Jianbin Xiang

Genetic and molecular alterations in pancreatic cancer: Implications for personalized medicine

Recent advances in human genomics and biotechnologies have profound impacts on medical research and clinical practice. Individual genomic information, including DNA sequences and gene expression profiles, can be used for prediction, prevention, diagnosis, and treatment for many complex diseases. Personalized medicine attempts to tailor medical care to individual patients by incorporating their genomic information. In a case of pancreatic cancer, the fourth leading cause of cancer death in the United States, alteration in many genes as well as molecular profiles in blood, pancreas tissue, and pancreas juice has recently been discovered to be closely associated with tumorigenesis or prognosis of the cancer. This review aims to summarize recent advances of important genes, proteins, and microRNAs that play a critical role in the pathogenesis of pancreatic cancer, and to provide implications for personalized medicine in pancreatic cancer.

MiR-301a Promotes Colorectal Cancer Cell Growth and Invasion by Directly Targeting SOCS6

Background/Aims: Colorectal cancer (CRC) is one of the most common malignancies worldwide, and microRNAs play a crucial role in CRC biology. The purpose of this study was to investigate the exact functions and potential mechanisms of action of miR-301a in CRC. Methods: Quantitative real-time PCR was conducted to assess the expression of miR-301a. Cell proliferation was detected using MTT and colony formation assay, and cell invasion and migration were evaluated using Transwell assay. Luciferase reporter assay was used to identify the direct regulation of suppressor of cytokine signaling 6 (SOCS6) by miR-301a. Results: We first confirmed the upregulation of miR-301a in CRC tissues and cell lines. Gain-of-function and loss-of-function studies in the human CRC cell lines, SW480 and SW620, showed that miR-301a acts as an oncogene by increasing cell proliferation, migration and invasion as well as tumor growth. Furthermore, SOCS6 was identified as a target gene of miR-301a. Reintroduction of SOCS6 partially abrogated miR-301a-induced cell proliferation, migration and invasion. Conclusion: These data suggest that miR-301a promotes CRC progression by directly downregulating SOCS6 expression, and miR-301a may represent a novel biomarker for the prevention and treatment of CRC.

Effects of RNA interference on CD80 and CD86 expression in bone marrow-derived murine dendritic cells.

To investigate whether RNA interference (RNAi) induced by small interfering RNA (siRNA) could suppress CD80 and CD86 expression in bone marrow‐derived murine dendritic cells (DC). The bone marrow‐derived DC of mice were separated and cultured in vitro, chemically synthesized siRNA were then transferred into the cells by LipofectAMINE 2000, and the siRNA transfection efficacy was assessed by both fluorescence microscope and flow cytometry. The mRNA expression and protein synthesis were analysed by real‐time RT‐PCR and flow cytometry. The cell viability of transfected DC was determined by annexin V and propidium iodine staining. Transfection of bone marrow‐derived murine DC with a non‐silencing FITC‐labelled control siRNA demonstrated a high (71.86%) transfection efficiency without affecting cellular viability. CD80‐1 siRNA was the most effective siRNA to block CD80 expression in three candidates. Similarly, CD86‐3 siRNA was extraordinarily effective in repressing the expression of CD86. Cotransfection of siRNA specific to CD80 and CD86 can enhance gene silencing that is not affected by DC activation‐inducing signals. CD80 and CD86 siRNA suppressed the expression of CD80 and CD86 to 31.05 ± 2.41% and 25.43 ± 0.85%, respectively, of the level in untreated cells (P < 0.05). siRNA is capable of triggering RNAi in bone marrow‐derived DC; it can specifically and effectively knock down CD80 and CD86 gene expression. This approach is a useful tool by which costimulatory molecules of DC can be studied as well as a potential therapeutic option for allograft rejection.

Comparison of clinical safety and outcomes of early versus delayed laparoscopic cholecystectomy for acute cholecystitis: a meta-analysis.

Objective. To compare the clinical safety and outcomes of early laparoscopic cholecystectomy versus delayed laparoscopic cholecystectomy for acute cholecystitis. Methods. Pertinent studies were selected from the Medline, EMBASE, and Cochrane library databases, references from published articles, and reviews. Seven randomized controlled trials (early laparoscopic cholecystectomy versus delayed laparoscopic cholecystectomy) were selected. Conventional meta-analysis according to Cochrane Collaboration was used for the pooling of the results. Results. Seven trials with 1106 patients were included. There was no significant difference between the two groups in terms of bile duct injury (Peto odds ratio 0.49 (95% confidence interval 0.05 to 4.72); P = 0.54) or conversion to open cholecystectomy (risk ratio 0.91 (95% confidence interval 0.69 to 1.20); P = 0.50). The total hospital stay was shorter by 4 days for early laparoscopic cholecystectomy (mean difference −4.12 (95% confidence interval −5.22 to −3.03) days; P < 0.00001). Conclusion. Early laparoscopic cholecystectomy during acute cholecystitis is safe and shortens the total hospital stay.

