Differential synergistic effects of palbociclib and doxorubicin on doxorubicin-resistant cancer cells with diverse tumor origins.

Palbociclib is a dual inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6). Palbociclib has frequently been studied in breast cancer cells and has also been linked to function of P-glycoprotein (P-gp), main protein responsible for cancer drug resistance. However, the effect of Palbociclib on cancer drug resistance and specifically doxorubicin-resistant cells overexpressing P-gp have limitedly been studied in the literature.

Synthesis, Anticancer Activity, and Modeling of Alkylsulfonyl Benzimidazole Derivatives: Unveiling Potent Bcl-2 Inhibitors for Breast Cancer.

A series of alkylsulfonyl 1-benzo[]imidazole derivatives were synthesized and evaluated for anticancer activity against human breast cancer cells, MCF-7 . The cytotoxic potential was determined using the xCELLigence real-time cell analysis, and expression levels of genes related to microtubule organization, tumor suppression, apoptosis, cell cycle, and proliferation were examined by quantitative real-time polymerase chain reaction. Molecular docking against Bcl-2 was carried out using AutoDock Vina, while ADME studies were performed to predict the physicochemical and drug-likeness properties of the synthesized compounds.

Drug metabolism and inflammation related distinct miRNA signature of colchicine resistant familial Mediterranean fever patients.

Objective: Colchicine is the primary treatment for familial Mediterranean fever (FMF). Although colchicine is safe and effective in FMF patients, around 5-10% of patients show resistance to the drug. This study investigates the possibility of a link between colchicine resistance and the distinct miRNA profiles in colchicine resistant FMF patients.

Investigation of the Therapeutic Effects of Palbociclib Conjugated Magnetic Nanoparticles on Different Types of Breast Cancer Cell Lines.

Introduction: Drug targeting and controlled drug release systems in cancer treatment have many advantages over conventional chemotherapy in terms of limiting systemic toxicity, side effects, and overcoming drug resistance.

Methods And Results: In this paper, fabricating nanoscale delivery system composed of magnetic nanoparticles (MNPs) covered with poly-amidoamine (PAMAM) dendrimers and using its advantages were fully used to help the chemotherapeutic drug, Palbociclib, effectively reach tumors, specifically and stay stable in the circulation longer. In order to determine whether conjugate selectivity can be increased for the specific drug type, we have reported different strategies for loading and conjugation of Palbociclib to different generations of magnetic PAMAM dendrimers.

Vancomycin Containing PDLLA and PLGA/β-TCP Inhibit Biofilm Formation but Do Not Stimulate Osteogenic Transformation of Human Mesenchymal Stem Cells.

Aims: Chronic osteomyelitis, including implant-related prosthetic joint infection, is extremely difficult to cure. We develop vancomycin containing release systems from poly(d,l-lactide) (PDLLA) and poly(d,l-lactide-co-glycolide) (PLGA) composites with beta-tricalcium phosphate (β-TCP) to treat methicillin-resistant osteomyelitis. We ask whether vancomycin containing PDLLA/β-TCP and PLGA/β-TCP composites will prevent early biofilm formation, allow cell proliferation and osteogenic differentiation, and stimulate osteogenic signaling molecules in the absence of an osteogenic medium.

Development of a microfluidic platform to maintain viability of micro-dissected tumor slices in culture.

One of the issues limiting the development of personalized medicine is the absence of realistic models that reflect the nature and complexity of tumor tissues. We described a new tissue culture approach that combines a microfluidic chip with the microdissected breast cancer tumor. "Tumor-on-a-chip" devices are suitable for precision medicine since the viability of tissue samples is maintained during the culture period by continuously feeding fresh media and eliminating metabolic wastes from the tissue.

Characterization of Gemcitabine Loaded Polyhydroxybutyrate Coated Magnetic Nanoparticles for Targeted Drug Delivery.

Background: Targeted drug delivery is one of the recent hot topics in cancer therapy. Because of having a targeting potential under the magnetic field and a suitable surface for the attachment of different therapeutic moieties, magnetic nanoparticles are widely studied for their applications in medicine.

Objective: Gemcitabine loaded polyhydroxybutyrate coated magnetic nanoparticles (Gem-PHB-MNPs) were synthesized and characterized for the treatment of breast cancer by the targeted drug delivery method.

Determination of the relationship between doxorubicin resistance and Wnt signaling pathway in HeLa and K562 cell lines.

