Chengyong Dong

Nogo-B receptor promotes the chemoresistance of human hepatocellular carcinoma via the ubiquitination of p53 protein.

Nogo-B receptor (NgBR), a type I single transmembrane domain receptor is the specific receptor for Nogo-B. Our previous work demonstrated that NgBR is highly expressed in breast cancer cells, where it promotes epithelial mesenchymal transition (EMT), an important step in metastasis. Here, we show that both in vitro and in vivo increased expression of NgBR contributes to the increased chemoresistance of Bel7402/5FU cells, a stable 5-FU (5-Fluorouracil) resistant cell line related Bel7402 cells. NgBR knockdown abrogates S-phase arrest in Bel7402/5FU cells, which correlates with a reduction in G1/S phase checkpoint proteins p53 and p21. In addition, NgBR suppresses p53 protein levels through activation of the PI3K/Akt/MDM2 pathway, which promotes p53 degradation via the ubiquitin proteasome pathway and thus increases the resistance of human hepatocellular cancer cells to 5-FU. Furthermore, we found that NgBR expression is associated with a poor prognosis of human hepatocellular carcinoma (HCC) patients. These results suggest that targeting NgBR in combination with chemotherapeutic drugs, such as 5-FU, could improve the efficacy of current anticancer treatments.

Mixed acinar-endocrine carcinoma of pancreas: A case report and brief review of the literature

Mixed acinar-endocrine carcinoma (MAEC) of the pancreas is a rare entity. We present a 65-year-old Chinese female who was admitted with jaundice and nagging epigastric pain with intermittent diarrhea for 1 month. She eventually underwent abdominal magnetic resonance imaging, which showed an 8×6 cm mass in the head of the pancreas and showed two abnormal lesions in the liver simultaneously. MAEC of the pancreas with synchronous hepatic metastasis was confirmed with immunohistochemistry after Whipple operation and hepatic partial resection of the lesions. Postoperative recovery of this patient was uneventful, and no evidence of recurrence or metastasis was observed after 12 months of follow-up. MAEC of pancreas is thought to be extremely rare and lack of typical clinical symptoms. The prognosis is poor overall, but early detection with complete resection may be beneficial to patients.

Spontaneously removed biliary stent drainage versus T-tube drainage after laparoscopic common bile duct exploration.

AbstractSeveral studies have shown the safety and feasibility of laparoscopic common bile duct exploration (LCBDE) as a minimally invasive treatment options for choledocholithiasis. Use of T-tube or biliary stent drainage tube placement after laparoscopic choledochotomy for common bile duct (CBD) stones is still under debate. This study tried to confirm the safety of spontaneously removable biliary stent in the distal CBD after LCBDE to allow choledochus primary closure. A total of 47 patients with choledocholithiasis underwent LCBDE with primary closure and internal drainage using a spontaneously removable biliary stent drainage tube (stent group, N = 22) or T-tube (T-tube group, N = 25). Operative parameters and outcomes are compared. Surgical time, intraoperative blood loss, length of hospital stay, drainage tube removal time, postoperative intestinal function recovery, and cost of treatment were all significantly lower in the stent group as compared to that in the T-tube group (P < 0.05 for all). Otherwise, Bile leakage between the two groups had no significant difference (P > 0.05). The biliary stent drainage tube was excreted spontaneously 4 to 14 days after surgery with the exception of one case, where endoscopic removal of biliary tube was required due to failure of its spontaneous discharge. LCBDE with primary closure and use of spontaneously removable biliary stent drainage showed advantage over the use of traditional T-tube drainage in patients with choledocholithiasis.

Microfluidic-based biomimetic models for life science research

The advances in microfluidic technology have recently generated various microfluidic-based biomimetic models as novel three-dimensional (3D) models for life science research, offering some great advantages over conventional two-dimensional (2D) models, classical scaffold-free or scaffold-based 3D approaches and animal models. These biomimetic models could simulate the microenvironment of in vivo tissues and organs by controlling spatiotemporal gradients of chemical substances and imitating mechanical activities of living tissues and organs. They provide platforms for real-time observation of physiological and pathological processes, toxicology effect and drug effects in tissues and organs for life science research. Without a doubt, microfluidic-based biomimetic models would serve as a powerful tool for developing diagnosis and treatment methods for various diseases. In this study, we briefly summarized the fabrication of microfluidic-based biomimetic models and their use as 3D tissue/organ models.

