MiR-16: A novel hereditary marker in breast cancer and their offspring.

OBJECTIVE: To analyse micro ribonucleic acid-16 in sera of invasive intraductal breast carcinoma in stage III and compare its expression in their daughters and healthy women. METHODS: The study took place from January 2013 till December 2015. This case-control study was conducted at the Ziauddin Cancer Hospital, Karachi, and comprised breast cancer patients and healthy individuals. Stage III invasive intraductal breast cancer patients (cases), their age-matched healthy individuals (control group A) and patients' daughters (control group B) were included. Subjects with stage I cancer and their daughters and subjects with stage IV and their daughters were also included. Serum tests were run on real-time quantitative reverse transcription polymerase chain reaction. Threshold cycle was determined and fold change was calculated. Fold change was applied between the groups. SPSS 20 was used for data analysis. RESULTS: Of the 194 participants, there were 50(25.8%) cases, 50(25.8%) group A controls, 35(18%) group B controls, 20(10.3%) stage I patients, 11(5.7%) daughters of stage 1 patients, 20(10.3%) patients of stage IV and 8(4.1%) daughters of stage IV patients. Micro ribonucleic acid-16 was higher in cases than controls (p=0.001). Group B showed significant gene expression than group A (p=0.001). Stage IV patients and daughters showed expression of micro ribonucleic acid-16 (p=0.001). Triple negative receptor cases showed a greater expression of gene (p=0.001). CONCLUSIONS: Micro ribonucleic acid-16 can be used as a prognostic, diagnostic as well as a predictive marker in breast cancer patients and their offspring.

Lead-induced morphometric changes in the kidneys of albino rats ameliorated by ginkgo biloba extract (EGb 761).

OBJECTIVE: To observe the effects of ginkgo biloba extract on lead-induced morphometric changes in the kidneys of albino rats. METHODS: This randomised controlled study was conducted at the Institute of Basic Medical Sciences, Dow University of Health Sciences, Karachi, from April 2009 to March 2010, and comprised male Wistar albino rats weighing between 150-180 gm who were randomly divided into three equal groups, A, B and C. These were further split into subgroups 1, 2, 3 and 4 according to the duration of the experiment (one, two, four and six weeks). Group A rats were given 1 ml normal saline intraperitoneally daily, group B rats were given lead acetate 8mg/kg intraperitoneally daily, while group C animals received 100mg/kg ginkgo biloba extract orally along with 8mg/kg lead acetate injection. The animals were sacrifised at the end of the prescribed period, and kidneys were retrieved, fixed, stained and examined under light microscope. SPSS 16 was used for data analysis. RESULTS: Of the 120 rats, there were 40(33.3%) in each group. Time-dependent deterioration was observed in the histological architecture of kidneys in group B animals compared to the group A animals, whereas less marked changes were observed in the protected group C animals. In group B animals, the diameter of proximal convoluted tubules increased, the number of proximal convoluted tubules and their nuclei decreased, whereas diameter of the nuclei decreased after an initial increase during the first and second weeks. These parameters remained largely undisturbed in group A animals, whereas changes in group C animals were comparable with those in the controlled group A animals. CONCLUSIONS: Ginkgo biloba extract had a protective effect on lead-induced morphometric changes in the kidneys of albino rats.

Investigative and extrapolative role of microRNAs' genetic expression in breast carcinoma.

MicroRNAs (miRs) are non-coding ribonucleic acids consisting of about 18-22 nucleotide bases. Expression of several miRs can be altered in breast carcinomas in comparison to healthy breast tissue, or between various subtypes of breast cancer. These are regulated as either oncogene or tumor suppressors, this shows that their expression is misrepresented in cancers. Some miRs are specifically associated with breast cancer and are affected by cancer-restricted signaling pathways e.g. downstream of estrogen receptor-α or HER2/neu. Connection of multiple miRs with breast cancer, and the fact that most of these post transcript structures may transform complex functional networks of mRNAs, identify them as potential investigative, extrapolative and predictive tumor markers, as well as possible targets for treatment. Investigative tools that are currently available are RNA-based molecular techniques. An additional advantage related to miRs in oncology is that they are remarkably stable and are notably detectable in serum and plasma. Literature search was performed by using database of PubMed, the keywords used were microRNA (52 searches) AND breast cancer (169 searches). PERN was used by database of Bahria University, this included literature and articles from international sources; 2 articles from Pakistan on this topic were consulted (one in international journal and one in a local journal). Of these, 49 articles were shortlisted which discussed relation of microRNA genetic expression in breast cancer. These articles were consulted for this review.

Diagnostic, prognostic and predictive value of MicroRNA-21 in breast cancer patients, their daughters and healthy individuals.

MicroRNA-21 (miR-21) located on 17q23.1 expressed in breast cancer has anti-apoptotic ability and causes tumor cell growth. It is also involved in functions such as signal transduction pathways effecting normal cell growth and differentiation. The primary objective of the study was to identify presence of miR-21 in the serum levels of stage III invasive ductal carcinoma patients and compare its expression with age matched healthy individuals and daughters of index cases. The secondary objective was to evaluate the significance of serum miR-21 gene expression with histologically proven estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) proteins. A total of 132 subjects were recruited: 50 (cases) of stage III invasive ductal carcinoma patients who had not undergone any chemotherapy or surgery were randomly picked with exclusion of females with other types of breast carcinoma. Age-matched, 50 healthy individuals (control A) were selected by purposive sampling after confirmation of no palpable lump/s in their breasts together with 32 daughters of index cases (control B). Serum tests were run on Real Time quantitative Reverse Transcription PCR, threshold cycle was determined and fold change calculated.Normality of continuous variables was assessed by Shapiro-Wilk's test, groups compared by student t-test, Mann-Whitney test and Fisher exact test, P-value ≤ 0.05 was considered significant. We observed that miR-21 was significantly higher in cases as compared to control A and B (P = 0.001) however control B showed significant gene expression as compared to control A (P = 0.001). The cases were also divided as positive or negative for ER, PR and HER2. High expression of miR-21 in females with stage III invasive ductal carcinoma had been calculated as compared to its age matched healthy subjects. It was observed that triple negative cases showed a greater expression of gene as compared to other groups (P = 0.001). Expression of miR-21 in daughters of the cases was significantly higher as compared to healthy controls but lesser than females with invasive intraductal carcinoma. This result strengthens the concept of inheritability of disease with prediction of miR-21 as a potentially strong diagnostic and prognostic biomarker of breast cancer.