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.

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Serum levels of AFP, hCG and CEA were initially and serially measured in 59 patients with testicular germ cell tumors, and serially in 37 with ovarian and 3 with extragonadal germ cell tumors. Patients with seminoma/dysgerminoma or mature teratoma had normal serum AFP and sporadically slightly elevated hCG. Some patients with embryonal carcinoma, pure or with admixture of seminoma, had serum AFP elevated to maximum 100 U/ml, yet its use for monitoring therapy was limited. Patients with yolk sac tumors had elevated AFP and sometimes CEA levels, those with choriocarcinoma had elevated hCG, and those with compound tumors had one or more of the markers highly elevated. High AFP and/or hCG levels indicated the presence of the relevant tumor cells both in the primary and in residual tumor and/or metastases, also those missed in histological material, and thus were useful in restaging. Unfortunately, their absence in serum did not exclude the presence of marker-negative subpopulations of tumor cells. Changes in marker values paralleled the effects of treatment: the level increasing from any nadir heralded recurrence in patients in remission; elevated or increasing levels during therapy implied resistance to the therapy; decreasing levels indicated regression even though a return to the normal range did not mean eradication of all tumor cells.

Serum levels of ovarian carcinoma antigen (CA 125) and breast carcinoma antigen (CA 15.3) were determined in 237 patients with breast carcinoma, 121 before any therapy and 116 after initial treatment, during uneventful follow-up or at the time of relapse. The aim was to assess how often the CA 125 test failed, i.e., was false-negative inpatients in whom the CA 15.3 test was true-positive and, more important, whether it gave diagnostic information in patients in whom the CA 15.3 test failed. Before surgery or other initial therapy, serum CA 125 and CA 15.3 gave similar information in 85.1 percent of the patients: true-positive in 4.1 percent and false negative in 81.0 percent; CA 125 gave less information in 13.2 percent; and more information in only 1.7 percent. During follow-up, serum CA 125 and CA 15.3 gave similar information in 73.3 percent of the patients: true-positive (i.e., rising persistently from a nadir or elevated above 65 U/ml) in 23.3 percent, true-negative in 36.2 percent, and false-negative in 13.8 percent; CA 125 gave less information in 25.0 percent: false negative in 22.4 percent and false-positive in 2.6 percent; and more information in only 1.7 percent. Therefore, the CA 125 test appears useless for staging and is redundant when the CA 15.3 test is employed, for management of patients with breast cancer.

Serum levels of carcinoembryonic antigen (CEA) and breast carcinoma antigen (CA 15.3) were determined in patients with breast carcinoma: in 129 before initial surgical or nonsurgical treatment and in 134 afterwards. Before any initial treatment, CEA was elevated in 15% of patients with Stage IV disease and CA 15.3 was high in 11% with Stage III and 48% with Stage IV. While monitoring management active disease was associated with elevated serum CEA in 66% of the patients, with elevated CA 15.3 in 73% and with at least one of the markers elevated in 86%. Both tests had high specificity (93% and 98%). The rise in serum CEA and, even more so, of serum CA 15.3 roughly paralleled the increase in bulk of the tumor: from locoregional disease through metastases to the lungs, bones, lungs with bones, and liver. Decreases in the levels of serum CEA and CA 15.3 reflected response to therapy, increases in the level of at least one marker-treatment failure, and levels fluctuating above the normal range indicated stationary disease. During follow-up, the predictive value of a negative test (levels within the normal range), suggesting that the patient might be free of disease, was 61% for CEA alone, 67% for CA 15.3 alone, and 80% for the two tests combined. We conclude that an elevated serum level of only one of the markers was useful for staging, implying advanced disease. Determination of both markers jointly was useful for monitoring the effectiveness of the therapy and for follow-up aimed at detection of relapse.

In the pathogenesis of human lung diseases, much of the experimental evidence has indicated involvement of the neutrophil chemotactic factor interleukin-8 (IL-8). Since IL·-8 is secreted by alveolar capillary wall macrophages, local production of IL-8 may act as a mechanism for polymorphonuclear cell migration into lung tissues. In this study, the concentrations of IL-8 were measured by ELISA in plasma and bronchoalveolar lavage (BAL) fluid of 49 patients. The study was divided into three patient groups: group A, 17 with bacterial pneumonia (7 non-smokers and 10 smokers); group B, 23 with pulmonary tuberculosis (9 non-smokers and 14 smokers), and control group, 9 non-smokers. The concentration of ΓL-8 in BAL fluids was increased significantly in groups A and B (non-smokers and smokers) in comparison to the control group. In addition, there were significant differences between non-smokers versus smokers in IL-8 concentration in group A (non-smokers = 170.6 ± 32 versus smokers = 350 ± 89 pg/ml, p < 0.001) and group B (non-smokers = 146.6 ± 31 versus smokers = 305.5 ± 54 pg/ml, p < 0.001). No significant differences in plasma IL-8 concentration were observed in different patient groups (smokers and non-smokers). The present study suggests that the increased local production (BAL) of IL-8 is associated with lung diseases, such as bacterial pneumonia and pulmonary tuberculosis, and that smoking can increase IL-8 production.

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