Cindy Bandala

miR-485 Acts as a Tumor Suppressor by Inhibiting Cell Growth and Migration in Breast Carcinoma T47D Cells

MicroRNAs (miRNAs) are small, non-coding RNAs (18-25 nucleotides) that post-transcriptionally modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. In this context, the present study aimed to evaluate the in vitro effects of miR-485 mimics in breast carcinoma T47D cells. Forty-eight hours after T47D cells were transfected with miR-485 mimics, an MTT (3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide) assay was utilized to determine the effects on cell viability. Colony formation and cell migration assays were adopted to determine whether miR-485 affects the proliferation rates and cell migration of breast carcinoma T47D cells. Our results showed that ectopic expression of miR-485 resulted in a significant decrease in cell growth, cell colony formation, and cell migration. These findings suggest that miR- 485 might play an important role in breast cancer by suppressing cell proliferation and migration.

Human papillomavirus genotypes among females in Mexico: a study from the Mexican institute for social security.

BACKGROUND The aetiological relationship between human papillomavirus (HPV) infection and cervical cancer (CC) is widely accepted. Our goal was to determine the prevalence of HPV types in Mexican women attending at the Mexican Institute for Social Security from different areas of Mexico. MATERIALS AND METHODS DNAs from 2,956 cervical samples were subjected to HPV genotyping: 1,020 samples with normal cytology, 931 with low-grade squamous intraepithelial lesions (LGSIL), 481 with high grade HGSIL and 524 CC. RESULTS Overall HPV prevalence was 67.1%. A total of 40 HPV types were found; HPV16 was detected in 39.4% of the HPV-positive samples followed by HPV18 at 7.5%, HPV31 at 7.1%, HPV59 at 4.9%, and HPV58 at 3.2%. HPV16 presented the highest prevalence both in women with altered or normal cytology and HPV 18 presented a minor prevalence as reported worldwide. The prevalence ratio (PR) was calculated for the HPV types. The analysis of PR showed that HPV16 presents the highest association with CC, HPV 31, -33, -45, -52 and -58 also demonstrating a high association. CONCLUSIONS The most prevalent HPV types in cervical cancer samples were -16, -18, -31, but it is important to note that we obtained a minor prevalence of HPV18 as reported worldwide, and that HPV58 and -52 also were genotypes with an important prevalence in CC samples. Determination of HPV genotypes is very important in order to evaluate the impact of vaccine introduction and future cervical cancer prevention strategies.

Effect of Botulinum Toxin A on Proliferation and Apoptosis in the T47D Breast Cancer Cell Line

The present study was performed to assess the activity of the botulinum toxin A on breast cancer cells. The T47D cell line was exposed to diverse concentrations of the botulinum toxin A and cell viability and apoptosis were estimated using MTT and propidium iodine/annexin V methods, respectively. Botulinum toxin A exerted greater cytotoxic activity in T47D cells in comparison with MCF10A normal cells; this appeared to be via apoptotic processes caspase-3 and -7. In conclusion, botulinum toxin A induces caspase-3 and -7 dependent apoptotic processes in the T47D breast cancer cell line.

RNA Expression of Cytochrome P450 in Mexican Women with Breast Cancer

Involvement of cytochrome P450 genes (CYPs) in breast cancer (BCa) may differ between populations, with expression patterns affected by tumorigenesis. This may have an important role in the metabolism of anticancer drugs and in the progression of cancer. The aim of this study was to determine the mRNA expression patterns of four cytochrome P450 genes (CYP2W1, 3A5, 4F11 and 8A1) in Mexican women with breast cancer. Real- time PCR analyses were conducted on 32 sets of human breast tumors and adjacent non-tumor tissues, as well as 20 normal breast tissues. Expression levels were tested for association with clinical and pathological data of patients. We found higher gene expression of CYP2W1, CYP3A5, CYP4F11 in BCa than in adjacent tissues and only low in normal mammary glands in our Mexican population while CYP8A1 was only expressed in BCa and adjacent tissues. We found that Ki67 protein expression was associated with clinicopathological features as well as with CYP2W1, CYP4F11 and CYP8A1 but not with CYP3A5. The results indicated that breast cancer tissues may be better able to metabolize carcinogens and other xenobiotics to active species than normal or adjacent non-tumor tissues.

