The significance of NAD + metabolites and nicotinamide N-methyltransferase in chronic kidney disease.

Dysregulation of nicotinamide adenine dinucleotide (NAD +) metabolism contributes to the initiation and progression of age-associated diseases, including chronic kidney disease (CKD). Nicotinamide N-methyltransferase (NNMT), a nicotinamide (NAM) metabolizing enzyme, regulates both NAD + and methionine metabolism. Although NNMT is expressed abundantly in the kidney, its role in CKD and renal fibrosis remains unclear. We generated NNMT-deficient mice and a unilateral ureter obstruction (UUO) model and conducted two clinical studies on human CKD to investigate the role of NNMT in CKD and fibrosis. In UUO, renal NNMT expression and the degraded metabolites of NAM increased, while NAD + and NAD + precursors decreased. NNMT deficiency ameliorated renal fibrosis; mechanistically, it (1) increased the DNA methylation of connective tissue growth factor (CTGF), and (2) improved renal inflammation by increasing renal NAD + and Sirt1 and decreasing NF-κB acetylation. In humans, along with CKD progression, a trend toward a decrease in serum NAD + precursors was observed, while the final NAD + metabolites were accumulated, and the level of eGFR was an independent variable for serum NAM. In addition, NNMT was highly expressed in fibrotic areas of human kidney tissues. In conclusion, increased renal NNMT expression induces NAD + and methionine metabolism perturbation and contributes to renal fibrosis.

Genomic Evidence for Speciation with Gene Flow in Broadcast Spawning Marine Invertebrates.

How early stages of speciation in free-spawning marine invertebrates proceed is poorly understood. The Western Pacific abalones, Haliotis discus, H. madaka, and H. gigantea, occur in sympatry with shared breeding season and are capable of producing viable F1 hybrids in spite of being ecologically differentiated. Population genomic analyses revealed that although the three species are genetically distinct, there is evidence for historical and ongoing gene flow among these species. Evidence from demographic modeling suggests that reproductive isolation among the three species started to build in allopatry and has proceeded with gene flow, possibly driven by ecological selection. We identified 27 differentiation islands between the closely related H. discus and H. madaka characterized by high FST and dA, but not high dXY values, as well as high genetic diversity in one H. madaka population. These genomic signatures suggest differentiation driven by recent ecological divergent selection in presence of gene flow outside of the genomic islands of differentiation. The differentiation islands showed low polymorphism in H. gigantea, and both high FST, dXY, and dA values between H. discus and H. gigantea, as well as between H. madaka and H. gigantea. Collectively, the Western Pacific abalones appear to occupy the early stages speciation continuum, and the differentiation islands associated with ecological divergence among the abalones do not appear to have acted as barrier loci to gene flow in the younger divergences but appear to do so in older divergences.

Prognostic factors of recovery with medication in patients with taste disorders.

OBJECTIVES: We aimed to elucidate the prognostic factors of the patients with taste disorders who were treated with popular and common medication in Japan. MATERIALS AND METHODS: A retrospective study on the medical charts of a total of 255 patients with taste disorders who were treated primarily with oral medication including a zinc agent. RESULTS: The factors below were significantly linked with poor prognosis: 1) male gender, 2) taste disorders that began 3 months before starting treatment and 3) a severe taste disorder grade at the initial visit. CONCLUSIONS: We have concluded that the prognosis for the patients with taste disorders who were treated by popular and standard medication therapy in Japan recently was significantly linked to gender, the period of 3 months before starting the treatment and the severity of the disorder at the time of diagnosis. In addition, we recognized some limitations we should resolve in further research including a method of measuring "umami" and so on. CLINICAL RELEVANCE: Better awareness of these factors should be clinically useful when we manage patients with taste disorders. Earlier treatment should be started to cure the symptoms.

Combination treatment with the cap-dependent endonuclease inhibitor baloxavir marboxil and a neuraminidase inhibitor in a mouse model of influenza A virus infection.

