Comparison between three age-stratified cohorts reveals poor prognosis of young patients with tongue carcinoma.

Objectives: Investigation of the prognosis of young patients with tongue carcinoma has been the focus of several recent studies aimed at improving future precision treatment. Most studies have been two-cohort investigations comparing young and older patients, who have wide discrepancies in prognosis. Older patients, especially those aged >70 years, often have a poor general condition. This affects the prognosis of the older cohort and accounts for the discrepancies observed in two-cohort studies. Accordingly, in this study, older patients (aged ≥71 years) were separated and compared to young and middle-aged patients. Methods: A total of 257 patients with oral tongue carcinoma referred during 2011-2017 were analyzed. Patients were sorted into young (aged ≤40 years), middle-aged (aged ≥41 and ≤70 years), and older (aged ≥71 years) groups. Overall survival (OS) and disease-free survival (DFS) were compared among the groups. Furthermore, patterns of recurrence rates were compared. Results: Compared with young patients, there was no difference in OS or DFS for older patients (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.5-2.7 and HR: 0.7, 95% CI: 0.4-1.2, respectively) in a multivariate analysis. There was also no difference in OS (HR: 0.6, 95% CI: 0.3-1.3) for middle-aged patients. However, middle-aged patients had low recurrence rates (HR: 0.5, 95% CI: 0.3-0.8). With respect to the recurrence type, middle-aged patients had a low local recurrence rate (HR: 0.3, 95% CI: 0.1-0.7). Conclusion: Three-cohort studies should be conducted to evaluate whether the prognosis of young patients with tongue carcinoma is truly poor in terms of future precision treatment.

[A case of amyotrophic lateral sclerosis presenting with rapid progression of respiratory deterioration due to severe obesity].

A 55-year-old woman with extreme obesity presenting with limb weakness since 1 year was diagnosed with amyotrophic lateral sclerosis (ALS) based on clinical findings and needle electromyography. She had a habit of overeating, and her body mass index (BMI) was 38.2. MRI showed an enlargement of the right central cerebral sulcus, and N-isopropyl-p-[|123I]-iodoamphetamine single-photon emission computed tomography demonstrated reduced blood flow predominantly in the right frontal lobes, suggesting overlapping frontotemporal dementia (FTD). She maintained adequate dietary intake, and her BMI was stable at 38.2 until 3 months after diagnosis. However, over the next 2 months, her dietary intake decreased owing to pronounced bulbar palsy and BMI decreased to 34.5. At this point, forced vital capacity decreased from 69.3% to 39.0%, while forced expiratory volume in 1 second decreased from 75.3% to 47.7%. Consequently, noninvasive ventilation at night was initiated, followed by tracheostomy invasive ventilation at the emergency department after 2 months. We assume that the frontotemporal lobar degeneration pathology progressed to the frontal lobe and hypothalamus over time, which increased the patient's excessive appetite and body weight. Her obesity reduced the compliance of the thorax and increased the workload of the respiratory muscles, resulting in rapid respiratory deterioration. Additionally, the extensive neurodegeneration, extending to the area other than the primary motor cortex, might have played a pivotal role in rapid ALS progression. High-calorie nutritional management is generally recommended in patients with ALS. Although the prognosis of patients with ALS having BMI under 27 can be improved via high calorie intake and BMI maintenance, the nutritional management strategy for patients with ALS and high obesity (BMI ≥ 35) remains unclear. Through this case we emphasize that in patients with ALS and FTD excessive appetite and obesity can lead to rapid respiratory deterioration, and therefore, prudent calorie management is recommended.

Prognostic Factors of Potential Early Recurrence of Hypopharyngeal Carcinoma.

BACKGROUND/AIM: Prognostic factors of hypopharyngeal carcinoma have been reported previously. However, recurrent cases of this disease occurring within 6 months of treatment have been excluded or poorly documented in many studies. We aimed to evaluate the prognostic factors of hypopharyngeal carcinoma recurrence within 6 months. PATIENTS AND METHODS: A total of 120 patients were eligible for this retrospective study. Recurrent cases of hypopharyngeal carcinoma occurring within 6 months of treatment were evaluated and compared with non-recurrent cases. RESULTS: Recurrence within 6 months was detected in 28/50 cases. In univariate analyses, classification markers (pT≥4a and cN≥2b) were statistically significant prognostic factors for early recurrence (p=0.04 and p=0.04, respectively); however, only pT≥4a was predictive of recurrence in multivariate analyses (p=0.02). CONCLUSION: Risk stratification according to the prognostic factor pT≥4a will allow physicians to identify patients who should be followed meticulously within the first 6 months.

A case report of Kuttner tumor mimicking a malignant tumor, leading to overtreatment.

