INTRODUCTION: Decreased serum albumin (SA) levels have been used extensively as prognostic indicators in many chronic debilitating diseases. The decrease may be partly compensated by globular proteins. The failure of globulins to compensate may reflect advanced disease. We examined the prognostic value of the level of serum globulins in colorectal and breast cancers.
METHODS: Data of 80 patients with advanced colon and breast cancers were analysed. Of these, 46 patients died within six months of measurement of their serum proteins, and the rest were followed-up for more than six months after measurements of their serum proteins were taken. A mathematical formula, representing the globulin compensation index (GCI), was recently developed from the measured SA levels and globulins. Patients were then classified into three categories: negative GCI and negative compensation; GCI of 0 to less than 1.0 with partial compensation; and GCI equal or greater than 1.0 with full compensation.
RESULTS: Among the deceased patients, 45.7 percent had negative GCI, compared to 26.5 percent of patients in the survivors group. For partial compensation, 30.4 percent of patients were from the deceased group, and 32.4 percent were from the survivors group. For full compensation (elevated GCI), 23.9 percent of patients were from the deceased group, compared to 41.1 percent from the survivors group (p-value equals 0.031).
CONCLUSION: Patients with low GCI are more likely to have bad prognoses, whereas those with higher GCI have more favourable prognoses. Globulin compensation may be a reliable prognostic factor in advanced colorectal and breast cancers, and possibly in other chronic illnesses. The GCI may serve as a useful tool in the measurement of this compensation.
Human mammaglobin is a member of the uteroglobin proteins family that has recently been tested as a specific marker for breast cancer. While low levels may be seen in normal breast tissue, expression is increased dramatically in breast cancer and is correlated with higher grade. Detection in blood and body fluids is also correlated with cancer metastasis, and its levels with prognosis. This promises to be a useful screen for early detection of breast cancer, especially in high risk individuals. Mammoglobin has also been used for immunotherapeutic targeting of breast cancer cells. However, there are some controversies regarding its diagnostic efficacy and prognostic value, which warrant further study.
The p53 gene is a tumour suppressor gene that encodes a 393-amino-acid nuclear DNA-binding phosphoprotein. The significance of p53 detection is that p53 mutation is linked with chemo-resistance and transformation to more aggressive disease in a large number of tumour types and it was confirmed that mutant p53 is involved in neoplastic transformations. In addition, the expression of p53 has been closely correlated with clinicopathological findings. Since breast cancer has been reported as one of the most frequent malignancies in women in Malaysia, the expression of p53 was studied in 382 cases of invasive ductal carcinoma of the breast, obtained from three major hospitals in the North-East States of Malaysia. The study utilized an enzyme immunohistochemistry assay for the detection of p53. It was found that p53 was expressed in 29.6% of all the study cases. Furthermore, its expression was significantly correlated with the age and the clinical grading of the disease. No significant statistical correlations were depicted with lymph node status, tumour size, side of tumour, and expression of estrogen and progesterone receptors. Nevertheless, knowledge of the p53 status may be valuable in making clinical decisions regarding diagnosis, prognosis and therapy.
Survivin is an inhibitor of apoptosis protein and regulates the cell cycle in the G2/M phase. Survivin is expressed during embryonic and fetal development, selectively over-expressed in common human cancers and completely down-regulated in normal adult tissue. This work was aimed at studying the expression of the survivin homologues and their subcellular distribution in fetal and normal adult tissues of rat. Survivin expression was evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded tissue sections of fetal and normal adult tissues of rat using the polyclonal serum SUR12A-CFI. This serum demonstrated intense positive survivin staining in adult kidney, ovary and oviduct, and a variable expression in different fetal organs, with particularly intense expression detected in the adrenal gland, liver, stomach, small intestine, colon, kidney and skin. In both fetal and adult tissues, the expression was predominantly cytoplasmic. It was concluded that survivin was abundantly and prominently expressed during fetal development in rat and that the polyclonal anti-human survivin antibody SUR12A-CFI is reactive with rat survivin.
