Deciphering the d-/l-lactate-producing microbiota and manipulating their accumulation during solid-state fermentation of cereal vinegar.

Symphony orchestra of multi-microorganisms characterizes the solid-state acetic acid fermentation process of Chinese cereal vinegars. Lactate is the predominant non-volatile acid and plays indispensable roles in flavor formation. This study investigated the microbial consortia driving the metabolism of D-/l-lactate during fermentation. Sequencing analysis based on D-/l-lactate dehydrogenase genes demonstrated that Lactobacillus (relative abundance: > 95%) dominated the production of both d-lactate and l-lactate, showing species-specific features between the two types. Lactobacillus helveticus (>65%) and L. reuteri (~80%) respectively dominated l- and d-lactate-producing communities. D-/l-lactate production and utilization capabilities of eight predominant Lactobacillus strains were determined by culture-dependent approach. Subsequently, D-/l-lactate producer L. plantarum M10-1 (d:l ≈ 1:1), l-lactate producer L. casei 21M3-1 (D:L ≈ 0.2:9.8) and D-/l-lactate utilizer Acetobacter pasteurianus G3-2 were selected to modulate the metabolic flux of D-/l-lactate of microbial consortia. The production ratio of D-/l-lactate was correspondingly shifted coupling with microbial consortia changes. Bioaugmentation with L.casei 21M3-1 merely enhanced l-lactate production, displaying ~4-fold elevation at the end of fermentation. Addition of L.plantarum M10-1 twice increased both D- and l-lactate production, while A. pasteurianus G3-2 decreased the content of D-/l-isomer. Our results provided an alternative strategy to specifically manipulate the metabolic flux within microbial consortia of certain ecological niches.

Interferon-γ in the tumor microenvironment promotes the expression of B7H4 in colorectal cancer cells, thereby inhibiting cytotoxic T cells.

The bioactivity of interferon-γ (IFN-γ) in cancer cells in the tumor microenvironment (TME) is not well understood in the current immunotherapy era. We found that IFN-γ has an immunosuppressive effect on colorectal cancer (CRC) cells. The tumor volume in immunocompetent mice was significantly increased after subcutaneous implantation of murine CRC cells followed by IFN-γ stimulation, and RNA sequencing showed high expression of B7 homologous protein 4 (B7H4) in these tumors. B7H4 promotes CRC cell growth by inhibiting the release of granzyme B (GzmB) from CD8+ T cells and accelerating apoptosis in CD8+ T cells. Furthermore, interferon regulatory factor 1 (IRF1), which binds to the B7H4 promoter, is positively associated with IFN-γ stimulation-induced expression of B7H4. The clinical outcome of patients with CRC was negatively related to the high expression of B7H4 in cancer cells or low expression of CD8 in the microenvironment. Therefore, B7H4 is a biomarker of poor prognosis in CRC patients, and interference with the IFN-γ/IRF1/B7H4 axis might be a novel immunotherapeutic method to restore the cytotoxic killing of CRC cells.

A modified method for isolation of bladder cancer stem cells from a MB49 murine cell line.

BACKGROUND: The vaccine was efficiently effective against bladder cancer in earlier studies. However, a part of the mouse bladder tumour regrew due to regression after a period of time as the cancer stem cells could not be eliminated. In this study, we showed a modified method for the isolation of MB49 bladder cancer stem cells (MCSCs). METHODS: Through a comparison of different serum-free culture mediums (SFM), MCSCs were isolated by a combination of the limited dilution method and the optimal SFM method. The characterizations of MCSCs were verified by the fluorescence activated cell sorting, the quantitative polymerase chain reaction, the western blotting, the cell proliferation assay, the soft agar assay, the transwell assay, the resistance to chemotherapy assay and the tumor xenograft formation assay. RESULTS: The optimal SFM contained a RPMI1640+ epidermal growth factor (20 ng/ml), a basic fibroblast growth factor (20 ng/ml), a leukemia inhibitory factor (20 ng/ml), a B-27 serum-free supplement (20 µl/ml), and a bovine serum albumin (4 µg/ml). MCSCs possessed the high expression of cancer stem cell markers (CD133, CD44, OCT4, NANOG, and ABCG2) and the ability of differentiation. In functional comparisons, MCSCs had higher proliferative abilities, lower susceptibility to chemotherapy, greater migration in vitro, and stronger tumorigenic abilities in vivo. CONCLUSION: MCSCs displayed specific cancer stem cells properties. Our study showed MCSCs were isolated successfully with a modified method using a combination of limited dilution and SFM methods.

