Study of prevalence and influencing factors of depression in tumor patients and the therapeutic effects of fluoxetine.

OBJECTIVE: To observe the depression in patients with malignant tumor and influencing factors of the disease, as well as to investigate the effects of fluoxetine on depressive symptoms in cancer patients and the immune function. PATIENTS AND METHODS: 262 patients with malignant tumors, confirmed by pathological and radiological diagnosis as malignant tumor were randomly divided into 2 groups: the control group with chemotherapy; the treatment group with chemotherapy and 20 mg/d fluoxetine for six weeks. Before and after treatment, the scores of QLQ-C30 scale and changes of immune parameters were observed, including the determination of NK and T cell subsets. RESULTS: The prevalence of depression in cancer patients was not related to the tumor location. But gender, age, tumor stage, the income level of satisfaction and chronic cancer pain were related to the occurrence of depression in cancer patients (p < 0.05). In the fluoxetine treatment groups, by QLQ-C30 scores, in quality of life scores including body, function, social and cognitive function, and single symptoms including nausea, vomiting, constipation, diarrhea, and economic difficulties, the differences were not statistically significant. The QLQ-C30 scores of overall quality of life and emotional function were rising in the fluoxetine treatment group. The QLQ-C30 scores of the pain, shortness of breath, fatigue, loss of appetite, insomnia symptoms were decreased, which had a statistical significance (p < 0.05) compared with the control group. To compare with the control group, the scores of HAMD were decreasing in the fluoxetine treatment group, which had a statistical significance (p < 0.05). Before treatment, the NK cells, CD3+, CD4+, CD4+/CD8+ ratios of tumor patients decreased significantly, while CD8+ increased. After 6 weeks of treatment, NK cells, CD3+, CD4+, CD4+/CD8+ ratios increased significantly and CD8+ decreased. CONCLUSIONS: Sex, age, tumor stage, income satisfaction, and cancer pain were relevant factors in patients with tumor-associated depression. If depression can be detected in the early stage, and oral fluoxetine therapy can be conducted, it can improve the depression situation and immune function of patients with malignant tumor.

Onset of Inflammation With Ischemia: Implications for Donor Lung Preservation and Transplant Survival.

Lungs stored ahead of transplant surgery experience ischemia. Pulmonary ischemia differs from ischemia in the systemic organs in that stop of blood flow in the lung leads to loss of shear alone because the lung parenchyma does not rely on blood flow for its cellular oxygen requirements. Our earlier studies on the ischemia-induced mechanosignaling cascade showed that the pulmonary endothelium responds to stop of flow by production of reactive oxygen species (ROS). We hypothesized that ROS produced in this way led to induction of proinflammatory mediators. In this study, we used lungs or cells subjected to various periods of storage and evaluated the induction of several proinflammatory mediators. Isolated murine, porcine and human lungs in situ showed increased expression of cellular adhesion molecules; the damage-associated molecular pattern protein high-mobility group box 1 and the corresponding pattern recognition receptor, called the receptor for advanced glycation end products; and induction stabilization and translocation of hypoxia-inducible factor 1α and its downstream effector VEGFA, all of which are participants in inflammation. We concluded that signaling with lung preservation drives expression of inflammatory mediators that potentially predispose the donor lung to an inflammatory response after transplant.

Surface-expressed lamellar body membrane is recycled to lamellar bodies.

Monoclonal antibody (MAb) 3C9, an antibody generated to the lamellar body of rat lung type II pneumocytes, specifically labels the luminal face of the lamellar body membrane. To follow the retrieval of lamellar body membrane from the cell surface in these cells, MAb 3C9 was instilled into rat lungs. In vivo, it was endocytosed by type II cells but not by other lung cells. In type II cells that were isolated from rat lungs by elastase digestion and cultured on plastic for 24 h, MAb 3C9 first bound to the cell surface, then was found in endosomes, vesicular structures, and multivesicular bodies and, finally, clustered on the luminal face of lamellar body membranes. The amount internalized reached a plateau after 1.5 h of incubation and was stimulated with the secretagogue ATP. In double-labeling experiments, internalized MAb 3C9 did not completely colocalize with NBD-PC liposomes or the nonspecific endocytic marker TMA-DPH, suggesting that lamellar body membrane is retrieved back to existing lamellar bodies by a pathway different from that of bulk membrane and may be one pathway for surfactant endocytosis. The lamellar body membrane components are retrieved as subunits that are redistributed among the preexisting lamellar bodies in the cell.