OBJECTIVES: Baloxavir marboxil (formerly S-033188) is a first-in-class, orally available, cap-dependent endonuclease inhibitor licensed in Japan and the USA for the treatment of influenza virus infection. We evaluated the efficacy of delayed oral treatment with baloxavir marboxil in combination with a neuraminidase inhibitor in a mouse model of lethal influenza virus infection. METHODS: The inhibitory potency of baloxavir acid (the active form of baloxavir marboxil) in combination with neuraminidase inhibitors was tested in vitro. The therapeutic effects of baloxavir marboxil and oseltamivir phosphate, or combinations thereof, were evaluated in mice lethally infected with influenza virus A/PR/8/34; treatments started 96 h post-infection. RESULTS: Combinations of baloxavir acid and neuraminidase inhibitor exhibited synergistic potency against viral replication by means of inhibition of cytopathic effects in vitro. In mice, baloxavir marboxil monotherapy (15 or 50 mg/kg twice daily) significantly and dose-dependently reduced virus titre 24 h after administration and completely prevented mortality, whereas oseltamivir phosphate treatments were not as effective. In this model, a suboptimal dose of baloxavir marboxil (0.5 mg/kg twice daily) in combination with oseltamivir phosphate provided additional efficacy compared with monotherapy in terms of virus-induced mortality, elevation of cytokine/chemokine levels and pathological changes in the lung. CONCLUSIONS: Baloxavir marboxil monotherapy with 96 h-delayed oral dosing achieved drastic reductions in virus titre, inflammatory response and mortality in a mouse model. Combination treatment with baloxavir acid and oseltamivir acid in vitro and baloxavir marboxil and oseltamivir phosphate in mice produced synergistic responses against influenza virus infections, suggesting that treating humans with the combination may be beneficial.

Sensitization of transient receptor potential vanilloid 4 and increasing its endogenous ligand 5,6-epoxyeicosatrienoic acid in rats with monoiodoacetate-induced osteoarthritis.

Transient receptor potential vanilloid 4 (TRPV4) receptor modulates pain, and this has been noted in several animal models. However, the involvement of TRPV4 in osteoarthritic (OA) pain remains poorly understood. This study assessed the functional changes in TRPV4 and the expression of its endogenous ligand 5,6-epoxyeicosatrienoic acid (5,6-EET) in a rat monoiodoacetate (MIA)-induced OA pain model (MIA rats). Monoiodoacetate-treated rats showed reduced grip strength as compared to sham-treated rats, and this loss in function could be recovered by the intraarticular administration of a TRPV4 antagonist (HC067047 or GSK2193874). By contrast, the intraarticular administration of the TRPV4 agonist, GSK1016790A, increased the pain-related behaviors in MIA rats but not in sham rats. TRPV4 expression was not increased in knee joints of MIA rats; however, the levels of phosphorylated TRPV4 at Ser824 were increased in dorsal root ganglion neurons. In addition, 5,6-EET was increased in lavage fluids from the knee joints of MIA rats and in meniscectomy-induced OA pain model rats. 5,6-EET and its metabolite were also detected in synovial fluids from patients with OA. In conclusion, TRPV4 was sensitized in the knee joints of MIA rats through phosphorylation in dorsal root ganglion neurons, along with an increase in the levels of its endogenous ligand 5,6-EET. The analgesic effects of the TRPV4 antagonist in the OA pain model rats suggest that TRPV4 may be a potent target for OA pain relief.

First-principles analysis on role of spinel (111) phase boundaries in Li4+3xTi5O12 Li-ion battery anodes.

The practical anode material Li4+3xTi5O12 is known to undergo a two-phase separation into Li7Ti5O12 and Li4Ti5O12 during charging/discharging. This phase-separated Li4+3xTi5O12 exhibits electron conduction, although individual phases are expected to be insulators. To elucidate the role played by spinel (111) phase boundaries on these physical properties, first principles calculations were carried out using the GGA+U method. Two-phase Li7Ti5O12/Li4Ti5O12 models are found to exhibit metallic characteristics near their phase boundaries. These boundaries provide conduction paths not only for electrons, but also for Li ions. Judging from the formation energy of Li vacancies/interstitials, the phase boundaries preferentially uptake or release Li via in-plane conduction and then continuously shift in a direction perpendicular to the phase boundary planes. The continuous phase boundary shift leads to a constant electrode potential. A three-dimensional network of cubic {111} planes may contribute to smooth electrochemical reactions.

