Synthesis and antiproliferative activity of goniobutenolides A and B, 5-halogenated crassalactone D derivatives and the corresponding 7-epimers.

A new synthesis of goniobutenolides A (1) and B (2) and the corresponding 7-epimers has been achieved starting from diacetone d-glucose. The key step of the synthesis is a new one-pot sequence that commenced with Z-selective Wittig (or Horner-Wadsworth-Emmons) olefination, followed by successive γ-lactonisation and β-elimination. The above-mentioned unsaturated lactones were then converted to the corresponding 5-halogenated crassalactone D derivatives by using the appropriate haloetherification protocol.

Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions.

Background: The intestinal epithelium forms a barrier that food allergens must cross in order to induce sensitization. The aim of this study was to evaluate the impact of the plant-derived food cysteine protease--actinidin (Act d1) on the integrity of intestinal epithelium tight junctions (TJs).

Methods: Effects of Act d1 on the intestinal epithelium were evaluated in Caco-2 monolayers and in a mouse model by measuring transepithelial resistance and in vivo permeability.

Sensitization of K562 Leukemia Cells to Doxorubicin by the Viscum album Extract.

Toxicity of conventional chemotherapeutics highlights the requirement for complementary or alternative medicines that would reduce side effects and improve their anticancer effectiveness. European mistletoe (Viscum album) has long been used as a complementary and alternative medicine supporting cancer therapy. The aim of this study was to investigate synergistic antitumor action of V.

Investigation of antitumor potential of Ni(II) complexes with tridentate PNO acylhydrazones of 2-(diphenylphosphino)benzaldehyde and monodentate pseudohalides.

Square-planar azido Ni(II) complex with condensation product of 2-(diphenylphosphino)benzaldehyde and Girard's T reagent was synthesized and its crystal structure was determined. Cytotoxic activity of the azido complex and previously synthesized isothiocyanato, cyanato and chlorido Ni(II) complexes with this ligand was examined on six tumor cell lines (HeLa, A549, K562, MDA-MB-453, MDA-MB-361 and LS-174) and two normal cell line (MRC-5 and BEAS-2B). All the investigated nickel(II) complexes were cytotoxic against all tumor cell lines.

Immunohistochemical expression of nestin in rhabdomyosarcoma: implications for clinicopathology and patient outcome.

Rhabdomyosarcoma (RMS) is a highly malignant cancer. Over the last two decades, prognosis for RMS patients has significantly improved, with the exception of those in the high-risk group. In order to identify new prognostic factors, we investigated the expression of nestin in RMS cells and its correlation with clinicopathological features and patient outcome.

Rilmenidine suppresses proliferation and promotes apoptosis via the mitochondrial pathway in human leukemic K562 cells.

Imidazoline I1 receptor signaling is associated with pathways that regulate cell viability leading to varied cell-type specific phenotypes. We demonstrated that the antihypertensive drug rilmenidine, a selective imidazoline I1 receptor agonist, modulates proliferation and stimulates the proapoptotic protein Bax thus inducing the perturbation of the mitochondrial pathway and apoptosis in human leukemic K562 cells. Rilmenidine acts through a mechanism which involves deactivation of Ras/MAP kinases ERK, p38 and JNK.

Recurrent Laryngeal Nerve Liberations and Reconstructions: A Single Institution Experience.

Background: Recurrent laryngeal nerve (RLN) palsy rates vary from 0.5 to 10%, even 20% in thyroid cancer surgery. The aim of this paper was to present our experience with RLN liberations and reconstructions after various mechanisms of injury.

Pediatric glioblastoma: a single institution experience.

Purpose: The aim of this study was to evaluate characteristics of childhood glioblastoma multiforme, effectiveness of treatment modalities, and detect factors related to outcome.

Methods: A detailed analysis was performed on a series of 15 patients treated between 2000 and 2013, based on their clinical, radiologic, pathologic, treatment, and follow-up data.

Results: Median survival time of children with glioblastoma was 13.

A Review of NEPA, a Novel Fixed Antiemetic Combination with the Potential for Enhancing Guideline Adherence and Improving Control of Chemotherapy-Induced Nausea and Vomiting.

Combination antiemetic regimens targeting multiple molecular pathways associated with emesis have become the standard of care for prevention of chemotherapy-induced nausea and vomiting (CINV) related to highly and moderately emetogenic chemotherapies. Antiemetic consensus guidelines from several professional societies are widely available and updated regularly as new data emerges. Unfortunately, despite substantial research supporting the notion that guideline conformity improves CINV control, adherence to antiemetic guidelines is unsatisfactory.

