Comparison of clinical features of patients with or without severe gastrointestinal complications in aggressive gastrointestinal lymphomas

BACKGROUND Aggressive primary gastrointestinal non-Hodgkin lymphoma(PGINHL)is an uncommon and heterogeneous group of lymphoid malignancies,that differs from indolent lymphoma and has a high incidence of severe gastrointestinal complications(GICs).AIM To investigate and compare the clinicopathological characteristics,treatments and outcomes in the GICs and No-GICs group with aggressive PGINHL.METHODS This retrospective analysis was performed on aggressive PGINHL patients between January 2013 and December 2021 at our hospital.The independent influence factors of GICs were obtained by univariate and multivariate Logistic regression analysis,the selected variables significantly related to GICs were selected as the final predictors to construct nomogram.Kaplan-Meier curves further analyzed the survival of patients in GICs and No-GICs groups.Survival analysis of GICs group was performed using Cox regression.RESULTS We focused on 124 aggressive PGINHL cases,which had a relatively high incidence 48.4%(60/124 cases)of GICs,the most common histological type in GICs group was diffuse large B-cell lymphoma(DLBCL)(n=49,81.7%).In the GICs group,small intestine was the most common anatomic site of lesion(43.3%),followed by large intestine(31.7%),and then stomach and esophagus(25.0%).Multivariate Logistic regression analysis showed that the independent risk factors for GICs were the small intestine[odd ratio(OR)=3.33;95%confidence interval(CI):1.47-9.41;P=0.009),aggressive B-cell(OR=0.09;95%CI:0.01-0.83;P=0.033),maximum tumor diameter(OR=1.25;95%CI:1.07-1.47;P=0.005),invaded deep serous layer(OR=3.38;95%CI:1.24-9.19;P=0.017).We developed a nomogram to predict risk of GICs in aggressive PGINHL patients based on independent risk factors.The value of area under curve calculated by receiver operating characteristic curve was 0.815,and calibration curve and decision curve analysis further indicated that the prediction effect was superior.The majority of patients with GICs were given combination therapy(chemotherapy combined with surgery or radiation).Event-free survival and overall survival in GICs group were no worse than those in the No-GICs group.CONCLUSION The complication rate of GICs in patients with aggressive PGINHL was relatively high,particularly in PGI-DLBCL.The independent risk factors for GICs were the small intestine,PGI-TNKL,bulky tumor,and depth of invasion.A combination treatment,involving surgery,improved survival in the GICs group.

Aggressive fibromatosis of the sigmoid colon:A case report

BACKGROUND Aggressive fibromatosis(AF),also known as desmoid tumor or desmoid-type fibromatosis,is a rare soft tissue neoplasm that can occur in almost any part of the body.Although it is a benign disease,AF is aggressive and infiltrative and has a high recurrence rate after surgery.Common sites for intra-abdominal AF are the small bowel mesentery,retroperitoneum,and pelvis.AF in the colon is extremely rare.CASE SUMMARY Here,we report the first case of sigmoid colon AF,which was accidentally discovered in a 27-year-old woman during laparoscopic myomectomy.Computed tomography confirmed a slightly enhanced mass in the sigmoid colon.Subsequent colonoscopy did not reveal a mass in the colonic lumen,but a suspected external compress was found in the sigmoid colon.Surgical disease involving a gastrointestinal stromal tumor was suspected.The patient underwent laparoscopic exploration,and sigmoidectomy with a negative margin was performed to excise the mass.Postoperative immunohistochemistry revealed that the mass was an AF.The patient recovered well and was recurrence-free at the 30-month follow-up without adjuvant therapy.CONCLUSION AF should be considered in the differential diagnosis of subepithelial colon masses.Radical resection alone can achieve good outcomes.

