Conventional therapies for metastatic cancers have limited efficacy. Recently, cancer therapies targeting noncancerous cells in tumor microenvironments have shown improved clinical outcomes in ...patients. However, further advances in our understanding of the metastatic tumor microenvironment are required to improve treatment outcomes. Adipocytes are distributed throughout the body, and as a part of the metastatic tumor microenvironment, they interact with cancer cells in almost all organs. Adipocytes secrete various factors that are reported to exert clinical effects on cancer progression, including engraftment, survival, and expansion at the metastatic sites. However, only a few studies have comprehensively examined their impact on cancer cells. In this review, we examined the impact of adipocytes on cancer by describing the adipocyte-secreted factors that are involved in controlling metastatic cancer, focusing on adipokines, such as adiponectin, leptin, visfatin, chemerin, resistin, apelin, and omentin. Adipocyte-secreted factors promote cancer metastasis and contribute to various biological functions of cancer cells, including migration, invasion, proliferation, immune evasion, and drug resistance at the metastatic sites. We propose the establishment and expansion of "adipo-oncology" as a research field to enhance the comprehensive understanding of the role of adipocytes in metastatic cancers and the development of more robust metastatic cancer treatments.
The effects of localized source currents on Earth’s magnetotelluric (MT) responses have been reported in the literature in terms of the changes in period and subsurface structure. The focus in this ...study is on the bias within the MT responses arising from variations in the vertical and horizontal distances of the source current. The MT responses at the periods of field aligned resonance (20 and 200 s) were calculated at various distances from the source current. A slight change in source distance causes a shift in the MT responses. The shift of apparent resistivity at 20 and 200 s exceeds 10% and 50% of the original values, respectively. Such features are found especially over the altitude range of the ionospheric E layer (i.e., 100–150 km), where MT source currents often flow. The vertical distance of the source field varies because the distribution of conductivity with altitude in the ionosphere and the region controlling the ionospheric electrical process change temporally. Thus, in assessing the temporal changes in MT responses, we should treat them carefully by checking the ionospheric environment.
During cryopreservation, spermatozoa may suffer cold and cryo-induced injuries ―associated with alterations in cell defense systems― that are detrimental to their function and subsequent fertility. ...This study aimed to determine the efficacy of supplementing the semen freezing extender with the antioxidant reduced glutathione (GSH) in cattle. Semen was collected from four bulls and diluted in a freezing extender supplemented with or without GSH (0, 1, 5, and 10 mM) before the cooling step of the cryopreservation process. After thawing, the quality of the frozen-thawed semen was investigated for motility, viability, acrosomal and DNA integrity, and subsequent embryo development after in vitro fertilization of bovine oocytes. Additionally, semen from one of the bulls was used to analyze semen antioxidative potential, sperm penetration into oocytes, male pronucleus formation rate, and embryo DNA integrity. The sperm quality varied among bulls after GSH supplementation. One bull had decreased sperm total motility, and two bulls had decreased sperm DNA integrity. GSH supplementation had positive effects on embryo development for three bulls. Two of them showed both improved cleavage and blastocyst formation rates, while the other one only showed an improved cleavage rate. We observed positive effects on early male pronucleus formation and no negative effects on DNA integrity and cell number in blastocyst stage embryos. Although the effect varies depending on individual bulls and GSH concentration, GSH supplementation in semen may improve in vitro embryo production from frozen semen.
Purpose
This study aimed at evaluating the efficacy of amide proton transfer (APT) imaging in differentiation of type II and type I uterine endometrial carcinoma.
Materials and methods
Thirty-three ...patients diagnosed with uterine endometrial carcinoma, including 24 with type I and 9 with type II carcinomas, underwent APT imaging. Two readers evaluated the magnetization transfer ratio at 3.5 ppm MTR
asym
(3.5 ppm) in each type of carcinoma. The average MTR
asym
(APT
mean
) and the maximum MTR
asym
(APT
max
) were analyzed. The receiver operating characteristic (ROC) curve analysis was performed.
