Novel 5,6-disubstituted pyridazin-3(2H)-one derivatives were designed and synthesized as combretastatin A-4 analogues. Our objective was to overcome the spontaneous cis to trans isomerization of the compound. We therefore replaced the cis-double bond with a pyridazine ring. The antiproliferative activity of the novel analogues was evaluated against four human cancer cell lines (HL-60, MDA-MB-435, SF-295 and HCT-8). We found the analogues had little activity either against selected cell lines or against purified tubulin. Molecular modeling studies may account for their inactiviy.

The number of patients with colorectal cancer, the third most frequently diagnosed malignancy in the world, has increased markedly over the past 20 years and will continue to increase in the future. Despite recent advances in chemotherapy, currently used anticancer molecules are unable to improve the prognosis of advanced or recurrent colorectal cancer, which remains incurable. The transport of classical drugs by nanoparticles has shown great promise in terms of improving drug distribution and bioavailability, increasing tissue half-life and concentrating anticancer molecules in the tumor mass, providing optimal drug delivery to tumor tissue, and minimizing drug toxicity, including those effects associated with pharmaceutical excipients. In addition, colon cancer targeting may be improved by incorporating ligands for tumor-specific surface receptors. Similarly, nanoparticles may interact with key drug-resistance molecules to prevent a reduction in intracellular drug levels drug. Recently published data have provided convincing pre-clinical evidence regarding the potential of active-targeted nanotherapeutics in colon cancer therapy, although, unfortunately, only a few of these therapies have translated into early-phase clinical trials. As nanotechnology promises to be a new strategy for improving the prognosis of colon cancer patients, it would be very useful to analyze recent progress in this field of research. This review discusses the current status of nanoparticle-mediated cancer-drug delivery, the challenges restricting its application, and the potential implications of its use in colon cancer therapy.

Cyclooxygenase-2 (COX-2)  inhibitor，celecoxib，causes growth inhibition of human gastric carcinoma cells, but it remains unclear whether it inhibites Helicobacter pylori-induced invasion of gastric cancer cells. The adenine nucleotide translocator (ANT) is a mitochondrial bi-functional protein. We speculated that ANT-dependent pathways might contribute to H. pylori-induced invasion and metastasis of gastric cancer cells. Therefore，in the present study we evaluate the effect of celecoxib on H. pylori-induced gastric cancer cell motility and invasion and explode the role of adenine nucleotide ANTs in pylori-induced gastric cancer cell motility and invasion of gastric AGS cells. Our results demonstrate that celecoxib induces anoikis-like apoptosis and suppresses the proliferation and invasion of gastric cancer cells induced by H. pylori in culture. RT-PCR and Western blot results indicated that celecoxib upregulated the expression of ANT1 and ANT3，however, Celecoxib could not increase expression of ANT2. Our results suggest that celecoxib could be an effective means for suppressing proliferation and invasion of gastric cancer cells induced by H. pylori through adenine nucleotide translocator -dependent mechanism.

The new complex of {[Co(4,4'-Bipy)(H2O)4]∙(Pyri)∙3H2O}n (4,4'-Bipy = 4,4'-bipyridyl, H2Pyri = 3,5-Pyridinedicarboxylic acid) has been synthesized and characterized by IR, element analysis and X-ray single-crystal diffraction. The binding of the complex with extracted HeLa cells was investigated by UV and fluorescence spectrum. Gel electrophoresis assay demonstrated the ability of the complex cleaving the extracted HC-DNA. The complex exhibited a higher cytotoxicity against tumor cells in vitro. Furthermore, the apoptotic tests indicated the complex had an apoptotic effect on HeLa cells.

A series of dehydroepiandrosterone derivatives containing dihydrazone unit were synthesized via a convenient condensation procedure, and which were evaluated for their potential anticancer activities. The preliminary assays indicated that some of the newly synthesized compounds exhibited good antitumor activities against human hepatocellular liver carcinoma (HepG2), heptoma (Huh-7), gastric cancer (BGC-823) and breast adenocarcinoma (MCF-7) cell lines compared with 5-fluorouracil (5-FU), which might be considered as promising lead scaffold for further design and synthesis of potential anticancer agents.

Cardiac glycosides represent group of compounds isolated from plants and some animals. They have been using in the therapy of heart failure for many years. In spite of the fact that cytotoxic effect of many cardiac glycosides has been demonstrated. The mechanism of the cytotoxic action is very complicated and complex, where Na+/K+-ATPase plays crucial role. On the other hand, Na+/K+-ATPase is regulated by many endogenous factors including hormones or FXYD proteins, which role in the regulation of cell cycle is intensively studied. This review focuses the role of Na+/K+-ATPase in the regulation of cell growth, cell cycle and cell proliferation and involvement of cardiac glycosides in the regulation of Na+/K+-ATPase. Cytotoxic effect of cardiac glycosides is discussed in the connection with possible apoptotic mechanisms induced by these compounds. Novel strategies in cancer therapy based on the cardiac glycosides as well as possibilities in the overcoming multidrug resistance by cardiac glycosides are discussed too. The goal of this review is to present cardiac glycosides as not only pharmaceuticals used in heart failure, but also as potent cytotoxic agents with possible involvement in cancer treatment.

