Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system. Immune editing is one of the key aspects why tumors evade surveillance causing the tumors to lie dormant in patients for years through "equilibrium" and "senescence" before re-emerging. In addition, tumors exploit several immunological processes such as targeting the regulatory T cell function or their secretions, antigen presentation, modifying the production of immune suppressive mediators, tolerance and immune deviation. Besides these, tumor heterogeneity and metastasis also play a critical role in tumor growth. A number of potential targets like promoting Th1, NK cell, γδ T cell responses, inhibiting Treg functionality, induction of IL-12, use of drugs including phytochemicals have been designed to counter tumor progression with much success. Some natural agents and phytochemicals merit further study. For example, use of certain key polysaccharide components from mushrooms and plants have shown to possess therapeutic impact on tumor-imposed genetic instability, anti-growth signaling, replicative immortality, dysregulated metabolism etc. In this review, we will discuss the advances made toward understanding the basis of cancer immune evasion and summarize the efficacy of various therapeutic measures and targets that have been developed or are being investigated to enhance tumor rejection.
MR imaging-derived elastance index correlates with ICP over a wide range of ICP values. The sensitivity of the technique allows differentiation between normal and elevated ICP.
Fifty patients were treated for trigeminal neuralgia by percutaneous microcompression of the trigeminal ganglion. A No. 4 Fogarty balloon catheter was inserted under brief general anesthesia, using biplane fluoroscopy. This procedure is essentially a percutaneous simplication of the older Taarnhøj-Sheldon-Pudenz operation. The follow-up period ranged from 0.5 to 4.5 years. Pain recurred in 12% of cases during that time, and it is anticipated that within 5 years the recurrence rate will reach 20%, which is approximately the same rate as for the alternative established procedures. The advantages of this technique are freedom from discomfort on the part of the patient, a remarkable ease of performance on the part of the operator, absence of associated mortality, and a minimal morbidity rate.
Targeted therapies and the consequent adoption of “personalized” oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity “broad-spectrum” therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested; many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to help us address disease relapse, which is a substantial and longstanding problem, so a proposed agenda for future research is offered.
Percutaneous microcompression of the trigeminal ganglion for the relief of trigeminal neuralgia is a technically simple, nonpainful procedure, carried out under brief general anesthesia. One hundred patients treated by this method have been followed for 1 to 10 years; treatment has been technically successful in 97% of cases. Relief persisted at five years in 80%, and it is estimated that at 10 years the figure will be 70%. There were no deaths, no cerebral damage, no keratitis, and no analgesia dolorosa; 4% of the patients reported dysesthesia.
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