Novel benzofurane-pyrazole derivatives with anti-inflammatory, cyclooxygenase inhibitory and cytotoxicity evaluation

Novel benzofurane-pyrazolone hybrids have been synthesized for evaluating their anti-inflammatory and cytotoxic properties. 4-(2-chloroacetyl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one were reacted with alpha-hydroxy aldehyde or alpha-hydroxy ketone derivatives to obtain nine novel pyrazolone derivatives. Structures were successfully elucidated by H-1 NMR, C-13 NMR, IR and HRMS. Enzyme inhibitory activity was measured on cyclooxygenases (COXs) as considered to address anti-inflammatory activity. Compound 2 showed the highest activity on both COX-1 and COX-2 subtypes with 12.0 mu M and 8.0 mu M IC50, respectively. This activity was found close to indomethacin COX-2 inhibition measured as 7.4 mu M IC50. Rest of the compounds (1, 3-9) showed 10.4-28.1 mu M IC50 on COX-2 and 17.0-35.6 mu M IC50 on COX-1 (Compound 1 has no activity on COX-1). Tested compounds (1-9) showed activity on NO production. Only compound was the 4, which showed a low inhibition on IL-6 levels. Cell viability was up to 60% at 100 mu M for all compounds (1-9) on RAW 264.7 and NIH3T3 cell lines, thus compounds were reported to be noncytotoxic

Primary Cutaneous Adenoid Cystic Carcinoma

Adenoid cystic carcinoma is a malignant tumor usually localized in the salivary glands. It can also develop in serous glands such as the breast, main bronchi, uterine cervix, Bartholin's gland of the vulva, prostate gland, and external auditory canal. It is more common in the white race. Most of the primary cutaneous adenoid cystic carcinoma cases occur on the scalp. Despite the high rate of metastasis, long-term survival can be observed because the progression of the disease is slow. Distant organ metastases such as lungs, bone, liver and brain have also been reported in the literature at 40%. Its treatment is wide excision of the lesion and demonstration of tumor negative margin in pathological sampling. In this case report, we wanted to present surgical and oncological treatment to a 65-year-old female patient with lung metastasis diagnosed with adenoid cystic carcinoma on the scalp

Novel cyanothiouracil and cyanothiocytosine derivatives as concentration-dependent selective inhibitors of U87MG glioblastomas: Adenosine receptor binding and potent PDE4 inhibition

Thiouracil and thiocytosine are important heterocyclic pharmacophores having pharmacological diversity. Antitumor and antiviral activity is commonly associated with thiouracil and thiocytosine derivatives, which are well known fragments for adenosine receptor affinity with many associated pharmacological properties. In this respect, 33 novel compounds have been synthesized in two groups: 24 thiouracil derivatives (4a-x) and 9 thiocytosine derivatives (5a-i). Antitumor activity of all the compounds was determined in the U87 MG glioblastoma cell line. Compound 5e showed an anti-proliferative IC50 of 1.56 μM, which is slightly higher activity than cisplatin (1.67 μM). The 11 most active compounds showed no signficant binding to adenosine A1, A2A or A2B receptors at 1 μM. Brain tumors express high amounts of phosphodiesterases. Compounds were tested for PDE4 inhibition, and 5e and 5f showed the best potency (5e: 3.42 μM; 5f: 0.97 μM). Remakably, those compounds were also the most active against U87MG. However, the compounds lacked a cytotoxic effect on the HEK293 healthy cell line, which encourages further investigation.National Institute of Diabetes and Digestive and Kidney DiseasesUnited States Department of Health & Human Services National Institutes of Health (NIH) - US

Is There Increased Risk of Childhood Cancers after Assisted Reproductive Techniques?

