Notes

IntelligentPooling: Useful Thompson Testing with regard to mHealth.
The identified connection between Nrp2, insulin receptor signaling and autophagy may guide the development of novel combination-treatment strategies for aggressive CRC.The aim of this retrospective study was to investigate the tolerability and survival outcomes of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment in patients with a performance status ≥ 2. The data for 517 patients treated with EGFR-TKIs between January 2011 and January 2018 at a regional hospital in northern Taiwan were analyzed. Clinical and pathological features were collected, and univariate as well as multivariable analyses were undertaken to identify potential prognostic factors. The overall objective response rate, median progression-free survival (PFS), and median overall survival (OS) were 56.3%, 11.4 months, and 15.3 months, respectively. The mutation status (exon 19 deletion), locally advanced disease, dose adjustment, and the lack of liver and pleural metastasis were independent and favorable prognostic factors for PFS. Age less then 60 years, mutation status (exon 19 deletion), dose adjustment, and lack of lung, liver, and no pleural metastasis were independent and favorable prognostic factors for OS. GFR-TKIs demonstrated acceptable efficacy and safety in the current cohort. Dose adjustment was identified as an independent prognostic factor for both PFS and OS, regardless of which EGFR-TKIs were used. The current research provided novel evidence of the clinical prescription of frontline EGFR-TKIs for EGFR-mutated lung adenocarcinoma patients with a PS score ≥2.Despite advances in the curative approach, the survival rate of advanced colorectal cancer (CRC) patients is still poor, which is likely due to the emergence of cancer cell clones resistant to the available therapeutic options. We have already shown that CD44v6-positive CRC stem cells (CR-CSCs) are refractory toward standard anti-tumor therapeutic agents due to the activation of the PI3K pathway together with high HER2 expression levels. Tumor microenvironmental cytokines confer resistance to CR-CSCs against HER2/PI3K targeting by enhancing activation of the MAPK pathway. Here, we show that the CSC compartment, spared by BRAF inhibitor-based targeted therapy, is associated with increased expression levels of CD44v6 and Myc and retains boosted clonogenic activity along with residual tumorigenic potential. Inhibition of Myc transcription, downstream of the MAPK cascade components, and PI3K pathway activity was able to overcome the protective effects of microenvironmental cytokines, affecting the survival and the clonogenic activity of CR-CSCs, regardless of their mutational background. Likewise, the double targeting induced stabilization of mouse tumor avatars. Altogether, these data outline the rationale for dual kinase targeting of CR-CSCs to prevent their adaptive response, which would lead to disease progression.
Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, highly aggressive embryonal brain tumor most commonly presenting in young children.

We performed a nationwide, population-based study of AT/RT (ICD-O-3 code 9508/3) in Taiwan using the Taiwan Cancer Registry Database and the National Death Certificate Database.

A total of 47 cases (male/female = 2918; median age at diagnosis, 23.3 months (IQR 12.5-87.9)) were diagnosed with AT/RT between 1999 and 2014. AT/RT had higher prevalence in males (61.70%), in children < 36 months (55.32%), and at infratentorial or spinal locations (46.81%). selleck products Survival analyses demonstrated that patients ≥ 3 years of age (
= 21 (45%)) had a 5y-OS of 41% (
< 0.0001), treatment with radiotherapy only (
= 5 (11%)) led to a 5y-OS of 60%, treatment with chemotherapy with or without radiotherapy (
= 27 (62%)) was associated with a 5y-OS of 45% (
< 0.0001), and patients with a supratentorial tumor (
= 11 (23%)) had a 5y-OS of 51.95%. Predictors of better survival on univariate Cox proportional hazard modeling and confirmed with multivariate analysis included older age (≥1 year), supratentorial sites, and the administration of radiotherapy, chemotherapy, or both. Gender had no effect on survival.