Activation of the Wnt signaling in some types of cancer and its relation with chemotherapy resistance is a very interesting issue that has been emphasized in recent years. Although, it is known that increase in the activity of β-catenin is important in blast transformation and drug resistance, the underlying mechanisms are still unclear. In this study, changes in the expression levels of 186 genes that are thought to be important in drug resistance and Wnt signaling pathways were determined by using qPCR method in doxorubicin-sensitive and -resistant HeLa and K562 cell lines.

Co-delivery of Doxorubicin and D-α-Tocopherol Polyethylene Glycol 1000 Succinate by Magnetic Nanoparticles.

Background: Although conventional chemotherapy is the most common method for cancer treatment, it has several side effects such as neuropathy, alopecia and cardiotoxicity. Since the drugs are given to body systemically, normal cells are also affected, just like cancer cells. However, in recent years, targeted drug delivery has been developed to overcome these drawbacks.

Half generations magnetic PAMAM dendrimers as an effective system for targeted gemcitabine delivery.

Tumor-specific delivery of anticancer drugs by magnetic nanoparticles will maximize the efficacy of the drug and minimize side effects, and reduce systemic toxicity. The magnetic core of these nanoparticles provides an advantage for selective drug targeting as they can be targeted to the tumor site and accumulated in cancer cells by means of an external magnetic field. Magnetic nanoparticles can be coated with Polyamidoamine (PAMAM) dendrimer and loaded with drugs.

Loading of Gemcitabine on chitosan magnetic nanoparticles increases the anti-cancer efficacy of the drug.

Targeted delivery of anti-cancer drugs increase the efficacy, while decreasing adverse effects. Among various delivery systems, chitosan coated iron oxide nanoparticles (CsMNPs) gained attention with their biocompatibility, biodegradability, low toxicity and targetability under magnetic field. This study aimed to increase the cellular uptake and efficacy of Gemcitabine.

An update on molecular biology and drug resistance mechanisms of multiple myeloma.

Multiple myeloma (MM), a neoplasm of plasma cells, is the second most common hematological malignancy. Incidance rates increase after age 40. MM is most commonly seen in men and African-American population.

Identification of XRCC1 Arg399Gln and XRCC3 Thr241Met Polymorphisms in a Turkish Population and Their Association with the Risk of Chronic Lymphocytic Leukemia.

DNA repair systems are essential for cellular functions. Defects due to sequence variations in DNA repair genes can lead severe failure of cell functions and causing many cancer types including leukemia. The aim of this study was to investigate the relationship between XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms and susceptibility to chronic lymphocytic leukemia (CLL) in Turkish patients.

Detection of XRCC1 gene polymorphisms in Turkish head and neck squamous cell carcinoma patients: a comparative analysis with different populations.

Purpose: X-ray repair cross-complementing (XRCC1) is one of the most important genes for the maintenance of genomic integrity and protection of cells from DNA damage. Although tobacco and alcohol consumption are the major risk factors for the development of head and neck squamous cell carcinoma (HNSCC), sequence variation in XRCC1 gene may alter HNSCC susceptibility. Reports on the relationship between HNSCC and polymorphisms in XRCC1 gene have been inconsistent so far.

Association between XRCC3 Thr241Met polymorphism and laryngeal cancer susceptibility in Turkish population.

DNA repair systems are essential for normal cell function. Genetic alterations in the DNA repair genes such as X-ray repair cross-complementing group 3 (XRCC3), can cause a change in protein activity which results in cancer susceptibility. The aim of this study was to investigate the association of XRCC3 Thr241Met single nucleotide polymorphism (SNP), smoking and alcohol consumption with the risk of laryngeal cancer in Turkish population.

Different types of cell cycle- and apoptosis-related gene expressions alter in corticosteroid-, vincristine-, and melphalan-resistant u-266 multiple myeloma cell lines.

Objective: Hemophilia B is caused by coagulation defects in the factor IX gene located in Xq27.1 on the X chromosome. A wide range of mutations, showing extensive molecular heterogeneity, have been described in hemophilia B patients.

Association of -174G/C interleukin/6 gene polymorphism with the risk of chronic lymphocytic, chronic myelogenous and acute myelogenous leukemias in Turkish patients.

Purpose: The purpose of this study was to evaluate the relationship between -174G/C interleukin-6 (IL-6) gene promoter polymorphism and susceptibility to chronic lymphocytic (CLL), chronic myelogenous (CML) and acute myelogenous leukemia (AML) in Turkish patients.