Background and Aims: Assisted reproductive techniques (ART) havebeen determined to be a risk factors for multiple pregnancy, perinatalcomplications and congenital malformations in children. In this study,we aimed to determine the role of possible risk factors for assistedreproductive techniques in childhood malignancies.Methods: 300 patients between the ages of 0-18 years who wereadmitted to Istanbul Medical Faculty, Department of Pediatric Hema-tology and Oncology, between 2000-2019 and 300 healthy childrenbetween 0-14 years of age who were admitted to Departmens of SocialPediatrics, period of May-June 2018 are included. SPSS 22.0 program was used in statistical analysis. The study was approved by the ClinicalResearch Ethics Committee (17.05.2018 / 181360).Results: The mean age of the case group was 8.3±2.1, control groupwas 6.1±1.2 years. The case group consisted of 131 solid tumors and169 leukemia-lymphoma. 17 of 300 patients in the case group wereborn ART, 21 of 300 patients in the control group were born after ART,there was no statistically significant difference (p = 0.12). Five (6.8%)of the 73 ALL patients in the case group, two of the 38 NBL patients(5.2%), one of 10 germ cell tumors (10%), one of 26 NHL (3.8%), oneof 50 HL (2%), one of 15 RMS (6.6%), two of 17 LCH (11.7%), one of 19wilms tumors (5.2%), one of 8 hepatoblastomas (12,5%) were born withART. The patient who was diagnosed with infantile hemangioendothe-lioma and congenital mesoblastic nephroma in the study were born asaresultofART.Conclusions: Our results did not support retrospectively as a possi-ble risk factor of birth as a result of fertility treatment in children withcancer. The rates of developing tumors in children with healthy donorsused in infertile families will also contribute to the questions betweenART and childhood tumors in the futur

Is there increased risk of childhood cancers after assisted reproductive techniques?

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Effectiveness and Safety of Initiation and Titration of Insulin Glargine 300 U/mL in Insulin-Naive Patients with Type 2 Diabetes Mellitus Uncontrolled on Oral Antidiabetic Drug Treatment in Turkey: The EASE Study

Objective: The aim of the study was to evaluate the effectiveness and safety of insulin glargine 300 U/ mL (Gla-300) in insulin-naive patients with type 2 diabetes mellitus (T2DM) inadequately controlled on oral antidiabetic drug (OADs) treatment in Turkey. Methods: One hundred eight patients from 20 centers enrolled in the study. Starting from baseline, Gla-300 was self-administered subcutaneously and once daily in the evening. The primary outcome was the mean change in glycated hemoglobin A1c (HbA1c) from baseline to week 24. Results: The mean (±SD) Hb1Ac level of 9.4% (±0.8) at baseline decreased to 7.5% (±0.9) at week 12 (P <.1) and to 7.3% (±0.9) at week 24 (P <.1). Although none of the patients were within the target Hb1Ac level of ≤7% at baseline, the percentage of patients who achieved the target Hb1Ac level was 30.4% at week 12 and increased to 42.9% at week 24. Gla-300 treatment achieved the Hb1Ac target in 21 (19.4%) patients without experiencing a hypoglycemic event and in 27 (25.0%) patients who experienced at least one hypoglycemic event. For each self-monitoring blood glucose time point, significant improvements were observed as compared to baseline (P <.001). Statistically significant improvement (P <.001) was seen in the treatment satisfaction questionnaire – status version scores between baseline and week 24. Conclusion: This study indicated that Gla-300 is effective to provide a successful glycemic control with low risk of hypoglycemia added to OADs in insulin-naive patients with T2DM, and it has the potential to improve the quality of life of patients

Growth curves for Turkish Girls with Turner Syndrome: Results of the Turkish Turner Syndrome Study Group

OBJECTIVE: Children with Turner syndrome (TS) have a specific growth pattern that is quite different from that of healthy children. Many countries have population-specific growth charts for TS. Considering national and ethnic differences, we undertook this multicenter collaborative study to construct growth charts and reference values for height, weight and body mass index (BMI) from 3 years of age to adulthood for spontaneous growth of Turkish girls with TS. METHODS: Cross-sectional height and weight data of 842 patients with TS, younger than 18 years of age and before starting any therapy, were evaluated. RESULTS: The data were processed to calculate the 3rd, 10th, 25th, 50th, 75th, 90th and 97th percentile values for defined ages and to construct growth curves for height-for-age, weight-for-age and BMI-for-age of girls with TS. The growth pattern of TS girls in this series resembled the growth pattern of TS girls in other reports, but there were differences in height between our series and the others. CONCLUSION: This study provides disease-specific growth charts for Turkish girls with TS. These disease-specific national growth charts will serve to improve the evaluation of growth and its management with growth-promoting therapeutic agents in TS patients