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1.
Clin Radiol ; 77(11): 855-863, 2022 11.
Article in English | MEDLINE | ID: mdl-36055826

ABSTRACT

AIM: To evaluate the usefulness of synthetic magnetic resonance imaging (MRI) performed before the initiation of neoadjuvant chemotherapy (NAC) in predicting whether breast cancers can achieve a pathological complete response (pCR) after the completion of NAC. MATERIALS AND METHODS: This retrospective study investigated 37 consecutive patients with 39 breast cancers (pCR: 14, and non-pCR: 25) who underwent dynamic contrast-enhanced (DCE)-MRI and synthetic MRI before the initiation of NAC. Using synthetic MRI images, quantitative values (T1 and T2 relaxation times, proton density [PD] and their standard deviations [SD]) were obtained in breast lesions, before (Pre-T1, Pre-T2, Pre-PD, SD of Pre-T1, SD of Pre-T2, SD of Pre-PD) and after (Gd-T1, Gd-T2, Gd-PD, SD of Gd-T1, SD of Gd-T2, SD of Gd-PD) contrast agent injection. The aforementioned quantitative values and several morphological features that were identified on DCE-MRI were compared between pCR and non-pCR. RESULTS: Multivariate analyses revealed that the SD of Pre-T2 (p=0.038) was significant and was an independent predictor of pCR, with an area under the receiver operating characteristics curve of 0.829. The sensitivity, specificity, and accuracy of the SD of Pre-T2 with an optimal cut-off value of 11.5 were 71.4%, 80%, and 76.3%, respectively. CONCLUSIONS: The SD of Pre-T2 obtained from synthetic MRI was used successfully to predict those breast cancers that would achieve a pCR after the completion of NAC; however, these results are preliminary and need to be verified by further studies.


Subject(s)
Breast Neoplasms , Neoadjuvant Therapy , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Contrast Media/therapeutic use , Female , Humans , Magnetic Resonance Imaging/methods , Neoadjuvant Therapy/methods , Protons , Retrospective Studies , Treatment Outcome
2.
Phys Rev Lett ; 124(13): 131301, 2020 Apr 03.
Article in English | MEDLINE | ID: mdl-32302154

ABSTRACT

Using only cosmic microwave background polarization data from the polarbear experiment, we measure B-mode polarization delensing on subdegree scales at more than 5σ significance. We achieve a 14% B-mode power variance reduction, the highest to date for internal delensing, and improve this result to 22% by applying for the first time an iterative maximum a posteriori delensing method. Our analysis demonstrates the capability of internal delensing as a means of improving constraints on inflationary models, paving the way for the optimal analysis of next-generation primordial B-mode experiments.

3.
Science ; 368(6486): 67-71, 2020 04 03.
Article in English | MEDLINE | ID: mdl-32193363

ABSTRACT

The Hayabusa2 spacecraft investigated the small asteroid Ryugu, which has a rubble-pile structure. We describe an impact experiment on Ryugu using Hayabusa2's Small Carry-on Impactor. The impact produced an artificial crater with a diameter >10 meters, which has a semicircular shape, an elevated rim, and a central pit. Images of the impact and resulting ejecta were recorded by the Deployable CAMera 3 for >8 minutes, showing the growth of an ejecta curtain (the outer edge of the ejecta) and deposition of ejecta onto the surface. The ejecta curtain was asymmetric and heterogeneous and it never fully detached from the surface. The crater formed in the gravity-dominated regime; in other words, crater growth was limited by gravity not surface strength. We discuss implications for Ryugu's surface age.

