High ANKZF1 expression is associated with poor overall survival and recurrence-free survival in colon cancer.

Aim: To investigate the association and prognostic value of ANKZF1 gene for survival in colorectal cancer, the mechanism of ANKZF1 level alteration and correlated signaling pathways ANKZF1 is involved. Patients & methods: The Cancer Genome Atlas COREAD dataset was analyzed by bioinformatical investigation. Results: High ANKZF1 expression is associated with poor overall survival (hazard ratio [HR]: 2.094; 95% CI: 1.188-3.689; p = 0.011) and recurrence-free survival (HR: 1.762; 95% CI: 1.021-3.042; p = 0.042) in colon cancer. Bioinformatical analysis showed ANKZF1 was upregulated by amplification and exon expression. ANKZF1 was associated with angiogenesis and cancer signaling pathways. Conclusion: High ANKZF1 is an independent factor of poor survival (overall survival and recurrence-free survival) in colon cancer by taking part in angiogenesis and some cancer signaling pathways.

Immunohistochemical HER2 expression not associated with clinicopathological characteristics of stage I-III gastric cancer patients.

BACKGROUND/AIMS: The aim of this study was to investigate the association of human epidermal growth factor receptor 2 (HER2) expression with clinicopathological characteristics of resectable gastric cancer patients. METHODOLOGY: A total of 394 stage I-III surgical gastric cancer patients who were detected of immunohistochemical (IHC) HER2 expression postoperatively were included in this retrospective study. Association of IHC HER2 over-expression (3+) rate with clinicopathological characteristics was tested by univariate and multivariate analyses. RESULTS: IHC HER2 over-expression rate was 5.1% (95% CI 3.1%-7.7%). By univariate analyses, none of the clinicopathological characteristics was associated with the IHC HER2 over-expression compared to negative expression (0/1+) (p>0.05), with the exception of a higher rate (12.2%) of IHC HER2 (3+) in moderate differentiation subset (p=0.02). However, the multivariate analyses didn't selected any characteristic as an independent risk factor of IHC HER2 over-expression or the combination of IHC HER2 (2/3+). CONCLUSIONS: IHC HER2 over-expression rate is relatively low among stage I-III gastric cancer patients, and might be generally not associated with clinicopathological characteristics.

Individualized leukemia cell-population profiles in common B-cell acute lymphoblastic leukemia patients.

Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development, including IL-7Rα (CD127), cytoplasmic CD79a (cCD79a), CD19, VpreB (CD179a), and sIgM, which are successive and essential for progression of B cells along their developmental pathway. Analysis of the immunophenotypes of 48 common ALL cases showed that the immunophenotypic patterns were highly heterogeneous, with the leukemic cell population differing from case to case. Through the comprehensive analysis of immunophenotypic patterns, the profiles of patient-specific composite leukemia cell populations could provide detailed information helpful for the diagnosis, therapeutic monitoring, and individualized therapies for common ALL.

[Zebra fish cell movements during gastrulation].

During zebrafish gastrulation, large cellular rearrangements create the formation of the three germ layers, ectoderm, mesoderm, and endoderm. This process includes three types of conserved morphogenetic movement: epiboly, involution, and convergent extension. Specially, the anterior movement of prechordal plate progenitors is essential for the location and differentiation of mesendoderm progenitors, and the pechordal plate progenitors'coherent migration is thought to be a good model to study the mechanism of cell movement in vivo. Gastrulation migration is known to be controlled by many signaling pathways such as Wnt/planar cell polarity signaling; however, the underlying molecular mechanism for cellular behavior remains unknown. At present, it is generally agree that cell adhesion and cytoskeletal rearrangement are critical factors during zebrafish gastrulation cell migration. In addition, the role of extraembryonic tissue (yolk syncytial layer) during gastrulation is concerned increasingly. Here, we described the essential factors for controlling cellular behaviors and highlighted the major issues and questions that require further investigation during zebra fish gastrular cell migration in order to provide a complete map containing all the factors for regulating gastrulation cell migration and their interactions on a cellular level.

[Lumen morphogenesis and molecular mechanisms in tubular organs during zebrafish embryonic development].

