Multifaceted role of microRNAs in gastric cancer stem cells: Mechanisms and potential biomarkers.

MicroRNAs (miRNAs) have received much attention in the past decade as potential key epigenomic regulators of tumors and cancer stem cells (CSCs). The abnormal expression of miRNAs is responsible for different phenotypes of gastric cancer stem cells (GCSCs). Some specific miRNAs could be used as promising biomarkers and therapeutic targets for the identification of GCSCs. This review summarizes the coding process and biological functions of miRNAs and demonstrates their role and efficacy in gastric cancer (GC) metastasis, drug resistance, and apoptosis, especially in the regulatory mechanism of GCSCs. It shows that the overexpression of onco-miRNAs and silencing of tumor-suppressor miRNAs can play a role in promoting or inhibiting tumor metastasis, apart from the initial formation of GC. It also discusses the epigenetic regulation and potential clinical applications of miRNAs as well as the role of CSCs in the pathogenesis of GC. We believe that this review may help in designing novel therapeutic approaches for GC.

Analysis of related factors of behavioral problems in children with congenital pseudarthrosis of tibia

SUMMARY OBJECTIVE: This study aimed to investigate the factors associated with behavioral problems in children with congenital pseudarthrosis of the tibia. METHODS: Random sampling is utilized to obtain a sample of 90 patients. The behavioral problems of the patients are detected by Achenbach Children's Behavior Scale. Parental emotional problems are investigated by the Self-Rating Depression Scale and Self-Rating Anxiety Scale. RESULTS: The results demonstrate that the detection rate of behavioral problems in children with congenital pseudarthrosis of the tibia is 53.3% (48/90). Among these behavioral problems, an abnormal rate is higher in the four dimensions: thinking, violation of discipline, social interaction, and aggression. The anxiety and depression scores of caregivers are statistically higher in the abnormal group than in the normal group. The results of the multivariate analysis show that the anxiety degree of the parents had a significant impact on the behavior of the children. CONCLUSIONS: Children with congenital pseudarthrosis of the tibia are facing the issues of high rates of behavioral problems. Parents of children with congenital pseudarthrosis of the tibia had higher levels of anxiety and depression than parents of normal children. The anxiety and depressive state of mind of parents or caregivers had a significant impact on the behavior of children with congenital pseudarthrosis of the tibia.

CircPVT1 promotes the tumorigenesis and metastasis of osteosarcoma via mediation of miR-26b-5p/CCNB1 axis.

INTRODUCTION: Osteosarcoma (OS) is the most aggressive malignancy among the bone tumors in the world. Circular RNAs (circRNAs) have been reported to be participated in multiple cancers, including OS. Meanwhile, circPVT1 has been proved to be upregulated in OS. However, the mechanism by which circPVT1 mediates the tumorigenesis of OS remains to be further explored. MATERIALS AND METHODS: Protein and gene expressions in OS cells were measured by western blot and RT-qPCR, respectively. Cell growth was assessed by flow cytometry and colony formation, respectively. In addition, cell migration was assessed by wound healing, and invasion was evaluated by Transwell assay. Meanwhile, the correlation among circPVT1, miR-26b-5p and CCNB1 was explored by RNA pull-down and dual luciferase assay. Finally, in vivo model was established to explore the role of circPVT1 in OS in vivo. RESULTS: CircPVT1 and CCNB1 were significantly upregulated in OS cells, while miR-26b-5p was downregulated. Knockdown of circPVT1 notably inhibited proliferation and induced apoptosis of OS cells. CircPVT1 shRNA significantly suppressed the OS cell invasion and migration. Meanwhile, circPVT1 sponged miR-26b-5p and CCNB1 was found to be the direct target of miR-26b-5p. Furthermore, silencing of circPVT1 inhibited the growth and metastasis of OS in vivo. CONCLUSION: Silencing of circPVT1 notably suppressed the tumorigenesis and metastasis of OS via miR-26b-5p/CCNB1 axis. Therefore, circPVT1 might be used as a target for OS treatment.

Comparative efficacy of 10 Chinese herbal injections combined with GP regimen chemotherapy for patients with advanced NSCLC a systematic review and network meta-analysis.

