Ultrasonographic and clinicopathologic features of benign Brenner tumors of the ovary

Objective The aim of this study was to summarize and analyze the ultrasonographic and clinicopathologic features of benign brenner tumors of the ovary.Methods Forty-six patients with brenner tumors of the ovary were included,and the imaging and pathologic features of the tumors were analyzed.Results Thirty-eight cases were unilateral,while eight cases were bilateral.The tumors were located only in the left ovary in 32 patients and in the right ovary in six patients.The median diameter of the tumors was 62 mm,and the diameter ranged from 15 to 270 mm.Vascular tumors were not observed.Most of the tumors(22/46)showed micro-perfusion,while 16 tumors showed no blood flow signal.Acoustic signal shadows after the cysts were observed in 26 tumors,accounting for 57%of all brenner tumors.Fourteen patients showed unilocular or multilocular tumors with no distinct characteristics on ultrasonography.Sixteen masses showed a multilocular solid structure,accompanied by calcification and a post-mass shadow;the solid structure showed mild-to-moderate vascularization on Doppler examination.Sixteen masses showed a pure solid structure,accompanied by calcification,resulting in an acoustic shadow behind the tumor;the solid structure showed mild-to-moderate vascularization on Doppler examination.Conclusion Some ultrasonographic features,including calcification with shadow,poor blood circulation of solid components,and mass localization,are helpful in the diagnosis of benign brenner tumors.

Safety and efficacy of acute normovolemic hemodilution during liver surgery: a Meta-analysis

Objective The aim of this study was to evaluate the safety and efficacy of acute normovolemic hemodilution(ANH) during liver surgery.Methods Structured searches of the Pub Med,Chinese Biological Medicine Database,and Cochrane Library electronic databases were performed,followed by a meta-analysis of outcomes,including intraoperative blood transfusion(s),intraoperative bleeding,postoperative hematocrit(Hct) levels,postoperative prothrombin time(PT),and number of patients who underwent transfusions during liver surgery.Results In total,14 eligible studies were included in the meta-analysis,which revealed that ANH for liver resection was associated with a reduction in intraoperative blood transfusions [weighted mean difference(WMD)-1.99;95% confidence interval(CI)-2.82 to -1.16;P<0.00001].The ANH group experienced less intraoperative bleeding(WMD -72.81;95% CI -136.12 to -9.50;P<0.00001) and exhibited a lower postoperative Hct level(WMD -3.38;95% CI -7.14 to -0.67;P<0.00001) than the control group.Moreover,meta-analysis revealed that postoperative prothrombin time was not affected by ANH(WMD -0.02;95% CI -0.18 to -0.32;P=0.65).Finally,the number of patients requiring allogeneic transfusion was significantly smaller in the ANH group than in the control group(odds ratio 0.13;95% CI 0.09 to 0.18;P=0.24).Conclusion Results of the present meta-analysis indicated that ANH can reduce intraoperative bleeding and the need for blood transfusions.In addition,ANH did not negatively affect the coagulation system after surgery;therefore,ANH appears to be safe and effective during liver surgery.

Quantitative monitoring and mutations of ctDNA before and after non-small cell lung cancer radical surgery

