IL-6 mediated JAK/STAT3 signaling pathway in cancer patients with cachexia

CONCLUSION: STAT3 may be considered as a therapeutic target for cachectic patients with gastric, lung and breast cancer. Furthermore, IL-6 mediates STAT3 activation in cachectic gastric and breast cancer patients (Tab. 5, Fig. 2, Ref. 62)

Evaluation of Curcumin Therapeutic Effects on Histological Subtypes of Canine Mammary Gland Tumours

Canine mammary gland tumors (CMGTs) are the most frequent types of cancer in bitches and proposed as a model of human breast cancer. The anticancer effect of curcumin on human breast cancer has been extensively studied. The aim of this study was to evaluate the therapeutic effect of curcumin in two different histologies (simple carcinoma [SC] and squamous cell carcinoma [SCC]) of CMGTs. Primary canine mammary cells were isolated from the tumoral tissues surgically resected from two bitches (Case 1 and Case 2). Cell viability, apoptotic percentage, cell cycle progression and the changes in the cell morphology were evaluated. Curcumin inhibited the growth of both SC (Case 1) and SCC (Case 2) cells. However, Case 1 cells (43.48% +/- 3.87% at 0.5 mu M) were more sensitive to curcumin than Case 2 cells (59.36% +/- 2.09% at 0.5 mu M). Curcumin induced total apoptotic cell death through G0/G1 arrest, and this effect was more profound in Case 1 cells. Furthermore, cytoplasmic vacuolization, apoptotic bodies and membrane blebbing were observed in both cells following curcumin treatment. Our findings provide a novel approach for the effects of curcumin as a natural compound on CMGTs. Further investigations should be performed to investigate the molecular mechanisms of the differences in curcumin efficacy for different histological subtypes

The Predictive Role of MMP-2, MMP-9, TIMP-1 and TIMP-2 Serum Levels in the Complete Response of the Tumor to Chemotherapy in Breast Cancer Patients

Objective We investigated the serum levels of MMPs and TIMPs in breast cancer (BC) patients to predict the response rate to/after treatment with or without neoadjuvant chemotherapy. BC is the most common cancer in women and MMPs are responsible for the breakdown of ECM proteins during organogenesis and TIMPs are restricted the ECM destruction by MMPs. However, the predictive role of MMPs and TIMPs in the treatment response of BC patients has not identified. Methods This study consisted of 96 BC patients (34 neoadjuvant treatment and 62 surgically treated) and 35 healthy individuals. ELISA was used to determine the level of MMP-2, MMP-9, TIMP-1, and TIMP-2 from serum samples of BC patients. Results The mean levels of MMP-9 and TIMP-2 were significantly increased in all BC patients at diagnosis and after chemotherapy, but MMP-2 was considerably lower at diagnosis. There was only a significant difference in the TIMP-1 levels after chemotherapy as well as HER2 and ER status in the neoadjuvant and surgically treated group. Additionally, MMP-2 and MMP-9 serum levels negatively correlated with tumor size and metastatic lymph nodes in BC patients after chemotherapy. Conclusions BC patients with high levels of MMP-9 and TIMP-2 can be used to predict the stage of the tumor and CR to chemotherapy and higher TIMP-1 serum level after chemotherapy could be related to better response to chemotherapy

Anti-inflammatory effects of nobiletin on TLR4/TRIF/IRF3 and TLR9/IRF7 signaling pathways in prostate cancer cells

Background: Toll-like receptors (TLRs) are often expressed in natural immune cells as well as in tumor cells. TLR4 exhibits both tumor promoting and tumor-suppressing roles and higher TLR9 expression is an important marker of poor prognosis in prostate cancer (PCa). Nobiletin (NOB) is an O-methylated flavonoid and NOB has been proven to have anti-cancer effect in PCa cells. However, there is no study in the literature investigating the potential anti-inflammatory effects of NOB on the TLR signaling pathways in cancer. Therefore, we aimed to explore the potential anti-inflammatory effects of NOB on the TLR4/TRIF/IRF3 and TLR9/IRF7 signaling pathways in different types of PCa cell lines, for the first time. Material and methods: In the current study, the cytotoxic effect of NOB PC-3 (hormone-independent and metastatic) and LNCaP cells (hormone-dependent) was evaluated by WST-1 assay. Furthermore, the inhibitory effects of NOB on TLR4/TRIF/IRF3 and TLR9/IRF7signaling pathway were determined by RT-PCR, western blotting and ELISA analysis. Results: NOB demonstrated an inhibitory effect on PCa cell growth and LNCaP cells were more sensitive to NOB than PC-3 cells due to androjen receptor status. Furthermore, NOB alone could suppress TLR4/TRIF/IRF3 and TLR9/IRF7 signaling pathways through the downregulation of their associated pathways (mRNA and related protein levels) and the release of IFN-alpha and IFN-beta compared to LPS or CpG-ODN stimulated PCa cells. Conclusions: NOB potentially inhibited TLR4 and TL9-dependent signaling pathway in PCa cells. However, the efficacy of NOB was different in PCa cells due to the hormone status and aggressive features

Comparison of the anti-cancer activity of 5-aminolevulinic acid-mediated photodynamic therapy after continuous wave and pulse irradiation in different histological types of canine mammary sarcoma tumors

Canine mammary sarcoma tumors (CMST) are the most aggressive tumors with poor prognosis in dogs. Due to inadequate treatment options for CMST, recent studies have focused on alternative treatment strategies. We previously determined the optimized protocol of 5-ALA-based photodynamic therapy (PDT) in canine liposarcoma. However, its molecular mechanisms in the treatment of different histological types of CMST remain unclear.In this context, we, for the first time, assessed 5-aminolevulinic acid (5-ALA)-PDT-mediated anti-cancer activity and its molecular mechanism after continuous wave (CW) and pulse radiation (PR) on three different histological types (liposarcoma, chondrosarcoma, and osteosarcoma) of CMST cells by WST-1, Annexin V, ROS, acridine orange/propidium iodide staining, RT-PCR, and western blot analysis.Our findings showed that 5-ALA/PDT significantly suppressed the proliferation of CMST cells (p < 0.01) and induced apoptosis via increased ROS level and overexpression of Caspase-9 and Caspase-3 mRNA and cleaved protein levels in especially liposarcoma and chondrosarcoma cells following CW and PR irradiation at 9 J/cm(2). However, the response of CMST cells to 5-ALA was different upon CW and PR irradiation due to differences in their origin.Collectively, our findings provided the first evidence that 5-ALA-based PDT could be used as an alternative treatment strategy, especially liposarcoma and chondrosarcoma. However, further in vitro and in vivo studies are required to elucidate the underlying molecular mechanism of the efficacy of 5-ALA in CMST cells at the molecular level