Aggressive variant prostate cancer:A case report and literature review

BACKGROUND Aggressive variant prostate cancer(AVPC)is a rare disease that progresses rapidly.The first-line treatment for AVPC is currently unknown.We examined a rare case of AVPC with rare brain and bladder metastases.A summary review of the mechanism of development,clinicopathological manifestations,associated treatments and prognosis of this disease is presented.CASE SUMMARY The patient was diagnosed with prostate cancer(PCA),and was actively treated with endocrine therapy,radiotherapy,chemotherapy,and traditional Chinese medicine.Unfortunately,he was insensitive to treatment,and the disease progressed rapidly.He died five years after being diagnosed with PCA.CONCLUSION We should reach consensus definitions of the AVPC and other androgen receptorindependent subtypes of PCA and develop new biomarkers to identify groups of high-risk variants.It is crucial to complete a puncture biopsy of the tumor or metastatic lesion as soon as possible in patients with advanced PCA who exhibit clinical features such as low Prostate-specific antigen levels,high carcinoembryonic antigen levels,and insensitivity to hormones to determine the pathological histological type and to create a more aggressive monitoring and treatment regimens.

Cecal microbiota transplantation:unique influence of cecal microbiota from divergently selected inbred donor lines on cecal microbial profile,serotonergic activity,and aggressive behavior of recipient chickens

Background Accumulating evidence from human trials and rodent studies has indicated that modulation of gut microbiota affects host physiological homeostasis and behavioral characteristics.Similarly,alterations in gut micro-biota could be a feasible strategy for reducing aggressive behavior and improving health in chickens.The study was conducted to determine the effects of early-life cecal microbiota transplantation(CMT)on cecal microbial composi-tion,brain serotonergic activity,and aggressive behavior of recipient chickens.Methods Chicken lines 63 and 72 with nonaggressive and aggressive behavior,respectively,were used as donors and a commercial strain Dekalb XL was used as recipients for CMT.Eighty-four 1-d-old male chicks were randomly assigned to 1 of 3 treatments with 7 cages per treatment and 4 chickens per cage(n=7):saline(control,CTRL),cecal solution of line 6_(3)(6_(3)-CMT),and cecal solution of line 7_(2)(7_(2)-CMT).Transplantation was conducted via oral gavage once daily from d 1 to 10,and then boosted once weekly from week 3 to 5.At weeks 5 and 16,home-cage behavior was recorded,and chickens with similar body weights were assigned to paired aggression tests between the treat-ments.Samples of blood,brain,and cecal content were collected from the post-tested chickens to detect CMT-induced biological and microbiota changes.Results 63-CMT chickens displayed less aggressive behavior with a higher hypothalamic serotonergic activity at week 5.Correspondingly,two amplicon sequence variants(ASVs)belonging to Lachnospiraceae and one Ruminococ-caceae UCG-005 ASV were positively correlated with the levels of brain tryptophan and serotonin,respectively.7_(2)-CMT chickens had lower levels of brain norepinephrine and dopamine at week 5 with higher levels of plasma serotonin and tryptophan at week 16.ASVs belonging to Mollicutes RF39 and GCA-900066225 in 7_(2)-CMT chickens were nega-tively correlated with the brain 5-hydroxyindoleacetic acid(5-HIAA)at week 5,and one Bacteroides ASV was negatively correlated with plasma serotonin at week 16.Conclusion Results indicate that CMT at an early age could regulate aggressive behavior via modulating the cecal microbial composition,together with central serotonergic and catecholaminergic systems in recipient chickens.The selected CMT could be a novel strategy for reducing aggressive behavior through regulating signaling along the microbiota-gut-brain axis.

Letter to the editor: Aggressive variant prostate cancer: An exemplary case study and comprehensive literature survey

This article enthusiastically explores the study of highly aggressive variant prostate cancer(AVPC),acknowledging its relatively rare yet highly menacing presence within the realm of prostate cancer.The paper delves into the patho-logical characteristics of AVPC,diagnostic and therapeutic challenges,and the potential applications of precision medicine and molecular imaging in the future.