Objective The aim of this study was to study the quantitative expression of circulating tumour DNA(ctDNA) in patients with non-small cell lung cancer(NSCLC) before and after radical operation and to explore the correlation between gene mutations in non-small cell lung cancer tissues and those in ctDNA.Methods We randomly assigned 5 NSCLC patients from the Department of Thoracic Surgery of Fujian Medical University Union Hospital. All the patients had undergone radical surgery. Venous blood samples were collected from the 5 NSCLC patients at two time points(before the operation and 21–37 days after the operation) for monitoring ctDNA levels. This was done by isolating plasma from venous blood using high velocity centrifugation, extracting DNA from the plasma using the QIAamp Circulating Nucleic Acid kit, and then quantifying the ctDNA levels. The results were analyzed using the Wilcoxon Rank Sum Test. Moreover, the ctDNA levels were compared with those of carcinoembryonic antigen(CEA), which was detected simultaneously with the ctDNA. Then, DNA samples from the tumor tissues and peripheral blood cells and ctDNA were sequenced using the Hiseq2000 sequencing platform(Illumina) and the mutant genes were screened out. Mutations that occurred within the tumor tissues were used as positive control, whereas those found in the pre-operative blood cells were used as a negative control. Based on the mutational analysis of ctDNA genes, a total of 508 cancer-related genes were screened. Results The median values of the pre-and post-operative ctDNA levels in the 5 patients with NSCLC were 0.612(0.518–0.876) and 0.430(0.372–0.612) ng/μL, respectively. There was a significant difference between the two groups(P < 0.05). The pre-operative CEA level was slightly higher than the post-operative level(P > 0.05). In one of the cases, LC tissues showed multiple mutations, consistent with pre-operative ctDNA. Moreover, isogenic mutations of the same type were not detected in post-operative ctDNA or peripheral blood cells. Conclusion Mutations found in the lung cancer(LC) ctDNA gene were consistent with the mutation type of LC tissue. Hence, the quantitative and qualitative analysis of ctDNA is a promising novel molecular biomarker for the evaluation of tumor burden changes in NSCLC.

Preliminary research on dendritic cells loaded with resistant breast cancer antigens in breast cancer-bearing nude mice

Objective The aim of the study was to investigate the inhibitory effects of dendritic cells （DCs） loaded with resistant breast cancer antigens on breast cancer in nude mice. Methods A single-cell suspension was prepared from a primary breast cancer and chemotherapeutic drugs were screened using the ATP-PCA susceptibility testing system. Cancer cells were treated with 1/10 × IC50, 1/5 × IC50, 1/2 × IC50, 1 × IC50, and 2 × IC50 medium until their growth became steady in the 2 ×IC50 medium, Peripheral b{ood mononuclear cells （PBMCs） were obtained from the peripheral blood of patients with leukapheresis. The obtained adherent ceils were induced by granulocyte-macrophage colony-stimulating factor （GM-CSF） and interleukin-4 （IL-4） to generate DCs, which carried resistant strain cell lysis compounds or non-treated cancer cell lysis compounds. The former mature DCs carried resistant breast tumor antigens. A breast tumor-bearing nude mouse model was established with these resistant strains and the mice were randomly divided in three groups. The mice in the treatment group were injected with DCs loaded with resistant breast cancer antigens. The control group consisted of mice injected with DCs loaded with primary tumor cell antigens and the blank group consisted of mice injected with the same volume of normal saline. Changes in the cancers were observed. Results After treatment with the effector cells, the cancer volume and weight were significantly different to those before treatment in every group of mice （P 〈 0.05）. The tumor volume in the blank group was the largest （3.362 ± 0.068 cm^3） and the tumor weight was 637.50 ± 59.398 mg. Compared to the blank group, the tumor volume in the experimental group was the smallest （1.273 ±0.071 cm^3） and the tumor weight was 206.81 ±32.711 mg. Conclusion DCs loaded with resistant breast cancer antigens demonstrated a significant inhibition effect on the cancers of breast tumor-bearing nude mice.

Analysis of the intestinal flora in patientswith primary liver cancer

Objective To investigate the differences in intestinal flora of patients with primary liver cancer and ofhealthy individuals and to investigate the effect of the differential flora on the development of liver cancer.Methods Overall, 67 patients with primary liver cancer who received systematic and complete treatmentbetween January 2019 and December 2020 at the Sixth People’s Hospital of Qingdao and had completeclinical data were enrolled in this study, and 26 individuals who were healthy on physical examination inthe same period were used as healthy controls. Macro genome and 16s ribosome Deoxyribo Nucleic Acid(rDNA) high-throughput sequencing were performed on the stool flora of the enrolled patients and controls,and the differences in the intestinal flora were analyzed using the LEfSe bioinformatics software.Results Compared with the control samples, all the tested patient samples showed statistically significantdifferences in the number of colonies of 5 bacterial phyla, 5 orders, 8 families, 11 genera, and 14 species(P < 0.05).Conclusion Compared with healthy people, patients with primary liver cancer have significant differencesin the intestinal flora composition. The alteration of the intestinal flora may be correlated with the occurrenceof primary liver cancer, and the intestinal flora may become a novel target for the prevention and treatmentof primary liver cancer.