Perfusion heterogeneity in breast tumors for assessment of angiogenesis.

OBJECTIVES: The purpose of this study was to investigate the perfusion heterogeneity of malignant and benign breast tumors and assay their vascular architecture changes and molecular expression, thereby evaluating the relevance between imaging and histologic characteristics of angiogenesis. METHODS: Real-time grayscale contrast-enhanced sonography was performed in 310 women with 317 breast tumors. The enhancement patterns and perfusion parameters for malignant and benign tumors were analyzed by contrast-enhanced sonography with microvascular imaging and quantitative time-intensity curve analysis. Structural characteristics were observed by light and electron microscopy. The microvessel density, vascular endothelial growth factor (VEGF) expression, and human kinase insert domain-containing receptor (KDR) expression for all tumors were assessed by immunohistochemical staining of CD31, KDR, and VEGF. RESULTS: Surgical pathologic analysis showed 163 malignant and 154 benign tumors. Significant morphologic differences, including perfusion defects, vessel distortion, vessel dilatation, and heterogeneous enhancement, were observed between the malignant and benign groups (P < .05). The mean perfusion parameters (peak intensity, ascending slope, area under the curve, and wash-out time) were greater in the malignant tumors (P < .05). There were significant differences in the peak intensity, ascending slope, area under the curve, and wash-out time between peripheral and central regions of the malignant tumors (P < .05) but none in the benign tumors. Vessels had various morphologic and distributional characteristics in the peripheral and central regions of the malignant tumors. The microvessel density and VEGF and KDR expression were significantly higher in the malignant group (P < .05), especially in the peripheral regions. CONCLUSIONS: Perfusion heterogeneity was closely associated with the tumor microvascular architecture and molecular expression. Perfusion features, especially regional morphologic and hemodynamic features, can provide valuable information for differentiating malignant from benign breast tumors.

FMNL2 is a positive regulator of cell motility and metastasis in colorectal carcinoma.

FMNL2 is a member of diaphanous-related formins which act as effectors of Rho family GTPases and control the actin-dependent processes such as cell motility or invasion. We previously found that FMNL2 overexpression in metastatic cell lines and tissues of colorectal carcinoma is associated with more aggressive tumour behaviour. Here we used gain-of-function and loss-of-function approaches to investigate the effects of FMNL2 on colorectal carcinoma in vitro and in vivo. Forced expression of FMNL2 caused a significant increase in tumour cell proliferation, motility, invasion in vitro, and metastasis in vivo, whereas FMNL2 depletion showed opposite effects. We examined gene expression profiles following knockdown of FMNL2 in SW480/M5 cells. Expression of 323 genes was up-regulated by more than two-fold, whereas 222 genes were down-regulated by more than two-fold in FMNL2-depleting SW480/M5 cells. Gene ontology analysis showed that most of genes belong to functional categories such as cell cycle, cytoskeleton, transcription factor, and G-protein modulator. Pathway analysis revealed that cytoskeletal regulation by the Rho GTPase pathway, the Wnt pathway, the G-protein pathway, and the P53 pathway were affected by FMNL2. Many of these genes are in functional networks associated with cell proliferation, metastasis, Wnt or the Rho signalling pathway involved in the regulation of FMNL2. The expression of five differentially expressed genes including CXXC4, CD200, VAV1, CSF1, and EPHA2 was validated by real-time PCR and western blot analysis. Thus, FMNL2 is a positive regulator of cell motility, invasion, and metastasis of colorectal carcinoma.

[Infantile DiGeorge syndrome: autopsy diagnosis and clinicopathologic analysis in 5 cases].