4.
Sci Rep ; 10(1): 3558, 2020 02 26.
Article in English | MEDLINE | ID: mdl-32103035

ABSTRACT

Redox-sensitive metallic elements, Mn and Fe, are oxidized in deep sea waters and form abundant ferromanganese crusts and nodules on the world's ocean floors at ultraslow rates of growth. This process of oxidation and the mechanism of precipitation are yet unknown. In this paper, the results of the first successful, long-term, on-site experiment of mineral precipitation that ascertains modern, ongoing hydrogenetic deposition of oxide materials from normal seawaters at water depths of 900-4500 m of geologically active and inactive environments are presented. We succeeded in the in-situ precipitation experiment on the sea floor and characterized the precipitates using high-resolution and submicron-scale chemical, mineralogical, and structural analyses. The installed artificial plates of glass, ceramics, and plastic yielded spread-out particles of sizes varying from one to a few micrometers in diameter, of coccoid-like irregular shapes, with a maximum of 1,000-10,000 individual particles/mm2/year after 12-15 years of exposure. The results indicated a continuous substantial growth of the hydrogenetic minerals if both Mn and Fe are supplied to the bottom waters. The mineralogical, chemical, and structural properties of the precipitates are similar to those of the natural precipitates on the seabed that are made up of hydrogenetic ferromanganese crusts and nodules, together with settling sediments, suspended hydrothermal particles, or microbial precipitates from cultivated Mn-oxidizing bacteria. Our work presents new realistic insight into proposed genetic models of marine hydrogenetic ferromanganese deposits in modern diverse ocean environments.

5.
Clin Radiol ; 74(12): 944-949, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31630766

ABSTRACT

AIM: This study evaluated the relationship between three-dimensional (3D) mean computed tomography (CT) attenuation values of ground-glass nodules (GGN) and pathological invasiveness in early lung adenocarcinoma. The diagnostic accuracy of 3D CT attenuation values was compared with that of two-dimensional (2D) CT attenuation values and standardised uptake value on positron-emission tomography (PET). MATERIALS AND METHODS: Surgical and radiological data from 96 pure or part-solid GGNs of <20 mm were analysed retrospectively. Mean 2D and 3D CT attenuation values of the tumours were obtained with semi-automated volumetric software. Pathological invasiveness was diagnosed according to the International Association for the Study of Lung Cancer (IASLC))/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification. Pre-invasive lesions and minimally invasive adenocarcinomas were classified as non-invasive adenocarcinoma. Univariate and multivariate analyses determined relationships between pathological invasiveness and clinical/radiological findings. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cut-off value for detecting invasive adenocarcinoma. RESULTS: A total of 66 non-invasive and 30 invasive adenocarcinoma cases between 2010 and 2016 were analysed. Univariate analysis revealed four tumour invasiveness-associated predictors: maximum diameter, SUVmax, mean 2D CT attenuation value, and mean 3D CT attenuation value (p<0.05). Multivariate analysis revealed that the maximum diameter, SUVmax, and mean 3D CT attenuation value were significant predictors of pathological invasiveness (p=0.023, 0.022, 0.004). The area under the ROC curve to predict invasive adenocarcinoma for mean 3D CT attenuation value was 0.838 and the cut-off value was -489 HU. CONCLUSION: The mean 3D CT attenuation value could distinguish pre-invasive lesions and minimally invasive adenocarcinoma from invasive adenocarcinoma.


Subject(s)
Adenocarcinoma/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Solitary Pulmonary Nodule/diagnostic imaging , Tomography, X-Ray Computed/methods , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Imaging, Three-Dimensional , Lung/diagnostic imaging , Lung/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Invasiveness/diagnostic imaging , Retrospective Studies , Solitary Pulmonary Nodule/diagnosis , Solitary Pulmonary Nodule/pathology
6.
Science ; 364(6437): 268-272, 2019 04 19.
Article in English | MEDLINE | ID: mdl-30890588

ABSTRACT

The Hayabusa2 spacecraft arrived at the near-Earth carbonaceous asteroid 162173 Ryugu in 2018. We present Hayabusa2 observations of Ryugu's shape, mass, and geomorphology. Ryugu has an oblate "spinning top" shape, with a prominent circular equatorial ridge. Its bulk density, 1.19 ± 0.02 grams per cubic centimeter, indicates a high-porosity (>50%) interior. Large surface boulders suggest a rubble-pile structure. Surface slope analysis shows Ryugu's shape may have been produced from having once spun at twice the current rate. Coupled with the observed global material homogeneity, this suggests that Ryugu was reshaped by centrifugally induced deformation during a period of rapid rotation. From these remote-sensing investigations, we identified a suitable sample collection site on the equatorial ridge.

