Transforming growth factor-beta (TGFbeta) is present, predominantly in latent forms, in normal and malignant breast tissue. The mechanisms by which latent TGFbeta is activated physiologically remain largely an enigma. The objective of this study was to assess whether the proteases, cathepsin D and prostate specific antigen (PSA) could activate latent TGFbeta1 and TGFbeta2 in conditioned media of the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 human breast cancer cell lines, newly purchased from ATCC. Both of the cell lines were seeded in 6-well plates 2 days prior to treatment with varying concentrations of cathepsin D and PSA. Active TGFbeta1 and TGFbeta2 in the media were then measured by ELISA after 4, 8, 24 and 72 hours of treatment. TGFbeta1 and TGFbeta2 mRNA expression of both cell lines were measured by RT-PCR to determine whether any increase in level of active TGFbeta1 and TGFbeta2 was due to increased production. There was a significant increase in only active TGFbeta2 levels in the MDA-MB-231 cell line with both treatments. Cathepsin D and PSA did not have any effect on TGFbeta1 and TGFbeta2 mRNA expression. Cathepsin D and PSA were unable to activate latent TGFbeta1 and TGFbeta2 in these two breast cancer cell lines. A constant level of TGFbeta2 mRNA in the control and treated MDA-MB-231 cells suggests that the increase in level of active TGFbeta2 was not a result of increased production but was likely to be due to activation by a mechanism independent of cathepsin D and PSA.
Matched MeSH terms: Breast Neoplasms/drug therapy*; Breast Neoplasms/metabolism
The management of pulmonary metastasis from breast carcinoma is challenging and often consists of palliation of symptoms. Surgical resection of pulmonary metastasis is considered inappropriate in view of the disseminated nature of the disease and limited life expectancy. It can however be a worthwhile option if imaging, including bone scans rule out metastatic disease in other part of the body. We report a patient with pulmonary metastasis from breast carcinoma who was successfully treated with pulmonary wedge resection of the metastatic lesion.
Breast cancer is the most common cancer among Malaysian women. There is a marked geographical difference in the worldwide incidence of breast cancer, with a higher incidence in developed countries compared to developing countries. From 1998 to 2001, new cases of breast cancer presenting to the breast clinics at Hospital Kuala Lumpur and University Malaya Medical Centre, Malaysia, were reviewed; the race, age and stage at presentation were analysed. Of 774 cases seen in Hospital Kuala Lumpur, only 5.2% (40/774) were impalpable breast cancers diagnosed on mammography. The prevalent age group was 40 to 49 years, and the median age was 50 years. The average size of the tumour was 5.4 cm in diameter. Malay women appear to have larger tumours and a later stage at presentation than other ethnic groups; 50% to 60% were in late stages (Stages 3 and 4). During the same period, 752 new cases of breast cancer were seen in the University Malaya Medical Centre. The average tumour size was 4.2 cm, and 30% to 40% were in late stages. The age incidence was similar. The delay in presentation of breast cancer was attributed to a strong belief in traditional medicine, the negative perception of the disease, poverty and poor education, coupled with fear and denial. A prospective, population-based study is required to determine the demographic pattern of breast cancer and the factors delaying presentation. These findings will have important implications in future programmes to promote the early detection of breast cancer, as well as in understanding geographical as well as racial variations in the incidence of breast cancer.
Matched MeSH terms: Breast Neoplasms/diagnosis*; Breast Neoplasms/epidemiology*; Breast Neoplasms/pathology
It has recently been shown that tocotrienols are the components of vitamin E responsible for inhibiting the growth of human breast cancer cells in vitro, through an estrogen-independent mechanism. Although tocotrienols act on cell proliferation in a dose-dependent manner and can induce programmed cell death, no specific gene regulation has yet been identified. To investigate the molecular basis of the effect of tocotrienols, we injected MCF-7 breast cancer cells into athymic nude mice. Mice were fed orally with 1 mg/d of tocotrienol-rich fraction (TRF) for 20 wk. At end of the 20 wk, there was a significant delay in the onset, incidence, and size of the tumors in nude mice supplemented with TRF compared with the controls. At autopsy, the tumor tissue was excised and analyzed for gene expression by means of a cDNA array technique. Thirty out of 1176 genes were significantly affected. Ten genes were downregulated and 20 genes up-regulated with respect to untreated animals, and some genes in particular were involved in regulating the immune system and its function. The expression of the interferon-inducible transmembrane protein-1 gene was significantly up-regulated in tumors excised from TRF-treated animals compared with control mice. Within the group of genes related to the immune system, we also found that the CD59 glycoprotein precursor gene was up-regulated. Among the functional class of intracellular transducers/effectors/modulators, the c-myc gene was significantly down-regulated in tumors by TRF treatment. Our observations indicate that TRF supplementation significantly and specifically affects MCF-7 cell response after tumor formation in vivo and therefore the host immune function. The observed effect on gene expression is possibly exerted independently from the antioxidant activity typical of this family of molecules.
