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1.
Oncotarget ; 9(27): 18970-18984, 2018 Apr 10.
Article in English | MEDLINE | ID: mdl-29721176

ABSTRACT

BACKGROUND: Febrile neutropenia (FN) is the most serious hematologic toxicity of systemic chemotherapy. However, accurate prediction of FN development has been difficult because the risk varies largely depending on the chemotherapy regimen and various individual factors. METHODS: We retrospectively analyzed diverse clinical factors including pretreatment hematological parameters to clarify the reliable predictors of FN development during chemotherapy with a docetaxel, cisplatin, and fluorouracil (TPF) regimen in patients with head and neck squamous cell carcinoma. RESULTS: Among the 50 patients, grade ≥3 neutropenia, grade 4 neutropenia, and FN developed in 36 (72%), 21 (42%), and 12 (24%) patients, respectively. Multivariate logistic regression revealed that a pretreatment absolute monocyte count (AMC) <370/mm3 is an independent predictor of TPF chemotherapy-induced FN (odds ratio=6.000, p=0.017). The predictive performance of the model combining AMC and absolute neutrophil count (ANC), in which the high-risk group was defined as having an AMC <370/mm3 and/or ANC <3500/mm3, was superior (area under the curve [AUC]=0.745) to that of the model with a cutoff for AMC alone (AUC=0.679). CONCLUSIONS: On the basis of our results, we recommend primary prophylactic use of granulocyte colony-stimulating factor and/or antibiotics selectively for patients predicted to be at high risk for TPF chemotherapy-induced FN.

2.
Auris Nasus Larynx ; 45(5): 1130-1134, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29753583

ABSTRACT

Pyoderma gangrenosum is a rare ulcerative condition associated with various systemic diseases. Lesions on the lower extremities and the trunk are common, but lesions on the nose are rare. Here we report a case of pyoderma gangrenosum on the nose. A 33-year-old woman presented with fever, nasal obstruction, and painful swelling on the nasal bridge. Physical examination revealed swellings on the nasal septal mucosa bilaterally. Computed tomography showed a septal abscess and a subcutaneous abscess on the nasal bridge. The lesions worsened despite treatment with intravenous antibiotics and abscess drainage. Meanwhile, the patient also complained of bloody stools and was diagnosed with ulcerative colitis. Therefore, pyoderma gangrenosum on the nose was suspected, and was diagnosed by exclusion of other diseases. Treatment with systemic corticosteroids was started and the nasal lesions improved rapidly. However, saddle nose deformity occurred. A review of the literature reveals that pyoderma gangrenosum on the nose can cause ulcerations, septal abscess, and sinusitis. Further, there is a high likelihood of nasal complications, including saddle nose deformity, septal perforation, and skin defects. Pyoderma gangrenosum should be included in the differential diagnosis when nasal ulceration, abscesses, and sinusitis do not improve with antibiotics and drainage.


Subject(s)
Abscess/diagnostic imaging , Nasal Septum/diagnostic imaging , Nose Diseases/diagnosis , Pyoderma Gangrenosum/diagnosis , Abscess/therapy , Adrenal Cortex Hormones/therapeutic use , Adult , Anti-Bacterial Agents/therapeutic use , Colitis, Ulcerative/complications , Disease Progression , Drainage , Female , Humans , Nose Diseases/complications , Nose Diseases/therapy , Pyoderma Gangrenosum/complications , Pyoderma Gangrenosum/therapy , Tomography, X-Ray Computed
3.
Appl Biochem Biotechnol ; 168(6): 1672-80, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22961352

