Bao-Feng Wang

Mycobacterium tuberculosis Infection in Solid Organ Transplant Recipients : Experience From a Single Center in China

OBJECTIVE We sought to explore the prevalence, clinical manifestations, diagnostic procedures, and treatment of tuberculosis (TB) after solid organ transplantation. PATIENTS AND METHODS In this study, we retrospectively analyzed data of 1947 renal transplant recipients and 85 liver transplant recipients. RESULTS TB developed in 28 organ transplant recipients with a prevalence of 1.38% (28/2032). The median interval between transplantation and development of TB was 32 months (range, 1-142 months). Mycobacterium tuberculosis isolation, histologic signs of caseating granulomas, and TB-DNA detection directly supported the diagnosis in 10 (35.71%), 7 (25.00%), and 5 (17.86%) patients, respectively. In addition, 6 patients (21.43%) highly suspected of TB infection received tentative antituberculosis treatment with favorable responses. Most renal transplant recipients (22/25; 78.57%) received isoniazid, rifampicin (or rifabutin), and ethambutal (or pyrazinamide) for a mean duration of 10 months (range, 6-14 months). Three liver transplant recipients received a different protocol: isoniazid, rifabutin, ethambutal, and ofloxacin for 3 months; then isoniazid and rifabutin for 6 months. Upon follow-up, 8 subjects (28.57%) died; 5 of the deaths were related to TB. During the antituberculosis therapy, toxic hepatitis was seen in 12 patients (42.86%); cyclosporine levels decreased in 15 patients (53.57%); and allograft rejection developed in 6 of them. CONCLUSIONS The peak incidences of TB in liver and kidney transplantations are in the first year and after the first year posttransplantation, respectively. Response to antituberculosis treatment should be considered to make a diagnosis among patients highly suspected of TB infections. Except in special circumstances, antituberculosis treatment protocols including isoniazid and rifampicin for about 10 months seem significantly effective and tolerable for non-liver transplant patients. Fluoroquinolones should be emphasized in posttransplantation TB treatment.

Antitumor effects of rapamycin in pancreatic cancer cells by inducing apoptosis and autophagy.

Rapamycin (Rapa), an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. This study aims to investigate the effects of Rapa suppressing proliferation of pancreatic carcinoma PC-2 cells in vitro and its molecular mechanism involved in antitumor activities. MTT assays showed that the inhibition of proliferation of PC-2 cells in vitro was in a time- and dose-dependent manner. By using transmission electron microscopy, apoptosis bodies and formation of abundant autophagic vacuoles were observed in PC-2 cells after Rapa treatment. Flow cytometry assays also showed Rapa had a positive effect on apoptosis. MDC staining showed that the fluorescent density was higher and the number of MDC-labeled particles in PC-2 cells was greater in the Rapa treatment group than in the control group. RT-PCR revealed that the expression levels of p53, Bax and Beclin 1 were up-regulated in a dose-dependent manner, indicating that Beclin 1 was involved in Rapa induced autophagy and Rapa induced apoptosis as well as p53 up-regulation in PC-2 cells. The results demonstrated that Rapa could effectively inhibit proliferation and induce apoptosis and autophagy in PC-2 cells.

Prognosis evaluation in alpha-fetoprotein negative hepatocellular carcinoma after hepatectomy: Comparison of five staging systems

AIMS Alpha-fetoprotein (AFP) loses its potentials in treatment evaluation and prognosis prediction in patients with AFP negative (<or=20 ng/ml) hepatocellular carcinoma (HCC). The present study was to identify the risk factors affecting postoperative survival of AFP negative patients and to determine the optimal staging system in predicting the survival of these patients. METHODS The data of 306 in total and 98 AFP negative patients amongst were retrospectively reviewed. The risk factors affecting survivals of the patients were identified. And various staging systems were compared, including the sixth tumor node metastasis (TNM) system, Okuda staging, Cancer of the Liver Italian Program (CLIP) score, the Barcelona Clinic Liver Cancer (BCLC) staging system, and the Japan Integrated Staging (JIS) score. RESULTS AFP negative patients tended to have intact tumor capsule and earlier staged tumor by TNM, CLIP and BCLC. The independent risk factors worsening overall survival of AFP negative patients were absence of tumor capsule, Child-Pugh classification B, hepatitis B surface antigen positive and BCLC stage B-C. The risk factors promoting tumor recurrence were tumor size of >3 cm, distribution in two lobes, Okuda stage B-C and BCLC stage B-C. CONCLUSION Normal AFP level implies earlier staged tumors. BCLC has the strongest potential in prognosis evaluation in AFP negative patients.

