This study aims at investigating the blood level of Cu, Zn, Se, and Cd in breast cancer patients and the association between such level and the frequency of micronucleated lymphocytes. Fifty stage I breast cancer patients were recruited for this study at the time of diagnosis and before receiving any treatment or surgery. The control group consisted of 150 normal females matched to the patients for age (± 5 years). The whole blood level of Cu, Zn, Se, and Cd was determined using spectrophotometry. The frequency of micronucleated lymphocytes in the blood was determined using the cytokinesis-block micronucleus assay. The level of Cu, Zn, and Se was significantly lower (p = 0.0006, <0.0001, and <0.0001, respectively) in breast cancer patients, as compared to controls. The level of Cd was significantly (p < 0.0001) higher in the patients, as compared to controls. The frequency of lymphocytes with one micronucleus was significantly (p < 0.0001) higher in the patients, as compared to controls. In breast cancer patients, the frequency of micronucleated lymphocytes showed different associations with different levels of these trace elements. High Cd, low Zn, low Se, and both high and low Cu levels were significantly associated with micronucleus formation in lymphocytes. A similar association was found in the normal control group only in relation to high Se and Cd levels. Breast cancer patients seem to have abnormal levels of Cu, Zn, Se, and Cd, and such abnormality is associated with micronucleus formation in lymphocytes.
To develop an effective pharmaceutical treatment for a disease, we need to fully understand the biological behavior of that disease, especially when dealing with cancer. The current available treatment for cancer may help in lessening the burden of the disease or, on certain occasions, in increasing the survival of the patient. However, a total eradication of cancer remains the researchers' hope. Some of the discoveries in the field of medicine relied on observations of natural events. Among these events is the spontaneous regression of cancer. It has been argued that such regression could be immunologically-mediated, but no direct evidence has been shown to support such an argument. We, hereby, provide compelling evidence that spontaneous cancer regression in humans is immunologically-mediated, hoping that the results from this study would stimulate the pharmaceutical industry to focus more on cancer vaccine immunotherapy. Our results showed that patients with>3 primary melanomas (very rare group among cancer patients) develop significant histopathological spontaneous regression of further melanomas that they could acquire during their life (P=0.0080) as compared to patients with single primary melanoma where the phenomenon of spontaneous regression is absent or minimal. It seems that such regression resulted from the repeated exposure to the tumor which mimics a self-immunization process. Analysis of the regressing tumors revealed heavy infiltration by T lymphocytes as compared to non-regressing tumors (P<0.0001), the predominant of which were T cytotoxic rather than T helper. Mature dendritic cells were also found in significant number (P<0.0001) in the regressing tumors as compared to the non regressing ones, which demonstrate an active involvement of the different arms of the immune system in the multiple primary melanoma patients in the process of tumor regression. Also, MHC expression was significantly higher in the regressing versus the non-regressing tumors (P <0.0001), which reflects a proper tumor antigen expression. Associated with tumor regression was also loss of the melanoma common tumor antigen Melan A/ MART-1 in the multiple primary melanoma patients as compared to the single primary ones (P=0.0041). Furthermore, loss of Melan A/ MART-1 in the regressing tumors significantly correlated with the presence of Melan A/ MART-1-specific CTLs in the peripheral blood of these patients (P=0.03), which adds to the evidence that the phenomenon of regression seen in these patients was immunologically-mediated and tumor-specific. Such correlation was also seen in another rare group of melanoma patients, namely those with occult primary melanoma. The lesson that we could learn from nature in this study is that inducing cancer regression using the different arms of the immune system is possible. Also, developing a novel cancer vaccine is not out of reach.
