Differential baseline and response profile to IFN-γ gene transduction of IL-6/IL-6 receptor-α secretion discriminate primary tumors versus bone marrow metastases of nasopharyngeal carcinomas in culture

<p>Abstract</p> <p>Background</p> <p>Understanding of immunobiology of bone marrow metastases (designated BM-NPC) <it>versus </it>primary tumors (P-NPC) of the nasopharynx is far from complete. The aim of this study was to determine if there would be differences between cultured P-NPCs and BM-NPCs with respect to (i) constitutive IL-6 and the IL-6 receptor gp80 subunit (IL-6Rα) levels in the spent media of nontransduced cells, and (ii) IL-6 and IL-6Rα levels in the spent media of cells transduced with a retroviral vector containing the <it>IFN-γ </it>gene.</p> <p>Methods</p> <p>A panel of NPC cell lines were transduced with the <it>IFN-γ </it>gene through a retroviral vector. Four clonal sublines were isolated <it>via </it>limiting dilution methods. Cytofluorometric analysis was performed for the detection of cell surface antigens of HLA class I, HLA class II and ICAM-1. ELISA was used to assay for IFN-γ, IL-6 and IL-6Rα in the spent media of cultured cell lines.</p> <p>Results</p> <p>Our results showed that in day 3 culture supernatants, low levels of soluble IL-6 were detected in 5/5 cultured tumors derived from P-NPCs, while much higher constitutive levels of IL-6 were detected in 3/3 metastasis-derived NPC cell lines including one originated from ascites; the difference was significant (<it>p </it>= 0.025). An inverse relationship was found between IL-6Rα and IL-6 in their release levels in cultured P-NPCs and metastasis-derived NPCs. In <it>IFN-γ</it>-transduced-P-NPCs, IL-6 production increased and yet IL-6Rα decreased substantially, as compared to nontransduced counterparts. At variance with P-NPC cells, the respective ongoing IL-6 and IL-6Rα release patterns of BM-NPC cells were not impeded as much following <it>IFN-γ </it>transduction. These observations were confirmed by extended kinetic studies with representative NPC cell lines and clonal sublines. The latter observation with the clonal sublines also indicates that selection for high IL-6 or low IL-6Rα producing subpopulations did not occur as a result of <it>IFN-γ</it>-transduction process. P-NPCs, which secreted constitutively only marginal levels of IFN-γ (8.4 ~ 10.5 pg/ml), could be enhanced to produce higher levels of IFN-γ (6.8- to 10.3-fold increase) after <it>IFN-γ </it>transduction. Unlike P-NPCs, BM-NPCs spontaneously released IFN-γ at moderate levels (83.8 ~ 100.7 pg/ml), which were enhanced by 1.3- to 2.2-fold in the spent media of their <it>IFN-γ</it>-transduced counterparts.</p> <p>Conclusion</p> <p>Our results showed that cultured P-NPCs and BM-NPCs could be distinguished from one another on the basis of their differential baseline secretion pattern of IFN-γ, IL-6 and IL-6Rα, and their differential response profiles to <it>IFN-γ </it>gene transfer of the production of these three soluble molecules. These results suggest that the IL-6 and IFN-γ pathways in a background of genetic instability be involved in the acquisition of metastatic behaviour in BM-NPCs.</p

Eighty percent partial splenic embolization is a safe and effective procedure in management of cirrhotic hypersplenism

Background: Partial splenic embolization (PSE) has been proposed in patients with cirrhotic hypersplenism in cases when thrombocytopenia causes clinical manifestations or if there are contraindications to subsequent therapeutic procedures. We provide a retrospective review of the safety and favorable treatment results of 80% splenic embolization in patients with cirrhotic hypersplenism in our institute. Methods: Thirteen consecutive patients with cirrhotic hypersplenism were included in a 4-year study period. The indications for PSE were as follows: percutaneous treatment of hepatocellular carcinoma (HCC) (n = 3), transarterial chemoembolization plus hepatic arterial infusion chemotherapy for HCC (n = 2), preparation for major surgery (n = 5), and severe purpura (n = 3). PSE was performed with up to 80% reduction of splenic blood flow by radiological intervention. A tight protocol of prophylactic antibiotics was introduced. Patient demographics, procedure-related complication, and efficacy of PSE were analyzed. Results: The mean follow-up time was 26.1 ± 12.3 months. All the patients tolerated the procedure. The minor complication of postembolization syndromes such as fever and abdominal pain occurred in 38.5% and 61.5% of patients, respectively. Only a major complication of transient ascites needs diuretic therapy occurred in two patients. Pre-PSE platelet count was 35,077 ± 11,049/mm3, and it significantly increased 1 week after PSE, with a mean increase of platelet count to 384% of pre-PSE level (P < 0.001). The effect of PSE sustained to maintain the platelet count significantly at a mean level of 112,636 ± 33,341/mm3, 114,571 ± 30,696/mm3, and 118,000 ± 31,035/mm3 at 12, 24, and 36 months, respectively. Conclusion: Our series demonstrated that 80% PSE is a safe and effective method to treat patients with cirrhotic hypersplenism. It could not only increase the platelet count within a short period of time but also maintain it at an acceptable level for a long duration. Under a tight protocol of prophylactic antibiotic and delicate technique of PSE, there was no any septic complication developed in our series