The expression of vascular endothelial growth factor(VEGF)/endostatin(ES)and VEGF receptor 2(VEGFR2)/ES is associated with NSCLC prognosis

Objective The aim of our study was to detect the expression of angiogenesis inhibitory proteins and angiogenesis promotive proteins in the postoperative tumor tissue of non-small cell lung cancer(NSCLC)patients.We also investigated the relationship of protein expression with clinical characteristics and prognosis.Methods We examined the expression of vascular endothelial growth factor(VEGF),VEGF receptor 2(VEGFR2),and endostatin(ES)proteins in 255 specimens resected from NSCLC patients,using immune histochemistry(IHC).We then evaluated the relationships between the expression of the three proteins and clinical characteristics such as stage,histological type,differentiation,gender,tobacco use,and age.According to the value of VEGF/ES,we divided the cohort into angiogenesis-promoting group A,angiogenesis-inhibiting group A,and balance group A.The survival differences in the three groups were evaluated to determine the prognostic value of VEGF/ES.Similarly,we tested the prognostic value of VEGFR2/ES.Results VEGF-positive expression was observed in 93 patients(36.4%).VEGF expression was not correlated with the clinical characteristics.VEGFR2-positive expression was observed in 103 patients(40.4%).The expression of VEGFR2 was correlated with the clinical stage(χ^(2)=21.414,P=0.045)and histological type(χ^(2)=26.911,P=0.008).ES-positive expression was observed in 140 patients(54.9%).The expression of ES was correlated with the clinical stage(χ^(2)=26.504,P=0.009).When evaluating the prognostic values of VEGF/ES and VEGFR2/ES,the prognosis of the angiogenesis balance group was similar to that of the angiogenesis-inhibiting group.The minimum survival time was observed in the angiogenesis-promoting group.Conclusion VEGF/ES and VEGFR2/ES in resected tumors have prognostic value in postoperative NSCLC patients.The survival time of the population with predominant angiogenic factors was short.

Effects of MIF on proliferation,migration,and STAT1 pathway of colon cancer cells

Objective This study aimed to investigate how macrophage migration inhibitory factor(MIF)regulates the interaction of signal transducer and activator of transcription 1(STAT1)with CD74,and affects colon cancer proliferation and invasion.Methods After transfecting MIF small interfering RNA into the SW480 cell line,the expression of STAT1 and CD74 mRNA was detected by qRT-PCR and western blotting.Transwell and MTT assays were performed to detect the colon cancer cell invasion and proliferation ability.Co-immunoprecipitation was used to detect the interaction between CD74 and STAT1 proteins in the treated and control groups.Results The cellular biological assays(MTT and Transwell)showed that the proliferation and invasion ability of colon cancer cells decreased after MIF knockdown;the results showed significant statistical difference(P<0.05).The results of the co-immunoprecipitation assay suggested that MIF knockdown in colon cancer cells could inhibit the binding of CD74 and STAT1 proteins;statistical difference was observed between the two groups(P<0.05).Conclusion MIF can increase the proliferation and invasion of colon cancer cells by promoting the combination of CD74 and STAT1.