Relationship of physical distress to dizziness in patients with fibromyalgia.

CONCLUSIONS: The feelings of dizziness and unsteadiness of the patients with fibromyalgia supposed specifically amplified by the hypersensitivity mechanism of CSS (central sensitivity syndrome) of them. The severity of subjective pain and physical distress according to the questionnaires were not correlated with the objective body sway on the stabilometer. OBJECTIVES: Fibromyalgia manifests primarily as chronic pain of the entire body, but is also often associated with a variety of physical symptoms including dizziness and unsteadiness. This study assessed whether objective measures of body sway and unsteadiness of them are associated with their subjective dizziness findings. METHOD: Subjects were 24 patients diagnosed with fibromyalgia, but one patient who had the past history of sudden deafness was excluded. The 23 patients were assessed by a stabilometer as the objective measures of body sway, and JFIQ (Japanese version of the fibromyalgia impact questionnaire), DHI (dizziness handicap inventory) and ABC (activities-specific balance confidence) as the subjective questionnaires. RESULTS: The significant correlations were shown between the scores of JFIQ and DHI, JFIQ and ABC, and DHI and ABC. Then, the body sway index of stabilometer environmental area was significantly correlated with DHI score. However, the stabilometer index was not correlated neither with JFIQ or ABC.

Novel microsatellite marker development from the unassembled genome sequence data of the marbled flounder Pseudopleuronectes yokohamae.

Various genome-scale data have been increasingly published in diverged species, but they can be reused for other purposes by re-analyzing in other ways. As a case study to utilize the published genome data, we developed microsatellite markers from the genome sequence data (assembled contigs and unassembled reads) of the marbled flounder Pseudopleuronectes yokohamae. No microsatellites were identified in the contig sequences, whereas the computer software found 781,773 sequences containing microsatellites with di- to hexa-nucleotide motif in the unassembled reads. For 86,732 unique sequences among them, a total of 331,368 primer pairs were designed. Screening based on PCR amplification, polymorphisms and accurate genotyping resulted in sixteen primer sets, which were later characterized using 45 samples collected in Onagawa Bay, Miyagi, Japan. The presence of null alleles was suggested at four loci in the studied population but no evidence of allelic dropout was found. The observed number of alleles and heterozygosity was 2-20 and 0-0.88889, respectively, indicating polymorphisms and usefulness for population genetic analyses of this species. In addition, a large number of the microsatellite primers developed in this study are potentially applicable also for kinship estimation, individual fingerprint and linkage map construction.

Protocadherin-1 is a glucocorticoid-responsive critical regulator of airway epithelial barrier function.

BACKGROUND: Impaired epithelial barrier function renders the airway vulnerable to environmental triggers associated with the pathogenesis of bronchial asthma. We investigated the influence of protocadherin-1 (PCDH1), a susceptibility gene for bronchial hyperresponsiveness, on airway epithelial barrier function. METHODS: We applied transepithelial electric resistance and dextran permeability testing to evaluate the barrier function of cultured airway epithelial cells. We studied PCDH1 function by siRNA-mediated knockdown and analyzed nasal or bronchial tissues from 16 patients with chronic rhinosinusitis (CRS) and nine patients with bronchial asthma for PCDH1 expression. RESULTS: PCDH1 was upregulated with the development of epithelial barrier function in cultured airway epithelial cells. Immunocytochemical analysis revealed that PCDH localized to cell-cell contact sites and colocalized with E-cadherin at the apical site of airway epithelial cells. PCDH1 gene knockdown disrupted both tight and adhesion junctions. Immunohistochemical analysis revealed strong PCDH1 expression in nasal and bronchial epithelial cells; however, expression decreased in inflamed tissues sampled from patients with CRS or bronchial asthma. Dexamethasone (Dex) increased the barrier function of airway epithelial cells and increased PCDH1 expression. PCDH1 gene knockdown eradicated the effect of Dex on barrier function. CONCLUSION: These results suggest that PCDH1 is important for airway function as a physical barrier, and its dysfunction is involved in the pathogenesis of allergic airway inflammation. We also suggest that glucocorticoids promotes epithelial barrier integrity by inducing PCDH1.

