Marine microalgae have been prominently featured in cancer research. Here, we examined cytotoxic effect and apoptosis mechanism of crude ethanol extracts of an indigenous microalga, Chaetoceros calcitrans (UPMAAHU10) on human breast cell lines. MCF-7 was more sensitive than MCF-10A with IC50 value of 3.00 ± 0.65, whilst the IC50 value of Tamoxifen against MCF-7 was 12.00 ± 0.52 μg/mL after 24 hour incubation. Based on Annexin V/Propidium iodide and cell cycle flow cytometry analysis, it was found that inhibition of cell growth by EEC on MCF-7 cells was through the induction of apoptosis without cell cycle arrest. The apoptotic cells at subG0/G1 phase in treated MCF-7 cells at 48 and 72 hours showed 34 and 16 folds increased compared to extract treated MCF-10A cells which showed only 6 and 7 folds increased at the same time points, respectively. Based on GeXP study, EEC induced apoptosis on MCF-7 cells via modulation of CDK2, MDM2, p21Cip1, Cyclin A2, Bax and Bcl-2. The EEC treated MCF-7 cells also showed an increase in Bax/Bcl-2 ratio that in turn activated the caspase-dependent pathways by activating caspase 7. Thus, marine microalga, Chaetoceros calcitrans may be considered a good candidate to be developed as a new anti-breast cancer drug.
Current chemotherapeutic drugs kill cancer cells mainly by inducing apoptosis. However, they become ineffective once cancer cell has the ability to metastasize, hence the poor prognosis and high mortality rate. Therefore, the purpose of this study was to evaluate the antimetastatic potential of Phyllanthus (P. niruri, P. urinaria, P. watsonii, and P. amarus) on lung and breast carcinoma cells.
The output of state-of-the-art reverse-engineering methods for biological networks is often based on the fitting of a mathematical model to the data. Typically, different datasets do not give single consistent network predictions but rather an ensemble of inconsistent networks inferred under the same reverse-engineering method that are only consistent with the specific experimentally measured data. Here, we focus on an alternative approach for combining the information contained within such an ensemble of inconsistent gene networks called meta-analysis, to make more accurate predictions and to estimate the reliability of these predictions. We review two existing meta-analysis approaches; the Fisher transformation combined coefficient test (FTCCT) and Fisher's inverse combined probability test (FICPT); and compare their performance with five well-known methods, ARACNe, Context Likelihood or Relatedness network (CLR), Maximum Relevance Minimum Redundancy (MRNET), Relevance Network (RN) and Bayesian Network (BN). We conducted in-depth numerical ensemble simulations and demonstrated for biological expression data that the meta-analysis approaches consistently outperformed the best gene regulatory network inference (GRNI) methods in the literature. Furthermore, the meta-analysis approaches have a low computational complexity. We conclude that the meta-analysis approaches are a powerful tool for integrating different datasets to give more accurate and reliable predictions for biological networks.
The aim of the present study was to evaluate the association between the Glyoxalase I (GLOI) Ala111Glu polymorphism and breast cancer risk among the major Malaysian ethnic groups, the Malays, Chinese and Indians, as well as clinico-pathological characteristics of these patients. Genotyping of GLOI gene was performed on blood samples obtained from 387 patients and 252 normal healthy women who had no history of any malignancy using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype and allele frequencies of GLOI polymorphism were not significantly different between the patients and normal individuals among the Malays (P= 0.721, 0.402), Chinese (P= 0.208, 0.079) and Indians (P= 0.612, 0.349), respectively. The Malay, Chinese and Indian women who were Glu/Glu homozygotes (P= 0.419, 0.093, 0.367), Ala/Glu heterozygotes (P= 0.648, 0.182, 0.402) and carriers of Glu allele (P= 0.402, 0.079, 0.349), respectively, were not associated with breast cancer risk. The Glu allele genotype was significantly associated with absence of progesterone receptor (P= 0.036). Thus, the polymorphic variant of the GLOI gene might not be a useful genetic marker to identify Malaysian Malay, Chinese or Indian women who could be at greater risk of developing breast cancer.
Study site: Universiti Malaya Medical Centre (UMMC)
To provide current insights into the opinions, attitudes, and knowledge of menopausal women in Asia regarding menopause and hormone replacement therapy (HRT).
Second cancer induction in the contralateral breast (CB) is an issue of some concern in breast radiotherapy especially for women under the age of 45 years at the time of treatment. The CB dose from 2-field and 3-field techniques in post-mastectomy chest wall irradiations in an anthropomorphic phantom as well as in patients were measured using thermoluminescent dosimeters (TLDs) at the local radiotherapy center. Breast and chest wall radiotherapy treatments were planned conformally (3D-CRT) and delivered using 6-MV photons. The measured CB dose at the surface fell sharply with distance from the field edge. However, the average ratio of the measured to the calculated CB dose using the pencil beam algorithm at the surface was approximately 53%. The mean and median measured internal dose at the posterior border of CB in a phantom was 5.47+/-0.22 cGy and 5.44 cGy, respectively. The internal CB dose was relatively independent of depth. In the present study the internal CB dose is 2.1-4.1% of the prescribed dose which is comparable to the values reported by other authors.
