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1.
J Microbiol Methods ; 219: 106898, 2024 04.
Article in English | MEDLINE | ID: mdl-38360297

ABSTRACT

Fluorinated solvents have been used as oxygen carriers in closed microbial cultures to sustain aerobic conditions. However, the growth-promoting effects of fluorinated solvents remain unclear. Therefore, this study aimed to elucidate the mechanism by which fluorinated solvents promote microbial growth and to explore alternative materials that can be easily isolated after culture. Escherichia coli and HFE-7200, a fluorinated solvent, were used to explore factors other than oxygen released by fluorinated solvents that promote microbial growth. E. coli growth was promoted in gas-permeable cultures, and HFE-7200 alleviated medium acidification. Gas chromatography confirmed that HFE-7200 functioned as a scavenger of carbon dioxide produced by E. coli metabolism. Because fluorinated solvents can dissolve various gases, they could scavenge metabolically produced toxic gases from microbial cultures. Furthermore, using polytetrafluoroethylene, a solid fluorine material, results in enhanced bacterial growth. Such solid materials can be easily isolated and reused for microbial culture, suggesting their potential as valuable technologies in food production and biotechnology.


Subject(s)
Carbon Dioxide , Escherichia coli , Fluorine/metabolism , Fluorine/pharmacology , Gases/metabolism , Gases/pharmacology , Solvents/pharmacology , Oxygen/metabolism
2.
J Gastroenterol ; 59(3): 263-278, 2024 03.
Article in English | MEDLINE | ID: mdl-38261000

ABSTRACT

BACKGROUND: We have previously reported apolipoprotein A2-isoforms (apoA2-is) as candidate plasma biomarkers for early-stage pancreatic cancer. The aim of this study was the clinical development of apoA2-is. METHODS: We established a new enzyme-linked immunosorbent sandwich assay for apoA2-is under the Japanese medical device Quality Management System requirements and performed in vitro diagnostic tests with prespecified end points using 2732 plasma samples. The clinical equivalence and significance of apoA2-is were compared with CA19-9. RESULTS: The point estimate of the area under the curve to distinguish between pancreatic cancer (n = 106) and healthy controls (n = 106) was higher for apoA2-ATQ/AT [0.879, 95% confidence interval (CI): 0.832-0.925] than for CA19-9 (0.849, 95% CI 0.793-0.905) and achieved the primary end point. The cutoff apoA2-ATQ/AT of 59.5 µg/mL was defined based on a specificity of 95% in 2000 healthy samples, and the reliability of specificities was confirmed in two independent healthy cohorts as 95.3% (n = 106, 95% CI 89.4-98.0%) and 95.8% (n = 400, 95% CI 93.3-97.3%). The sensitivities of apoA2-ATQ/AT for detecting both stage I (47.4%) and I/II (50%) pancreatic cancers were higher than those of CA19-9 (36.8% and 46.7%, respectively). The combination of apoA2-ATQ/AT (cutoff, 59.5 µg/mL) and CA19-9 (37 U/mL) increased the sensitivity for pancreatic cancer to 87.7% compared with 69.8% for CA19-9 alone. The clinical performance of apoA2-is was blindly confirmed by the National Cancer Institute Early Detection Research Network. CONCLUSIONS: The clinical performance of ApoA2-ATQ/AT as a blood biomarker is equivalent to or better than that of CA19-9.


Subject(s)
CA-19-9 Antigen , Pancreatic Neoplasms , Humans , Biomarkers, Tumor , Apolipoprotein A-II , Reproducibility of Results , Early Detection of Cancer , Pancreatic Neoplasms/diagnosis , Protein Isoforms
3.
Sci Rep ; 13(1): 3825, 2023 03 07.
Article in English | MEDLINE | ID: mdl-36882499

ABSTRACT

Multidrug-resistant tuberculosis (MDR-TB) is a major clinical problem. Because Mycobacterium, the causative agent of tuberculosis, are slow-growing bacteria, it takes 6-8 weeks to complete drug susceptibility testing, and this delay contributes to the development of MDR-TB. Real-time drug resistance monitoring technology would be effective for suppressing the development of MDR-TB. In the electromagnetic frequency from GHz to THz regions, the spectrum of the dielectric response of biological samples has a high dielectric constant owing to the relaxation of the orientation of the overwhelmingly contained water molecule network. By measuring the change in dielectric constant in this frequency band in a micro-liquid culture of Mycobacterium, the growth ability can be detected from the quantitative fluctuation of bulk water. The 65-GHz near-field sensor array enables a real-time assessment of the drug susceptibility and growth ability of Mycobacterium bovis (BCG). We propose the application of this technology as a potential new method for MDR-TB testing.