Aggressive angiomyxoma of the epididymis: A case report

BACKGROUND Aggressive angiomyolipoma is an extremely rare benign mesenchymal tumor that was originally described as a locally recurrent mucinous spindle cell tumour.Agg-ressive angiomyolipoma originates from myofibroblasts,vascular smooth muscle cells,or fibroblasts,and displays various phenotypes of myofibroblasts and abnor-mal muscle arteries.Aggressive angiomyolipoma was first identified in 1983 and fewer than 50 male patients have been reported to date.It is an extremely rare mesenchymal tumour and often confused with other diseases.Patients with epididymal aggressive angiomyolipoma lack typical symptoms,most of which occur incidentally,although some patients may experience mild pain,discomfort,and swelling.Pain may be exacerbated by pressure from the mass.CASE SUMMARY A 66-year-old male was admitted to the hospital on January 14,2022 with chief complaint of swelling in the left scrotum for one year.There was no apparent cause for the swelling.The patient did not consult with any doctor or receive any treatment for the swelling.The enlarged scrotum increased in size gradually until it reached approximately the size of a goose egg,and was accompanied by discom-fort and swelling of the left cavity of the scrotum.The patient had no history of any testicular trauma,infection,or urinary tract infection.The patient urinated freely,1-2 times at night,without urgency,dysuria(painful urination),or haematuria.There was no significant family history of malignancy.The patient underwent excision of the enlarged tumour and the left epididymis under general anaes-thesia on January 18,2022.Twelve months of follow-up revealed no recurrence.The patient was satisfied with the treatment.CONCLUSION Aggressive angiomyolipoma is extremely rare clinically and often confused with other diseases.The pathogenesis of aggressive angiomyolipoma is unclear and the clinical presentation is mostly a painless enlarged mass.The diagnosis of aggressive angiomyolipoma requires a combination of medical history,preoperative imaging such as computed tomography and magnetic resonance imaging,cytological examination and preoperative and postoperative pathological biopsy.The preferred treatment is surgery,with the possibility of a new alternative treatment option after hormonal therapy.Aggressive angiomyolipoma should be considered in the differential diagnosis of parametrial tumors of the male genital area that present as clinically significant masses.The high recurrence rate of aggressive angiomyolipoma may be related to incomplete tumor resection,and patients with aggressive angiomyolipoma are advised to undergo annual postoperative follow-up and imaging for recurrence.

Jurisdiction的政治含义——基于西方中世纪政治史的考察

Jurisdiction不仅仅指司法权和管辖权,它首先指一般性的政治权力。中世纪早期的社会政治经济条件决定了司法权是政治权力的唯一存在方式。多元政治共同体、政治权力中心和法律体系并存的局面导致了"管辖权竞争"。在竞争过程中,不仅作为内部管理机制的管辖权逐步体系化,形成了等级化的司法体系,为现代民族国家的诞生奠定了基本的制度基础;更重要的是,作为外部权力界限的管辖权也逐步明确,形成了以王权为核心、王国为基本政治单位的"国际"政治法律格局。Jurisdiction的历史积淀充分反映了西方法治主义的诸多重要理念、制度基础和对现代民族国家诞生的重大影响。

Impact of social isolation and resident intruder stress on aggressive behavior in the male rat

Stress studies frequently utilize physical stressors to establish animal models of stress. In the majority of cases, these models are not consistent with human circumstances. The present study simulated a social isolation plus resident intruder stress model in the rat. The rats were subjected to daily social isolation and resident intruder stress for 2 weeks. Behaviors were then tested. Rats subjected to social stress exhibited different aggressive behavior styles; some rats had greater scores on composite aggression behaviors, as well as locomotor and exploratory activity, but lower scores on latency than others. The high-aggressive group exhibited predominantly anger-out, while the low-aggressive group exhibited anger-in. Results suggest that social isolation plus resident intruder may serve as an appropriate model for anger-in and anger-out emotion modeling in the rat.