Preoperative diagnosis with multimodal approaches might lead to overtreatment. Cautious understanding of cytology and dynamic contrast-enhanced magnetic resonance imaging is required when a Kuttner tumor is cited as differential diagnosis.

Weekly Cetuximab and Paclitaxel for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: Head and neck cancers account for 8% of all cancer cases worldwide. However, identifying the optimal treatment for recurrent or metastatic head and neck cancer (R/MHNSCC) has been challenging. The aim of this study was to evaluate the efficacy, safety, and prognostic factors of the outcome of patients with R/MHNSCC who were treated with weekly cetuximab and paclitaxel (Cmab-PTX). PATIENTS AND METHODS: The records of R/MHNSCC patients who were treated with Cmab-PTX in our institution between June 2013 and September 2017 were collected. We analyzed Overall survival (OS), progression-free survival (PFS), prognostic factors and adverse events. RESULTS: The records of 59 patients treated with Cmab-PTX were analyzed. The median PFS was 5.7 months, and the median OS was 11.8 months. Patients who had been administered cetuximab previously had shorter PFS and OS than those who had not. CONCLUSION: Cmab-PTX may be considered as a treatment option in head and neck R/MHNSCC patients.

Electrochemical deposition of large-sized mesoporous nickel films using polymeric micelles.

Stable mesoporous nickel (Ni) films can be prepared using polystyrene-b-poly-(oxyethylene) (PS-b-PEO) micelles as sacrificial templates. In this method, positively charged Ni precursors form hydrogen bonds with the PEO segments of the micelles, which are then co-electrodeposited on the surface of a working electrode. Changing the applied voltage during electrodeposition modifies the deposition rate and ultimately controls the architecture of the mesoporous Ni film.

Nafion®-coated mesoporous Pd film toward remarkably enhanced detection of lactic acid.

Mesoporous metal films can detect biomarkers with high sensitivity. Further coating the mesoporous metal with polymers enhances sensing selectivity by favoring specific biomarkers against other interferents. In the present study, we report the fabrication of a Nafion®-coated mesoporous Pd film to filtrate interferents present in sweat during non-invasive biosensing. By using a Nafion®-coated mesoporous Pd film, lactic acid, a metabolite present in sweat, can be successfully detected with high sensitivity.

Fabrication of Mesoporous Cu Films on Cu Foils and Their Applications to Dopamine Sensing.

We previously succeeded to prepare stable mesoporous Cu films on Au-coated conductive working electrodes by using polystyrene-b-poly(oxyethylene) (PS63 000 -b-PEO26 000 ) micelles as template and sulfuric acid to increase ionic conductivity. In the present study, we report the preparation of mesoporous Cu films on Cu foil. By changing the Cu salts and electrodeposition potentials, we discuss how these parameters influence the final product. Without having to filtrate interefering species, such as uric acid, ascorbic acid and glucose, the dopamine concentration can be precisely determined by applying a suitable potential. Therefore, non-invasive electrochemical sensing based on mesoporous films will be useful for daily diagnosis of mental disorder.

Use of a glass bead-containing liquid medium for efficient production of a soil-free culture with polychlorinated biphenyl-dechlorination activity.

We established a soil-free culture capable of dechlorinating polychlorinated biphenyls (PCBs) in Kanechlor-300 and Kanechlor-400 by establishing a PCB-dechlorinating soil culture in liquid medium containing 0.5 mm glass beads. PCB-dechlorination activity in liquid cultures with glass beads appeared to depend on the size of the glass beads, and soil-free cultures with 0.05-, 1.0- or 2.0 mm glass beads did not dechlorinate PCBs. Soil-free culture without glass beads also failed to dechlorinate PCBs. The soil-free culture containing 0.5 mm glass beads dechlorinated 42.6 ± 12.0 mol% in total PCBs. This soil-free culture was more effective than soil culture for dechlorinating PCBs ranging from dichlorinated PCBs to tetrachlorinated PCBs. Clone analysis of the 16S rRNA gene sequences showed that one of the predominant groups of microorganisms in the soil-free culture comprised heat-tolerant and spore-forming bacteria from the phylum Firmicutes. Heat treatment (100 °C, 10 min) did not destroy the PCB-dechlorination activity of the soil-free culture with glass beads. These results suggest that unknown species of the phylum Firmicutes were involved in PCB dechlorination in the soil-free culture. In this study, we succeeded in using a liquid medium containing glass beads as an inorganic soil substitute and showed that such a medium enhances PCB-dechlorination activity. Our study provides valuable information for developing PCB-bioremediation techniques using dechlorinating bacteria in anoxic contaminated soils and sediments.

Effect of magnetite nanoparticles on living rate of MCF-7 human breast cancer cells.