Surgical outcome of laparoscopic colectomy for colorectal cancer in obese patients: A comparative study with open colectomy

The aim of the present study was to assess the short-term outcome and survival time of 166 obese patients who received laparoscopic and open colectomy for colorectal cancer (CRC) between January 2007 and December 2012. All 166 patients included in the study had a BMI >28. Laparoscopic or open colectomy procedures were performed on 64 and 102 patients, respectively. The short-term outcome and post-operative survival rates were compared. The patient characteristics were similar between the two groups. Laparoscopic colectomy correlated with an increased duration of surgery compared with open colectomy (183 vs. 167 min, respectively; P<0.05) but intraoperative blood loss was decreased (168 vs. 188 ml, respectively; P<0.05). Hospitalization costs were slightly higher following the laparoscopic procedure compared with open surgery, but this was affordable for the majority of patients (¥56,484 vs. ¥56,161, respectively; P<0.05). The incidence of wound infection (17 vs. 31%; P<0.05) and abdominal abscess rates (6 vs. 18%; P<0.05) were reduced in the laparoscopic group compared with the open group. Pathological characteristics were identified to be similar and no significant differences were identified in overall (log-rank test; P=0.85) and disease-free (log-rank test; P=0.85) survival between the two types of surgery (log-rank test; P=0.76). The current retrospective study demonstrated an improved short-term outcome in laparoscopic colectomy for CRC patients with a BMI >28 compared with patients who underwent the open procedure. Laparoscopic colectomy is technically and oncologically safe and must be popularized in obese CRC patients.

miRNA expression profile of colon cancer stem cells compared to non-stem cells using the SW1116 cell line.

Colorectal cancer (CRC) is one of the major causes of cancer-related mortality worldwide. Recent studies revealed that there is a relationship between CRC occurrence and microRNA (miRNA) function. Stem cells are a type of cells that have the ability to self-renew and to proliferate extensively while maintaining the undifferentiated state. Cancer stem cells (CSCs) are closely linked to tumor recurrence and metastasis. To this end, we evaluated the miRNA expression differences between colon CSCs and non-stem cells using the SW1116 cell line, to determine the relationship between tumor stem cells and tumor biological behavior. We isolated populations of colon CSCs with the CD133+/CD44+ and CD133-/CD44- surface phenotype from a human SW1116 colon adenocarcinoma cell line using flow cytometry. The expression of miRNA and mRNA of both sets of cells was examined with miRNA and mRNA arrays. Bioinformatic methods were used to analyze microarray results. We completed gene ontology analysis, pathway analysis, miRNA target gene prediction with databases. We identified a colon stem cell miRNA expression profile comprising 31 upregulated and 31 downregulated miRNAs, such as miR29a, miR29b, miR449b and miR4524. Some of these differentially expressed miRNAs may be involved in the regulation of stem cell differentiation. Gene ontology and pathway analyses showed that the differences are closely related to the function of the cell cycle, cell differentiation, signaling pathway, cytoskeletal proteins and cell-matrix adhesion in colon cancer stem cells. We found that miRNAs play an important role in regulating the expression of colon CSC characteristics. By regulating the expression of CSC signaling pathways, cytoskeleton and membrane proteins, miRNAs give tumor stem cells the macrobiological behavior of recurrence and metastasis. This study provides a new perspective on CRC metastasis and recurrence.

Graded function of CD80 and CD86 in initiation of T‐cell immune response and cardiac allograft survival

CD28 and cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4), which have opposing functions in T‐cell responses, share the two ligands, CD80 (B7‐1) and CD86 (B7‐2). To understand the functions of CD80 and CD86, respectively, CD80low dendritic cells (DCs) and CD86low DCs were prepared by using RNA interference. Then CD80 and CD86 functions were analysed by in vitro mixed lymphocyte reaction and cytokine production assay. Effect on cardiac allograft survival was assayed in vivo. In this study, graded stimulatory function of CD80 and CD86, stronger inhibition of proliferation, and stronger prolongation of transplant survival were observed when CD80 and CD86 were blocked simultaneously.

Prognostic factors associated with locally recurrent rectal cancer following primary surgery (Review)

Locally recurrent rectal cancer (LRRC) is defined as an intrapelvic recurrence following a primary rectal cancer resection, with or without distal metastasis. The treatment of LRRC remains a clinical challenge. LRRC has been regarded as an incurable disease state leading to a poor quality of life and a limited survival time. However, curative reoperations have proved beneficial for treating LRRC. A complete resection of recurrent tumors (R0 resection) allows the treatment to be curative rather than palliative, which is a milestone in medicine. In LRRC cases, the difficulty of achieving an R0 resection is associated with the post-operative prognosis and is affected by several clinical factors, including the staging of the local recurrence (LR), accompanying symptoms, patterns of tumors and combined therapy. The risk factors following primary surgery that lead to an increased rate of LR are summarized in this study, including the surgical, pathological and therapeutic factors.

Myeloid-derived suppressor cells participate in preventing graft rejection.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells and have a tremendous potential to suppress immune responses. MDSCs accumulate during tumor progression, autoimmunity, chronic infection, transplantation, and other pathological conditions and can potently suppress T-cell function. Here, we discuss recent findings that describe the molecular mechanisms of MDSCs suppressing T-cell immune responses as well as recent observations that MDSCs may have roles in transplant tolerance.

Brain metastases from colorectal cancer: microenvironment and molecular mechanisms.

Colorectal cancer is one of the most common digestive tract malignancies in the world. Owing to the newer and more effective systemic therapies, the life of colorectal cancer patients can be remarkably prolonged, and the incidence of brain metastases is increasing. However, little is known about the underlying mechanisms of brain metastasis from colorectal cancer. Here we review the tumor microenvironment and metastasis associated molecules in brain metastases from colorectal cancer. A further understanding of these mechanisms will help us to propose better strategies for colorectal cancer patients with brain metastasis and improve their life quality.