Histone modification as a drug resistance driver in brain tumors

Patients with brain tumors,specifically,malignant forms such as glioblastoma,medulloblastoma and ependymoma,exhibit dismal survival rates despite advances in treatment strategies.Chemotherapeutics,the primary adjuvant treatment for human brain tumors following surgery,commonly lack efficacy due to either intrinsic or acquired drug resistance.New treatments targeting epigenetic factors are being explored.Post-translational histone modification provides a critical regulatory platform for processes such as chromosome condensation and segregation,apoptosis,gene transcription,and DNA replication and repair.This work reviews how aberrant histone modifications and alterations in histone-modifying enzymes can drive the acquisition of drug resistance in brain tumors.Elucidating these mechanisms should lead to new treatments for overcoming drug resistance.

Diagnostic accuracy of real-time tissue elastography for breast cancer:a meta-analysis

Objective The present study aimed to determine the accuracy of real-time tissue elastography （RTE） for the diagnosis of breast cancer. Methods The search was conducted in the PubMed, Web of Science, Cochrane Library, and China Biology Medicine databases from inception through December 31, 2014, without language restrictions. The meta-analysis was conducted using STATA version 12.0 and Meta-Disc version 1.4. We calculated the summary statistics for sensitivity （Sen）, specificity （Spe）, positive and negative likelihood ratio （LR＋/LR–）, diagnostic odds ratio （DOR）, and summary receiver operating characteristic （SROC） curve. Results Ten studies that met al inclusion criteria were included in the meta-analysis. A total of 608 ma-lignant breast lesions and 1292 benign breast tumors were assessed. Al breast lesions were histological y confirmed after RTE. The pooled Sen was 0.83 （95% CI = 0.79–0.86）; the pooled Spe was 0.86 （95% CI = 0.84–0.88）. The pooled LR＋ was 9.87 （95% CI = 2.66–36.71）; the pooled LR– was 0.20 （95% CI = 0.17–0.23）. The pooled DOR of RTE for the diagnosis of breast cancer was 62.21 （95% CI = 33.88–114.24）. The area under the SROC curve was 0.9334 （standard error = 0.00125）. We found no evidence of publica-tion bias （t = –0.57, P = 0.582）. Conclusion RTE may have high diagnostic accuracy for the dif erential diagnosis of benign and malig-nant breast tumors. RTE may be a good tool for breast cancer diagnosis.

Controversies and future directions in the management of gallbladder cancer

Gallbladder cancer(GBC)is a rare malignancy worldwide,with 140,000 new patients each year and more than 100,000 deaths annually.The review aims to address the controversial aspects of managing GBC.Regional differences of the study worldwide remain pending,and comparative mutational profiles will provide more information on the pathogenesis of GBC.However,certain pathologic aspects are discussed,such as the staging of early GBC,outcome differences between T2 pathologically staged patients,and the necessity of a uni-form pathologic report.The surgical management of GBC is still under debate.The extent of liver resection,type of lymphadenectomy,and selection of patients for extended resection are aspects of the disease that require revision.Laparoscopic and robotic approaches were initially slow to develop.However,with time,they have demonstrated their value in the surgical management of GBC.The OMEGA survey,performed to analyze the management practice of surgical treatment of GBC worldwide,demonstrated differences from the recom-mended guidelines.The OMEGA study,the largest cohort study,examined the outcomes of surgical intervention in 3676 patients from 133 centers.Regarding future directions,the value of collaborative efforts between centers and regions must be emphasized to better un-derstand the different aspects of the disease and globally improve therapeutic strategies for GBC.

Effect of postoperative adjuvant chemotherapyon the prognosis of patients with ypT0-3N0 rectalcancer undergoing neoadjuvant chemoradiotherapy

