Targeting the tumor stroma is an important strategy in cancer treatment. Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are two main components in the tumor microenvironment (TME) in hepatocellular carcinoma (HCC), which can promote tumor progression. Plasminogen activator inhibitor-1 (PAI-1) upregulation in HCC is predictive of unfavorable tumor behavior and prognosis. However, the crosstalk between cancer cells, TAMs and CAFs, and the functions of PAI-1 in HCC remain to be fully investigated. In the present study, macrophage polarization and key paracrine factors were assessed during their interactions with CAFs and cancer cells. Cell proliferation, wound healing and Transwell and Matrigel assays were used to investigate the malignant behavior of HCC cells in vitro. It was found that cancer cells and CAFs induced the M2 polarization of TAMs by upregulating the mRNA expression levels of CD163 and CD206, and downregulating IL-6 mRNA expression and secretion in the macrophages. Both TAMs derived from cancer cells and CAFs promoted HCC cell proliferation and invasion. Furthermore, PAI-1 expression was upregulated in TAMs after being stimulated with CAF-conditioned medium and promoted the malignant behavior of the HCC cells by mediating epithelial-mesenchymal transition. CAFs were the main producer of C-X-C motif chemokine ligand 12 (CXCL12) in the TME and CXCL12 contributed to the induction of PAI-1 secretion in TAMs. In conclusion, the results of the present study suggested that CAFs promoted the M2 polarization of macrophages and induced PAI-1 secretion via CXCL12. Furthermore, it was found that PAI-1 produced by the TAMs enhanced the malignant behavior of the HCC cells. Therefore, these factors may be targets for inhibiting the crosstalk between tumor cells, CAFs and TAMs.
Objective: The aim of this study was to investigate the potential of an intraoperative 3D hologram, which was a computer graphics model liver, with mixed reality techniques in liver surgery. Summary Background Data: The merits for the application of a hologram for surgical support are: 1) no sterilized display monitor; 2) better spatial awareness; and 3) 3D images shared by all the surgeons. Methods: 3D polygon data using preoperative computed tomography data was installed into head mount displays, HoloLens (Microsoft Corporation, Redmond, WA). Results: In a Wi-Fi-enabled operative room, several surgeons wearing HoloLens succeeded in sharing the same hologram and moving that hologram from respective operators’ angles by means of easy gesture-handling without any monitors. The intraoperative hologram contributed to better imagination of tumor locations, and for determining the parenchymal dissection line in the hepatectomy for the patients with more than 20 multiple colo-rectal liver metastases. In another case, the hologram enabled a safe Gliisonean pedicle approach for hepato-cellular carcinoma with a hilar anatomical anomaly. Surgeons could easily compare the real patient's anatomy and that of the hologram just before the hepatic hilar procedure. Conclusions: This initial experience suggested that an intraoperative hologram with mixed reality techniques contributed to “last-minute simulation,” not for “navigation.” The intraoperative hologram might be a new next-generation operation-supportive tool in terms of spatial awareness, sharing, and simplicity.
Brown adipose tissue (BAT) is responsible for cold-and diet-induced thermogenesis, and thereby contributes to the control of whole-body energy expenditure (EE) and body fat content. BAT activity can be assessed by fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) in human subjects. Grains of paradise (GP, Aframomum melegueta), a species of the ginger family, contain pungent, aromatic ketones such as 6-paradol, 6-gingerol and 6-shogaol. An alcohol extract of GP seeds and 6-paradol are known to activate BAT thermogenesis in small rodents. The present study aimed to examine the effects of the GP extract on whole-body EE and to analyse its relation to BAT activity in men. A total of nineteen healthy male volunteers aged 20-32 years underwent FDG-PET after 2 h of exposure to cold at 198C with light clothing. A total of twelve subjects showed marked FDG uptake into the adipose tissue of the supraclavicular and paraspinal regions (BAT positive). The remaining seven showed no detectable uptake (BAT negative). Within 4 weeks after the FDG-PET examination, whole-body EE was measured at 278C before and after oral ingestion of GP extract (40 mg) in a single-blind, randomised, placebocontrolled, crossover design. The resting EE of the BAT-positive group did not differ from that of the BAT-negative group. After GP extract ingestion, the EE of the BAT-positive group increased within 2 h to a significantly greater (P,0·01) level than that of the BAT-negative group. Placebo ingestion produced no significant change in EE. These results suggest that oral ingestion of GP extract increases wholebody EE through the activation of BAT in human subjects.Key words: Grains of paradise: 6-Paradol: Brown adipose tissue: Energy expenditure Brown adipose tissue (BAT) is the major site for sympathetically activated thermogenesis during cold exposure and spontaneous overfeeding, at least in small rodents (1) . Recent studies using fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) combined with computed tomography (CT) have revealed the existence of metabolically active BAT in adult human subjects (2 -4) . It is now established that, in healthy adults, BAT is activated by acute cold exposure and significantly contributes to cold-induced thermogenesis (2 -5) . It has also been demonstrated that the prevalence and activity of BAT are lower in subjects with higher adiposity, being negatively correlated with BMI, body fat content and visceral fat (2,3) . Moreover we found that the prevalence of BAT decreased with age, being more than 50 % in the twenties, but less than 10 % in the fifties and sixties, and that decreased BAT activity is associated with age-related accumulation of body fat (6) . It is thus likely that BAT, based on its thermogenic activity, contributes to the control of whole-body energy expenditure (EE) and body fat metabolism in human subjects, as established in small rodents, and thereby is a promising target for interventions to prevent and treat obesity. A number of food ingredients have been p...
