Platelets contribute to the initiation of colitis-associated cancer by promoting immunosuppression.

Essentials Inflammation plays a key role in the development of colorectal cancer. Understanding mechanisms of cancer initiation might reveal new anticancer preventive strategy. Hyperactive platelets promote tumor formation by fostering immune evasion of cancer. Platelet inhibition by clopidogrel prevents carcinogenesis by restoring antitumor immunity. SUMMARY: Background Clinical and experimental evidence support a role for inflammation in the development of colorectal cancer, although the mechanisms are not fully understood. Beyond thrombosis and hemostasis, platelets are key actors in inflammation; they have also been shown to be involved in cancer. However, whether platelets participate in the link between inflammation and cancer is unknown. Objective To investigate the contribution of platelets and platelet-derived proteins to inflammation-elicited colorectal tumor development. Methods We used a clinically relevant mouse model of colitis-associated cancer. Platelet secretion and platelet reactivity to thrombin were assessed at each stage of carcinogenesis. We conducted an unbiased proteomic analysis of releasates of platelets isolated at the pretumoral stage to identify soluble factors that might act on tumor development. Plasma levels of the identified proteins were measured during the course of carcinogenesis. We then treated the mice with clopidogrel to efficiently inhibit platelet release reaction. Results At the pretumoral stage, hyperactive platelets constituted a major source of circulating protumoral serum amyloid A (SAA) proteins. Clopidogrel prevented the early elevation of the plasma SAA protein level, decreased colitis severity, and delayed the formation of dysplastic lesions and adenocarcinoma. Platelet inhibition hindered the expansion and function of immunosuppressive myeloid cells, as well as their infiltration into tumors, but increased the number of tissue CD8+ T cells. Platelets and releasates of platelets from mice with cancer were both able to polarize myeloid cells towards an immunosuppressive phenotype. Conclusions Thus, platelets promote the initiation of colitis-associated cancer by enhancing myeloid cell-dependent immunosuppression. Antiplatelet agents may help to prevent inflammation-elicited carcinogenesis by restoring antitumor immunity.

[Atypical and rare cardiac revelation about Sheehan's syndrome: A report of three cases]. / Révélations cardiaques atypiques rares du syndrome de Sheehan : à propos de trois cas.

Sheehan syndrome is a potentially serious complication in the postpartum period corresponding to ischemic necrosis of the anterior pituitary related to postpartum haemorrhage. We report three original observations showing an unusual mode of revelation of this syndrome. The first observation is that of a 46-year-old patient admitted initially to resuscitation for a recovered cardiorespiratory arrest, severe hypoglycemia and profound hyponatremia. The second is that of a 45-year-old patient, admitted for recurrent cardiac tamponade after pericardial and pleural puncture and pericardial drainage; clinical survey found signs of slight panhypopituitarism. The latest case is that of a patient of 44 years, admitted to pericardial effusion average abundance revealed by dyspnea and tachypnea with hypotension. The interrogation of all patients revealed the concept of an old hemorrhagic syndrome, absence of lactation and secondary amenorrhea thereafter. Laboratory tests showed insufficient thyroid-stimulating, low cortisol, a hypogonadism hypogonadism. The pituitary magnetic resonance imaging showed an empty sella in the three cases. Patients were placed under replacement therapy with L-thyroxine and hydrocortisone with good clinical, biological and echocardiographic evolution. The three cases illustrate a rare heart atypical presentation for Sheehan's syndrome and underline the importance of early diagnosis and suitable replacement therapy of this syndrome to avoid this complication that can be life threatening.