Targeting tumor associated macrophages: The new challenge for nanomedicine

The engineering of new nanomedicines with ability to target and kill or re-educate Tumor Associated Macrophages (TAMs) stands up as a promising strategy to induce the effective switching of the tumor-promoting immune suppressive microenvironment, characteristic of tumors rich in macrophages, to one that kills tumor cells, is anti-angiogenic and promotes adaptive immune responses. Alternatively, the loading of monocytes/macrophages in blood circulation with nanomedicines, may be used to profit from the high infiltration ability of myeloid cells and to allow the drug release in the bulk of the tumor. In addition, the development of TAM-targeted imaging nanostructures, can be used to study the macrophage content in solid tumors and, hence, for a better diagnosis and prognosis of cancer disease. The major challenges for the effective targeting of TAM with nanomedicines and their application in the clinic have already been identified. These challenges are associated to the undesirable clearance of nanomedicines by, the mononuclear phagocyte system (macrophages) in competing organs (liver, lung or spleen), upon their intravenous injection; and also to the difficult penetration of nanomedicines across solid tumors due to the abnormal vasculature and the excessive extracellular matrix present in stromal tumors. In this review we describe the recent nanotechnology-base strategies that have been developed to target macrophages in tumors.     

Toll-like receptors: Significance,ligands, signaling pathways,and functions in mammals

This review attempts to cover the implication of the toll-like receptors (TLRs) in controlling immune functions with emphasis on their significance, function, regulation and expression patterns. The tripartite TLRs are type I integral transmembrane receptors that are involved in recognition and conveying of pathogens to the immune system. These paralogs are located on cell surfaces or within endosomes. The TLRs are found to be functionally involved in the recognition of self and non-self-antigens, maturation of DCs and initiation of antigen-specific adaptive immune responses as they bridge the innate and adaptive immunity. Interestingly, they also have a significant role in immunotherapy and vaccination. Signals generated by TLRs are transduced through NFκB signaling and MAP kinases pathway to recruit pro-inflammatory cytokines and co-stimulatory molecules, which promote inflammatory responses. The excess production of these cytokines leads to grave systemic disorders like tumor growth and autoimmune disorders. Hence, regulation of the TLR signaling pathway is necessary to keep the host system safe. Many molecules like LPS, SOCS1, IRAK1, NFκB, and TRAF3 are involved in modulating the TLR pathways to induce appropriate response. Though quantification of these TLRs helps in correlating the magnitude of immune response exhibited by the animal, there are several internal, external, genetic and animal factors that affect their expression patterns. So it can be concluded that any identification based on those expression profiles may lead to improper diagnosis during certain conditions.     

A Comparative Analysis of Current Lipid Treatment Guidelines: Nothing Stands Still

Lipid treatment guidelines have continued to evolve as new evidence emerges. We sought to review similarities and differences of 5 lipid treatment guidelines from the American College of Cardiology/American Heart Association, Canadian Cardiovascular Society, European Society for Cardiology/European Atherosclerosis Society, U.S. Preventive Services Task Force, and U.S. Veterans Affairs/Department of Defense. All guidelines utilize rigorous evidentiary review, highlight statin therapy for primary and secondary prevention of atherosclerotic cardiovascular disease, and emphasize a clinician-patient risk discussion. However, there are differences in statin intensities, use of risk estimators, treatment of specific patient subgroups, and consideration of safety concerns. Clinicians should understand these similarities and differences in current and future guideline recommendations when considering if and how to treat their patients with statin therapy.     

Validation and reliability of distress thermometer in Chinese cancer patients

Objective:To examine the validation and reliability of the distress thermometer(DT) recommended by National Comprehensive Cancer Network(NCCN) in Chinese cancer patients.Methods:A total of 574 Chinese cancer patients from Beijing Cancer Hospital completed the detection of DT,the Hospital Anxiety and Depression Scale(HADS) and Symptom Checklist 90(SCL-90),Receiver Operating Characteristic(ROC) curve and Area Under the Curve(AUC) were used to analyze the validation relative to HADS and SCL-90.The patients with DT≥4 and whose distress caused by emotional problems were interviewed with the MiNi International Neuro-psychiatric Interview(MINI)(Chinese Version 5.0).This version was used to analyze cancer patients’ psychological and Psychiatric symptoms during the cancer process;3.Another 106 cancer patients in rehabilitation stage and stable condition were asked to fill in DT two times,at the base time and after 7-10 days.Results:Data of ROC indicates that a DT cutoff score of 4 yielded AUC of 0.80 with a optimal sensitivity(0.80) and specificity(0.70) relative to HADS,and AUC of 0.83 with the greatest sensitivity(0.87) and specificity(0.72) against SCL-90.The DT also has acceptable test-retest reliability(r=0.800,P=0.000);According to the interview results,the most common psychiatric problems cancer patients have adjustment disorder,depression,and anxiety.Conclusion:The data suggest that DT has acceptable overall accuracy and reliability as a screening tool for testing distress severity and specific problems causing distress in Chinese cancer patients.It is worth being used in oncology clinic,the rapid screening and interview could help caregivers to identify psychological and psychiatric problems of cancer patients and provide useful information for further treatment.     

Microglandular Adenosis

Microglandular adenosis (MGA) of the breast is a very rare and benign proliferative lesion. Most patients complain of a palpable breast mass that may arouse a clinical suspicion of breast cancer. Histopathologically, it is hard to distinguish MGA from breast cancer because of the lack of a myoepithelial layer and infiltrative proliferation. Several studies have reported a strong relationship between MGA and carcinoma arising in MGA, so the mass should be excised completely in cases of MGA determined from a core needle biopsy rather than observation. A 72-years-old woman presented with a palpable breast mass. On physical examination, a mass was palpable in the right upper outer quadrant area and somewhat fixed to the surrounding tissues and pectoralis major muscle. We could not detect any mass or dense lesion on mammography because of a grade 4 dense breast. Ultrasonographic findings revealed a low echoic lesion with indistinct margins. The result of a core needle biopsy was MGA, which was confirmed by excision. We report one case of MGA, which was believed to breast cancer clinically.