Objective The aim of this study was to investigate the effect of adjuvant chemotherapy (AC) on theprognosis of patients with ypT0-3N0 rectal cancer undergoing neoadjuvant chemoradiotherapy.Methods The study participants were 110 patients with locally advanced rectal cancer. Thirty-fourpatients did not receive postoperative AC treatment, and the other 76 patients received postoperative ACtreatment. The differences in the 5-year overall survival (OS) and disease-free survival (DFS) between thetwo groups were compared.Results Age was an important determinant of the patients’ decision to undergo postoperative treatment.Patients who did not receive AC treatment were significantly older than those who received AC treatment(P < 0.05). The tumor location (distance above anal margin) in the AC group was significantly larger thanthat in the non-AC group (P < 0.05). Moreover, there was no significant difference in the 5-year DFS andOS between the two groups. Postoperative AC did not significantly improve the prognosis of patients withrectal cancer. Age, tumor differentiation, and the number of resected lymph nodes were independent factorsaffecting the OS of patients (P < 0.05). Older patients, patients with lower degree of tumor differentiation,and patients with <12 resected lymph nodes showed worse prognosis (P < 0.05).Conclusion Patients with rectal cancer whose ypT0-3N0 stage is reduced after neoadjuvantchemoradiotherapy, especially those without adverse prognostic factors, do not need AC after surgery.

Correlation analysis of breast fibroadenoma and the intestinal flora based on 16S rRNA sequencing

Objective To analyze the characteristics of the intestinal microflora in patients with breast fibroadenoma using 16S ribosomal RNA(rRNA)high-throughput sequencing.Methods Fecal samples from 20 patients with breast fibroadenoma and 36 healthy subjects were randomly collected and analyzed using high-throughput sequencing technology for 16S rRNA V4 region sequencing,and the alpha diversity(Chao index,Shannon index)was calculated using Mothur(v.1.39.5)software.Beta diversity was analyzed using QIIME(v1.80).SPSS software(version 23.0)and the t-test of two independent samples were used to analyze differences in the abundance of bacteria between the two groups.Results Compared with that in the healthy control group,theαdiversity of the intestinal microflora in breast fibroadenoma patients increased,but the difference was not statistically significant(P>0.05).At the phylum level,significant differences were observed between the two groups.The abundance of Firmicutes was higher in the breast fibroadenoma group(P<0.05),whereas the abundance of Synergistetes was higher in the healthy control group(P<0.005).A total of five bacterial genera showed significant differences between the two groups:the breast fibroadenoma group showed higher levels of Bautia(P<0.005),Coprococcus(P<0.005),Roseburia(P<0.05),and Ruminococcus(P<0.005),whereas Sutterella was more abundant in the healthy control group than in the breast fibroadenoma group(P<0.05).Conclusion The diversity and abundance of the intestinal flora in patients with breast fibroadenoma are significantly different from those in healthy subjects,suggesting that an imbalance in the intestinal flora is correlated with the occurrence of breast fibroadenoma.

Intervention for oxaliplatin-induced hypersensitivity in China:a cross-sectional internet-based survey

Objective This cross-sectional study aimed at investigating the intervention status and the influence of oncologists on oxaliplatin-induced hypersensitivity reactions(OIHR).Methods Snowball sampling was used to send questionnaires to oncologists in various provinces and cities in China,via the internet,to collect data on their socio-demographic characteristics,the occurrence of OIHR,and the current status of interventions.One-way ANOVA and T-test of geographic samples were used to explore the relationship between the incidence of OIHR and intervention measures.Results A total of 401 valid questionnaires were collected,most respondents were 30–40 years old,and most oncologists had 5 years of working experience.The proportions of glucocorticoid and H1 receptor antagonist use for OIHR prevention were 67.83%and 38.65%,respectively.The proportion of oncologists with longer working years and higher professional titles who used glucocorticoids for OIHR prevention was higher,and the observed OIHR incidence was lower.Pretreatment with glucocorticoids may be an effective preventive measure and can reduce the incidence of the OXA allergic reactions(P<0.05).Conclusion The risk awareness of junior oncologists to OIHR prevention should be strengthened,and clinical efficacy evaluation of glucocorticoids in OIHR prevention should be further promoted.

microRNAs regulation and its role as biomarkers in diseases

MicroRNAs （miRNAs）, approximately 21 to 23 nucleotides （nt） in length, belong to a set of smal non-coding RNA molecules that were not thought to be functional until the recent decades. miRNAs play important roles in many diseases such as various kinds of cancers and immune disorders. Many studies have focused on the relationship between miRNAs and diseases. miRNAs are significant mediators in human growth and development and in the genesis and development of diseases. Almost 30% of the activity of protein-coding genes is forecasted to be regulated by miRNAs in mammals, and some miRNAs are regarded as potential therapeutic targets for various diseases. In this review, we outline some functions of miRNAs, especialy those related to diseases.

