Relevance of Fc Gamma Receptor Polymorphisms in Cancer Therapy With Monoclonal Antibodies.

Therapeutic monoclonal antibodies (mAbs), including immune checkpoint inhibitors (ICIs), are an important breakthrough for the treatment of cancer and have dramatically changed clinical outcomes in a wide variety of tumours. However, clinical response varies among patients receiving mAb-based treatment, so it is necessary to search for predictive biomarkers of response to identify the patients who will derive the greatest therapeutic benefit. The interaction of mAbs with Fc gamma receptors (FcγR) expressed by innate immune cells is essential for antibody-dependent cellular cytotoxicity (ADCC) and this binding is often critical for their efficacy.

Dosage of anti-PD-1 monoclonal antibodies: a cardinal open question.

Discovery and clinical development of monoclonal antibodies with the ability to interfere in the regulation of the immune response have significantly changed the landscape of oncology in recent years. Among the active agents licensed by the regulatory agencies, nivolumab and pembrolizumab are paradigmatic as the most relevant ones according to the magnitude of available data derived from the extensive preclinical and clinical experience. Although in both cases the respective data sheets indicate well-defined dosage regimens, a review of the literature permits to verify the existence of many issues still unresolved about dosing the two agents, so it must be considered an open question of potentially important consequences, in which to work to improve the effectiveness and efficiency of use.

Development and validation of an HPLC-DAD method for determination of oleuropein and other bioactive compounds in olive leaf by-products.

Background: Oil mills could benefit by preparing their own aqueous extracts from olive leaves. Accordingly, the present study aimed to measure the bioactive compounds richness of such extracts, especially oleuropein. A water-based microwave extraction procedure was developed and a selective and precise high-performance liquid chromatography with diode array detection (HPLC-DAD) method was validated for the determination of oleuropein and others bioactive compounds from olive leaves.

Therapeutic drug monitoring of nivolumab in routine clinical practice. A pilot study.

Objective: A review of the literature about the anti-programmed death 1 monoclonal antibody nivolumab permits to verify the existence  of several issues still unresolved about their dosing schedule. The aim of the present work was to explore possibilities of nivolumab treatment  personalization through therapeutic drug monitoring, in order to  improve their effectiveness and efficiency.

Method: Observational, prospective study carried out from May 2017  through June 2019 in patients with different tumor diagnoses treated with nivolumab.

A novel genomic signature predicting FDG uptake in diverse metastatic tumors.

Background: Building a universal genomic signature predicting the intensity of FDG uptake in diverse metastatic tumors may allow us to understand better the biological processes underlying this phenomenon and their requirements of glucose uptake.

Methods: A balanced training set (n = 71) of metastatic tumors including some of the most frequent histologies, with matched PET/CT quantification measurements and whole human genome gene expression microarrays, was used to build the signature. Selection of microarray features was carried out exclusively on the basis of their strong association with FDG uptake (as measured by SUVmean35) by means of univariate linear regression.

Determining personalized treatment by gene expression profiling in metastatic breast carcinoma patients: a pilot study.

Purpose: The present study evaluates the massive study of gene expression in metastatic breast carcinoma (MBC) patients using microarray gene expression profiling (MAGE) complemented with conventional sequencing, immunohistochemistry (IHC) and fluorescent "in situ" hybridization (FISH), seeking to optimize the treatment in a subset of heavily pretreated patients and with limited life expectancy.

Patients, Material And Methods: MBC patients in hormone therapy progression with survival expectancy of at least 3 months (m) have been included. The MAGE contains gene probes representing genes known to potentially interact with available drugs as cited in the literature.

Cancer Immunotherapy with Cytokine-Induced Killer Cells.

Cytokine-induced killer (CIK) cells form under certain stimulation conditions in cultures of peripheral blood mononuclear cells (PBMCs). They are a heterogeneous immune cell population and contain a high percentage of cells with a mixed T-NK phenotype (CD3+CD56+). The ready availability of a lymphocyte source, together with the high proliferative rate and potent anti-tumor activity of CIK cells, has allowed their use as immunotherapy in a wide variety of neoplasms.

Microarray phosphatome profiling of breast cancer patients unveils a complex phosphatase regulatory role of the MAPK and PI3K pathways in estrogen receptor-negative breast cancers.