Subject(s)
Mycobacterium bovis , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Humans , Microbial Sensitivity Tests , Tuberculosis, Multidrug-Resistant/drug therapy , Water
4.
Molecules ; 27(9)2022 Apr 30.
Article in English | MEDLINE | ID: mdl-35566237

ABSTRACT

While bulk water and hydration water coexist in cells to support the expression of biological macromolecules, how the dynamics of water molecules, which have long been only a minor role in molecular biology research, relate to changes in cellular states such as cell death has hardly been explored so far due to the lack of evaluation techniques. In this study, we developed a high-precision measurement system that can discriminate bulk water content changes of ±0.02% (0.2 mg/cm3) with single-cell-level spatial resolution based on a near-field CMOS dielectric sensor operating at 65 GHz. We applied this system to evaluate the temporal changes in the bulk water content during the cell death process of keratinocytes, called corneoptosis, using isolated SG1 (first layer of stratum granulosum) cells in vitro. A significant irreversible increase in the bulk water content was observed approximately 1 h before membrane disruption during corneoptosis, which starts with cytoplasmic high Ca2+ signal. These findings suggest that the calcium flux may have a role in triggering the increase in the bulk water content in SG1 cells. Thus, our near-field CMOS dielectric sensor provides a valuable tool to dissect the involvement of water molecules in the various events that occur in the cell.


Subject(s)
Keratinocytes , Water , Cell Death , Epidermis/metabolism , Keratinocytes/metabolism , Water/metabolism
5.
Biosens Bioelectron ; 176: 112935, 2021 Mar 15.
Article in English | MEDLINE | ID: mdl-33418183

ABSTRACT

In this study, the growth of Escherichia coli was monitored using a complementary metal-oxide-semiconductor (CMOS) near-field sensor array. Each of the 1488 integrated elements, arranged in a 3 mm square, has a resonator that oscillates at 65 GHz. The effective capacitance of the resonator is altered by changes in the dielectric properties of the sensor surface, which shifts the resonance frequency. Growth curves of E. coli at different initial concentrations (OD600 = 0.01, 0.03, and 0.05) were monitored. A suspension with initial turbidity of OD600 = 0.05 was cultured in a medium, and the sensor successfully distinguished between viable E. coli and heat-treated dead E. coli in 20 min. Moreover, the apparent suppression of growth was observed in the presence of 500 µg/mL streptomycin. As the sensor is composed of arrayed elements, and the area of sensitivity distribution of the element is larger than the size of one bacteria, the variation in the output value of each element may reflect the number and movement of bacteria. This study revealed that the presence of viable E. coli could be rapidly confirmed by using the change in permittivity caused by the displacement of media by E. coli near the sensor surface.


Subject(s)
Biosensing Techniques , Escherichia coli , Electric Capacitance , Oxides , Semiconductors
6.
Cancers (Basel) ; 12(9)2020 Aug 31.
Article in English | MEDLINE | ID: mdl-32878320

ABSTRACT

Pancreatic cancer (PC) is among the most lethal malignancies due to an often delayed and difficult initial diagnosis. Therefore, the development of a novel, early stage, diagnostic PC marker in liquid biopsies is of great significance. In this study, we analyzed the differential glycomic profiling of extracellular vesicles (EVs) derived from serum (two cohorts including 117 PC patients and 98 normal controls) using lectin microarray. The glyco-candidates of PC-specific EVs were quantified using a high-sensitive exosome-counting system, ExoCounter. An absolute quantification system for altered glycan-containing EVs elevated in PC serum was established. EVs recognized by O-glycan-binding lectins ABA or ACA were identified as candidate markers by lectin microarray. Quantitative analyses using ExoCounter revealed that the ABA- or ACA-positive EVs were significantly increased in the culture of PC cell lines or in the serum of PC patients including carbohydrate antigen 19-9 negative patients with high area under curve values. The elevated numbers of EVs in PC serum returned to normal levels after pancreatectomy. Histological examination confirmed that the tumors stained with ABA/ACA. These specific EVs with O-glycans recognized by ABA/ACA are elevated in PC sera and can act as potential biomarkers in a liquid biopsy for PC patients screening.