Results
The APT
max
was significantly higher in type II carcinomas than in type I carcinomas (reader1,
p
= 0.004; reader 2,
p
= 0.014; respectively). However, APT
mean
showed no significant difference between type I and II carcinomas. Based on the results reported by reader 1, the area under the curve (AUC) pertaining to the APT
max
for distinguishing type I from type II carcinomas was 0.826, with a cut-off, sensitivity, and specificity of 9.90%, 66.7%, and 91.3%, respectively. Moreover, based on the results reported by reader 2, the AUC was 0.750, with a cut-off, sensitivity, and specificity of 9.80%, 62.5%, and 87.5%, respectively.
Conclusion
APT imaging has the potential to determine the type of endometrial cancer.
AIM To determine the efficacy of rifaximin for hepatic encephalopathy(HE) with the linkage of gut microbiome in decompensated cirrhotic patients.METHODS Twenty patients(12 men and 8 women; median ...age, 66.8 years; range, 46-81 years) with decompensated cirrhosis(Child-pugh score > 7) underwent cognitive neuropsychological testing, endotoxin analysis, and fecal microbiome assessment at baseline and after 4 wk of treatment with rifaximin 400 mg thrice a day. HE was determined by serum ammonia level and number connection test(NCT)-A. Changes in whole blood endotoxin activity(EA) was analyzed by endotoxinactivity assay. Fecal microbiome was assessed by 16 S ribosome RNA(rR NA) gene sequencing.RESULTS Treatment with rifaximin for 4 wk improved hyperammonemia(from 90.6 ± 23.9 μg/d L to 73.1 ± 33.1 μg/dL; P < 0.05) and time required for NCT(from 68.2 ± 17.4 s to 54.9 ± 20.3 s; P < 0.05) in patients who had higher levels at baseline. Endotoxin activity was reduced(from 0.43 ± 0.03 to 0.32 ± 0.09; P < 0.05) in direct correlation with decrease in serum ammonia levels(r = 0.5886, P < 0.05). No statistically significant differences were observed in the diversity estimator(Shannon diversity index) and major components of the gut microbiome between the baseline and after treatment groups(3.948 ± 0.548 at baseline vs 3.980 ± 0.968 after treatment; P = 0.544), but the relative abundances of genus Veillonella and Streptococcus were lowered.CONCLUSION Rifaximin significantly improved cognition and reduced endotoxin activity without significantly affecting the composition of the gut microbiome in patients with decompensated cirrhosis.
Sodium‐glucose cotransporter 2 inhibitors (SGLT2‐Is) comprise a new class of antidiabetic agents that inhibit glucose reabsorption in the renal proximal tubules. Although a recent report demonstrated ...the potential ability of SGLT2‐Is to attenuate cancer growth of SGLT2‐expressing cancer cells, little is known about the effects of SGLT2‐Is on hepatocellular carcinoma (HCC). Here, we investigate the anti‐cancer properties of a SGLT2‐I, canagliflozin, against human liver cancer cells. SGTL2 mRNA and protein expression were detected in Huh7 and HepG2 cells, although not in HLE as well as primary human hepatocytes and hepatic stellate cells. Canagliflozin exerted antiproliferative effects on SGLT2‐expressing Huh7 and HepG2 cells in a dose‐dependent manner by inhibiting glycolytic metabolism including glucose uptake, lactate and intracellular ATP production. This agent also induced G2/M arrest and apoptosis with inhibited phosphorylation of ERK, p38 and AKT and cleavage of caspase3. Xenograft tumor growth assay showed that oral administration of canagliflozin (10 mg/kg/day) significantly reduced subcutaneous tumor burdens in a glycemic status‐independent manner, and attenuated intratumor vascularization in Huh7‐ and HepG2‐derived xenograft tumors in BALB/c nude mice. In vitro, canagliflozin suppressed the increased human umbilical vein endothelial cell (HUVEC) proliferation and tubular formation which were observed in Huh7 or HepG2 co‐cultures. By contrast, canagliflozin had no effect on tumor growth and intratumor angiogenesis in SGLT2‐null HLE‐derived xenograft models. These results indicate that SGLT2‐I therapy is a potential new strategy for the treatment of HCC.
What's new?
