Genomic based analyses reveal unique mutational profiling and identify prognostic biomarker for overall survival in Chinese small-cell lung cancer.

OBJECTIVE: As an aggressive subtype of lung cancer, small-cell lung cancer (SCLC) presents a poor prognosis. Although molecular and clinical characteristics have been established for SCLC, limited investigation has been performed for predicting survival of SCLC patients. METHODS: Genomic alterations were profiled in Chinese SCLC patients (N = 37) using targeted sequencing. Clonal mutation burden (CMB) integrated the number of mutations with the clonal structure of the tumor. Specific pathways involving DNA damage repair (DDR) and cell cycle as well as CMB were studied as potential biomarkers for prognosis of SCLC. RESULTS: TP53 and RB1 gene mutations were the most common alterations (91.9% and 83.8%, respectively), followed by LRP1B, FAM135B, SPTA1, KMT2D, FAT1, and NOTCH3. Survival analysis revealed that mutation status of the DDR pathway was associated with worse OS in our cohort. Importantly, patients with higher CMB exhibited worse OS in our cohort and this observation was successfully validated in the cBioportal cohort. Moreover, multivariate analysis demonstrated CMB as a promising independent prognostic factor for OS in Chinese SCLC patients. Interestingly, patients with loss of function of RB1, validated by immunohistochemistry staining, appeared to have worse OS. CONCLUSIONS: The mutational profiling of Chinese SCLC patients signified an ethnicity dependent component. CMB was firstly found to be associated with OS of Chinese SCLC patients and could be regarded as a prognostic marker for SCLC.

Dehydrocostus Lactone Enhances Chemotherapeutic Potential of Doxorubicin in Lung Cancer by Inducing Cell Death and Limiting Metastasis.

BACKGROUND Natural compounds have been utilized in inhibiting metastasis alone or in combination with other anti-tumor agents. Dehydrocostus lactone (DHC), a natural sesquiterpene lactone, was used to investigate its effect on proliferation of lung cancer cells and on the anti-angiogenic efficacy of doxorubicin. MATERIAL AND METHODS Cell proliferation was assessed by MTT assay and clonogenic assay. Apoptosis and migration were assessed by flow cytometry and wound-healing assay, respectively. Western blotting and qPCR were performed for gene and protein expression analysis. Matrigel plug assay was performed for angiogenesis assessment. RESULTS Results of the study show that DHC inhibited the survival and proliferation of lung cancer cells (A549 and H460) and enhanced the growth-inhibitory properties of DOX. Cotreatment of DHC enhanced the apoptosis-inducing effects of DOX by activating caspase-9 and caspase-3 followed by cleavage of PARP. Treatment of A549 and H460 cells with DHC caused suppression of HIF-1α, Akt and pAkt, GSK-3ß and pGSK-3ß, as well as ERK, pERK, mTOR, and p-mTOR. DHC enhanced the effect of DOX by inhibiting migration of A549 cells as observed by wound-healing assay. DHC caused synergistic inhibition of MMP-2 and MMP-9 genes when treated in combination with DOX. DHC further enhanced the anti-angiogenic properties of DOX in mice implanted with Matrigel plugs. DHC suppressed the proliferation of lung cancer cells and enhanced the anti-angiogenic properties of DOX. CONCLUSIONS The putative mechanism behind the metastasis-limiting effects of DHC may involve the suppression of Akt/GSK-3ß and inhibition of MMP-2 and MMP-9 in lung cancer cells.

Branched-chain amino acid transaminase 1 (BCAT1) promotes the growth of breast cancer cells through improving mTOR-mediated mitochondrial biogenesis and function.

Branched-chain amino acids (BCAAs) are important nutrient signals that have direct and indirect effects. BCAA catabolism is a conserved regulator of physiological aging and participates in diverse physiological and pathological processes, including carcinoma development. The roles of BCAA catabolism in human breast cancer remains unknown. Here we provide evidence that BCAA catabolism is involved in human breast cancer. The plasma and tissue levels of BCAAs are increased in breast cancer, which is accompanied by the elevated expression of the catabolic enzymes, including branched-chain amino acid transaminase 1 (BCAT1). Knockdown of BCAT1 represses the growth rate and colony formation capacity of breast cancer cells, opposing results are observed when BCAT1 is overexpressed. BCAT1 can promote mitochondrial biogenesis, ATP production and repress mitochondrial ROS in breast cancer cells by regulating the expression of related genes. Mechanism study reveals that BCAT1 activates the mTOR, but not AMPK or SIRT1, signaling to promote mitochondrial biogenesis and function, and subsequently facilitates growth and colony formation of breast cancer cells. Taken together, we demonstrate that BCAA catabolism is activated in human breast cancer, and abolishment of BCAA catabolism by knocking down BCAT1 inhibits breast cancer cell growth by repressing mTOR-mediated mitochondrial biogenesis and function.