Matched MeSH terms: Breast Neoplasms/radiotherapy*
We report on a Malaysian kindred with Li-Fraumeni syndrome. The proband was an 8-year-old girl who presented with embryonal rhabdomyosarcoma of the trunk at the age of 8 months and developed a brain recurrence at the age of 7 years, which was 5 years after remission. A younger sister later developed adrenocortical carcinoma at the age of 6 months. Their mother and maternal grandmother were diagnosed with breast cancer at the ages of 26 and 38 years, respectively. TP53 mutation detection in this family revealed a duplication of a GGCGTG motif starting at nucleotide 17579 in exon 10, resulting in an in-frame insertion of two amino acids between residues 334 and 336 in the tetramerization domain of the p53 protein. This mutation was found in the proband and her affected sister as well as her mother. In addition, the mutation was detected in two other siblings (a brother aged 3 years and a sister aged 18 months) who have not yet developed any malignancy. Sequencing of TP53 in the father and two other asymptomatic siblings revealed wild-type TP53. To our knowledge, this is a first report of a Li-Fraumeni syndrome family in Southeast Asia.
We describe a semi-automated technique for the quantitative assessment of breast density from digitized mammograms in comparison with patterns suggested by Tabar. It was developed using the MATLAB-based graphical user interface applications. It is based on an interactive thresholding method, after a short automated method that shows the fibroglandular tissue area, breast area and breast density each time new thresholds are placed on the image. The breast density is taken as a percentage of the fibroglandular tissue to the breast tissue areas. It was tested in four different ways, namely by examining: (i) correlation of the quantitative assessment results with subjective classification, (ii) classification performance using the quantitative assessment technique, (iii) interobserver agreement and (iv) intraobserver agreement. The results of the quantitative assessment correlated well (r2 = 0.92) with the subjective Tabar patterns classified by the radiologist (correctly classified 83% of digitized mammograms). The average kappa coefficient for the agreement between the readers was 0.63. This indicated moderate agreement between the three observers in classifying breast density using the quantitative assessment technique. The kappa coefficient of 0.75 for intraobserver agreement reflected good agreement between two sets of readings. The technique may be useful as a supplement to the radiologist's assessment in classifying mammograms into Tabar's pattern associated with breast cancer risk.
Hypothesis. Withania somnifera is an herb with antioxidant, anti-inflammatory, anticancer, antistress, and adaptogenic properties. Previous studies have shown its antistress effects in animals. Traditional Indian medicine has used it for centuries to alleviate fatigue and improve general well-being.
Matched MeSH terms: Breast Neoplasms/drug therapy*
Although it may sound unpleasant, camel urine has been consumed extensively for years in the Middle East as it is believed to be able to treat a wide range of diseases such as fever, cold, or even cancer. People usually take it by mixing small drops with camel milk or take it directly. The project aims to study the effects of camel urine in inhibiting the growth potential and metastatic ability of 4T1 cancer cell line in vitro and in vivo. Based on the MTT result, the cytotoxicity of camel urine against 4T1 cell was established, and it was dose-dependent. Additionally, the antimetastatic potential of camel urine was tested by running several assays such as scratch assay, migration and invasion assay, and mouse aortic ring assay with promising results in the ability of camel urine to inhibit metastatic process of the 4T1 cells. In order to fully establish camel urine's potential, an in vivo study was carried out by treating mice inoculated with 4T1 cells with 2 different doses of camel urine. By the end of the treatment period, the tumor in both treated groups had reduced in size as compared to the control group. Additional assays such as the TUNEL assay, immunophenotyping, cytokine level detection assay, clonogenic assay, and proteome profiler demonstrated the capability of camel urine to reduce and inhibit the metastatic potential of 4T1 cells in vivo. To sum up, further study of anticancer properties of camel urine is justified, as evidenced through the in vitro and in vivo studies carried out. Better results were obtained at higher concentration of camel urine used in vivo. Apart from that, this project has laid out the mechanisms employed by the substance to inhibit the growth and the metastatic process of the 4T1 cell.
Matched MeSH terms: Breast Neoplasms/drug therapy*
To date, because of limited budgets and lower incidence of breast cancer, the majority of Asian countries do not have population-based screening programmes, but instead offer opportunistic screening. However, there have been few studies which have assessed the motivators for women attending such programmes and the appropriateness of the programmes in terms of targeting women at risk.
INTRODUCTION: Globally many women suffer from depression during pregnancy. This study investigated the impact of antenatal depressive symptoms on the duration of breastfeeding up to 6 months among women in Sabah, Malaysia.