A network tubular system is an important structure in the body and organ of metazoa. The lumen of tube is fundamental units in the structure, which serve to transport material, divide the organ into different functional compartments and separate the organ from the environment. The defects of lumen formation will lead to abnormalities of the organ morphogenesis and disorder of the function. Zebrafish (Danio rerio)is an important model for development research. Meanwhile easy observation of tubular organ, the relevant mutants, and transgene linages make zebrafish to become an excellent model to study the formation of lumen in the tubular organs, including the blood vessels, neural tube, gut, exocrine pancreas, and pronephric duct, which undergo the typical morphogenesis of lumen that is involved in the organs' development. The process of lumen formation is mainly consisted of induction of extracellular signals, polarization of epithelial cell, directional transportation in the polar cells, the aggregation and transportation of fluid in the lumen, and the reconstruction of cytoskeleton in polar cells and controlled by the precise and complicated molecular networks during embryonic development. This review will summarize our current knowledge on lumen morphogenesis in four kinds of typical tubular organs during zebrafish embryonic development and the related molecular mechanisms as well as to supply helpful reference to the future studies.

Correlation between serum CA724 and gastric cancer: multiple analyses based on Chinese population.

Serum tumor biomarker carbohydrate antigen 724 (CA724) is noticeable for gastric cancer. Correlation between CA724 and gastric cancer was investigated based on Chinese population. Chinese Biomedical Database, Chinese Journal Full-text Database and PubMed were searched. Gastric cancer patients were proven by biopsy, and control included health volunteers or benign gastric diseases. Participants received at least one test of CA724, CA125, CA153, CA199, CA242 or CEA. Meta-analysis, summary ROC (SROC) and post hoc analysis were performed by RevMan 5.0 and SPSS 11.5. Totally, 33 eligible studies were analyzed. Meta-analysis showed CA724 had the highest odds ratio 32.86 compared to control, orderly followed by CA242, CA199, CEA, CA125 and CA153. Accumulated accuracy rate of CA724 was 77 %, superior to others. In SROC analysis, specificity of all studies was above 0.70, but sensitivity of few studies was above 0.70; CA724 was selected as the preferable single test, followed by CA242, CA199, CEA, CA125 and CA153. If threshold of both specificity and sensitivity up to 0.70, CA153 was unacceptable; if up to 0.80, only CA724 and CA242 were considerable. In CA724-combined patterns, CA724+CEA+CA199 combination performed best by increasing sensitivity to 0.74 without impairing specificity, while CA724 + CA199 pattern was not a proper combination. CA724 was the most correlative serum tumor biomarker for gastric cancer in Chinese population. Sensitivity of serum CA724 is limited, but CA724+CEA+CA199 combination is considerable to improve sensitivity without impairing specificity.

Prognostic significance of relevant markers of cancer stem cells in colorectal cancer - a meta analysis.

BACKGROUND/AIMS: To evaluate the correlation between the expression of stem cell makers and prognosis in colorectal cancer. METHODOLOGY: Eligible studies evaluating the correlation between stem cell makers and prognosis were selected based on the references in PubMed, Embase and Cochrane libraries. Outcome measures included overall survival, relevant pathological parameters. Meta-analyses were performed by RevMan 5.0. RESULTS: Seventeen eligible articles involving 3098 patients were included. Meta-analysis showed CD44 expression is not significant difference of 5-year overall survival rate (OR=0.69, p=0.22) and relevant clinical parameters, such as histological grade (OR=1.98, p=0.06), dukes grade (OR=0.77, p=0.43) and metastasis (OR=1.03, p=0.89). Likewise, there is no correlation between CD44v6 and dukes stage (OR=0.56, p=0.23), metastasis (OR= 2.81, p=0.33), except for histological grade (OR=0.48, p=0.02). However, CD44v6 positive cells (OR=0.36, p=0.02) were significantly associated with poor overall survival. CONCLUSIONS: Based on current retrospective evidence, a stem cell maker, CD44 cannot become a prognostic marker in colorectal cancer. In contrast, CD44v6, an isoform of CD44 plays a significant role to predict clinic outcome.

