No abstract

Macrophages have a leading position in the tumor microenvironment (TME) which paves the way to carcinogenesis. Initially, monocytes and macrophages are recruited to the sites where the tumor develops. Under the guidance of different microenvironmental signals, macrophages would polarize into two functional phenotypes, named as classically activated macrophages (M1) and alternatively activated macrophages (M2). Contrary to the anti-tumor effect of M1, M2 exerts anti-inflammatory and tumorigenic characters. In progressive tumor, M2 tumor-associated macrophages (TAMs) are in the majority, being vital regulators reacting upon TME. This review elaborates on the role of TAMs in tumor progression. Furthermore, prospective macrophage-focused therapeutic strategies, including drugs not only in clinical trials but also at primary research stages, are summarized followed by a discussion about their clinical application values. Nanoparticulate systems with efficient drug delivery and improved antitumor effect are also summed up in this article.

Currently, mechanisms and therapeutic approaches have been thoroughly studied in various prevalent malignant tumors, such as breast and lung cancer. However, there is inevitable tumor progression and drug resistance. Uncovering novel treatment strategies to inhibit tumor development is important. Ferroptosis, a form of cell death associated with iron and lipid peroxidation, has drawn extensive attention. In this paper, we reviewed the underlying mechanisms of ferroptosis (i.e., iron, glutathione, and lipid metabolism) and its role in various tumors (i.e., lung cancer, liver carcinoma, breast cancer, and pancreatic cancer). Moreover, we summarized ferroptosis-related anti-tumor drugs and emphasized the potential of combined treatment of anti-tumor drugs and radiotherapy in an effort to provide novel anti-tumor treatments.

Abstract. The expression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) was analyzed in immunohistochemical preparations from 46 primary parotid mucoepidermoid carcinomas (MEC). For the cases with lymph node metastases, the receptor expressions were investigated in parallel samples, primary tumour and metastasis, from each patient (n=11). The goal was to evaluate whether any of these receptors are suitable as a target for radionuclide-based imaging and therapy. The HercepTest scoring was used for the analysis of both HER2 and EGFR expression (0, 1+, 2+ or 3+). EGFR overexpression (2+/3+) was found in 67.4% (31/46) of the primary tumours. Out of the 11 cases with evaluated paired samples, EGFR overexpression was observed in 81.8% (9/11) of the primary tumours and 72.7% (8/11) of the corresponding lymph node metastases. There was only one patient who had EGFR overexpression in the primary tumours which changed to negative in the lymph node metastases but no changes occurred reciprocally. The HER2 overexpression was only found in 4.3% (2/46) of the primary mucoepidermoid carcinoma and none of the lymph node metastases (0/11). EGFR and HER2 stainings were mainly found in the cell membranes. It was concluded that the majority of parotid mucoepidermoid carcinomas express EGFR strongly in their cell membranes and that lymph node metastases generally express EGFR to approximately the same extent as in the primary tumours. The stability in the EGFR expression is encouraging in the effort to develop radionuclide-based EGFR imaging agents. It is also possible that EGFR targeting agents (e.g. Iressa, Tarceva, Erbitux or radiolabelled antibodies) can be applied for the therapy of mucoepidermoid carcinoma.

Photodynamic therapy (PDT) is a promising treatment modality for the management of malignant diseases. However, general acceptance of PDT has been hampered due to the limited tissue penetration of light and unavailability of suitable photosensitizers (PSs). The innovative combination of the conventional radiotherapy (RT) with PDT might reduce the unacceptable normal tissue toxicity while maintaining the desired tumor suppression effect. There have been a number of attempts to examine the interaction of PDT and RT; however, the previous results presented are ambiguous. The exact mechanisms for the variable responses of diverse panel of cell lines to the combination therapeutic regimen are still unclear. Novel ways are being explored to overcome the weaknesses of the conventional PDT and RT treatment regimen. The novel application to enable PDT of deep cancers is the utilization of scintillating nanoparticles as an intracellular light source for PDT activation. Upon simulation by X-rays, the nanoparticles emit scintillation or persistent luminescence to activate the PS to generate singlet oxygen. For future clinical applications, several questions are worthy of further elucidation, including the specific light dose, PS dose, radiation dose, the risk of complications, and the accurate time interval between administration of PDT and administration of RT.