Health self-management experiences of colorectal cancer patients in postoperative recovery: A qualitative study.

PURPOSE: Health self-management helps improve health-related quality of life and life satisfaction, as well as cancer survival. The study aim was to explore the essence of the health self-management experiences and support needs of colorectal cancer patients after surgeries. METHODS: The study was based on phenomenology research methodology. Purposive sampling was used to obtain a heterogeneous sample to provide rich information regarding the research questions. Participants were recruited from colorectal surgery outpatient clinics in a hospital in Taiwan. Data were collected by semi-structured in-depth interviews and analyzed by thematic content analysis. Strategies adapted from Lincoln and Guba were used to enhance the trustworthiness of the study. RESULTS: Ten participants, 5 males and 5 females, were interviewed. Their health self-management experience fell into 3 overarching themes and 9 related subthemes. Our results show that (1) seeking support when experiencing discomfort, (2) when life changes, re-adjust accordingly, and (3) staying positive and self-perseverance are the essences of the health self-management experiences and support needs of postoperative colorectal cancer patients. CONCLUSIONS: Postoperative colorectal cancer patients experienced tremendous physical and psychosocial challenges after returning home from the hospital. Although burdened with multiple stressors, these patients were able to seek support, learning to practice self-care, facing cancer positively, and exhibit positive growth in life. Patients with colorectal cancer have to constantly adjust to the impacts of their diseases. The study results may provide as a reference for supporting postoperative adjustment and promoting health self-management among patients with colorectal cancer.

SHSST-cyclodextrin complex inhibits TGF-ß/Smad3/CTGF to a greater extent than silymarin in a rat model of carbon tetrachloride-induced liver injury.

At present, cirrhosis is an incurable liver disease. Transforming growth factor ß (TGF­ß) is important in myofibroblast induction during the cirrhosis initiation process. The current approach in the development of hepatoprotective drugs depends on TGF­ß inhibition. San Huang Shel Shin Tang (SHSST) is a traditional herbal decoction able to exert a protective effect on the liver, however, similar to silymarin, it is limited by its hydrophobicity. In the present study, SHSST was modified with ß­cyclodextrin to form a hydrophilic complex, which improved its bioavailability. In the carbon tetrachloride­induced acute injury animal model, the effects of pretreatment with silymarin, baicalein, SHSST and the SHSST­ß­CD­complex (SHSSTc) at a low and high dose were assessed. The biopsy results revealed marked liver protection following treatment with silymarin, baicalein and SHSST and these effects were improved further following pretreatment with SHSSTc. Protein analysis demonstrated that the hepatoprotective effects of silymarin occurred through inhibition of the TGF­ß/Smad­3/connective tissue growth factor (CTGF) signaling pathway. SHSSTc exerted the same protective mechanism, however, SHSSTc suppressed CTGF level to a greater extent compared with the groups treated with SHSST or silymarin. Only pretreatment with SHSST and SHSSTc exhibited partial enhancement in the expression of proteins involved in the regulation of liver regeneration, including extracellular­signal­regulated kinase 5, phospho­nuclear factor of activated T cells 3 and phospho­GATA4.

Endothelin-1 enhances cell migration through COX-2 up-regulation in human chondrosarcoma.

BACKGROUND: Chondrosarcoma is a type of highly malignant tumor with a potent capacity of local invasion and distant metastasis. The effect of endothelin-1 (ET-1) on migration activity in human chondrosarcoma cells is not clearly understood. Here, we found that ET-1 increased the migration and expression of cyclooxygenase (COX)-2 in human chondrosarcoma cells. METHODS: ET-1-mediated COX-2 expression was assessed by qPCR and Western blot analysis. The mechanisms of action of ET-1 in different signaling pathways were studied using Western blotting. Knockdown of proteins was achieved by transfection with siRNA. Chromatin immunoprecipitation assays were used to study in vivo binding of c-Jun to the COX-2 promoter. RESULTS: Human chondrosarcoma tissues had significant expression levels of ET-1 and COX-2, which were higher than that in normal cartilage. Exogenous ET-1 increased cell migration and the expression of COX-2. In addition, COX-2 protein levels and cell migration ability were abolished by ET receptor antagonists. Activation of the mitogen-activated protein kinase (MAPK) and activator protein-1 (AP-1) pathways after ET-1 treatment was demonstrated, and ET-1-induced COX-2 expression and cell migration activity were inhibited by the specific inhibitor and mutant of MAPK and AP-1 cascades. ET-1 increased the binding of c-Jun to the AP-1 element on the COX-2 promoter. Furthermore, knockdown of ET-1 decreased cell metastasis in vitro and in vivo. CONCLUSIONS: Our results indicated that ET-1 enhances the cell migration of chondrosarcoma by increasing COX-2 expression through the ET receptors, MAPK, and AP-1 signal transduction pathway. GENERAL SIGNIFICANCE: We link high ET-1 and COX-2 expression to chondrosarcoma.

RANKL increases migration of human lung cancer cells through intercellular adhesion molecule-1 up-regulation.