Early prognosis of metastasis risk in inflammatory breast cancer by texture analysis of tumour microscopic images.

Inflammatory breast cancer (IBC) is a rare and aggressive type of locally advanced breast cancer. The purpose of this study was to determine the value of microscopic tumour histomorphology texture for prognosis of local and systemic recurrence at the time of initial IBC diagnosis. This retrospective study included a group of 52 patients selected on the basis of non-metastatic IBC diagnosis, stage IIIB.

Heteropentanuclear Oxalato-Bridged nd-4f (n=4, 5) Metal Complexes with NO Ligand: Synthesis, Crystal Structures, Aqueous Stability and Antiproliferative Activity.

A series of heteropentanuclear oxalate-bridged Ru(NO)-Ln (4d-4f) metal complexes of the general formula (nBu4N)5[Ln{RuCl3(μ-ox)(NO)}4], where Ln=Y (2), Gd (3), Tb (4), Dy (5) and ox=oxalate anion, were obtained by treatment of (nBu4N)2[RuCl3(ox)(NO)] (1) with the respective lanthanide salt in 4:1 molar ratio. The compounds were characterized by elemental analysis, IR spectroscopy, electrospray ionization (ESI) mass spectrometry, while 1, 2, and 5 were in addition analyzed by X-ray crystallography, 1 by Ru K-edge XAS and 1 and 2 by (13)C NMR spectroscopy. X-ray diffraction showed that in 2 and 5 four complex anions [RuCl3(ox)(NO)](2-) are coordinated to Y(III) and Dy(III), respectively, with formation of [Ln{RuCl3(μ-ox)(NO)}4](5-) (Ln=Y, Dy).

FLORENCE: a randomized, double-blind, phase III pivotal study of febuxostat versus allopurinol for the prevention of tumor lysis syndrome (TLS) in patients with hematologic malignancies at intermediate to high TLS risk.

Background: Serum uric acid (sUA) control is of key relevance in tumor lysis syndrome (TLS) prevention as it correlates with both TLS and renal event risk. We sought to determine whether febuxostat fixed dose achieves a better sUA control than allopurinol while preserving renal function in TLS prevention.

Patients And Methods: Patients with hematologic malignancies at intermediate to high TLS risk grade were randomized to receive febuxostat or allopurinol, starting 2 days before induction chemotherapy, for 7-9 days.

Breast cancer in postmenopausal patients: Impact of age.

Purpose: We analyzed the significance of age together with other classic prognostic parameters on the course of breast cancer in postmenopausal patients.

Methods: Our study included 151 postmenopausal patients with primary breast cancer, of which 55% received adjuvant tamoxifen therapy and 45% did not receive any kind of therapy. Probabilities of disease-free interval (DFI) were estimated using the Kaplan-Meier method and were compared by the log-rank test.

The relationship between proliferation activity and parathyroid hormone levels in parathyroid tumors.

Purpose: This article examines as to whether the Ki-67 index may be useful as a marker for cell proliferation, as well as to whether Ki-67 immunohistochemical expression and parathyroid hormone (PTH) levels are useful in distinguishing between parathyroid carcinoma (PC) and adenoma.

Methods: A retrospective analysis of 50 patients (10 with PC and 40 with adenoma) who had been previously diagnosed with primary hyperparathyroidism (PHPT) was conducted. Normal parathyroid glands served as the control group.

Can we use frozen section analysis of sentinel lymph nodes mapped with methylene blue dye for decision making upon one-time axillary dissection in breast carcinoma surgery in developing countries?

Purpose: To evaluate the accuracy of intraoperative frozen section analysis (FSA) of sentinel lymph nodes (SLNs) mapped using methylene blue dye (MBD) and its usefulness for selecting patients with breast carcinomas and positive axillary lymph nodes (ALNs) for one-time axillary dissection.

Methods: 152 female patients with T1/T2 breast carcinomas and clinically negative ALNs were selected for mapping using MBD (1%) from October 2010 to December 2011. Patients underwent FSA of mapped SLNs and ALN dissection.

Potential clinical relevance of uPA and PAI-1 levels in node-negative, postmenopausal breast cancer patients bearing histological grade II tumors with ER/PR expression, during an early follow-up.

We evaluated urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) prognostic value in postmenopausal, node-negative breast cancer patients bearing tumors with estrogen receptor (ER)/progesterone receptor (PR) expression, treated with locoregional therapy alone, within an early follow-up. We focused our analysis on tumors of histological grade II in order to improve its prognostic value and, consequently, to improve a decision-making process. The cytosol extracts of 73 tumor samples were used for assessing several biomarkers.