OBJECTIVE: To investigate clinicopathological features of DiGeorge syndrome (DGS). METHOD: The clinical features, histological and immunohistochemical findings were analyzed in 5 cases of DGS by autopsy. RESULTS: Five cases of DGS in male infants aged 4 days, 1 month, 7 months, 10 months, and 13 months respectively. Gross and microscopic observations revealed that thymic cortex was depleted of lymphocytes or showed few, dispersed lymphocytes. The thymic medulla showed predominantly epithelial cells with calcified Hassall bodies as well as lymphocyte depletion. T lymphocytes were also scarce in the tonsils, lymph nodes, spleen, and mucosa-associated lymphatic tissue of ileum. In addition, 3 of the 5 patients also showed parathyroid aplasia or dysplasia, and congenital hypertrophy of the ventricular septum. CONCLUSIONS: The pathological changes indicate that clinicians should be aware of defects of immune system if the infants suffer from severe infections. Pathologists should recognize the importance of abnormalities of lymphohematopoietic tissues in the diagnosis of primary immunodeficiency diseases such as DGS.

Modulating microbiota metabolism via bioaugmentation with Lactobacillus casei and Acetobacter pasteurianus to enhance acetoin accumulation during cereal vinegar fermentation.

Acetoin, giving a creamy yogurt aroma and buttery taste, exists in cereal vinegar as an important flavor substance and is mainly produced by the metabolism of Lactobacillus and Acetobacter during multispecies solid-state acetic acid fermentation. However, the impacts of Lactobacillus-Acetobacter interactions on acetoin accumulation and the microbial metabolism during acetic acid fermentation are not completely clear. Here, six strains isolated from vinegar fermentation culture and associated with acetoin metabolism, namely, Lactobacillus reuteri L-0, L. buchneri F2-6, L. brevis 4-20, L. fermentum M10-7, L. casei M1-6 and Acetobacter pasteurianus G3-2, were selected for microbial growth and metabolism analysis in monoculture and coculture fermentations. Lactobacillus sp. and A. pasteurianus G3-2 respectively utilized glucose and ethanol preferentially. In monocultures, L. casei M1-6 (183.7 mg/L) and A. pasteurianus G3-2 (121.0 mg/L) showed better acetoin-producing capacity than the others. In the bicultures with Lactobacillus sp. and A. pasteurianus G3-2, biomass analysis in the stationary phase demonstrated that significant growth depressions of Lactobacillus sp. occurred compared with monocultures, possibly due to intolerance to acetic acid produced by A. pasteurianus G3-2. Synergistic effect between Lactobacillus sp. and A. pasteurianus G3-2 on enhanced acetoin accumulation was identified, however, cocultures of two Lactobacillus strains could not apparently facilitate acetoin accumulation. Coculture of L. casei M1-6 and A. pasteurianus G3-2 showed the best performance in acetoin production amongst all mono-, bi- and triculture combinations, and the yield of acetoin increased from 1827.7 to 7529.8 mg/L following optimization of culture conditions. Moreover, the interactions of L. casei M1-6 and A. pasteurianus G3-2 regulated the global metabolism of vinegar microbiota during fermentation through performing in situ bioaugmentation, which could accelerate the production of acetic acid, lactic acid, acetoin, ethyl acetate, ethyl lactate, ligustrazine and other important flavoring substances. This work provides a promising strategy for the production of acetoin-rich vinegar through Lactobacillus sp.-A. pasteurianus joint bioaugmentation.

Cdc42 subcellular relocation in response to VEGF/NRP1 engagement is associated with the poor prognosis of colorectal cancer.