High scavenger receptor class B type I expression is related to tumor aggressiveness and poor prognosis in breast cancer.

Scavenger receptor class B type I (SR-BI) has been linked to the development and progression of breast cancer. However, its clinical significance in breast cancer remains unclear. Here, we evaluated SR-BI expression in a well-characterized breast cancer tissue microarray by immunohistochemistry. High SR-BI expression was observed in 54 % of all breast cancer cases and was significantly associated with advanced pTNM stage (P = 0.002), larger tumor size (P = 0.023), lymph node metastasis (P = 0.012), and the absence of ER (P = 0.014). The Kaplan-Meier survival analysis revealed that patients with high SR-BI expression had significantly shorter overall survival (OS) (P = 0.004). Moreover, multivariate analysis with adjustment for other prognostic factors confirmed that SR-BI was an independent prognostic factor for patient outcome (P = 0.017). Overall, our study demonstrated that high SR-BI expression was related to conventional parameters indicative of more aggressive tumor type and may serve as a new prognostic marker for poor clinical outcome in human breast cancer.

HBV-associated intrahepatic cholangiocarcinoma with high serum alpha-fetoprotein: a case report with review of literature.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor. The etiology of ICC remains poorly understood. Recently, hepatitis B virus (HBV) infection has been implicated as a potential risk factor for ICC, particularly in HBV-endemic areas. Elevation of serum alpha-fetoprotein (AFP) is seen in approximately 20 % of ICC patients. However, serum AFP levels higher than 10,000 ng/mL have only been reported in a few ICC patients. We report an unusual case of HBV-associated ICC occurring in a male with a markedly elevated serum AFP. CASE PRESENTATION: A 60-year-old East Asian male presented with complaints of epigastric distention and right shoulder pain. Laboratory tests showed HBV infection, HBV deoxyribonucleic acid (DNA) slightly elevated (21 IU/mL) and serum AFP markedly elevated (12,310 ng/mL). Computed tomography (CT) scan found a large and irregular mass in the left lobe of the liver. The patient underwent the left hepatic lobe resection. Histopathological examination showed chronic hepatitis B in the background liver and the immunohistochemical (IHC) findings strongly supported the diagnosis of ICC with aberrant expression of AFP. Serum AFP and HBV DNA declined to normal level postoperatively. The patient received four cycles of gemcitabine plus oxaliplatin and took entecavir to prevent HBV reactivation. The patient kept disease free for 18 months in the latest follow-up. CONCLUSION: ICC patients with HBV infection should be distinguished from other ICC cases, based on distinct clinicopathological features and favorable outcome. Screening for HBV infection should be carried out before initiation of chemotherapy. Antiviral therapy is indicated for prevention of HBV reactivation.

DNA Repair Genes ERCC1 and BRCA1 Expression in Non-Small Cell Lung Cancer Chemotherapy Drug Resistance.

