Mystery Story about Erythropoietin (Epo) and Erythropoietin Receptor (EpoR) are Disguised?

In this review we would like to focus our attention upon very controversial reports on Erythropoietin (Epo) and Erythropoietin Receptor (EpoR) expression in cancer patients. The effects of Epo on cancerous tissues are poorly understood. Hypoxia results in an increase in the level of the production of both Epo and EpoR via activation of the hypoxia-inducible factor 1 (HIF-1) pathway. HIF-1α, promotes the expression of vascular endothelial growth factor (VEGF). The signaling through VEGF in both a paracrine and an autocrine manner is required for the homeostasis of adult vessels. Macrophages stimulate vessel sprouting via a soluble factor other than VEGF, rather than through direct contact with endothelial cells. The intriguing questions are set about many researches to link Epo/EpoR expression and function in order to establish one of the mechanisms of tumor growth, disease progression of cancer patient. However, it is uncertain role in tumour angiogenesis as promoter and stimulator of tumour growth which should need to be furtherly validated.

Nutrition in cancer patients.

Cachexia is defined as an unintended loss of stable weight exceeding 10%. Patients with advanced cachexia express anorexia, early satiety, severe weight loss, weakness, anemia, and edema. Anorexia represents the result of a failure of the usual appetite signals whereas cachexia is the debilitating state of involuntary weight loss. This syndrome, referred to as the cancer anorexia-cachexia syndrome, (CACS) and usually consists of a combination of anorexia, tissue wasting, malnutrition, weight loss and loss of compensatory increase in feeding. CACS represents the result of a complex interaction between cancer growth and host response and is associated with a poor response to chemotherapy and with an increase in drug-related toxicity. In advanced cachexia (mostly in metastatic cancer and terminally disease) any interventions with nutritional suplements are ineffective. Therefore, nutritional support in the reversion of tumor cachexia and in the importance of maintaining patient weight, muscle mass, quality of life, has the exceptional importance, becouse good nutritional status of patients leads to the possibility of more aggressive and longer treatment and thus to longer survival.

Nutritional support in patients with colorectal cancer during chemotherapy: does it work?

BACKGROUND/AIMS: Early intervention with nutritional supplementation has been shown to halt malnutrition and may improve outcome in some patients with colorectal cancer. The aim of this study was to investigate whether dietary counseling, oral nutrition and megestrol acetate during chemotherapy affected nutritional status and survival in patients with advanced disease. METHODOLOGY: Six hundred and twenty-eight patients with colorectal advanced disease were included in the study from January 2000 through December 2009 and divided into one of two groups. Group I consisted of 315 patients who were monitored prospectively and were given nutritional support. Group II included 313 patients without nutritional counseling and support. After the completion of chemotherapy all patients were evaluated (BMI, NST, Appetite Loss Scale and ECOG). RESULTS: After the completion of chemotherapy, there were lower proportions of patients in Group I with a BMI<20, NST>=5, loss of appetite and decreased weight gain. Nutritional counseling and supplemental feeding temporarily halted weight loss and improved appetite. This improvement may have implications for patient survival. Patients with early nutritional support lived 19.1 months while patients in the control group had a survival of 12.4 months (p=0.022). CONCLUSIONS: This study demonstrated that concurrent individualized dietary counseling and nutritional support are effective in improving nutritional status thereby lessening chemotherapy-induced morbidity.

Etiology and oncogenesis of pancreatic carcinoma.