Downregulation of the circadian clock gene period 2 aggravates prognosis in breast cancer patients with obesity

Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however,the underlying mechanisms linking obesity to breast cancer outcomes remain elusive.This study aimed to identify and validate novel prognostic markers associated with breast cancer in patients with obesity.Methods:We conducted a reanalysis of gene expression profiles from normal-weight,overweight,and obese breast cancer patients to identify candidate genes.Subsequently,we validated the protein levels of these candidates using immunohistochemistry.Finally,we investigated the association between candidate genes and breast cancer prognosis at Tongji Hospital,utilizing data from an 8-year follow-up through the Kaplan-Meier method and univariate and multivariate Cox regression models.Results:The fold change of the circadian clock gene period 2(PER2),which exhibited a declining trend with increasing body mass index,was 0.76 in obese patients compared with normal-weight patients.The expression rates of PER2 protein were 44.7%,51.5%,and 61.3%in normal-weight,overweight,and obese patients,respectively.The 8-year recurrence-free survival rates were 75.9%,69.6%,and 64.1%,whereas the 8-year overall survival rates were 86.8%,83.0%,and 76.1%in normal-weight,overweight,and obese patients,respectively(P<0.05).Furthermore,the 8-year recurrence-free survival rates were 66.2%and 76.4%,and the 8-year overall survival rates were 79.9%and 86.3%in the low and high PER2 expression groups,respectively(P<0.05).The unadjusted hazard ratio for PER2 was 1.550(95%confidence interval,1.029–2.335),and the adjusted hazard ratio was 3.003(95%confidence interval,1.838–4.907).Conclusions:Our findings indicate that low PER2 expression serves as an independent risk factor for breast cancer prognosis and may contribute to the unfavorable outcomes observed in obese patients.

Clinical and pathological characteristics and expression of related molecules in patients with airway disseminated lung adenocarcinoma

Objective:Lung adenocarcinoma exhibits diverse genetic and morphological backgrounds,in addition to considerable differences in clinical pathology and molecular biological characteristics.Among these,the phenomenon of spread through air space(STAS),a distinct mode of lung cancer infiltration,has rarely been reported.Therefore,this study aimed to explore the relationship between STAS tumor cells and the clinical and molecular characteristics of patients with lung adenocarcinoma,as well as their impact on prognosis.Methods:This study included 147 patients who were diagnosed with lung adenocarcinoma at the Inner Mongolia Autonomous Region Cancer Institute between January 2014 and December 2017.Surgical resection specimens were retrospectively analyzed.Using univariate and multivariate Cox analyses,we assessed the association between STAS and the clinicopathological features and molecular characteristics of patients with lung adenocarcinoma.Furthermore,we investigated the effects on patient prognosis.In addition,we developed a column–line plot prediction model and performed internal validation.Results:Patients with positive STAS had a significantly higher proportion of tumors with a diameter≥2 cm,with infiltration around the pleura,blood vessels,and nerves,and a pathological stage>IIB than in STAS-negative patients(P<0.05).Cox multivariate survival analysis revealed that clinical stage,STAS status,tumor size,and visceral pleural invasion were independent prognostic factors influencing the 5-year progression-free survival in patients with lung adenocarcinoma.The predictive values and P values from the Hosmer-Lemeshow test were 0.8 and 0.2,respectively,indicating no statistical difference.Receiver operating characteristic curve analysis demonstrated areas under the curve of 0.884 and 0.872 for the training and validation groups,respectively.The nomogram model exhibited the best fit with a value of 192.09.Conclusions:Clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis are independent prognostic factors for patients with STAS-positive lung adenocarcinoma.The nomogrambased on the clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis showed good accuracy,differentiation,and clinical practicality.