BACKGROUND Surgery combined with chemotherapy is an important therapy for non-small cell lung cancer (NSCLC). However, chemotherapy drug resistance seriously hinders the curative effect. Studies show that DNA repair genes ERCC1 and BRCA1 are associated with NSCLC chemotherapy, but their expression and mechanism in NSCLC chemotherapy drug-resistant cells has not been elucidated. MATERIAL AND METHODS NSCLC cell line A549 and drug resistance cell line A549/DDP were cultured. Real-time PCR and Western blot analyses were used to detect ERCC1 and BRCA1 mRNA expression. A549/DDP cells were randomly divided into 3 groups: the control group; the siRNA-negative control group (scramble group); and the siRNA ERCC1 and BRCA1siRNA transfection group. Real-time PCR and Western blot analyses were used to determine ERCC1 and BRCA1 mRNA and protein expression. MTT was used to detect cell proliferation activity. Caspase 3 activity was tested by use of a kit. Western blot analysis was performed to detect PI3K, AKT, phosphorylated PI3K, and phosphorylated AKT protein expression. RESULTS ERCC1 and BRCA1 were overexpressed in A549/DDP compared with A549 (P<0.05). ERCC1 and BRCA1siRNA transfection can significantly reduce ERCC1 and BRCA1 mRNA and protein expression (P<0.05). Downregulating ERCC1 and BRCA1 expression obviously inhibited cell proliferation and increased caspase 3 activity (P<0.05). Downregulating ERCC1 and BRCA1 significantly decreased PI3K and AKT phosphorylation levels (P<0.05). CONCLUSIONS ERCC1 and BRCA1 were overexpressed in NSCLC drug-resistant cells, and they regulated lung cancer occurrence and development through the phosphorylating PI3K/AKT signaling pathway.

E-cadherin mediates adhesion of Aspergillus fumigatus to non-small cell lung cancer cells.

A spergillus fumigatus is a widely distributed microorganism, and recently, A. fumigatus culture filtrate has been shown to trigger apoptotic cell death in several human cancer cell lines, including non-small lung cancer (NSCLC) cells, A549. Nevertheless, the molecular adhesion of A. fumigatus to these cancer cells to trigger cell death remains unknown. Here, we knocked down E-cadherin in A549 cells and examined its effects on A. fumigatus. The blastospores of A. fumigatus were incubated with the complete protein extracts from A549 cells, using an affinity purification procedure. Preliminary exploration of E-cadherin-interacting protein on the surface of Aspergillus fumigates was done by immunoprecipitation and mass spectrometry analysis. We found that the adhesion of the blastospores to A549 cells was significantly reduced by E-cadherin suppression in A549 cells, suggesting that E-cadherin of A549 cells may mediate the surface adhesion of A. fumigatus blastospore. Mass spectrometry (MS) analysis predicted two binding proteins for E-cadherin on A. fumigatus, AfA24A6.130c and XP_747789. Finally, the growth of E-cadherin-depleted A549 cells significantly increased by infection of A. fumigatus in vivo. Thus, our study suggests that E-cadherin mediates adhesion of A. fumigatus to NSCLC cells to trigger cell death and provides molecular evidence for the treatment of NSCLC with controlled A. fumigatus infection.

The comparison of outcomes between hypofractionated and conventional 3D-CRT regimens used in combination with TACE as first-line treatment of advanced hepatocellular carcinoma.

Treatment of primary hepatocellular carcinoma (HCC) with transcatheter hepatic arterial chemoembolization (TACE) and three-dimensional conformal radiotherapy (3D-CRT) achieves good short-term but poor long-term survival. We retrospectively assessed whether outcomes differ between hypofractionated and conventional 3D-CRT regimens. Patients were treated in our institution between June 2005 and October 2009. All patients received two cycles of TACE followed by either hypofractionated 3D-CRT (6-8 Gy fractions for 3-4 weeks to 48-64 Gy) or conventional 3D-CRT (2 Gy fractions for 6-7 weeks to 60-70 Gy) 4 weeks later. We assessed data from 110 patients (55 in each 3D-CRT group). Overall response rates were similar in the two groups. Acute adverse event rates were not significantly higher in the hypofractionated 3D-CRT group than in the conventional 3D-CRT group; two patients and one patient, respectively, died of late radiation-induced liver failure. Overall survival at 1 year was 83.6 % in the hypofractionated 3D-CRT group versus 68.8 % in the conventional 3D-CRT group (P = 0.019), and at 3 years, it was 31.7 versus 13.9 % (P = 0.004). Median survival was 27.97 versus 16.13 months (P = 0.002). Hypofractionated 3D-CRT seemed to provide better overall survival than conventional 3D-CRT regimens combined with TACE as a first-line treatment for advanced HCC.

A polysaccharide from the fruiting bodies of Agaricus blazei Murill induces caspase-dependent apoptosis in human leukemia HL-60 cells.