In Vitro and In Vivo Antitumor Activity of Scutellaria barbate Extract on Murine Liver Cancer

In the present study, we investigated the in vitro and in vivo antitumor effects of crude extract of Scutellaria barbate (CE-SB) on mouse hepatoma H22 cells. The MTT assay was used to determine the growth inhibition of H22 cells in vitro. The in vivo therapeutic effects of CE-SB were determined using H22 tumor bearing mice. Besides, the body weight, tumor weight, thymus index and spleen index of H22 bearing mice were also measured. The tumor inhibitory rate (IR) was calculated according to the mean weight of tumor (MWT). The phagocytotic function of macrophages was examined by observing peritoneal macrophages phagocytize chicken RBC. The results showed that CE-SB could inhibit the growth of hepatoma H22 Cells in vitro and in vivo. Furthermore, CE-SB could improve immune function of H22 tumor bearing mice. Together these results indicate that CE-SB has antitumor activity and seems to be safe and effective for the use of anti-tumor therapy.

Total flavonoids of Scutellaria barbata inhibit invasion of hepatocarcinoma via MMP/TIMP in vitro.

Metastasis is the major cause of cancer-related deaths. Targeting the process of metastasis has been proposed as a strategy to fight cancer. Scutellaria barbata D. Don (S. barbata), a traditional Chinese medicine, is used for treatment of many diseases, including cancer. This study aimed to determine the anti-metastatic effect of total flavonoids of S. barbata (TF-SB) using the human hepatocarcinoma MHCC97H cell line with high metastatic potential. Our results show that TF-SB could significantly inhibit the proliferation and invasion of MHCC97H cells in a dose-dependent manner. MMP-2 and MMP-9 expression were obviously decreased after TF-SB treatment at both the mRNA and protein level. TIMP-1 and TIMP-2 expression were simultaneously increased. The present study indicates that TF-SB could reduce the metastatic capability of MHCC97H cell, probably through decrease of the MMP expression, and simultaneous increase of the TIMP expression.

The expression and significance of five types of miRNAs in breast cancer.

Background This study aimed to investigate the expression and significance of 5 types of miRNAs in breast cancer to provide a theoretical and practical foundation for using these miRNAs in the diagnosis and treatment of breast cancer, thereby improving medical services. Material/Methods Stem-loop real-time RT-PCR was used to detect the expression levels of miR-145, miR-21, miR-10b, miR-125a, and miR-206 in 35 cases of breast cancer and adjacent normal breast tissues, and to analyze the relationship of miRNAs expression with clinicopathological features of breast cancer. The expression levels of estrogen receptor (ER) and progesterone receptor (PR) were examined by immunohistochemistry. Fluorescence in situ hybridization was used for the detection of HER-2 and TOP 2A. Results The expression levels of miR-145, miR-125a, and miR-206 in breast cancer were lower than those in adjacent normal tissues. MiR-145 was negatively correlated with tumor size, lymph node metastasis, ER, HER-2, and TOP 2A (P<0.05), regardless of age, menstruation, and PR. MiR-125a was correlated with negative node status, negative HER-2 status (P<0.05), whereas tumor size, age, menstruation, ER, and PR were independent factors. MiR-206 expression was correlated with negative ER status, negative PR status, and negative HER-2 status (P<0.05), regardless of age, menstruation, lymph node metastasis, and TOP 2A. MiR-21 and miR-10b expression in breast cancer tissues was significantly higher than that in adjacent tissues (P<0.05). MiR-21 in post-menstrual patients with lymph node metastasis was highly expressed (P<0.05), and had no correlations with tumor size, ER, PR, and TOP 2A expression. MiR-10b expression was positively correlated with breast cancer tumor size, lymph node metastasis, and TOP 2A status (P<0.05), but had no correlations with age, menstruation, ER, PR, and HER-2. Conclusions MiR-145, miR-21, miR-10b, miR-125a, and miR-206 may play important roles in breast cancer development and invasion.

Saikosaponin-D Enhances Radiosensitivity of Hepatoma Cells under Hypoxic Conditions by Inhibiting Hypoxia-Inducible Factor-1α

Background: Our previous study revealed that the combination of Saikosaponin-d (SSd) and radiation is more effective in the treatment of liver cancer than the application of either of these monotherapeutic methods. However, the molecular mechanisms of the radiosensitizing effect of SSd on liver cancer remained ill defined. Methods: Cells were treated with different interventions; afterward, cell viability, apoptosis, and cell survival of SMMC-7721 and HepG2 hepatoma cells were examined. Xenograft tumor models were established by subcutaneously injecting SMMC-7721 cells. The molecular mechanism was assessed by western blot. Results: SSd dose-dependently increased radiosensitivity of hepatoma cells under hypoxic condition. The growth inhibitory effect of the combined treatment was correlated with cell apoptosis. Further mechanistic analysis indicated that SSd induced the upregulation of p53 and Bax as well as the downregulation of Bcl-2 by attenuating HIF-1α expression under hypoxic condition. These effects were enhanced when the HIF-1α inhibitor PX-478 was introduced. In vivo data also presented a more significant suppression of tumor xenograft growth from the combined therapy than from either of the monotherapeutic methods. Conclusions: Our study provides evidence for a radiosensitizing effect of SSd on hepatoma cells under hypoxic conditions by inhibiting HIF-1α expression. Thus, SSd can be used as a potential sensitizer in hepatoma radiotherapy.

