Octav Ginghina

Impact of multicellular tumor spheroids as an in vivo-like tumor model on anticancer drug response

The incidence of colorectal cancer is higher in men than in women, amounting to 15% of cancer-related diseases as a whole. As such, undesirable effects, arising from the administration of current chemotherapeutic agents (the FOLFIRI/FOLFOX combinations), which are exerted on the remaining non-cancerous tissues and/or cells, have contributed to the occurrence of resistance to multiple drugs, thus markedly reducing their efficacy. However, the delivery of chemotherapeutic agents may be improved and their action may be more selectively targeted to diseased tissues/cells by means of developing biotechnologies and nano-techniques. Thus, the current focus is on creating biological tissue and related tumor models, by means of three-dimensional (3D) spheres, in an attempt to bridge the gap between results obtained in the pre-clinical phase and promising outcomes obtained in clinical trials. For this purpose, the characterization and use of so-called ‘multicellular tumor spheroids’, may prove to be invaluable. In this study, we focus on describing the efficacy of a model 3D system as compared to the traditional 2D tumor spheres in determining drug response, highlighting a potentially greater effect of the drugs following the encapsulation of respective liposomes. The results obtained demonstrate the successful preparation of a suspension of liposomes loaded with folinic acid, oxaliplatin and 5-fluorouracil (5-FU), and loaded with meso-tetra (4-sulfonatophenyl) porphyrin. Following its use on HT-29 colorectal cancer cells, an important comparative reduction was noted in the viability of the HT-29 cells, demonstrating the efficacy of multicellular tumor spheroids carrying liposomes loaded with therapeutic drugs. These findings indicate that the method of drug encapsulation in liposomes may improve the treatment efficacy of chemotherapeutic agents.

Update on radionuclide therapy in oncology (Review)

Unstable isotopes and their capacity to emit ionizing radiation have been employed in clinical practice not only for diagnostic, but also for therapeutic purposes, with significant contribution in several fields of medicine and primarily in the management of oncologic patients. Their efficacy is associated with their ability to provide the targeted delivery of ionizing radiation for a determined duration. These compounds can be used for curative or palliative treatment, as well as for a diagnostic-therapeutic (theranostic) approach. This review summarises the most recent trends in radionuclide treatment for several malignancies, including prostate cancer, neuroendocrine tumours, and hematological and thyroid malignancies, in which radionuclide-based therapies have been employed with high effectiveness.

Poly(HydroxyButyrate-co-HydroxyValerate) (PHBHV) Nanocarriers for Silymarin Release as Adjuvant Therapy in Colo-rectal Cancer

The aim of this study was to address one of the major challenges of the actual era of nanomedicine namely, the bioavailability of poorly water soluble drugs such as Silymarin. We developed new, biodegradable, and biocompatible nanosized shuttles for Silymarin targeted delivery in colon-cancer cells. The design of these 100 nm sized carrier nanoparticles was based on natural polymers and their biological properties such as cellular uptake potential, cytotoxicity and 3D penetrability were tested using a colon cancer cell line (HT-29) as the in vitro culture model. Comparative scanning electron microscopy (SEM) and atomic force microscopy (AFM) measurements demonstrated that the Silymarin loaded Poly(3-HydroxyButyrate-co-3-HydroxyValerate) (PHBHV) nanocarriers significantly decreased HT-29 cells viability after 6 and 24 h of treatment. Moreover, in vivo-like toxicity studies on multicellular tumor spheroids showed that the Silymarin loaded PHBHV nanocarriers are able to penetrate 3D micro tumors and significantly reduce their size.

Colon Cancer Cells Gene Expression Signature As Response to 5- Fluorouracil, Oxaliplatin, and Folinic Acid Treatment

5-FU cytotoxicity mechanism has been assigned both to the miss-incorporation of fluoronucleotides into RNA and DNA and to the inhibition of thymidylate synthase. 5-FU is one of the most widely used chemotherapeutic drugs, although it has severe side effects that may vary between patients. Pharmacogenetic studies related to 5-FU have been traditionally focused on the rate-limiting catabolic enzyme, dihydropyrimidine dehydrogenase that breaks 80–85% of 5-FU into its inactive metabolite. Choosing the right dosing scheme and chemotherapy strategy for each individual patient remains challenging for personalized chemotherapy management. In the general effort toward reduction of colorectal cancer mortality, in vitro screening studies play a very important role. To accelerate translation research, increasing interest has been focused on using in vivo-like models such as three-dimensional spheroids. The development of higher throughput assays to quantify phenotypic changes in spheroids is an active research area. Consequently, in this study we used the microarray technology to reveal the HT-29 colorectal adenocarcinoma cells gene expression signature as response to 5-FU/OXP/FA treatment in a state of the art 3D culture system. We report here an increased reactive oxygen species production under treatment, correlated with a decrease in cell viability and proliferation potential. With respect to the HT-29 cells gene expression under the treatment with 5-FU/OXP/FA, we found 15.247 genes that were significantly differentially expressed (p < 0.05) with a fold change higher that two-fold. Among these, 7136 genes were upregulated and 8111 genes were downregulated under experimental conditions as compared to untreated cells. The most relevant and statistic significant (p < 0.01) pathways in the experiment are associated with the genes that displayed significant differential expression and are related to intracellular signaling, oxidative stress, apoptosis, and cancer.

A rare case of advanced lung cancer presenting as a symptomatic gastric tumor

Although gastric metastases have been estimated to occur in less than 2% of cancer patients, an increased use of upper digestive tract endoscopy allows for a higher detection of secondary gastric tumors. We describe the case of a 66-year-old male patient presenting with mild pain in the sternum and upper abdominal area. Physical examination revealed a right parietal skull tumor, with no other significant clinical changes. Upon exclusion of an acute coronary syndrome, upper digestive tract endoscopy was performed, showing the presence of an ulcerated tumor located in the gastric fundus. Histopathologic examination of the biopsy sample and immunohistochemical tests suggested a pulmonary origin of the gastric tumor. Whole body computer tomography showed the presence of tumors in the gastric fundus, left lung, liver, kidneys, bones and brain. Transbronchial biopsy of the lung tumor certified the diagnosis of non-small cell lung cancer, with the same immunohistochemical profile as the gastric tumor. Hence, it was considered the origin of the metastases. Biopsy of the skull tumor also had the identical tumor histology. Whole brain radiotherapy was performed for the brain metastases and subsequent chemotherapy was administered. Although non-specific, gastrointestinal signs and symptoms occurring in lung cancer patients should alert the clinicians as to the possibility of gastrointestinal metastases and prompt endoscopic evaluation.