Polysaccharides are the major active ingredients of fungus Agaricus blazei for treating and preventing cancer. However, there are no reports showing anti-tumor activity of A. blazei polysaccharides (ABP) on human leukemia (HL)-60 cells in vitro and in vivo. In this study, we demonstrated that ABP efficiently inhibited proliferation of cultured HL-60 cells, which was associated with the induction of apoptosis. The increase in ABP-induced apoptosis was accompanied by loss of mitochondria membrane potential (∆Ψm), cytochrome c release from the mitochondria, activation of caspase-3, degradation of poly(ADP-ribose) polymerase (PARP), and the elevated ratio of Bcl-2-associated X (Bax)/B-cell lymphoma 2 (Bcl-2). Moreover, z-DEVD-fmk, a caspase-3 inhibitor, reversed the cytotoxic effects and apoptotic characteristics induced by ABP in HL-60 cells. Furthermore, we confirmed that ABP could obviously inhibit the solid cancer growth of leukemia HL-60 in tumor xenograft model. These data demonstrated that ABP effectively induced the apoptosis of HL-60 cells via a signaling cascade of mitochondrial caspase-3-dependent pathway.

Introducing Bacillus natto and Propionibacterium shermanii into soymilk fermentation: A promising strategy for quality improvement and bioactive peptide production during in vitro digestion.

Herein, the texture properties, polyphenol contents, and in vitro protein digestion characteristics of soymilk single- or co-fermented by non-typical milk fermenter Bacillus natto (B. natto), Propionibacterium freudenreichii subsp. shermanii (P. shermanii), and traditional milk fermenter were evaluated. Co-fermenting procedure containing B. natto or P. shermanii could raise the amounts of gallic acid, caffeic acid, and GABA when compared to the unfermented soymilk. Co-fermented soymilk has higher in vitro protein digestibility and nutritional protein quality. Through peptidomic analysis, the co-work of P. shermanii and Lactobacillus plantarum (L. plantarum) may release the highest relative percentage of bioactive peptides, while the intervention of B. natto and Streptococcus thermophilus (S. thermophilus) resulted in more differentiated peptides. The multi-functional bioactive peptides were mainly released from glycine-rich protein, ß-conglycinin alpha subunit 1, and ACB domain-containing protein. These findings indicated the potential usage of B. natto/S. thermophilus or P. shermanii/L. plantarum in bio-enhanced soymilk fermentation.

[Efficacy and safety of low-frequency rotary magnetic fields in the treatment of patients with advanced malignant tumors].

OBJECTIVE: To investigate the clinical efficacy and safety of low-frequency rotary magnetic fields in the treatment of patients with advanced malignant tumors. METHODS: 137 patients with advanced malignant tumors were exposed to 400 r/min, 0.4 T low-frequency rotary magnetic fields. An area including the primary tumor, local metastasis and metastatic lymph nodes was exposed daily, 2 hours per day for 30~50 days (average time of 42 days). RESULTS: All of the 137 patients completed the low-frequency rotary magnetic field treatment. There were 28 cases with complete response, 54 cases with partial response, and the clinical benefit rate was 59.9%. The tumor type, initial KPS and QOL showed statistical significance in the clinical benefit rate (P < 0.05). The median overall survival was 12 months, and the 1-year, 2-year and 3-year survival rates were 47.0%, 11.8%, 3.4%, respectively. The tumor type, initial KPS and QOL were identified by univariate log-rank test as significant prognostic factors for overall survival (P < 0.05). Multivariate analysis showed that the initial QOL was an independent prognostic factors (P = 0.037) . During the treatment, asthenia and local pain were observed in 11 patients, and 6 patients had mild tachycardia (increased 3 to 5/min) and/or temperature elevation (0.5 to 1.0°C). All above symptoms disappeared spontaneously. No treatment-related death was observed. CONCLUSIONS: Low-frequency rotary magnetic fields is an effective and safe method in the treatment of patients with advanced malignant tumors, and may prolong survival significantly.

Neutron-Absorption Properties of B/Cu Composites.

