171,052 research outputs found
Diagnostic and prognostic value of TPA in breast cancer Madeddu G, Farris A, Casu AR, Saiu MA, Eriu R, Costanza C, Arras ML, Costanza C, Campus S.
No full textExperimental Drugs for Chemotherapy- and Cancer-Related Anemia
No full textClelia Madeddu,1 Manuela Neri,2 Elisabetta Sanna,2 Sara Oppi,3 Antonio Macciò2 1Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 2Department of Gynecologic Oncology, A. Businco Hospital, ARNAS G. Brotzu, Cagliari, Italy; 3Hematology and Transplant Center, A. Businco Hospital, ARNAS G. Brotzu, Cagliari, ItalyCorrespondence: Antonio Macci༪. Businco Hospital, ARNAS G. Brotzu, via Jenner, Cagliari, 09100, ItalyTel +390706754228Email [email protected]: Anemia in cancer patients is a relevant condition complicating the course of the neoplastic disease. Overall, we distinguish the anemia which arises under chemotherapy as pure adverse event of the toxic effects of the drugs used, and the anemia induced by the tumour-associated inflammation, oxidative stress, and systemic metabolic changes, which can be worsened by the concomitant anticancer treatments. This more properly cancer-related anemia depends on several overlapping mechanism, including impaired erythropoiesis and functional iron deficiency, which make its treatment more difficult. Standard therapies approved and recommended for cancer anemia, as erythropoiesis-stimulating agents and intravenous iron administration, are limited to the treatment of chemotherapy-induced anemia, preferably in patients with advanced disease, in view of the still unclear effect of erythropoiesis-stimulating agents on tumour progression and survival. Outside the use of chemotherapy, there are no recommendations for the treatment of cancer-related anemia. For a more complete approach, it is fundamentally a careful evaluation of the type of anemia and iron homeostasis, markers of inflammation and changes in energy metabolism. In this way, anemia management in cancer patient would permit a tailored approach that could give major benefits. Experimental drugs targeting hepcidin and activin II receptor pathways are raising great expectations, and future clinical trials will confirm their role as remedies for cancer-related anemia. Recent evidence on the effect of integrated managements, including nutritional support, antioxidants and anti-inflammatory substances, for the treatment of cancer anemia are emerging. In this review article, we show standard, innovative, and experimental treatment used as remedy for anemia in cancer patients.Keywords: hemoglobin, cancer-related anemia, chemotherapy-induced anemia, energy metabolism, inflammation, iron homeostasis, erythropoietin, interleukin-
Blocking inflammation to improve immunotherapy of advanced cancer
No full textThe ability to induce functional reprogramming of regulatory T (Treg) cells in the tumor microenvironment is an extremely important therapeutic opportunity. However, when discussing such an approach, the opposing effect that the activation of the Treg cell compartments may have in inducing the immune inflammatory response and its link with the efficacy of immunotherapy should be considered. In fact, Treg reprogramming has a dual effect: immediate, with mechanisms that activate immunosurveillance, and late, mediated by the macrophage activation that yields an inflammatory status that is deleterious for the antineoplastic efficiency of the immune system response. Persistence of the inflammatory response is associated with specific changes of oxidative and glycolytic metabolic pathways that interfere with conventional T-cell activation and function and may be one of the reasons for the failure of immunotherapy in advanced cancer patients. Therefore, in addition to modulating Treg cell action, the combined use of drugs able to block chronic inflammation mediated mainly by macrophages, to counteract the oxidative stress, and to positively regulate the metabolic derangements, could improve the effectiveness of modern immunotherapy. In conclusion, reprogramming of Treg cells may be an appropriate strategy for treating early stages of neoplastic diseases, whereas other immunosuppressive mechanisms should be the target of a combined immunotherapy approach in more advanced phases of cancer
Vitamin C supplementation in cancer cachexia and related-oxidative stress
No full textSeveral mechanisms may lead to oxidative stress (OS) in cancer patients. The first one is the altered energy metabolism which may account for symptoms such as anorexia/cachexia, nausea and vomiting which prevent a normal nutrition and thereby a normal supply of nutrients such as glucose, proteins and vitamins, leading eventually to accumulation of free radicals, which are known as reactive oxygen species (ROS), such as hydroxyl radicals, superoxide radicals and others. The second mechanism is a nonspecific chronic activation of the immune system with an excessive production of proinflammatory cytokines, which in turn may increase the ROS production. Indeed, a chronic inflammatory condition associated with increased OS has been suggested as one of the triggering mechanisms behind the tumor-induced immune suppression. A third mechanism may be the result of antineoplastic drugs administration: many of these drugs, particularly alkylating agents and cisplatin, are able to produce an excess of ROS and therefore lead to OS. In turn, OS plays a significant role in inducing and worsening cancer cachexia. Consistent experimental and clinical data indicate that OS is involved in the pathogenesis of cancer cachexia, although the extent of its contributory role remains to be established. Therefore, OS should be addressed when developing a therapeutic