Background:

Cancer is a potentially fatal diagnosis, but due to modern medicine there is a potential cure in many of these cases. The rate of treatment success depends on early disease detection and timely, effective delivery of tumour specific treatment. There are many ongoing researches aimed to improve diagnostics or treatment, but the option to use both modalities concomitantly is deficient. In this project we are using the advances in nanotechnology to develop new theranostic tool using single walled carbon nanotubes (SWCNT) and Quantum dots (QDs) for early cancer cell detection, and option to deliver targeted treatment. Method: SWCNTs were refluxed in HNO3/H2SO4 (1:3) at 120 °C for 120 minutes. Functionalised SWCNT was then covalently attached to octa-ammonium polyhedral oligomeric silsesquioxane (POSS), QDs and conjugated with antibodies for targeted cell detection. Fourier transforms infrared spectroscopy (FTIR), Transmission electron microscopy (TEM), UV/NIR analysis, Raman and UV-VIS spectroscopy were used in order to prove the successful conjugation. Toxicology study using alamar blue analysis and DNA assay was conducted in order to choose the best concentration of SWCNT, octa-ammonium-POSS and QDs before commencing the conjugation process. Human colorectal cancer cell line HT29, pancreas cancer cell line PANC-1 and mouse fibroblasts 3T3 were then treated with or without antibody conjugated SWCNT-POSS-QDs (CPQ) compound solution. The cell response was observed under the microscope after 24, 48 and 72 hours.

Results:

FTIR and Raman spectroscopies confirmed covalent binding of the SWCNTs to Octa-Ammonium-POSS. This was supported by TEM images and photos obtained, which showed well dispersed SWCNTs following its treatment with Octa-Ammonium-POSS compared to pristine SWCNT samples. UV-VIS graphs determined the presence of antibody within the compound. UV/NIR demonstrated QD fluorescence even after attachment of SWCNT-POSS. The cellular behaviour revealed high CPQ-antibody complex affinity towards cancer cells when compared to healthy cell line which internalised the complex only on day three. The pancreas cancer cell line had appearance of lysed pulp after 72 hours of incubation. Colonic cancer cells seemed to regain ability to populate from day three signifying that higher treatment payload is necessary.

Conclusion:

We have successfully manufactured novel compound consisting of Octa-Ammonium-POSS linked SWCNTs, QDs, and tumour specific antibodies. The complex has proven its potential as cell probing tool, and the attachment of antibodies has shown high affinity to cancer cells rendering this an attractive model for further theranostic developments.

Trastuzumab or lapatinib treatment with chemotherapy or hormonotherapy are the gold standard treatments for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (early breast cancer or metastatic breast cancer). Older patients have been largely underrepresented in clinical trials, and few data on trastuzumab or lapatinib efficacy and toxicity have been reported for this subgroup. This article has reviewed the main articles that have analyzed these items.

Approximately 60% of cancer incidence and 70% of cancer mortality occurs in individuals older than 65 years. The optimal approach to cancer therapy in older adults is often unclear. Historically, advanced age has been an exclusion criterion in clinical cancer trials, and older adults have been consistently underrepresented. As a result, there is a lack of information about treatment efficacy and tolerability in this population. Comprehensive Geriatric Assessment (CGA) is one of the most useful tools for the oncologist to make decisions related to older patients diagnosed with cancer. This tool has proved to be very useful to detect many deficits, tolerance to chemotherapy and survival in such patients. In this review, we analyze the role of CGA in decision making in geriatric oncology.

Focal Adhesion Kinase is a 125 kDa non-receptor kinase and overexpressed in many types of tumors. Recently, short noncoding RNAs, called microRNAs have been discovered as regulators of gene expression mainly through binding to the untranslated region (UTR) of mRNA. In this report we show that MiR-138 and MiR-135 down-regulated FAK expression in cancer cells. MiR-138 and MiR-135 inhibited FAK protein expression in different cancer cell lines. The computer analysis of 3'FAK-untranslated region (FAK-UTR) identified one conserved MiR-138 binding site (CACCAGCA) at positions 3514-3521 and one conserved MiR-135 (AAGCCAU) binding site at positions 4278-4284 in the FAK-UTR. By a dual-luciferase assay we demonstrate that MiR-138 and MiR-135 directly bound the FAK untranslated region using FAK-UTR-Target (FAK-UTR) luciferase plasmid and inhibited its luciferase activity. The site-directed mutagenesis of the MiR-13 and MiR-135 binding sites in the FAK-UTR abrogated MiR-138 and MiR-135-directed inhibition of FAK-UTR. Real-time PCR demonstrated that cells transfected with MiR-138 and MiR-135 expressed decreased FAK mRNA levels. Moreover, stable expression of MiR-138 and MiR-135 in 293 and HeLa cells decreased cell invasion and increased sensitivity to 5-fluorouracil (5-FU), FAK inhibitor, Y15, and doxorubicin. In addition, MiR-138 significantly decreased 293 xenograft tumor growth in vivo. This is the first report on regulation of FAK expression by MiR-135 and MiR138 that affected invasion, drug sensitivity, and tumor growth in cancer cells, which is important to the development of FAK-targeted therapeutics and understanding their novel regulations and functions.