SUBJECTS AND METHODS: A prospective cohort study of 2,072 women was conducted in Sabah during 2009-2010. Participants were recruited at 36-38 weeks of gestation and followed up at 1, 3, and 6 months postpartum. Depressive symptoms were assessed using the validated Malay version of the Edinburgh Postnatal Depression Scale (EPDS). Cox regression analyses were performed to determine the relationship between antenatal EPDS scores and cessation of breastfeeding before 6 months postpartum.
RESULTS: In total, 1,078 (52%) women with complete information on breastfeeding duration were included in the final sample. Approximately 99% of mothers were breastfeeding at discharge, and 87% of them continued to breastfeed at 6 months postpartum. Women with an antenatal EPDS score of 8 or above were twice more likely to stop breastfeeding before 6 months (adjusted hazards ratio=1.95; 95% confidence interval, 1.26, 3.01) than those who scored less than 4 on the EPDS.
CONCLUSIONS: Depressive symptoms during pregnancy appeared to be associated with early breastfeeding cessation for mothers residing in Sabah.
The mutation spectrum of the BRCA1 gene among ethnic groups from Asia has not been well studied. We investigated the frequency of mutations in the BRCA1 gene among Malay breast cancer patients from Singapore, independent of family history. By using the protein truncation test (PTT) and direct sequencing, BRCA1 mutations were detected in 6 of 49 (12.2%) unrelated patients. Four novel missense mutations in exon 11, T557A (1788A>G), T582A (1863A>G), N656S (2086A>G) and P684S (2169C>T) were identified in one patient. Two patients had missense mutations in exon 23, V1809A (5545T>C), which has been previously detected in individuals from Central and Eastern Europe. Three unrelated patients had the deleterious 2846insA frameshift mutation in exon 11. Methylation specific PCR (MSP) of the promoter region of the BRCA1 gene detected hypermethylation of tumor DNA in an additional 2 patients. Haplotype analysis using the microsatellite markers D17S855, D17S1323 and D17S1325 revealed a common haplotype for the three unrelated patients and their three relatives with the 2846insA mutation. These findings strongly suggest that the 2846insA mutation, the most common deleterious mutation in this study, may possibly be a founder mutation in breast cancer patients of Malay ethnic background.
Certain anti-idiotypic antibodies that bind to the antigen-combining sites of antibodies can effectively mimic the three-dimensional structures and functions of the external antigens and can be used as surrogate antigens for active specific immunotherapy. Extensive studies in animal models have demonstrated the efficacy of these vaccines for triggering the immune system to induce specific and protective immunity against bacterial, viral and parasitic infections as well as tumors. Several monoclonal anti-idiotype antibodies that mimic distinct human tumor-associated antigens have been developed and characterized. Encouraging results have been obtained in recent clinical trials using these anti-idiotype antibodies as vaccines. In this article, we will review the current literature and discuss the potential of this novel therapeutic approach for various human cancers.
Recent developments in breastfeeding are reviewed in relation to species-specific adaptive suckling and the level of maturity of the newborn. Scientific advantages and advances are noted concerning biochemistry, protective substances, emotional differences, child spacing and economics. The significance of unimpaired maternal reflexes and the need for information is stressed with regard to successful lactation and as common causes of inadequacy. The components needed in varying degrees, in breastfeeding programmes are mentioned briefly.
This study examines the possibility that estimation of the effect of breast-feeding on infant survival is affected by selection bias, in that children who are healthier at birth may be more likely to be breast-fed. Data are from the 1976 Malaysian Family Life Survey. "Ordinary logit models for breast-feeding and survival are estimated, and the results suggest that selection is indeed present. For example, children of higher birth weight appear to be more likely to be breast-fed and likely to survive. In addition, weight at birth and the duration of breast-feeding appear to be linked." Using birth weight as an indicator for the child's health, the authors conclude that "the direct influence of breast-feeding on survival remains of overwhelming importance even after corrections for selection bias are made."
PIP:
The International Fertility Research Program is carrying out several studies focused on breastfeeding's contraceptive protection. A longitudinal study is investigating the relationship between breastfeeding and the return of ovulation and fertility after childbirth. The impact of factors such as the early introduction of supplementary foods, resumption of menses, and sexual practices on the return of ovulation will be analyzed. The study, which will be conducted at 4 geographic sites, will include a total of 100 women who are breastfeeding and a control group of 40 nonlactating mothers. Its ultimate goal will be to determine the optimum time for breastfeeding women with different cultural needs to start using contraceptives. A second study will seek to determine whether progestogen-only oral contraceptives (OCs) have advantages for lactating women. Trials in India, Malaysia, Argentina, and Egypt will compare 1000 lactating women who use progestogen-only OCs with an equal number of women who use nonhormonal contraception in terms of contraceptive acceptance and side effects and infant weight gain. The third study will survey breastfeeding patterns in relation to changing child spacing trends in a sample of 4000 women from Lagos, Nigeria. Analyzed will be the proportions of women who are using a modern method of fertility control, the proportions protected from unwanted pregnancy by the traditional practices of prolonged breastfeeding and sexual abstinence, and determinants of recent changes in the prevalence and duration of breastfeeding.