Mobilization of monocytic myeloid-derived suppressor cells is regulated by PTH1R activation in bone marrow stromal cells

Myeloid-derived suppressor cells(MDSCs)are bone marrow(BM)-derived immunosuppressive cells in the tumor microenvironment,but the mechanism of MDSC mobilization from the BM remains unclear.We investigated how BM stromal cell activation by PTH1R contributes to MDSC mobilization.PTH1R activation by parathyroid hormone(PTH)or PTH-related peptide(PTHrP),a tumor-derived counterpart,mobilized monocytic(M-)MDSCs from murine BM without increasing immunosuppressive activity.In vitro cell-binding assays demonstrated thatα4β1 integrin and vascular cell adhesion molecule(VCAM)-1,expressed on M-MDSCs and osteoblasts,respectively,are key to M-MDSC binding to osteoblasts.Upon PTH1R activation,osteoblasts express VEGF-A and IL6,leading to Src family kinase phosphorylation in M-MDSCs.Src inhibitors suppressed PTHrP-induced MDSC mobilization,and Src activation in M-MDSCs upregulated two proteases,ADAM-17 and MMP7,leading to VCAM1 shedding and subsequent disruption of M-MDSC tethering to osteoblasts.Collectively,our data provide the molecular mechanism of M-MDSC mobilization in the bones of tumor hosts.

Multi-analyte analysis of cytokines that predict outcomes in patients with hepatocellular carcinoma treated with radiotherapy

AIM To analyze cytokine levels and to identify their association with outcome in patients with hepatocellular carcinoma(HCC) treated with radiotherapy(RT). METHODS Patients with HCC who were treated with RT were eligible for this prospective study. Blood samples were collected before and after RT, and serum cytokine levels including interleukin(IL)-1, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor-α were analyzed. RESULTS Between 2008 and 2009, 51 patients were enrolled in this study. Baseline IL-6 level was high in patients with a history of pre-RT treatment. Median survival was 13.9 mo with alpha-fetoprotein(AFP) as a significant factor(P = 0.020). Median failure-free survival(FFS) for infield, outfield-intrahepatic and extrahepatic failures were 23.3, 11.5 and 12.0 mo, respectively. Sex and baseline IL-6 level were associated with infield FFS, and baseline IL-10 level was correlated with outfield-intrahepatic FFS. For extrahepatic FFS, AFP was significant(P =0.034). Patients with a baseline IL-6 level of ≥ 9.7 pg/m L showed worse infield FFS(P = 0.005), and this significance was observed only in treatment-non-na?ve patients(P = 0.022). CONCLUSION In addition to AFP, cytokines seem useful in predicting infield and outfield-intrahepatic failure. Serum cytokines could be useful biomarkers for predicting RT outcome in HCC.

Synthesis of Fe_3O_4-coated silica aerogel nanocomposites

Fe3O4:SiO2 nanocomposite powders were synthesized by a two-step process,which included the precipitation of FeCl2 and FeCl3 and the gelation of silicic acid solution derived from water glass.At first,Fe3O4 nanoparticles having a crystallite size of 20 nm were obtained by controlling the ratio of Fe(II) and Fe(III) precursors.In the second step,Fe3O4 particles were embedded in SiO2 matrix by the hydrolysis and subsequent condensation of the silicic acid solution containing Fe3O4 particles.It was found that the Fe3O4 nanoparticles homogenously disperse in the SiO2 matrix.The Fe3O4:SiO2 nanocomposite exhibited an enhanced thermal stability against oxidation compared with pure Fe3O4.FT-IR analysis indicates the presence of the Si-O-Fe bond in the Fe3O4:SiO2 (1:10,mole fraction) nanocomposite.

Complete restoration of congenital conductive hearing loss by staged surgery: A case report

BACKGROUND Stapedial tendon ossification is a rare disease,with only a few reports.The stapedial tendon originates from the apex of the pyramidal eminence and is attached to the neck of the stapes.In stapedial tendon ossification,the stapes is fixed,causing conductive hearing loss.In most cases,complete hearing restoration is achieved by dividing the stapedial tendon after exploratory tympanotomy.CASE SUMMARY A 28-year-old woman presented to our hospital with the major complaint of bilateral hearing loss that started during childhood.Exploratory tympanotomy was performed due to suspicion of otosclerosis or middle ear anomalies.We found bilateral conductive hearing loss due to stapedial tendon ossification with a middle ear anomaly during surgery.There have been several reports of complete recovery of hearing after resection of the stapedial tendon.However,in this case,recovery of hearing was insufficient,even with the division of the stapedial tendon.In the second surgery,the stapes anomaly and footplate fixation were confirmed,and hearing was completely recovered after stapedotomy.Therefore,we report this case with a review of the relevant literature.CONCLUSION This is the first case of stapedial tendon ossification and fixation of the footplate surgically diagnosed on both sides.With surgical treatment,successful results are expected.

Clinical outcomes of endoscopic resection of superficial nonampullary duodenal epithelial tumors: A 10-year retrospective, single-center study

BACKGROUND Although premalignant duodenal lesions such as adenomas are uncommon,the incidences of these lesions have increased in recent times,and thus,the demand for minimally invasive treatments such as endoscopic resection(ER)has also increased.However,ER in the duodenum is more challenging than ER in other locations of the gastrointestinal tract.AIM To evaluate the safety and efficacy of ER for superficial nonampullary duodenal epithelial tumors(SNADETs)METHODS We performed a retrospective observational study on 56 consecutive patients(58 lesions)diagnosed with SNADETs that underwent ER from January 2011 to December 2020 at Yeungnam University Hospital.Patient demographics,lesion characteristics,and procedural and technical data were collected,and clinical outcomes,including procedure-related complications,completeness of resection,and recurrence were analyzed.RESULTS Median patient age was 57 years[range,26–77,30(53.6%)men].Endoscopic mucosal resection(EMR)was performed on 57 lesions(98.3%)and snare polypectomy on one(1.7%).Lesions consisted of 52 adenomas with low-grade dysplasia(89.7%),3 adenomas with high-grade dysplasia(5.2%),and 3 intramucosal adenocarcinomas(5.2%).There were 16 cases of intraprocedural bleeding(27.6%)and 1 case of delayed bleeding(1.7%),and all these 17 cases were successfully managed endoscopically.No perforation or procedure-related death occurred.Larger lesion size was associated with an increased risk of EMR-related bleeding(P=0.033).During a median follow-up period of 23 mo(range 6–100 mo),no local recurrence occurred,despite the fact one-third of the patients(19 lesions,32.8%)underwent piecemeal resection and 3 patients(3 lesions,5.2%)that underwent en bloc resection had a pathologically determined positive lateral margin.No patient died from a primary duodenal neoplasm.CONCLUSION The majority of SNADETs can be safely and curatively resected by EMR,and thus,based on consideration of the high incidence of fatal complications attributable to ESD,we conclude EMR,including piecemeal resection,should be considered the treatment of first choice for SNADETs.