The dynamic interactions of cancer cells with their microenvironment consisting of stromal cells (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity of cancer cell, clonal evolution and to increase the multidrug resistance ending in cancer cell progression and metastasis. The reciprocal cell-cell/ECM interaction and tumor cell hijacking of non-malignant cells force stromal cells to lose their function and acquire new phenotypes that promote development and invasion of tumor cells. Understanding the underlying cellular and molecular mechanisms governing these interactions can be used as a novel strategy to indirectly disrupt cancer cell interplay and contribute to the development of efficient and safe therapeutic strategies to fight cancer. Furthermore, the tumor-derived circulating materials can also be used as cancer diagnostic tools to precisely predict and monitor the outcome of therapy. This review evaluates such potentials in various advanced cancer models, with a focus on 3D systems as well as lab-on-chip devices.

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Lung cancer is a leading cause of cancer-related deaths worldwide, with less than a 5-year survival rate for both men and women. Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma oncogene (KRAS) signaling pathways play a critical role in the proliferation and progression of various cancers, including lung cancer. Genetic studies have shown that amplification, over-expression, or mutation of EGFR is an early and major molecular event in many human tumors. KRAS mutation is a negative factor in various cancer, including non-small-cell lung cancer, and complicates therapeutic approaches with adjuvant chemotherapy and anti-EGFR directed therapies. This article is dedicated to evaluating the synergistic effect of a novel EGFR inhibitor AZD8931 and KRAS small interfering RNA (siRNA) on the proliferation and apoptosis of lung adenocarcinoma cancer cells. A549 lung cancer cells were treated with KRAS siRNA and the EGFR inhibitor alone or in combination. The cytotoxic effects of KRAS siRNA and te EGFR inhibitor were determined usingMTT assay, and induction of apoptosis was determined by FACS analysis. Suppression of KRAS, Her-2, and EGFR expression by treatments was measured by qRT-PCR and western blotting. KRAS siRNA and the EGFR inhibitor significantly reduced the proliferation of A549 cells as well as KRAS and EGFR mRNA levels 24 hr after treatment. The results also indicated that the silencing of KRAS and EGFR has synergistic effects on the induction of apoptosis on the A549 cells. These results indicated that KRAS and EGFR might play important roles in the progression of lung cancer and could be potential therapeutic targets for treatment of lung cancer.

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Botulinum neurotoxins (BoNTs) result in severe and often fatal disease, botulism. Common remedial measures such as equine antitoxin and human botulism immunoglobulin in turn are problematic and time-consuming. Therefore, diagnosis and therapy of BoNTs are vital. The variable domain of heavy-chain antibodies (VHH) has unique features, such as the ability to identify and bind specifically to target epitopes and ease of production in bacteria and yeast. The Pichia pastoris is suitable for expression of recombinant antibody fragments. Disulfide bond formation and correct folds of protein with a high yield are some of the advantages of this eukaryotic host. In this study, we have expressed and purified the camelid VHH against BoNT/E in P. pastoris. The final yield of P. pastoris-expressed antibody was estimated to be 16 mg/l, which is higher than that expressed by Escherichia coli. The nanobody expressed in P. pastoris neutralized 4LD50 of the BoNT/E upon i.p. injection in 25% of mice. The nanobody expressed in E. coli extended the mice's survival to 1.5-fold compared to the control. This experiment indicated that the quality of expressed protein in the yeast is superior to that of the bacterial expression. Favorable protein folding by P. pastoris seems to play a role in its better toxin-binding property.

Objective: GCK rs780094 polymorphism is a single nucleotide polymorphism that has been associated with obesity, type II diabetes and dyslipidemia in some populations, conditions that highly related to NAFL etiology. The present study aimed to evaluate the relationship between NAFLD and rs780094 polymorphism in patients with NAFLD in Tabriz city, northwest of Iran. The rs780094 polymorphism was determined in 74 patients with NAFLD by PCR-RFLP technique. Demographic information was collected using a questionnaire and biochemical analysis was performed using standard laboratory methods. Results: There was a significant difference between case and control subjects for alanine aminotransferase, aspartate aminotransferase, HDL-C and triglycerides (P < 0.05). Analysis by PCR-RFLP method revealed that there were no significant differences between NAFLD and healthy subjects for rs780094 polymorphism in the study population. The results of this study indicated that rs780094 polymorphism is not associated with NAFLD in subjects from Tabriz city.

Ocular drug delivery is one of the most challenging endeavors among the various available drug delivery systems. Despite having suitable drugs for the treatment of ophthalmic disease, we have not yet succeeded in achieving a proper drug delivery approach with the least adverse effects. Nanotechnology offers great opportunities to overwhelm the restrictions of common ocular delivery systems, including low therapeutic effects and adverse effects because of invasive surgery or systemic exposure. The present review is dedicated to highlighting and updating the recent achievements of nano-based technologies for ocular disease diagnosis and treatment. While further effort remains, the progress illustrated here might pave the way to new and very useful ocular nanomedicines.