First-in-human phase I study of immunomodulatory E7046, an antagonist of PGE-receptor E-type 4 (EP4), in patients with advanced cancers.

Background: E7046 is a highly selective, small-molecule antagonist of the E-type prostanoid receptor 4 (EP4) for prostaglandin E2, an immunosuppressive mediator of the tumor immune microenvironment. This first-in-human phase 1 study assessed the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose (MTD) and recommended phase 2 dose of E7046.

Methods: This first-in-human study enrolled 30 patients with advanced tumors of cancer types associated with high levels of myeloid infiltrates.

Current challenges and problems in teaching pathophysiology in Ukraine - another reaction to Churilov's paper.

Pathophysiology in Ukraine has rich traditions and achievements in the scientific areas, as well as in teaching academic discipline. Its history, the main Ukrainian scientific schools and their famous representatives are briefly described. The content of existing study program, the main approaches to teaching, and some methodological and organizational problems needed to be solved are characterized.

Biological effects of tolerable level chronic boron intake on transcription factors.

The mechanism of boron effect on human transcription and translation has not been fully understood. In the current study it was aimed to reveal the role of boron on the expression of certain transcription factors that play key roles in many cellular pathways on human subjects chronically exposed to low amounts of boron. The boron concentrations in drinking water samples were 1.

Association between complete response and outcomes in transplant-eligible myeloma patients in the era of novel agents.

Objectives: Achieving complete response (CR) has been linked to improved progression-free (PFS) and overall (OS) survival in myeloma. A meta-analysis was conducted to investigate whether this holds true in the era of novel agents (bortezomib, lenalidomide, thalidomide).

Methods: A total of 24 studies in newly diagnosed patients undergoing autologous stem cell transplantation (ASCT) that reported associations between responses and long-term outcomes (PFS/OS rates post-ASCT by response, or hazard ratios with 95% confidence intervals from Cox models) were identified and analyzed.

Clinical development of new drug-radiotherapy combinations.

In countries with the best cancer outcomes, approximately 60% of patients receive radiotherapy as part of their treatment, which is one of the most cost-effective cancer treatments. Notably, around 40% of cancer cures include the use of radiotherapy, either as a single modality or combined with other treatments. Radiotherapy can provide enormous benefit to patients with cancer.

Is Boric Acid Toxic to Reproduction in Humans? Assessment of the Animal Reproductive Toxicity Data and Epidemiological Study Results.

Boric acid and sodium borates are classified as toxic to reproduction in the CLP Regulation under "Category 1B" with the hazard statement of "H360FD". This classification is based on the reprotoxic effects of boric acid and sodium borates in animal experiments at high doses. However, boron mediated reprotoxic effects have not been proven in epidemiological studies so far.

Bortezomib, thalidomide and dexamethasone, with or without cyclophosphamide, for patients with previously untreated multiple myeloma: 5-year follow-up.

This follow-up extension of a randomised phase II study assessed differences in long-term outcomes between bortezomib-thalidomide-dexamethasone (VTD) and VTD-cyclophosphamide (VTDC) induction therapy in multiple myeloma. Newly diagnosed patients (n = 98) were randomised 1:1 to intravenous bortezomib (1·3 mg/m(2); days 1, 4, 8, 11), thalidomide (100 mg; days 1-21), and dexamethasone (40 mg; days 1-4, 9-12), with/without cyclophosphamide (400 mg/m(2); days 1, 8), for four 21-day cycles before stem-cell mobilisation/transplantation. After a median follow-up of 64·8 months, median time-to-next therapy was 51·8 and 47·9 months with VTD and VTDC, respectively.

[Association of allelic polymorphisms of genes matrix Gla-protein system with ischemic atherothrombotic stroke].

There are results of the determination of 10 polymorphisms of matrix Gla-protein system (gene MGP-T(-138)-->C (rs1800802), G(-7)-->A (rs1800801), Thr83-->Ala (rs4236), gene VDR-FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236), gene GGCX-Arg325-->Gln (rs699664), gene VKORS1-T(2255)-->C (rs2359612), gene BMP-2-Ser37-->Ala (rs2273073)) into 170 patients with ischemic atherothrombotic stroke (IATS) and 124 healthy individual is (control group). It is established that there is a connection between the IATS and polymorphic variants of genes MGP (G(-7)-->A) and VKORC1 (T(2255)-->C). The risk of IATS in carriers of minor allele A/A (G(-7)-->A polymorphism) in 2.