7.
Phys Chem Chem Phys ; 22(35): 19468-19479, 2020 Sep 21.
Article in English | MEDLINE | ID: mdl-32761010

ABSTRACT

The biological functions of proteins depend on harmonization with hydration water surrounding them. Indeed, the dynamical transition of proteins, such as thermal denaturation, is dependent on the changes in the mobility of hydration water. However, the role of hydration water during dynamical transition is yet to be fully understood due to technical limitations in precisely characterizing the amount of hydration water. A state-of-the-art CMOS dielectric sensor consisting of 65 GHz LC resonators addressed this issue by utilizing the feature that oscillation frequency sensitively shifts in response to the complex dielectric constant at 65 GHz with extremely high precision. This study aimed to establish an analytical algorithm to derive the hydration number from the measured frequency shift and to demonstrate the transition of hydration number upon the thermal denaturation of human serum albumin. The determined hydration number in the native state drew a "global" hydration picture beyond the first solvation shell, with substantially reduced uncertainty of the hydration number (about ±1%). This allowed the detection of a rapid increase in the hydration number at about 55 °C during the heating process, which was in excellent phase with the irreversible rupture of the α-helical structure into solvent-exposed extended chains, whereas the hydration number did not trace the forward path in the subsequent cooling process. Our result indicates that the weakening of water hydrogen bonds trigger the unfolding of the protein structure first, followed by the changes in the number of hydration water as a consequence of thermal denaturation.


Subject(s)
Serum Albumin, Human/chemistry , Water/analysis , Algorithms , Electrochemical Techniques/statistics & numerical data , Hot Temperature , Humans , Hydrogen Bonding , Protein Denaturation , Water/chemistry
8.
Anticancer Res ; 39(9): 4687-4698, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31519568

ABSTRACT

BACKGROUND/AIM: Propagermanium (PG) inhibits the CCL2/CCR2 axis, and has been shown to function as an immune modulator. This study investigated its anti-tumor mechanism in patients with refractory cancers. MATERIALS AND METHODS: Five healthy volunteers and 23 patients with refractory oral (n=8) or gastric (n=15) cancer received PG (30 mg/day). We performed flow cytometry (FCM) of peripheral blood mononuclear cells and in vitro killing assays. RESULTS: FCM revealed that CD16+/CD56Dim NK cells (i.e., mature, cytolytic subset) increased, and the apoptosis induction rate of cancer cells increased after PG administration. Among gastric cancer patients, median OS was 172.0 days. Two patients showed complete remission of lung or liver metastasis. Survival of patients with oral cancer also tended to be prolonged. CONCLUSION: PG induces NK cell maturation, and may potentiate anti-tumor activity.


Subject(s)
Antineoplastic Agents/pharmacology , Cell Differentiation/drug effects , Cell Differentiation/immunology , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Neoplasms/immunology , Neoplasms/mortality , Organometallic Compounds/pharmacology , Cell Line, Tumor , Drug Resistance, Neoplasm , Germanium , Humans , Kaplan-Meier Estimate , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Lymphocyte Subsets/immunology , Lymphocyte Subsets/metabolism , Neoplasms/diagnosis , Neoplasms/drug therapy , Propionates , Tomography, X-Ray Computed
9.
ACS Appl Mater Interfaces ; 11(14): 13761-13767, 2019 Apr 10.
Article in English | MEDLINE | ID: mdl-30892010

ABSTRACT

The present study reports a new series of electrolytes for nonhumidified intermediate temperature fuel cells (IT-FCs). This series of new mixed electrolytes, composed of phosphoric acid (PA) and diethylmethylammonium trifluoromethanesulfonate ([dema][TfO]), was designed as nonhumidified IT-FC electrolytes. The mixed electrolytes show a higher thermal stability than pure PA, which is dehydrated at ITs. The thermal stability of the mixed electrolytes could be explained by the interaction between the triflate group in [dema][TfO] and PA, as indicated by Fourier transform infrared and proton nuclear magnetic resonance (1H NMR) spectroscopies. On the other hand, the ionic conductivity and proton transference number of the mixed electrolytes were similar to those of the pure PA. However, the oxygen reduction reaction (ORR) activity of a platinum catalyst is significantly enhanced in the mixed electrolytes, which was due to the several orders of magnitude increase in oxygen solubility by the addition of [dema][TfO] to PA. Specifically, for the equimolar fraction mixed electrolyte, the diffusion coefficient and the solubility of oxygen were ca. 1.47 × 10-5 cm2 s-1 and ca. 1.28 mmol dm-3 at 150 °C, respectively. The addition of [dema][TfO] to PA could significantly enhance the ORR activity. Therefore, the PA_[dema][TfO] mixed electrolyte can be one of the solutions to develop nonhumidified intermediate FC electrolytes.