7.
Leukemia ; 31(12): 2670-2677, 2017 12.
Article in English | MEDLINE | ID: mdl-28490812

ABSTRACT

Epigenetic signaling pathways are implicated in tumorigenesis and therefore histone deacetylases (HDACs) represent novel therapeutic targets for cancers, including multiple myeloma (MM). Although non-selective HDAC inhibitors show anti-MM activities, unfavorable side effects limit their clinical efficacy. Isoform- and/or class-selective HDAC inhibition offers the possibility to maintain clinical activity while avoiding adverse events attendant to broad non-selective HDAC inhibition. We have previously reported that HDAC3 inhibition, either by genetic knockdown or selective inhibitor BG45, abrogates MM cell proliferation. Here we show that knockdown of HDAC3, but not HDAC1 or HDAC2, as well as BG45, downregulate expression of DNA methyltransferase 1 (DNMT1) mediating MM cell proliferation. DNMT1 expression is regulated by c-Myc, and HDAC3 inhibition triggers degradation of c-Myc protein. Moreover, HDAC3 inhibition results in hyperacetylation of DNMT1, thereby reducing the stability of DNMT1 protein. Combined inhibition of HDAC3 and DNMT1 with BG45 and DNMT1 inhibitor 5-azacytidine (AZA), respectively, triggers synergistic downregulation of DNMT1, growth inhibition and apoptosis in both MM cell lines and patient MM cells. Efficacy of this combination treatment is confirmed in a murine xenograft MM model. Our results therefore provide the rationale for combination treatment using HDAC3 inhibitor with DNMT1 inhibitor to improve patient outcome in MM.


Subject(s)
DNA (Cytosine-5-)-Methyltransferase 1/genetics , Gene Expression Regulation, Neoplastic , Histone Deacetylases/metabolism , Multiple Myeloma/genetics , Multiple Myeloma/metabolism , Acetylation , Animals , Apoptosis , Cell Line, Tumor , DNA (Cytosine-5-)-Methyltransferase 1/metabolism , Disease Models, Animal , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Gene Knockdown Techniques , Histone Deacetylase Inhibitors/pharmacology , Humans , Mice , Models, Biological , Multiple Myeloma/drug therapy , Multiple Myeloma/pathology , Protein Stability , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , RNA Interference , Xenograft Model Antitumor Assays
8.
Leukemia ; 31(12): 2661-2669, 2017 12.
Article in English | MEDLINE | ID: mdl-28487543

ABSTRACT

Recent studies have delineated cancer-type-specific roles of histone 3 lysine 27 (H3K27) demethylase KDM6B/JMJD3 depending on its H3K27 demethylase activity. Here we show that KDM6B is expressed in multiple myeloma (MM) cells; and that shRNA-mediated knockdown and CRISPR-mediated knockout of KDM6B abrogate MM cell growth and survival. Tumor necrosis factor-α or bone marrow stromal cell culture supernatants induce KDM6B, which is blocked by IKKß inhibitor MLN120B, suggesting that KDM6B is regulated by NF-κB signaling in MM cells. RNA-seq and subsequent ChIP-qPCR analyses reveal that KDM6B is recruited to the loci of genes encoding components of MAPK signaling pathway including ELK1 and FOS, and upregulates expression of these genes without affecting H3K27 methylation level. Overexpression of catalytically inactive KDM6B activates expression of MAPK pathway-related genes, confirming its function independent of demethylase activity. We further demonstrate that downstream targets of KDM6B, ELK1 and FOS, confer MM cell growth. Our study therefore delineates KDM6B function that links NF-κB and MAPK signaling pathway mediating MM cell growth and survival, and validates KDM6B as a novel therapeutic target in MM.