CD133+ CD44+ subgroups may be human small intestinal stem cells.

The identification and separation of small intestinal epithelial stem cells are still on the preliminary stage. In this study, we planned to utilize immunohistochemistry, fluorescence-activated cell sorting (FACS) and RT-PCR to investigate the possibility of CD133 and CD44 as markers of human small intestinal epithelial stem cells. The expressions of CD133, CD44 and Lgr5 were studied by immunohistochemistry. Four subgroups of CD133(+)CD44(+), CD133(+)CD44(-), CD133(-)CD44(+), CD133(-)CD44(-) were sorted out through FACS and the expression level of Lgr5 gene was measured by RT-PCR and polyacrylamide gel electrophoresis (PAGE) with silver stained. Ten cases of samples were available for analyzing. By immunohistochemical staining, few cells with positive expressions of CD133, CD44 and Lgr5 were distributed in the bottom of crypts with the expression locations somewhat overlapped. The average percentage of CD133(+)CD44(+) cells was 0.0580 ± 0.0403%, while the corresponding contents of CD133(+)CD44(-) cells, CD133(-)CD44(+) cells and CD133(-)CD44(-) cells were 0.4000 ± 0.1225%, 0.7000 ± 0.2646% and 76.5600 ± 3.5529% respectively. Ten times of positive expressions of Lgr5 were detected in the CD133(+)CD44(+) groups, while 9/10, 8/10 and 4/10 times for CD133(+)CD44(-), CD133(-)CD44(+) and CD133(-)CD44(-) subgroups respectively. With the help of Quantityone 4.62 software, the densities of corresponding place to Lgr5 and reference gene were obtained. The density ratios of corresponding place to Lgr5 to reference gene were significant difference between subgroups (P < 0.001). By means of LSD method, the density ratios in CD133(+)CD44(+) subgroups had statistical differences from the other subgroups (P < 0.05). We concluded CD133(+)CD44(+) cells may be human small intestinal epithelial stem cells, which need further researches to confirm.

Expression profile, molecular functions, and prognostic significance of miRNAs in primary colorectal cancer stem cells.

MicroRNAs (miRNAs) are known to drive the pathogenesis of colorectal cancer (CRC) via the regulation of cancer stem cells (CSCs). We studied the miRNA expression profile of primary CSCs isolated from patients with CRC (pCRCSCs). Compared to pCRCSC-derived differentiated cells, 98 differentially expressed miRNAs were identified in pCRCSCs. Target genes encoding pCRCSC-related miRNAs were identified using a combination of miRNA target databases and miRNA-mRNA regulatory networks from the same patient. The pCRCSC-related miRNA target genes were associated with pathways contributing to malignant phenotypes, including I-kappa B kinase/NF-kappa B signaling, signal transduction by p53 class mediator, Ras signaling, and cGMP-PKG signaling. The pCRCSC-related miRNA expression signature was independently associated with poor overall survival in both the training and validation cohorts. We have thus identified several pCRCSC-related miRNAs with oncogenic potential that could serve as prognostic biomarkers for CRC.

Effects of heterochromatin in colorectal cancer stem cells on radiosensitivity.

BACKGROUND AND OBJECTIVE: Radiotherapy (RT) is a major non-surgical modality in the comprehensive treatment for colorectal adenocarcinoma. The radioresistance of cancer stem cells (CSCs) is a key factor that influences therapeutic effectiveness. This study was to investigate the effects of specific chromosome structure and histone modification in CSCs in colorectal adenocarcinoma radioresistance. METHODS: Samples were collected from resected human colorectal adenocarcinomas. Subcutaneous colorectal cancer model was established in nude mice. Immunohistochemistry showed that xenografts generated from bulk colorectal cancer cells resembled the original tumor specimen. Flow cytometry was performed to sort CSCs (CD133+) and non-CSCs (CD133-) from both resected samples of colorectal adenocarcinoma and xenograft before and after high single-dose radiation. The markers labeling heterochromatin (H3K9me3, HP1-alpha and H3K4me1) and euchromatin (H3K4me3) in CD133+ and CD133- nucleus were detected by immunofluorescence. RESULTS: There was distinct difference in chromatin structure between colorectal CSCs (CD133+) and non-CSCs (CD133-). The chromatin displayed compact patches in CD133+ nucleus, but loosely latticed structure in CD133- nucleus; immunofluorescence verified that the compact patches existing in CSCs was generated from heterochromatin construction. In addition, the vacuole-like defect in heterochromatin regions of CSCs was observed within 24 h after exposure to 10 gray (Gy) single-dose RT. Interestingly, this phenomenon was repaired from 96 h, and recovered to dense plaque structure in heterochromatin regions of CSCs after 144 h. However, no significant difference in non-CSCs was observed after RT exception for a loose chromatin structure. CONCLUSIONS: CSCs play a role in radiosensitivity in colorectal cancer. The mechanism may be related to heterochromatin formation and histone methylation.