10.
Gan To Kagaku Ryoho ; 45(4): 667-669, 2018 Apr.
Article in Japanese | MEDLINE | ID: mdl-29650829

ABSTRACT

We report a case of Stage IV gastric cancer showing pathological complete response(pCR)after neo-adjuvant chemotherapy( NAC)using S-1 and oxaliplatin(SOX).A woman 73-year-old was diagnosed as harming type 3 Stage IV gastric cancer with para-aortic lymph node(PAN)metastasis.She underwent 4 courses of NAC with SOX regimen.After the treatment, both the primary tumor and the metastatic PAN decreased in size remarkably.She underwent distal gastrectomy with D2 plus PAN dissection with curative intent.Pathological diagnosis revealed complete disappearance of cancer cells in both the primary lesion of the stomach and all dissected lymph nodes, confirming pCR.She is alive without recurrence 4 months after surgery.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoadjuvant Therapy , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Aged , Drug Combinations , Female , Gastrectomy , Humans , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Oxonic Acid/administration & dosage , Stomach Neoplasms/surgery , Tegafur/administration & dosage
11.
BMC Cancer ; 15: 333, 2015 Apr 30.
Article in English | MEDLINE | ID: mdl-25925261

ABSTRACT

BACKGROUND: Cancer-associated fibroblasts (CAFs), which reside around tumor cells, are suggested to play a pivotal role in tumor progression. Here we performed microarray analyses to compare gene expression profiles between CAFs and non-cancerous gastric fibroblasts (NGFs) from a patient with gastric cancer and found that fibroblast growth factor 9 (FGF9) was a novel growth factor overexpressed in CAFs. We then examined the biological effects of FGF9 during progression of gastric cancer. METHODS: Expression of FGF9 in CAFs and NGFs, and their secreted products, were examined by Western blotting. The effects of FGF9 on AGS and MKN28 gastric cancer cells in terms of proliferation, invasion and anti-apoptosis were assessed by WST-1 assay, invasion chamber assay and FACS, respectively. Furthermore, the intracellular signaling by which FGF9 exerts its biological roles was examined in vitro. RESULTS: FGF9 was strongly expressed in CAFs in comparison with NGFs, being compatible with microarray data indicating that FGF9 was a novel growth factor overexpressed in CAFs. Treatment with FGF9 promoted invasion and anti-apoptosis through activation of the ERK and Akt signaling pathways in AGS and MKN28 cells, whereas these effects were attenuated by treatment with anti-FGF9 neutralizing antibody. In addition, FGF9 treatment significantly enhanced the expression of matrix metalloproteinase 7 (MMP7) in both cell lines. CONCLUSIONS: FGF9 is a possible mediator secreted by CAFs that promotes the anti-apoptosis and invasive capability of gastric cancer cells.


Subject(s)
Apoptosis/genetics , Fibroblast Growth Factor 9/biosynthesis , Matrix Metalloproteinase 7/biosynthesis , Stomach Neoplasms/genetics , Antibodies, Neutralizing/administration & dosage , Apoptosis/drug effects , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Proliferation/genetics , Fibroblast Growth Factor 9/administration & dosage , Fibroblast Growth Factor 9/genetics , Fibroblasts/drug effects , Fibroblasts/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Humans , MAP Kinase Signaling System/drug effects , Matrix Metalloproteinase 7/genetics , Neoplasm Invasiveness/genetics , Signal Transduction/genetics , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology
12.
Gastric Cancer ; 18(3): 485-94, 2015 Jul.
Article in English | MEDLINE | ID: mdl-24908114