The incidence of cancer and its related morbidity and mortality remain on the increase in both developing and developed countries. Cancer remains a huge burden on the health and social welfare sectors worldwide and its prevention and cure remain two golden goals that science strives to achieve. Among the treatment options for cancer that have emerged in the past 100 years, cancer vaccine immunotherapy seems to present a promising and relatively safer approach as compared to chemotherapy and radiotherapy. The identification of different tumour antigens in the last fifteen years using a variety of techniques, together with the molecular cloning of cytotoxic T lymphocytes (CTLs)- and tumour infiltrating lymphocytes (TILs)-defined tumour antigens allowed more refining of the cancer vaccines that are currently used in different clinical trials. In a proportion of treated patients, some of these vaccines have resulted in partial or complete tumour regression, while they have increased the disease-free survival rate in others. These outcomes are more evident now in patients suffering from melanoma. This review provides an update on melanoma vaccine immunotherapy. Different cancer antigens are reviewed with a detailed description of the melanoma antigens discovered so far. The review also summarises clinical trials and individual clinical cases in which some of the old and current methods to vaccinate against or treat melanoma were used. These include vaccines made of autologous or allogenic melanoma tumour cells, melanoma peptides, recombinant bacterial or viral vectors, or dendritic cells.
Background: Chronic renal failure is one of the main health problems in Egypt. Arterio-venous fistulas, grafts, as well as conventional sites for placement of the dialysis catheters are liable to thrombosis; stenosis, and occlusions, so alternative routes are considered as life-saving ways in such cases. Transhepatic permcath is one of the new and up to date methods for inferior vena cava and right atrium catheterization. Few studies with rather limited nomber are available to evaluate transhepatic permcath. The aim of our study is to emphasize the technique, complications, and efficacy of application of percutaneous transhepatic hemodialysis catheters. Results: Two hundred-ninety six chronic renal dialysis patients were included in this prospective interventional study. They include 180 males and 116 females with mean age of 53.2 years ± 11.7 years ranging from 38 to 65 years. Percutaneous transhepatic hemodialysis catheters were inserted for all patients. Technical success of the procedure was achieved in all cases (100%). Post-procedure patency and function of the catheters were followed up with mean follow-up period 750 days. Mean of primary and secondary devices service intervals were 290 and 270 days respectively. Mean time catheter in situ was 280 days. Mean cumulative duration of catheter in situ was 557 days. Catheters migration, sepsis, thrombosis, and exit site infection rates were 0.14, 0.15, 0.18, and 0.32 per 100 catheter-days respectively. Three patients had hepatic subcapsular hematoma (1%). No mortality or other complications were related to the procedure. Conclusions: Combined ultrasound and fluoroscopic-guided transhepatic permanent dialysis catheter application for patients with exhausted classic venous access routes and non-functioning/thrombosed AV fistulas or grafts showed excellent technical success with good short and mid-term patency rates and low complications rates. Thus, this study encourages us to expand this promising technique for application of dialysis catheter in indicated cases.
Nongenetic breast cancer risk factors have never been evaluated in Kuwait. Accordingly, we aimed at examining these factors as well as the immune profile of the patients. Fifty stage I breast cancer patients and 50 age group-matched normal controls were assessed for the level of their peripheral blood lymphocyte subsets and for risk factors associated with their demographic and reproductive characteristics and with diet. The percentages of CD4+ T lymphocytes, CD4+:CD8+ ratio, and CD19+ B lymphocytes were significantly higher in the patients as compared to controls, while the percentages of CD8+ T lymphocytes and natural killer (CD56+) cells were significantly reduced. Risk factors associated with the disease included higher BMI, lack of regular exercise and physical activity in the past 5 years, early age at menarche, late age at first pregnancy, lack of previous information about breast cancer, hormonal therapy, and presence in Kuwait during the invasion/liberation. Other parameters included significantly more frequent consumption of carbohydrate, sweets, animal fat, and vegetable oil (margarine) and less frequent consumption of fresh vegetables and olive oil. This is the first study to highlight the environmental risk factors associated with breast cancer among the Kuwaiti women. We recommend introducing a nationwide campaign to further investigate these factors and to address them accordingly.
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