Current and future targets and therapies in metastatic colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer and the second cause of cancer-related deaths worldwide. Despite early diagnosis and treatment improvement, the majority of patients will still suffer from metastatic disease (mCRC), which has a poor prognosis. Molecular diversity of CRC requires personalized targeted approach for improving patient outcomes.

Depletion of the transcriptional coactivators CREB-binding protein or EP300 downregulates CD20 in diffuse large B-cell lymphoma cells and impairs the cytotoxic effects of anti-CD20 antibodies.

Monoclonal antibodies targeting CD20 are central in the treatment of B-cell lymphomas. In diffuse large B-cell lymphoma (DLBCL), inactivating mutations of the histone acetyltransferases CREB-binding protein (CBP) and EP300 are common. Moreover, knockdown of CBP in DLBCL has been shown to result in aberrant transcriptional silencing.

Clinical outcomes of an intraoperative surgical margin assessment using the fresh frozen section method in patients with invasive breast cancer undergoing breast-conserving surgery - a single center analysis.

Breast conserving treatment (BCT) is a safe standard therapeutic method in patients with early invasive breast cancer. However, it is associated with an increased risk of residual neoplastic tissues in surgical margins. The aim of this study was to assess the outcome of the use of the intraoperative pathologic analysis by the frozen section (FS) method for evaluation of the extent of the primary lumpectomy.

Radiotherapy in lymphoepithelioma-like carcinoma of the skin: review of the literature and report of a recurrent and metastatic case.

Primary lymphoepithelioma-like carcinoma of the skin (LELCS) is a very rare cutaneous neoplasm. Only about 70 cases have been documented in the literature. There are no prospective data regarding treatment methods.

OLIG2 is a novel immunohistochemical marker associated with the presence of PAX3/7-FOXO1 translocation in rhabdomyosarcomas.

Background: The most frequent histological types of rhabdomyosarcoma (RMS) in children are embryonal (ERMS) and alveolar (ARMS) tumours. The majority of ARMS are characterized by the presence of PAX3/7-FOXO1 gene fusion and have a worse prognosis than fusion gene-negative ARMS. However, identification of PAX3/7-FOXO1 fusion status is challenging when using formalin-fixed, paraffin-embedded (FFPE) material.

Effects of the Proteasome Inhibitor Bortezomib in Combination with Chemotherapy for the Treatment of Mantle Cell Lymphoma: A Meta-analysis.

Objective: The efficacy and the safety of bortezomib-based chemotherapy were characterized in mantle cell lymphoma (MCL) patients.

Materials And Methods: The PubMed, Cochrane Library, Clinical Key, Science Direct, Oxford Journals, and China National Knowledge Internet databases were searched up to 1 May 2019. The selected trials needed to match the inclusion criteria and be carried out to evaluate quality appraisal and the synthesis of efficacy and safety.

Autocrine activin A signalling in ovarian cancer cells regulates secretion of interleukin 6, autophagy, and cachexia.

Background: The majority of patients with advanced cancer develop cachexia, a weight loss syndrome that severely reduces quality of life and limits survival. Our understanding of the underlying mechanisms that cause the condition is limited, and there are currently no treatment options that can completely reverse cachexia. Several tumour-derived factors and inflammatory mediators have been suggested to contribute to weight loss in cachectic patients.

Maternal factors, ultrasound and placental function parameters in early pregnancy as predictors of birth weight in low-risk populations and among patients with pre-gestational diabetes.

Objectives: The aim of our work was to assess the usefulness of maternal factors, ultrasound and placental function parameters during early pregnancy as predictors of birth weight in populations of healthy pregnant women and women suffering from pregestational diabetes.

Material And Methods: A study group comprised 97 healthy women and 160 women with pregestational diabetes (PGDM, type 1), all in singleton pregnancy. Ultrasound examination was performed between weeks 11 and 14, and in weeks 20 and 30 of gestation, based on recommendations of the Polish Society of Gynecologists and Obstetricians, Ultrasonography Division.

Prognostic Impact of Canonical TGF-β Signaling in Urothelial Bladder Cancer.

: Dysregulation of TGF-β signaling plays multiple roles in cancer development and progression. In the canonical TGF-β pathway, TGF-β regulates the expression of hundreds of target genes via interaction with Smads, signal transducers and transcriptional modulators. We evaluated the association of TGF-β1, Smad2, and Smad4, the key components of canonical TGFβ pathway, with clinicopathologic characteristics of urothelial bladder cancer, and assessed their prognostic value in prediction of patients' outcome.

