The methods of preoperative biliary drainage for resectable hilar cholangiocarcinoma patients: A protocol for systematic review and meta analysis.

OBJECTIVES: To compare the clinical outcomes of endoscopic biliary drainage (EBD) with those of percutaneous transhepatic biliary drainage (PTBD) in patients with resectable hilar cholangiocarcinoma (HCCA) and evaluate the effect of EBD and PTBD on tumor prognosis. MATERIALS AND METHODS: PubMed, EMBASE, and Cochrane Library databases were searched for articles about the comparison between PTBD and EBD. Data were analyzed by Revman 5.3. RESULTS: PTBD showed a lower risk of drainage-related complications than EBD (OR, 2.73; 95%CI, 1.52-4.91; P < .05). PTBD was also associated with lower risk of pancreatitis (OR, 8.47; 95%CI, 2.28-31.45; P < .05). The differences in preoperative cholangitis, R0 resection, blood loss and recurrence showed no statistically significance between EBD and PTBD (all P > .05). Several literatures have reported the tumor implantation metastasis after PTBD. Since no well-designed prospective randomized controlled studies have explored in this depth, this article is unable to draw conclusions on this aspect. CONCLUSION: PTBD is a reasonable choice for PBD, and EBD should only be used as preoperative drainage for HCCA by more experienced physicians. There is a greater need to design prospective randomized controlled studies to obtain high-level evidence-based medicinal proof. It is worth noting that, whether EBD or PTBD, accurate selective biliary drainage should be the trend.

Paclitaxel induces apoptosis through the TAK1-JNK activation pathway.

Paclitaxel (PTX) has previously been used to treat tumours of various tissue origins, such as lung, breast, ovarian, prostate cancers and leukemia. PTX-induced apoptosis is associated with p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), nuclear factor-kappa B (NF-κB) and c-Jun N-terminal kinase or stress-activated protein kinase (JNK/ SAPK) pathways. Transforming growth factor-beta-activated kinase 1 (TAK1) and TAK1-binding protein 1 (TAB1) play an important role in cell apoptosis through the p38, ERK, NF-κB and JNK signal transduction pathways. To investigate the role of TAK1 in PTX-induced cell apoptosis, we treated HEK293 and 8305C cells with 0-20 µM PTX for 6, 12 or 24 h. To investigate whether TAK1 can cooperate with PTX for cancer treatment, we transfected cells with TAK1, TAB1 or control plasmid and treated them with PTX (3-10 µM) for 9-24 h. Apoptosis rates were analysed by flow cytometry (Annexin V/PI). Endogenous TAK1 and TAB1, caspase-7 cleavage, poly ADP-ribose polymerase (PARP) cleavage, Bcl-xL level, phospho-p44/42, phospho-JNK and phospho-p38 were detected by western blot. We show that in HEK293 and 8305C cells, PTX enhanced the endogenous TAK1/TAB1 level and induced cell apoptosis in a dose- and time-dependent manner. Upon TAK1 overexpression in HEK293 cells treated with PTX, apoptosis rate, JNK phosphorylation and PARP cleavage increased contrary to heat-shocked or untreated cells. CRISPR editing of the tak1 gene upon PTX treatment resulted in lower phospho-JNK and PARP cleavage levels than in cells transfected with the control or the TAK1- or TAB1 + TAK1-containing plasmids. TAK1-K63A could not induce JNK phosphorylation or PARP cleavage. We conclude that PTX induces HEK293 and 8305C cell apoptosis through the TAK1-JNK activation pathway, potentially highlighting TAK1's role in chemosensitivity.

Mechanisms and therapeutic potentials of cancer immunotherapy in combination with radiotherapy and/or chemotherapy.

Immunotherapies based on T cells have gained significant success in the treatment of diverse cancers, however, several limitations also exist, including low response, acquired resistance and severe side effects, which lead to unfavorable outcomes. Recent studies found that traditional therapies, radiotherapy and/or chemotherapy may affect the immune condition in situ and cause abscopal effect, which may improve the response of immunotherapies, enhance the efficiency, and reduce the untoward effect. Here, we review the mechanisms uncovering the cancer immunotherapy and immunogenic effects of radiotherapy and chemotherapy, aiming to highlight the principles underlying the therapeutic potentials of cancer immunotherapy in combination with radiotherapy and/or chemotherapy and ultimately guide better designs for future synergistic cancer therapies.

Long noncoding RNAs in cancer-immunity cycle.

The imbalance of immune status in cancer microenvironment plays an important role in the development and progression of cancer. Immunotherapy based on this has become an important field of cancer research in recent years. Many studies on long noncoding RNA (lncRNA) in cancer have focus on its regulation in cancer development and metastasis. Recent studies have suggested that lncRNAs play crucial roles in different phases of cancer immunity, including antigen releasing, antigen presentation, immune activation, immune cells migration, infiltrating into cancer tissues, and killing cancer cells. The functional studies of lncRNAs in cancer immuntity revealed the complicated molecular mechanisms in cancer immunity from a new point of view, which may provide novel potential targets for cancer immunotherapies. Based on the classical cancer-immunity cycle theory, we review the recent studies on the functions and mechanisms of immune-related lncRNAs in different stages of cancer immunity, to summarize the relationship between lncRNAs, and cancer immunity and to provide a framework for further research.

Prenatal diagnosis of β-thalassaemia using cell-free fetal DNA in maternal plasma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the clinical feasibility of cell-free fetal DNA (cffDNA)-based noninvasive prenatal diagnosis of β-thalassemia.</p><p><b>METHODS</b>Nine samples of amniotic fluid were obtained to detect the 8 common and 9 relatively rare mutation sites of β-thalassaemia in Guangdong Province. The maternal blood samples were also collected for extracting and purification of the cffDNA, and a duplex PCR was performed using 3 pairs of primers and the fetal β-globin genotype was analyzed by reverse dot-blot hybridization.</p><p><b>RESULTS</b>Among the 9 cases, 5 showed fetal genotypes of β-thalassemia inherited from the father by examination of the amniotic fluid, and 2 fetuses were identified to have β-thalassemia genes inherited from the father determined based on the cffDNA in the maternal blood.</p><p><b>CONCLUSIONS</b>The cffDNA-based noninvasive prenatal diagnosis is feasible for β-thalassemia, but the contamination of the maternal background DNA results in a low detection rate.</p>