ABSTRACT

BACKGROUND: Microenvironments control cancer growth and progression. We explored the prognostic impact of stromal reaction and cancer stromal cells on relapse risk and survival after curative gastrectomy in gastric cancer patients. METHODS: Tissue samples were obtained from 107 patients with gastric adenocarcinoma who underwent curative (R0) gastrectomy. Primary stromal cells isolated from gastric cancer tissue (GCSC) and normal gastric tissue (Gastric stromal cell: GSC) in each patient were cultured and subjected to comprehensive proteome (LC-MS/MS) and real-time RT-PCR analysis. Expression of Ephrin A2 receptors (EphA2) in cancers and GCSC was evaluated immunohistochemically. Intermingling of EphA2-positive cancer cells and GCSC (IC/A2+) and overexpression of EphA2 in cancer cells (Ca/A2+) in invasive parts of tumors were assessed, as were relationships of IC/A2+, Ca/A2+, and clinicopathological factors with relapse-free survival and overall survival. RESULTS: Proteome analysis showed that EphA2 expression was significantly higher in GCSC than GSC. Real-time RT-PCR analysis showed that levels of EphA1/A2/A3/A5 and EphB2/B4 were ≥2.0-fold higher in GCSC than GSC. Ca/A2 and IC/A2 were positive in 65 (60.7 %) and 26 (24.3 %) patients, respectively. Relapse was significantly more frequent in IC/A2-positive than in IC/A2-negative (HR, 2.12; 95 % CI, 1.16-5.41; p = 0.0207) patients. Among the 54 patients who received S-1 adjuvant chemotherapy, relapse-free survival (RFS) was significantly shorter in those who were IC/A2-positive than in those who were IC/A2-negative and Ca/A2-negative (HR, 2.83; 95 % CI, 1.12-12.12; p = 0.0339). Multivariable analysis indicated that pathological stage (p = 0.010) and IC/A2+ (p = 0.008) were independent risk factors for recurrence. CONCLUSION: IC/A2+ was predictive of relapse after curative (R0) gastrectomy.


Subject(s)
Adenocarcinoma/pathology , Receptor, EphA2/metabolism , Stomach Neoplasms/pathology , Stromal Cells/metabolism , Adenocarcinoma/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/surgery , Chemotherapy, Adjuvant , Disease-Free Survival , Drug Combinations , Humans , Immunohistochemistry , Oxonic Acid/therapeutic use , Prognosis , Receptor Protein-Tyrosine Kinases/genetics , Receptor Protein-Tyrosine Kinases/metabolism , Receptor, EphA2/genetics , Receptor, EphA3 , Receptor, EphA5/genetics , Receptor, EphA5/metabolism , Receptor, EphB2/genetics , Receptor, EphB2/metabolism , Retrospective Studies , Stomach Neoplasms/drug therapy , Stomach Neoplasms/mortality , Stomach Neoplasms/surgery , Stromal Cells/pathology , Tegafur/therapeutic use , Tumor Microenvironment
13.
Surgery ; 154(1): 78-88, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23601903

ABSTRACT

BACKGROUND: CC chemokine ligand 20 (CCL20) and CC chemokine receptor 6 are believed to stimulate the recruitment of neutrophils and activation of macrophages against bacterial pathogens through the activation of T helper cells. We analyzed the role of CCL20 in the acute phase of sepsis. METHODS: The effect of a neutralizing, anti-mouse CCL20 monoclonal antibody (mAb) was examined in 2 murine models of sepsis: Cecal ligation and puncture (CLP) and Escherichia coli peritonitis. Immune cell migration, bacterial clearance, and expression of 17 cytokines and 5 chemokines were quantified in E coli-induced peritonitis. Expression of CCL20 in various tissues was determined, and apoptotic cells in jejunum were measured. RESULTS: Anti-CCL20 mAb increased mortality in CLP and E coli peritonitis (P = .029 and .024, respectively by Kaplan-Meier method and log-rank test). The 48-hour survival rate in anti-CCL20 mAb- and control immunoglobulin (Ig)G-treated mice was 37% (11/30) vs 62% (18/29) in CLP and 28% (11/40) vs 48% (19/40) in bacterial peritonitis. Neutralization of CCL20 showed no effect on leukocyte infiltration into the peritoneal cavity or bacterial clearance at 24 hours. CCL20 was induced strongly and predominantly in jejunum after bacterial infection, and neutralizing CCL20 increased apoptosis of epithelial cells in jejunum crypt. Inhibition of CCL20 increased serum tumor necrosis factor (TNF)-α (3.3-fold greater than control mice) and decreased serum interleukin (IL)-1α and IL-6. CONCLUSION: Neutralization of CCL20 before induction of sepsis increased mortality during sepsis accompanied with increasing epithelial apoptosis in the jejunum and augmenting serum TNF-α.