Background: Numerous studies have indicated that some Chinese herbal injections (CHIs) might have a beneficial treatment effect when used in combination with chemotherapy. However, the results of these studies have been inconsistent. The aim of this network meta-analysis (NMA) was to evaluate and compare the clinical efficacy and safety of different CHIs combined with gemcitabine plus cisplatin (GP) regimen chemotherapy with that of GP regimen chemotherapy alone in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: Eight databases were systematically searched to identify randomized clinical trials (RCTs) from the date of inception of the database to August 11, 2021. The primary outcome measures were the objective response rate (ORR) and adverse reactions (including nausea and vomiting, and leukopenia). The secondary outcome measures were median survival time (MST) and quality of life (QOL). The quality of the included studies was assessed using the Cochrane risk of bias tool. Standard pair-wise and Bayesian NMAs were carried out to compare the effectiveness and safety of different CHIs combined with GP regimen chemotherapy using WinBUGS 14 and Stata 15.1 software. Sensitivity analysis and Egger's test were also performed to check robust. Results: A total of 92 eligible RCTs involving 7,728 patients and 10 CHIs were included. The results showed that Kangai injection (KAI), Kanglaite injection (KLT), Aidi injection and Compound Kushen (CKSI) injection displayed obvious advantages in both efficacy and safety. Aidi+GP (79.0%) showed great advantages of ORR, and KAI+GP and KLT+GP had the lowest probability in terms of leukopenia (4.4%) and nausea and vomiting (24.2%). Besides, KLT+GP was shown to positively affect MST. According to the subgroup analyses, CHIs might have a limited effect in reducing adverse reactions, and have a similar effect in squamous cell carcinoma and adenocarcinoma. Conclusions: KAI+GP of adjuvant drugs, Aidi+GP and CKSI+GP of anticancer drugs appeared to be the advantageous treatment options for patients with advanced NSCLC, owing to its superior therapeutic performance and reduced adverse reactions. KLT+GP might prolong survival. Nevertheless, additional results from multicenter trials and high-quality studies will be pivotal in supporting our findings.

[Study on difference of effect of Huoxue drugs and Yiqi Huoxue drugs on tumor metastasis based on immune remodeling].

Tumor metastasis is an important cause of tumor treatment failure. Its molecular mechanism is closely related to tumor cells remodeling immune cells and immunosuppressive microenvironment, so as to create a suitable soil for tumor cell invasion and growth. "Huoxue Huayu" is one of the important therapeutic principles in cancer treatment, but the influence of Huoxue drugs on tumor metastasis has been controversial in clinical application. In this paper, we systematically summarized the comparative study of Huoxue drugs and Yiqi Huoxue drugs in tumor metastasis in recent years, and discussed the differences of molecular mechanisms of Huoxue drugs and Yiqi Huoxue drugs in anti-tumor metastasis from the perspective of immune remodeling, so as to provide scientific basis for clinical rational application of Huoxue drugs and Yiqi Huoxue drugs.

The characteristics and related factors of insomnia among postoperative patients with gastric cancer: a cross-sectional survey.

PURPOSE: This study aims to explore the characteristics and related factors of insomnia of patients after operation for gastric cancer. METHODS: A cross-sectional survey was carried out and finally 115 patients with insomnia after operation for gastric cancer were included. The general information, gastric cancer-related information, sleep quality, and other symptoms were investigated. RESULTS: ① The Pittsburgh sleep quality index score of most insomnia patients after gastric cancer surgery was 11-15 points, and the sleep quality rating was "poor". ② The sleep quality of patients with insomnia after surgery for gastric cancer is related to the number of chemotherapy cycles, fatigue, and depression. ③ The probability of reduced sleep quality with the number of chemotherapy cycles >6 is 3.640 times that of ≤6. The probability of reduced sleep quality during moderate to severe fatigue was 4.390 times that of patients with no or mild fatigue. CONCLUSION: Attention to related factors may be associated with improvement of sleep quality in patients with gastric cancer after surgery.

The neurofibromatosis type I gene promotes autophagy via mTORC1 signalling pathway to enhance new bone formation after fracture.