Ombrabulin plus cisplatin versus placebo plus cisplatin in patients with advanced soft-tissue sarcomas after failure of anthracycline and ifosfamide chemotherapy: a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Ombrabulin (AVE8062) disrupts the vasculature of established tumours and has shown preclinical synergistic anti-tumour activity when combined with cisplatin. In this phase 3 trial, we aimed to assess the efficacy and safety of ombrabulin plus cisplatin compared with placebo plus cisplatin in patients with advanced soft-tissue sarcomas.

Methods: We did this multinational, randomised, double-blind, placebo-controlled phase 3 study at 44 centres in ten countries.

Correlation of tumor size as independent factor and disease stage with local recurrence of non-small cell lung carcinoma and its operability.

Purpose: To analyze the correlation of non-small cell lung carcinoma (NSCLC) primary tumor size, independently, and the initial disease stage with the incidence of local recurrence (LR) and disease-free survival (DFS), as well as the LR operability.

Methods: The research was conducted on 114 patients operated due to NSCLC at the Institute for Lung Diseases of the Clinical Center of Serbia and the Institute for Oncology and Radiology of Serbia from January 2002 to December 2010, who developed LR during the 5-year follow-up. Diagnostic methods and surgical approaches were standard, defined by protocols.

The Influence of Adjuvant Radiotherapy in Atypical and Anaplastic Meningiomas: A Series of 88 Patients in a Single Institution.

Objective: Atypical and anaplastic meningiomas (World Health Organization classification grade II and III) represent a small and heterogeneous subgroup of meningiomas that has a more aggressive biological nature and higher frequency of recurrence. The atypical form accounts for 4.7%-7.

The influence of methylenetetrahydrofolate reductase and thymidylate synthetase gene polymorphisms on lung adenocarcinoma occurrence.

Purpose: Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthetase (TYMS) are suggested as risk factors for lung cancer. The purpose of this study was to analyze the association of MTHFR C677T polymorphism and variable number tandem repeat 2R/3R and single nucleotide polymorphism G>C in the 3R allele of the TYMS gene with lung adenocarcinoma.

Methods: A case-control study including lung adenocarcinoma patients and healthy subjects was performed.

Overall human papilloma virus and types 16/18 prevalence in women with normal cervical cytology in Serbia: is it time for human papillomavirus testing and/or vaccination?

Purpose: Infection with high-risk human papilloma viruses (HR-HPV), especially types 16/18, is the main factor in cervical carcinogenesis. Although the incidence of cervical cancer in Serbia is among the highest ones in Europe, data about HPV infection are insufficient. The aim of this study was to investigate the presence of overall and HPV16/18 infections in women with healthy appearance and cytologically (Pap) normal cervix.

Prolonged survival after neoadjuvant chemotherapy related with specific molecular alterations in the patients with nonsmall-cell lung carcinoma.

Lung cancer is the most common cause of neoplasia-related death worldwide. Accounting for approximately 80% of all lung carcinomas, the non-small cell lung carcinoma (NSCLC) is the most common clinical form with its two predominant histological types, adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Although surgical resection is the most favorable treatment for patients with NSCLC, relapse is still high, so neoadjuvant chemotherapy (NAC) is an accepted treatment modality.

Synthesis, characterization, DFT calculation and biological activity of square-planar Ni(II) complexes with tridentate PNO ligands and monodentate pseudohalides. Part II.

Three square-planar complexes of Ni(II) with condensation derivative of 2-(diphenylphosphino)benzaldehyde and 4-phenylsemicarbazide and monodentate pseudohalides have been synthesized and characterized on the basis of the results of X-ray, NMR and IR spectroscopy and elemental analysis. Investigated complexes exhibited moderate antibacterial and cytotoxic activity. The most pronounced cytotoxic activity (in the range of cisplatin) to HeLa cell line was observed for ligand and all the complexes.

Difference between Luminal A and Luminal B Subtypes According to Ki-67, Tumor Size, and Progesterone Receptor Negativity Providing Prognostic Information.

Background: The St. Gallen International Expert Consensus of 2011 proposes a new classification system for breast cancer based on its division into five subgroups. The criteria to identify these subtypes were recently refined at the 2013 Conference.

Clinical characteristics, tumor, node, metastasis status, and mutation rate in domain of epidermal growth factor receptor gene in serbian patients with lung adenocarcinoma.

Objective: Mutation rate in domain of EGFR gene varies between populations of lung cancer patients. Primary aim of this study was to analyze clinical and pathological characteristics, and tumor, node, metastasis status and stage of diseases, in relation to mutation status.

Methods: After histological confirmation of lung adenocarcinoma tissue obtained during bronchoscopy was consecutively sent for EGFR testing.