[The expression and clinical significance of AKT2, phosphorylated AKT2 in non-small cell lung cancer].

OBJECTIVE: To study the expression and clinical significance of AKT2, phosphorylated AKT2 (p-AKT2) in non-small cell lung cancer (NSCLC). METHODS: The tumor tissues were obtained from 137 cases of NSCLC, the expressions of AKT2 and p-AKT2 in the tissues were measured by immunohistochemistry. The statistic analysis was carried on to study the correlation of AKT2, p-AKT2 expression to the type of lung cancer, TNM stage, pathological grading. Survival analysis was also studied. RESULTS: The positive rates of AKT2 in lung adenocarcinoma and squamous carcinoma were 60.5% and 54.1% respectively (P > 0.05). While the positive rates of p-AKT2 in lung adenocarcinoma and squamous carcinoma were 68.4% and 47.5% (P < 0.05). The expressions of AKT2 and p-AKT2 were not correlated with age, gender, TNM stage and cell differentiation degree. Further more, survival analysis revealed that 5-year survival rate and median survival time for the patients with positive expression of p-AKT2 were significantly poorer than those with negative expression (20% vs 56%, (28.464 +/- 2.235) months vs (39.214 +/- 3.075) months, P < 0.053, while there were no significant differences with regard to AKT2 expression. CONCLUSION: The positive expression of p-AKT2 in lung adenocarcinoma was higher than that in lung squamous carcinomas. p-AKT2 may be a prognostic factor for non-small cell lung cancer.

Peritoneal Metastatic Cancer Stem Cells of Gastric Cancer with Partial Mesenchymal-Epithelial Transition and Enhanced Invasiveness in an Intraperitoneal Transplantation Model.

OBJECTIVES: This preliminary study is aimed at enriching and isolating peritoneal metastatic cancer stem cells (pMCSCs) of gastric cancer and assessing their epithelial-mesenchymal transition (EMT) phenotype and invasiveness. METHODS: Cancer stem cells of human gastric cancer (CSC-hGC) were previously isolated and transfected with green fluorescent protein and luciferase genes to validate the mouse model of peritoneal metastasis established via transplantation. The first and second generations ([G1] and [G2], respectively) of pMCSCs were isolated from intraperitoneally transplanted CSC-hGC (pMCSC-tGC) by spherical culture. CSC and EMT-related markers and regulators in the two generations of intraperitoneally transplanted tumors were examined by immunohistochemistry, immunofluorescence staining, and quantitative PCR. Cell mobility was examined by a transwell assay. RESULTS: The nude mouse model of intraperitoneally transplanted CSC-hGC was successful in establishing sequential formation of peritoneal tumors and enrichment of pMCSCs. CD44 and CD54 were consistently expressed in the two generations of transplanted tumors. In vitro cell (migration) assays and immunocytofluorescence assays showed that in pMCSC-tGC[G2], E-cad, Survivin, and Vimentin expression was stable; α-SMA expression was decreased; and OVOL2, GRHL2, and ZEB1 expression was increased. PCR analysis indicated that in pMCSC-tGC[G2], the mRNA expression of E-cad, α-SMA, MMP9, MMP2, and Vimentin was downregulated, while that of ZEB1, OVOL2, and GRHL2 was upregulated. In vivo tumor (homing) assays and immunohistochemical assays demonstrated that in pMCSC-tGC[G2], E-cad and Snail were upregulated, while α-SMA was downregulated. The numbers of migrated and invaded pMCSC-tGC[G1] and pMCSC-tGC[G2] were significantly higher than those of CSC-hGC in migration and invasion assays. CONCLUSIONS: pMCSCs might be a specific subpopulation that can be sequentially enriched by intraperitoneal transplantation. pMCSCs exhibited a tendency towards partial mesenchymal-epithelial transition, enhancing their invasiveness during homing and the formation of peritoneal tumors. However, these preliminary findings require validation in further experiments.