Subject(s)
Jumonji Domain-Containing Histone Demethylases/metabolism , MAP Kinase Signaling System , Multiple Myeloma/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Cell Survival/genetics , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Jumonji Domain-Containing Histone Demethylases/genetics , Multiple Myeloma/genetics , Multiple Myeloma/mortality , Multiple Myeloma/pathology , NF-kappa B/metabolism , Proto-Oncogene Proteins c-fos/metabolism , RNA Interference , Signal Transduction , ets-Domain Protein Elk-1/metabolism
9.
B-ENT ; 13(1 Suppl 27): 37-43, 2017.
Article in English | MEDLINE | ID: mdl-29557561

ABSTRACT

Residual cholesteatoma revealed by endoscopy after microsurgery. OBJECTIVE: To endoscopically examine common sites of residual cholesteatoma occurrence after microscopic ear surgery. METHODS: Thirty patients (15 men and 15 women; age range: 7-81 years) who underwent treatment for middle ear cholesteatoma (20 patients with pars flaccida :holesteatoma and 10 patients with pars tensa cholesteatoma) were selected. Following the removal of the cholesteatoma matrix via microscopy, residual matrix presence was assessed using an endoscope system. Additional resection was performed if the residual matrix was detected. Sites of residual matrix and their rates of incidence were then investigated. RESULTS: Residual matrix was observed in nine out of the 30 (30%) patients by endoscopy after microscopic surgery. Residual matrix was observed in eight out of the 20 (40%) patients with pars flaccida cholesteatoma and in one out of :he 10 (10%) patients with pars tensa cholesteatoma. Residual matrix was observed in six out of the 14 (43%) patients who underwent canal wall up (CWU) tympanomastoidectomy and in three out of the 13 (23%) patients who underwent -anal wall down (CWD) tympanomastoidectomy. Sites of residual matrix included the tegmen tympani in two patients, he medial scutal surface in three patients, the tympanic sinus in two patients and the anterior epitympanic recess in three patients. The risk of residual matrix was greater in patients with pars flaccida cholesteatoma than in those with pars tensa :holesteatoma. The attic, tympanic sinus and anterior epitympanic recess are common sites of residual cholesteatoma. CONCLUSION: Endoscopy is advantageous for the assessment of residual cholesteatoma in hidden areas.


Subject(s)
Cholesteatoma, Middle Ear/pathology , Cholesteatoma, Middle Ear/surgery , Endoscopy , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Microsurgery , Middle Aged , Neoplasm, Residual , Otologic Surgical Procedures/methods , Retrospective Studies , Young Adult
10.
Geobiology ; 14(4): 374-89, 2016 07.
Article in English | MEDLINE | ID: mdl-27027643

ABSTRACT

Many physical and chemical processes control the extent of Fe(III) oxyhydroxide reduction by dissimilatory Fe(III)-reducing bacteria. The surface precipitation of secondary Fe minerals on Fe(III) oxyhydroxides limits the extent of microbial Fe(III) reduction, but this phenomenon has not yet been observed in nature. This paper reports the observation of secondary Fe-mineral (goethite) encrustation on ferrihydrite surface within freshwater sediment up to 10 cm deep. The sediment surface was characterized by the predominance of ferrihydrites with biogenic stalks and sheaths. An Fe(II)-oxidizing bacterium (Gallionellaceae) was detected by 16S rRNA gene analysis at sediment depths of 1 and 2 cm. Fe(2+) concentration in the sediment pore water was relatively higher at 2-4 cm depths. The 16S rRNA genes affiliated with dissimilatory Fe(III)-reducing bacteria were detected at 1, 2, and 4 cm depths. The results of the Fe K-edge extended X-ray absorption fine structure (EXAFS) analysis suggested the presence of goethite and siderite at depths below 3 cm. However, the change in the Fe-mineral composition was restricted to sediment depths between 3 and 4 cm, despite the presence of abundant ferrihydrite at depths below 4 cm. An increase in CH4 concentration was observed at deeper than 6 cm. Stable isotopic analysis of CH4 in the pore water indicated that acetoclastic CH4 occurred at depths below 7 cm. Transmission electron microscope observations suggested the presence of goethite and siderite on stalks and sheaths at depths below 3 cm. Results from conversion electron yield EXAFS analysis suggested that goethite dominated at 10 cm depth, thereby indicating that ferrihydrite was encrusted by goethite at this depth. Moreover, the incomplete reduction of ferrihydrite below depths of 4 cm was not due to the lack of organic carbon, but was possibly due to the surface encrustation of goethite on ferrihydrite.


