Sex hormone binding globulin in breast cancer.

The present study was undertaken to determine the significance of sex hormone binding globulin, the major and specific binding protein for testosterone and estradiol, in breast cancer. Among breast cancer patients, lower serum levels of Sex hormone binding globulin and higher levels of testosterone were observed. Sex hormone binding globulin showed an inverse relationship with testosterone and total cholesterol, and a direct relation with HDL-cholesterol. By the western blot analyses, Sex hormone binding globulin was detected in all biological samples that we examined. In the breast tumor tissue sections, immuno-staining for Sex hormone binding globulin was confined in cell cytoplasm and 29% cases were positive, which showed no association with the investigated prognostic markers of breast cancer such as ER and HER-2/neu over-expression. In this study, decreased circulating levels of Sex hormone binding globulin in breast cancer patients possibly indicate higher bioavailable estrogens.

Distribution of prognostically unfavourable product of c-erbB-2 oncogene and EGF-R in carcinomas of the breast and uterine cervix.

A comparative study was undertaken between cancer of the uterine cervix (n = 50) and female breast cancer (n = 50) with reference to the expression of c-erbB-2 oncoprotein (HER-2/neu) and that of epidermal growth factor receptor (EGF-R), both being highly homologous structurally. Expressions of EGF-R and c-erbB-2 oncoprotein were viewed in breast and cervical cancer tissues by immunochemical staining. Cervical cancer cases showed much higher expression of EGF-R which also revealed significant association with the expression of c-erbB-2 oncoprotein and tumour grading. Among breast cancer cases, over-expression of EGF-R correlated significantly with metastasis of lymph node; and expression of c-erbB-2 oncoprotein showed a significant relationship with histological grading of the tumour. Moreover, an association was noticed between the tumour grade and the concomitant immuno positive expression of EGF-R and c-erbB-2. Our study revealed an existence of a conflicting pattern in the expression of EGF-R and c-erbB-2 oncoprotein between carcinomas of the breast and uterine cervix.

Oncoprotein c-erbB-2 in squamous cell carcinoma of the uterine cervix and evaluation of its significance in response of disease to treatment.

Tissues from 50 cases of squamous cell carcinoma of the uterine cervix were analysed for immunohistochemical expression of c-erbB-2 oncoprotein and the patients were followed-up for 2 years. Immunopositivity of c-erbB-2 was studied with reference to clinical stage, histopathological differentiation and response to the cancer therapy. Expression of c-erbB-2 protein was found to be higher (37.5%) in cases with stage II disease, whereas more expressions were noticed in poorly differentiated squamous cell carcinoma (33.3%). Among cases who showed complete response to the treatment, 20.8% were positive for c-erbB-2 oncoprotein. On the contrary, 36.8% of prognostically unfavourable cases revealed positivity for c-erbB-2 immunostaining. However, the difference between c-erbB-2 expressions of these two said groups of patients, which were divided in accordance with the response to treatment, did not attain to statistical significance. Study on c-erbB-2 among larger number of patients with cervical carcinoma may prove to be an important factor in response to cancer therapy.

Effect of cancer treatment modalities on serum lipids and lipoproteins among women with carcinoma of the breast.

Serum lipids and lipoproteins were studied in 61 breast cancer patients before initiation of therapy and subsequently during and after completion of cancer therapy. Different serum lipid fractions were estimated by enzymatic method. It was observed that mean levels of serum triglycerides, total cholesterol and low density lipoprotein (LDL)-cholesterol among untreated breast cancer patients decreased significantly after treatment. On the contrary, an increasing trend in the levels of high density lipoprotein (HDL)-cholesterol was noticed in patients during the course of treatment. This study reflects the effects of cancer therapy in the alteration of levels of different serum lipid fractions in the patients with breast cancer.

Status of epidermal growth factor receptors family in hormone-dependent carcinomas of the breast and prostate with reference to serum lipids and lipoproteins.

There are numerous growing evidences of resemblance between carcinomas of the breast and prostate. A total of 45 cases of these two hormone-dependent cancers along with appropriate controls were subjected for status of epidermal growth factor receptors as well as serum lipid profile. Paraffin embedded tissue sections from aforesald tumours were analysed by immunohistochemical staining for epidermal growth factor receptor (EGF-R), c-erbB-2 oncoprotein, estrogen receptor (ER) and progesterone receptor (PgR). Sera from same individuals were studied for serum lipid profile analysis. The study revealed that immunoexpression of all receptor proteins (EGF-R). c-erbB-2 was significantly higher in breast carcinoma. In addition, mean levels of triglycerides, total cholesterol, LDL-cholesterol were found to be significantly elevated while the level of HDL-cholesterol was observed to be lower among patients with breast cancer as compared to matched controls. Further, ER-positive breast cancer cases have significantly higher mean level of HDL-cholesterol when compared with ER-negative breast cancer patients. Contrary to this, no alteration in different serum lipid fractions was noticed among the patients with prostate cancer. However, a positive relationship was noticed between immunoexpressions of EGF-R and c-erbB-2 in prostate cancer.

