Role of estrogen receptor signaling in breast cancer metastasis.

Metastatic breast cancer is a life-threatening stage of cancer and is the leading cause of death in advanced breast cancer patients. Estrogen signaling and the estrogen receptor (ER) are implicated in breast cancer progression, and the majority of the human breast cancers start out as estrogen dependent. Accumulating evidence suggests that ER signaling is complex, involving coregulatory proteins and extranuclear actions. ER-coregualtory proteins are tightly regulated under normal conditions with miss expression primarily reported in cancer. Deregulation of ER coregualtors or ER extranuclear signaling has potential to promote metastasis in ER-positive breast cancer cells. This review summarizes the emerging role of ER signaling in promoting metastasis of breast cancer cells, discusses the molecular mechanisms by which ER signaling contributes to metastasis, and explores possible therapeutic targets to block ER-driven metastasis.

Oxidation of hemoglobin and redistribution of band 3 promote erythrophagocytosis in visceral leishmaniasis.

In visceral leishmaniasis (VL), oxidative assault on erythrocytes perturbs their cellular environment and makes them vulnerable to premature hemolysis. In this study, we assessed the contribution of oxidation-induced modifications of hemoglobin and membrane protein band 3 in the reduced survival of red cells in VL. Oxidative transformation of oxyhemoglobin to hemichrome enhanced its interaction with erythrocyte membrane in the infected animals. Association between denatured globin and band 3 contributed to the formation of insoluble copolymer of macromolecular dimension. Disulfide bonding appeared to be necessary in the making of high molecular weight aggregates during copolymerization. Hemichrome induced clustering of band 3 promoted generation of epitopes on erythrocyte cell surface. This provided a signal favoring immunologic recognition of redistributed band 3 by autologous IgG followed by erythrophagocytosis. An eventual outcome of the sequence of events pointed to early removal of affected red cells from circulation during the disease.

Therapeutic use of quercetin in the control of infection and anemia associated with visceral leishmaniasis.

Flavonoids are a broad class of plant phenolics that are known to possess a well-established protective effect against membrane lipoperoxidative damages. Oxidative damage of erythrocytes has been implicated in the reduced survival of erythrocytes during leishmanial infection. This study reveals the efficacy of five naturally occurring flavonoids in arresting the development of anemia during the postinfection period. Among the compounds studied, quercetin was most successful in inhibiting the oxidation of proteins and lipids on the red cell membranes of infected animals. Apart from its antianemic property, quercetin also seemed to be highly potent in lowering the parasite load in the spleen. Combination therapy of quercetin with the antileishmanial drug stibanate produced a better decay of .OH in the erythrocytes of the infected animals compared to that induced by quercetin or drug treatment alone. Similar results were obtained in successful prevention of proteolytic degradation resulting in an aversion to early lysis of red cells after simultaneous treatment with quercetin and stibanate. Subsequent studies demonstrated the therapeutic efficacy of the combination treatment in the abatement of both anemia and parasitemia under the diseased condition.