Bone fracture is one of the most common injuries. Despite the high regenerative capacity of bones, failure of healing still occurs to near 10% of the patients. Herein, we aim to investigate the modulatory role of neurofibromatosis type I gene (NF1) to osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and new bone formation after fracture in a rat model. We studied the NF1 gene expression in normal and non-union bone fracture models. Then, we evaluated how NF1 overexpression modulated osteogenic differentiation of BMSCs, autophagy activity, mTORC1 signalling and osteoclastic bone resorption by qRT-PCR, Western blot and immunostaining assays. Finally, we injected lentivirus-NF1 (Lv-NF1) to rat non-union bone fracture model and analysed the bone formation process. The NF1 gene expression was significantly down-regulated in non-union bone fracture group, indicating NF1 is critical in bone healing process. In the NF1 overexpressing BMSCs, autophagy activity and osteogenic differentiation were significantly enhanced. Meanwhile, the NF1 overexpression inhibited mTORC1 signalling and osteoclastic bone resorption. In rat non-union bone fracture model, the NF1 overexpression significantly promoted bone formation during fracture healing. In summary, we proved the NF1 gene is critical in non-union bone healing, and NF1 overexpression promoted new bone formation after fracture by enhancing autophagy and inhibiting mTORC1 signalling. Our results may provide a novel therapeutic clue of promoting bone fracture healing.

Efficacy and safety of Kanglaite injection combined with first-line platinum-based chemotherapy in patients with advanced NSCLC: a systematic review and meta-analysis of 32 RCTs.

BACKGROUND: As a Chinese medicine injections, Kanglaite injection (KLT) is a complementary or alternative therapy for first-line platinum-based chemotherapy. However, the effect that certain factors, including the dose of KLT, chemotherapy cycles, evaluation criteria, or supportive treatment, have on the efficacy of the objective response rate (ORR), median survival time (MST), and adverse reactions is still unknown. METHODS: Eight databases were systematically searched from the inception dates to December 1, 2019, using the keywords Kanglaite, chemotherapy, and non small cell lung carcinoma to identify randomized clinical trials (RCTs). Analyses were performed using Review Manager 5.3 and Stata 15.1. RESULTS: There were 32 randomized controlled trials, involving 2,577 participants, that fulfilled the inclusion criteria. Compared with first-line platinum-based chemotherapy alone, KLT combined with chemotherapy could increase the ORR [risk ratio (RR), 1.41 (95% CI: 1.28 to 1.56); absolute risk difference (ARD), 0.13 (95% CI: 0.1 to 0.17)], decrease the risk ratio of adverse reactions [nausea and vomiting: RR, 0.58 (95% CI: 0.42 to 0.81); ARD, -0.17 (95% CI: -0.26 to -0.08); leukopenia: RR, 0.61 (95% CI: 0.44 to 0.86); ARD, -0.16 (95% CI: -0.24 to -0.08)], prolong MST, and increase disease control rate and Karnofsky performance status. According to the subgroup analyses, KLT combined with cisplatin or paraplatin plus paclitaxel (TP) failed to demonstrate a significant association with the ORR. And when lacking the use of supportive treatment, this combination would not decrease the RR of both adverse reactions compared with chemotherapy alone. CONCLUSIONS: KLT plus first-line platinum-based chemotherapy, except when chemotherapy regimens were TP, increased efficacy and quality of life in patients with advanced NSCLC. We are unsure whether this combination offers a low risk of adverse reactions. Additional high-quality RCTs are warranted to assess the effects of the combined therapy further.

Comparative efficacy of Chinese herbal injections combined with GP regimen chemotherapy for patients with advanced NSCLC: A protocol for systematic review and network meta-analysis.