Genomic Resources Notes accepted 1 February 2015 - 31 March 2015.

This article documents the public availability of (i) raw transcriptome sequence data, assembled contigs and BLAST hits of the Antarctic plant Colobanthus quitensis grown in two different climatic conditions, (ii) the draft genome sequence data (raw reads, assembled contigs and unassembled reads) and RAD-tag read data of the marbled flounder Pseudopleuronectes yokohamae, (iii) transcriptome resources from four white campion (Silene latifolia) individuals from two morphologically divergent populations and (iv) nuclear DNA markers from 454 sequencing of reduced representation libraries (RRL) based on amplified fragment length polymorphism (AFLP) PCR products of four species of ants in the genus Tetramorium.

S-777469, a novel cannabinoid type 2 receptor agonist, suppresses itch-associated scratching behavior in rodents through inhibition of itch signal transmission.

We have previously reported that S-777469 [1-([6-ethyl-1-(4-fluorobenzyl)-5-methyl-2-oxo-1,2-dihydropyridine-3-carbonyl]amino)-cyclohexanecarboxylic acid], a novel cannabinoid type 2 receptor (CB2) agonist, significantly suppressed compound 48/80-induced scratching behavior in mice in a dose-dependent manner when it was administered orally. Here, we demonstrated that the inhibitory effects of S-777469 on compound 48/80-induced scratching behavior are reversed by pretreatment with SR144528, a CB2-selective antagonist. In addition, we investigated the effects of S-777469 on itch-associated scratching behavior induced by several pruritogenic agents in mice and rats. S-777469 significantly suppressed scratching behavior induced by histamine or substance P in mice or by serotonin in rats. In contrast, the H1-antihistamine fexofenadine clearly inhibited histamine-induced scratching behavior but did not affect scratching behavior induced by substance P or serotonin. Moreover, S-777469 significantly inhibited histamine-induced peripheral nerve firing in mice. In conclusion, these results suggest that S-777469 produces its antipruritic effects by inhibiting itch signal transmission through CB2 agonism.

[Time course of changes in gustatory function test results and subjective symptoms, and predictive factors for response in patients with taste disorder receiving 24-week zinc replacement treatment].

In a taste disorder, an agreement between patients' complaints and gustatory function test results is not necessarily found both at the initial hospital visit and during the course of treatment; therefore, it is difficult to assess treatment responses and review treatment strategies based on the assessed treatment responses. The present study investigated the time course of changes in disc gustometry results and subjective symptom scores measured at 4-week intervals in 44 patients with a taste disorder who were considered eligible for zinc replacement treatment and who received polaprezinc at a dose of 150 mg/day (equivalent to a 34 mg/day dose of zinc) for up to 24 weeks. The study also examined the potential differences in treatment outcomes according to the predictive factors for response such as patient background and assessed disc gustometry results during the course of treatment. Results indicated that disc gustometry results and subjective symptom scores showed different time courses of changes. The response rate as measured by disc gustometry was 47.7% at week 12 of treatment, and showed a subsequent slow increase to 56.8% at week 24. On the other hand, subjective symptom scores showed a time-proportional improvement up to week 24. Among the patients included in the present study, a clear difference was found according to the presence or absence of an improving trend as determined by disc gustometry at week 12 of treatment, although there were no differences in ultimate treatment responses, including categories of taste disorder, according to patient background. Patients showing a trend toward improvement had significantly better treatment responses in terms of both ultimate response rates and subjective symptom scores, whereas patients showing no trend toward improvement were less likely to respond to the subsequent 12-week continued treatment.

