58 research outputs found
A Human Head and Neck Squamous Cell Carcinoma Cell Line with Acquired cis-Diamminedichloroplatinum-Resistance Shows Remarkable Upregulation of BRCA1 and Hypersensitivity to Taxane
Recently, an inverse
relationship between resistance to
platinum-based chemotherapeutic agents and
taxanes has been implicated in breast and
ovarian cancers, and a possible pivotal role for
BRCA1 has also been suggested. Because
cis-diamminedichloroplatinum
(CDDP) and taxanes are the most active antitumor
agents against head and neck squamous cell
carcinoma (HNSCC), we analyzed the sensitivity
of nine HNSCC cell lines and their previously
established derived CDDP-resistant cell lines to
two representative taxanes: docetaxel and
paclitaxel. None of the nine original cell lines
showed any cross resistance between CDDP and
taxanes, but one of the CDDP-resistant cell
lines, RPMI2650CR, demonstrated hypersensitivity
to both taxanes when compared to the parental
cell line, RPMI2650. Furthermore, RPMI2650CR
exhibited increased expression of BRCA1. These
data suggest that (i) taxanes are a good
candidate for a second-line therapeutic drug for
HNSCC patients with acquired CDDP resistance
and (ii) BRCA1 can be a candidate marker for
predicting an inverse CDDP/taxane sensitivity
phenotype in HNSCC
Soymilk Improves Muscle Weakness in Young Ovariectomized Female Mice
Estrogens play a key role in an extensive range of physiological functions in various types of tissues throughout the body in females. We previously showed that estrogen insufficiency caused muscle weakness that could be rescued by estrogen administration in a young female ovariectomized (OVX) mouse model. However, long-term estrogen replacement therapy increases risks of breast cancer and cardiovascular diseases. Soymilk contains plant-based protein and isoflavones that exert estrogen-like activity. Here we examined the effects of prolonged soymilk intake on muscle and its resident stem cells, called satellite cells, in the estrogen-insufficient model. Six-week-old C57BL/6 OVX female mice were fed with a dried soymilk-containing diet. We found that prolonged soymilk intake upregulated grip strength in OVX mice. Correspondingly, cross-sectional area of tibialis anterior muscle was significantly increased in OVX mice fed with soymilk. Furthermore, soymilk diet mitigated dysfunction of satellite cells isolated from OVX mice. Thus, these results indicated that prolonged soymilk intake is beneficial for improving muscle weakness in an estrogen-insufficient state in females
Novel SLC30A2 mutations in the pathogenesis of transient neonatal zinc deficiency
[Importance] Transient neonatal zinc deficiency (TNZD) occurs in breastfed infants due to abnormally low breast milk zinc levels. Mutations in the solute carrier family 30 member 2 (SLC30A2) gene, which encodes the zinc transporter ZNT2, cause low zinc concentration in breast milk. [Objective] This study aimed to provide further insights into TNZD pathophysiology. [Methods] SLC30A2 sequencing was performed in three unrelated Japanese mothers, whose infants developed TNZD due to low-zinc milk consumption. The effects of the identified mutations were examined using cell-based assays and luciferase reporter analysis. [Results] Novel SLC30A2 mutations were identified in each mother. One harbored a heterozygous missense mutation in the ZNT2 zinc-binding site, which resulted in defective zinc transport. The other two mothers exhibited multiple heterozygous mutations in the SLC30A2 promoter, the first mutations in the SLC30A2 regulatory region reported to date. [Interpretation] This report provides new genetic insights into TNZD pathogenesis in breastfed infants
CHAC1 overexpression in human gastric parietal cells with Helicobacter pylori infection in the secretory canaliculi
Background
Cation transport regulator 1 (CHAC1), a newly discovered enzyme that degrades glutathione, is induced in Helicobacter pylori (H. pylori)‐infected gastric epithelial cells in culture. The CHAC1‐induced decrease in glutathione leads to an accumulation of reactive oxygen species and somatic mutations in TP53. We evaluated the possible correlation between H. pylori infection and CHAC1 expression in human gastric mucosa.
Materials and Methods
Both fresh‐frozen and formalin‐fixed paraffin‐embedded tissue samples of gastric mucosa with or without H. pylori infection were obtained from 41 esophageal cancer patients that underwent esophago‐gastrectomy. Fresh samples were used for real‐time polymerase chain reaction for H. pylori DNA and CHAC1 mRNA, and formalin‐fixed samples were used for immunohistochemistry with anti‐CHAC1 and anti‐H. pylori monoclonal antibodies. Double‐enzyme or fluorescence immunohistochemistry and immuno‐electron microscopy were used for further analysis.
