Frequency of S492R mutations in the epidermal growth factor receptor: analysis of plasma DNA from patients with metastatic colorectal cancer treated with panitumumab or cetuximab monotherapy.

Background: Antibodies against epidermal growth factor receptor (EGFR), panitumumab, a fully human monoclonal antibody, and cetuximab, a human/mouse chimeric monoclonal antibody, have shown clinical efficacy in metastatic colorectal cancer (mCRC). In the phase 3 noninferiority ASPECCT (ClinicalTrials.gov, NCT01001377) study, panitumumab was demonstrated to be noninferior to cetuximab and provided a similar overall survival benefit for patients with chemotherapy-refractory wild-type exon 2 mCRC.

A randomised, open-label, phase 2 study of the IDO1 inhibitor epacadostat (INCB024360) versus tamoxifen as therapy for biochemically recurrent (CA-125 relapse)-only epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer.

Objective: Indoleamine 2,3-dioxygenase-1 (IDO1) is a key regulator of immune tolerance in ovarian cancer. This study investigated efficacy and safety of the IDO1 enzyme inhibitor epacadostat versus tamoxifen in patients with biochemical-only recurrence (CA-125 elevation) following complete remission after first-line chemotherapy for advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer.

Methods: In this open-label, phase 2 study (NCT01685255), patients were randomised 1:1 to epacadostat 600mg or tamoxifen 20mg twice daily for successive 28-day cycles and stratified by time since completion of first-line chemotherapy to first CA-125 elevation (3 to <12 or ≥12months).

Final results and outcomes by prior bevacizumab exposure, skin toxicity, and hypomagnesaemia from ASPECCT: randomized phase 3 non-inferiority study of panitumumab versus cetuximab in chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer.

Purpose: The primary analysis of the ASPECCT study demonstrated that panitumumab was non-inferior to cetuximab for overall survival (OS) in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC). Here, we report the final analysis results of ASPECCT.

Patients And Methods: Patients with wild-type KRAS exon 2 mCRC who progressed on or were intolerant to irinotecan- or oxaliplatin-based chemotherapy were randomised to receive panitumumab 6 mg/kg once every 2 weeks or cetuximab (400 mg/m) followed by 250 mg/m weekly.

Phase I, open-label, randomized, parallel study to evaluate the pharmacokinetics, safety, and tolerability of one intramuscular injection of risperidone ISM at different dose strengths in patients with schizophrenia or schizoaffective disorder (PRISMA-1).

The aim of this study was to characterize the pharmacokinetics and to evaluate the safety of risperidone ISM in patients with schizophrenia or schizoaffective disorder after a single gluteal intramuscular injection at three different dose strengths (50, 75, and 100 mg). A total of 36 patients were randomized and blood samples were collected to measure the plasma concentrations. The pharmacokinetic of the active moiety was biphasic for all three dose groups, and the mean plasma concentration was 21.

A fight for life and dignity: A case of massive traumatic brain injury and the paths for treatment and neurorehabilitation.

We present a clinical case of treatment and neurorehabilitation of a patient with severe neurological deficit due to extensive traumatic lesion of the left hemisphere of the brain. Until recently, such cases were considered incurable and remained marginalized throughout their lives. This clinical case illustrates the compensatory brain possibilities under long-term integrated multidisciplinary treatment and neurorehabilitation with mandatory application of medical, medico-psychological, medico-pedagogical, and medico-social methods, the importance and intensity of which vary at different stages of the disease.

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial.

Background: Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2-positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain.

Methods: In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2-positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.

Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study.

Background: The anti-EGFR monoclonal antibodies panitumumab and cetuximab are effective in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer. We assessed the efficacy and toxicity of panitumumab versus cetuximab in these patients.

Methods: For this randomised, open-label, phase 3 head-to-head study, we enrolled patients (from centres in North America, South America, Europe, Asia, Africa, and Australia) aged 18 years or older with chemotherapy-refractory metastatic colorectal cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, and wild-type KRAS exon 2 status.

Autistic children display elevated urine levels of bovine casomorphin-7 immunoreactivity.

Elevated concentrations of circulating casomorphins (CM), the exogenous opioid peptides from milk casein, may contribute to the pathogenesis of autism in children. Because several mass spectrometry studies failed to detect casomorphins in autistic children, it was questioned whether these peptides can be detected in body fluids by mass spec. Here we demonstrated, using a novel high sensitivity ELISA method, that autistic children have significantly higher levels of urine CM-7 than control children.

Production of nitrogen oxide derivatives under the influence of NO-synthase inhibitors and natural compounds in mice with transplanted tumors.

Aim: The aim of the present study was to investigate the dynamics of nitric oxide derivative (NOD) formation in mice with transplanted tumors and to analize whether synthetic NO-synthase inhibitors, NO-donors and natural compounds could modulate NOD synthesis.

Materials And Methods: In the study F(1)(C(57)BlxCBA), CBA/Lac, BDF and Balb/c mice were used. Endogenous NOD synthesis in mice with transplanted Ehrlich carcinoma (EC) and Lewis lung carcinoma (LLC) was estimated by measuring urine nitrates (NA) and nitrites (NI) excretion and their concentration in tumor tissue determined by cadmium-reduction method.

[Assesment of Parameters of QT Interval in Children and Adolescents.].