BACKGROUND: Many research has indicated that some Chinese herb injections (CHIs) might be beneficial in combination with chemotherapy, however, with inconsistent results. Hence, the purpose of this network meta-analysis is to evaluate different CHIs plus cisplatin and gemcitabine (GP) with GP alone in terms of clinical efficacy and safety for treating patients with advanced NSCLC. METHODS: A comprehensive systematic search of clinical randomized controlled trials (RCTs) published in the PubMed, Embase, Web of Science (ISI), Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang Database and China Biological Medicine Database (CBM) databases will be conducted to identify eligible studies up to the date of May 2020. The primary outcome measures objective response rate and adverse reactions (nausea and vomiting, leukopenia). The secondary outcome measures median survival time (MST), disease control rate, and quality of life. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The network meta-analysis will be performed using WinBUGS 14 and Stata 15.1 software. RESULTS: Based on the current evidence, the potential rank of the efficacy and safety of CHIs plus GP chemotherapy for advanced NSCLC will be assessed, and a prioritization regimen will be summarized. CONCLUSION: Evidence from this systematic review could be useful for patients, clinical practitioners, and guideline-makers to select an optimum proposal of CHIs plus GP for advanced NSCLC. ETHICS AND DISSEMINATION: It is not necessary for ethical approval because it is based on published studies. The protocol will be disseminated in a peer-reviewed journal or presented at a topic-related conference. PROSPERO REGISTRATION NUMBER: CRD42020167142.

Combination of intramedullary rod, wrapping bone grafting and Ilizarov's fixator for the treatment of Crawford type IV congenital pseudarthrosis of the tibia: mid-term follow up of 56 cases.

BACKGROUND: The purpose of this study was to investigate the initial union rate, refracture rate and residual deformities of congenital pseudarthrosis of the tibia (CPT), using combined surgery including pseudarthrosis resection, intramedullary rodding, autogenous iliac bone grafting and Ilizarov's fixator, with a mean 5.2 years follow-up. METHODS: We retrospectively reviewed the records and diagrams of patients with Crawford type IV congenital pseudarthrosis of the tibia between February 2007 and March 2010. Patients managed by pseudarthrosis resection, intramedullary rod of the tibia, wrapping autogenous iliac bone grafting and Ilizarov's fixator were enrolled. We evaluated the bone union rate, tibial alignment, limb length discrepancy (LLD), valgus deformity of the ankle and the frequencies of refracture during period of follow-up. RESULTS: There were 56 cases enrolled in the study, with a mean follow-up 5.2 years (range, 3 to 6.7 years). The mean age of the patients at surgery was 3.5 years (range, 1.5 to 12.4 years). Fifty (89.2 %) of the 56 patients had primary bone union at site of pseudarthrosis, while 5 obtained union after second surgery and 1 failed. The average time spent to obtain pseudarthrosis initial union was 4.5 months (range, 3.0 to 10.0 months) and mean duration of Ilizarov treatment was 4.7 months (range, 3.2 to 10.4 months). Eleven (19.6 %) patients had proximal tibial valgus with a mean angle of 9.5° (range, 5 to 24°), while 10 (17.9 %) patients had ankle valgus deformities with a mean of 12.3° (range, 6 to 21°). Sixteen (28.6 %) patients had an average 2.2 cm LLD (range, 1.5-4.2 cm). Of the 50 cases who obtained initial bone union of pseudarthrosis, 13 (26.0 %) had refracture which need cast immobilization or secondary surgery. CONCLUSIONS: This combined surgery obtained initial union rate of 89.2 % at primary surgery while the refracture rate is 26.0 %. However, residual deformities such as proximal tibial valgus, LLD and ankle valgus were also existed which should be pay more attention to and dealt with. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov under the name "The Effect of Combined Surgery in Management of Congenital Pseudarthrosis of Tibia" ( NCT02640040 ), which was released on August 31, 2015.

MiR-384 regulated IRS1 expression and suppressed cell proliferation of human hepatocellular carcinoma.

Acquired evidence indicated that microRNAs (miRNAs) played essential roles in cancer development, including hepatocellular carcinoma (HCC). Functions and mechanisms of miRNAs involved in HCC remain largely unknown. Here, we found that miR-384 was significantly downregulated in HCC cells and tissues by RT-PCR. Gain and loss of function studies revealed that miR-384 significantly suppressed HCC cell proliferation. Insulin receptor substrate 1(IRS1) was identified as a direct and functional target of miR-384. Moreover, miR-384 decreased IRS1 expression, subsequently downregulating cyclin D1 and upregulating p21 and p-Rb expression. In addition, promotion of cell proliferation caused by miR-384-in was counteracted by silencing IRS1 expression with siRNAs. Taken together, our data provided convincing evidence that miR-384 exerted suppressive effect on HCC cell proliferation through the direct inhibition of IRS1 expression, suggesting miR-384 may serve as a potential therapeutic target for HCC.