Sodium‐glucose cotransporter 2 inhibitors (SGLT2‐Is) comprise a new class of antidiabetic agents that inhibit glucose reabsorption in the renal proximal tubules. Although recent evidence suggests that SGLT2‐Is can attenuate growth of SGLT2‐expressing cancer cells, little is known about their effects on hepatocellular carcinoma (HCC). Our study shows that the SGLT2‐I canagliflozin directly inhibits the growth of SGLT2‐expressing liver cancers by reducing glucose uptake and inhibiting glycolytic metabolism. Furthermore, canagliflozin attenuates proangiogenic activity in SGLT2‐expressing liver cancers. Because SGLT2‐Is are already used extensively without serious side effects, these agents may emerge as a new therapeutic strategy for HCC patients.
Targeting self-renewal is an important goal in cancer therapy and recent studies have focused on Notch signalling in the maintenance of stemness of glioma stem cells (GSCs). Understanding ...cancer-specific Notch regulation would improve specificity of targeting this pathway. In this study, we find that Notch1 activation in GSCs specifically induces expression of the lncRNA, TUG1. TUG1 coordinately promotes self-renewal by sponging miR-145 in the cytoplasm and recruiting polycomb to repress differentiation genes by locus-specific methylation of histone H3K27 via YY1-binding activity in the nucleus. Furthermore, intravenous treatment with antisense oligonucleotides targeting TUG1 coupled with a drug delivery system induces GSC differentiation and efficiently represses GSC growth in vivo. Our results highlight the importance of the Notch-lncRNA axis in regulating self-renewal of glioma cells and provide a strong rationale for targeting TUG1 as a specific and potent therapeutic approach to eliminate the GSC population.
For semen suppliers, predicting the low fertility of service bull candidates before artificial insemination would help prevent economic loss; however, predicting bull fertility through in vitro ...assessment of semen is yet to be established. In the present study, we focused on the methylated CpG sites of sperm nuclear DNA and examined methylation levels to screen new biomarkers for predicting bull fertility. In frozen-thawed semen samples collected from Japanese Black bulls, for which the sire conception rate (SCR) was recorded, the methylation level of each CpG site was analyzed using human methylation microarray. According to regression analysis, 143 CpG sites related to SCR were significantly differentially methylated. Whole genome bisulfite sequence data were obtained from three semen samples and the differentially methylated regions (DMRs) that included the target CpG sites selected by human methylation microarray were confirmed. Using combined bisulfite restriction analysis, fertility-related methylation changes were detected in 10 DMRs. With the exception of one DMR, the methylation levels of these DMRs were significantly different between groups with high fertility (> 50%) and low fertility (< 40%). From multiple regression analysis of methylation levels and SCR, three DMRs were selected that could effectively predict bull fertility. We suggest that these fertility-related differences in spermatozoal methylation levels could be new epigenetic biomarkers for predicting bull fertility.
Extracellular vesicles (EVs) are membrane vesicles that are released from cells and mediate cell-cell communication. EVs carry protein, lipid, and nucleic acid cargoes that interact with recipient ...cells to alter their phenotypes. Evidence is accumulating that tumor-derived EVs can play important roles in all steps of cancer progression. Here, we review recent studies reporting critical roles for EVs in four major areas of cancer progression: promotion of cancer invasiveness and motility, enhancement of angiogenesis and vessel permeability, conditioning premetastatic niches, and immune suppression.
Abstract
Brain metastases (BM) occur in at least 10% of cancer patients, and are one of the main causes of cancer-related deaths and significant deterioration in the quality of life of cancer ...patients due to the neurological deterioration caused by brain compression and tumor invasion. Whole-brain irradiation has been emphasized as the standard treatment for BM. However, recent clinical trials including the JLGK0901 and JCOG0504 trials conducted in Japan have established therapeutic evidence for the use of stereotactic radiosurgery with regular follow-up with magnetic resonance imaging for BM. In addition to surgery and stereotactic radiotherapy, advances in drug therapy for BM, such as tyrosine kinase inhibitors and immune checkpoint inhibitors, are expected. This review describes the history and the recent evidence of the diagnosis and treatment of BM.
Recent clinical trials have established therapeutic evidence for the use of stereotactic radiosurgery with regular follow-up with magnetic resonance imaging for brain metastases.
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