Growing Teratoma Syndrome Secondary to Ovarian Giant Immature Teratoma in an Adolescent Girl: A Case Report and Literature Review

AbstractGrowing teratoma syndrome (GTS) is a rare clinical entity first described by Logothetis et al in 1982. Although it is unusual for GTS to be located in the ovary, this report is of a case of an adolescent girl who underwent a complete surgical resection of the mass. Histopathology confirmed only an immature teratoma had originated from the ovary and so she received adjuvant chemotherapy with blemycin, etopside, and cisplatin over 4 cycles. Results from an abdominal enhanced CT (computed tomography) 9 years later revealed a giant mass had compressed adjacent tissues and organs. Laparotomy was performed and a postoperative histopathology showed the presence of a mature teratoma, and so the diagnosis of ovarian GTS was made. One hundred one cases of ovarian GTS from English literature published between 1977 and 2015 were collected and respectively analyzed in large samples for the first time.The median age of diagnosis with primary immature teratoma was 22 years (range 4–48 years, n = 56). GTS originating from the right ovary accounted for 57% (27/47, n = 47) whereas the left contained 43% (20/47, n = 47). Median primary tumor size was 18.7 cm (range 6–45 cm, n = 28) and median subsequent tumor size was 8.6 cm (range 1–25 cm, n = 25). From the primary treatment to the diagnosis of ovarian GTS, median tumor growth speed was 0.94 cm/month (range 0.3–4.3 cm/month, n = 21). Median time interval was 26.6 months (range 1–264 months, n = 41). According to these findings, 5 patients did have a pregnancy during the time interval between primary disease and GTS, making our patient the first case of having a pregnancy following the diagnosis of ovarian GTS. Because of its high recurrence and insensitiveness to chemotherapy, complete surgical resection is the preferred treatment and fertility-sparing surgery should be considered for women of child-bearing age.Anyhow GTS of the ovary has an excellent prognosis. Patients with GTS had no evidence of recurrence or were found to be disease free during a 40.3-month (range 1–216 months, n = 48) median follow-up. Moreover, regular follow-ups with imaging and serum tumor markers are important and must not be neglected.

Melatonin enhances the anti-tumor effect of sorafenib via AKT/p27-mediated cell cycle arrest in hepatocarcinoma cell lines

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, often diagnosed in late stages when most therapeutic methods are not very effective. The introduction of the multikinase inhibitor sorafenib as the standard of care has opened a window of hope for patients with advanced HCC, patients with very poor prognosis; however, patients usually develop acquired resistance to sorafenib limiting its therapeutic benefits. Melatonin (MT), an indoleamine compound produced in the pineal gland, has shown a substantial beneficial effect in increasing the efficacy of common anticancer drugs and decreasing their toxic effects. Here we demonstrate that MT potentiated the sorafenib-mediated inhibition of cell viability and colony formation in HCC cell lines. Moreover, combined treatment of MT and sorafenib enhanced the cell cycle arrest of HCC cells at the G0/G1 phase. Co-treatment of sorafenib and MT was found to upregulate p27, an inhibitor of several cyclin-dependent kinases (CDK), and downregulate p-AKT, c-myc, cyclin D1 and CDK4/6 protein expression. Furthermore, overexpression of p-AKT using SC79 reversed the effect of sorafenib and MT combination on cell viability and growth of HCC cells. These results suggest that the AKT pathway might be critical for the enhanced anticancer effect observed after co-treatment with MT and sorafenib. Taken together, our findings demonstrated that AKT/p27-mediated cell growth arrest induced by MT increased the sensitivity of HCC cells to the effect of sorafenib.