Subject(s)
Apoptosis , Chemokine CCL20/physiology , Jejunum/pathology , Sepsis/mortality , Animals , Cell Movement , Chemokine CCL20/antagonists & inhibitors , Chemokines/biosynthesis , Cytokines/biosynthesis , Disease Models, Animal , Leukocytes/physiology , Male , Mice , Mice, Inbred BALB C , Peritoneal Cavity/cytology , Peritonitis/microbiology , Th17 Cells/physiology
14.
Am J Physiol Gastrointest Liver Physiol ; 304(6): G568-73, 2013 Mar 15.
Article in English | MEDLINE | ID: mdl-23370674

ABSTRACT

Prostaglandin E(2) (PGE(2)) plays a major role in pain processing and hypersensitivity. This study investigated whether PGE(2) levels are increased in the esophageal mucosa after acid infusion and whether increases in PGE(2) are associated with heartburn. Furthermore, expression of the PGE(2) receptor EP1 was investigated in human esophageal mucosa. Fourteen healthy male volunteers were randomized to 30-min lower esophageal acid (1% HCl) or saline perfusion. Before and after acid perfusion, endoscopic biopsies were taken from the distal esophagus. PGE(2) concentration (pg/mg protein) and EP1 mRNA and protein in biopsy samples were measured by ELISA, RT-PCR, and Western blotting. Symptom status of heartburn was evaluated with a validated categorical rating scale with a higher values corresponding to increasing intensity. PGE(2) levels in the esophageal mucosa significantly increased after acid infusion (before vs. after acid infusion: 23.2 ± 8.6 vs. 68.6 ± 18.3, P < 0.05), but not after saline infusion (before vs. after saline infusion: 9.3 ± 2.5 vs. 9.0 ± 3.2, NS). Time to first sensation (min) after acid infusion was less than after saline (saline vs. acid infusion: 22.1 ± 4.1 vs. 5.4 ± 1.5, P < 0.05). Intensity of heartburn in the acid-infusion group was also significantly greater compared with saline (saline vs. acid infusion: 54.3 ± 13.1 vs. 178.5 ± 22.8, P < 0.01). Changes in PGE(2) levels in the esophagus correlated with symptom intensity score (r = 0.80, P = 0.029). EP1 mRNA and protein expression were observed in the normal human esophageal mucosa. Esophageal PGE(2) expression is associated with mucosal acid exposure and heartburn.


Subject(s)
Esophagus , Heartburn , Hydrochloric Acid/pharmacology , Mucous Membrane/metabolism , Pain Threshold/physiology , Prostaglandins E/metabolism , Administration, Mucosal , Adult , Biopsy/methods , Esophagoscopy/methods , Esophagus/metabolism , Esophagus/pathology , Esophagus/physiopathology , Heartburn/chemically induced , Heartburn/metabolism , Heartburn/physiopathology , Humans , Male , Nontherapeutic Human Experimentation , Receptors, Prostaglandin E/metabolism , Sodium Chloride/pharmacology
15.
Int J Clin Oncol ; 18(1): 38-45, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22105894

ABSTRACT

BACKGROUND: Imatinib mesylate, a small-molecule tyrosine kinase inhibitor, is currently used for adjuvant therapy of patients who have undergone resection of high-risk gastrointestinal stromal tumors (GISTs). There are no data concerning the efficacy and safety of postoperative adjuvant therapy with imatinib for Japanese or East Asian patients with GIST. METHODS: A single-arm, open-label, multicenter trial was conducted in 17 hospitals in Japan. The eligibility criteria included histologically proven primary high-risk GISTs with macroscopic complete resection. Patients were treated with imatinib at a dose of 400 mg/day for 1 year after surgery. The primary endpoint was recurrence-free survival as assessed by Kaplan-Meier analysis. The secondary endpoints were overall survival and safety. This study was registered with ClinicalTrials.gov, number NCT00171977. RESULTS: A total of 64 patients were enrolled between September 2004 and July 2006. The median age of the patients was 59.5 years. Forty-nine (76.6%) patients completed the 1-year treatment, whereas 15 (23.4%) patients did not complete the treatment owing to recurrence, toxicities, and consent withdrawal. At the median follow-up period of 109 weeks, 20 patients had recurrence. The 3-year recurrence rate was 42.7% (95% confidence interval 29.2-56.3%), which exceeded the expected recurrence rate in this trial. The recurrence-free and overall survival rates at 2 years were 71.1 and 93.7%, respectively. The most frequent adverse drug reaction of any grade was eyelid edema (48.4%), followed by neutropenia (40.6%), leukopenia (39.1%), nausea (39.1%), rash (37.5%), and peripheral edema (37.5%), most of which were mild and manageable. CONCLUSIONS: Adjuvant therapy with imatinib at 400 mg/day for 1 year is well tolerated by Japanese patients and possibly reduces the risk of early recurrence of high-risk GISTs.