Superparamagnetic and ferromagnetic magnetite nanoparticles, with diameters of approximately 13 and 44 nm, respectively, were synthesized and their uptake amount and heating efficiency were evaluated for application to magnetic hyperthermia. Both nanoparticles had almost the same zeta-potential (+10.2 mV) and hydrodynamic size (∼1 µm) and there was no significant difference in their uptake amount 18 h after they were added to the medium. After internalization, the ferromagnetic nanoparticles incorporated in human breast cancer cells (MCF-7) showed a higher heating efficiency than the superparamagnetic nanoparticles when an external magnetic field (4 kW, 250 kHz) high enough to produce heat by hysteresis loss was applied, followed by cellular death of MCF-7 with high ferromagnetic nanoparticle content.

Liposomal polyamine-dialkyl phosphate conjugates as effective gene carriers: chemical structure, morphology, and gene transfer activity.

Synthetic cationic lipids are promising transfection agents for gene therapy. We report here that polyamine conjugates of dialkyl phosphates, combined with natural lipids and assembled in the form of liposomes (polycationic liposome: PCL), possess high transfection activity in the COS-1 cell line. Furthermore, we describe the functional morphology of the PCL/DNA complexes as revealed by atomic force microscopy (AFM). The conjugates were synthesized from dialkyl phosphates (with alkyl chain lengths of 12, 14, or 16 carbons) by reaction with the polyamine molecules, spermidine, spermine, or polyethylenimine (PEI(1800)). [Dewa, T., et al. Bioconjugate Chem. 2004, 15, 824]. The PCL composed of the spermidine and C16 conjugate combined with phospholipid and cholesterol (conjugate/phospholipid/cholesterol = 1/1/1 as a molar ratio) exhibited 3.6 times higher activity than that of a popular commercial product. Systematic tests revealed clear correlations of the transgene activity with physical properties of the polyamine, in particular, that longer alkyl chains and the lower molecular weight polyamines (spermidine, spermine) favor high efficacy at the higher nitrogen/phosphate ratio = 24 (N/P, stoichiometric ratio of nitrogen in the conjugate to phosphate in DNA). The low molecular weight polyamine-based PCLs, which formed 150-400 nm particles with plasmid DNA (lipoplexes), exhibited approximately 3-fold higher gene transfer activity than micellar aggregates (lacking phospholipid and cholesterol) of the corresponding conjugate. In contrast, the PEI-based PCL formed large aggregates (approximately 1 microm), that, like the micellar aggregate form, had low activity. Activity of the low molecular weight polyamine-based PCLs increased linearly with the N/P of the lipoplex up to N/P = 24. Formation of lipoplexes was examined by agarose gel electrophoresis, dynamic light scattering (DLS), and AFM. At the lower N/P = 5, large aggregates of complex (approximately 1 microm), in which DNA molecules were loosely packed, were observed. At higher N/P, lipoplexes were converted into smaller particles (150-400 nm) having a lamellar structure, in which DNA molecules were tightly packed. Such morphological features of the lipoplex correlate with the dependence of transfection on the N/P in that the lamellar structures gave superior transfection. AFM also indicated that the lipoplexes disassembled significantly, releasing DNA, when the lipoplexes were exposed to acidic conditions (pH 4). The significance for transfection activity of the metamorphosis of bilayer lipoplexes is discussed relative to that of the less active micellar aggregate form, which is unresponsive to pH change.

A novel Dehalobacter species is involved in extensive 4,5,6,7-tetrachlorophthalide dechlorination.

The purpose of this study was the enrichment and phylogenetic identification of bacteria that dechlorinate 4,5,6,7-tetrachlorophthalide (commercially designated "fthalide"), an effective fungicide for rice blast disease. Sequential transfer culture of a paddy soil with lactate and fthalide produced a soil-free enrichment culture (designated the "KFL culture") that dechlorinated fthalide by using hydrogen, which is produced from lactate. Phylogenetic analysis based on 16S rRNA genes revealed the dominance of two novel phylotypes of the genus Dehalobacter (FTH1 and FTH2) in the KFL culture. FTH1 and FTH2 disappeared during culture transfer in medium without fthalide and increased in abundance with the dechlorination of fthalide, indicating their growth dependence on the dechlorination of fthalide. Dehalobacter restrictus TEA is their closest relative, with 97.5% and 97.3% 16S rRNA gene similarities to FTH1 and FTH2, respectively.

Reductive Dechlorination of Polychlorinated Biphenyls and Dibenzo-p-Dioxins in an Enrichment Culture Containing Dehalobacter Species.