Phosphatases are proteins with the ability to dephosphorylate different substrates and are involved in critical cellular processes such as proliferation, tumor suppression, motility and survival. Little is known about their role in the different breast cancer (BC) phenotypes. We carried out microarray phosphatome profiling in 41 estrogen receptor-negative (ER-) BC patients, as determined by immunohistochemistry (IHC), containing both ERBB2+ and ERBB2- in order to characterize the differences between these two groups.

[Influence of genetic polymorphisms in UGT1A1, UGT1A7 and UGT1A9 on the pharmacokynetics of irinotecan, SN-38 and SN-38G].

Objective: To evaluate the influence of genetic polymorphism in UGT1A1, UGT1A7 and UGT1A9 on the population pharmacokinetics of irinotecan and its metabolites, SN-38 and SN-38G.

Methods: Plasma concentrations of irinotecan, SN-38 and SN- 38G from 72 patients were pooled to develop a population pharmacokinetic model using NONMEM VII. M3 method was used to account for plasma concentrations below the limit quantification.

Epidermal growth factor receptor (EGFR) mutations in a series of non-small-cell lung cancer (NSCLC) patients and response rate to EGFR-specific tyrosine kinase inhibitors (TKIs).

INTRODUCTION Epidermal growth factor receptor (EGFR) mutation related to tyrosine kinase inhibitors' (TKIs) responsiveness in non-small cell lung cancer (NSCLC) has become an important issue for therapeutic decision-making in NSCLC patients. MATERIAL AND METHODS Sixty-nine Caucasian NSCLC patients were screened for mutations in the tyrosine kinase (TK) domain of EGFR by direct sequencing from December 2005 to September 2010. RESULTS Activating mutations in the EGFR TK domain were found in 8 of 69 (11.

A novel EGFR nonsense mutation in a non-small-cell lung cancer (NSCLC) patient who did not derive any clinical benefit with combination chemotherapy and erlotinib.

Most of the somatic epidermal growth factor receptor (EGFR) mutations described to date in non-smallcell lung cancer (NSCLC) patients are located in the kinase domain and are considered activating mutations. Some of these mutations are associated with response to specific EGFR tyrosine kinase inhibitors (TKI) such as gefitinib and erlotinib. Here we report a case of a previously undescribed EGFR nonsense mutation in a lung adenocarcinoma patient who did not derive any clinical benefit with combination chemotherapy and erlotinib.

Phylogeny and molecular evolution of the tribe Harpalini (Coleoptera, Carabidae) inferred from mitochondrial cytochrome-oxidase I.

The tribe Harpalini is a group of ground beetles with a world-wide distribution that comprises approximately 2000 species and about 238 genera and subgenera. Hypotheses about the phylogenetic relationships of the subtribes of Harpalini are implicit within the systematic criteria put forward by different authors. A 759 bp fragment of the mitochondrial COI was sequenced in 119 specimens (107 species) of 52 genera and subgenera that represent the main lineages of Harpalines, and 3 species of other tribes used as outgroups.

Home-based self-measurement of blood pressure: a proposal using new reference values (the PURAS study).

Objectives: To establish reference values for blood pressure by means of self-measurement of blood pressure (BP) conducted at home.

Design: Descriptive study of the distribution of self-measured BP at home and its correspondence with clinic-based measurements of BP.

Methods: The aim of this study is to define the home BP levels that correspond to clinic BP thresholds 140/90 mmHg (hypertension) and 130/85 mmHg (normality).

[Can or should blood pressure be measured at pharmacy offices?].

Objective: To evaluate concordance between blood-pressure (BP) measurements at the pharmacy office (PhO) and the nurse office (NO) in the health care centre (HCC).

Design: Descriptive study.

Setting: Community.

[Home self-measurements of blood pressure and relationship with diagnosis of hypertension and target organ damage: comparative study with ambulatory monitoring].

Background: The diagnosis of arterial of hypertension (AH) requires an accurate and precise measurement methodology. The habitual techniques overstimate the prevalence of AH and have a poor correlation with organ damage. The objective of the study is to know the associations between self-measurements of blood pressure (BP) at home and target organ damage of AH.

[Idiopathic retroperitoneal fibrosis. An atypical case of multisystem presentation].

Idiopathic retroperitoneal fibrosis (IRF) is a disease difficult to diagnose. It is considered by different authors of autoimmune origin given its similarity to other connective tissue diseases. We present the case of a female patient diagnosed by a postmortem study, of IRF with multiorgan involvement (lymph nodes, serose tissue, liver, spleen, adrenal glands, thyroid and kidneys) and atypical presentation, not finding other similar cases in the national literature.