Kjelleruphays2547

Conversely, nausea and vomiting occurring within the first 42 days of lapatinib plus capecitabine therapy was significantly associated with worsened OS (HR [95% CI] Grade 1 = 1.08 [0.82-1.42], Grade 2+ = 1.52 [1.13-2.03]; p = 0.027). Conclusions Rash and hand-foot syndrome occurring early after the initiation of on lapatinib plus capecitabine were significantly associated with improved OS, while early nausea and vomiting was associated with worse OS. In HER2-positive ABC patients initiating lapatinib plus capecitabine, consideration should be given to more closely monitoring patients at risk of nausea and vomiting, while rash and hand foot syndrome are AE associated with improved survival. © The author(s).The increasing incidence of hepatocellular carcinoma (HCC) is a major challenge worldwide. In the past few years, an increasing number of studies have suggested that circular RNAs (circRNAs) play an important role in the development of human tumors, including HCC, but our understanding of their function is still limited. In this study, we investigated differences in the expression of circRNA MAN2B2 (circMAN2B2) in hepatocellular tissues and paired normal tissues. We found that knockdown of circMAN2B2 expression in the HCC cell lines Hep-G2 and Huh-7 significantly inhibited cell proliferation by sponging (miRNA) miR-217 and inhibiting its function. Through a series of experiments, we also demonstrated that miR-217 functioned as a tumor suppressor molecule in HCC cells and regulated the expression of mitogen-activated protein kinase 1 (MAPK1). selleck compound Restoration of MAPK1 rescued repression of cell proliferation induced by circMAN2B2 knockdown. In summary, our study indicated that circMAN2B2 acted as an onco-miRNA in HCC by sponging miRNA-217 to promote MAPK1 expression. © The author(s).Background The influence of body composition parameters in cancer prognosis attracted researchers' attention. This study investigated the role of visceral fat and skeletal muscle in the prognosis and efficacy of chemotherapy in metastatic gastric cancer (MGC). Methods This study included MGC patients without gastrectomy treated with EOF regimen (epirubicin, oxaliplatin and fluorouracil), who participated in a Phase II clinical trial (NCT00767377) with available PACS image data. The visceral fat area (VFA) and skeletal muscle area (SMA) were measured using standard computed tomography (CT). Results A total of 46 patients were enrolled in the study. Patients with low baseline VFA and SMA had significantly shorter PFS and OS. In addition, the loss of VFA and SMA also predicts significantly shorter PFS and OS. A prognostic index that included two risk factors, severe loss of VFA and SMA, was used to categorize the patients into two groups good-risk group (0 risk factors), poor-risk group (1 or 2 risk factors). Compared with the good-risk group, the poor-risk group displayed a 3.562-fold-increased risk of progression [hazard ratio (HR) 3.652, 95 % CI 1.653-7.678; P =0.001] and 2.859-fold-increased risk of death [hazard ratio (HR) 2.859, 95 % CI 1.271-6.434; P =0.011]. Conclusion Low baseline VFA and SMA, as well as the severe loss of VFA and SMA predict poor prognosis for MGC patients treated by EOF regimen. In patients with severe loss of VFA and/or SMA after 2-cycle chemotherapy, the decision of subsequent chemotherapy should be made after deliberate consideration. © The author(s).Background Lymph node examination is a prognostic indicator for colon cancer (CC) patients. The aim of this study was to develop and validate a preoperative risk prediction model for inadequate lymph node examination. Methods 24284 patients diagnosed as stage I-III CC between 2010-2014 were extracted from SEER database and randomly divided into development cohort (N=12142) and internal validation cohort (N=12142). 680 patients diagnosed as stage I-III CC between 2012-2014 were extracted from our hospital as external validation cohort. Logistic regression analysis was performed and risk score of each factor was calculated according to model formula. Model discrimination was assessed using C-statistics. Results Preoperative risk factors were identified as gender, age, tumor site and tumor size. Patients with total risk score of 0-6 were considered as low risk group while patients scored ≥13 were considered as high risk group. The model had good discrimination and calibration in all cohorts and could apply to patients in the SEER database (American population) and patients in our hospital (Chinese population). Conclusions The model could accurately predict the risk of inadequate lymph node examination before surgery and might provide useful reference for surgeons and pathologists. © The author(s).Efficacious anticancer therapies for targeting plasma membrane receptors with antibody based therapeutics are often contingent on sufficient endocytic delivery of receptor and conjugate to lysosomes. This results in downregulation of receptor activity and, in the case of antibody-drug conjugates (ADCs), intracellular release of a drug payload. The oncogenic receptor HER2 is a priority therapeutic target in breast cancer. Known as an "endocytosis resistant" receptor, HER2 thwarts the receptor downregulating efficiency of the frontline treatment trastuzumab and reduces the potential of trastuzumab-based therapies such as trastuzumab-emtansine. We previously demonstrated that strategically inducing trastuzumab and HER2 crosslinking in breast cancer cells promoted endocytosis and lysosomal delivery of the HER2-trastuzumab complex, stimulating downregulation of the receptor. Here we reveal that HER3, but not EGFR, is also concomitantly downregulated with HER2 after crosslinking. This is accompanied by strong activation of MEK/ERK pathway that we show does not directly contribute to HER2/trastuzumab endocytosis. We show that crosslinking induced trastuzumab endocytosis occurs via clathrin-dependent and independent pathways and is an actin-dependent process. Detailed ultrastructural studies of the plasma membrane highlight crosslinking-specific remodelling of microvilli and induction of extensive ruffling. Investigations in a cell model of acquired trastuzumab resistance demonstrate, for the first time, that they are refractory to crosslinking induced HER2 endocytosis and downregulation. This implicates further arrest of HER2 internalisation in developing trastuzumab resistance. Overall our findings highlight the potential of receptor crosslinking as a therapeutic strategy for cancer while exposing the ability of cancer cells to develop resistance via endocytic mechanisms. © The author(s).