Fatal hepatitis B virus (HBV) reactivation in lymphoma patients with “resolved” HBV infection (hepatitis B surface antigen HBsAg negative and hepatitis B core antibody anti‐HBc positive) can occur, ...but the true incidence and severity remain unclear. From June 2009 to December 2011, 150 newly diagnosed lymphoma patients with resolved HBV infection who were to receive rituximab‐CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)‐based chemotherapy were prospectively followed. HBV DNA was checked at baseline, at the start of each cycle of chemotherapy, and every 4 weeks for 1 year after completion of rituximab‐CHOP chemotherapy. Patients with documented HBV reactivation were treated with entecavir at a dosage of 0.5 mg/day for 48 weeks. HBV reactivation was defined as a greater than 10‐fold increase in HBV DNA, compared with previous nadir levels, and hepatitis flare was defined as a greater than 3‐fold increase in alanine aminotransferase (ALT) that exceeded 100 IU/L. Incidence of HBV reactivation and HBV‐related hepatitis flares was 10.4 and 6.4 per 100 person‐year, respectively. Severe HBV‐related hepatitis (ALT >10‐fold of upper limit of normal) occurred in 4 patients, despite entecavir treatment. Patients with hepatitis flare exhibited significantly higher incidence of reappearance of HBsAg after HBV reactivation (100% vs. 28.5%; P = 0.003). Conclusion: In lymphoma patients with resolved HBV infections, chemotherapy‐induced HBV reactivation is not uncommon, but can be managed with regular monitoring of HBV DNA and prompt antiviral therapy. Serological breakthrough (i.e., reappearance of HBsAg) is the most important predictor of HBV‐related hepatitis flare. (Hepatology 2014;59:2092–2100)
This study investigated the epidemiology and risk factors associated with invasive fungal infections (IFIs) during induction chemotherapy in a cohort of Taiwanese patients with newly-diagnosed acute ...myeloid leukemia (AML). IFIs are a significant complication in the management of immunocompromised cancer patients; such infections are associated with a high incidence of morbidity and mortality, particularly in many South-Asian countries, where IFI rates are increasing. We retrospectively analyzed IFI incidence data from 105 patients with newly diagnosed AML at a single center undergoing their first course of induction chemotherapy without primary antifungal prophylaxis between November 2008 and December 2014. Of 21 cases documented as proven/provable IFIs 16 (76%) were invasive aspergillosis, 2 (10%) were mucormycosis infections, and 3 (14%) were proven yeast infections. The lung was the most commonly affected site (n = 16; 76%); 2 patients (10%) developed fungal sinusitis. IFI cases were more often males (P = 0.020). In multivariate analysis, patients with neutropenia lasting>30 days were more than twice as likely to develop IFI (OR, 2.24 95% CI, 2.81-31.11, P<0.001). We also confirmed patients with smoker and receiving parenteral nutrition during chemotherapy were significant associated with IFIs. Our findings suggest that antifungal prophylaxis should be considered for patients with AML during induction chemotherapy, particularly in patients from Southeastern Asia, an area of potentially high IFI rates. We recommend that clinicians determine which patients receiving induction chemotherapy for AML are at high risk of developing IFI, to allow for targeted therapeutic prophylaxis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tryptanthrin, an alkaloid applied in traditional Chinese medicine, exhibits a variety of pharmacological activities. This study aimed to investigate the anti‐tumor activity of the tryptanthrin ...derivative (8‐cyanoindolo2,1‐bquinazoline‐6,12‐dione CIQ) in breast cancer cells. In both MDA‐MB‐231 and MCF‐7 breast cancer cells, CIQ inhibited cell viability and promoted caspase‐dependent apoptosis. At the concentration‐ and time‐dependent ways, CIQ increased the levels of p‐ERK, p‐JNK, and p‐p38 in breast cancer cells. We found that exposure to the JNK inhibitor or the ERK inhibitor partially reversed CIQ's viability. We also observed that CIQ increased reactive oxygen species (ROS) generation, and upregulated the phosphorylation and expression of H2AX. However, the pretreatment of the antioxidants did not protect the cells against CIQ's effects on cell viability and apoptosis, which suggested that ROS does not play a major role in the mechanism of action of CIQ. In addition, CIQ inhibited the invasion of MDA‐MB‐231 cells and decreased the expression of the prometastatic factors (MMP‐2 and Snail). These findings demonstrated that the possibility of this compound to show promise in playing an important role against breast cancer.