Is aggressive intravenous fluid resuscitation beneficial in acute pancreatitis? A meta-analysis of randomized control trials and cohort studies

BACKGROUND There is conflincting evidence on the intravenous fluid(IVF)strategy for acute pancreatitis(AP).We perform a metaanalysis of the available evidence.AIM To investigate if aggressive IVF therapy in AP patients is beneficial to decrease mortality and improve outcomes.METHODS Metaanalysis of available randomized controlled trials and cohort studies comparing aggressive IVF vs non-aggressive IVF resuscitation.RESULTS There was no significant difference in mortality between the aggressive(n=1229)and non-aggressive IVF(n=1397)patients.Patients receiving aggressive IVF therapy had higher risk for acute kidney injury and acute respiratory distress syndrome.There also was no significant difference in the overall incidence of systemic inflammatory response syndrome,persistent organ failure,pancreatic necrosis when comparing both study groups.CONCLUSION Early aggressive IVF therapy did not improve mortality.Moreover,aggressive IVF therapy could potentially increase the risk for acute kidney injury and pulmonary edema leading to respiratory failure and mechanical ventilation.Studies are needed to investigate which subset of AP patients could benefit from aggressive IVF therapy.

Prostate cancer risk and aggressiveness associated with the CYPIB1 4326C/G （Leu432Val） polymorphism： a meta-analysis of 2788 cases and 2968 controls

To derive a precise estimation of the associations between the cytochrome P450 1B 1 （CYPIB1） 4326C/G variants and prostate cancer （PCa） risk or aggressiveness, a meta-analysis was performed using all eligible published studies. Odds ratios （ORs） with 95% confidence intervals （CIs） were estimated to assess the association in seven literature studies with 2788 cases and 2968 controls. In the overall analysis, no significant association was found between the CYPIB1 4326C/G polymorphism and PCa risk, but ethnicity subgroup analyses and a case-source analysis revealed significant associations. The 4326G allele showed a significant association with increased PCa risk in Asians （OR= 1.52, 95% Ch 1.20-1.92）, and significant associations were also observed in a heterozygote comparison （OR= 1.40, 95% Ch 1.03-1.89）, a homozygote comparison （0R=2.38, 95% Ch 1.31-4.33） and in a dominant genetic model （OR = 1.52, 95% Ch 1.14-2.01）. Moreover, the 4326G allele was also significantly correlated with an increased risk of sporadic PCa （OR= 1.13, 95% Ch 1.04-1.24）, and significant associations were observed in a heterozygote comparison （OR= 1.16, 95% Ch 1.02-1.33）, a homozygote comparison （OR= 1.24, 95% Ch 1.03-1.49） and a dominant genetic model （OR= 1.19, 95% Ch 1.05- 1.34）. The overall analyses and all subgroup analyses showed no significant association between the 4326C/G polymorphism and PCa aggressiveness. Our meta-analysis showed that CYPIB1 4326G allele is significantly associated with an increased PCa risk in Asians and in sporadic PCa cases.

Relationship between Levels of Testosterone and Cortisol in Saliva and Aggressive Behaviors of Adolescents

Objective To explore the endocfinal factors which influence the aggressive behavior of adolescents. Methods The levels of cortisol （CORT）, testosterone （T）, prolactin （PRL）, and growth hormone （GH） in saliva from 20 aggressive students and 20 non-aggressive control students were measured by radioimmunoassay （RIA）. The students were matched for their gender, age, grade, stage of pubertal development, and economic status of their families. Results The salivary T levels were 22.20±14.50 pg/mL and 19.54±12.52 pg/mL in aggressive male and female students, 13.20±6.85 pg/mL and 5.24±3.03 pg/mL in non-aggressive male and female students （P〈0.05）. The male aggressive students had a lower level of CORT in saliva than non-aggressive male students （P〈0.05）. There were no significant differences in the salivary levels of PRL or GH between the aggressive and non-aggressive groups. Correlation analysis revealed a negative relationship in male students between the salivary CORT levels and the aggression factor scores of the child behavior checklist （CBCL）. In addition, the data also showed a positive relationship between the salivary T levels and the aggression factor scores of CBCL in female students. Multiple linear regression analysis showed that the salivary CORT level was an independent predictive factor for aggressive behaviors in adolescent boys. The higher the CORT level, the less aggressive the boys were. Conclusion CORT and T levels may play a certain role in adolescent aggressive behaviors.