Although pancreatic cancer often invades peripancreatic adipose tissue, little information is known about cancer‐adipocyte interaction. We first investigated the ability of adipocytes to de‐differentiate to cancer‐associated adipocytes (CAAs) by co‐culturing with pancreatic cancer cells. We then examined the effects of CAA‐conditioned medium (CAA‐CM) on the malignant characteristics of cancer cells, the mechanism underlying those effects, and their clinical relevance in pancreatic cancer. When 3T3‐L1 adipocytes were co‐cultured with pancreatic cancer cells (PANC‐1) using the Transwell system, adipocytes lost their lipid droplets and changed morphologically to fibroblast‐like cells (CAA). Adipocyte‐specific marker mRNA levels significantly decreased but those of fibroblast‐specific markers appeared, characteristic findings of CAA, as revealed by real‐time PCR. When PANC‐1 cells were cultured with CAA‐CM, significantly higher migration/invasion capability, chemoresistance, and epithelial‐mesenchymal transition (EMT) properties were observed compared with control cells. To investigate the mechanism underlying these effects, we performed microarray analysis of PANC‐1 cells cultured with CAA‐CM and found a 78.5‐fold higher expression of SAA1 compared with control cells. When the SAA1 gene in PANC‐1 cells was knocked down with SAA1 siRNA, migration/invasion capability, chemoresistance, and EMT properties were significantly attenuated compared with control cells. Immunohistochemical analysis on human pancreatic cancer tissues revealed positive SAA1 expression in 46/61 (75.4%). Overall survival in the SAA1‐positive group was significantly shorter than in the SAA1‐negative group (P = .013). In conclusion, we demonstrated that pancreatic cancer cells induced de‐differentiation in adipocytes toward CAA, and that CAA promoted malignant characteristics of pancreatic cancer via SAA1 expression, suggesting that SAA1 is a novel therapeutic target in pancreatic cancer.
BackgroundLight emitting‐diodes (LED) have various effects on living organisms and recent studies have shown the efficacy of visible light irradiation from LED for anticancer therapies. However, the mechanism of LED's effects on cancer cells remains unclear. The aim of the present study was to investigate the effects of LED on colon cancer cell lines and the role of photoreceptor Opsin 3 (Opn3) on LED irradiation in vitro.MethodsHuman colon cancer cells (HT‐29 or HCT‐116) were seeded onto laboratory dishes and irradiated with 465‐nm LED at 30 mW/cm2 for 30 minutes. Cell Counting Kit‐8 was used to measure cell viability, and apoptosis and caspase 3/8 expression were evaluated by AnnexinV/PI and reverse transcription‐polymerase chain reaction (RT‐PCR), respectively. Autophagy and expression of LC‐3 and beclin‐1 were also evaluated by autophagy assays, RT‐PCR and Western blotting. We further tested Opn3 knockdown by Opn3 siRNA and the Gi/o G‐protein inhibitor NF023 in these assays.ResultsViability of HT‐29 and HCT‐116 cells was lower in 465‐nm LED‐irradiated cultures than in control cultures. LC‐3 and beclin‐1 expressions were significantly higher in LED‐irradiated cultures, and autophagosomes were detected in irradiated cells. The reductive effect of cancer cell viability following blue LED irradiation was reversed by Opn3 knockdown or NF023 treatment. Furthermore, increased LC‐3 and beclin‐1 expression that resulted from blue LED irradiation was suppressed by Opn3 knockdown or NF023 treatment.ConclusionBlue LED irradiation suppressed the growth of colon cancer cells and Opn3 may play an important role as a photoreceptor.
In order to search for radical scavengers which could be used as raw materials for cosmetics, phenyl propanoids (eugenol, isoeugenol, dehydrodieugenol, dehydrodieugenol B and coniferyl aldehyde) were examined for their hydroxyl radical (.OH) scavenging ability. A Fenton system was used to produce .OH. In order to see scavenging by these phenyl propanoids, competition reactions between a spin trap, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), and these phenyl propanoids for .OH were studied. The relative yield of the spin adduct of .OH (DMPO-OH) was measured by electron spin resonance spectroscopy. The approximate rate constants of the reactions between these phenyl propanoids and .OH estimated by measuring the reduced height of the ESR signals of DMPO-OH were found to be at least in the order of 10(9) M-1 s-1 (diffusion-controlled). Also, using the TBA tests, the reactions between .OH and several compounds reactive with .OH were investigated in the presence of the phenyl propanoids and it was found that the phenyl propanoids compete with such reactive compounds for .OH. These results indicate that these phenyl propanoids can be used as antioxidants for skin damage perhaps caused by .OH generated by UV-light.
Ca2+ response to veratridine in CA1 pyramidal cells | 755
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