Matched MeSH terms: Breast Neoplasms/genetics*; Breast Neoplasms/pathology*
Breast cancer is one of the commonest cancers among women in Malaysia. The relation between lifestyle practices and the risk of breast cancer in Chinese women aged 21-55 years were assessed using data collected from June to October 2001, via a face-to face interview in a case control study in the Breast Clinics of Kuala Lumpur Hospital and University Malaya Medical Centre. A total of 89 cases with breast cancer were compared with 85 controls without the disease. Our study showed that breastfeeding had an odds ratio of 4.43 after adjustment for confounders. The results add to the evidence of a protective association between breast feeding practices and breast cancer particularly among Chinese women receiving treatment at two government hospitals in the Klang Valley.
Matched MeSH terms: Breast Neoplasms/ethnology; Breast Neoplasms/etiology*; Breast Neoplasms/epidemiology*
Bioassay guided fractionation of the roots of Cyathostemma argenteum using the brine shrimp resulted in the isolation of two uncommon flavanones, 2,5-dihydroxy-7-methoxy flavanone 1 and 2,5-dihydroxy-6,7-dimethoxy flavanone 2 while the stem bark yielded the related compounds 5-hydroxy-7-methoxy flavone 3 and 5-hydroxy-6,7-dimethoxy flavone 4. The alkaloids liriodenine 5 and discretamine 6 as well as benzyl benzoate 7 were isolated from the roots and 6 was also isolated from the stembark. In cytotoxicity tests using four human breast cancer cell lines, 1 and 2 were weakly toxic to MCF-7 cells (IC(50) = 19.6 and 19.0 microM, respectively) but showed little activity against MCF-7 cells resistant to doxorubicin or against two oestrogen receptor-deficient cell lines. Compound 5, but not 6 and 7, was moderately cytotoxic against all four cell lines. These results are discussed in the context of the traditional use of C. argenteum in the treatment of breast cancer.
Matched MeSH terms: Breast Neoplasms/drug therapy; Breast Neoplasms/pathology
We have analyzed unfractionated sera of newly diagnosed patients (n=10) with breast carcinoma (BC), prior to treatment, and patients (n=5) with fibrocystic disease of the breast (FDB) by two-dimensional gel electrophoresis (2-DE) and silver staining. The patients' 2-DE serum protein profiles obtained were then subjected to image analysis and compared to similar data generated from sera of normal healthy female controls (n=10) of the same range of age. The relative expression of alpha1-antichymotrypsin (ACT), clusterin, and complement factor B was significantly higher in all BC patients as compared to normal controls. However, the expression of alpha1-antitrypsin (AAT) in BC patients was apparently lower than that of the controls. Similar differential expression of ACT was detected in the FDB patients. The aberrant expression of the serum acute-phase proteins of patients with BC and FDB was confirmed by competitive enzyme-linked immunosorbent assay (ELISA). Similar altered proteins expression was also observed from immunohistochemical studies of malignant (n=5) and benign (n=5) breast lesions of the respective patients performed using antisera to the aberrantly expressed proteins. However, the malignant breast lesions were instead positively stained for AAT. The differential expression of the serum proteins was apparently abrogated when a six-month follow-up study was performed on nine of the BC patients subsequent to treatment.
Matched MeSH terms: Breast Neoplasms/metabolism*; Breast Neoplasms/pathology
Prebiopsy localization of impalpable breast lesions (IBL) assures removal of suspicious mammographically detected lesions. Specimen radiograph of the excised specimen is mandatory to confirm complete excision. The aim of this study was to audit our series of percutaneous hookwire localization and to determine the positive biopsy rate of the mammographically detected impalpable breast lesion in our center. Thirty-eight patients with suspicious IBL underwent excision biopsy under mammographic localization in our unit from late February 1998 to May 2003. The excised specimen is immobilized and compressed within the Transpec device. This device incorporates a reference grid visible in the specimen radiograph. Hence, the target lesion marked in the reference grid of the specimen radiograph will allow precise examination and exact localization of the suspicious lesion by the pathologist. The positive biopsy rate for malignant lesion was 26.3%, the majority fall in the range of 40-59 age group. Thirty-two (84.2%) of the patients had clustered micro-calcifications, 4 (10.5%) had impalpable mass lesions and in 2 (5.3%) spiculated lesions were seen on the preoperative mammogram. Mammographic feature of clustered micro-calcification accounts for all the malignant lesions in our series. Utilization of Transpec device has shown to be practical, reliable and cost effective in the management of IBL. Nonetheless, it should be emphasized that optimal specimen radiography and pathological correlation requires close cooperation between radiologist, surgeon and pathologist.