Subject(s)
Archaea/isolation & purification , Bacteria/isolation & purification , Ferric Compounds/metabolism , Geologic Sediments/chemistry , Geologic Sediments/microbiology , Iron Compounds/chemistry , Minerals/chemistry , Archaea/classification , Archaea/metabolism , Bacteria/classification , Bacteria/metabolism , Cluster Analysis , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , Fresh Water , Oxidation-Reduction , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , X-Ray Absorption Spectroscopy
11.
Eur J Surg Oncol ; 41(10): 1324-32, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26251341

ABSTRACT

BACKGROUND: Peritoneal lavage cytology cancer-positive (CY1) is a critical prognostic factor and is taken as representing stage IV in gastric cancer. There is no consensus treatment strategy for CY1-gastric cancer, and the detailed clinicopathological features remain obscure. PATIENTS AND METHODS: Among 790 gastric cancer patients between 2005 and 2009, 52 cases of CY1 were identified (6.6%). A multivariate prognostic model was applied to the univariate prognostic factors to identify independent prognostic factors and factors associated with long-term survival in CY1-gastric cancer. RESULTS: (1) Five-year overall survival (OS) was 17.6% in CY1-gastric cancer as compared with 93.9% in CYX and 77.7% in CY0 (77.7%), where tumors with pT2 or beyond were included in 11% of CYX, 73% of CY0, and 98% of CY1 cases. (2) On univariate analysis, factors associated with a negative prognosis were the presence of peritoneal dissemination (p = 0.029) and high preoperative serum albumin (p = 0.011) in CY1-gastric cancer. The multivariate Cox proportional hazards and logistic regression model using propensity score identified preoperative albumin as a critical independent prognostic indicator. (3) Long-term survivors were identified and, were often characterized by long-term postoperative adjuvant treatment. CONCLUSION: Reduced preoperative serum albumin and absence of peritoneal dissemination may be predictive factors for long-term survival in patients with advanced gastric cancer with positive cytology test. Long-term postoperative adjuvant therapy might improve survival of patients with CY1.


Subject(s)
Hypoalbuminemia/blood , Peritoneal Neoplasms/secondary , Serum Albumin/metabolism , Stomach Neoplasms/blood , Stomach Neoplasms/mortality , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Disease-Free Survival , Docetaxel , Drug Combinations , Female , Gastrectomy , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Oxonic Acid/administration & dosage , Peritoneal Lavage , Peritoneal Neoplasms/mortality , Preoperative Period , Prognosis , Proportional Hazards Models , Retrospective Studies , Stomach Neoplasms/pathology , Stomach Neoplasms/therapy , Taxoids/administration & dosage , Tegafur/administration & dosage
12.
Leukemia ; 29(9): 1918-27, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25801913

ABSTRACT

Histone deacetylase (HDAC) inhibitors have been extensively investigated as therapeutic agents in cancer. However, the biological role of class IIa HDACs (HDAC4, 5, 7 and 9) in cancer cells, including multiple myeloma (MM), remains unclear. Recent studies show HDAC4 interacts with activating transcription factor 4 (ATF4) and inhibits activation of endoplasmic reticulum (ER) stress-associated proapoptotic transcription factor C/EBP homologous protein (CHOP). In this study, we hypothesized that HDAC4 knockdown and/or inhibition could enhance apoptosis in MM cells under ER stress condition by upregulating ATF4, followed by CHOP. HDAC4 knockdown showed modest cell growth inhibition; however, it markedly enhanced cytotoxicity induced by either tunicamycin or carfilzomib (CFZ), associated with upregulating ATF4 and CHOP. For pharmacological inhibition of HDAC4, we employed a novel and selective class IIa HDAC inhibitor TMP269, alone and in combination with CFZ. As with HDAC4 knockdown, TMP269 significantly enhanced cytotoxicity induced by CFZ in MM cell lines, upregulating ATF4 and CHOP and inducing apoptosis. Conversely, enhanced cytotoxicity was abrogated by ATF4 knockdown, confirming that ATF4 has a pivotal role mediating cytotoxicity in this setting. These results provide the rationale for novel treatment strategies combining class IIa HDAC inhibitors with ER stressors, including proteasome inhibitors, to improve patient outcome in MM.