Pancreatic cancer is the fourth leading cause of cancer death overall. The factors that favor the development of pancreatic cancer can be divided into hereditary and acquired. Cancerogenesis is best explained by a "multi-hit" hypothesis, charcterized with the developmental sequence of cellular mutatitions, forcing mutant cell to inappropriate proliferation and preventing its repair and programmed cell death (apoptosis). The most common mutations involve K-ras gene, epidermal growth factor (EGF-R) and HER2 gene. Continuous stimulation and secretion of vascular endothelial growth factor (VEGF) enhances the permeability of blood vessels provides nutrient supply to tumor site through newly formed vascular channels. This phenomena is known as vasculogenic mimicry. Loss of function of tumor-suppressor genes has been documented in pancreatic cancer, especially in CDKN2a, p53, DPC4 and BRCA2 genes. SDKN2A gene inactivation occurs in 95% of pancreatic adenocarcinoma. As regards acquired factors, smoking is only confirmed risk factor that increases the risk of pancreatic cancer. Diabetes, alcohol consumption, central obesity in men, infection with Helicobacter pylori and chronic pancreatitis are suspected, but not proven risk factors. Consumption of fruits and vegetables does not protect, while the consumption of meat processed at high temperatures increases the risk of pancreatic cancer. According to some studies, lykopene and folate levels are reduced in pancreatic carcinoma patients, reduced folate intake increases the risk of pancreatic carcinoma (48%), and this risk can be diminished by introducing folate-rich foods to diet, not by using pharmaceutical products. Occupational exposure to chlorinated hydrocarbons, vinyl chloride, nickel, chromium, insecticides and acrylic amide minimally increases the risk for pancreatic cancer. Exposure to cadmium (metal industry) associated with smoking result in the accumulation of cadmium in pancreatic tissue and the possible impact on carcinogenesis.

Effects of nutritional support in patients with colorectal cancer during chemotherapy.

Nutritional support, addressing the specific needs of this patient group, is required to help improve prognosis, and reduce the consequences of cancer-associated nutritional decline. Early intervention with nutritional supplementation has been shown to halt malnutrition, and may improve outcome in some patients. In our study we tried to assess the influence of nutritional support (counseling, oral liquids, megestrol acetate) on nutritional status and symptoms prevalence in patients with colorectal cancer during chemotherapy. Group I consisted of 215 (55%) patients with medium age 68 +/- 2.6 years who were monitored prospectively and were given nutritional support. Group II included 173 (45%) patients (medium age 67 +/- 2.9 years) without the proper nutritional counseling, in whom the data were collected retrospectively during a 6 years period of time. After evaluation Nottingham Screening Tool Score, Appetite Loss Scale and Karnofsky Performance Status) all patients in the group I received nutritional counseling, 153 of them (72%) were taking form of enteral food supplement and 103 (48%) patients were using megestrol acetate. Evaluating the initial risk measurements according to BMI, decrease in weight gain and NST, we did not find any significant difference between the two groups. After chemotherapy completion, patients in group I had a 15.3% drop of those who's BMI was < 20.65% patients increased their body weight, with an average weight gain of 1.5 kg (0.6-2.8 kg). Contrary, in group II we found increase in weight loss > or = 2 kg/month in 39% of patients. The appetite improvement was detected on Appetite Loss Scale from 3.1 (pre-chemotherapy) to 4.7 (post-chemotherapy) in group I, especially in those receiving megestrol acetate. In both groups Karnofsky Performance Status didn't change significantly reflecting the impact of the disease itself and chemotherapy procedures to the patient's condition. Nutritional counseling, supplemental feeding and pharmacological support do temporarily stop weight loss and improve appetite, social life and quality of life in those groups of patients. However, this improvement have no implications on patients KPS and course of their disease.

Endogenous erythropoietin and erythropoietin receptors in colorectal cancer; can we answer the questions?

Erythropoietin (Epo) is glycoprotein hormone which binds on erythropoietin receptors (EpoR) promoting proliferation and differentiation. Studies have shown that EpoR, apart from erythrocyte precursors, is expressed on no hematopoietic tissue and various tumor cells. Despite the progress in modern medicine, colorectal carcinoma (CRC) is still the leading cause of increased morbidity and mortality between oncology patients worldwide. Its precursors are benign villous adenomas, which in certain percentage progress to cancer. Anemia of chronic disease is common finding in CRC patients. Some of them are treated with Epo. Epo/EpoR seems to correlate with tumor progression and metastasizing. Therefore, the identification of at-risk group remains a clinical challenge. Vascular endothelial growth factor (VEGF) is a signal protein that stimulates angiogenesis and concentration of VEGF is positive correlated with tumor growth in numerous tumors. The importance of Epo in tumor pathogenesis has led to a growing interest in the potential prognostic value. By our point of view there are many open questions about role of Epo/EpoR in CRC.