Matched MeSH terms: Breast Neoplasms/diagnosis; Breast Neoplasms/pathology
The aim of the study was: to obtain the profile of patients (with regards to age and family history of breast cancer) with a palpable breast mass. To determine the validity of ultrasound in the assessment of the palpable breast mass by determining the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ultrasound in distinguishing a malignant mass. To determine the most discriminating ultrasound characteristics for differentiating benign and malignant masses. Seventy patients who had fine needle aspiration cytology of a palpable breast mass were subjected to an ultrasound assessment of the mass. The ultrasound findings were classified as benign, indeterminate or malignant. These findings were then compared with either the cytology or histology results in cases that eventually had surgical excision. The age of the patients ranged from 15 to 66 years old The majority was in the third and fourth decades with an average age of 25 years. The 8 patients with a proven malignant breast mass were aged between 39 and 66 years old. They did not have any family history of breast cancer. Only 4 patients had a family history of breast carcinoma and all proved to have a benign breast lesion. Ultrasound had a sensitivity of 100%, specificity of 85.7%, positive predictive value of 50%, negative predictive value of 100% and accuracy of 87.5% for distinguishing a malignant mass. For benign masses: 93.7% had well-defined margins, 81.3% had homogenous internal echoes, 91.7% had depth-width ratio of less than 1.0 and 89% were compressible. For malignant masses: 87.5% had either ill-defined or irregular margins, 87.5% had inhomogenous internal echoes and mixed posterior echoes, and 100% were incompressible. The majority of patients with a palpable breast mass were aged below 40 years old. Most of the patients with a malignant breast mass were aged 40 years and older. Neither a positive nor a negative family history of breast cancer had any significance on outcome. Ultrasound had high sensitivity, specificity and accuracy in distinguishing a malignant mass. The most discriminating benign ultrasound characteristic was compressibility. The most discriminating malignant ultrasound characteristic was ill-defined and irregular margins.
Matched MeSH terms: Breast Neoplasms/ultrasonography*
Skin-sparing mastectomy is still in its infancy in Malaysia. The option of skin-sparing mastectomy is rarely given to patients as many general surgeons perform the conventional mastectomy. This could also be compounded by the lack of awareness amongst the local surgeons on the safety, surgical technique and treatment outcome of this relatively new procedure. This case report demonstrates the feasibility of this procedure performed on a Malaysian patient with a comparable outcome of those reported in the Western countries.
Vitamin E is important not only for its cellular antioxidant and lipid-lowering properties, but also as an antiproliferating agent. It has also been shown to contribute to immunoregulation, antibody production, and resistance to implanted tumors. It has recently been shown that tocotrienols are the components of vitamin E responsible for growth inhibition in human breast cancer cells in vitro as well as in vivo through estrogen-independent mechanisms. Although tocotrienols act on cell proliferation in a dose-dependent manner and can induce programmed cell death, no specific gene regulation has yet been identified. In order to investigate the molecular basis of the effect of a tocotrienol-rich fraction (TRF) from palm oil, we performed a cDNA array analysis of cancer-related gene expression in estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231) human breast cancer cells. The human breast cancer cells were incubated with or without 8 mug/mL of tocotrienols for 72 h. RNA was subsequently extracted and subjected to reverse transcription before being hybridized onto cancer arrays. Tocotrienol supplementation modulated significantly 46 out of 1200 genes in MDA-MB-231 cells. In MCF-7 cells, tocotrienol administration was associated with a lower number of affected genes. Interestingly, only three were affected in a similar fashion in both cell lines: c-myc binding protein MM-1, 23-kDa highly basic protein, and interferon-inducible protein 9-27 (IFITM-1). These proteins are most likely involved in the cell cycle and can exert inhibitory effects on cell growth and differentiation of the tumor cell lines. These data suggest that tocotrienols are able to affect cell homeostasis, possibly independent of their antioxidant activity.