Subject(s)
Endoplasmic Reticulum Stress , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylases/metabolism , Multiple Myeloma/metabolism , Apoptosis/drug effects , Apoptosis/genetics , Bone Marrow Cells/drug effects , Bone Marrow Cells/metabolism , Cell Death/drug effects , Cell Death/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Endoplasmic Reticulum Stress/drug effects , Endoplasmic Reticulum Stress/genetics , Gene Knockdown Techniques , Histone Deacetylases/genetics , Humans , Interleukin-6/metabolism , Isoenzymes , Multiple Myeloma/genetics , Multiple Myeloma/pathology , Proteasome Inhibitors/pharmacology , Repressor Proteins/genetics , Repressor Proteins/metabolism , Signal Transduction/drug effects , Stromal Cells/drug effects , Stromal Cells/metabolism
13.
Chem Commun (Camb) ; 51(26): 5717-20, 2015 Apr 04.
Article in English | MEDLINE | ID: mdl-25719744

ABSTRACT

Visible-light-controlled polymerization was achieved by a bichromophoric organopalladium catalyst which possesses a naphthyl-substituted cyclometallated Ir(III) light-absorbing moiety. The complex was highly active toward styrene polymerization upon visible-light irradiation, and its photoactivity toward polymerization and dimerization was switchable. On the basis of the switching activity, controlled copolymerization of styrene and vinyl ether was achieved upon photo-irradiation to give the corresponding copolymers.

15.
Skin Res Technol ; 21(1): 76-83, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24889490

ABSTRACT

BACKGROUND/AIMS: The matrix of intercellular lipids (ICL) of stratum corneum (SC) plays an important role in the barrier function of SC. It is important to understand the structure of the ICL matrix for dermatology and cosmetic science. Several methods exist for the analysis of the structure; however, it is difficult to conduct these analyses noninvasively. METHODS: We have developed a method for the analysis of the lateral packing of ICL using Raman spectroscopy. As a proof-of-principle experiment, we prepared a human SC sheet sample and analyzed its structure by the proposed method and by a conventional method involving X-ray diffraction. We compared the results of both methods. In addition, we applied the proposed method to living human skin, and we analyzed the lateral packing of ICL of SC taken from three separate body sites. RESULTS: The results of our method corresponded to those of the conventional method. We detected regional differences of ICL lateral packing using our method in vivo. The results indicated that the packing of ICL in SC taken from the forearm and upper arm are more ordered than that taken from the cheek. CONCLUSION: The results verify that our developed method allows the evaluation of the lateral packing of ICL inside the SC layer of the skin in vivo. Using this method, we can detect regional differences of SC samples taken from various body sites.


Subject(s)
Epidermis/chemistry , Lipids/analysis , Spectrum Analysis, Raman/instrumentation , Spectrum Analysis, Raman/methods , Abdomen , Adult , Arm , Cheek , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Temperature , Tissue Distribution
17.
Br J Cancer ; 111(4): 763-71, 2014 Aug 12.
Article in English | MEDLINE | ID: mdl-24937671

