Multikinase Treatment of Glioblastoma: Evaluating the Rationale for Regorafenib.

We explored the rationale for treating glioblastoma (GBM) with regorafenib. In 103 newly diagnosed GBM patients, we assessed mutations, copy number variants (CNVs), fusions, and overexpression in 46 genes encoding protein kinases (PKs) potentially targeted by regorafenib or its metabolites and performed a functional enrichment analysis to assess their implications in angiogenesis. We analyzed regorafenib's binding inhibitory activity and target affinity for these 46 PKs and focused on a subset of 18 genes inhibited by regorafenib at clinically achievable concentrations and on 19 genes involved in angiogenesis.

The C250T Mutation of Might Grant a Better Prognosis to Glioblastoma by Exerting Less Biological Effect on Telomeres and Chromosomes Than the C228T Mutation.

Unlabelled: The aim of this study was to determine how mutations impact glioblastoma prognosis.

Materials And Methods: mutations were assessed in a retrospective cohort of 258 uniformly treated glioblastoma patients. RNA-sequencing and whole exome sequencing results were available in a subset of patients.

Gal-1 Expression Analysis in the GLIOCAT Multicenter Study: Role as a Prognostic Factor and an Immune-Suppressive Biomarker.

Glioblastoma (GBM) is the most frequent primary malignant brain tumor and has a dismal prognosis. Unfortunately, despite the recent revolution of immune checkpoint inhibitors in many solid tumors, these have not shown a benefit in overall survival in GBM patients. Therefore, new potential treatment targets as well as diagnostic, prognostic, and/or predictive biomarkers are needed to improve outcomes in this population.

In silico validation of RNA-Seq results can identify gene fusions with oncogenic potential in glioblastoma.

RNA-Sequencing (RNA-Seq) can identify gene fusions in tumors, but not all these fusions have functional consequences. Using multiple data bases, we have performed an in silico analysis of fusions detected by RNA-Seq in tumor samples from 139 newly diagnosed glioblastoma patients to identify in-frame fusions with predictable oncogenic potential. Among 61 samples with fusions, there were 103 different fusions, involving 167 different genes, including 20 known oncogenes or tumor suppressor genes (TSGs), 16 associated with cancer but not oncogenes or TSGs, and 32 not associated with cancer but previously shown to be involved in fusions in gliomas.

Safety and Efficacy of Crizotinib in Combination with Temozolomide and Radiotherapy in Patients with Newly Diagnosed Glioblastoma: Phase Ib GEINO 1402 Trial.

Background: MET-signaling and midkine (ALK ligand) promote glioma cell maintenance and resistance against anticancer therapies. ALK and c-MET inhibition with crizotinib have a preclinical therapeutic rationale to be tested in newly diagnosed GBM.

Methods: Eligible patients received crizotinib with standard radiotherapy (RT)/temozolomide (TMZ) followed by maintenance with crizotinib.

Influence of age on treatment and prognosis of invasive cervical cancer.

Objective: Invasive cervical cancer is considered a young women's disease, however up to 20 % of cases develop cervical cancer at advanced ages. The aim was to characterize invasive cervical cancer in women aged 65 and older assessing age-specific survival differences.

Study Design: A retrospective study including cervical cancer patients was conducted at Hospital del Mar Barcelona from July-2007 to December-2016.

Developing indicators for quality assurance in cytopathology. Catalan Society of Cytopathology.

Background: Quality control in cytology must be established through reliable and easily measurable indicators.

Methods: From the Catalan Society of Cytopathology a group of experts has been established to write a document with 13 indicators that cover the entire cytological process, based on its Cytopathology Quality Guide. It has been elaborated through guides and documents with scientific evidence and DELPHI methodology in order to reach a structured consensus on the opinions of a group of experts.

Glioblastoma TCGA Mesenchymal and IGS 23 Tumors are Identifiable by IHC and have an Immune-phenotype Indicating a Potential Benefit from Immunotherapy.