Autoantibodies to survivin have been reported in lung cancers and in gastrointestinal cancers. A few reports have also described a low prevalence of autoantibodies to survivin and at low titres in the sera of breast cancer patients with no implications for their clinical usefulness. This study was designed to re-examine the prevalence and the clinical correlations of autoantibodies to the tumour protein survivin, in the sera of patients with infiltrating ductal carcinoma of the breast using an ELISA assay. In spite of the low prevalence of autoantibodies to survivin (7%, n = 57), their presence was associated with grade III tumours, with tumour sizes exceeding 10cm, with axillary lymph nodal involvement and with metastases. Moreover, all the autoantibody-positive cases were estrogen and progesterone receptors negative. Furthermore, all the autoantibody-positive cases expressed survivin with high scores.
The albumin globulin ratio (A/G ratio) is meant to represent the ratio of alterations in serum proteins, since, in liver disease, globulins (G) rise following serum albumin (SA) decrease. pathophysiological value, its' use has been limited. Alternatively, we have developed an index, the globulin compensation index (GCI) to measure the changes in serum globulins when albumin is decreased. The index is calculated as follows: G - 25 / 35 - SA. The GCI has been tested using retrospective patients' data from the Hospital Universiti Sains Malaysia. Analysis of the data shows that the GCI may be of potential value in showing the actual serum protein status, especially in cases where globulins are decreased along with albumin. Furthermore, globulin rise in cases with reduced albumin was found in 72.3% of cases of hepatic diseases, whereas this finding occurred in up to 32.3% of cases of non-hepatic, systemic diseases.
The utilization of the chemical laboratory resources at the Hospital Sains Malaysia was evaluated. More than 100,000 test requests received and performed over a 12-month period, were analyzed retrospectively. The analysis conducted included the abnormal results obtained, the degree of duplication of tests, and the extent of test-panel ordering. It was found that a relatively moderate degree of over-ordering was evident. The findings suggested that the main reasons for over-ordering were the use of panel tests of ordering, in addition to a small, yet significant degree of duplication. Strategies for cutting down the test ordering have been reviewed and discussed.
Survivin is a 16.5-kDa intracellular protein also known as AP14 or BIRC5. It inhibits apoptosis and regulates cell division and belongs to the inhibitors of apoptosis (IAP) gene family. In the majority of neoplasms investigated for survivin expression, high levels of the IAP proteins were predictive of tumour progression, either in terms of disease-free survival or overall survival, thus providing significant prognostic information. Hence, the prognostic value of survivin expression in tumour masses of invasive ductal carcinoma has been investigated. It was found that negative and low expression of survivin correlated significantly with favourable outcomes. Conversely, high expression correlated with unfavourable outcomes. The five-year survival rate was higher among the cases with low and negative survivin expression, compared to those with higher survivin expression. However, this correlation was found to be insignificant statistically. Furthermore, a statistical model has been devised to explain the combined effects of survivin expression and its sub-cellular localisation, p-53 expression and lymph nodal involvement, on the outcomes of these patients.
This work studied the correlations between survivin, bcl-2 and p53 in infiltrating ductal carcinoma of the breast. A total number of 382 cases were collected from 3 hospitals in northeastern Malaysia. Survivin, bcl-2 and p53 were detected by immunohistochemistry on samples prepared from tissue blocks. Significant correlations were found between tumor histological grades and tumor size and lymph node involvement. Highly significant statistical correlations (p<0.001) were found in expression of the markers under study. It is concluded that such significant correlations may imply that the alterations in the expression take place in a concerted fashion, implying that many of these cases may share common abnormalities.
The human fibroblast MRC-5 cells incubated with PHB granules (TM) added at a final concentration of 4 mg/ml showed a time-course pattern of survival. The percentages of dead cells obtained were at the rate of 3.8% after 7 days, respectively. When the MRC-5 cells grown in different material, using the test concentration of 4 mg/ml PCM, they were found to show a similar time-course increasing pattern of death as that obtained with PHB. However, the death was noted in the cells incubated for 7 days, the death rates obtained was 40.54% respectively.