Copper has high electrical and thermal conductivity, which is frequently employed in structural and functional materials. In this research, powder metallurgy was used to incorporate boron nanosheets into metal matrix composites to create boron dispersion-enhanced copper matrix composites. The neutron-absorption characteristics of composite materials were investigated, as well as the link between neutron-absorption cross-section and neutron energy. The results told us that the morphology of the second phase on the particle surface is closely related to the size of Cu-B particles, copper and boron correspond atomically to each other on the interface without dislocation or lattice distortion, forming a completely coherent interface, and that the neutron absorption cross-section decreases exponentially as neutron energy increases. In low-energy neutrons with energies less than 0.1 eV, the increase of boron content and 10B abundance in Cu-B alloy will enhance the neutron-absorption capacity of the alloy. Boron dispersion-strengthened copper matrix composites have good neutron-absorption capacity, and the microstructure and size of boron do not affect the neutron-absorption performance of composites with the same content of boron. The hardness of the B-dispersion-strengthened Cu matrix composite obtained by nanoindentation test is about 3.04 GPa. Copper matrix composites with boron dispersion reinforcement exhibit high hardness and neutron-absorption characteristics.

Preliminary study on establishing the discriminant equation in pathological grading of hepatocellular carcinoma using immunohistochemical marker parameters.

Context: Identifying the pathological diagnosis for patients with primary hepatocellular carcinoma (HCC) depends on recognizing the microscopic cytological morphology and pathological molecular marker expressions. However, there are nearly 100 markers of primary HCC, most of which are discretely distributed. Thus, the diagnostical process lacks certainty. Aims: Settings and Design: A preliminary study. Methods and Material: A total of 37,012 pathological molecular markers were selected in this study from 1,034 randomly selected patients with primary HCC from January 2014 to June 2019. Patient information included demographic and pathological characteristics, immunohistochemical and blood biochemical indicators, and other biological laboratory data. Statistical Analysis Used: The discriminant analysis method (parametric and non-parametric) was used in two-thirds of the dataset to quantitatively establish the discriminant equation of gender, age, and positive variables determined by the Cochran-Armitage trend test for pathologic grading. The remaining one-third dataset was used to verify the discriminative ability. Results: According to the fitted discriminant equation, only CD34, CD68, Glypican-3, HepPar-1, and Ki-67 (%) exhibited high sensitivity for the diagnosis of primary HCC. Among these five indicators, glypican-3 demonstrated a relatively high correlation with Ki-67 (%). CK19 and CK7 were highly correlated. Glypican-3 demonstrated a higher positive rate in poorly differentiated tumors, whereas HepPar-1 exhibited a higher positive rate in well-differentiated tumors. Conclusions: Gender, age, HepPar-1, Ki-67 (%), and Glypican-3 demonstrated higher accuracy in discriminating the pathological grades of I/II, but the ability to discriminate pathological grades III/IV was insufficient. Additionally, other factors were found to affect pathological grading.

Erratum: FBXO22 Suppresses Metastasis in Human Renal Cell Carcinoma via Inhibiting MMP-9-Mediated Migration and Invasion and VEGF-Mediated Angiogenesis.

[This corrects the article DOI: 10.7150/ijbs.31293.].

TLR7 regulates dendritic cell-dependent B-cell responses through BlyS in immune thrombocytopenic purpura.

OBJECTIVES: Immune thrombocytopenic purpura (ITP) is an autoimmune disorder in which anti-platelet antibodies induce platelet destruction owing to an imbalanced immune response. Several studies have established that B cells play an important role in the production of anti-platelet antibodies and that dendritic cells (DC) are professional antigen-presenting cells of the immune system that may lead to the development of autoantibody through B cells. We aimed at investigating the role of B cells and DC in the pathogenesis of ITP through B-lymphocyte stimulator (BlyS) and toll-like receptor 7 (TLR7) signals. METHODS: Twenty-two patients with ITP and 20 healthy controls were enrolled in this study. Serum BlyS, its mRNA and TLR7 mRNA were measured using ELISA kits or RT-PCR, and CD14(+) or CD19(+) monocytes were investigated for the pathogenesis of ITP with in vitro culture systems. RESULTS: We demonstrated that serum BlyS levels in patients with ITP were significantly higher than those in healthy controls and that there was a positive correlation between serum BlyS levels and glycoprotein-specific antibody levels in patients with ITP. We found that TLR7 regulates dendritic cell-dependent B-cell responses through BlyS in patients with ITP. Dendritic cells stimulated with R848 (TLR7 ligand) are able to produce vast amounts of BlyS, which is crucial for B-cell survival, proliferation and differentiation, and increase anti-platelet antibodies production in in vitro coculture systems. CONCLUSIONS: These findings provide new insights into the pathogenesis of ITP by which TLR7 regulates DC-dependent B-cell responses through BlyS.