Optimizing laboratory defined macroprolactin algorithm.

Introduction: Macroprolactinaemia is a well-known analytical problem in diagnostics of hyperprolactinaemia usually detected with polyethylene glycol (PEG) precipitation method. Since there is no harmonization in macroprolactin detection and reporting results, this study proposes and evaluates the usefulness of in-house developed algorithm. The aims were to determine the most suitable way of reporting results after PEG treatment and the possibilities of rationalizing the precipitation procedure.

Prognostic factors in patients with T1 glottic cancer treated with radiotherapy.

Purpose: Presentation of long-term results of radiation treatment in patients with T1 glottic cancer and evaluation of prognostic factors.

Methods: We performed a retrospective analysis in a group of 569 patients with T1 squamous cell glottic carcinoma treated with radiotherapy at the Center of Oncology in Cracow between 1977 and 2007. In all, 503 (88%) patients presented with T1a stage disease and 66 (12%) with T1b.

miR-625-3p and lncRNA GAS5 in Liquid Biopsies for Predicting the Outcome of Malignant Pleural Mesothelioma Patients Treated with Neo-Adjuvant Chemotherapy and Surgery.

Combining neo-adjuvant chemotherapy and surgery is part of multimodality treatment of malignant pleural mesothelioma (MPM), but not all patients benefit from this approach. In this exploratory analysis, we investigated the prognostic value of circulating miR-625-3p and lncRNA GAS5 after neo-adjuvant chemotherapy. 36 MPM patients from the SAKK 17/04 trial (NCT00334594), whose blood was available before and after chemotherapy were investigated.

Labeled as lucky: contradictions between what women and healthcare professionals experience regarding the need for help after the early stages of gynecological cancer.

Purpose: To explore how participants perceived a nurse-led, person-centered intervention, Guided Self-Determination Gynecological Cancer (GSD-GYN-C) and how participants felt it influenced the challenges they faced and their rehabilitation after gynecological cancer surgery.

Methods: Participants were invited from a previously conducted randomized trial where GSD-GYN-C improved physical quality of life in the intervention group. Ten semi-structured interviews were conducted, transcribed, and analyzed using thematic analysis.

Apoptosis induction and cell cycle arrest of pladienolide B in erythroleukemia cell lines.

Splicing of pre-mRNA into functional mRNA, carried out by the spliceosome, represents a crucial step in eukaryotic gene expression. Mutations and other deregulation in some of the spliceosome components have been identified in multiple pathologies, including hematological malignancies. In this context, we evaluated the therapeutic potential of a splicing inhibitor, Pladienolide B (Pla-B), in two erythroleukemia cell lines.

Prostate cancer prognosis in men with other malignancies prior to radical prostatectomy.

Objectives: Cancer survivors are often diagnosed with subsequent prostate cancer. To improve medical care of these patients, we examined the oncological outcomes in men with prostate cancer and a cancer history.

Patients And Methods: We retrospectively analyzed data from 25,422 prostate cancer patients, who underwent a radical prostatectomy between 1992 and 2016.

A retrospective cohort study of PD-L1 prevalence, molecular associations and clinical outcomes in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape Project.

Introduction: The PD-L1 biomarker is an important factor in selecting patients with non-small cell lung cancer for immunotherapy. While several reports suggest that PD-L1 positivity is linked to a poor prognosis, others suggest that PD-L1 positive status portends a good prognosis.

Methods: PD-L1 positivity prevalence, assessed via immunohistochemistry (IHC) on tissue microarrays (TMAs), and its association with clinicopathological characteristics, molecular profiles and patient outcome- Relapse-free Survival (RFS), Time-to-Relapse (TTR) and Overall Survival (OS)- is explored in the ETOP Lungscape cohort of stage I-III non-small cell lung cancer (NSCLC).

A phase III randomized, multicentre, double blind, active controlled trial to compare the efficacy and safety of two different anagrelide formulations in patients with essential thrombocythaemia - the TEAM-ET 2·0 trial.

Anagrelide is an established treatment option for essential thrombocythaemia (ET). A prolonged release formulation was developed with the aim of reducing dosing frequency and improving tolerability, without diminishing efficacy. This multicentre, randomized, double blind, active-controlled, non-inferiority trial investigated the efficacy, safety and tolerability of anagrelide prolonged release (A-PR) over a reference product in high-risk ET patients, either anagrelide-naïve or -experienced.