Computed Tomography Findings of Gossypiboma

Gossypiboma is composed of non-absorbable surgical material with a cotton matrix. Gossypiboma is usually under-reported and is a severe medicolegal issue. Thus, we describe the computed tomography (CT) findings of gossypiboma in our institution. From January 2003 to June 2006, gossypibomas diagnosed in our institution and their data regarding sex, age, previous operation, location, the interval between the operation and the diagnosis of gossypiboma, clinical presentation, indication of CT, CT findings and further management were collected. There were 6 cases of gossypiboma, 4 men and 2 women. Three of our cases had previous chest surgery and the other 3 cases had previous abdominal surgery. The locations of 3 (50%) cases were in the left anterior subphrenic space. The mean interval between original operation and diagnosis was 24.6 ± 33.4 months (range, 17 days to 8 years). With regard to CT findings, 3 (50%) cases had an isodense mass and 3 (50%) had a typical mass containing curvilinear opaque structures. The mean size of the gossypibomas was 62 × 62 × 67 mm. Because gossypiboma is due solely to human factors and is a severe medicolegal issue, continuous education should be considered

Withaferin A targeting both cancer stem cells and metastatic cancer stem cells in the UP-LN1 carcinoma cell model

Aim: As our understanding of cancer stem cell (CSC) biology improves, search for inhibitory agents of CSCs and metastatic CSCs (mCSCs) positive for CXCR4 is warranted. Withaferin A (WA), a withanolide extracted from the medicinal plant Withania somnifera, has been shown to exhibit anti-cancer effects through multiple mechanisms. Whether WA could selectively target CSCs, mCSCs, or non-CSCs of a gastrointestinal (GI) carcinoma tumor remains unclear.Methods: Side-population (SP) analysis, flow cytometric phenotyping and sorting, non-invasive imaging in conjunction with xenotransplantation, and immunohistology were used in this investigation.Results: Using the lymph node metastatic GI cancer cell line UP-LN1, consisting of CD44high/CD24low floating (F) and CD44low/CD24high adherent (A) cell subsets, this study demonstrated that as compared with parental UP-LN1 cells or A cells, WA preferentially reduced F-cell proliferation, tumor sphere formation, and SP cells in vitro in greater effi ciencies by apoptosis. This action was mechanistically mediated via the down-regulation of CXCR4/CXCL12 and STAT3/interleukin-6 axes, both of which are instrumental in the acquisition of metastatic ability. Attenuation of interferon-γ-induced CXCR4 expression in F cells by knockdown with siRNA or blocking with an anti-CXCR4 antibody, followed by Western blot analysis, showed signifi cantly reduced metastatic potential in vitro. The extent of in vitro anti-invasive effect of WA on the IFN-γ-treated F cells was signifi cantly greater than on the F cells without WA treatment, or F cells treated with control siRNA or with control IgG antibody. The observed in vitro effects of WA on the CSC and mCSC targeting were validated by data obtained with non-invasive imaging in NOD/SCID mouse xenotransplantation.Conclusion: WA could effi ciently block the formation of both CSCs and mCSCs in the UP-LN1 cell line, suggesting that WA may be considered an effective therapeutic agent for this type of GI malignancies

Coronary artery fistula: A rare congenital disorder detected by multidetector computed tomography

AbstractConventional angiography is generally considered the standard procedure for diagnosis of coronary artery disease. With improvements in multidetector computed tomography (CT), CT coronary angiography (CTCA) is a new and rapidly emerging noninvasive imaging technique for coronary imaging. We report the three rarest types of congenital coronary artery fistulae detected by CTCA. CTCA is a practical tool for diagnosis of coronary artery anomalies and reveals the origin, course, termination, and connections of the fistula