Microscopic indications of malignancy and hallmark molecules of cancer are pivotal to determining cancer patient prognosis and subsequent medical intervention. Here, we found that compared to apical expression of Cdc42, which indicated that basal expression of Cdc42 occurred at the migrating cell front, glandular basal expression of Cdc42 (cell division cycle 42) in tissues indicated poorer prognoses for colorectal cancer (CRC) patients. The current study shows that activated Cdc42 was rapidly recruited to the migrating CRC cell front after VEGF stimulation through engagement of membrane-anchored neuropilin-1 (NRP1). When VEGF signalling was blocked with NRP1 knockdown or ATWLPPR (A7R, antagonist of VEGF/NRP1 interaction), Cdc42 activation and relocation to the cell front was attenuated, and filopodia and invadopodia formation was inhibited. The VEGF/NRP1 axis regulates directional migration, invasion, and metastasis through Cdc42 activation and relocation resulting from actin filament polymerisation of the extensions of membrane protrusions. Collectively, the immuno-micromorphological pattern of subcellular Cdc42 at the cell front indicated aggressive behaviours and predicted poor prognosis in CRC patients. Disruption of the intra- and extracellular interactions of the VEGF/NRP1 axis or Cdc42 relocation could be performed in clinical practice because it might inhibit cancer cell motility and metastasis.

Transgelin as a suppressor is associated with poor prognosis in colorectal carcinoma patients.

We performed comparative proteomic analysis of colorectal cancer to investigate potential target proteins correlated with carcinogenesis and prognosis. Among them, transgelin, a 22 kDa protein also called SM22, was identified as a novel tumor suppressor protein, but little is known about this protein in tumors so far. A remarkable reduced expression of transgelin was found in colorectal cancer samples compared with normal colorectal mucosa. The effect of 5-aza-2'-deoxycytidine as a demethylation agent would obviously restore the original expression level of transgelin, implicating DNA hypermethylation of transgelin is important in the regulation of transgelin transcription in colorectal cancer. As a control, the investigation at cell line level confirms that transgelin protein comes from epithelium but not mesenchymal cells. Further, immunohistochemical staining for transgelin was performed on paraffin sections of 62 and 126 cases of normal colorectal mucosa and colorectal cancer specimens, respectively. As compared to normal colorectal tissue, we observed a significantly lower transgelin expression in colorectal cancer samples (P<0.001). Survival analysis demonstrated that patients without transgelin expression had shorter overall survival, whereas patients with transgelin expression had better survival (P=0.006). Multivariate analysis showed that negative transgelin expression was an independent prognostic indicator for patient's survival. Our results suggest that transgelin as a suppressor may serve as important biomarker of malignancy. Loss of transgelin involves gene promoter hypermethylation and is closely associated with poor overall survival in colorectal cancer patients.

[Evaluation of angiogenesis in the tumorigenesis and progression of breast cancer].

OBJECTIVES: To investigate the expression of CD34, vascular endothelial growth factor (VEGF) and its receptor Flk-1/KDR in precancerous lesion, atypical hyperplasia (AH) and infiltrating carcinoma of breast cancer and to explore the correlation between angiogenesis abnormality and the tumor progression. METHODS: One hundred and sixty cases of resected tissues from breast cancer patients were enrolled in the study and were divided into 5 groups: 30 cases as normal controls, 30 cases with simple hyperplasia, 30 cases with AH, 20 cases with intraductal carcinoma in situ and 50 cases with infiltrating ductal carcinoma. The expression of CD34, VEGF and its receptor, Flk-1/KDR in those tissues were determined with immunohistochemical techniques. The micro vascular density (MVD) in those tissues was determined with the expression of CD34. RESULTS: The expression level of CD34, VEGF and Flk-1/KDR were different among the groups, with the highest expression in the infiltrating ductal carcinoma group. With the progression of breast cancer, the major indexes showed no significant changes in the early stage of progression, but the expression of VEGF and Flk-1/KDR increased significantly from AH stage. Meanwhile, the MVD increased in the same way. There was significant difference between AH and intraductal carcinoma group in the expression of VEGF and Flk-1/KDR (P<0.05), but not in the MVD (P>0.05). CONCLUSIONS: Abnormality in angiogenesis may be an early event in the tumorigenesis of breast cancer. Abnormal expression of VEGF and Flk-1/KDR may be the initiating factor of angiogenesis in the process of breast hyperplasia-AH-breast cancer, it could be the molecular target of early diagnosis and treatment.

High expression of PRKDC promotes breast cancer cell growth via p38 MAPK signaling and is associated with poor survival.