Recurrent aggressive mesenteric desmoid tumor successfully treated with sorafenib: A case report and literature review

BACKGROUND Desmoid tumors(DT) are locally advanced but histologically benign monoclonal neoplasms that can occur from any musculoaponeurotic structure. The aim of this report is to analyze a rare clinical case of an aggressive intra-abdominal DT successfully treated with sorafenib.CASE SUMMARY A 36-year-old man presented with increasing colicky abdominal pain and a selfpalpable mass in his left abdomen. Fourteen years earlier he was diagnosed with a large intra-abdominal tumor, which adhered to the left colonic flexure, part of the major gastric curvature and the spleen. Subsequent exploratory laparotomy revealed a voluminous mass in the epigastrium, arising from the posterior surface of the stomach and invading the superior mesenteric vessels, transverse mesocolon and the small bowel mesentery. As the tumor was unresectable, a jejunojejunal bypass was performed. Traditional therapeutic interventions proved insufficient, and the patient was started on sorafenib with a subsequent fulldisease response.CONCLUSIONDT's pathogenesis has been associated with mutations in the adenomatous polyposis coli(APC) gene or beta-catenin gene CTNNB1, sex steroids or previous surgical trauma. Local treatment modalities, such as surgery or radiotherapy, are implemented in aggressively progressing or symptomatic patients. Sorafenib is a hopeful therapeutic option against DTs, while several pharmacological agents have been successfully used.

An Exploration of the Relation between Hunting and Aggressiveness: Using Inmates Networks at Prison Secondary School as an Illustration

Aim of this research is to explore the relation of hunting with aggressiveness. For this purpose, two samples of prison inmates (who were students of the prison secondary school) were collected (class A = 23, class B = 12). The network indicators for superficial, idiosyncratic and strategic behavior (particularly, aggressiveness), applied in Bekiari and Hasanagas (2016), which were based on the primary network variables (outdegree, indegree, Katz status, pagerank, authority) were used. Non-network variables were also used for the criminal profile of the inmates. The data were sampled with questionnaire. Spearman test was conducted for detecting correlation between aggressiveness and hunting and Principal Component Analysis was used for formulating a typology. The following results were produced: The criminal profile seems hardly to be related with hunting experience or attitude. The relation of hunting experience and attitude with the superficial, idiosyncratic and strategic aggressiveness was examined. These three occasions of aggressiveness are expected to describe the incidental reaction, impulsive and adaptive reaction, respectively. The hunting is quite irrelevant to the incidental reaction. The impulsiveness seems to be more strongly correlated with hunting. In case of adaptiveness, there are many similarities with impulsiveness. The typology which is based on the existence (or not) of hunting experience seems to be more insightful, as it reveals a gradual involvement of aggressiveness dimensions, from incidentality to impulsiveness and further to adaptiveness. The following behavioral patterns of gradually enhanced aggressiveness appear: incidentally just provoking, impulsively being aggressive but without harming, and adaptively being aggressive and harming.

Examining Relations of Aggressive Communication in Social Networks

Aim of this research is the detection of aggressive communication parameters and typology. A network sample of 62 students (male = 32, female = 30) and 4 instructors (male = 2, female = 2) at the physical education and sport sciences dept. at the University of Thessaly has been collected in 2016. A standardized questionnaire consisting of network and non-network part was used. Social network analysis (algebraic analysis) combined with conventional statistics has been used. Basic results are the following ones: Persons dedicated to sport appear to target others and be targeted. Dedication to study content is proved to play a role of a refuge against criticism. High grade and ambition seem to protect against negative comments. Physical qualification (tallness) seems also to discourage rudeness. Spatial-regional discrimination is also revealed. Mockery seems to be even a cause of absence from the courses. A superiority-induced aggressiveness (on economic basis) has been detected. Threat may be regarded as a behavioral extension of mockery (or inversely). In the course of study time, more aggressive persons emerge who even threat others. High grade students are unattractive for arguing. Internet seems to develop communication stimuli. The tendency for professional distinction is connected with arguing. Younger students show an integration deficit in terms of argumentation. Communicational types (three profiles of targets: “depreciated assaulted”, “attractive”, “repellent”, and two profiles of general involvement: “lively”, “controversial”) have emerged. A typology of targets is depicting a sharper fragmentation than a typology of general involvement (targeted and acting).