Selenium, nickel, and calcium levels in cancerous and non-cancerous prostate tissue samples and their relation with some parameters.

In the present study, tissue samples of patients with cancerous and non-cancerous prostate were analyzed for their Se, Ni, and Ca contents. Possible relationship between Se, Ni, and Ca concentrations and some parameters including preoperative prostate-specific antigen (PSA) levels, histopathological neurovascular invasion, extra-capsular extension, seminal vesicle invasion, positive surgical margins, PSA relapse after radical prostatectomy, and total Gleason scores were obtained. Inductively coupled plasma (ICP) optical emission spectrometry and ICP-mass spectrometry instruments were used for the determination of analytes interested.

Lead determination at ng/mL level by flame atomic absorption spectrometry using a tantalum coated slotted quartz tube atom trap.

Flame atomic absorption spectrometry (FAAS) still keeps its importance despite the relatively low sensitivity; because it is a simple and economical technique for determination of metals. In recent years, atom traps have been developed to increase the sensitivity of FAAS. Although the detection limit of FAAS is only at the level of µg/mL, with the use of atom traps it can reach to ng/mL.

Retrospective matched-pairs analysis of bortezomib plus dexamethasone versus bortezomib monotherapy in relapsed multiple myeloma.

Bortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent bortezomib are lacking. This retrospective analysis compared second-line treatment with bortezomib-dexamethasone and bortezomib using 109 propensity score-matched pairs of patients treated in three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. Propensity scores were estimated using logistic regression analyses incorporating 13 clinical variables related to drug exposure or clinical outcome.

[Analysis of the effect of N5, N10-methylenetetrahydrofolate reductase gene C(677)-->T polymorphism on the ischemic stroke development in persons with various risk factors].

The results ofMTHFR gene C(677)-->T (rs1801133) polymorphism determined in 170 patients with ischemic atherothrombotic stroke (IATS) and 124 healthy subjects (control group) are presented in the paper. It has been shown that in patients with IATS, the frequencies of main homozygotes (CC), heterozygotes (CT) and minor homozygotes (TT) are 52.4, 35.

[Analysis of matrix Gla-protein (MGP) G-7A polymorphism association with ischemic atherothrombotic stroke in persons with risk factors].

G-7A polymorphism (rs1800801) of matrix Gla protein (MGP) gene in 170 patients with ischemic atherothrombotic stroke (IATS) and in 124 persons of the control group was determined. It was shown that in patients with IATS the distribution of the major allele homozygotes, heterozygotes and minor allele homozygotes was 35.9; 48.

[The polymorphism of matrix Gla-protein gene in ischemic atherothrombotic stroke patients].

Matrix Gla protein (MGP) gene allelic polymorphism in 170 patients with ischemic atherothrombotic stroke (IATS) and in 124 healthy people was determined. It was shown that in patients with IATS interrelation of main homozygotes, heterozygotes and minor homozygotes is 61,2, 31,2, 7,6% for T-138 --> C (rs1800802) promoter polymorphism (in control -59.7, 35.

Tellurium speciation analysis using hydride generation in situ trapping electrothermal atomic absorption spectrometry and ruthenium or palladium modified graphite tubes.

Speciation of tellurium can be achieved by making use of different kinetic behaviors of Te(IV) and Te(VI) upon their reaction with sodium borohydride using hydride generation. While Te(IV) can form H(2)Te, Te(VI) will not form any volatile species during the course of hydride formation and measurement by atomic absorption spectrometry. Quantitative reduction of Te(VI) was achieved through application of a microwave assisted prereduction of Te(VI) in 6.

The clinical development of molecularly targeted agents in combination with radiation therapy: a pharmaceutical perspective.

This paper explores historical and current roles of pharmaceutical industry sponsorship of clinical trials testing radiation therapy combinations with molecularly targeted agents and attempts to identify potential solutions to expediting further combination studies. An analysis of clinical trials involving a combination of radiation therapy and novel cancer therapies was performed. Ongoing and completed trials were identified by searching the clinicaltrials.

Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase, in patients with advanced solid tumors.

The purpose of this study was to determine the maximum-tolerated dose (MTD), pharmacokinetics and safety profile for two different dosing regimens of barasertib, a selective inhibitor of Aurora B Kinase. In this Phase I trial, patients with advanced solid malignancies were treated with escalating doses of barasertib, administered as either a 48-h continuous infusion or as two 2-h infusions on consecutive days, both every 14 days of a 28-day cycle. Thirty-five patients were treated.

[Matrix Gla-protein and its role in vascular wall calcification].

Data on the structure of matrix Gla-protein (MGP), its chemical characteristics, regulation of synthesis and post-translational modifications are described. The information on the structure of the MGP gene, its well distributed polymorphisms are presented. Factors that regulate expression and activity of MGP include vitamin D, retinoic acid, extracellular calcium ions, cytokines, and some hormones.

Indium determination using slotted quartz tube-atom trap-flame atomic absorption spectrometry and interference studies.

Sensitivity enhancement of indium determination by flame atomic absorption spectrometry (FAAS) was achieved; using a slotted quartz tube (SQT-FAAS) and slotted quartz tube atom trap (SQT-AT-FAAS). SQT was used as an atom trap (AT) where the analyte is accumulated in its inner wall prior to re-atomization. The signal is formed after re-atomization of analyte on the trap surface by introduction of 10 μL of isobutyl methyl ketone (IBMK).

[The frequency of allelic polymorphism of matrix Gla-protein gene in acute coronary syndrome patients].

Allelic polymorphisms of matrix Gla protein (MGP) gene were determinated in 115 patients with acute coronary syndrome (ACS) and in 110 practically healthy people. It was shown that interrelation of major homozygotes, heterozygotes and minor homozygotes by T-138-->C MGP promoter polymorphism in patients with ACS were 59.8%, 32.

[Comparative characteristic of energy supply disturbances in arterial and venous walls of rabbits with alloxan diabetes and monoiodacetate intoxication].

We showed here that energy metabolism in thoracic rabbit aorta and posterior vena cava is disturbed two weeks following the induction of alloxan-induced diabetes and monoiodacetate intoxication. In the vessels studied, the alterations are manifested in the decrease in the intensity of glucose uptake, oxygen consumption, lactic acid production, and ATP resynthesis. Simultaneously, the ATP content is significantly reduced.

Assessment of DNA integrity (COMET assay) in sperm cells of boron-exposed workers.

An extension of a male reproductive study conducted in a boric acid/borate production zone at Bandırma, Turkey, is presented. The relation between DNA-strand breaks (COMET assay, neutral and alkaline version) in sperm cells and previously described sperm quality parameters was investigated in boron-exposed males. A correlation between blood boron levels and mean DNA-strand breaks in sperm was weak, and DNA-strand breaks in sperm were statistically not different between control and exposed groups.

Prevalence of prostate cancer in high boron-exposed population: a community-based study.

We investigated the possible relationship between boron exposure and prostate cancer (PCa) for men living and being employed at boron mines in villages with rich boron minerals. Out of 456 men studied, 159 were from villages with rich boron sources and boron levels in drinking water of >1 mg L(-1) and these men formed the study group, while 63 from villages with rich boron sources and boron levels in drinking water of <1 mg L(-1) were enrolled into control group 1. A further 234 subjects from other villages with no boron mines were considered as control group 2.

Reproductive toxicity parameters and biological monitoring in occupationally and environmentally boron-exposed persons in Bandirma, Turkey.

Boric acid and sodium borates have been considered as being "toxic to reproduction and development", following results of animal studies with high doses. Experimentally, a NOAEL (no observed adverse effect level) of 17.5 mg B/kg-bw/day has been identified for the (male) reproductive effects of boron in a multigeneration study of rats, and a NOAEL for the developmental effects in rats was identified at 9.

Effects of chronic boron exposure on semen profile.

The possible changes in semen quality were studied in men living in a boron mining area. The subjects in the boron group had exposure to boron at an average level of 6.5 mg/day, as determined by urinary analysis.