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PURPOSE: We investigated the role of tumor-associated macrophages (TAMs) on the epithelial to mesenchymal transition (EMT) of colorectal cancer cells and determined the potential mechanism involved in the metastatic process. MATERIALS AND METHODS: In this study, flow cytometry was used to detect the expression of target proteins. We used transwell assay to evaluate the migration of cancer cells under specific conditions. Using real-time polymerase chain reaction, we examined the expressions of cytokines and EMT-related markers in mRNA level. Animal assay was performed for analysis in vivo and hematoxylin and eosin was used to visualize the effect of TAMs on tumor metastasis. We also used immunohistochemistry and Western blotting to detect the expression of target proteins. RESULTS: Here, we observed enrichment of TAMs in colorectal tumor tissues, resulting in high metastasis in clinical therapy. Moreover, those TAMs could facilitate the EMT progression of colorectal cancer cells, which is induced by the transforming growth factor-β (TGF-β) derived from TAMs, leading to the invasion and migration of cancer cells. CONCLUSION: Our results demonstrated that TAMs contributed the EMT progression through a TGF-β/Smad2,3-4/Snail signaling pathway, and disrupting this pathway with TGF-β receptor inhibitor could suppress metastasis, readjusting our focus to the connection of TAMs and cancer metastasis.
Subject(s)
Animals , Blotting, Western , Colorectal Neoplasms , Cytokines , Eosine Yellowish-(YS) , Flow Cytometry , Hematoxylin , Immunohistochemistry , Macrophages , Neoplasm Metastasis , Real-Time Polymerase Chain Reaction , RNA, MessengerABSTRACT
Objective To investigate the effect of early cerebrospinal fluid replacement on nuclear factor-κB (NF-κB) level and clinical outcomes in patients with aneurismal subarachnoid hemorrhage (aSAH) after endovascular embolization.Methods Patients with aSAH received aneurysm embolization were enrolled.They were divided into a cerebrospinal fluid replacement group and a non-cerebrospinal fluid replacement group according to the treatment scheme.All patients were treated with cerebral aneurysm coil embolization within 3 days after admission.The cerebrospinal fluid replacement group performed lumbar puncture cerebrospinal fluid replacement within 24 h after coil embolization,once every other day,20-30 ml of cerebrospinal fluid was replaced each time and 3 mg dexamethasone was injected intrathecally.The NF-κB levels in cerebrospinal fluid were detected at day 1,7 and 14 after the coil embolization.The primary outcome measures were the clinical outcomes determined by the modified Rankin scale (mRS) and the Glasgow outcome scale (GOS) at 3 months after onset.Good outcome was defined as mRS score 0-2 or GOS ＞ 3.The secondary outcome measures included severe complications (hydrocephalus,cerebral vasospasm,cerebral infarction,and rebleeding) and death.Results A total of 81 patients with aSAH received aneurysm embolization were enrolled,including 42 in the cerebrospinal fluid replacement group and 39 in the non-cerebrospinal fluid replacement group.There was no significant differences in the baseline data between the cerebrospinal fluid replacement group and the non-cerebrospinal fluid replacement group (all P ＞0.05).The duration of neck stiffness in the cerebrospinal fluid replacement group was significantly shorter than that in the non-cerebrospinal fluid replacement group (11.3 ± 3.2 d vs.16.5 ± 3.5 d;t =6.985,P ＜ 0.001).The cerebrospinal fluid NF-κB levels were progressively reduced at day 1,7 and 14 after coil embolization in the cerebrospinal fluid rephcement group and non-cerebrospinal fluid rephcement group (all P ＜0.05),but the ccerebrospinal fluid levels of NF-κB in the cerebrospinal fluid replacement group at each time point were significantly lower than those in the non-cerebrospinal fluid replacement group (all P ＜ 0.01).The good outcome rates evaluated according to the mRS score (92.9％ vs.56.4％;x2 =14.446,P ＜ 0.001) and GOS score (97.6％ vs.76.9％;x2 =8.004,P=0.005) in the cerebrospinal fluid replacement group at 3 months were significantly higher than those in the non-cerebrospinal fluid replacement group,and the incidence of cerebral vasospasm was significantly lower than that in the non-cerebrospinal fluid replacement group (14.3％ vs.33.3％;x2 =4.086,P =0.043).Conelusiom Cerebrospinal fluid replacement therapy can reduce the incidence of cerebral vasospasm in patients with aSAH receiving aneurysm embolization and improve clinical outcomes.Its mechanism may be associated with the decrease of NF-κB level in cerebrospinal fluid.