Effects of thymidine phosphorylase on tumor aggressiveness and 5-fluorouracil sensitivity in cholangiocarcinoma

AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of endogenous TP, had TP expression transiently knocked down using siRNA. Cell growth, migration, in vitro angiogenesis, apoptosis, and cytotoxicity were assayed in TP knockdown and wild-type cell lines. RESULTS: TP mRNA and protein expression were decreased by 87.1% ± 0.49% and 72.5% ± 3.2%, respectively, compared with control cells. Inhibition of TP significantly decreased migration of KKU-M139, and suppressed migration and tube formation of human umbilical vein endothelial cells. siRNA also reduced the ability of TP to resist hypoxia-induced apoptosis, while suppression of TP reduced the sensitivity of KKU-M139 to 5-fluorouracil. CONCLUSION: Inhibition of TP may be beneficial in decreasing angiogenesis-dependent growth and migration of cholangiocarcinoma but may diminish the response to 5-fluorouracil chemotherapy.

Application of ultrasound in aggressive angiomyxoma: Eight case reports and review of literature

Aggressive angiomyxoma （AAM） is a rare tumour that often occurs in soft tissues of the female genital tract. Eight cases of AAM are reported in this article, and the clinical features and ultrasound and magnetic resonance imaging （MRI） results of the eight cases are reviewed and summarized. The main complaints of all the patients were palpable and painless masses in the vulva or scrotum. The lesions were mainly located in the vulva, pelvis, and perineal region, with a large scope of involvement. The sonographic features of AAM were characteristic. On sonography, all of the masses were of irregular shape and showed hypoechogenicity, with a heterogeneous inner echotexture. Intratumoural and peritumoural blood fows were detected by colour Doppler imaging. On real-time ultrasonic imaging, prominent deformation of the lesions was observed bycompressing the masses with the probe. Some special imaging features were also revealed, including a la-minated or swirled appearance of inner echogenicity, and a fnger-like or tongue-like growth pattern. On MRI imaging, the lesions showed intermediate-intensity signals and intermediate to high-intensity signals on TI-weighted and T2-weighted sequences. A rapid and uneven enhancement pattern was demonstrated. After the comparison of sonographic features with MRIand pathological findings, we found the relevance of the ultrasonographic characteristics with MRI and his-tological features of AAM. Ultrasound can be a valuable imaging method for the preoperative diagnosis, eva-luation of scope, and follow-up of AAM.

Analysis of aggressiveness factors in hepatocellular carcinoma patients undergoing transarterial chemoembolization

AIM To investigate novel predictors of survival in hepatocellular carcinoma(HCC) patients following transarterial chemoembolization(TACE).METHODS One hundred sixty seven patients with un-resectable HCC were retrospectively analyzed to identify factors that might contribute to their HCC biology and aggressiveness. We correlated routine laboratory results(total bilirubin, AST, ALKP, GGTP, albumin etc.) to maximum tumor diameter, number of tumor nodules, portal vein thrombosis and blood alpha-fetoprotein levels. These 4 parameters were previously combined to form an aggressiveness index(AgI). We used The Wilcoxon ranksum(Mann-Whitney), to test the correlation between the AgI categories and liver function parameters. The Cox proportional hazards model was applied to evaluate the categories of AgI associated with overall survival. RESULTS The AgI was strongly correlated with survival in this novel patient population. Three year survival probability for AgI > or < 4 was 42.4% vs 61.8%; P < 0.0863 respectively. Several factors independently correlated with AgI using univariate multiple logistic regression of AgI with 8 laboratory parameters. Lower albumin levels had an OR of 2.56(95%CI: 1.120-5.863 P < 0.026), elevated Alkaline phosphatase and gamma glutamyl transpeptidase(GGTP) had ORs of 1.01(95%CI: 1.003-1.026, P < 0.017) and 0.99(95%CI: 0.99-1.00, P < 0.053) respectively. In a Cox proportional hazard model combining mortality for AgI score and liver function parameters, only GGTP levels and the AgI were independently associated with survival. An AgI > 4 had HR for mortality of 2.18(95%CI: 1.108-4.310, P < 0.024). GGTP's single unit change had a HR for mortality of 1.003(95%CI: 1.001-1.006, P < 0.016). These were considered in the final multivariate model with the total cohort. An AgI > 4 had a HR for mortality of 2.26(95%CI: 1.184-4.327, P < 0.016). GGTP had a HR of 1.003(95%CI: 1.001-1.004, P < 0.001).CONCLUSION Our study validates the AgI in a new population with un-resectable HCC patients undergoing TACE. The analysis establishes a correlation between GGTP and the AgI.

