Oleuropein in olive leaf, branch, and stem extracts: stability and biological activity in human cervical carcinoma and melanoma cells.

Olive leaves as a main byproduct of olive oil and fruit industry are a valuable source of phytochemicals such as polyphenols, with multiple biomedical effects. Apart from leaves, olive branches and stems make up a significant amount of olive waste. It is well known that the drying process and long-term storage affect the stability and concentration of polyphenols present in raw materials.

Transient and fully reversible changes in laboratory parameters and modifications of the cytokine profile during blinatumomab treatment in children with relapsed or refractory B-cell acute lymphoblastic leukemia.

We analyzed changes in laboratory parameters, including blood counts, liver enzymes, inflammation and coagulation markers, and cytokines, from 70 blinatumomab-treated pediatric patients (NCT01471782). Overall, trends were consistent in responders and nonresponders. Platelets and lymphocytes peaked on day (D) 10 in cycle 1 and returned to baseline on D42 and D29, respectively.

Thiazole derivatives as dual inhibitors of deoxyribonuclease I and 5-lipoxygenase: A promising scaffold for the development of neuroprotective drugs.

A library of 43 thiazole derivatives, including 31 previously and 12 newly synthesized in the present study, was evaluated in vitro for their inhibitory properties against bovine pancreatic DNase I. Nine compounds (including three newly synthesized) inhibited the enzyme showing improved inhibitory properties compared to that of the reference crystal violet (IC = 346.39 μM).

Adaptation to spindle assembly checkpoint inhibition through the selection of specific aneuploidies.

Both the presence of an abnormal complement of chromosomes (aneuploidy) and an increased frequency of chromosome missegregation (chromosomal instability) are hallmarks of cancer. Analyses of cancer genome data have identified certain aneuploidy patterns in tumors; however, the bases behind their selection are largely unexplored. By establishing time-resolved long-term adaptation protocols, we found that human cells adapt to persistent spindle assembly checkpoint (SAC) inhibition by acquiring specific chromosome arm gains and losses.

Carvacrol Derivatives as Antifungal Agents: Synthesis, Antimicrobial Activity and in Silico Studies on Carvacryl Esters.

Chemical modifications of natural monoterpenoids to various derivatives have been reported to result in enhancement of biological activities when compared to parent compounds. In this context a well-known biocide and food additive, carvacrol, served as a basic scaffold onto which a phenolic functionality transformation by introducing acyl groups was performed. By using this simple methodology, we obtained a small series of 25 esters.

CD19 expression in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia pre- and post-treatment with blinatumomab.

Blinatumomab is a BiTE (bispecific T-cell engager) immuno-oncology therapy, which has demonstrated significant activity in patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL); however, a subset of patients relapse. Monitoring expression of cluster of differentiation (CD)19 in relapsed patients is critical to inform sequencing of subsequent therapies. The expression of CD19 in 59 pediatric patients with R/R B-ALL was analyzed on the day of diagnosis of R/R B-ALL and on days 15 and 29 of cycle 1 of blinatumomab.

Anticancer effects of olive oil polyphenols and their combinations with anticancer drugs.

Cancer presents one of the leading causes of death in the world. Current treatment includes the administration of one or more anticancer drugs, commonly known as chemotherapy. The biggest issue concerning the chemotherapeutics is their toxicity on normal cells and persisting side effects.

SMAD4 Loss Is Associated with Cetuximab Resistance and Induction of MAPK/JNK Activation in Head and Neck Cancer Cells.

We previously demonstrated an association between decreased expression and cetuximab resistance in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to further elucidate the clinical relevance of SMAD4 loss in HNSCC. SMAD4 expression was assessed by IHC in 130 newly diagnosed and 43 patients with recurrent HNSCC.

GammaKey system for improved diagnostics with gamma cameras.

We designed the GammaKey system for the acquisition, storage and analysis of images from semi-analogue gamma scintillation cameras (GSCs). The GammaKey system, operating on a standard PC, replicates the functionality of earlier dedicated computer systems, allows the exchange of data in the DICOM format and has an open architecture enabling the development of new diagnostic techniques. The main purpose of the GammaKey is to enable the continued use of old GSCs which have functional scintillation crystals, but also to permit data exchange with new digital GSCs.