Methods: The frequencies of -174G/C polymorphism were studied in 23 unrelated CLL, 25 CML and 17 AML patients and 30 healthy individuals. Single nucleotide polymorphisms (SNPs) were genotyped by the PCR-RFLP method.

Idarubicin-loaded folic acid conjugated magnetic nanoparticles as a targetable drug delivery system for breast cancer.

Conventional cancer chemotherapies cannot differentiate between healthy and cancer cells, and lead to severe side effects and systemic toxicity. Another major problem is the drug resistance development before or during the treatment. In the last decades, different kinds of controlled drug delivery systems have been developed to overcome these shortcomings.

Polyhydroxybutyrate-coated magnetic nanoparticles for doxorubicin delivery: cytotoxic effect against doxorubicin-resistant breast cancer cell line.

In this study, polyhydroxybutyrate (PHB)-coated magnetic nanoparticles (MNPs) were prepared by coprecipitation of iron salts (Fe and Fe) by ammonium hydroxide. Characterizations of PHB-coated MNPs were performed by Fourier transform infrared spectroscopy, x-ray diffraction, dynamic light scattering, thermal gravimetric analysis, vibrating sample magnetometry, and transmission electron microscopy analyses. Doxorubicin was loaded onto PHB-MNPs, and the release efficiencies at different pHs were studied under in vitro conditions.

Synthesis of Doxorubicin loaded magnetic chitosan nanoparticles for pH responsive targeted drug delivery.

Targeted drug delivery is a promising alternative to overcome the limitations of classical chemotherapy. In an ideal targeted drug delivery system carrier nanoparticles would be directed to the tumor tissue and selectively release therapeutic molecules. As a novel approach, chitosan coated magnetic nanoparticles (CS MNPs) maintain a pH dependent drug delivery which provides targeting of drugs to the tumor site under a magnetic field.

Chitosan magnetic nanoparticles for pH responsive Bortezomib release in cancer therapy.

The use of nanotechnology in cancer treatment offers exciting opportunities, including the possibility of destroying tumors with minimal damage to healthy tissue by novel targeted drug delivery systems. pH differences between healthy and tumor microenvironment provide pH responsive release of drugs at tumor site via smart nanoparticles. In this study, chitosan coated superparamagnetic iron oxide nanoparticles (CS MNPs) were in situ synthesized by ionic crosslinking method as nanocarrier systems and loaded with the drug Bortezomib (Velcade(®)).

The -137G/C Polymorphism in Interleukin-18 Gene Promoter Contributes to Chronic Lymphocytic and Chronic Myelogenous Leukemia Risk in Turkish Patients.

Objective: Interleukin-18 (IL-18) is a cytokine that belongs to the IL-1 superfamily and is secreted by various immune and nonimmune cells. Evidence has shown that IL-18 has both anticancer and procancer effects. The aim of this study was to evaluate the relationship between IL-18 gene polymorphisms and susceptibility to chronic lymphocytic leukemias (CLL) and chronic myelogenous leukemias (CML) in Turkish patients.

Doxorubicin loading, release, and stability of polyamidoamine dendrimer-coated magnetic nanoparticles.

Nanotechnology is a promising alternative to overcome the limitations of classical chemotherapy. As a novel approach, dendrimer-coated magnetic nanoparticles (DcMNPs) maintain suitable drug delivery system because of their buildup of functional groups, symmetry perfection, nanosize, and internal cavities. They can also be targeted to the tumor site in a magnetic field.

Differential oncogene-related gene expressions in myeloma cells resistant to prednisone and vincristine.

Multidrug resistance in cancer may arise due to alterations in gene expression. In this study, sublines of drug-resistant multiple myeloma (MM) cells, namely RPMI-8226 and U-266, were examined for their differential oncogene-related gene expression levels and the relations to drug resistance were analyzed. Drug resistance was induced by application of the prednisone or vincristine using stepwise dose increments.

Differential gene expression analysis related to extracellular matrix components in drug-resistant RPMI-8226 cell line.

Drug resistance remains a major obstacle to the successful use of chemotherapeutic drugs for many types of cancers including multiple myeloma. It is becoming increasingly apparent that tumor microenvironment could provide a shelter to malignant plasma cells that allow their survival after initial drug exposure. This study demonstrates alterations in gene expression levels of several extracellular matrix (ECM) components in prednisone, vincristine and melphalan-resistant RPMI-8226 myeloma cells.