Purpose: Molecular subtype classifications in glioblastoma may detect therapy sensitivities. IHC would potentially allow the identification of molecular subtypes in routine clinical practice.

Experimental Design: Formalin-fixed, paraffin-embedded tumor samples of 124 uniformly treated, newly diagnosed patients with glioblastoma were submitted to RNA sequencing, IHC, and immune-phenotyping to identify differences in molecular subtypes associated with treatment sensitivities.

Prognostic value of stem cell markers in glioblastoma.

Glioblastoma (GB) is the most common primary brain tumour in adults and it is associated with a high mortality rate. According to the stem cell theory, the growth, relapse and treatment response of GB is determined by the stem cell subpopulation present in the tumour. Our aim is to study the prognostic value of stem cell markers (CD44, Nestin, Olig2 and SOX2) in a series of homogeneously treated GBs.

MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC, WNT and AKT pathways.

Ovarian cancer is the most lethal gynecological malignancy due to the silent nature on its early onset and the rapid acquisition of drug resistance. Histologically heterogeneous, it includes several subtypes with different mutational landscapes, hampering the development of effective targeted therapies. Non-coding RNAs are emerging as potential new therapeutic targets in cancer.

Role of Chlamydia trachomatis serology in conservative management of cervical intraepithelial neoplasia grade 2.

Objective: To evaluate the spontaneous progression of cervical intraepithelial neoplasia grade 2 (CIN2) in accordance with Chlamydia trachomatis (chlamydia) serology.

Methods: A prospective observational study included women diagnosed with CIN2 by cervical biopsy and managed conservatively for 24 months at Hospital del Mar, Barcelona, between December 2011 and October 2013. Serum anti-chlamydia immunoglobulin G (IgG), previous cytology, and high-risk human papillomavirus (HPV) genotyping were recorded at baseline.

Addition of IMP3 to L1CAM for discrimination between low- and high-grade endometrial carcinomas: a European Network for Individualised Treatment of Endometrial Cancer collaboration study.

Discrimination between low- and high-grade endometrial carcinomas (ECs) is clinically relevant but can be challenging for pathologists, with moderate interobserver agreement. Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) is an oncofoetal protein that is associated with nonendometrioid endometrial carcinomas but has been limited studied in endometrioid carcinomas. The aim of this study is to investigate the diagnostic and prognostic value of IMP3 in the discrimination between low- and high-grade ECs and its added value to L1CAM.

ALCAM shedding at the invasive front of the tumor is a marker of myometrial infiltration and promotes invasion in endometrioid endometrial cancer.

Endometrial cancer (EC) is the sixth deadliest cancer in women. The depth of myometrial invasion is one of the most important prognostic factors, being directly associated with tumor recurrence and mortality. In this study, ALCAM, a previously described marker of EC recurrence, was studied by immunohistochemistry at the superficial and the invasive tumor areas from 116 EC patients with different degree of myometrial invasion and related to a set of relevant epithelial and mesenchymal markers.

[The Spanish Society of Cytology: Quality control program of gynecological cytology].

Introduction: In Spain, the guidelines for cervical cancer screening include a recommendation to enroll in external quality control programs. The Spanish Society of Cytology (SEC) has initiated its own quality control program of gynecological cytology (QCPGC).

Aim: To describe and discuss the results of the second round of SEĆs QCPGC.

Utility of Human Papillomavirus Genotyping in the Management of Low-Grade Squamous Intraepithelial Lesions.

Objective: The aim of the study was to determine the usefulness of human papillomavirus (HPV) partial genotyping test in the triage of newly diagnosed low-grade squamous intraepithelial lesions (LSILs).

Materials And Methods: We analyzed 143 patients with LSIL diagnosed de novo. Lesions were classified as positive for HPV 16 or HPV 18, positive for HPV but not HPV 16 or HPV 18 (HPVno16no18) or no HPV detected (HPVneg).

Constitutive Cyclin O deficiency results in penetrant hydrocephalus, impaired growth and infertility.