ABSTRACT

BACKGROUND: Interleukin-22 (IL-22) has been recently highlighted owing to its biological significance in the modulation of tissue responses during inflammation. However, the role of IL-22 in carcinogenesis has remained unclear. Here, we investigated the pathophysiological significance of IL-22 expression in gastric cancer tissues and examined the mechanism by which IL-22 promotes gastric cancer cell invasion. METHODS: Human gastric cancer specimens were analysed by immunohistochemistry for expression of IL-22 and IL-22 receptor 1 (IL-22R1). The effects of IL-22-induced STAT3 and ERK signalling on invasive ability of gastric cancer cells were examined using a small-interfering RNA system and specific inhibitors. AGS cells were co-cultured with cancer-associated fibroblasts (CAFs) from human gastric cancer tissues and assessed by invasion assay. RESULTS: Interleukin-22 and its receptor were expressed in α-smooth muscle actin-positive stromal cells and tumour cells at the invasive front of gastric cancer tissues, respectively. The expression of IL-22 and IL-22R1 was significantly related to lymphatic invasion. Interleukin-22 treatment promoted the invasive ability of gastric cancer cells through STAT3 and ERK activation. The invasive ability of gastric cancer cells was significantly enhanced by co-culture with IL-22-expressing CAFs. CONCLUSIONS: Interleukin-22 produced by CAFs promotes gastric cancer cell invasion via STAT3 and ERK signalling.


Subject(s)
Fibroblasts/metabolism , Interleukins/metabolism , MAP Kinase Signaling System , STAT3 Transcription Factor/metabolism , Stomach Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Cell Line, Tumor , Coculture Techniques , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Phosphorylation , Protein Processing, Post-Translational , Receptors, Interleukin/metabolism , Stomach Neoplasms/pathology , Interleukin-22
18.
Blood Cancer J ; 4: e180, 2014 Feb 07.
Article in English | MEDLINE | ID: mdl-24510029

ABSTRACT

Relapsed or refractory Burkitt's lymphoma often has a poor prognosis in spite of intensive chemotherapy that induces apoptotic and/or necrotic death of lymphoma cells. Rapamycin (Rap) brings about autophagy, and could be another treatment. Further, anti-CD19-targeted liposomal delivery may enable Rap to kill lymphoma cells specifically. Rap was encapsulated by anionic liposome and conjugated with anti-CD19 antibody (CD19-GL-Rap) or anti-CD2 antibody (CD2-GL-Rap) as a control. A fluorescent probe Cy5.5 was also liposomized in the same way (CD19 or CD2-GL-Cy5.5) to examine the efficacy of anti-CD19-targeted liposomal delivery into CD19-positive Burkitt's lymphoma cell line, SKW6.4. CD19-GL-Cy5.5 was more effectively uptaken into SKW6.4 cells than CD2-GL-Cy5.5 in vitro. When the cells were inoculated subcutaneously into nonobese diabetic/severe combined immunodeficiency mice, intravenously administered CD19-GL-Cy5.5 made the subcutaneous tumor fluorescent, while CD2-GL-Cy5.5 did not. Further, CD19-GL-Rap had a greater cytocidal effect on not only SKW6.4 cells but also Burkitt's lymphoma cells derived from patients than CD2-GL-Rap in vitro. The specific toxicity of CD19-GL-Rap was cancelled by neutralizing anti-CD19 antibody. The survival period of mice treated with intravenous CD19-GL-Rap was significantly longer than that of mice treated with CD2-GL-Rap after intraperitoneal inoculation of SKW6.4 cells. Anti-CD19-targeted liposomal Rap could be a promising lymphoma cell-specific treatment inducing autophagic cell death.