Results
Significant CHAC1 overexpression was detected in H. pylori‐infected parietal cells that expressed the human proton pump/H,K‐ATPase α subunit, whereas a constitutively low level of CHAC1 mRNA expression was observed in the other samples regardless of the H. pylori infection status, reflecting the weak CHAC1 expression detected by immunohistochemistry in the fundic‐gland areas. Immuno‐electron microscopy revealed intact H. pylori cells in the secretory canaliculi of infected parietal cells. Some parietal cells exhibited positive nuclear signals for Ki67 in the neck zone of the gastric fundic‐gland mucosa with H. pylori infection.
Conclusion
Cation transport regulator 1 overexpression in H. pylori‐infected parietal cells may cause the H. pylori‐induced somatic mutations that contribute to the development of gastric cancer.This work was supported by the Japan Society
for the Promotion of Science KAKENHI (16K19077), and by the
Practical Research for Innovative Cancer Control from Japan Agency
for Medical Research and development, AMED
Association of glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS): a cross-sectional study
Background While survival of systemic lupus erythematosus (SLE) patients has improved substantially, problems remain in the management of their emotional health. Medium to high-dose glucocorticoid doses are known to worsen emotional health; the effect is unclear among patients receiving relatively low-dose glucocorticoids. This study aims to investigate the association between low glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS). Methods This cross-sectional study drew on data from SLE patients in 10 Japanese institutions. The participants were adult patients with SLE duration of >= 1 year who met LLDAS criteria at the study visit from April 2018 through September 2019. The exposure was the daily glucocorticoid dose (mg oral prednisolone). The outcome was the emotional health score of the lupus patient-reported outcome scale (range: 0 to 100). Multiple linear regression analysis was performed with adjustment for confounders including disease-related damage, activity, and psychotropic drug use. Results Of 192 patients enrolled, 175 were included in the analysis. Their characteristics were as follows: female, 89.7%; median age, 47 years (interquartile range (IQR): 37.0, 61.0). Median glucocorticoid dose was 4.0 mg (IQR 2.0, 5.0), and median emotional health score 79.2 (IQR 58.3, 91.7). Multiple linear regression analysis showed daily glucocorticoid doses to be associated with worse emotional health (beta coefficient = - 2.54 [95% confidence interval - 4.48 to - 0.60], P = 0.01). Conclusions Daily glucocorticoid doses were inversely associated with emotional health among SLE patients in LLDAS. Further studies are needed to determine whether glucocorticoid tapering leads to clinically significant improvements in emotional health
Results of the search for inspiraling compact star binaries from TAMA300's observation in 2000-2004
We analyze the data of TAMA300 detector to search for gravitational waves
from inspiraling compact star binaries with masses of the component stars in
the range 1-3Msolar. In this analysis, 2705 hours of data, taken during the
years 2000-2004, are used for the event search. We combine the results of
different observation runs, and obtained a single upper limit on the rate of
the coalescence of compact binaries in our Galaxy of 20 per year at a 90%
confidence level. In this upper limit, the effect of various systematic errors
such like the uncertainty of the background estimation and the calibration of
the detector's sensitivity are included.Comment: 8 pages, 4 Postscript figures, uses revtex4.sty The author list was
correcte
Observation results by the TAMA300 detector on gravitational wave bursts from stellar-core collapses
We present data-analysis schemes and results of observations with the TAMA300
gravitational-wave detector, targeting burst signals from stellar-core collapse
events. In analyses for burst gravitational waves, the detection and
fake-reduction schemes are different from well-investigated ones for a
chirp-wave analysis, because precise waveform templates are not available. We
used an excess-power filter for the extraction of gravitational-wave
candidates, and developed two methods for the reduction of fake events caused
by non-stationary noises of the detector. These analysis schemes were applied
to real data from the TAMA300 interferometric gravitational wave detector. As a
result, fake events were reduced by a factor of about 1000 in the best cases.
The resultant event candidates were interpreted from an astronomical viewpoint.
We set an upper limit of 2.2x10^3 events/sec on the burst gravitational-wave
event rate in our Galaxy with a confidence level of 90%. This work sets a
milestone and prospects on the search for burst gravitational waves, by
establishing an analysis scheme for the observation data from an
interferometric gravitational wave detector
Modified Bentall operation with bioprosthetic valve and Valsalva graft conduit:the "slit skirt" technique
We elucidated the efficacy of the slit skirt technique to prevent bleeding from the proximal anastomosis between the graft and aortic annulus. Between September 2008 and September 2014, 15 patients underwent a modified Bentall operation with the slit skirt technique at our institution. No patients had bleeding from the proximal anastomosis. No re-thoracotomy for bleeding was required. During midterm follow-up (median period, 21 months), no patient had pseudoaneurysms at the proximal suture line. We conclude that the slit skirt technique is useful to prevent bleeding from the proximal anastomosis after the Bentall operation
Dipeptidyl peptidase-4 inhibitor linagliptin attenuates neointima formation after vascular injury
Is visceral adiposity a modifier for the impact of blood pressure on arterial stiffness and albuminuria in patients with type 2 diabetes?
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