Preferential activation of the hedgehog pathway by epigenetic modulations in HPV negative HNSCC identified with meta-pathway analysis.

Head and neck squamous cell carcinoma (HNSCC) is largely divided into two groups based on their etiology, human papillomavirus (HPV)-positive and -negative. Global DNA methylation changes are known to drive oncogene and tumor suppressor expression in primary HNSCC of both types. However, significant heterogeneity in DNA methylation within the groups results in different transcriptional profiles and clinical outcomes.

Current role of EGF receptor monoclonal antibodies and tyrosine kinase inhibitors in the management of head and neck squamous cell carcinoma.

New agents and treatment strategies that can be safely and effectively integrated into current treatment paradigms for head and neck squamous cell carcinoma (HNSCC) are urgently needed. To date, the anti-EGF receptor (EGFR) monoclonal antibody, cetuximab, is the first and only molecularly targeted therapy to demonstrate a survival benefit for patients with recurrent or metastatic disease. Other anti-EGFR-targeted therapies, including monoclonal antibodies (e.

Nuclear epidermal growth factor receptor and p16 expression in head and neck squamous cell carcinoma.

Objectives/hypothesis: Epidermal growth factor receptor (EGFR) and p16 (a surrogate marker of human papillomavirus [HPV] infection) expression are strong prognostic factors in patients with head and neck squamous cell carcinoma (HNSCC).

Study Design: We examined expression levels of total and nuclear EGFR as well as p16 status based on evidence that nuclear EGFR may have a role in DNA damage repair.

Methods: An HPV-negative (SQ20B) and an HPV-positive (UMSCC47) HNSCC cell line were examined for EGFR and γH2AX expression.

Regulation of HIF-1α signaling and chemoresistance in acute lymphocytic leukemia under hypoxic conditions of the bone marrow microenvironment.

Overcoming resistance to chemotherapy is the main therapeutic challenge in the treatment of acute lymphocytic leukemia (ALL). Interactions between leukemia cells and the microenvironment promote leukemia cell survival and confer resistance to chemotherapy. Hypoxia is an integral component of bone marrow (BM) microenvironment.

Induction of vascular endothelial growth factor secretion by childhood acute lymphoblastic leukemia cells via the FLT-3 signaling pathway.

Human leukemia cells secrete VEGF, which can act in a paracrine manner within the bone marrow microenvironment to promote leukemia cell survival and proliferation. The FLT-3 receptor tyrosine kinase plays an essential role in regulating normal hematopoiesis, but its constitutive activation via mutation in acute leukemias is generally associated with poor outcome. The aim of this study was to investigate interactions between the FLT-3 and VEGF signaling pathways in acute leukemia using cell lines and ex vivo cultures of pediatric acute lymphoblastic leukemia cells following expansion of direct patient explants in immunodeficient mice.

A crucial requirement for Hedgehog signaling in small cell lung cancer.

Small-cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer for which there is no effective treatment. Using a mouse model in which deletion of Rb1 and Trp53 in the lung epithelium of adult mice induces SCLC, we found that the Hedgehog signaling pathway is activated in SCLC cells independently of the lung microenvironment. Constitutive activation of the Hedgehog signaling molecule Smoothened (Smo) promoted the clonogenicity of human SCLC in vitro and the initiation and progression of mouse SCLC in vivo.

Monoclonal immunoscintigraphy for detection of metastasis and recurrence of colorectal cancer.

Aim: To assess the clinical role of monoclonal immunoscintigraphy for the detection of metastasis and recurrence of colorectal cancer.

Methods: Monoclonal immunoscintigraphy was performed in patients operated on for colorectal adenocarcinoma suspected of local recurrence and metastatic disease. The results were compared with conventional diagnostics.

FLT-3: a new focus in the understanding of acute leukemia.

The FMS-like tyrosine kinase-3 (FLT-3), which belongs to the class III receptor tyrosine kinase family, is primarily expressed by hematopoietic cells and plays an important role in hematopoiesis. FLT-3 is also expressed in the majority of acute leukemias, in which the presence of FLT-3 activating mutations is associated with poor prognosis. Consequently, there has been a recent surge in the development of FLT-3 inhibitors for the molecular targeting of leukemia, and many of these are now in clinical trials.