Effects of long non-coding RNA GAS5 on proliferation and apoptosis of hepatocellular carcinoma cells through miR-26a-5p action

Objective Long non-coding RNAs(lncRNAs)regulate tumor development and progression by promoting tumor proliferation,invasion,and metastasis.The aim of the study was to investigate the effects of lncRNA growth arrest-special 5(GAS5)on proliferation and apoptosis of hepatocellular carcinoma(HCC)cells through miR-26a-5p action.Methods Expression levels of GAS5 were detected in cancerous and paracancerous tissue of 80 HCC patients by RT-qPCR.The starBase tool predicted that GAS5 had binding sites for the miRNA miR-26a-5p,which was also highly expressed in HCC tissue.The relationship between GAS5 and miR-26a-5p was confirmed using a luciferase reporter assay.The role of these lncRNAs was further explored by transfecting plasmids into SMMC-7721 cells and classifying the cells as follows:NC group,GAS5 group,anti-miR-26a-5p group,and GAS5+miR-26a-5p group.Cell proliferation,cell cycle,and apoptosis were detected in each group.The relationship between miR-26a-5p and phosphatase and tensin homolog deleted on chromosome 10(PTEN)was analyzed by TargetScan database prediction and luciferase reporter assay.Western blotting was used to quantify PTEN,phosphatidylinositol 3-kinase(PI3K),phosphorylated protein kinase B(p-Akt),cyclin D1,and human P27 protein(P27).Results GAS5 was downregulated,while miR-26a-5p was upregulated in HCC tissue compared to in paracancerous tissue.High GAS5 levels and low miR-26a-5p levels inhibited cell proliferation,increased the number of G0/G1 phase cells,promoted cell apoptosis,promoted PTEN and P27 expression,and inhibited PI3K,P-Akt,and cyclin D1 expression at the protein level.Upregulation of miR-26a-5p attenuated the effects of GAS5 upregulation on the proliferation,cell cycle,and apoptosis of HCC cells and on the expression of PTNE/PI3K/Akt signaling pathway-related proteins.Conclusion Low GAS5 levels regulate the proliferation and apoptosis of HCC cells via the PTNE/PI3K/Akt signaling pathway and are linked to upregulation of miR-26a-5p.

Safety and efficacy of EFGR and VEGF signaling pathway inhibition therapy in patients with colorectal cancer: a meta-analysis