Afatinib in NSCLC With HER2 Mutations: Results of the Prospective, Open-Label Phase II NICHE Trial of European Thoracic Oncology Platform (ETOP).

Introduction: Mutations in erb-b2 receptor tyrosine kinase 2 (HER2) oncogene are observed in approximately 3% of lung adenocarcinomas or mixed tumors with adenocarcinoma component. Activity of various biologically distinct HER2 inhibitors, including the pan-HER inhibitor afatinib, has been reported in several retrospective trials or small series in advanced pretreated NSCLC with HER2 mutations. We report the first prospective evaluation of afatinib for the treatment of this molecularly defined entity.

The estrogen receptor coactivator AIB1 is a new putative prognostic biomarker in ER-positive/HER2-negative invasive lobular carcinoma of the breast.

Purpose: According to the 2017 St Gallen surrogate definitions of the intrinsic subtypes, Ki67, progesterone receptor (PR) and Nottingham histological grade (NHG) are used for prognostic classification of estrogen receptor (ER) positive/HER2-negative breast cancer into luminal A- or luminal B-like. The aim of the present study was to investigate if additional biomarkers, related to endocrine signaling pathways, e.g.

Trends of incidence and survival of patients with chronic myelomonocytic leukemia between 1999 and 2014: A comparison between Swiss and American population-based cancer registries.

Background: Chronic myelomonocytic leukemia (CMML) is a rare hematopoietic malignancy. Treatment with hypomethylating agents (HMA) was introduced between 2004 and 2006 but its impact on population-based survival remains controversial. The aim of this study was to investigate epidemiological characteristics and survival before and after introduction of HMA treatment.

Effects of neratinib on health-related quality of life in women with HER2-positive early-stage breast cancer: longitudinal analyses from the randomized phase III ExteNET trial.

Background: We report longitudinal health-related quality-of-life (HRQoL) data from the international, randomized, double-blind, placebo-controlled phase III ExteNET study, which demonstrated an invasive disease-free survival benefit of extended adjuvant therapy with neratinib over placebo in human epidermal growth factor receptor-2-positive early-stage breast cancer.

Patients And Methods: Women (N  = 2840) with early-stage HER2-positive breast cancer who had completed trastuzumab-based adjuvant therapy were randomly assigned to neratinib 240  mg/day or placebo for 12  months. HRQoL was an exploratory end point.

Focus of infection and microbiological etiology in community-acquired infections in hospitalized adult patients in the Faroe Islands.

Background: The aim of the present study was to gain national data on the clinical and microbiological characteristics of community-acquired infections in the Faroe Islands and to compare these data with data from other geographical areas.

Methods: A prospective, observational study involving all patients > = 16 years admitted at the Department of Medicine at the National Hospital, Torshavn, Faroe Islands from October 2013 until April 2015.

Results: Of 5279 admissions, 1054 cases were with community-acquired infection and were included in the study.

Immunohistochemical detection of ALK protein identifies APC mutated medulloblastoma and differentiates the WNT-activated medulloblastoma from other types of posterior fossa childhood tumors.

Expression of the ALK gene strongly correlates with the WNT-activated medulloblastomas, which are routinely identified by detection of CTNNB1 mutation. However, some tumors have mutations in other than CTNNB1 genes. Therefore, we investigated if ALK expression may identify WNT-activated tumors without CTNNB1 mutation.

Epidemiology of community-acquired sepsis in the Faroe Islands - a prospective observational study.

Introduction: The aim of the study was to gather nation-wide epidemiological and clinical data in order to characterize community-acquired sepsis in the Faroe Islands, and to compare these data with epidemiological studies performed in other geographical areas.

Methods: A prospective, observational study conducted from October 2013 until April 2015 to characterize sepsis, and to calculate incidence rates for community-acquired sepsis of any severity, community-acquired severe sepsis, community-acquired septic shock and community-acquired sepsis without community-acquired severe sepsis or community-acquired septic shock.

Results: Of 5279 admissions, 583 cases fulfilled the criteria for community-acquired sepsis of any severity.

Quantitative Analysis of Tumor-associated Tissue Eosinophilia in Recurring Bladder Cancer.

The relatively high incidence of recurrence of bladder cancer is a serious problem in clinical practice. At present, there are no objective microscopic criteria for evaluation of the tendency for local relapse. Besides the phenotypic properties of the tumor parenchymal cells, possible signs in regard to recurrence could also be derived from the peculiarities of the tumor stroma.