Underexpressed microRNA-199b-5p targets hypoxia-inducible factor-1α in hepatocellular carcinoma and predicts prognosis of hepatocellular carcinoma patients.

BACKGROUND AND AIM: MicroRNAs are short noncoding RNA molecules that are responsible for the posttranscriptional regulation of target genes. The aim of this study was to determine whether microRNA-199b-5p (miR-199b) plays a role in the progression and prognosis of hepatocellular carcinoma (HCC), and to elucidate whether hypoxia-inducible factor-1α (Hif1α) is regulated by miR-199b. METHODS: In this study, 35 matched HCCs and cirrhosis tissues were assayed for miR-199b and Hif1α expression. To evaluate the role of miR-199b, we assessed cell proliferation rate and clonogenic survival of miR-199b- or negative control-transfected cells by MTT and clone formation assay, respectively. In addition, the regulation of Hif1α by miR-199b was evaluated by Western blotting and luciferase assay. MiR-199b was downregulated in 77% of HCCs, whereas Hif1α protein was upregulated in 69% of cases. A significant inverse correlation between miR-199b and Hif1α was observed in HCCs. RESULTS: Patients with lower levels of miR-199b expression had poorer overall survival and progression-free survival rates, whereas patients with higher levels of miR-199b expression had better survival. Moreover, miR-199b could restrain cell growth and obviously enhance the radiosensitizing effect of HepG2 cells. MiR-199b and pGL3-Hif1α vector-transfected cells showed suppressed Hif1α protein expression and significant reduced luciferase activity. CONCLUSIONS: Underexpressed miR-199b, which may be via the upregulation of Hif1α in HCCs, is inversely correlated with survival and directly correlated with the malignant status of HCC patients.

[Efficacy of late accelerated hyperfractionated conformal radiotherapy combined with capecitabine for esophageal carcinoma].

OBJECTIVE: To evaluate the efficacy of late accelerated hyperfractionated conformal radiotherapy (LACF) combined with capecitabine on esophageal carcinoma. METHODS: One hundred and sixty eight patients of esophageal cancer were randomly divided into 3 groups, including the radiotherapy alone group (CF) which received conventional conformal radiotherapy to a total of 60 - 66 Gy, LCAF group which received conventional fractionated conformal radiotherapy during the first two-thirds of the treatment to a dose about 40 Gy/20F/4W, then followed by late accelerated hyperfractionated conformal radiotherapy, twice daily radiotherapy at 1.3 Gy per fraction to a total dose about 64 - 69 Gy, and LCAF + C group (late accelerated hyperfractionated radiotherapy combined with capecitabine), in which patients were treated as the same as the LCAF group, except that they were treated with capecitabine (1.5 g po bid) from beginning of the radiotherapy to the end. RESULTS: The short-term results of the 3 groups were 74.0%, 85.5% and 95.2%, respectively (P = 0.006). The local control rates at 1, 3 and 5 years were 64.0%, 30.0%, 24.0% in the CF group, 81.8%, 65.5%, 58.2% in the LCAF group and 90.1%, 77.8%, 74.6% in the LCAF+C group, respectively. The 1-, 3- and 5-year survival rates of the 3 groups were 58.0%, 20.0%, 8.0%; 78.2%, 36.4%, 17.0% and 85.7%, 55.6%, 30.2%, respectively. The effect of LCAF+C group was better than that of LCAF group and CF group. The incidence of acute tracheitis and acute esophagitis in the LCAF+C group and LCAF group was higher than that in the CF group, but there was no stastistically significant difference between the 2 groups. There was no statistically significant difference in distant metastasis in the 3 groups. CONCLUSIONS: Capecitabine, as an effective chemosensitizater combined with late accelerate hyperfractionated radiotherapy can improve the short-term results of treatment of esophageal cancer. The value of this combined treatment in distant metastasis reqires further study in the clinic.

[Clinical value of preoperative serum VEGF, CRP and IL-6 levels in colorectal carcinoma].