Expression and localization of taste receptor genes in the vallate papillae of rats: effect of zinc deficiency.

CONCLUSION: We found a difference in expression sites between TAS2Rs and ENaC (epithelial sodium channels). The number of TAS2R-positive cells and ENaC-positive cells were decreased in zinc-deficient diet rats. These findings suggest that decreased expression of taste receptor genes may play an important role in the onset of zinc deficiency-associated taste disorder. OBJECTIVE: The present study was aimed at histologically investigating the expression and localization of TAS2Rs and ENaC in the vallate taste buds of rats. Changes in expression of the taste receptor genes in zinc-deficient rats were also investigated. METHODS: The vallate papillae of five rats fed a normal diet and five rats fed a zinc-deficient diet were used. In situ hybridization was performed to investigate the expression and localization of TAS2Rs and ENaC. TAS2R-positive cells per taste bud were counted, and differences in number between the normal and zinc-deficient diet rats were investigated. RESULTS: In the normal rats, expression of TAS2Rs was observed specifically in the taste bud cells. In contrast, ENaC-positive cells were observed in a part of the taste bud cells and a large number of epithelial cells. Fewer cells were positive for TAS2Rs and ENaC in the zinc-deficient diet rats.

Why do patients with fibromyalgia complain of ear-related symptoms? Ear-related symptoms and otological findings in patients with fibromyalgia.

While fibromyalgia is frequently associated with ear-related symptoms such as feeling of ear fullness, earache, and tinnitus, the pathogenesis of these ear-related symptoms in fibromyalgia patients is unknown. Here, we focused on clarifying the pathogenesis of ear fullness, a particularly common symptom observed in fibromyalgia patients. Twenty patients diagnosed with fibromyalgia on outpatient psychosomatic treatment complaining of ear-related symptoms answered our questionnaire and underwent neurotological examination, including pure tone audiometry and Eustachian tube function testing. While ear-related symptoms were significantly exacerbated after onset of fibromyalgia, we noted no correlation between the presence or absence of feeling of ear fullness and abnormal findings on neurotological examination. Given our findings, we suspect that onset of ear fullness may be associated not with abnormal findings in the middle and inner ear function tests but with other causes, such as central desensitization.

[The effect of zinc agent in 219 patients with zinc deficiency-inductive/ idiopathic taste disorder: a placebo controlled randomized study].

Diagnosis and treatment of taste disorders are challenging because the disorder can only be determined by the awareness of the patient. Hence, these disorders still require comprehensive evidence. We conducted a randomized, placebo-controlled double-blind study to investigate the effect of polaprezinc, a zinc-containing agent, in 219 patients with either zinc deficiency-inductive or an idiopathic taste, disorder. As a result, the zinc-treated arm experienced a statistically significant improvement against the placebo-treated arm in the perceptible threshold scores of the filter-paper disk method 8 weeks after the administration of the investigational drug. Moreover, the effect lasted for 4 weeks after discontinuation of the drug. However, the effective ratios based on the initial criteria were 55.6% in the treatment group and 43.2% in the placebo, where no statistical significance was recorded. Sex and degree of depression could be two of the potential factors to explain this discrepancy. Furthermore, the effect was not significant among male patients and patients with a high depression score based on the Self-rating Depression Scale (SDS) test. These results indicate that determining the symptom among such patients remains undisclosed. Whereas, in approximately 77%, or 168 patients with "normal" SDS scores and with completely impaired taste qualities, the ratio of effective cases reached 60.9% in the zinc-treated group, the ratio of the placebo-treated group reached 39.5%, resulting in a statistical significance. This may be partly because of a problem in the adaption of male subjects to the gustatory analyses, especially to the identification of saltiness and sourness. Care must also be taken regarding the depressive state of patients when diagnosing and treating taste disorders. Taste disorders caused by depression may not be cured by zinc supplementation due in part to the fact that the symptom is based on a mental issue, and due in part to the conservative responding bias generated by the depression itself, which may inhibit accurate and precise diagnosis of the disorder. In conclusion, administration of a zinc agent is effective for patients with taste disorders, provided selection of appropriate patients is performed, and that proper examination and evaluation are conducted. The present study also indicated that examining depressiveness based on the SDS scores and investigating disturbance of each taste quality using the filter-paper disk method are recommended for the diagnosis and determination of the treatment effect of a taste disorder.