Lamellar body membrane turnover is stimulated by secretagogues.

Lamellar bodies are specialized cellular organelles used for storage of surfactant by alveolar type II cells of the lung. We utilized monoclonal antibody (MAb) 3C9, which recognizes an integral lamellar body-limiting membrane protein of 180 kDa, to follow lamellar body trafficking. (125)I-labeled MAb 3C9 bound to the surface of type II cells and was internalized by the cells in a time- and concentration-dependent manner that was inhibitable by excess unlabeled antibody. The internalized antibody remained undegraded over a 4-h time period. The L2 rat lung cell line that does not have lamellar bodies did not bind iodinated 3C9. Exposure of type II cells to the secretagogues ATP, phorbol 12-myristate 13-acetate, and cAMP resulted in a 1.5- to 2-fold enhancement of binding and uptake of MAb 3C9. Calphostin C inhibited phorbol 12-myristate 13-acetate-stimulated phospholipid secretion and also reduced binding and uptake of MAb 3C9 by type II cells. Treatment of type II cells with phenylarsine oxide to obstruct clathrin-mediated endocytosis had no effect on the internalization of MAb 3C9 while markedly blocking the uptake of surfactant protein A and transferrin. An actin-mediated process was important for lamellar body membrane uptake because incubation with cytochalasin D partially inhibited MAb 3C9 incorporation by type II cells. These studies are compatible with enhanced lamellar body membrane turnover associated with surfactant secretion and indicate that this process can be monitored by the trafficking of the antigen reporter MAb 3C9.

Inhibition of lung surfactant secretion from alveolar type II cells and annexin II tetramer-mediated membrane fusion by phenothiazines.

We investigated the effects of phenothiazines on lung surfactant secretion from rat alveolar epithelial type II cells and on annexin II tetramer (Anx IIt)-mediated membrane fusion. Trifluoperazine and promethazine inhibited ATP-stimulated phosphatidylcholine (PC) secretion from type II cells in a dose-dependent manner. Concentrations that cause 50% inhibition (IC50) were approximately 3 and 25 microM for trifluoperazine and promethazine, respectively. Promethazine also inhibited PC secretion of type II cells stimulated by other secretagogues, including calcium ionophore A23187, phorbol 12-myristate 13-acetate, and terbutaline that are known to stimulate PC secretion via different signal transduction pathways. Since we have recently determined that Anx IIt is involved in PC secretion of type II cells, we examined whether phenothiazines influence Anx IIt's activity. Trifluoperazine and promethazine inhibited Anx IIt's ability to aggregate phosphatidylserine (PS) liposomes, to fuse PS/phosphatidylethanolamine (PE) liposomes, and to fuse PS/PE liposomes with lamellar bodies. These results suggest a relationship between lung surfactant secretion and Anx IIt-mediated membrane fusion.

Annexin II binds to the membrane of A549 cells in a calcium-dependent and calcium-independent manner.

We investigated the nature of annexin II binding to the biological membranes using a lung epithelium-derived cell line A549. The cytosolic and membrane fractions of A549 cells were separated in the presence of 5 mM EGTA. Both fractions contain annexin II monomer and tetramer as evaluated by western blots using specific monoclonal antibodies against p36 and p11 subunits of annexin II. A substantial amount of annexin II was associated with the membrane fraction even after extensive washing with EGTA buffer, indicating the presence of two pools of annexin II. The EGTA-resistant membrane-bound annexin II could be partially extracted by 1% Triton X-100 or 60 mM n-octyl-beta-D-glucopyranoside, and completely by 30 mM CHAPS or 0.1% deoxycholate. This fraction of annexin II was also extracted by 0.1 M Na2CO3, pH 11 and partitioned into the aqueous phase after being treated with Triton X-114, demonstrating that the EGTA-resistant annexin II is a peripheral membrane protein. When the cells were lysed in varying concentrations of Ca2+, annexin II translocated from cytosolic fraction to membrane fraction at 4-25 microM Ca2+. To identify proteins closely associated with annexin II the membrane fraction was treated with the bifunctional chemical cross-linker disulfosuccinimidyl tartarate, followed by western blot analysis using anti-p36 or anti-p11 antibodies. We find that both p36 and p11 were cross-linked to a 51 kDa protein. In addition, p11 also binds to several proteins with molecular mass of 91, 65, 40 and 36 kDa. Our results suggest that annexin II may bind to the A549 cell membranes via specific membrane-associated proteins.