ABSTRACT

Due to the complex mechanisms involved in butanol-induced stress response, butanol tolerance phenotype is difficult to engineer even in microorganisms with well-defined genetic backgrounds. We therefore aimed to isolate butanol-tolerant microorganisms from environmental samples as potential alternative hosts for butanol production. Soil samples collected were subjected to butanol stress. A microbial strain capable of 2.5-3 % (w/v) butanol tolerance was isolated and identified as Enterococcus faecium by 16S rDNA analysis. The isolate grew readily under both aerobic and anaerobic conditions and was capable of producing butanol anaerobically. In comparison with the obligate anaerobe Clostridium acetobutylicum, the growth under both aerobic and anaerobic conditions of the isolated strain, together with no detection of butyrate and lack of two-phase fermentation suggests different metabolic networks from the obligate anaerobe C. acetobutylicum. Under anaerobic condition, butanol reached up to 0.4 gl(-1) in a batch culture without heterologous introduction of butanol biosynthetic pathway. Besides butanol tolerance, the isolated E. faecium IB1 showed high tolerance to 10 % (w/v) ethanol and 3 % (w/v) isobutanol. With distinct features including high butanol tolerance and natural butanol production, the isolated E. faecium IB1 with minimum metabolic engineering can be explored as a potential host for butanol production.


Subject(s)
Butanols/metabolism , Enterococcus faecium/isolation & purification , Enterococcus faecium/metabolism , Soil Microbiology , Enterococcus faecium/genetics , Fermentation , Metabolic Networks and Pathways , Molecular Sequence Data
4.
Gan To Kagaku Ryoho ; 39(9): 1375-8, 2012 Sep.
Article in Japanese | MEDLINE | ID: mdl-22996772

ABSTRACT

Hair loss is one of the most common side effects of chemotherapies such as FEC and taxane, and it greatly affects quality of life. We conducted a questionnaire survey of breast cancer patients who were treated with adjuvant chemotherapy about their hair loss. Eighty-five patients participated. They all had lost their hair and suffered from persistent changes in their hair condition, ranging from thinning to curly. More than 80% of patients had worn wigs until their hair had grown back. Furthermore, a few patients did not remove their wigs for 2 years after treatment. Unfortunately, there is no prevention or medication to combat hair loss due to chemotherapy at present, so cumulative examinations are awaited. We must provide appropriate information and support to the patient.


Subject(s)
Alopecia/chemically induced , Antineoplastic Agents/adverse effects , Breast Neoplasms/drug therapy , Hair/anatomy & histology , Surveys and Questionnaires , Adult , Alopecia/psychology , Antineoplastic Agents/therapeutic use , Breast Neoplasms/psychology , Female , Humans , Male , Middle Aged , Quality of Life
5.
Gan To Kagaku Ryoho ; 37(2): 255-8, 2010 Feb.
Article in Japanese | MEDLINE | ID: mdl-20154480

ABSTRACT

From results of ACTS-GC,postoperative adjuvant chemotherapy,administration of S-1 for one year has become the standard for gastric cancer of Stage II and III except T1. We inspected problems of adjuvant chemotherapy by S-1 by dose rate, an adverse event,and compliance. For the period from July 2006 to December 2008,among 41 cases of stage II/stage III gastric cancer, S-1 was as started as adjuvant therapy by for 28 cases (68.3%). Among 14 cases (63.6%) considered able to complete S-1 treatment for one year, 7 cases (31.8%) had to have their dose reduced or their administration schedule changed. No adverse event of grade 3/4 was found, but cancellation or reduced dose was necessary due to anorexia, malaise, diarrhea, severe skin reaction, and leukopenia resulting from myelosuppression. Thirteen patients took no S-1, and two (4.9%) of them took UFT, while 11 cases (26.8%) became a no-treatment follow-up group for reasons of age, coexisting symptoms and other reasons. The problem in the future is to improve compliance, and to establish a treatment strategy for patients who do not meet administration criteria and for patients for whom continuation of drug administration is impossible.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Oxonic Acid/adverse effects , Stomach Neoplasms/drug therapy , Tegafur/adverse effects , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant/adverse effects , Drug Combinations , Female , Humans , Male , Middle Aged , Neoplasm Staging , Oxonic Acid/therapeutic use , Recurrence , Stomach Neoplasms/pathology , Tegafur/therapeutic use
6.
FEMS Microbiol Lett ; 299(1): 95-9, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19686341