In this study, we interrogated the mechanism by which the immunosuppressant FTY720 mediates anticancer effects in oral squamous cell carcinoma (OSCC) cells. FTY720 differentially suppressed the ...viability of the OSCC cell lines SCC4, SCC25, and SCC2095 with IC
values of 6.1, 6.3, and 4.5 μM, respectively. This antiproliferative effect was attributable to the ability of FTY720 to induce caspase-dependent apoptosis. Mechanistic evidence suggests that FTY720-induced apoptosis was associated with its ability to inhibit Akt-NF-κB signaling, to facilitate the proteasomal degradation of the antiapoptotic protein Mcl-1, and to increase reactive oxygen species (ROS) generation. Both overexpression of Mcl-1 and inhibition of ROS partially protected cells from FTY720-induced caspase-9 activation, PARP cleavage and cytotoxicity. In addition, FTY720 induced autophagy in OSCC cells, as manifested by LC3B-II conversion, decreased p62 expression, and accumulation of autophagosomes. Inhibition of autophagy by bafilomycin A1 protected cells from FTY720-induced apoptosis. Together, these findings suggest an intricate interplay between autophagy and apoptosis in mediating the tumor-suppressive effect in OSCC cells, which underlies the translational potential of FTY720 in fostering new therapeutic strategies for OSCC.
The global, randomized NAPOLI‐1 phase 3 trial reported a survival benefit with liposomal irinotecan (nal‐IRI) plus 5‐fluorouracil/leucovorin (nal‐IRI+5‐FU/LV) in patients with metastatic pancreatic ...ductal adenocarcinoma (mPDAC) after previous gemcitabine‐based therapy. Median overall survival (OS) with nal‐IRI+5‐FU/LV was 6.1 vs 4.2 months with 5‐FU/LV alone (unstratified hazard ratio HR = 0.67, P = .012). Herein, we report efficacy and safety results from a post‐hoc subgroup analysis of Asian patients treated at Asian centers. Primary study endpoint was OS; secondary endpoints included progression‐free survival (PFS), objective response rate (ORR), and safety. Patients receiving nal‐IRI+5‐FU/LV (n = 34) had significantly longer median OS versus 5‐FU/LV (n = 35) (8.9 vs 3.7 months; unstratified HR = 0.51, P = .025). Patients had significantly increased median PFS with nal‐IRI+5‐FU/LV versus 5‐FU/LV (4.0 vs 1.4; unstratified HR = 0.48, P = .011), and increased ORR (8.8% vs 0; P = .114). nal‐IRI monotherapy (n = 50) numerically improved efficacy endpoints versus 5‐FU/LV (n = 48): median OS was 5.8 versus 4.3 months (HR = 0.83, P = .423) and median PFS was 2.8 versus 1.4 months (HR = 0.69, P = .155). Grade ≥3 neutropenia was reported more frequently with nal‐IRI+5‐FU/LV versus 5‐FU/LV (54.5% vs 3.4%), and incidence of grade ≥3 diarrhea was comparable between the two arms (3.0% vs 6.9%). This subgroup analysis confirms nal‐IRI+5‐FU/LV as an efficacious treatment option that improves survival in Asian patients with mPDAC that progressed after gemcitabine‐based therapy, with a safety profile agreeing with previous findings. The nal‐IRI+5‐FU/LV regimen should represent a new standard of care for these patients in Asia. (Clinicaltrials.gov: NCT01494506)
The global NAPOLI‐1 phase 3 trial (NCT01494506) evaluated the safety and efficacy of liposomal irinotecan (nal‐IRI) and 5‐fluorouracil/leucovorin (5‐FU/LV) compared with 5‐FU/LV in patients with metastatic pancreatic adenocarcinoma that progressed following gemcitabine‐based therapy. We report data from a post‐hoc subgroup analysis focusing on Asian patients at centers in South Korea and Taiwan. Our findings are consistent with those from the primary analysis and show that, despite association with higher incidence of manageable grade 3‐4 neutropenia, the nal‐IRI+5‐FU/LV regimen is an effective treatment option in Asian patients with gemcitabine‐failed metastatic pancreatic cancer.
Hispolon, a polyphenol compound isolated from Phellinus linteus, has been reported to exhibit antioxidant, antiproliferative, and antitumor activities. This study aimed to explore the antitumor ...effects of hispolon on glioblastoma multiforme (GBM) cells in vitro and in vivo. The results revealed that hispolon significantly inhibited GBM cell proliferation and induced apoptosis through caspase-9 and caspase-3 activation and PARP cleavage. Hispolon also induced cell cycle G2/M phase arrest in GBM cells, as supported by flow cytometry analysis and confirmed by a decrease in cyclin B1, cdc2, and cdc25c protein expressions in a dose- and time-dependent manner. Furthermore, hispolon suppressed the migration and invasion of GBM cells by modulating epithelial–mesenchymal transition (EMT) markers via wound healing, transwell assays, and real-time PCR. Moreover, hispolon significantly reduced tumor growth in DBTRG xenograft mice and activated caspase-3 in hispolon-treated tumors. Thus, our findings revealed that hispolon is a potential candidate for the treatment of GBM.
Bright & blue: A strategy for reducing metal‐chelate internal strain enables the preparation of blue emitting iridium(III) carbene complexes (see picture; Ir red, N light blue, F green). The ...phosphorescent OLED fabricated from one of these complexes shows remarkable CIE coordinates of (0.16, 0.13) and peak efficiencies of 6.0 % photons per electron, 6.3 cd A−1, and 4.0 lm W−1.