19.
Geobiology ; 12(2): 133-45, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24382149

ABSTRACT

We designed a new culture method for neutrophilic iron-oxidizing bacteria using liquid medium (i) to study the formation and mineralogical characteristics of biogenic iron oxides (BIOS) and (ii) to apply BIOS to various scientific and engineering applications. An iron-oxidizing bacterium, Mariprofundus ferrooxydans PV-1(T) (ATCC, BAA-1020), was cultured using a set of diffusion chambers to prepare a broad anoxic-oxic interface, upon which BIOS formation is typically observed in natural environments. Iron oxide precipitates were generated in parallel with bacterial growth. A scanning electron microscopy analysis indicated that the morphological features of the iron oxide precipitates in the medium (in vitro BIOS) were similar to those of BIOS collected from natural deep-sea hydrothermal environments in the Northwest Eifuku Seamount field in the northern Mariana Arc (in situ BIOS). Further chemical speciation of both the in vitro and in situ BIOS was examined with X-ray absorption fine structure (XAFS). A bulk XAFS analysis showed that the minerals in both BIOS were mainly ferrihydrite and oligomeric stages of amorphous iron oxyhydroxides with edge-sharing octahedral linkages. The amount of in vitro BIOS produced with the diffusion-chamber method was greater than those produced previously with other culture methods, such as gel-stabilized gradient and batch liquid culture methods. The larger yields of BIOS produced with the new culture method will allow us to clarify in the future the mineralization mechanisms during bacterial growth and to examine the physicochemical properties of BIOS, such as their adsorption to and coprecipitation with various elements and substances.


Subject(s)
Bacteriological Techniques/instrumentation , Bacteriological Techniques/methods , Ferric Compounds/metabolism , Geologic Sediments/microbiology , Proteobacteria/metabolism , Ferric Compounds/analysis , Geologic Sediments/analysis , Hydrothermal Vents/microbiology , Microscopy, Electron, Scanning , Oxidation-Reduction , X-Ray Absorption Spectroscopy
20.
Clin Toxicol (Phila) ; 51(9): 846-9, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24044532

ABSTRACT

CONTEXT: In acute glufosinate poisoning, sudden respiratory arrest and convulsion can occur after a latent period of 4-60 h. There is still no factor that accurately predicts the occurrence of these symptoms. OBJECTIVE: To elucidate the predictors of severe effects following acute glufosinate poisoning. MATERIALS AND METHODS: This study is a retrospective observational case series. The subjects were 16 patients who had acute glufosinate poisoning. They were divided into a group with respiratory arrest or convulsion during hospitalization (severe group) and a group without (non-severe group). The following characteristics (or predictors) were compared between the groups: age, sex, calculated amount of glufosinate (volume of ingested poison (glufosinate-containing herbicide) × glufosinate concentration of the product), time duration from poison ingestion to arrival at our hospital, use of gastric lavage, use of whole bowel irrigation, Glasgow Coma Scale, laboratory parameters, PaO2/FiO2 ratio (P/F ratio), shock index, and presence or absence of systemic inflammatory response syndrome (SIRS) on arrival. RESULTS: The P/F ratio was significantly lower in the severe group than in the non-severe group (median, 287.5 vs. 409.0; P = 0.049). The receiver operating characteristic (ROC) curve was plotted for the predictor of increasing severity based on the P/F ratio. The area under the curve was 0.714, and the optimal cutoff point for increasing severity was 374.0. The sensitivity was 75.0%, specificity of 71.4%, and accuracy of 75.0%. The shock index was significantly higher (median, 0.52 vs. 0.41; P = 0.031). Significantly more patients had SIRS in the severe group than in the non-severe group (P = 0.015). Logistic regression analysis was performed with a backward elimination procedure. SIRS was selected as the independent predictor of increasing severity (odds ratio, 29.810; 95% confidence interval, 1.011-878.952; P = 0.049). DISCUSSION AND CONCLUSION: Severe effects following acute glufosinate poisoning were associated with two positive SIRS criteria. A low P/F ratio may be useful for predicting the occurrence of respiratory complications.


Subject(s)
Aminobutyrates/toxicity , Enzyme Inhibitors/toxicity , Herbicides/toxicity , Neurotoxicity Syndromes/physiopathology , Respiratory Insufficiency/etiology , Seizures/etiology , Systemic Inflammatory Response Syndrome/etiology , Adult , Aged , Aged, 80 and over , Female , Glutamate Decarboxylase/antagonists & inhibitors , Glutamate-Ammonia Ligase/antagonists & inhibitors , Humans , Male , Middle Aged , Neurotoxicity Syndromes/blood , Neurotoxicity Syndromes/immunology , Oxygen/blood , Pulmonary Circulation/drug effects , ROC Curve , Retrospective Studies , Severity of Illness Index , Young Adult
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