ABSTRACT

A vanillin-tolerant strain of Saccharomyces cerevisiae was screened and its intracellular ergosterol levels were compared with several laboratory yeast strains to study the potential relationship between ergosterol content and vanillin tolerance. Saccharomyces cerevisiae NBRC1950 was selected as a vanillin-tolerant strain. Its ergosterol content was higher than those of the laboratory strains. The results of DNA microarray and quantitative reverse transcriptase-polymerase chain reaction analysis showed that five genes involved in ergosterol biosynthesis (ERG28, HMG1, MCR1, ERG5, and ERG7) were upregulated in NBRC 1950 compared with strain X2180, suggesting that high expression of genes involved in ergosterol biosynthesis may cause high ergosterol content in strain NBRC 1950. The S. cerevisiae HX strain, which was a high-ergosterol-containing strain derived from X2180, was more tolerant to vanillin than the parental strain, suggesting that high ergosterol content may, in part, be responsible for vanillin tolerance. These findings provide a biotechnological basis for the molecular engineering of S. cerevisiae with increased tolerance to vanillin.


Subject(s)
Benzaldehydes/pharmacology , Ergosterol/biosynthesis , Ethanol/metabolism , Fermentation , Saccharomyces cerevisiae/metabolism , Gene Expression Regulation, Fungal , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism
7.
J Antibiot (Tokyo) ; 62(5): 277-82, 2009 May.
Article in English | MEDLINE | ID: mdl-19329983

ABSTRACT

In situ click chemistry is a target-guided synthesis technique for discovering potent protein ligands by assembling azides and alkynes into triazoles inside the affinity site of a target protein. We report the rapid discovery of a new and potent inhibitor of bacterial chitinases by the use of in situ click chemistry. We observed a target-templated formation of a potent triazole inhibitor of the chitinase-catalyzed chitin hydrolysis, through in situ click chemistry between a biologically active azide-containing scaffold and structurally unrelated alkyne fragments. Chitinase inhibitors have chemotherapeutic potential as fungicides, pesticides and antiasthmatics. Argifin, which has been isolated and characterized as a cyclopentapeptide natural product by our research group, shows strong inhibitory activity against chitinases. As a result of our efforts at developing a chitinase inhibitor from an azide-bearing argifin fragment and the application of the chitinase template and a library of alkynes, we rapidly obtained a very potent and new 1,5-disubstituted triazole inhibitor against Serratia marcescens chitinase (SmChi) B. The new inhibitor expressed 300-fold increase in the inhibitory activity against SmChiB compared with that of argifin. To the best of our knowledge, our finding of an enzyme-made 1,5-disubstituted triazole, using in situ click chemistry is the second example reported in the literature.


Subject(s)
Chitinases/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Peptides, Cyclic/chemistry , Azides/chemical synthesis , Cyclization , Drug Evaluation, Preclinical , Enzyme Inhibitors/chemical synthesis , Mass Spectrometry , Reverse Transcriptase Polymerase Chain Reaction , Spectrophotometry, Infrared , Triazoles/chemical synthesis , Triazoles/pharmacology
8.
Biotechnol Biofuels ; 1(1): 3, 2008 Apr 15.
Article in English | MEDLINE | ID: mdl-18471310