Effect of distraction osteogenesis in patient with tibial shortening after initial union of Congenital Pseudarthrosis of the Tibia (CPT): a preliminary study.

BACKGROUND: The purpose of our retrospective study was to evaluate the preliminary result of distraction osteogenesis in patient with tibial shortening after initial union of Congenital Pseudarthrosis of the Tibia (CPT). METHODS: All the CPT cases with tibial shortening after initial union managed by proximal tibial lengthening using Ilizarov technique were identified. All the patient charts and radiograms were reviewed. RESULTS: Between March 2007 and January 2012, 11 CPT cases were included with an average follow-up of 41 months (range, 34-51 months). The mean age at surgery was 8.5 years (range, 3.9-14.5y). The average length of discrepancy was 5.6 cm (range, 2.0-8.2 cm). Eight (8) cases had radiological findings of proximal tibial dysplasia, while the other 3 cases had not. The average distraction length gained was 5.3 cm (range, 3.5-8.0 cm) with a mean elongation rate of 21.4% (range, 15-30%). The Healing Index (HI) was 63.1 d/cm (range, 47-77 d/cm). In the 8 patients with proximal tibial dysplasia, 5 cases had lateral callus, 3 had central callus, and poor bone regeneration was observed in all of them with an average HI of 67 d/cm. In the other 3 patients without proximal tibial dysplasia, concave shaped callus was identified with an average HI of 52.7 d/cm. None of the patients had re-fracture, nonunion, axis deviation or angulation of the distraction area. Ankle joint stiffness was found in 2 of the patients. No evidence of knee contracture was detected. There were 5 cases with pin-tract infection which was managed by pin-tract nurse and oral administration of antibiotics. CONCLUSIONS: We concluded that proximal tibial lengthening after initial union of CPT was effective for management of tibial shortening, however it was characterized by poor bone regeneration with different types of callus from normal, greater healing index and prolonged fixator wearing. We recommended that tibial lengthening could be considered when the limb length discrepancy (LLD) was more than 4 cm in younger children after primary union of CPT.

Hypoxia-induced snail expression through transcriptional regulation by HIF-1α in pancreatic cancer cells.

BACKGROUND: Intratumoral hypoxia and epithelial-mesenchymal transition are involved in tumor invasion and metastasis. AIMS: This study investigated the molecular mechanisms that relay the hypoxia signal into the epithelial-mesenchymal transition and metastasis. METHODS: Morphology analysis and tumor cell migration and invasion assays were performed to detect phenotypic changes of pancreatic cancer cells under normoxic and hypoxic conditions after lentiviral HIF-1α shRNA transfection. Quantitative reverse transcription polymerase chain reaction, western blot, and immunohistochemistry were used to detect gene expression in pancreatic cancer cell lines and tissues or normal pancreatic tissues. Luciferase, gel shift, and ChIP assays were used to assess gene regulation. RESULTS: Under hypoxic conditions, these tumor cells underwent typical morphological and molecular changes to epithelial-mesenchymal transition. Moreover, Snail expression was induced by hypoxic conditions and was regulated by HIF-1α expression at the transcriptional level through HIF-1α-binding to the second site of hypoxia-responsive elements of the Snail gene promoter. In addition, Snail expression was associated with HIF-1α expression in pancreatic cancer tissues, and expression of both was associated with tumor metastasis and poor patient survival. CONCLUSIONS: Our study provides key evidence that HIF-1α and Snail are responsible for hypoxia-induced metastasis phenotypes in pancreatic cancer and that HIF-1α and Snail expression can be used as biomarkers to predict tumor metastasis and patient survival.

Interleukin-12 prevents colorectal cancer liver metastases in mice.

Interleukin (IL)-12 has emerged to be a prospective molecule for antitumor therapies with many types of cancers. Here we examine the effect of IL-12 treatment in preventing the colorectal cancer liver metastasis in a mice model. At different doses, we found that IL-12 treatment decreased the formation of liver metastasis sites and the percentage of metastasis volume in the liver. Additionally, this treatment leads to improved survival function of mice after tumor cell transplantation. We believe that IL-12 based therapy provided a novel treatment to colorectal cancer patients suffering from liver metastasis.