The Role of HER2 in Self-Renewal, Invasion, and Tumorigenicity of Gastric Cancer Stem Cells.

BACKGROUND: Deregulation of HER2 expression could affect the biological characteristics of gastric cancer cells and treatment option for gastric cancer patients. This research aims to investigate the impact of HER2 on biological characteristics of gastric cancer stem cells (GCSCs) and prognosis of gastric cancer patients. METHODS: HER2 knockdown in GCSCs were constructed by lentivirus transfection. Alterations of proliferation, self-renewal, invasion, migration, colony formation, and tumorigenicity of GCSCs were examined. The changes of gene expressions after HER2 interference in GCSCs were detected by gene microarray. The impact of concentration of serum HER2 and expression of HER2 in tumor tissues on survival of 213 gastric cancer patients was also analyzed. RESULTS: Down-regulation of HER2 decreased the self-renewal, colony formation, migration, invasion, proliferation, and chemotherapy resistance of GCSCs. However, the tumorigenicity of GCSCs in vivo was increased after down-regulation of HER2. The results of gene microarray showed that HER2 gene might regulate the signal transduction of mTOR, Jak-STAT, and other signal pathways and affect the biological characteristics of GCSCs. Furthermore, survival analyses indicated that patients with high concentration of HER2 in serum had a favorable overall survival. However, there was no significant correlation between expression of HER2 in tumor tissue and overall survival. CONCLUSION: Interference of HER2 in GCSCs decreased the capacity of self-renewal, proliferation, colony formation, chemotherapy resistance, invasion, and migration but might increase the tumorigenicity in vivo. Patients with high concentration of HER2 in serum seemed to have a favorable prognosis.

[Co-expression and prognostic significance of hnRNP B1 and CD44 in non-small cell lung cancers].

OBJECTIVE: To study the co-expression and prognostic significance of hnRNP B1 and CD44 in non-small cell lung cancers (NSCLC). METHODS: The co-expressions of CD44 and hnRNP B1 in the tissues from 88 cases of NSCLC were measured by immunohistochemistry. The relationship between the expressions and the prognosis of NSCLC was analysed. RESULTS: The NSCLC had a high expression of hnRNP B1 (68.18%) and CD44 (52.27%). The cells had the longest average life [(59.607 +/- 4.092) months] in the conditions of high expressed hnRNP B1 and low expressed CD44, and shortest average life [(21.357 +/- 3.545) months] in the conditions of low expressed hnRNP B1 and high expressed CD44. CONCLUSION: Combined detection of hnRNP B1 and CD44 can help forecast the prognosis of NSCLC.

[Multiparametric flow cytometry analyzes the expressions of immunophenotype CD133, CD34, CD44 in lung cancer naive cells].