Invasion of distant tissues by tumor cells is the primary cause of therapeutic failure in the treatment of malignant lung cancer cells. Receptor activator of nuclear factor-κB ligand (RANKL) and its receptor, RANK, play a key role in osteoclastogenesis and tumor metastasis. Intercellular adhesion molecule-1 (ICAM-1, also called CD54), a member of the immunoglobulin supergene family, is an inducible surface glycoprotein that mediates adhesion-dependent cell-to-cell interactions. The effects of RANKL on cell migration and ICAM-1 expression in human lung cancer cells are largely unknown. We found that RANKL directed the migration and increased ICAM-1 expression in human lung cancer (A549) cells. Pretreatment of A549 cells with the MAPK kinase (MEK) inhibitor PD98059 or U0126 inhibited RANKL-mediated migration and ICAM-1 expression. Stimulation of cells with RANKL increased the phosphorylation of MEK and extracellular signal-regulating kinase (ERK). In addition, an NF-κB inhibitor (PDTC) and IκB protease inhibitor (TPCK) also inhibited RANKL-mediated cell migration and ICAM-1 up-regulation. Taken together, these results suggest that the RANKL and RANK interaction acts through MEK/ERK, which in turn activates NF-κB, resulting in the activation of ICAM-1 and contributing to the migration of human lung cancer cells.

Leptin increases motility and integrin up-regulation in human prostate cancer cells.

Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to distant organs. Leptin, an adipocyte-derived cytokine that is closely associated with obesity, has recently been shown to be involved in carcinogenesis and cancer progression. The aim of this study was to investigate whether leptin is associated with the motility of prostate cancer cells. We found that leptin increased the migration of human prostate cancer cells and expression of αvß3 integrin on these cells. Leptin-mediated migration and increased integrin expression were attenuated by OBRl receptor antisense oligonucleotide (ODN). Activation of insulin receptor substrate (IRS-1), phosphatidylinositol 3-kinase (PI3K), Akt, and NF-κB pathways after leptin treatment was demonstrated. Furthermore, leptin-induced integrin expression and migration activity were inhibited by specific inhibitors; small interfering RNAs (siRNAs); and mutants of the IRS-1, PI3K, Akt, and NF-κB cascades. Therefore, this study shows that leptin stimulates the migration of human prostate cancer cells, one of the mechanisms underlying leptin-directed migration was transcriptional up-regulation of αvß3 integrin expression through the OBR1/IRS-1/PI3K/Akt/NF-κB signal transduction pathway.

Porphyromonas gingivalis-related cardiac cell apoptosis was majorly co-activated by p38 and extracellular signal-regulated kinase pathways.

BACKGROUND AND OBJECTIVE: Little is known about the pathogenesis of apoptosis caused in cardiac tissues by periodontitis pathogens. The purpose of this study was to determine the related effect of periodontal pathogen Porphyromonas gingivalis on cardiac cell apoptosis. METHODS: DNA fragmentation, nuclear condensation and activated apoptotic caspases were measured by agarose gel electrophoresis, nuclear DAPI (4',6-diamidine-2-phenylindole dihydrochloride) stain and western blotting analysis following the surrounding medium of P. gingivalis and/or pre-administration of SB203580 (p38 inhibitor), U0126 [mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor], LY294002 [phosphoinositide 3-kinase (PI3K) inhibitor], cyclosporine A (CsA: calcineurin inhibitor), and Sp600125 [c-Jun N-terminal kinase (JNK) inhibitor] in cultured cardiac H9c2 cells. RESULTS: The surrounding medium of periodontal pathogen P. gingivalis increased DNA fragmentation, nuclear condensation and the activated apoptotic caspase-3, -8, and -9 proteins in H9c2 cells. DNA fragmentation and nuclear condensation of H9c2 cells treated with P. gingivalis medium were completely blocked by SB203580 plus U0126 and were decreased after pre-administration of SB203580 only, U0126 only, LY294002, CsA, but were increased by Sp600125. CONCLUSION: Our findings suggest that the development of cardiac cell apoptosis can be directly induced by P. gingivalis medium. Porphyromonas gingivalis-related H9c2 cell apoptosis was mainly co-activated by p38 and ERK pathways and may be involved in death receptor-dependent (caspase 8) and mitochondria (caspase 9)-dependent apoptotic pathways. Porphyromonas gingivalis-related cardiac cell apoptosis was also partially mediated by PI3K or calcineurin signaling pathways, whereas the JNK pathway might play a protective role in P. gingivalis-related cardiac cell apoptosis.

Impaired IGF-I signalling of hypertrophic hearts in the developmental phase of hypertension in genetically hypertensive rats.

Insulin-like growth factor-I (IGF-I) signalling is reported to contribute to the modulation of blood pressure and set survival and hypertrophic responses in cardiac tissue. However, whether IGF-I signalling normally acts in cardiac tissues of hypertensive rats is unknown. In this study, using spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SPSHR), both with early blood pressure increases, and Wistar-Kyoto (WKY) rats as controls, we measured the hypertrophic and IGF-I signalling activity changes in rat hearts at 4, 6 and 12 weeks of age. Both SHR and SPSHR were found to have significantly increased blood pressures and ratios of heart- and left ventricle- to body weight at 12 weeks of age. However, IGF-IR and its downstream signalling, including the protein levels of PI3K and phosphorylated Akt, known to maintain physiological cardiac hypertrophy and cardiomyocyte survival, were downregulated. The results of dot blotting showed that cardiac mRNA levels of IGF-I in hypertensive rats were higher than those in controls starting from the age of 4 weeks. This difference suggests the increased ligand IGF-I mRNA levels may be a compensatory response caused by the impaired IGF-I signalling. Moreover, enhanced cardiac cytosolic cytochrome-c, a mitochondria-dependent apoptotic pathway component, tended to occur in both hypertensive rats, although it did not reach a significant level. These findings indicate that impaired IGF-IR signalling occurs at early stages, and it may contribute, at least partially, to the development of hypertension and pathological cardiac hypertrophy and to cardiomyocyte apoptosis at later stages in SHR and SPSHR.