Subject(s)
Antineoplastic Agents/administration & dosage , Benzamides/administration & dosage , Drug-Related Side Effects and Adverse Reactions/physiopathology , Gastrointestinal Stromal Tumors/drug therapy , Piperazines/administration & dosage , Pyrimidines/administration & dosage , Adult , Aged , Benzamides/adverse effects , Chemotherapy, Adjuvant , Disease-Free Survival , Drug-Related Side Effects and Adverse Reactions/chemically induced , Drug-Related Side Effects and Adverse Reactions/classification , Female , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/surgery , Humans , Imatinib Mesylate , Japan , Kaplan-Meier Estimate , Male , Middle Aged , Piperazines/adverse effects , Postoperative Period , Protein Kinase Inhibitors/adverse effects , Pyrimidines/adverse effects , Recurrence , Treatment Outcome
16.
Anticancer Res ; 32(10): 4405-12, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23060565

ABSTRACT

BACKGROUND: Serum dermokine (DK) is a novel biomarker for early colorectal cancer. To our knowledge this is the first study of DK expression in intraductal papillary mucinous neoplasm (IPMN) and pancreatic cancer. MATERIALS AND METHODS: DK expression in human pancreatic cancer cell lines and tissues was assessed. We compared the sensitivities of common diagnostic markers, carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), s-pancreas-1 antigen (SPAN-1), pancreatic cancer-associated antigen (DUPAN-2), and Nation Cancer Center-Stomach-439 (NCC-ST-439) in 26 patients with pancreatic neoplasms. RESULTS: DK was expressed in pancreatic cancer cell lines. Immunohistochemical staining revealed that DK was expressed in atypical and cancerous tissues, but not in the normal pancreatic tissues. Serum DK was relatively high in patients with IPMN. The sensitivities of a serum multimarker test including DK was 76.5% (n=13/17) for IPMA/IPMC/invasive carcinoma derived from IPMN, and 100% (n=9/9) for ordinary invasive ductal carcinoma. CONCLUSION: Serum DK is a potential biomarker in IPMN and invasive ductal carcinoma, when used in combination with conventional biomarkers.


Subject(s)
Adenocarcinoma, Mucinous/pathology , Biomarkers, Tumor/metabolism , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Papillary/pathology , Pancreatic Neoplasms/pathology , Proteins/metabolism , Adenocarcinoma, Mucinous/metabolism , Biomarkers, Tumor/analysis , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Papillary/metabolism , Cell Line, Tumor , Humans , Immunohistochemistry , Intercellular Signaling Peptides and Proteins , Pancreatic Neoplasms/metabolism
17.
Hepatogastroenterology ; 58(109): 1372-6, 2011.
Article in English | MEDLINE | ID: mdl-21937410

ABSTRACT

BACKGROUND/AIMS: The purpose of this study was to identify risk factors related to severe pancreatic fistula in patients who underwent distal pancreatectomy (DP). METHODOLOGY: From 2000 to 2008, 63 patients underwent DP. We retrospectively identified the risk factors for Grade B or C postoperative pancreatic fistula (POPF) occurring after DP. POPF was classified according to the International Study Group on Pancreatic Fistula definition. RESULTS: Postoperative mortality and morbidity rate were 0% and 61%, respectively. POPF developed in 32 patients (51%); 21 of fistulas were classified as Grade A, nine as Grade B and two as Grade C. The incidence of severe POPF (Grade B or C) was significantly associated with two factors by univariate analyses: polyethylene glycolic acid (PGA) felt with fibrin sealant and blood loss during operation. To clarify the useful manner in DP, multivariate analysis was performed using 5 surgery-related factors. The use of polyethylene glycolic acid felt (PGA) with fibrin sealant and blood loss during operation were the significant factors for severe POPF (p=0.026 and 0.012, respectively). CONCLUSIONS: Using PGA felt with fibrin sealant for the pancreatic stump could reduce the risk of severe POPF.