Aim. To determine limits of interval QT in children and adolescents aged 0-17 years and to detect possible ethnic differences of its changes. Material and Method.

[Clinical Efficacy of Combination Therapy With Trimetazidine and Angiotensin Converting Enzyme Inhibitors in Patients With Hypertension and Ischemic Heart Disease Associated With Type II Diabetes].

Aim: To assess in a randomized open study effect of 12-15 week use of angiotensin converting enzyme inhibitors (ACEI) with and without trimetazidine on myocardial perfusion reserve in patients with ischemic heart disease (IHD) and/or hypertension associated with type II diabetes.

Material: Patients (n=69) receiving long term ACEI therapy with transient myocardial perfusion defects during dipyridamole stress test.

Methods: Control patients (n=29, including 15 with IHD) continued to receive an ACEI, while in trimetazidine group (n=40, including 21 IHD patients) trimetazidine (60 mg/day) was added to ACEI.

Transplantation Immunity. Contemporary Views.

"Transplantation immunity in Cyclosporin era" is a special chapter in science under name transplantation immunity. Nowadays, practically all the organs can be grafted: kidney, heart, lung, liver, pancreas both as organ, and as islet cells, bone marrow from relative and unrelative donors. The broad spectrum of grafted organs gave one more surprising peculiarity of transplantation immunity: it operates with different strength after transplantation of various organs.

Major Histocompatibility Complex.

At the 2nd Congress of Russian Immunologists, which is holding at the boundary not only two centuries, but and millennia, we had to present views, how the knowledge about major histocompatibility system has been changed (better to say has been progressed) for the brief historical period (50-60 years). 1. Having started from two, and then three component genetic HLA structure, the further studies gave image about multicomponent genetic composition of HLA, which is still not clarified up till now.

[Ultrastructural changes in organelles of the dog cerebral cortex astrocytes in post-ischemic period (morphometric analysis)].

Morphometric analysis of volume density of mitochondria, rough endoplasmic reticulum (RER), Golgi complex, vacuoles, lysosomes, fibrils, superficial density of mitochondria and RER, postischemic mitochondria/RER superficial and volume ratio and astrocyte ultrastructure was carried out experimentally in dogs. The findings obtained indicate that in early postischemic period (5-10 min-3-7 d) changes in astrocyte were reactive, although since the second wk of postischemic period metabolic processes in astrocytes were disturbed, which were manifested through structural changes maximally pronounced on d 14-21 of reparative period. At late reparative period (first-third month) astrocyte structure was normalised to significant extent.

Type D retrovirus specific sequences in lymphocytes of the children with Burkitt-type lymphoma and their parents.

Type D retroviruses cause immunodeficiency in monkey. Earlier we have revealed genetical and serological markers of type D retroviruses in children with Burkitt-type lymphoma. Using PCR/Southern blotting assay we have found sequences related to MPMV in PBMC's DNA from children with Burkitt-type lymphoma and from their parents.

Tooth enamel EPR dosimetry: sources of errors and their correction.

Some of the most important sources of systematic errors in dose determination using tooth enamel EPR spectroscopy and ways of reducing those errors are discussed. Enamel from the outside of the front teeth should not be used for dose determination because of induction of paramagnetic centers by solar light. The accuracy of the method in the low dose range is limited by variation in the shape of the EPR signal of unirradiated enamel, which can be described by an initial intrinsic signal and which varies for different samples with standard deviation of 20-30 mGy.

Determination of somatic mutant frequencies at glycophorin A and T-cell receptor loci for biodosimetry of acute and prolonged irradiation.

Somatic mutant frequencies at glycophorin A (GPA) and T-cell receptor (TCR) loci were assessed. The dependence of the GPA mutant frequency on doses of acute and prolonged irradiation was shown. In the case of acute irradiation the GPA mutant frequency displayed a three-fold greater dose-related increase as compared to prolonged irradiation.

[Metabolism of androgens in various histological variants of bone tumors].

The role of androgens in human normal and neoplastic bone tissues is still unclear. The paper presents data on metabolism of androgens in homogenates of malignant (osteosarcoma, chondrosarcoma, Ewing and giant cell) and benign primary tumors from 46 male and female patients aged 14-58 years. Using two substrates (testosterone and 5 alpha-dihydrotestosterone) for the first time are shown activities of main enzymes of androgen metabolism in all tumor types.

Markers of type D retroviruses in children with Burkitt's-type lymphoma.

Antibodies to gag-coded proteins of type D retroviruses have been detected in children with lymphadenopathy [1]. We tested 41 HIV noninfected children with lymphoproliferative diseases (27 cases of Burkitt's-type lymphoma, six cases of Hodgkin's disease, four cases of T-cell lymphoma, three cases of lymphoblastic lymphoma and one case of large-cell anaplastic lymphoma) for the presence of type D retroviral serological and genetical markers. Twenty-five healthy donors were tested as a control.

Evidence for formation of somatic cell hybrids in a population of irradiated cells.

Experiments using two genetically marked lines of Djungarian hamster cells (DM-15 HPRT- and DH-TK-) and the technique of hybrid selection in selective HAT medium revealed viable colonies in a mixed culture irradiated with a dose of 5 Gy. The sublines grown from these colonies were examined. Chromosome analysis showed that about 45% of those cells were hybrids inheriting chromosome markers of both parent strains.