BACKGROUND: DNA-Dependent Protein Kinase Catalytic Subunit (PRKDC), a key component of the DNA damage repair pathway, is associated with chemotherapy resistance and tumor progression. METHODS: Here we analyzed transcriptome data of ~2,000 breast cancer patients and performed functional studies in vitro to investigate the function of PRKDC in breast cancer. RESULTS: Our results revealed overexpression of PRKDC in multiple breast cancer subtypes. Consistent with patients' data, overexpression of PRKDC was also observed in breast cancer cell lines compared to normal breast epithelial cells. Knockdown of PRKDC in MCF-7 and T47D breast cancer cell lines resulted in proliferation inhibition, reduced colony formation and G2/M cell cycle arrest. Furthermore, we showed that PRKDC knockdown induced proliferation inhibition through activation of p38 MAPK, but not ERK MAPK, signaling pathway in breast cancer cells. Blockage of p38 MAPK signaling could largely rescue proliferation inhibition and cell cycle arrest induced by PRKDC knockdown. Moreover, we analyzed gene expression and clinical data from six independent breast cancer cohorts containing ~1,000 patients. In all cohorts, our results consistently showed that high expression of PRKDC was significantly associated with poor survival in both treated and untreated breast cancer patients. CONCLUSION: Together, our results suggest that high expression of PRKDC facilitates breast cancer cell growth via regulation of p38 MAPK signaling, and is a prognostic marker for poor survival in breast cancer patients.

PRKDC is a prognostic marker for poor survival in gastric cancer patients and regulates DNA damage response.

A hallmark of gastric cancer is the high rate of genomic instability associated with deregulation of DNA damage repair pathways. DNA-Dependent Protein Kinase Catalytic Subunit (PRKDC) is a key component of the non-homologous end-joining (NHEJ) pathway. By reanalyzing transcriptome data of 80 pairs of gastric cancer tumors and the adjacent normal tissues from non-treated patients, we identified PRKDC as the top upregulated DNA damage repair genes in gastric cancer. High expression of PRKDC is associated with poor survival of gastric cancer patients, and genomic amplification of the gene is frequently observed across most gastric cancer subtypes. Knockdown of PRKDC in gastric cell lines resulted in reduced proliferation and cell cycle arrest. Furthermore, we showed that loss of PRKDC induced DNA damage and enhanced gastric cancer cell chemosensitivity to DNA-damaging reagents. Together, our results suggest that PRKDC is a prognostic marker of poor survival and is a putative target to overcome chemoresistance in gastric cancer.

Prohibitin, relocated to the front ends, can control the migration directionality of colorectal cancer cells.

Directional migration is a cost-effective movement allowing invasion and metastatic spread of cancer cells. Although migration related to cytoskeletal assembly and microenvironmental chemotaxis has been elucidated, little is known about interaction between extracellular and intracellular molecules for controlling the migrational directionality. A polarized expression of prohibitin (PHB) in the front ends of CRC cells favors metastasis and is correlated with poor prognosis for 545 CRC patients. A high level of vascular endothelial growth factor (VEGF) in the interstitial tissue of CRC patients is associated with metastasis. VEGF bound to its receptor, neuropilin-1, can stimulate the activation of cell division cycle 42, which recruits intra-mitochondrial PHB to the front end of a CRC cell. This intracellular relocation of PHB results in the polymerization and reorganization of filament actin extending to the front end of the cell. As a result, the migration directionality of CRC cells is targeted towards VEGF. Together, these findings identify PHB as a key modulator of directional migration of CRC cells and a target for metastasis.

Differences and similarities between extremely severe oligozoospermia and cryptozoospermia in intracytoplasmic sperm injection.