Pinin associates with prognosis of hepatocellular carcinoma through promoting cell proliferation and suppressing glucose deprivation-induced apoptosis

The roles of Pinin have been well studied in epithelial cell-cell adhesion and RNA alternative splicing, which suggests its involvement in cancer progression. However, little is known about the association between Pinin expression and hepatocellular carcinoma (HCC) tumorigenesis. In this study we report increased expression of Pinin in HCC tissues and cells. Elevated levels of Pinin closely associates with pathological grade and overall survival of patients with hepatocellular carcinoma. Suppression of Pinin expression via lentivirus mediated shRNA knockdown inhibits HCC cell proliferation, colony formation, cell viability, but promotes glucose deprivation (GD)-induced cell apoptosis. On the contrary, overexpression of Pinin reverses these effects observed in Pinin depleted cells. Meanwhile, overexpression of Pinin attenuates GD initiated poly ADP-ribose polymerase (PARP) cleavage and ERK1/2 dephosphorylation, which can be completely blocked with MEK1/2 inhibitor U0126. Therefore, we conclude that Pinin contributes to HCC progression and resistance to GD-induced apoptosis via maintaining ERK1/2 activation and hence may be a potential therapeutic target in hepatocellular carcinoma treatment.

One type of duplex appendix: horseshoe appendix

A horseshoe appendix is a subtype of duplex appendix, in which the appendix is shaped like a circle that may lead to an internal hernia and result in intestinal necrosis. This subtype is extremely rare, with only 13 cases reported worldwide to date, and easily triggers a series of medico-legal consequences due to the neglect of another infection base of the appendix. We describe a 22-year-old man who presented with a 3-day history of fever and was diagnosed with pneumonia. After receiving antibiotics for 3 days in the Department of Pneumology, he was found to have a periappendiceal abscess. He underwent appendectomy after 3 days of conservative treatment failure in the Department of General Surgery. During the operation, we found that he had a horseshoe appendix with the two bases forming a circle, each communicating with the cecum. We provide a review of 13 cases presented in the literature, with a discussion of the clinical features, diagnosis, and surgical approach of the horseshoe appendix to make the general surgeon get a clear concept of this type of appendicitis.

Fluorescence imaging of hepatocellular carcinoma with a specific probe of COX-2

Hepatocellular carcinoma (HCC) is the major subtype of primary liver cancer. Although the standard treatment method based on surgery has generally extended life, it still causes the second and sixth most prevalent cancer-related death in men and women, respectively. The recurrence of cancer caused by unclear resection margins and any remaining undiscovered metastatic nodules should take a large proportion of responsibility for the poor prognosis after resective surgery. Therefore, a practical and effective method that can be used during hepatectomy to specifically identify HCC is a potentially significant area deserving attention. Tests involving fluorescence have been used in many biological systems. In this study, we use a probe that can combine with cyclooxygenase-2 (COX-2) and subsequently emit fluorescence to identify HCC cells and heteroplastic tumors in a mouse model. The results show that this specific probe can clearly differentiate HCC, with differences that could be observed with the naked eye in human samples. The biotechnology of knocking down COX-2 and its inhibitor were used on human HCC cell line SMMC7721, and the outcomes confirmed the above results. The toxic effect also showed that the probe had no harmful effect on normal liver cells. Taken together, our study demonstrates that a COX-2-specific fluorescence probe may be a new and effective method to identify HCC, especially during surgery.

The Nogo-B receptor promotes human hepatocellular carcinoma cell growth via the Akt signal pathway: DONG et al.

Nogo‐B receptor (NgBR) is a type I receptor with a single transmembrane domain and specifically binds to ligand Nogo‐B. A previous study demonstrated that NgBR was highly expressed in human breast invasive ductal carcinoma and promoted epithelial‐mesenchymal transition in breast tumor cells. Our recent work found that NgBR expression was associated with a poor prognosis in human patients with hepatocellular carcinoma (HCC). Here, we elucidate that the increased expression of NgBR contributes toward the increased cell growth of human HCC cells both in vitro and in vivo. Cell viability and clonogenic survival analysis results demonstrated that knockdown of NgBR inhibits the cell growth in human HCC cells, which correlates with a reduction in the phosphorylation of Akt levels. Furthermore, overexpression of NgBR by the cotransfected pIRES‐NgBR plasmid together with NgBR siRNA in human HCC cells can rescue impaired phosphorylation of Akt levels in NgBR knockdown human HCC cells. In addition, cell viability analyses showed that NgBR overexpression can rescue the cell growth inhibition presented in human HCC NgBR knockdown cells. Taken together, our results suggest that NgBR potentially acts as an oncogene in HCC by increasing Akt activity. Thus, NgBR may represent a new potential diagnostic and therapeutic target for the treatment of HCC.