Superselective intra-arterial chemoradiation therapy for functional laryngeal preservation in advanced squamous cell carcinoma of the glottic larynx.

CONCLUSION: Superselective intra-arterial chemotherapy is a safe and useful treatment that preserves the vocal, swallowing, and feeding functions of the larynx in T3 cancer supplied by the superior laryngeal artery and T4a cancer not extending beyond the thyroid cartilage. OBJECTIVE: To evaluate the outcomes of superselective intra-arterial chemotherapy for squamous cell carcinoma of the glottic larynx. METHODS: Sixty-four patients with squamous cell carcinoma of the glottic larynx underwent treatment of the primary tumor using induction chemotherapy with two cycles of intra-arterial docetaxel and cisplatin, plus continuous intravenous infusion of 5-fluorouracil for 120 h starting on day 2; followed by two cycles of concurrent chemoradiation therapy. Residual neck lymph node metastases were treated by neck dissection. RESULTS: The overall 5- and 10-year survival rates were 70.4% and 62.9%, respectively. The 5- and 10-year survival rates were 96.3% and 89.9%, respectively, in the 29 patients with T3 cancer, and 50.4% and 44.1%, respectively, in the 35 patients with T4a cancer. The overall 5- and 10-year laryngeal preservation rates were 71.0% and 60.6%, respectively. The 5- and 10-year laryngeal preservation rates were 92.5% and 87.4%, respectively, in patients with T3 cancer, and 48.6% and 35.6%, respectively in patients with T4a cancer. No irreversible adverse effects were reported.

Multidrug resistance in mucoepidermoid carcinoma of the parotid gland--immunohistochemical investigations of P-glycoprotein expression.

UNLABELLED: Abstract Conclusion: P-glycoprotein is abundantly expressed in certain parotid mucoepidermoid carcinoma tissues, known historically to be multidrug resistant. This discovery may be important in incrementally advancing our ability to develop alternative pharmacologic strategies to improve multi-modality tumor control. OBJECTIVE: P-glycoprotein plays a functional role in promoting the efflux of drug metabolites in certain malignant tumors. With this understanding we immunohistochemically investigated the expression of P-glycoprotein in parotid mucoepidermoid carcinoma tissues and examined prognostic factors that contribute to the treatment of parotid cancer. METHODS: Thirteen patients with mucoepidermoid carcinoma of the parotid gland were included. P-glycoprotein expression was immunohistochemically investigated by a modified avidin-biotin-peroxidase complex method using four different antibodies. RESULTS: P-glycoprotein expression was observed in a higher percentage of patients with higher grade malignancy. The tumor size-related difference in P-glycoprotein expression was only significant for staining with one antibody, and no significant differences were observed with or without induction chemotherapy.

Assessment of human papilloma virus infection in adult laryngeal papilloma using a screening test.