N-myc downstream-regulated gene 1/Cap43 may function as tumor suppressor in endometrial cancer.

PURPOSE: N-myc downstream-regulated gene 1 (NDRG1) reportedly regulates tumor progression in various cancers. Our previous studies showed that NDRG1 was aberrantly overexpressed in human endometrial cancer tissues. The purpose of the present study was to investigate the role of NDRG1 in endometrial carcinogenesis. METHODS: A short hairpin RNA (shRNA)-mediated gene silencing strategy was employed to stably suppress the expression of NDRG1 in endometrial cancer Ishikawa cells. The influence of NDRG1 silencing on cancer cell biological behaviors was examined through observing in vitro tumor cell proliferation, colony formation, cell migration and invasion. Moreover, the mammalian NDRG1 expression vector pcDNA3.1(+)/NDRG1 was constructed to determine the effects of NDRG1 overexpression on cell proliferation and migration. Additionally, gene expression microarray analysis was conducted to identify NDRG1 downstream target genes after NDRG1 knockdown. RESULTS: It was demonstrated that NDRG1 knockdown significantly enhanced Ishikawa cell proliferation and dramatically promoted cell migration and invasion. Furthermore, overexpression of NDRG1 in Ishikawa cells greatly inhibited cell proliferation and migration. Through microarray analysis and data mining, a large cohort of NDRG1-repressed target genes were identified. Additionally, through comparing the current microarray results with those obtained previously in studies of cervical and ovarian cancer cells conducted by us, 19 more specific common downstream target genes were identified. CONCLUSIONS: It was demonstrated that NDRG1 might carry out a tumor suppressor function during endometrial carcinogenesis. The identification of downstream target genes should afford meaningful hints for prospective investigations. The tumor suppressor function of NDRG1 may open a new window for the target therapy of endometrial cancer.

A novel mono-carbonyl analogue of curcumin induces apoptosis in ovarian carcinoma cells via endoplasmic reticulum stress and reactive oxygen species production.

The aim of the present study was to investigate the apoptosis of human ovarian cancer cell lines, A2780 and CP70, induced by a novel curcumin analogue, B19. The proliferation of cells was detected with methyl thiazolyl tetrazolium (MTT) assay and apoptosis was examined by flow cytometry. Reactive oxygen species (ROS) were assessed by the fluorescent indicator DCF-DA. The protein expression of the endoplasmic reticulum (ER) stress pathways, GRP78, XBP-1, ATF-4 and CHOP, was examined with Western blotting. A growth inhibitory effect was observed after treatment with B19 in a dose-dependent manner and with more potential than curcumin. At 20 µM, B19 induced significant apoptosis in CP70 cells. Furthermore, B19 induced the ER stress response, while curcumin had no effect on ER stress. These results suggest that B19 has more effective antitumor properties than curcumin, and is associated with the activation of ER stress and ROS in ovarian cancer cells.

Differences in phenotype and gene expression of prostate stromal cells from patients of varying ages and their influence on tumour formation by prostate epithelial cells.

Prostate cancer (PCa) is an age-related disease, and the stromal microenvironment plays an important role in prostatic malignant progression. However, the differences in prostate stromal cells present in young and old tissue are still obscure. We established primary cultured stromal cells from normal prostatic peripheral zone (PZ) of donors of varying ages and found that cultured stromal cells from old donors (PZ-old) were more enlarged and polygonal than those from young donors (PZ-young). Furthermore, based on immunocytochemical and ultrastructural analysis, the components of stromal cells changed from a majority of fibroblasts to a mixture of fibroblasts and myofibroblasts with increasing donor age. Using a three-dimensional in vitro culture system, we found that PZ-old stromal cells could enhance the proliferation, migration and invasion of cocultured benign BPH-1 and PC-3 cells. Using an in vivo tissue recombination system, we also found that PZ-old stromal cells are more effective than PZ-young cells in promoting tumour formation by BPH-1 cells of high passage (>100) and PC-3 cells. To probe the possible mechanism of these effects, we performed cDNA microarray analysis and profiled 509 upregulated genes and 188 downregulated genes in PZ-old cells. Among the changed genes, we found genes coding for a subset of paracrine factors that are capable of influencing adjacent epithelial cells; these include hepatocyte growth factor (HGF), fibroblast growth factor 5 (FGF5), insulin-like growth factor 2 (IGF2), insulin-like growth factor-binding protein 4 (IGFBP4), IGFBP5 and matrix metallopeptidase 1 (MMP1). Changes in the expression of these genes were further confirmed by quantitative real-time polymerase chain reaction (PCR), Western blotting and enzyme-linked immunosorbent assays. Overall, our findings indicate that stromal cells from prostate PZ of old donors are more active than similar cells from young donors in promoting the malignant process of adjacent epithelial cells. This finding hints at a new potential strategy for the prevention of PCa.