The dechlorination of polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins was examined in an enrichment culture (KFL culture) that contained two phylotypes of Dehalobacter, FTH1 and FTH2. The KFL culture dechlorinated 2,3,4,5-tetrachlorobiphenyl, 2,3,4-trichorobiphenyl (2,3,4-TriCB), and 1,2,3-trichlorodibenzo-p-dioxin (1,2,3-TriCDD). Quantitative real-time PCR targeting FTH1 and FTH2 revealed significant increases with the addition of PCBs and 1,2,3-TriCDD, suggesting halorespiring growth of the Dehalobacter species in the KFL culture. This study demonstrated the reductive dechlorination of PCBs and 1,2,3-TriCDD by Dehalobacter species in a sediment-free culture and a novel dechlorination pathway, the conversion of 2,3,4-TriCB to 4-monochlorobiphenyl via 3,4-dichlorobiphenyl.

Anaerobic biodegradation of biphenyl in various paddy soils and river sediment.

The anaerobic degradation of biphenyl was investigated in four uncontaminated Japanese paddy soils and one river sediment sample contaminated with benzene and chlorinated aliphatics. Two of the paddy soils and the sediment were capable of degrading biphenyl anaerobically without any additional medium or electron acceptors. The half-lives of biphenyl biodegradation in the three samples were 212 d in the Kuridashi soil, 327 d in the Kamajima soil, and 429 d in the river sediment. The Kuridashi soil metabolized 1+/-0.3% of [U-14C]-biphenyl into CO2 and 5+/-2% into water-soluble metabolites after 45 d of incubation. Submerged conditions, which result in lower nitrate and iron oxide contents, and neutral pH, appeared to be the common properties among the samples that influenced their degradation capacities. The addition of 10mM sulfate and 20mM Fe(III) as electron acceptors did not enhance the biphenyl degradation rate, whereas 10mM nitrate completely inhibited biphenyl degradation. The addition of different electron donors (lactate, acetate, or pyruvate) slightly slowed the degradation. Molybdate (an inhibitor of sulfate-reducing bacteria) had an inhibitory effect on biphenyl biodegradation, but bromoethanesulfonic acid (an inhibitor of methanogens) did not. Most biphenyl degradation was observed when only water was added, with no other electron acceptors or donors. These results suggest that sulfate-reducing bacteria and fermentative microbial populations play important roles in anaerobic biphenyl biodegradation in paddy soil.

Effects of inhibitors on anaerobic microbial consortium with enhanced dechlorination activity in polychlorinated biphenyl mixture.

Characterization was carried out on the anaerobic microbial consortium with enhanced degradation activity toward polychlorinated biphenyls in Kanechlor-300 and Kanechlor-400 mixtures in a burnt soil (BS) culture. The addition of molybdate to the BS culture resulted in the accumulation of less-chlorinated biphenyls such as 4,4'-dichlorinated biphenyl and 2,3',4-trichlorinated biphenyl; however, no such accumulation occurred without molybdate supplementation. No significant effect was observed in individual congeners in the BS culture supplemented with 2-bromoethane sulfonic acid. Analyses involving both the polymerase chain reaction-denaturing gradient gel electrophoresis of partial 16S rRNA genes and respiratory quinones showed that the predominant microorganisms in the BS culture were anaerobic Firmicutes, while sulfate reducers of the phyla Deltaproteobacteria, Firmicutes and Chloroflexi were absent in the culture amended with the inhibitors. No positive correlation was observed between the dechlorination activity and a PCR-based detection of gene fragments of known dechlorinating bacteria. These results suggest that sulfate reducers played an important role in the enhanced anaerobic dechlorination of PCBs in the BS culture.

Enhanced anaerobic biodegradation of polychlorinated biphenyls in burnt soil culture.

Anaerobic microbial degradation of polychlorinated biphenyls (PCBs) in Kanechlors-300 and -400 was enhanced significantly by adding burnt soil originally obtained from an uncontaminated paddy soil to the microbial culture. The maximum PCB-degrading activity was 0.49 nmol-Cl/ml-culture/day (238 ng-total-PCBs/ml-culture/day), where the degradation was observed in most of the congeners in Kanechlors-300 and -400: not only in meta- and para-substituted congeners but also ortho-substituted congeners. The degradation of PCBs occurred during the increase in the microbial population with acetate as the main electron donor. The ratio between the consumption of electron donors and the dechlorination of PCBs was revealed to be 93.9 nmol-Cl/mmol-e-donor, which is also the dechlorination efficiency over 56 d of incubation. The addition of acetate and lactate several times into the culture rejuvenated the activity.

Electrotransformation of Clostridium paraputrificum M-21 with some plasmids.

Clostridium paraputrificum M-21 was transformed with several shuttle plasmids constructed for Clostridium acetobutylicum-Escherichia coli and Clostridium perfringens-E. coli by electroporation. The Clostridium stercorarium xylanase gene xyn10B was successfully expressed in C. paraputrificum M-21 and the expressed protein did not suffer from proteolysis by host protease(s). This system will provide us with a genetic tool for genetic and metabolic engineering of this bacterium.