OBJECTIVES: Human papilloma virus (HPV) infection is involved in both juvenile and adult laryngeal papilloma. We wished to determine which types of adult laryngeal papilloma were clinically related to HPV infection. We hypothesized that multiple-site and recurrent papillomas would have a strong relationship to HPV and conducted the present study to test this hypothesis. METHODS: Thirteen male patients with adult laryngeal papilloma who underwent resection of papilloma between August 2006 and September 2009 were studied. We examined the relationships between whether the tumor was solitary or multiple, presence or absence of recurrence after surgery, and HPV infection. High-risk HPV types (HPV-DNA types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) and low-risk HPV types (6, 11, 42, 43, and 44) were tested by a liquid-phase hybridization method. In addition, HPV typing was performed for patients positive for low-risk HPV types. Twenty patients with laryngeal carcinoma or laryngeal leukoplakia were enrolled as the control group. RESULTS: In the laryngeal papilloma group, all patients tested were negative for high-risk HPV and 69.2% were positive for low-risk HPV. Typing performed for seven of the patients who tested positive for low-risk HPV showed that one patient was positive for HPV-11, whereas the remaining six patients were positive for HPV-6. All patients with recurrent laryngeal papillomatosis (RLP) were positive for low-risk HPV. All patients who were positive for low-risk HPV had RLP. Tumor samples from repeat operations were positive for low-risk HPV in all patients tested. HPV was not detected in the control group. CONCLUSIONS: The relationship between RLP and low-risk HPV was strong, with all cases that were positive for low-risk HPV showing recurrence. Tumor tissue resected at the time of repeat surgery was positive for low-risk HPV in all cases tested.

Long-term follow-up and salvage surgery in patients with T2N0M0 squamous cell carcinoma of the glottic larynx following concurrent chemoradiation therapy with cisplatin and 5-fluorouracil for laryngeal preservation.

CONCLUSION: Patients who received concurrent chemoradiation therapy or radiation therapy alone were followed over a long term. The complete response (CR), 10-year survival, and 10-year larynx preservation rates were 87.5%, 95.3%, and 75.1%, respectively. Statistically, concurrent chemoradiation therapy contributes to laryngeal preservation but not to the survival rate. OBJECTIVE: To determine the additive and synergistic effects of anticancer chemotherapy combined with chemoradiation therapy for squamous cell carcinoma (SCC) of the glottic larynx. METHODS: Eighty-nine patients with untreated T2N0M0 SCC of the glottic larynx were included. Thirty-two patients received treatment cycles consisting of intravenous cisplatin (CDDP) on day 1 (80 mg/m(2)) and intravenous 5-fluorouracil (5-FU) over 120 h on days 2-6 (600 mg/m(2)/day) every 4 weeks. Radiotherapy was delivered by a 4 MV linac X-ray machine at a dose of 66 Gy. Fifty-seven patients received radiotherapy alone. RESULTS: After chemoradiation therapy, the overall response, CR, 10-year survival, and 10-year larynx preservation rates were 100%, 87.5%, 95.3%, and 75.1%, respectively. Side effects included leukopenia, neutropenia, mucositis, and dermatitis. Seven patients (21.9%) required salvage surgery. Pathological findings confirmed that the treatment regimen caused marked cancer tissue degeneration. Histologic examination of surgical specimens suggested that the safety margin for partial laryngectomy was 4 mm from the gross tumor.

Concurrent chemoradiation therapy with docetaxel (DOC) for laryngeal preservation in T2N0M0 glottic squamous cell carcinomas.

CONCLUSION: Concurrent chemoradiation therapy with docetaxel (DOC) at a dose of 10 mg/m(2) twice a week contributed to laryngeal preservation. OBJECTIVE: To determine laryngeal preservation following concurrent chemoradiation therapy with DOC. METHODS: A total of 141 patients with untreated T2N0M0 squamous cell carcinoma of the glottic larynx were included in the study. The treatments were either radiation therapy alone or DOC intravenously administered at a dose of 10 mg/m(2) once or twice a week during radiotherapy with 4 MV linac X-ray (total of 66 Gy for 33 days). RESULTS: The response and CR rates were 100% and 90.5% in the once-weekly combination group, and 100% and 97.6% in the twice-weekly combination group, respectively. The 5-year survival rates were 76.8% in the once-weekly combination group and 96.8% in the twice-weekly combination group. The 5-year laryngeal preservation rates were 83.8% in the once-weekly combination group and 97.6% in the twice-weekly combination group. The most common side effects were mucositis, dermatitis, and alopecia. The patients who received DOC twice a week showed more severe cancer tissue degeneration, and pathological examination of serial sections indicated that the safety margin for partial laryngectomy was considered to be 3 mm from the gross tumor with good glottal closure.