Serum lipids, lipoproteins and sex-hormone binding globulin in breast cancer.

Serum levels of various lipid parameters, i.e., triglycerides, total cholesterol, alpha lipoprotein or high density lipoprotein (HDL)-cholesterol and beta lipoprotein or low density lipoprotein (LDL)-cholesterol were measured in a total of 138 histologically proven cases of breast cancer along with 146 control women. The mean levels of serum triglycerides, total cholesterol and LDL-cholesterol were found to be significantly higher in breast cancer cases as compared to controls. However, lower mean levels of serum HDL-cholesterol and sex-hormone binding glubulin (SHBG) were observed in breast cancer patients than the control subjects. The results indicate a probable relation between serum lipids and the activity of sex-hormones. Moreover, the study reflects an overall disturbance of lipid metabolism in the pathological process of breast cancer.

Serum oestradiol in women with carcinomas of the breast and uterine cervix.

Endogenous oestrogens are thought to be involved in breast cancer, but few studies could show the direct relationship between hormones and pathological process of the disease. In the present study, oestradiol was estimated in the serum of pre-and postmenopausal breast cancer patients along with normal healthy controls and patients with carcinoma of the uterine cervix which is not dependent on oestrogens. Premenopausal patients with breast cancer showed higher levels of oestradiol as compared to premenopausal control women as well as cervical cancer patients. Whereas, no statistically significant differences were observed in serum oestradiol levels amongst postmenopausal groups of breast cancer, cervical cancer and normal women. The result of the study reflects the association of oestradiol as well as its difference in the pathological events of pre and postmenopausal breast cancer.

A rare case of two malignancies: Carcinoma of the breast and uterine cervix.

A female patient who had two primary cancers was investigated. Biochemical analysis of patient's serum for different parameters indicated an alteration in the metabolic process. Prognostically, the patient has shown favourable clinical features.

Glutathione level and its relation to radiation therapy in patients with cancer of uterine cervix.

Glutathione functions as an important antioxidant in the destruction of hydrogen peroxide and lipid peroxides by providing substrate for the glutathione peroxidase and also promotes the ascorbic acid. Glutathione plays a vital role in detoxification of xenobiotics, carcinogens, free radicals and maintenance of immune functions. The study was aimed to determine plasma glutathione as well as erythrocyte glutathione and glutathione peroxidase in patients with invasive cervical carcinoma (n = 30) before initiation and after completion of radiotherapy and subsequently, at the time of first three monthly follow-up visit. The levels of plasma glutathione, erythrocyte glutathione and glutathione peroxidase activity were found to be lower in all cervical cancer patients as compared to age matched normal control women. The study indicates a change in antioxidant status in relation with the glutathione system among patients with invasive carcinoma of the uterine cervix. This study also demonstrates the effect of radiation therapy on this antioxidant system.

Immunohistochemical expression of c-erbB-2 oncoprotein and EGF-R in pre- and postmenopausal breast cancer.

Tissues from 40 cases each of premenopausal and postmenopausal breast cancer were studied immunohistochemically for epidermal growth factor receptor (EGF-R) and c-erbB-2 oncoprotein. In the premenopausal group, immunopositivity for c-erbB-2 was 15% and for EGF-R 22.5%, whereas in the postmenopausal group, 45% of cases were positive for c-erbB-2 and 42.5% for EGF-R. The difference in immunoexpression of c-erbB-2 between the two groups was significant. A significant correlation was observed between the concomitant expression of c-erbB-2 as well as EGF-R and lymph node involvement. Furthermore, an association was found between c-erbB-2 positivity and histological grading of the tumour. It is interesting that the pattern of the investigated parameters indicates the difference in the pathological events of pre- and postmenopausal breast cancer.

Natural killer and lymphokine-activated killer cell functions in chronic myeloid leukemia.