Subject(s)
Pancreatectomy/adverse effects , Pancreatic Fistula/etiology , Postoperative Complications/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Fibrin Tissue Adhesive , Humans , Male , Middle Aged , Polyethylene Glycols/administration & dosage , Polyglycolic Acid/administration & dosage , Risk Factors , Surgical Mesh
18.
Gan To Kagaku Ryoho ; 38(9): 1390-5, 2011 Sep.
Article in Japanese | MEDLINE | ID: mdl-21918333

ABSTRACT

In Japan, a one-year administration of S-1 is the standard adjuvant treatment for stage II/III gastric cancer after curative gastrectomy with a D2 lymph-node dissection.The treatment is recommended in the Japanese Guidelines for Treatment of Gastric Cancer(3rd Edition).Using data from results of a 5-year follow-up of the ACTS-GC trial, it was confirmed that using S-1 significantly improves the 5-year overall survival over surgery alone.However, the recurrence rate of stage III gastric cancer is still too high.More powerful treatment using multiple drugs is needed for this disease.This paper presents a new perspective for the development of post-operative adjuvant chemotherapy in the future, based on clinical trials recently reported.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Chemotherapy, Adjuvant , Clinical Trials as Topic , Drug Combinations , Humans , Neoplasm Staging , Oxonic Acid/therapeutic use , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Tegafur/therapeutic use
19.
Hepatogastroenterology ; 57(101): 858-64, 2010.
Article in English | MEDLINE | ID: mdl-21033242

ABSTRACT

BACKGROUND/AIMS: Some hepatocellular carcinoma (HCC) cases undergo surgery because tumor progression cannot be controlled by various non-surgical therapies. This retrospective study sought to clarify the clinicopathologic features of such HCC cases. METHODOLOGY: Among cases with solitary small HCCs (< or = 3.0cm at the time of detection), the clinicopathologic features of 7 patients who had undergone hepatectomy after various non-surgical therapies (Salvage (S) group) were analyzed and compared with those of 30 patients who received hepatectomy as the initial treatment (Control (C) group). RESULTS: In S group, the serum alpha-fetoprotein level was higher (p = 0.045) and macroscopic ductal invasion was more common (p = 0.028) at the time of the operation. Lobectomy was more commonly performed (p = 0.034) and curability B (No residual cancer, but Stage III or IV) was more frequent (p = 0.011). Other organ recurrence was more common (p = 0.0044). The survival time after the initial treatment (post-initial treatment survival) was worse (p = 0.028). Univariate analyses revealed that those with maximum tumor sizes of > 3.0 cm at the time of the operation were significantly worse compared with the other patients (p = 0.012). CONCLUSIONS: The timing for changing from a non-surgical treatment to a surgical treatment is important.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy , Liver Neoplasms/surgery , Salvage Therapy , Aged , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Catheter Ablation , Chemoembolization, Therapeutic , Disease Progression , Female , Hepatic Duct, Common/pathology , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Retrospective Studies , Survival Analysis , Treatment Failure
20.
Surg Today ; 40(11): 1088-92, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21046511

ABSTRACT

Small intestinal bleeding is difficult to detect and can be life-threatening. Capsule endoscopy (CE) is a new, minimally invasive diagnostic procedure designed to detect gastrointestinal (GI) bleeding. We report the successful management of idiopathic ileal varices by capsule endoscopy and laparoscopic surgery. Massive bleeding occurred suddenly with intermittent melena, and the patient was finally admitted to a local hospital in hypovolemic shock. Her condition was stabilized with conservative therapy but the site of bleeding was not defined by endoscopy, computed tomography, scintigraphy, or angiography. Thus, she was transferred to our hospital. On admission, CE revealed idiopathic ileal varices, so we performed laparoscopic partial ileal resection immediately. Follow-up CE has shown no evidence of recurrence in the 2 years since surgery. Idiopathic ileal varices are rare, difficult to diagnose, and often fatal. Capsule endoscopy is a minimally invasive diagnostic procedure that detects this disorder in time for laparoscopic surgery to be performed effectively and safely.


Subject(s)
Capsule Endoscopy/methods , Double-Balloon Enteroscopy/methods , Gastrointestinal Hemorrhage/etiology , Ileum/blood supply , Laparoscopy/methods , Varicose Veins/diagnosis , Angiodysplasia/diagnosis , Capsule Endoscopy/instrumentation , Dilatation, Pathologic/diagnosis , Double-Balloon Enteroscopy/instrumentation , Female , Humans , Melena/etiology , Middle Aged , Tomography, X-Ray Computed , Varicose Veins/complications , Varicose Veins/surgery
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