Objective Epidermal growth factor receptor(EGFR) and vascular endothelial growth factor(VEGF) inhibitors are two targeted therapies for metastatic colorectal cancer(mCRC). However, few studies have focused on the safety and efficacy of combined targeted therapy against those of a single inhibition therapy of EFGR or VEGF. This meta-analysis aimed to compare the anti-tumor activity of the combined inhibition therapy and single inhibition therapy in patients with mCRC. Methods We searched PubMed, Medline, the Cochrane library, Embase, and annual meeting proceedings for relevant clinical trials. Objective response rate(ORR), progression-free survival(PFS), overall survival(OS), and adverse events were extracted and calculated.Results Nine trials comprising 3977 patients were selected for the analysis. The combined inhibition therapy showed a 3.7% improvement in ORR compared with single inhibition, and this difference was statistically significant [hazard ratio(HR) = 1.33; 95% confidence interval(CI), 1.01–1.74; P = 0.04]. Subgroup analysis showed that the combined EGFR and VEGF inhibitor therapy had an 11.65% improvement in ORR compared with VEGF inhibitor therapy(OR = 2.14; 95% CI, 1.34–3.40; P = 0.001). EGFR and VEGF inhibitor therapy and chemotherapy had an 18.08% improvement in ORR compared with chemotherapy(OR = 2.21; 95% CI, 1.05–4.64; P = 0.04). Moreover, EGFR and VEGF inhibitor therapy significantly improved PFS compared with VEGF inhibitor therapy(OR = 0.82; 95% CI, 0.69–0.97; P = 0.02). VEGF inhibitor therapy and chemotherapy significantly improved PFS compared with EGFR and VEGF inhibitor therapy and chemotherapy(OR = 1.20; 95% CI, 1.11–1.30; P = 0.00). In addition, EGFR and VEGF inhibitor therapy showed improved OS compared with VEGF inhibitor therapy(HR = 0.78, 95% CI: 0.65–0.94; P = 0.008). Finally, the combined inhibition therapy showed an obviously increased risk of cutaneous and mucosal effects(RR = 6.45; 95% CI: 2.71–15.36; P < 0.01), diarrhea/abdominal pain(RR = 1.97; 95% CI: 1.45–2.68; P < 0.01), fatigue/asthenia(RR = 1.60; 95% CI: 1.10–2.32; P = 0.01), dehydration or electrolyte disturbance(RR = 2.78; 95% CI: 1.48–5.21; P < 0.01), nail disorder(RR = 8.23; 95% CI: 1.52–44.57; P = 0.01), and dizziness/headache(RR = 3.43; 95% CI: 1.89–6.23; P < 0.01) compared with single inhibition therapy.Conclusion Compared with single inhibition therapy, the combined inhibition therapy significantly improved ORR, PFS, and OS in the treatment of mCRC patients. Compared with a single-targeted agent, the combined therapy of anti-EGFR and anti-VEGF drug provided an efficacy advantage, although it led to greater toxicity.

Milk fat globule epithelial growth factorⅧ(MFG-E8)sustains survival of cancer cells by prompting tumor angiogenesis and suppressing host immunities

Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progression and survival. MFG-E8 contains a signal sequence for secretion, two epidermal growth factor(EGF)-like domains at the NH2 terminus and two discoidin domains with blood-clotting factor V/factor Ⅷ(C1 and C2) at the COOH terminus. The second EGF domain contains an arginine-glycine-aspartic(RGD) integrin-binding motif that engages α_vβ_5 integrins to facilitate cell adhesion and induce integrinmediated signal transduction. Integrin α_vβ_3 associates with VEGF receptor 2, engagement of integrins can promote angiogenesis, which plays key roles in growth, proliferation, and survival of cancer cells. VEGF stimulates the expression of α_vβ_3 and α_vβ_5 integrins on angiogenic vasculature, thereby potentiating effects of VEGF receptor engagement. Mice expressing a mutant form of α_vβ_3 integrin are unable to undergo tyrosine phosphorylation, confirming the important role that this integrin plays in pathological angiogenesis and providing important mechanistic insights. The C-terminus discoidin-like domains promote binding to membrane phospholipids, functioning close to VEGF like angiogenesis. MFG-E8 is an opsonin for apoptotic cells, and it acts as a bridging protein between apoptotic cells and phagocytes. It also influences cell immunities by altering CD4^+ and/or CD8^+ cells. Antibody or small peptide works with MFG-E8 at different functional sites or interacts with EGF-like domains and/or discoidin-like domains may play an important role in anti-angiogenesis or immune restoration. Altering the structures and/or functions of MFG-E8 and/or its domains is promising for development of novel anti-cancer strategies.

Epinephrine use during chemotherapy to treat severe tracheal stenosis secondary to advanced esophageal cancer:A case report and review of the literature

Dyspnea from tracheal stenosis due to compression by a tumor is an emergency that complicates therapy in oncology.We report a case of advanced esophageal cancer in a 56-year-old male who developed severe dyspnea due to airway compression by mediastinal lymph node enlargement.We used epinephrine by subcutaneous injection and aerosol inhalation to temporarily relieve dyspnea while the patient received bevacizumab and chemotherapy.The dyspnea had subsided considerably after 5 days,and the mediastinal lymph nodes were significantly reduced after 2 cycles of chemotherapy.However,the patient died of massive tracheal hemorrhage 2 months later.