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<p><b>OBJECTIVE</b>To analyze clinical features and genetic mutations in a Chinese family affected with autosomal dominant caveolinopathies.</p><p><b>METHODS</b>Clinical data of the proband and her family members were collected. Genomic DNA was extracted from peripheral blood samples with a standard procedure. Next generation sequencing was carried out for the proband, and direct sequencing was employed to detect potential mutation of the CAV gene.</p><p><b>RESULTS</b>The proband presented with slowly progressing distal muscle weakness and atrophy, especially distal upper limbs and muscular soreness during early childhood, with her CK level moderately elevated and EMG showing myogenic and neurogenic injuries. Her sisters presented mild symptoms with hand muscle atrophy and fasciculation after exercise. A heterozygous missense mutation c.80G>A (p.Arg27Gln), which was reported as being pathogenic, was identified in the CAV3 gene in the proband and her sisters.</p><p><b>CONCLUSION</b>A heterozygous c.80G>A (p.Arg27Gln) mutation in the CAV3 gene probably underlies the autosomal dominant caveolinopathies in this Chinese family.</p>
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Female , Humans , Middle Aged , Caveolin 3 , Genetics , High-Throughput Nucleotide Sequencing , Muscular Dystrophies , Genetics , MutationABSTRACT
Objective To report the clinical features and inwardly rectifying potassium channel 18 (KCNJ18) gene mutation in a group of patients with thyrotoxic periodic paralysis (TTP).Methods Fiftyseven TTP cases (55 male and 2 female) were collected in our clinic from July 2002 to October 2011.The KCNJ18 gene was directly sequenced in 57 TTP patients and 50 health Chinese controls through the nested PCR.According to the results of gene screening,the clinical features of KCNJ18 patients and non-KCNJ18 patients were retrospectively summarized and analyzed.Results In 4 male patients with TPP,we found 3 novel heterogeneous mutations (p.Q126X,p.K360T,p.E388K) and 1 reported mutation (p.A200P) in the KCNJ18 gene.The age of onset was 19-25 years old,and the duration ranged from 2 to 8 hours.The 4 patients all presented severe muscle weakness.The attacks of muscle weakness preceded overt symptoms of hyperthyroidism in the 4 patients. Three patients showed recurrent weakness during the 13-28 months follow-up,while the episodic weakness never appeared when patients got euthyroid. Conclusions The mutations in the KCNJ18 gene are responsible for a part of Chinese patients with TPP.The patients with KCNJ18 mutations have a shorter disease course,severer manifestation,and higher prevalence of recurrence as compared with those TPP patients without KCNJ18 mutations.
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Objective To observe the effect of local mild hypothermia and Naloxone in the treatment of acute intracerebral hemorrhage. Methods Forty-five patients with acute intracerebral hemorrhage were randomly divided into 4 groups:a control group(12 patients),a hypothermia group(11 patients),a Naloxone group(11 patients)and a hypothemrmia plus Naloxone group(11 patients).The patients in the control group were managed with conventional interventions including the administration of 6-aminocaproic acid within 24 hours and dehydrant when intracranial pressure was high.Those in the hypothermia and Naloxone groups were treated with local hypothermia at 33～34 ℃ for 3 days or intravenous transfusion of Naloxone at 4 mg/d in addition to the conventional intervention.Those in the combination group were treated with local hypothermia and intravenous Naloxone in addition to the conventional intervention.Immediately after admission and 2 weeks after treatment,head CT scans were conducted to observe the volume of cerebral hematoma and edema.The patients' neurological function was scored according to the European Stroke Standards(ESS)before and after treatment. Results There was no significant difference among the 4 groups in terms of the volume of hematoma and edema or in their ESS scores before treatment.After treatment,any differences among the 4 groups with regard to hematoma volume were not significant.The volume of edema in the hypothermia group was similar to that in the combination group and significantly lower than that in the Naloxone andcontrol groups.Hematoma volume in the Naloxone group was significantly lower than that in the control group.After treatment,the ESS scores were significantly higher in the combination group than that in hypothermia group,and scores in the hypothermia group were significantly higher than in the Naloxone group.ESS scores in the Naloxone group were significantly higher that in the control group. Conclusion Local mild hypothermia and Naloxone treatment can inhibit cerebral edema and enhance recovery of neurological function in patients with intracerebral hemorrhage.Local mild hypothermia has advantages over Naloxone in inhibiting the development of cerebral edema and in promoting recovery of neurological function.Local mild hypothermia in combination with Naloxone further inhibits edema,and it can enhance neurological function to a greater extent.