ABSTRACT

BACKGROUND: Lignocellulosic materials are abundant and among the most important potential sources for bioethanol production. Although the pretreatment of lignocellulose is necessary for efficient saccharification and fermentation, numerous by-products, including furan derivatives, weak acids, and phenolic compounds, are generated in the pretreatment step. Many of these components inhibit the growth and fermentation of yeast. In particular, vanillin is one of the most effective inhibitors in lignocellulose hydrolysates because it inhibits fermentation at very low concentrations. To identify the genes required for tolerance to vanillin, we screened a set of diploid yeast deletion mutants, which are powerful tools for clarifying the function of particular genes. RESULTS: Seventy-six deletion mutants were identified as vanillin-sensitive mutants. The numerous deleted genes in the vanillin-sensitive mutants were classified under the functional categories for 'chromatin remodeling' and 'vesicle transport', suggesting that these functions are important for vanillin tolerance. The cross-sensitivity of the vanillin-sensitive mutants to furan derivatives, weak acids, and phenolic compounds was also examined. Genes for ergosterol biosynthesis were required for tolerance to all inhibitory compounds tested, suggesting that ergosterol is a key component of tolerance to various inhibitors. CONCLUSION: Our analysis predicts that vanillin tolerance in Saccharomyces cerevisiae is affected by various complicated processes that take place on both the molecular and the cellular level. In addition, the ergosterol biosynthetic process is important for achieving a tolerance to various inhibitors. Our findings provide a biotechnological basis for the molecular engineering as well as for screening of more robust yeast strains that may potentially be useful in bioethanol fermentation.

9.
Gan To Kagaku Ryoho ; 35(3): 467-70, 2008 Mar.
Article in Japanese | MEDLINE | ID: mdl-18347396

ABSTRACT

PURPOSE: The purpose was to investigate side effects of FEC100 treatment, particularly bone marrow suppression, nausea and vomiting. PATIENTS AND METHODS: We investigated side effects of FEC100 at the time of initial administration in 49 breast cancer patients (including 3 with recurrence). We used a 5-HT3 receptor antagonist as an antiemetic agent, steroids and Haloperidol, an antidopamine agent. Antibiotics were also administered for five days from day 10. RESULTS: The mean nadir of white blood cell count was 1,492+/-575 microL, and the mean day on which the nadir was reached was the 13.0+/-1.45th day. Leukopenia of less than 1,000 microL (grade 4) was seen in 8 (16.3%) of the 49 patients, and the incidence of leukopenia was particularly high (3/6, 50%) in patients with multiple bone metastases. Febrile neutropenia occurred in 4 (8.1%) of the 49 patients, 2 of those 4 patients having multiple bone metastasis. Fifteen (30.6%) of the 49 patients had nausea, and 3 patients (6.1%) had vomiting. CONCLUSION: The results indicate that side effects of FEC100 treatment are tolerable. However, care is needed for patients with multiple bone metastases because of the strong bone marrow suppression in such patients.


Subject(s)
Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cyclophosphamide/adverse effects , Epirubicin/adverse effects , Fluorouracil/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Cyclophosphamide/therapeutic use , Epirubicin/therapeutic use , Fluorouracil/therapeutic use , Humans , Neoplasm Staging
10.
Biosci Biotechnol Biochem ; 71(4): 1073-7, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17420574

ABSTRACT

We investigated GroEL substrates from Bacillus subtilis 168 using the single-ring mutant of B. subtilis GroEL. We identified 28 candidates for GroEL substrates, of which Spo0B, Ald, Eno, SpoIIP, and FbaA were involved in spore formation, and Rnc, Tuf, Eno, Tsf, and FbaA were essential for B. subtilis growth. As observed at the protein level, the amount of SpoIIP interaction with GroEL increased at 3 h after initiation of sporulation.


Subject(s)
Bacillus subtilis/metabolism , Chaperonin 60/metabolism , Spores, Bacterial/physiology , Amino Acid Substitution , Bacillus subtilis/genetics , Chaperonin 60/genetics , DNA Fragmentation , Electrophoresis, Polyacrylamide Gel , Hydrogen-Ion Concentration , Molecular Weight
11.
Biosci Biotechnol Biochem ; 70(10): 2357-62, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17031040

ABSTRACT

We investigated a temperature adaptation of Bacillus subtilis 168 in which chromosomal groEL was replaced with a psychrophilic groEL. This strain can grow at 50 degrees C but not at 51 degrees C, a temperature at which wild-type B. subtilis can grow. Using in vivo random mutagenesis by the B. subtilis mutator strain (mutS, mutM, mutY), two thermo-adaptants were isolated from the groEL substituted strain at 52 degrees C. They contained novel amino acid alterations in their ATP binding motif (T93I) and the inter-monomer contact (R285H) region of GroEL. These results suggest that GroEL participates in bacterial temperature adaptation.