The crude methanol extracts of Gelsemium elegans leaves were assessed for their cytotoxic activity using the microculture 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for cellular viability. This study utilized two different types of human cancer cell lines, CaOV-3 (human ovarian cancer cells) and MDA-MB-231 (human estrogen receptor negative breast cancer cells), allowing for comparison of toxicity of G. elegans against these two cancer cells lines. Our results showed that the methanol extract of G. elegans exhibited high cytotoxicity against the human ovarian cancer cell line CaOV-3 with an IC50 value of 5microg/ml after 96 h incubation. However, G. elegans displayed discernibly less toxicity against the MDA-MB-231 cells with an IC50 value 40microg/ml after 96 h incubation and this effect was dose- and time-dependent, up to 72h and 20-30 microg/ml. In conclusion, our results demonstrated that G. elegans is potently cytotoxic against the human ovarian cancer cell line CaOV-3 and to a lesser extend towards the human breast carcinoma cancer MDA-MB-231 cells, suggesting that the extract is selective towards CaOV-3 cells and may have a chemotherapeutic role for ovarian cancer treatment in the future.
The objective of this study was to determine the anti cancer effects of red spinach (Amaranthus gangeticus Linn) in vitro and in vivo. For in vitro study, microtitration cytotoxic assay was done using 3-(4,5-dimethylthiazol-2-il)-2,5-diphenil tetrazolium bromide (MTT) kit assay. Results showed that aqueous extract of A gangeticus inhibited the proliferation of liver cancer cell line (HepG2) and breast cancer cell line (MCF-7). The IC(50) values were 93.8 mu g/ml and 98.8 mu g/ml for HepG2 and MCF-7, respectively. The inhibitory effect was also observed in colon cancer cell line (Caco-2), but a lower percentage compared to HepG2 and MCF-7. For normal cell line (Chang Liver), there was no inhibitory effect. In the in vivo study, hepatocarcinogenesis was monitored in rats according to Solt and Farber (1976) without partial hepatectomy. Assay of tumour marker enzymes such as glutathione S-transferase (GST), gamma-glutamyl transpeptidase (GGT), uridyl diphosphoglucuronyl transferase (UDPGT) and alkaline phosphatase (ALP) were carried out to determine the severity of hepatocarcinogenesis. The result found that supplementation of 5%, 7.5% and 10% of A. gangeticus aqueous extract to normal rats did not show any significant difference towards normal control (P <0.05). The exposure of the rats to chemical carcinogens diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) showed a significant increase in specific enzyme activity of GGT, GST, UDPGT and ALP compared to normal control (P <0.05). However, it was found that the supplementation of A. gangeticus aqueous extract in 5%, 7.5% and 10% to cancer-induced rats could inhibit the activity of all tumour marker enzymes especially at 10% (P <0.05). Supplementation of anti cancer drug glycyrrhizin at suggested dose (0.005%) did not show any suppressive effect towards cancer control (P <0.05). In conclusion, A. gangeticus showed anticancer potential in in vitro and in vivo studies.
Matched MeSH terms: Breast Neoplasms/enzymology; Breast Neoplasms/prevention & control*
Breast cancer is the commonest female cancer in Malaysia with a prevalence of 86.2 cases per 100,000 women in 1996. Pronling breast cancer patients is important for better planning of preventive and screening strategies for Malaysian women. The aims of this cross-sectional study were to identify histological presentation, socio-demographic and reproductive characteristics and prevalence of risk or protective factors of breast cancer among women with breast cancer in Kelantan. A total of 175 female breast cancer patients who were diagnosed in 1991 to 2000, were interviewed using standardized questionnaires. The mean (sd) age was 47.0 (9.6) years with 77.7% Malay, 20.6% Chinese and 1.7% others. About half (52.6%) had 9 years or less of formal education, while 59.4% were housewives/unemployed and 60.6% had a monthly family income of less than RM1 ,000. The commonest histological type was innltrative ductal carcinoma (73 .7%) . Presentation of breast cancer with the stage lll or Vl was 59.4%. The prevalence of nulliparity · 13.1%, breastfeeding longer than two years - 58.9%, premenstrual period - 72.0%, menarche at 11 years old or less - 5 .7%, positive family history - 14.4%, overweight/obesity - 48.0%, oral contraceptives use 30.3%, hormone replacement therapy » 1.1%, cigarette smoking - 4.6%, consuming akohol - 3.4%, previous benign breast disease - 6.3%, previous breast biopsy - 2.9% and previous oophorectomy - 4.6%. The patients were younger compared to other studies. The ethnic distribution did not represent the population distribution of Kelantan. The prevalence of overweight/obesity and smoking were higher than the national prevalence among women, thus they should be included in the prevention strategies for breast cancer. Further studies are recommended to investigate why many of breast cancer patients in Kelantan presented at a younger age and at advanced stages of cancer.