Tim-3 promotes cell aggressiveness and paclitaxel resistance through NF-κB/STAT3 signalling pathway in breast cancer cells

Objective:Although T-cell immunoglobulin and mucin-domain containing molecule-3(Tim-3)has been recognized as a promising target for cancer immunotherapy,its exact role in breast cancer has not been fully elucidated.Methods:Tim-3 gene expression in breast cancer and its prognostic significance were analyzed.Associated mechanisms were then explored in vitro by establishing Tim-3-overexpressing breast cancer cells.Results:In a pooled analysis of The Cancer Genome Atlas(TCGA)database,Tim-3 gene expression levels were significantly higher(P<0.001)in breast cancer tissue,compared with normal tissues.Tim-3 was a prognosis indicator in breast cancer patients[relapse-free survival(RFS),P=0.004;overall survival(OS),P=0.099].Tim-3 overexpression in Tim-3 low breast cancer cells promoted aggressiveness of breast cancer cells,as evidenced by enhanced proliferation,migration,invasion,tight junction deterioration and tumor-associated tubal formation.Tim-3 also enhanced cellular resistance to paclitaxel.Furthermore,Tim-3 exerted its function by activating the NF-κB/STAT3 signalling pathway and by regulating gene expression[cyclin D1(CCND1),C-Myc,matrix metalloproteinase-1(MMP1),TWIST,vascular endothelial growth factor(VEGF)upregulation,concomitant with Ecadherin downregulation).Lastly,Tim-3 downregulated tight junction-associated molecules zona occludens(ZO)-2,ZO-1 and occludin,which may further facilitate tumor progression.Conclusions:Tim-3 plays an oncogenic role in breast cancer and may represent a potential target for antitumor therapy.

ABC transporters and the hallmarks of cancer:roles in cancer aggressiveness beyond multidrug resistance

The ATP-binding cassette transporters(ABC transporters)have been intensely studied over the past 50 years for their involvement in the multidrug resistance(MDR)phenotype,especially in cancer.They are frequently overexpressed in both naive and post-treatment tumors,and hinder effective chemotherapy by reducing drug accumulation in cancer cells.In the last decade however,several studies have established that ABC transporters have additional,fundamental roles in tumor biology;there is strong evidence that these proteins are involved in transporting tumor-enhancing molecules and/or in protein-protein interactions that impact cancer aggressiveness,progression,and patient prognosis.This review highlights these studies in relation to some well-described cancer hallmarks,in an effort to re-emphasize the need for further investigation into the physiological functions of ABC transporters that are critical for tum or development.Unraveling these new roles offers an opportunity to define new strategies and targets for therapy,which would include endogenous substrates or signaling pathways that regulate these proteins.

Applying Social Network Indicators in the Analysis of Verbal Aggressiveness at the School

The purpose of this study is to detect structures of verbal aggressiveness using multiple indicators of social networks analysis (out- and in-degree, pagerank, Katz, authority, incremental and proportional behavior). Standardized questionnaires have been distributed to 151 students and 45 teachers at primary and secondary schools. We performed complete analysis of social networks and further processing by applying principal component analysis. According to the results, a complex structure of verbal aggressiveness occurred in the classes (networks) and the structure was necessary to be explored with several network indicators (Katz, pagerank, incremental and proportional behavior etc.). Prejudices about the role of the gender in the aggressiveness (e.g. that female are more peaceful than male) are deconstructed. As for the typology of the incremental and proportional behavior two types were proposed: 1) the “personal attack” that the verbal aggressor aims the victim’s personality and 2) “social exclusion” that the strategy is to exclude the victim from the social surrounding.