Patients with extremely severe oligozoospermia (ESO) and cryptozoospermia (CO) are suitable using intracytoplasmic sperm injection (ICSI) as an infertility treatment. However, some andrologists are confused to distinguish ESO and CO in clinic diagnose. This study was designed for the first time to evaluate and compare patients with ESO and CO to determine whether these are useful clinical distinctions. A total of 270 infertile men in our center were classified into four groups as Group nonobstruction azoospermia (NOA, n = 44), Group ESO (n = 78), Group CO (n = 40), and Group obstruction azoospermia (OA, n = 108). Comparisons of the volume of bilateral testes, the level of follicle stimulating hormone (FSH) and inhibin B were obtained in four groups. Then comparisons of fertilization rates, cleavage rate, and excellent embryos rate were obtained when couples performed ICSI. All indexes (volume of bilateral testis, level of FSH and inhibin B) in Groups ESO and CO were no difference, while Groups OA versus NOA, OA versus ESO, and OA versus CO were significant differences (P < 0.05). The rates of fertilization were no differences in Groups ESO and CO while Groups OA versus ESO, OA versus CO were significant differences (P < 0.05). Therefore, the spermatogenic functions in patients with CO and ESO were similar, better than NOA but worse than OA. However, it would be helpful to evaluate their spermatogenesis using testicular biopsies, especially accompanied azoospermia in clinical practice.

Interaction between Oc-1 and Lmx1a promotes ventral midbrain dopamine neural stem cells differentiation into dopamine neurons.

Recent studies have shown that Onecut (Oc) transcription factors may be involved in the early development of midbrain dopaminergic neurons (mdDA). The expression profile of Oc factors matches that of Lmx1a, an important intrinsic transcription factor in the development of mDA neuron. Moreover, the Wnt1-Lmx1a pathway controls the mdDA differentiation. However, their expression dynamics and molecular mechanisms remain to be determined. To address these issues, we hypothesize that cross-talk between Oc-1 and Lmx1a regulates the mdDA specification and differentiation through the canonical Wnt-ß-catenin pathway. We found that Oc-1 and Lmx1a displayed a very similar expression profile from embryonic to adult ventral midbrain (VM) tissues. Oc-1 regulated the proliferation and differentiation of ventral midbrain neural stem cells (vmNSCs). Downregulation of Oc-1 decreased both transcript and protein level of Lmx1a. Oc-1 interacted with lmx1a in vmNSCs in vitro and in VM tissues in vivo. Knockdown of Lmx1a reduced the expression of Oc-1 and Wnt1 in vmNSCs. Inhibiting Wnt1 signaling in vmNSCs provoked similar responses. Our data suggested that Oc-1 interacts with Lmx1a to promote vmNSCs differentiation into dopamine neuron through Wnt1-Lmx1a pathway.

Myofibrotic malformation vessels: unique angiodysplasia toward the progression of hemorrhoidal disease.

BACKGROUND: The etiology and pathogenesis of hemorrhoids is unclear, although hemorrhoids are a worldwide disease in men and women, with peak prevalence at 45-65 years of age. Hemorrhoidal cushions as the anal venous plexi are normal anatomical structures from infancy. This study attempts to reveal the angiodysplasia and other pathological changes in association with different degrees of symptomatic hemorrhoids. MATERIALS AND METHODS: A total of 281 patients with internal hemorrhoids from degree I to IV underwent hemorrhoidectomy. The vascular changes were analyzed by microscopic assessment and software analysis, with Masson's trichrome, CD34, and smooth muscle actin. RESULTS: The hemorrhoidal tissues exhibited abnormal vessels in the mucosae and submucosae that we termed them as myofibrotic malformation vessels (MMVs). MMVs are not ascribed to arteries or veins because they exhibit enlarged and tortuous lumens with smooth muscle dysplasia and fibrotic deposition in the walls without overlying mucosal ulceration. The muscularis mucosae also showed smooth muscle dysplasia and fibrosis, even if it were interrupted by the intruding MMVs. The statistical data indicated that the severity of all the changes correlate positively with the progression of hemorrhoids (P<0.001). Hemorrhoidal patients are prone for reoccurrence even with prolapsing hemorrhoid when compared with the conventional hemorrhoidectomy. Multiple logistic regression analysis showed that MMVs in mucosal propria, mean thickness of mucosal muscularis layer, and fibrotic changes in MMV were independent risk factors for MMVs in hemorrhoidal disease. CONCLUSION: MMVs and muscularis mucosae dysplasia reciprocally contribute to hemorrhoidal exacerbation. The novel findings of this study propose that the characteristic features of MMVs and muscularis mucosae dysplasia of the anorectal tube ultimately cause symptomatic hemorrhoids, which could affect the clinical management of hemorrhoidal disease through the use of surgery to target the malformed vessels.

