Trastuzumab Mechanism of Action; 20 Years of Research to Unravel a Dilemma.

Trastuzumab as a first HER2-targeted therapy for the treatment of HER2-positive breast cancer patients was introduced in 1998. Although trastuzumab has opened a new avenue to treat patients with HER2-positive breast cancer and other types of cancer, some patients are not responsive or become resistant to this treatment. So far, several mechanisms have been suggested for the mode of action of trastuzumab; however, the findings regarding these mechanisms are controversial. In this review, we aimed to provide a detailed insight into the various mechanisms of action of trastuzumab.

Induction of Cell Cycle Arrest in MKN45 Cells after Schiff Base Oxovanadium Complex Treatment Using Changes in Gene Expression of CdC25 and P53.

Compounds containing heavy metals such as vanadium, nickel, and cobalt may be useful for the treatment of various diseases. Multiple studies have been carried out on the anticancer effects of vanadium-contained compounds on different cell types. This study aimed to evaluate the role of schiff base oxovanadium complex ([N,N'-bis(3-methoxy-salicylidene)-1,2-phenylenediamine]Vanadium(IV) Oxide Complex) on cell cycle arrest and different cell cycle phases in MKN45 cell of gastric cancer. Schiff base oxovanadium complex was used to assessthe amount of cytotoxicity via cell viability test. PI color and flow cytometry technique were applied to evaluate the effects of vanadium synthetic compounds on cell cycle phases; subsequently, we analyzed the change rates of gene expression in P53, GADD45, and CDC25 genes, which are involved in cell division phases. The findings indicated that the vital activities of time-dependent and concentration-dependent MKN45 cells with schiff base oxovanadium complex were significantly reduced; therefore, this complex is able to inhibit the migration of cancer cells and metastatic activities in a time-dependent mode. Cell cycle arrest was obtained after 48 h of treatment in phase G2/M at 1 microgram/milliliter (µg/ml) concentration. This is probably attributed to the increased gene expression of P53 and GADD45 genes and reduced gene expression of CDC25 gene. Compounds containing such heavy metals as vanadium decrease the growth, proliferation, and migration of MKN45 cells. They arrest cell cycle in phase G2/M via changing the controllers of cell division phases activated due to DNA damage.

Molecular Landscape in Alveolar Soft Part Sarcoma: Implications for Molecular Targeted Therapy.

Alveolar soft part sarcoma (ASPS) is a highly aggressive rare soft tissue sarcoma (STS) with poor prognosis especially in the metastatic form. ASPS is resistant to standard chemotherapy. Although, early diagnosis and surgical resection of operable tumor could lead to improved patient survival but novel treatment options are needed for advanced (metastatic) ASPS. This malignancy exhibits highly angiogenic behavior which reflects hyper-activation and over expression of angiogenic factors. Understanding the molecular events in this type of sarcoma is important in finding novel molecular based targeted therapies. We aim to review molecular aspects of ASPS growth and treatment.

Induction of Apoptosis and Inhibition of Invasion in Gastric Cancer Cells by Titanium Dioxide Nanoparticles.

OBJECTIVES: Nanoparticles induce oxidative stress in cells and damage them through the cell membrane and DNA damage, eventually resulting in cell death. This study aimed to evaluate the effect of titanium dioxide (TiO2) nanoparticles on apoptosis induction and invasion of gastric cancer cell line, MKN-45. METHODS: We used the MTT assay to assess proliferation of MKN-45 gastric cancer cells after exposure to different forms of TiO2 nanoparticles including amorph, brookite, anatase, and rutile coated with polyethylene glycol (PEG) and bovine serum albumin (BSA). Ethidium bromide and acridine orange staining were used to visualize cancer cell apoptosis, and the wound healing assay technique (migration test) was used to assay cancer cell invasion. RESULTS: Viability and proliferation of cancer cells in the presence of various forms of TiO2 nanoparticles were reduced (p ≤ 0.050). This reduction in cell proliferation and viability was directly related to concentration and duration of exposure to nanoparticles. Induction of cell death was seen in all groups (p ≤ 0.050). Increased cell invasion was seen in PEG-amorph TiO2 group compared to the control group. Cell invasion was decreased only in the brookite BSA group (p ≤ 0.050). CONCLUSIONS: Various forms of TiO2 nanoparticles reduced cell proliferation and induced apoptosis in cancer cells. Some forms of TiO2 nanoparticles such as brookite BSA also inhibited cell invasion. PEG-amorph TiO2 nanoparticles increased cell invasion. These differences seem to be due to the effects of different configurations of TiO2 nanoparticles. TiO2 may provide a new strategy for cancer treatment and more studies are needed.

Multimodal tumor suppression by miR-302 cluster in melanoma and colon cancer.

The miR-302 family is one of the main groups of microRNAs, which are highly expressed in embryonic stem cells (ESCs). Previous reports have indicated that miR-302 can reduce the proliferation rate of some cancer cells while compromising on their oncogenic potential at the same time without having the same effect on normal somatic cells. In this study we aimed to further investigate the role of the miR-302 cluster in multiple cancer signaling pathways using A-375 melanoma and HT-29 colorectal cancer cells. Our results indicate that the miR-302 cluster has the potential to modulate oncogenic properties of cancer cells through inhibition of proliferation, angiogenesis and invasion, and through reversal of the epithelial-to-mesenchymal transition (EMT) in these cells. We showed for the first time that overexpression of miR-302 cluster sensitized A-375 and HT-29 cells to hypoxia and also to the selective BRAF inhibitor vemurafenib. MiR-302 is a pleiotropically acting miRNA family which may have significant implications in controlling cancer progression and invasion. It acts through a reprogramming process, which has a global effect on a multitude of cellular pathways and events. We propose that reprogramming of cancer cells by epigenetic factors, especially miRNAs might provide an efficient tool for controlling cancer and especially for those with more invasive nature.