Cancer of the cervix is caused by micro-organisms called Human Papilloma Virus (HPV). This virus is only transmitted to women from their partners/spouses through sexual intercourse. In Malaysia, cancer of the cervix is the second most common cancer among females after breast cancer. The incidence is 21.5 per 100,000 population, with incidence among the Chinese being highest at 33.6 per 100,000 and among Malays the lowest being 12.6 per 100,000. For the past twenty years or so the Annual Reports of Ministry of Health recorded an average of 2500 new cases per year. Cancer of the cervix is preventable. The precursor cancer cells can be easily detected provided the women do regular screening tests called Pap Smear. In nearly all cases this cancer arises from the transformation
zone of the cervix. This is the zone in the cervical mucosa in which the epithelium abruptly changes from hardy squamous epithelium of the ectocervix to the fragile columnar epithelium of the endocervix.
Cervical cancer is the first solid tumour to be shown directly induced by virus. HPV is found in virtually all cervical carcinomas and their precursors.
Currently, breast cancer is the leading cause of cancer-related death in women. Therefore, there is an urgent need to develop alternative therapeutic measures against this deadly disease. Here, we report the cytotoxicity activity and the mechanism of cell death exhibited by the methanol extract prepared from Pereskia bleo (Kunth) DC. (Cactaceae) plant against human breast carcinoma cell line, T-47D. In vitro cytotoxicity screening of methanol extract of Pereskia bleo plant indicated the presence of cytotoxicity activity of the extract against T-47D cells with EC50 of 2.0 microg/ml. T-47D cell death elicited by the extract was found to be apoptotic in nature based a clear indication of DNA fragmentation which is a hallmark of apoptosis. In addition, ultrastructural analysis also revealed apoptotic characteristics (the presence of chromatin margination and apoptotic bodies) in the extract-treated cells. RT-PCR analysis showed the mRNA expression levels of c-myc, and caspase 3 were markedly increased in the cells treated with the plant extract. However, p53 expression was only slightly increased as compared to caspase 3 and c-myc. Thus, the results from this study strongly suggest that the methanol extract of Pereskia bleo may contain bioactive compound(s) that caused breast carcinoma, T-47D cell death by apoptosis mechanism via the activation of caspase-3 and c-myc pathways.
Metastatic eyelid tumours are rare and account for less than 2% of all eyelid neoplasms. We report a case of metastatic breast carcinoma to the eyelid in a 60-year-old Chinese lady presenting with a 2-year history of enlarging, painless nodular lower eyelid swelling. The 1 cm diameter lesion was provisionally diagnosed as a sebaceous cyst. However the excision biopsy revealed a mucinous carcinoma expressing oestrogen receptor protein. She had a past history of mastectomy one year previously and histology showed an infiltrating ductal carcinoma (oestrogen receptor status negative) without evidence of axillary lymph node metastasis. She had completed adjuvant radio- and chemotherapy. Further treatment of the current lesion involved a wide excision which did not show any residual malignancy. She had no other evidence of metastasis and was treated with letrozol. We highlight this case to create awareness among clinicians and opthalmologists on the possibility of metastatic disease as a cause of eyelid swelling, especially in patients with a history of cancer. It may also be the first sign of metastatic disease of an internal malignancy. A review of the literature is also presented.
This paper uses wavelets in the detection comparison of breast cancer among the three main races in Malaysia: Chinese, Malays, and Indians followed by a system that evaluates the radiologist's findings over a period of time to gauge the radiologist's skills in confirming breast cancer cases. The db4 wavelet has been utilized to detect microcalcifications in mammogram-digitized images obtained from Malaysian women sample. The wavelet filter's detection evaluation was done by visual inspection by an expert radiologist to confirm the detection results of those pixels that corresponded to microcalcifications. Detection was counted if the wavelet-detected pixels corresponded to the radiologist's identified microcalcification pixels. After the radiologist's detection confirmation a new client-server radiologist recording and evaluation system is designed to evaluate the findings of the radiologist over some period of cancer detection working time. It is a system that records the findings of the Malaysian radiologist for the presence of breast cancer in Malaysian patients and provides a way of registering the progress of detecting breast cancer of the radiologist by tracking certain metric values such as the sensitivity, specificity, and receiver operator curve (ROC). The initial findings suggest that no single race mammograms are easier for wavelets' detections of microcalcifications and for the radiologist confirmation even though for this study the Chinese race samples detection average were a few percentages less than the other two races, namely the Malay and Indian races.
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.
Matched MeSH terms: Breast Neoplasms/blood; Breast Neoplasms/diagnosis*