Hepatic and Renal Artery Rupture Due to Aspergillus and Mucor Mixed Infection After Combined Liver and Kidney Transplantation: A Case Report

Fungal infection is a major cause of death in patients who undergo organ transplantation. The incidence of Aspergillus or Mucor infection is low compared with Candida species. We report a case in which Aspergillus and Mucor infected both the hepatic and renal arteries, leading the 2 arteries to rupture at the same time. The patient died 4 days after the second operation. We review the recent literature about this topic and explore the possible route of transmission in our patient. We also discuss the prophylactic methods for Aspergillus and Mucor infections.

Interdigitating Dendritic Cell Sarcoma Involving Bone Marrow in a Liver Transplant Recipient

Liver transplantation is an effective treatment for patients with many kinds of liver diseases. However, an increased risk of de novo malignancy has been reported in liver transplant recipients; immunosuppressive drugs have generally been identified as the primary culprit. Interdigitating dendritic cell sarcoma (IDCS) is an exceedingly rare neoplasm arising from antigen-presenting cells of the immune system. In this study, we have reported a case of IDCS with bone marrow involvement occurring in a 61-year-old female liver transplant recipient at 2 years after the procedure. She was admitted to our center with fever, cough, and expectoration. Physical examination revealed firm and painless nodes in both cervical and axillary fossae. Routine examination revealed an abnormal white blood cell count and elevated serum lactate dehydrogenase. Computerized tomography of the chest, abdomen, and pelvis were negative. Viral infections were also excluded. To obtain a definite diagnosis, we performed an excisional lymph node biopsy and a bone marrow biopsy. Microscopically, the tumor was composed of spindle cells with pale to eosinophilic cytoplasm, ill-defined cell borders, and large pleomorphic nuclei with prominent nucleoli. Immunophenotypic analysis demonstrated positive staining for S-100, vimentin, CD163, and CD68. Follicular dendritic cell, lymphoid, epithelial, myoepithelial, and melanoma markers were negative. Histology revealed bone marrow involvement. Taken together, the above features were consistent with IDCS with bone marrow involvement. She responded to chemotherapy. This case demonstrates the importance of cancer prevention and early detection for liver transplant recipients.

The effect of RHIZOMA COPTIDIS and COPTIS CHINENSIS aqueous extract on radiation-induced skin injury in a rat model

BackgroundRadiation-induced skin injury is a common complication of radiotherapy. The RHIZOMA COPTIDIS and COPTIS CHINENSIS aqueous extract (RCE) can ameliorate radiation-induced skin injury in our clinical observation. But, the protective mechanism of RHIZOMA COPTIDIS and COPTIS CHINENSIS in radiation-induced skin injury remains unclear.MethodsIn this experiment, we developed a radiation-induced skin injury rat model to study the mechanism. The animals were randomly divided into control group, treatment group, radiation group, and treatment and radiation group. 5 rats in each group were separately executed on 2 d and 49 d post-radiation. The semi-quantitative skin injury score was used to measure skin reactions by unblinded observers, and hematoxylin and eosin staining was used to evaluate the damage areas by irradiation. The MDA content, SOD activity of skin and serum were measured to detect the oxidative stress.ResultsAcute skin reactions were caused by a single dose of 45 Gy of β-ray irradiation, and the skin injury could be found in all rats receiving irradiation based on the observation of HE staining of skin at different time-points, while RCE could significantly ameliorate those changes. The MDA content in serum and skin of control rats was 4.13 ± 0.12 mmol/ml and 4.95 ± 0.35 mmol/mgprot on 2 d post-radiation. The rats receiving radiation showed an increased content of MDA (5.54 ± 0.21 mmol/ml and 7.10 ± 0.32 mmol/mgprot), while it was 4.57 ± 0.21 mmol/ml and 5.95 ± 0.24 mmol/mgprot after treated with RCE (p < 0.05). Similar changes of the MDA content could be seen on 49 d post-radiation. However, the SOD activity of rats receiving radiation decreased compared with control group on both time-points, which was inhibited by RCE (p < 0.05). Meanwhile, no valuable changes could be found between control group and treatment group on 2 d and 49 d.ConclusionsOur study provides evidences for the radioprotective role of RCE against radiation-induced skin damage in rats by modulating oxidative stress in skin, which may be a useful therapy for radiation-induced skin injury.