Expression and prognostic significance of CD151, c-Met, and integrin alpha3/alpha6 in pancreatic ductal adenocarcinoma.

BACKGROUND: CD151, c-Met, and integrin alpha3/alpha6 are all involved in the hepatocyte growth factor (HGF)/c-Met signal pathway, which plays an important role in the malignant progression of tumors. AIMS: The purpose of this study was to explore the expression and prognostic significance of these proteins in pancreatic ductal adenocarcinoma (PDAC). METHODS: We used immunohistochemical methods to investigate the expression patterns of CD151, c-Met, and integrin alpha3/alpha6proteins in 71 patients with PDAC and in ten samples of normal pancreatic tissue. We also assessed correlations between these proteins and clinicopathological parameters and survival of PDAC patients using various statistical methods. RESULTS: CD151, c-Met, and integrin alpha3/alpha6 were all overexpressed in PDAC. CD151 and c-Met overexpressions were significantly associated with TNM stage (p=0.001 and p=0.038, respectively) and lymph node invasion (p=0.000, p=0.012, respectively). A significant positive linear correlation was found between CD151 and c-Met (r=0.583; p=0.000), integrin alpha3 (r=0.457; p=0.000), and integrin alpha6 (r=0.671; p=0.000). Overexpression of CD151, c-Met, integrin alpha3, or integrin alpha6 was related to poor survival of PDAC patients (p=0.000, p=0.000, p=0.005, and p=0.003, respectively), and CD151 and c-Met were independent factors in prognosis of PDAC. CONCLUSIONS: CD151, c-Met, and integrin alpha3/alpha6 were all overexpressed in PDAC. CD151 and c-Met might be new molecular markers to predict the prognosis of PDAC patients.

[Experience of the diagnosis and treatment of primary small intestine lymphoma].

OBJECTIVE: To report the experiences of the diagnosis and treatment of primary lymphoma of the small intestine (PSIL). METHODS: The clinical data of 15 patients with PSIL treated from January 2003 to July 2007 was investigated retrospectively. Of the 15 cases, 9 patients were male and 6 were female, the average age was 51.6 years (range, 18 - 73 years). Data of gender, age, clinical manifestation, laboratory examination, imageology examination, diagnosis and treatment of the patients was reviewed. RESULTS: The most common clinical manifestations were as follow: abdominal pain, abdominal lump, bowel obstruction, gastrointestinal hemorrhage and athrepsy. Serum tumor markers were checked normal. All the 15 cases were found with tumor by spiral CT, and 12 cases were diagnosed as PSIL. Eleven cases were given Ba-meal examinations, and positive results was found in 4 cases, and only 1 case was considered to be PSIL. All the 15 patients received operation. All the patients were diagnosed as non-Hodgkin lymphoma (NHL) by postoperative pathology (8 patients as diffuse large B-cell lymphoma, 5 as mucosa associated lymphoid tissue type B cell lymphoma and 2 as enteropathy-type intestinal T cell lymphoma). No perioperative death occurred. Ten patients received adjuvant chemotherapy with the regimen of CHOP (cyclophosphamide + epirubicin + vincristine + prednisone) after the operation. Fourteen cases were followed-up for a mean time of 30 months (range, 6 - 52 months). The 1- and 3-years survival rate was 85.7% and 57.1%, respectively. CONCLUSIONS: PSIL has no specific clinical manifestations, the diagnostic rate with barium study is low, spiral CT scan is a promising diagnostic method for PSIL. Operation combined with chemotherapy is important for PSIL.