approach for cachectic cancer patients. To counteract ROS and OS several approaches have been tried both in experimental systems and in humans. Among the most used antioxidant agents there are alpha lipoic acid, cysteine-containing compounds, amifostine, reduced glutathione(GSH) and vitamins. Antioxidant vitamins, which include vitamin C, are hypothesized to decrease cancer risk and prevent cancer progression by trapping organic free radicals and/or deactivating reactive oxygen molecules. Indeed, in our previous experimental and clinical studies in advanced-stage cancer patients we demonstrated: 1) the ability of antioxidant agents alpha-lipoic acid (ALA) and N-acetyl cisteine (NAC) to restore in vitro several important T cell functions, and 2) the ability of different antioxidant agents, including vitamin C, used alone or in combination, to reduce in vivo ROS levels and to increase the glutathione peroxidase (GPx) activity. In particular, in two recent studies vitamin C was used as a part of an antioxidant treatment in a combined treatment approach for cancer cachexia. In the first, a Phase II study, the combined treatment approach consisting of antioxidants, including Vitamin C, pharmaconutritional support, progestagen, and an anti-cyclooxygenase-2, resulted in a significant improvement of symptoms of cancer cachexia. In the second, a phase III randomised study, all patients received a basic antioxidant treatment including Vitamin C plus polyphenols, alpha-lipoic acid, carbocysteine, and vitamins A and E, all orally. Patients were then randomized to one of the following five arms: 1) medroxyprogesterone acetate/megestrol acetate; 2) pharmacologic nutritional support containing eicosapentaenoic acid; 3) L-carnitine; 4) thalidomide; or 5) medroxyprogesterone acetate/megestrol acetate plus pharmacologic nutritional support plus L-carnitine plus thalidomide. The accrual has been completed and the final results have been submitted for publication
Potential role of macrophage activation in mediating thrombotic complications associated with the different vaccines against COVID-19
No full textRole of human tissue kallikrein in gastrointestinal stromal tumour invasion
No full textBackground:
Human tissue kallikrein (hK1) generates vasodilator kinins from kininogen and promotes angiogenesis by kinin-dependent and kinin-independent mechanisms. Here, we investigate the expression and functional relevance of hK1 in human gastrointestinal stromal tumour (GIST).<p></p>
Methods:
Vascularisation and hK1 expression of GIST samples were assessed by immunohistochemistry. In two GIST cell lines, hK1 expression was assessed by PCR, and hK1 protein levels and activity were measured by ELISA and an amidolytic assay, respectively. The effect of hK1 silencing, inhibition or overexpression on GIST cell proliferation, migration and paracrine induction of angiogenesis was studied. Finally, local and systemic levels of hK1 were assessed in mice injected with GIST cells.<p></p>
Results:
Human tissue kallikrein was detected in 19 out of 22 human GIST samples. Moreover, GIST cells express and secrete active hK1. Titration of hK1 demonstrated its involvement in GIST invasive behaviour, but not proliferation. Furthermore, hK1 released by GIST cells promoted endothelial cell migration and network formation through kinin-dependent mechanisms. Gastrointestinal stromal tumour implantation in nude mice resulted in local and systemic hK1 expression proportional to tumour dimension.<p></p>
Conclusions:
Human tissue kallikrein is produced and released by GIST and participates in tumour invasion. Further studies are needed to validate hK1 as a diagnostic biomarker and therapeutic target in GIST
COVID-19 and cytokine storm syndrome: can what we know about interleukin-6 in ovarian cancer be applied?
No full textImproving early diagnosis along with timely and effective treatment of COVID-19 are urgently needed. However, at present, the mechanisms underlying disease spread and development, defined prognosis, and immune status of patients with COVID-19 remain to be determined. Patients with severe disease state exhibit a hyperinflammatory response associated with cytokine storm syndrome, hypercoagulability, and depressed cell-mediated immunity. These clinical manifestations, sharing similar pathogenesis, have been well-studied in patients with advanced ovarian cancer. The present review suggests treatment approaches for COVID-19 based on strategies used against ovarian cancer, which shares similar immunopathology and associated coagulation disorders. The chronicization of the hyperinflammatory cytokine storm in patients with severe COVID-19 highlights a defective resistance phase that leads to aspecific chronic inflammation, associated with oxidative stress, which impairs specific T-cell response, induces tissue and endothelial damage, and thrombosis associated with systemic effects that lead to severe multi-organ failure and death. These events are similar to those observed in advanced ovarian cancer which share similar pathogenesis mediated primarily by Interleukin-6, which is, as well demonstrated in ovarian cancer, the key cytokine driving the immunopathology, related systemic symptoms, and patient prognosis. Consistent with findings in other disease models with similar immunopathology, such as advanced ovarian cancer, treatment of severe COVID-19 infection should target inflammation, oxidative stress, coagulation disorders, and immunodepression to improve patient outcome. Correctly identifying disease stages, based on available laboratory data, and developing a specific protocol for each phase is essential for effective treatment
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