Cyclin O (encoded by ) is a member of the cyclin family with regulatory functions in ciliogenesis and apoptosis. Homozygous mutations have been identified in human patients with Reduced Generation of Multiple Motile Cilia (RGMC) and conditional inactivation of in the mouse recapitulates some of the pathologies associated with the human disease. These include defects in the development of motile cilia and hydrocephalus.

Pseudoprogression as an adverse event of glioblastoma therapy.

We explored predictive factors of pseudoprogression (PsP) and its impact on prognosis in a retrospective series of uniformly treated glioblastoma patients. Patients were classified as having PsP, early progression (eP) or neither (nP). We examined potential associations with clinical, molecular, and basal imaging characteristics and compared overall survival (OS), progression-free survival (PFS), post-progression survival (PPS) as well as the relationship between PFS and PPS in the three groups.

A Comparison of RNA-Seq Results from Paired Formalin-Fixed Paraffin-Embedded and Fresh-Frozen Glioblastoma Tissue Samples.

The molecular classification of glioblastoma (GBM) based on gene expression might better explain outcome and response to treatment than clinical factors. Whole transcriptome sequencing using next-generation sequencing platforms is rapidly becoming accepted as a tool for measuring gene expression for both research and clinical use. Fresh frozen (FF) tissue specimens of GBM are difficult to obtain since tumor tissue obtained at surgery is often scarce and necrotic and diagnosis is prioritized over freezing.

Activated leukocyte cell adhesion molecule (ALCAM) is a marker of recurrence and promotes cell migration, invasion, and metastasis in early-stage endometrioid endometrial cancer.

Endometrial cancer is the most common gynaecological cancer in western countries, being the most common subtype of endometrioid tumours. Most patients are diagnosed at an early stage and present an excellent prognosis. However, a number of those continue to suffer recurrence, without means of identification by risk classification systems.

Usefulness of p16 staining for managing histological high-grade squamous intraepithelial cervical lesions.

p16 (p16) tumor-suppressor protein is a biomarker of human papillomavirus (HPV) oncogenic activity that has revealed a high rate of positivity in histological high-gade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2 (HSIL/CIN2) lesions. However, there is a paucity of data regarding p16 status as a surrogate marker of HSIL/CIN2 evolution. The aim of this study was to evaluate the outcome of HSIL/CIN2 patients followed up without treatment for 12 months according to p16 immunohistochemical staining.

Value of p16(INK4a) and Ki-67 Immunohistochemical Staining in Cervical Intraepithelial Neoplasia Grade 2 Biopsies as Biomarkers for Cervical Intraepithelial Neoplasia Grade 3 in Cone Results.

Objective: To evaluate the usefulness of p16(INK4a) (p16) and Ki-67 staining in high-grade cervical intraepithelial neoplasia (CIN2) biopsies in order to predict CIN3 results in cone specimens, thereby sparing those not likely at risk for CIN3 from unnecessary cone excision.

Study Design: We retrospectively recruited patients with CIN2 colposcopy-directed biopsy treated by loop electrosurgical excision procedure. The expression of p16 and Ki-67 was qualitatively and quantitatively analyzed in all biopsies and cone specimens.

Nidogen 1 and Nuclear Protein 1: novel targets of ETV5 transcription factor involved in endometrial cancer invasion.

Endometrial cancer is the most frequent malignancy of the female genital tract in western countries. Our group has previously characterized the upregulation of the transcription factor ETV5 in endometrial cancer with a specific and significant increase in those tumor stages associated with myometrial invasion. We have shown that ETV5 overexpression in Hec1A endometrial cancer cells induces epithelial to mesenchymal transition resulting in the acquisition of migratory and invasive capabilities.

Cervista HPV HR test for cervical cancer screening: a comparative study in the Catalonian population.

Context: Almost all cervical cancers are related to the human papillomavirus (HPV). Future strategies for cervical cancer screening will be based on HPV detection. The Hybrid Capture 2 (HC2) test is currently the most widely used method to screen for HPV.