Anemia has also been identified as an adverse prognostic factor
mild (10 g/dl—normal),
moderate (8–10 g/dl), severe (6.5–8 g/dl) and life threatening (<6.5 g/dl or unstable patient) anemia
anemia in cancer patients is often multifactorial.
Cancer itself can directly cause or exacerbate anemia either by suppressing hematopoiesis through bone marrow infiltration
or production of cytokines that lead to iron sequestration, or by reduced red blood cell production
in inflammatory anemia, iron deficiency should be defined by a low transferrin saturation
of <20%, ferritin levels of <100 ng/ml and a low reticulocyte hemoglobin concentration of <32 pg
anemia to thrombocytosis, as commonly
seen in cancer patients
TNF-α inhibits hemoglobin production
treatment
itself may be a major cause of anemia
Other cytokines, such as interleukin-6 (IL-6), IL-1 and interferon-γ, have also been shown to inhibit erythroid precursors
in vitro [9], albeit to a lesser extent
In inflammation, from whatever cause, IL-6 induces the liver to produce hepcidin. Hepcidin decreases iron absorption from
the bowel and blocks iron utilization in the bone marrow
Numerous in vitro studies have illustrated the central role of TNF-α in the pathogenesis of anemia
nephrotoxic effects of particular cytotoxic agents such as platinum salts can also lead to the persistence
of anemia through reduced Epo production by the kidney
Currently two options are at the disposal of the clinician for the treatment of anemia in cancer patients: transfusion of
packed red blood cells and the use of erythropoiesis-stimulating agents (ESAs)
The goal of the treatment is to relieve the
symptoms of anemia such as fatigue and dyspnea.
Transfusion of 1 unit of packed red blood cells has been estimated to result
in an increase in the hemoglobin level of 1 g/dl in a normal-sized adult
a higher mortality rate in patients receiving
ESA treatment
Recent concerns regarding the risk of thromboembolism in patients treated with ESA have been corroborated by the meta-analyses
conducted by Tonnelli and Bennett
Great review of anemia in Cancer:
1) blood loss
2) increased RBC loss
3) decreased RBC production
Cancer infiltration of marrow can reduce hematopoiesis. Inflammatory cytokines can reduce hematopoiesis. Inflammatory cytokines can block Fe absorption. Chemo and radiation can cause anemia--particularily platinum based therapies.
Ovarian cancer is the most lethal gynecologic malignancy in the world
paclitaxel represents a breakthrough in the treatment of ovarian cancer, the overall 5-year survival rate of patients with stage III disease is still approximately 40%
Targeting cancer stem cells is an emerging concept in cancer therapy
Ovarian cancer stem cells play an important role in chemoresistance and cancer recurrence
Furthermore, recent studies indicate that niclosamide exhibits anticancer effects against various human cancer cells by acting on multiple cell signaling pathways and inducing mitochondrial uncoupling [16–21]
has low systemic bioavailability (~10%) when administered orally, which is beneficial for treating local parasitic infections of the intestines while minimizing systemic exposure
The nano-NI demonstrated significantly higher inhibitory effects on sphere formation than the original niclosamide did
the nano-NI formulation decreased the metabolic activity of ovarian cancer cells and caused a metabolic shift from oxidative phosphorylation to glycolysis
This toxicity evaluation showed that oral nano-NI had no toxic effect on either group of mice in terms of weight, plasma albumin levels, and blood cell counts, and revealed no adverse effects on vital organ function in the rodents, which suggests that nano-NI is safe for animals
niclosamide inhibits tumor cell growth by interrupting multiple pathways (Wnt, Notch, STAT3, NF-κB, and mTORc1) and the generation of reactive oxygen species in several cancer cells
The current standard therapy for ovarian cancer includes taxanes and platinum-based chemotherapy after cytoreductive surgery. Among treated patients, nearly 70 to 80% will experience disease recurrence