Subject(s)
Adaptation, Physiological/genetics , Bacillus subtilis/physiology , Chaperonin 60/physiology , Temperature , Adenosine Triphosphate/metabolism , Amino Acid Substitution , Bacillus subtilis/genetics , Binding Sites/genetics , Chaperonin 60/genetics , Mutagenesis , Selection, Genetic
12.
Cytokine ; 33(1): 28-35, 2006 Jan 07.
Article in English | MEDLINE | ID: mdl-16413198

ABSTRACT

AIM: Suramin is a symmetrical polysulfonated naphthylamine derivative of urea. There have been few studies on the effect of suramin on cytokines. We examined the effects of suramin on production of inflammatory cytokines. METHODS: We made an acute liver injury model treated with d-galactosamine (GalN) and lipopolysaccharide (LPS). Plasma AST, ALT, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 levels were measured. We compared with survival rate, histological found and NF-kappaB activity between with and without treatment of suramin. In macrophage like cell line, TNF-alpha and IL-6 production, TNF-alpha and IL-6 mRNA expression, and NF-kappaB activity was measured. RESULTS: The lethality of mice administered suramin with GalN/LPS was significantly decreased compared with that in mice without suramin. Changes of hepatic necrosis and apoptosis were slight in suramin-treated mice. Serum AST, ALT, TNF-alpha, IL-6 levels and NF-kappaB activity in the liver were significantly lower in mice administered suramin. In an in vitro model, suramin preincubation inhibited TNF-alpha and IL-6 production, TNF-alpha and IL-6 mRNA expression, and NF-kappaB activity. CONCLUSIONS: Suramin inhibits TNF-alpha and IL-6 production through the suppression of NF-kappaB activity from macrophages and shows therapeutic effects on acute liver damage.


Subject(s)
Cytokines/metabolism , Liver Failure, Acute/prevention & control , NF-kappa B/metabolism , Suramin/pharmacology , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Cell Line , Galactosamine , Interleukin-6/metabolism , Lipopolysaccharides , Liver/pathology , Liver Failure, Acute/chemically induced , Liver Failure, Acute/mortality , Male , Mice , Mice, Inbred C57BL , Survival Rate , Tumor Necrosis Factor-alpha/metabolism
13.
Hepatol Res ; 33(4): 298-305, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16297660

ABSTRACT

Genipin is a metabolite derived from the herbal medicine Inchinko-to. Little is known about the mechanism of genipin action on acute liver injury through inflammatory cytokines. We examined the effects of genipin on production of TNF-alpha in vivo and in vitro. Mice were given GalN/LPS with or without genipin treatment. All mice not given genipin died within 12h. But in mice given genipin, 8 of 15 mice survived for 24h after GalN/LPS administration. Histologically, hepatic necrosis and inflammatory cells infiltration were significantly slight in mice given genipin. Serum AST and ALT activity were significantly lower in mice given genipin. Serum and liver homogenate TNF-alpha levels were significantly lower in mice given genipin. However, in IL-6 and IL-1beta, there were no significant differences in mice given and not given genipin. TNF-alpha, NF-kappaB activation and TNF-alpha mRNA expression in a cultured mouse macrophage-like cell line J774.1 were significantly suppressed by genipin administration. In conclusion, the present findings suggest that genipin, a metabolite derived form the herbal medicine Inchinko-to improved acute liver dysfunction by suppressive effect of TNF-alpha production.

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