Fe3O4 and Fe3O4core Aushell-based Hyperthermia Reduces Expression of Proliferation Markers Ki-67, TOP2A and TPX2 in a Human Breast Cancer Cell Line.

BACKGROUND/AIM: Hyperthermia represents an adjuvant local anticancer strategy which relies on the increase of temperature beyond the physiological level. In this study, we investigated the anticancer potential of Fe3O4 and Fe3O4core Aushell nanoparticles as hyperthermic agents in terms of cytotoxicity and studied the expression of cellular markers of proliferation (changes in mRNA levels via real-time polymerase chain reaction). MATERIALS AND METHODS: The human breast cancer cell line SK-BR-1 was incubated with either Fe3O4 or Fe3O4core Aushell nanoparticles stabilized with tryptophan, prior to hyperthermia treatment. The normal HEK293 cell line was used as a control. Toxicity was determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay to estimate possible toxic effects of the tested nanoparticles. After RNA extraction and cDNA synthesis, mRNA expression of three indicators of proliferation, namely marker of proliferation Ki-67, DNA topoisomerase II alpha (TOP2A) and TPX2 microtubule nucleation factor (TPX2), was investigated. RESULTS: At each concentration tested, Fe3O4core Aushell nanoparticles showed greater toxicity compared to Fe3O4, while SK-BR-3 cells were more susceptible to their cytotoxic effects compared to the HEK293 cell line. The expression of Ki-67, TOP2A and TPX2 was reduced in SK-BR-3 cells by both Fe3O4 or Fe3O4core Aushell nanoparticles compared to untreated cells, while the only observed change in HEK293 cells was the up-regulation of TOP2A. CONCLUSION: Both Fe3O4core Aushell and Fe3O4 NPs exhibit increased cytotoxicity to the cancer cell line tested (SK-BR-3) compared to HEK293 cells. The down-regulation in SK-BR-3 cells of the three proliferative markers studied, Ki-67, TOP2A and TPX2, after incubation with NPs suggests that cells that survived thermal destruction were not actively proliferating.

An overview of hormonal directed pharmacotherapy for the treatment of prostate cancer.

INTRODUCTION: Prostate cancer is the most common malignancy in the male. Androgen-deprivation therapy (ADT) has been the mainstay in the treatment of metastatic prostate cancer however, due to the outgrowth of castration-resistant cell population the disease inevitably progresses to an aggressive, difficult to handle stage. AREAS COVERED: We have reviewed the literature regarding hormonal-directed therapy prostate cancer. New agents, namely abiraterone acetate, combined with prednisone, and next generation antiandrogens (enzalutamide, apalutamide and darolutamide) have shown considerable efficacy, not only in patients with metastatic but also in those with non-metastatic disease, either castration resistant (CRPC) or hormone sensitive (HSPC). EXPERT OPINION: The addition of abiraterone and of the second-generation antiandrogens to our therapeutic armamentarium has improved prognosis ofprostate cancer in the last decade. Abiraterone is a viable option in patients with metastatic disease (hormone-sensitive and castration-resistant), whereas all next-generation antiandrogens have demonstrated efficacy in terms of metastasis-free and overall survival in non-metastatic CRPC. In addition, enzalutamide has also been found efficacious in mCRPC and mHSPC, while apalutamide in mHSPC. Currently there are no reliable data to indicate a potential superiority of one of these agents over the others in CRPC or HSPC as there are no relevant head to head studies . Sequencing hormone treatment modalities, chemotherapies and immunotherapies have not reached a consensus as yet. Randomized controlled trials are warranted to clearly define the role of novel antiandrogens in the treatment of prostate cancer. The choice of treatment should be individualized following discussion with the patient .

Nanoparticle-Mediated Hyperthermia and Cytotoxicity Mechanisms in Cancer.

Hyperthermia has the potential to damage cancerous tissue by increasing the body temperature. However, targeting cancer cells whilst protecting the surrounding tissues is often challenging, especially when implemented in clinical practice. In this direction, there are data showing that the combination of nanotechnology and hyperthermia offers more successful penetration of nanoparticles in the tumor environment, thus allowing targeted hyperthermia in the region of interest. At the same time, unlike radiotherapy, the use of non-ionizing radiation makes hyperthermia an attractive therapeutic option. This review summarizes the existing literature regarding the use of hyperthermia and nanoparticles in cancer, with a focus on nanoparticle-induced cytotoxicity mechanisms.

Mediastinal and hilar sarcoid-like reaction in a patient treated with dabrafenib and trametinib for metastatic melanoma: A case report and review of the literature.

BRAF/MEK inhibitors are considered standard of care in the treatment of advanced BRAF-mutated malignant melanoma, and have been, in rare cases, associated with granulomatous reactions, mostly limited to skin lesions. The present study reported the case of a patient with metastatic melanoma developing a sarcoid-like reaction manifesting as asymptomatic mediastinal and right hilar lymphadenopathy while on antineoplastic therapy with dabrafenib and trametinib. To the best of our knowledge, this is the first reported case of isolated lymphadenopathy as a manifestation of drug-induced sarcoid-like reaction under dabrafenib and trametinib. Overall, only 17 other cases of granulomatosis have been reported in the literature. Although uncommon, such reactions should be considered in the differential diagnosis of lymph node enlargement, and distinguishing them from tumor progress is important and can be challenging in clinical practice.

The potential role of the combined PARP-1 and VEGF inhibition in severe SARS-CoV-2 (COVID-19) infection.

INTRODUCTION: During the evolution of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, several drug candidates have been proposed for repositioning towards a quest for more effective treatments. METHODOLOGY: We reviewed recent literature (Pubmed, Google, Clinicaltrials.gov), as of the middle of May 2021, for evidence regarding the potential benefit from poly(ADP-ribose)-polymerase inhibitors and vascular endothelial growth factor blockade in severe SARS-CoV-2 infection. RESULTS: poly(ADP-ribose)-polymerase inhibitors have been suggested as potential agents against coronavirus disease 2019 (COVID-19) by a variety of mechanisms. vascular endothelial growth factor-associated vascular permeability is implicated with increased vascular leakage and pulmonary oedema. Thus, anti-angiogenesis factors, such as bevacizumab are being investigated in critically ill COVID-19 patients. CONCLUSIONS: The synergistic potential of these two classes of inhibitors in severe COVID-19 management could be beneficial. Further research should be carried out in order to support this hypothesis.