MIF, secreted by human hepatic sinusoidal endothelial cells, promotes chemotaxis and outgrowth of colorectal cancer in liver prometastasis.

Growth and invasion of metastatic colorectal cancer (CRC) cells in the liver depend on microenvironment. Here, we showed that human hepatic sinusoidal endothelial cells (HHSECs) induce chemotaxis and outgrowth of CRC cells. Macrophage migration inhibitory factor (MIF), released by HHSECs, stimulated chemotaxis of CRC cells. MIF secreted by HHSECs, but not by CRC cells themselves, promoted migration and epithelial-mesenchymal transition (EMT) and facilitated proliferation and apoptotic resistance of CRC cells. In orthotopic implantation models in nude mice, exogenous MIF stimulated growth of CRC cells and metastasis. Furthermore, MIF accelerated mobility of CRC cells by suppressing F-actin depolymerization and phosphorylating cofilin. Noteworthy, MIF levels were correlated with the size of hepatic metastases. We suggest that HHSECs and paracrine MIF promote initial migration and proliferation of CRC cells in the hepatic sinusoids to generate liver metastases.

[Expression of proliferating cell nuclear antigen in craniopharyngioma and tumor recurrence].

OBJECTIVE: To investigate proliferating cell nuclear antigen labeling indices (PCNA-LI) in craniopharyngiomas in association with tumor recurrence. METHODS: Immunohistochemistry was employed to examine the expression of PCNA in 43 craniopharyngioma samples of different pathological types, and the relationship between PCNA-LI and tumor recurrence was evaluated. RESULTS: PCNA-LI was much higher in adamantinous tumors than in squamous papillary tumors that did not give rise to postoperative recurrence. Although PCNA-LI was higher in the recurrent lesions than in the primary tumor in adamantinoma group, the difference was not statistically significant. CONCLUSIONS: Craniopharyngioma cells with different pathological features may possess varied proliferating potentials, and active proliferation is the main factor for postoperative recurrence of adamantinoma.

[Effects of Helicobacter pylori infection on porcine gastric epithelial cell proliferation].

OBJECTIVE: To investigate the association between porcine gastric epithelial cell proliferation and Helicobacter pylori (Hp) infection. METHOD: Animal models of gastritis associated with Hp infection were established using "Chinese No.1 pigs". The expressions of proliferating cell nuclear antigen (PCNA) and DNA polyploid content in porcine gastric epithelial cells were quantitatively assayed by means of immunohistochemistry and Feulgen stain respectively. RESULTS: The values of PCNA labeling index (LI) in the porcine gastric epithelial cells of the experimental group were significantly higher than those of the control group (40.95+/-3.60 vs 29.4+/-12.82, P<0.01). The DNA diploid or approximate diploid content in the gastric mucosa of the pigs was significantly lower (70.78% vs 90.65%, P<0.01), but the proliferation polyploid and non-doubleploid of DNA significantly higher in the experimental group than in the control group (P<0.01). CONCLUSION: Hp infection may play a role to enhance the proliferation of gastric epithelial cells in pigs.

Metastatic cancer stem cells: from the concept to therapeutics.

Metastatic cancer stem cells (MCSCs) refer to a subpopulation of cancer cells with both stem cell properties and invasion capabilities that contribute to cancer metastasis. MCSCs have capability of self-renewal, potentials of multiple differentiation and development and/or reconstruction of cancer tissues. As compared with stationary cancer stem cells, MCSCs are capable of invasion to normal tissues such as vasculatures, resistance to chemo- and/or radio-therapies, escape from immune surveillance, survival in circulation and formation of metastasis. MCSCs are derived from invasive cancer stem cells (iCSCs) due to the plasticity of cancer stem cells, which is one of the characteristics of cancer cell heterogeneity. Both stages of iCSCs and MSCSs are the potential therapeutic targets for cancer metastasis in the future strategies of personalized cancer therapy.