OBJECTIVE: To study the expression of CD133, CD34 and CD44 in lung cancer, and distribution of cell subpopulations that generated by combination of different markers. METHODS: By collecting 10 normal lung tissues and 40 lung cancer fresh samples that were diagnosed pathologically, preparing single cell suspension, and labelling cells with CD133, CD34, CD44, CD117, CD43, CD45 and LIN(CD2, CD3, CD31, CD64) monoclone antibodies, we analyzed the distribution of the above-mentioned antibodies in lung cancer cells on FCM. By double-parameters plots, we analyzed the naive cell subpopulations that were generated through combination of positive and negative antigen expression. RESULTS: In lung cancer parenchymal-cells (LIN- CD45-) expressed CD133, CD34 and CD44 dim positive and, expressed CD117 and CD43 negative. The mann-Whitney rank test results shows that there was no significant difference for the expression of CD133, CD34, CD44 between lung cancer and normal lung tissue, and CD44+, CD133- CD34-, CD133+ CD44+, CD133+ CD44-, CD133+ CD34+, CD133- CD34+ and CD133- CD44+ expressed differently (P < 0.05) between lung adenocarcinoma and lung squamous cell carcinoma. The cluster analysis results suggest that they are classified to 4 subsets. CONCLUSION: CD133, CD34, CD44 could be the marker of lung cancer naive cells, which could contribute to study lung cancer cell development.

Targeting Myeloid-derived Suppressor Cells and Programmed Death Ligand 1 Confers Therapeutic Advantage of Ablative Hypofractionated Radiation Therapy Compared With Conventional Fractionated Radiation Therapy.

PURPOSE: Ablative hypofractionated radiation therapy (AHFRT) presents a therapeutic advantage compared with conventional fractionated radiation therapy (CFRT) for primary and oligometastatic cancers. However, the underlying mechanisms remain largely unknown. In the present study, we compared the immune alterations in response to AHFRT versus CFRT and examined the significance of immune regulations contributing to the efficacy of AHFRT. METHODS AND MATERIALS: We established subcutaneous tumors using syngeneic lung cancer and melanoma cells in both immunocompetent and immunocompromised mice and treated them with AHFRT and CFRT under the same biologically equivalent dose. RESULTS: Compared with CFRT, AHFRT significantly inhibited tumor growth in immunocompetent, but not immunocompromised, mice. On the cellular level, AHFRT reduced the recruitment of myeloid-derived suppressor cells (MDSCs) into tumors and decreased the expression of programmed death-ligand 1 (PD-L1) on those cells, which unlashed the cytotoxicity of CD8+ T cells. Through the downregulation of vascular endothelial growth factor (VEGF), AHFRT inhibited VEGF/VEGF receptor signaling, which was essential for MDSC recruitment. When combined with anti-PD-L1 antibody, AHFRT presented with greater efficacy in controlling tumor growth and improving mouse survival. By altering immune regulation, AHFRT, but not CFRT, significantly delayed the growth of secondary tumors implanted outside the irradiation field. CONCLUSIONS: Targeting MDSC recruitment and enhancing antitumor immunity are crucial for the therapeutic efficacy of AHFRT. When combined with anti-PD-L1 immunotherapy, AHFRT was more potent for cancer treatment.

A Bottleneck in Understanding Metastatic Cancer Stem Cell of Peritoneal Seeding from Gastric Cancer: A Null Result in Brief.

The capture of peritoneal metastatic cancer stem cell of human gastric cancer (pMCSC-hGC) is important to further understand the mechanism of peritoneal metastasis in gastric cancer patients. Previously, cancer stem cells (CSCs) of gastric and rectal cancers were captured and identified. However, the bottleneck of capturing pMCSC-hGC may be the scarce surgical specimen and limited volume of peritoneal metastatic lesions from gastric cancer. Only 5.2% of patients were diagnosed of unpredictive peritoneal seeding intraoperatively, while none cell sphere were successfully formed through the identical culture approach based on peritoneal metastatic nodules. The attempt to enrich and capture pMCSC of transplanted gastric cancer (pMCSC-tGC) in immunodeficiency mice model through intraperitoneal injection of CSC-hGC may be a considerable and feasible alteration.

The p70S6K Specific Inhibitor PF-4708671 Impedes Non-Small Cell Lung Cancer Growth.