Older age, supratentorial site, and treatment with radiotherapy, chemotherapy, or both significantly improves the survival of patients with AT/RT.
Older age, supratentorial site, and treatment with radiotherapy, chemotherapy, or both significantly improves the survival of patients with AT/RT.Infection with Epstein-Barr virus (EBV) worsens the prognosis in chronic lymphocytic leukemia (CLL), but the underlying mechanisms are not yet established. We intended to assess whether EBV affects the course of CLL by the deregulation of the CTLA-4/CD86 signaling pathway. We used polymerase chain reaction to measure the load of EBV DNA in the blood of 110 newly diagnosed patients with CLL. The expression of CTLA-4 and CD86 antigen on lymphocytes was assessed with flow cytometry. Additionally, CTLA-4 and CD86 serum concentrations were measured through enzyme-linked immunosorbent assays. Fifty-four percent of the patients had detectable EBV DNA [EBV(+)]. In EBV(+) patients the CTLA-4 and CD86 serum concentrations and their expressions on investigated cell populations were significantly higher than in EBV(-) patients. EBV load correlated positively with unfavorable prognostic markers of CLL and the expression of CTLA-4 on CD3+ lymphocytes (r = 0.5339; p = 0.027) and CD86 on CD19+ cells (r = 0.6950; p less then 0.001). During a median follow-up period of 32 months EBV(+) patients were more likely to require treatment or have lymphocyte doubling (p less then 0.001). Among EBV(+) but not EBV(-) patients, increased expressions of CTLA-4 lymphocytes were associated with elevated risks of progression. We propose that EBV coinfection may worsen prognosis in CLL patients, partly due to EBV-induced up-regulation of CTLA-4 expression.Aim To assess the outcomes of 737 consecutive patients with DCIS, with particular attention to the type of recurrences, other malignancies and causes of deaths. Material and Methods A retrospective analysis of 737 consecutive DCIS patients treated in one institution in the years 1996-2011 was carried out. The cumulative recurrence risk, DFS, OS depending on the method of treatment (mastectomy, breast-conserving treatment (BCT), breast-conserving surgery (BCS)) and cause of death were assessed. Results Sixty-six recurrences (42% DCIS, 58% invasive) were reported 61 in the breast and 5 outside the breast. The cumulative recurrence risk after a 15-year observation after mastectomy, BCT and BCS was 3.2%, 19.5% and 31.2%, respectively (p less then 0.001). The 15-year DFS after mastectomy, BCT and BCS was 72%, 65% and 48%, respectively (p less then 0.001). The 15-year OS after mastectomy, BCT and BCS was 75%, 83% and 70%, respectively (p = 0.329). Deaths due to DCIS progression were reported in four (0.5%) of the overall patients and in 10.5% of patients with invasive recurrences. The majority of deaths were linked to the age of the patients or other diseases, including other neoplasms, but not DCIS. Conclusions The highest number of recurrences was reported in patients after BCS, despite the fact that it was the lowest-risk group. In total, 79% of local recurrences were true recurrences and 58% were invasive recurrences. Local recurrences were effectively treated without an influence on the OS. The percentage of deaths due to DCIS was low and mainly concerned patients with locoregional and distant failure.Fibroepithelial lesions (FL) of the breast, in particular, phyllodes tumors (PT) and fibroadenomas, pose a significant diagnostic challenge. There are no generally accepted criteria that distinguish benign, borderline, malignant PT and fibroadenomas. Combined genome-wide DNA methylation and copy number variant (CNV) profiling is an emerging strategy to classify tumors. We compiled a series of patient-derived archival biopsy specimens reflecting the FL spectrum and histological mimickers including clinical follow-up data. DNA methylation and CNVs were determined by well-established microarrays. Comparison of the patterns with a pan-cancer dataset assembled from public resources including "The Cancer Genome Atlas" (TCGA) and "Gene Expression Omnibus" (GEO) suggests that FLs form a methylation class distinct from both control breast tissue as well as common breast cancers. Complex CNVs were enriched in clinically aggressive FLs. Subsequent fluorescence in situ hybridization (FISH) analysis detected respective aberrations in the neoplastic mesenchymal component of FLs only, confirming that the epithelial component is non-neoplastic. Of note, our approach could lead to the elimination of the diagnostically problematic category of borderline PT and allow for optimized prognostic patient stratification. Furthermore, the identified recurrent genomic aberrations such as 1q gains (including MDM4), CDKN2a/b deletions, and EGFR amplifications may inform therapeutic decision-making.Cancer is the second leading cause of death globally. One of the main hallmarks in cancer is the functional deregulation of crucial molecular pathways via driver genetic events that lead to abnormal gene expression, giving cells a selective growth advantage. Driver events are defined as mutations, fusions and copy number alterations that are causally implicated in oncogenesis. Molecular analysis on tissues that have originated from a wide range of anatomical areas has shown that mutations in different members of several pathways are implicated in different cancer types. In recent decades, significant efforts have been made to incorporate this knowledge into daily medical practice, providing substantial insight towards clinical diagnosis and personalized therapies. However, since there is still a strong need for more effective drug development, a deep understanding of the involved signaling mechanisms and the interconnections between these pathways is highly anticipated. Here, we perform a systemic analysis on cancer patients included in the Pan-Cancer Atlas project, with the aim to select the ten most highly mutated signaling pathways (p53, RTK-RAS, lipids metabolism, PI-3-Kinase/Akt, ubiquitination, b-catenin/Wnt, Notch, cell cycle, homology directed repair (HDR) and splicing) and to provide a detailed description of each pathway, along with the corresponding therapeutic applications currently being developed or applied. The ultimate scope is to review the current knowledge on highly mutated pathways and to address the attractive perspectives arising from ongoing experimental studies for the clinical implementation of personalized medicine.KRAS mutations account for the most frequent mutations in human cancers, and are generally correlated with disease aggressiveness, poor prognosis, and poor response to therapies. KRAS is required for adult hematopoiesis and plays a key role in B cell development and mature B cell proliferation and survival, proved to be critical for B cell receptor-induced ERK pathway activation. In mature B cell neoplasms, commonly seen in adults, KRAS and RAS-MAPK pathway aberrations occur in a relevant fraction of patients, reaching high recurrence in some specific subtypes like multiple myeloma and hairy cell leukemia. As inhibitors targeting the RAS-MAPK pathway are being developed and improved, it is of outmost importance to precisely identify all subgroups of patients that could potentially benefit from their use. Herein, we review the role of KRAS and RAS-MAPK signaling in malignant hematopoiesis, focusing on mature B cell lymphoproliferative disorders. We discuss KRAS and RAS-MAPK pathway aberrations describing type, incidence, mutual exclusion with other genetic abnormalities, and association with prognosis.
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