OBJECTIVE: To determine the preoperative serum VEGF, IL-6, and CRP levels in colorectal carcinoma, and to explore their correlation with disease status and prognosis. METHODS: Serum VEGF and IL-6 levels were assessed using ELISA, and CRP was measured by immunoturbidimetry. They were compared between the colorectal carcinoma group and the control group. The five-year survival rate and poor prognostic factors were analyzed by Kaplan-Meier and Log-rank method, respectively. RESULTS: The serum VEGF, IL-6, and CRP levels in colorectal carcinoma were (591 ± 312) pg/ml, (13.2 ± 3.7) pg/ml, and (1.14 ± 0.87) mg/dl, respectively, higher than that in the control group. The two groups showed significant difference in VEGF and CRP (P < 0.001, P = 0.002). VEGF expression was higher in male than that in female [(638 ± 387) pg/ml vs. (552 ± 271) pg/ml, P = 0.042]. The cases with tumor size smaller than 5 cm had lower VEGF expression compared with that in cases with tumor size ≥ 5 cm [(538 ± 275) pg/ml vs. (647 ± 331) pg/ml, P = 0.009]. IL-6 expression showed significant difference in males (11.7 ± 3.2) and females (15.2 ± 4.0) pg/ml, (P = 0.011). The five-year survival rate in the group with VEGF < 591 pg/ml was 86.8% (33/38), higher than that in the ≥ 591 pg/m group. High VEGF level tended to reduce survival (χ(2) = 0.933, P = 0.344). VEGF ≥ 591 pg/ml was a factor of poor prognosis in colorectal carcinoma, assessed by Log-rank methods (P < 0.05). Tumor size and VEGF concentration were risk factors of prognosis (P = 0.032, OR = 0.985; P = 0.011, OR = 0.976). CONCLUSIONS: Serum VEGF and IL-6 expressions have gender differences. Serum VEGF can be used as a biomaker of clinical diagnosis of colorectal cancer, and has an important significance on the prognosis of patients.

[The generation characteristics and purchasing points of Gamma Knife].

With the rapid development of the computer technology and the constant updating of the radiotherapy equipment, a huge improvement has been manifested by the new generation of the Gamma Knife radiotherapy system. Not only its functions are being improved, but also the treatment indications are expanding. These advances have been widely recognized by the clinical medical experts, breaking off the forbbiden zone of surgical operations, saving a lot of tumor patients with both malignant and benign lesions, who are not suitable for surgical operations due to local anatomical limitations. However, there are still a lot of clinicians being not clear about the funcitons and generations of Gamma Knife radiotherapy system. Moreover, variant guidances by different manufacturerers have given rise to confusions, especially on the equipment purchasing. Therefore, in this report we summarize the features of Gamma radiotherapy systems produced by different manufacturers in recent years, to supply reference data for the organization and expert buyers.

Long noncoding RNA VPS9D1-AS1 augments the malignant phenotype of non-small cell lung cancer by sponging microRNA-532-3p and thereby enhancing HMGA2 expression.

We investigated the influence of the long noncoding RNA VPS9D1 antisense RNA 1 (VPS9D1-AS1) on the malignant phenotype of non-small cell lung cancer (NSCLC) cells in vitro and in vivo. We also explored the mechanisms by which VPS9D1-AS1 exerts its oncogenic action during NSCLC progression. VPS9D1-AS1 expression was upregulated in NSCLC; the extent of its upregulation significantly correlated with patients' adverse clinicopathological characteristics and shorter overall survival. When VPS9D1-AS1 was knocked down in NSCLC cells, their proliferation, colony-forming capacity, migration, and invasiveness were lower, whereas their apoptosis rate was higher, compared to the control. VPS9D1-AS1 knockdown attenuated tumor growth of NSCLC cells in vivo. Mechanistically, VPS9D1-AS1 directly interacted with microRNA-532-3p (miR-532-3p) in NSCLC cells; the impact of VPS9D1-AS1 knockdown on NSCLC cells was attenuated by miR-532-3p inhibition. Furthermore, VPS9D1-AS1 knockdown decreased the expression of high mobility group AT-hook 2 (HMGA2) in NSCLC cells via miR-532-3p sponging. Recovery of HMGA2 expression partially reversed the inhibitory effects of VPS9D1-AS1 knockdown on NSCLC cells. Thus, VPS9D1-AS1 functions as a competing endogenous RNA that positively regulates HMGA2 expression by sponging miR-532-3p in NSCLC cells, suggesting that the VPS9D1-AS1-miR-532-3p-HMGA2 pathway can be a potential diagnostic and/or therapeutic target in NSCLC.