BACKGROUND: As a serine/threonine protein kinase, p70S6K plays an important role in tumor cells. Evidence has revealed overexpression of p70S6K and phosphorylated p70S6K (p-p70S6K) in various tumor tissues, with these proteins identified as independent prognostic markers in non-small cell lung cancer (NSCLC). In this study, we explored the role of the p70S6K specific inhibitor PF-4708671 in NSCLC. METHODS: Three NSCLC cell lines (A549, SK-MES-1, and NCI-H460) were treated with PF-4708671 at five different concentrations, including 0.1µM, 0.3µM, 1µM, 3µM and 10µM, and protein levels were determined by Western-blot. Then, PF-4708671's effects were assessed both in vitro (cell proliferation, apoptosis, cell cycle distribution, and invasion) and in vivo. RESULTS: The expression levels of p-p70S6K and the downstream effector S6 were significantly reduced by PF-4708671. Diametrically opposite, the downstream protein levels of BAD, Caspase3 and ERK had increased after treatment with PF-4708671. In addition, PF-4708671 drastically inhibited cell proliferation and invasion ability in A549, SK-MES-1 and NCI-H460 cells in vitro, causing cell cycle arrest in G0-G1 phase. Limited effects of PF-4708671 were observed on apoptosis in the three NSCLC cell lines assessed. Importantly, PF-4708671 could inhibit tumorigenesis in nude mice in vivo. CONCLUSION: These findings demonstrated that the p70S6K specific inhibitor PF-4708671 has inhibitory effects on NSCLC tumorigenesis in vitro and in vivo. Therefore, P70S6K should be considered a new potential therapeutic target, and PF-470867 may be used as targeted drug for cancer treatment.

Forced co-expression of IL-21 and IL-7 in whole-cell cancer vaccines promotes antitumor immunity.

Genetic modification of whole-cell cancer vaccines to augment their efficacies has a history of over two and a half decades. Various genes and gene combinations, targeting different aspects of immune responses have been tested in pursuit of potent adjuvant effects. Here we show that co-expression of two cytokine members of the common cytokine receptor γ-chain family, IL-21 and IL-7, in whole-cell cancer vaccines boosts antitumor immunity in a CD4(+) and CD8(+) T cell-dependent fashion. It also generates effective immune memory. The vaccine-elicited short-term effects positively correlated with enhanced infiltration of CD4(+) and CD8(+) effector T cells, and the long-term effects positively correlated with enhanced infiltration of effector memory T cells, especially CD8(+) effector memory T cells. Preliminary data suggested that the vaccine exhibited good safety profile in murine models. Taken together, the combination of IL-21 and IL-7 possesses potent adjuvant efficacy in whole-cell vaccines. This finding warrants future development of IL-21 and IL-7 co-expressing whole-cell cancer vaccines and their relevant combinatorial regimens.

Associations between serum CA724 and HER2 overexpression among stage II-III resectable gastric cancer patients: an observational study.

OBJECTIVES: Associations between serum tumor biomarkers and human epidermal growth factor receptor 2 (HER2) overexpression among locally advanced gastric cancer patients were yet to be determined and therefore warranted investigation. RESULTS: A total of 318 patients were analyzed. The odds ratios of CA724 were 4.79 (95% CI 1.55-14.79) and 6.29 (1.40-28.19) in comparing the HER2 (2+/3+) and HER2 (3+) with the negative group, respectively (p < 0.05). A combination of the four biomarkers yielded slightly but not significantly greater areas under the curve (AUC = 0.83; 0.71-0.94) than that of serum CA724 alone (0.80; 0.68-0.91); however, an index generated from the combination had better diagnostic performance with 85.7% sensitivity, 80.4% specificity and 97.8% negative predictive value to predict the strong overexpression of HER2 (3+). CA199, CEA or CA125 alone was not associated with HER2 overexpression. Leave-one-out cross-validation found a consistent association between serum CA724 and HER2 (2+/3+) overexpression. METHODS: Patients undergoing radical gastrectomy from 8/2012 to 12/2013 and with pathological stage II-III gastric cancer were retrospectively analyzed. HER2 expression of the surgical samples was estimated using immunohistochemistry; serum CA724, CA199, CEA and CA125 were preoperatively tested. Internal validation was performed using the leave-one-out approach. CONCLUSIONS: Serum CA724 is significantly associated with the overexpression of HER2 among locally advanced gastric cancer patients. The combination of CA724, CA199, CEA and CA125 is better than serum CA724 alone in predicting HER2 overexpression. External validation and further investigation of the biological mechanisms of these associations are required.