Human blood groups are polymorphic and inherited integral structures of the red cell membrane. More than 300 red cell antigens have been identified and further categorized into 30 major discrete systems. Their distribution varies in different communities and ethnic groups.
Human mammaglobin (hMAG) is a secreted protein which has been detected in breast epithelial cells of mammary glands and has been used as a specific marker for breast cancer.
Human cytomegalovirus (HCMV) is a species-specific DNA virus of the Herpetoviridae family. After a primary infection, HCMV persists in a latent form most probably in bone marrow progenitor cells or in peripheral blood monocytes. The virus can reactivate to result in shedding of the virus leading to virus dissemination and new infections. Immunocompromized patients are the ones most vulnerable to serious diseases occasionally acquired in blood transfusions. In a human population, HCMV seropositivity increases steadily with age to become approximately 100% in adults. This study was performed to detect seropositivity among regular blood donors in The Hospital of the Universiti Sains Malaysia, in the state of Kelantan. Using an enzyme immunoassay, it was found that 97.6% of blood donors were HCMV-positive. HCMV is highly prevalent and may be endemic in Kelantan. Hence, long-term strategies are required for the reduction of disease dissemination, and to prevent the exposure of immunocompromized patients to the virus.
The aim of this study was to screen and identify the types of thalassemia among blood donors at the Hospital Universiti Sains Malaysia (HUSM). Thalassemia screening was performed by hemoglobin electrophoresis. A total number of 80 blood samples were obtained from donors at the Transfusion Medicine Unit, HUSM. The ethnic origins of the donors were Malays (n=73, 91.3%) and non-Malays (n=7, 8.75%). Males comprised 88.1% of the donors. Thalassemia was detected in 16.25% (n=13) of the blood donors. Of those with thalassemia, 46.2% (6/13) were anemic. Microcytosis and hypochromia were detected in 84.6% (n=l1) and 84.6% (n=l1) of these donors, respectively. The types of thalassemias detected were Hb E, 11.25% (n=9/80) and beta thalassemia trait, 5% (n=4/80). Among the thalassemias detected, the Hb E hemoglobinopathy was comprised of Hb E/ alpha-thalassemia (38.5%: n=5), Hb E /beta-thalassemia (23.1%: n=3), Hb E trait (7.6%: n=1) and beta-thalassemia (30.8%: n=4). In conclusion, screening for thalassemia trait should be included as part of a standard blood testing before blood donation. Further studies are required to look at the effects of donated thalassemic blood.
INTRODUCTION: Survivin is a 16.5-kDa intracellular protein that inhibits apoptosis and regulates cell division, and belongs to the inhibitors of apoptosis gene family. It appears to have an important role in regulating apoptosis at the cell cycle checkpoints. Survivin has been found to have a differential distribution in cancer compared to normal tissue, as it is over-expressed in malignant tumours.
METHODS: In addition to the demographical analysis of the disease, data from 382 women with invasive ductal carcinoma of the breast were collected from three hospitals in Northeast Malaysia, and analysed for survivin expression by immunohistochemistry.
RESULTS: Invasive ductal carcinoma of the breast was found to be the most prevalent breast cancer type. Survivin was detected in 260 (68.1 percent) study cases. In addition, significant correlations have been shown between survivin expression on one hand, and tumour size and lymph node involvement on the other hand (p-value is less than 0.05). However, no significant correlations were found with other clinicopathological factors, such as tumour histological grade, tumour side, oestrogen and progesterone receptors. Nuclear expression of survivin was detected in 16.5 percent of the study cases, cytoplasmic expression was detected in 24.1 percent, and 27.5 percent of the cases expressed survivin in both nuclear and cytoplasmic locations simultaneously. The subcellular localisation of survivin was significantly correlated (p is less than 0.001) with the lymph node involvement indicating its value in predicting the aggressiveness of tumour cells, since it increases the resistance to apoptosis and promotes cell proliferation.
CONCLUSION: This is the fi rst known report on survivin expression in cancer in West Malaysia and Southeast Asia. It emphasises the importance of the detection of survivin in breast cancer to aid in diagnosis, confirm malignancy, and to assess the disease progress and response to therapy.