Aims and objectives
To measure the effect of chair resistance training (RT) on the quality of life (QoL) of older long‐term care residents with sarcopenic obesity (SO).
Background
Sarcopenia combined ...with obesity, commonly called SO, is considered to be related to health‐related QoL. Despite concerns regarding SO‐related long‐term healthcare issues, intervention studies on SO residents in nursing homes are scant in Taiwan.
Design
This research was a quasi‐experiment conducted according to the TREND Checklist. A total of 123 older persons were enrolled from six nursing facilities. The RT was implemented between October 2015–March 2016.
Method
The intervention group received progressive RT with sandbags/dumbbells twice a week for 3 months, whereas the comparison group received the usual care. QoL was the major outcome variable. Data were analysed using chi‐square test, Student's t test and generalised estimating equation (GEE).
Results
The various definition criteria for SO can influence the results of QoL in the older persons. From the body composition perspective, in the GEE analysis, the SO cut‐off points for neither skeletal muscle mass percentage (SMMp) nor appendicular skeletal muscle mass index demonstrated significant between‐group differences in the QoL variable after the 3‐month RT intervention. Between‐group analysis revealed a significant effect of time on anxiety/depression Exp(B): 0.41, 95% confidence interval: 0.18–0.93, p‐value < .05 in participants who met all three criteria of the definition of SO (low SMMp, low handgrip strength, and obesity). RT was one of the protective factors.
Conclusion
In the SO group, the effect of muscle strength on QoL is greater than the effect of changes in body composition after RT.
Relevance to clinical practice
This study analysed the influence of RT on QoL in subjects with different categories of SO. RT is one of the ways to promote QoL among the SO population. ClinicalTrials.gov Identifier: NCT02912338.
Most chemotherapeutic drugs for killing cancer cells are highly cytotoxic in normal cells, which limits their clinical applications. Therefore, a continuing challenge is identifying a drug that is ...hypersensitive to cancer cells but has minimal deleterious effects on healthy cells. The aims of this study were to evaluate the potential of 4β-hydroxywithanolide (4βHWE) for selectively killing cancer cells and to elucidate its related mechanisms.
Changes in survival, oxidative stress, DNA damage, and apoptosis signaling were compared between 4βHWE-treated oral cancer (Ca9-22) and normal fibroblast (HGF-1) cells. At 24 h and 48 h, the numbers of Ca9-22 cells were substantially decreased, but the numbers of HGF-1 cells were only slightly decreased. Additionally, the IC50 values for 4βHWE in the Ca9-22 cells were 3.6 and 1.9 µg/ml at 24 and 48 h, respectively. Time-dependent abnormal increases in ROS and dose-responsive mitochondrial depolarization can be exploited by using 4βHWE in chemotherapies for selectively killing cancer cells. Dose-dependent DNA damage measured by comet-nuclear extract assay and flow cytometry-based γ-H2AX/propidium iodide (PI) analysis showed relatively severer damage in the Ca9-22 cells. At both low and high concentrations, 4βHWE preferably perturbed the cell cycle in Ca9-22 cells by increasing the subG1 population and arrest of G1 or G2/M. Selective induction of apoptosis in Ca9-22 cells was further confirmed by Annexin V/PI assay, by preferential expression of phosphorylated ataxia-telangiectasia- and Rad3-related protein (p-ATR), and by cleavage of caspase 9, caspase 3, and poly ADP-ribose polymerase (PARP).
Together, the findings of this study, particularly the improved understanding of the selective killing mechanisms of 4βHWE, can be used to improve efficiency in killing oral cancer cells during chemoprevention and therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Colorectal cancer (CRC) is one of the most common malignancies worldwide. Isolinderalactone (ILL), a sesquiterpene isolated from the root extract of Lindera aggregata, has been reported to exhibit ...anti–proliferative and anti–metastatic activities in various cancer cell lines. However, the mechanisms associated with its antitumor effects on CRC cells remain unclear. ILL treatment significantly suppressed proliferation and induced cell cycle G2/M arrest in CRC cells by inhibiting the expression of cyclin B, p–cdc2, and p–cdc25c and up–regulating the expression of p21. In addition, ILL induced mitochondria–associated apoptosis through the up–regulation of cleaved –caspase–9 and –3 expression. ILL induced autophagy by increasing the levels of LC3B in CRC cells, which was partially rescued by treatment with an autophagy inhibitor (chloroquine). Furthermore, ILL increases the accumulation of reactive oxygen species (ROS) and activates the MAPK pathway. Application of the ROS scavenger, N–acetyl cysteine (NAC), effectively inhibited ILL toxicity and reversed ILL–induced apoptosis, cell cycle arrest, autophagy, and ERK activation. Taken together, these results suggest that ILL induces G2/M phase arrest, apoptosis, and autophagy and activates the MAPK pathway via ROS–mediated signaling in human CRC cells.
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