The natural killer (NK) and lymphokine-activated killer (LAK) cell activities of peripheral blood lymphocytes from chronic myeloid leukemia (CML) patients in remission and from healthy donors have been studied. Regression analysis to compare both cytotoxic responses in individual donors and the frequency of LAK cell precursors was also carried out. About 42% of CML patients in remission showed low NK activity (less than the mean percentage NK activity of healthy donors--2 SD) and were categorised as low NK responders. The stage of remission or the drugs used to bring about remission did not influence the NK status. The LAK activity of low NK as well as normal NK responder CML patients was significantly low against the NK-sensitive K562 cell line and the NK-resistant VIP (melanoma) and T-24 (bladder carcinoma) tumor targets, as assessed by linear regression analysis. Allogeneic leukemic cells were more resistant to killing, especially by patients' LAK cells. The frequency analysis of LAK cell precursors revealed a significant reduction in the LAK cell progenitor frequency in CML patients in remission.

Immunoreactivity of lymphocytes from draining lymph nodes, peripheral blood and tumor infiltrates from oral cancer patients.

Lymphocytes from metastatic (met) and nonmetastatic (non-met) regional lymph nodes, LNL peripheral blood (PBL) and tumor infiltrating lymphocytes (TIL) of patients with squamous cell carcinoma of the oral cavity and healthy donors were investigated for CD3, CD4, CD8 and HNK-1 phenotypes, Natural Killer (NK) cell Activity, Antibody Dependent Cellular Cytotoxicity (ADCC) and proliferative response to mitogen (PHA). Modulation of NK cytotoxicity with recombinant Interferon alpha (IFN-alpha) was also investigated in some cases. Lymphocytes from met and non-met lymph nodes showed no variation in the percentages of CD3+, CD4+ and CD8+ cells, when compared with each other and with PBL of oral cancer patients. TIL showed significantly less proportion of CD3+ and CD4+ cells. The percentage of HNK-1+ cells was significantly lower in LNL and TIL when compared to PBL of oral cancer patients. The mitogen responses of met and non-met LNL were comparable to each other and better than that of PBL from the same patients, while, TIL showed significant impairment in mitogen responses. The NK cytotoxicity and ADCC of PBL from oral cancer patients were comparable to healthy donors which could be augmented by rIFN alpha. LNL and TIL showed almost negligible NK and ADCC activities and NK activity could not be modulated by rIFN alpha. The results thus demonstrate that in oral cancer patients, lymphocytes from three compartments viz. PBL, LNL and TIL showed differential effector functions. The metastatic status of LN did not affect the immunoreactivity of LNL.

Natural killer and lymphokine-activated killer cell-mediated cytotoxicity in patients with oral cancer.

Peripheral blood lymphocytes (PBL) from untreated and treated oral cancer patients, lymph node lymphocytes (LNL) from metastatic (met) and nonmetastatic (non-met) lymph nodes, and tumor infiltrating lymphocytes (TIL) were tested for natural killer (NK) and lymphokine activated killer (LAK) cell cytotoxicity using appropriate targets in a short-term chromium release assay. The results showed that while both NK and LAK functions of PBL from oral cancer patients were comparable to those of normal healthy donors, the NK activity of metastatic and nonmetastatic LNL and TIL was highly compromised. On the other hand, potent LAK activity could be generated from all three lymphoid populations. Individual patients showing low NK activity displayed good LAK cytotoxicity, indicating that endogenous cells with low NK potential have adequate ability to respond to interleukin 2 (IL-2). LAK activity tested on autologous tumour targets revealed that TIL were the best source of LAK cells. followed by PBL and LNL.

Cell-mediated immune status in patients with squamous cell carcinoma of the oral cavity.

Sixteen untreated patients with squamous cell carcinoma of the oral cavity were tested for in vitro immune status in comparison with the normal healthy donors. The parameters investigated were total leukocyte and lymphocyte counts, percentages and absolute counts of T- and B-cells in circulation, subsets of T-cells identified by the Fc receptors, phytohemagglutinin (PHA), and mixed lymphocyte culture (MLC) responses, natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) activities, and circulating immune complexes (CICs). Eight of these patients were retested 3 to 6 months after surgery. The results showed that there was an increase in leukocyte and lymphocyte counts, an increase in the percentage and absolute number of B-lymphocytes, an increase in the percentage of T-gamma cells, suboptimal PHA and MLC responses, normal NK and ADCC activities, and increased levels of CICs in untreated oral cancer patients. In the postoperative stage, except for a reduction in leukocyte and lymphocyte counts, other abnormalities remained unchanged. The CICs in treated patients correlated with the tumor load in that in three patients showing recurrence, the CIC level remained elevated, whereas in patients without evidence of the disease the CIC level was either low or comparable to the upper normal limits.