tumor potential. Two patients with NPC, who had previously received multi-round therapy, were treated with cidofovir. Cidofovir was topically injected in and around the tumor once every 3 weeks (originally 75 mg/ml sulution, diluted to 15 mg/ml just before injection, 37.5 mg of cidofovir at a time). Tumor growth was suppressed for several months around the injection site in each patient. EBV-encoded RNAs in situ hybridization revealed the reduction of the tumor cell population; however, the EBER expression was still maintained in the NPC tumor cells. Although the anti-tumor mechanism remains unclear, these results suggest that cidofovir is actually an effective and safe agent for the treatment of NPC.

Isolation of sperm vesicles from adult male mayflies and other insects to prepare high molecular weight genomic DNA samples.

We describe here a simple and efficient protocol for genomic DNA isolation from adult males of insects: e.g., Ephemeroptera, Odonata, Orthoptera and Dictyoptera. To minimize contamination of external DNA source, the sperm vesicles were isolated from male individuals from which high molecular weight genomic DNA was extracted. According to this protocol, the genomic DNA samples obtained were high quality (intact), and abundant enough for genotyping analyses and molecular cloning. The protocol reported here enables us to process a huge number of individuals at a time with escaping from cross-contamination, and thus it is quite useful for conducting genetic studies at least in some species of insects. The large yield of high molecular weight DNA from single individual may be advantageous for non PCR-based experiments. As a case study of the protocol, partial coding sequences of histone H3 and EF-1alpha genes are determined for some insects with PCR-amplified DNA fragments.

Soluble-insoluble-soluble transitions of aqueous poly(N-vinylacetamide-co-acrylic acid) solutions.

Several poly(N-vinylacetamide-co-acrylic acid)s with various copolymer compositions have been synthesized, and their unique phase-transition behavior in aqueous salt (Na2SO4 or NaCl) solutions was investigated. Copolymers containing more than 51 mol % N-vinylacetamide (NVA) show reentrant soluble-insoluble-soluble transitions with increasing temperature. The soluble-insoluble transition temperature (T(p1)) increased linearly with increasing NVA content, whereas the insoluble-soluble transition temperature (T(p2)) was almost constant irrespective of the NVA content. Potentiometric titration of the copolymer solutions suggested that the acrylic acid (AA) carboxyl groups form hydrogen bonds with the NVA amide groups even under soluble conditions. Dehydration of the NVA amides and their consequent hydrogen bonding with the AA carboxyl groups during the soluble-insoluble transition process was indicated by FTIR measurements. Addition of salt (Na2SO4 or NaCl) to the aqueous media reduces the solvent quality and enhances the intra- and interchain interactions of the copolymers. Thus, T(p1) was observed to decrease and T(p2) was observed to increase with increasing salt concentration. However, the addition of urea to the media reverses the concentration dependence of T(p1) and T(p2) by disturbing the intra- and interchain interactions of the copolymers.