CYP2W1, CYP4F11 and CYP8A1 Polymorphisms and Interaction of CYP2W1 Genotypes with Risk Factors in Mexican Women with Breast Cancer

Breast cancer (BCa) is the leading type of cancer in Mexican women. Genetic factors, such as single nucleotide polymorphisms (SNP) of P450 system, have been reported in BCa. In this report, and for the first time in the literature, we analyzed the rs3735684 (7021 G>A), rs11553651 (15016 G>T) and rs56195291 (60020 C>G) polymorphisms in the CYP2W1, 4F11 and 8A1 genes in patients with BCa and in healthy Mexican women to identify a potential association between these polymorphisms and BCa risk. Patients and controls were used for polymorphism analysis using an allelic discrimination assay with TaqMan probes and confirmed by DNA sequencing. Links with clinic-pathological characteristics were also analyzed. Statistical analysis was performed using the standard χ2 or Fisher exact test statistic. No significant differences were observed in the distributions of CYP2W1 (OR 8.6, 95%CI 0.43-172.5 P>0.05; OR 2.0, 95%CI 0.76-5.4, P>0.05) and CYP4F11 (OR 0.3, 95%CI 0.01-8.4 P>0.05) genotypes between the patients and controls. Only the CYP8A1 CC genotype was detected in patients with BCa and the controls. All polymorphism frequencies were in Hardy-Weinberg Equilibrium (HWE) in the controls (P>0.05). We found a significant association between BCa risk and smoking, use of oral contraceptives or hormonal replacement therapy (HRT), obesity, hyperglycemia, chronic diseases, family history of cancer and menopausal status in the population studied (P<0.05). Tobacco, oral contraceptive or HRT, chronic diseases and obesity or overweight were strongly associated with almost eight, thirty-five, nine and five-fold increased risk for BCa. Tobaco, obesity and hyperglycemia significantly increased the risk of BCa in the patients carrying variant genotypes of CYP2W1 (P<0.05). These results indicate that the CYP2W1 rs3735684, CYP4F11 rs11553651 and CYP8A1 rs56195291 SNPs are not a key risk factor for BCa in Mexican women. This study did not detect an association between the CYP2W1, 4F11 and 8A1 genes polymorphisms and BCa risk in a Mexican population. However, some clinico-pathological risk factors interact with CYP2W1 genotypes and modifies susceptibility to BCa.

A non-invasive tool for detecting cervical cancer odor by trained scent dogs

BackgroundCervical Cancer (CC) has become a public health concern of alarming proportions in many developing countries such as Mexico, particularly in low income sectors and marginalized regions. As such, an early detection is a key medical factor in improving not only their population’s quality of life but also its life expectancy. Interestingly, there has been an increase in the number of reports describing successful attempts at detecting cancer cells in human tissues or fluids using trained (sniffer) dogs. The great odor detection threshold exhibited by dogs is not unheard of. However, this represented a potential opportunity to develop an affordable, accessible, and non-invasive method for detection of CC.MethodsUsing clicker training, a male beagle was trained to recognize CC odor. During training, fresh CC biopsies were used as a reference point. Other samples used included cervical smears on glass slides and medical surgical bandages used as intimate sanitary pads by CC patients. A double-blind procedure was exercised when testing the beagle’s ability to discriminate CC from control samples.ResultsThe beagle was proven able to detect CC-specific volatile organic compounds (VOC) contained in both fresh cervical smear samples and adsorbent material samples. Beagle’s success rate at detecting and discriminating CC and non-CC odors, as indicated by specificity and sensitivity values recorded during the experiment, stood at an overall high (>90%). CC-related VOC in adsorbent materials were detectable after only eight hours of use by CC patients.ConclusionPresent data suggests different applications for VOC from the uterine cervix to be used in the detection and diagnosis of CC. Furthermore, data supports the use of trained dogs as a viable, affordable, non-invasive and, therefore, highly relevant alternative method for detection of CC lesions. Additional benefits of this method include its quick turnaround time and ease of use while remaining highly accurate and robust.

Synaptic Vesicle Protein 2 (SV2) Isoforms

New molecular markers of cancer had emerged with novel applications in cancer prevention and therapeutics, including for breast cancer of unknown causes, which has a high impact on the health of women worldwide. The purpose of this research was to determine protein and mRNA expression of synaptic vesicle 2 (SV2) isoforms A, B and C in breast cancer cell lines. Cultured cell lines MDA-MB-231, SKBR3, T47D were lysed and their protein and mRNA expression analyzed by real-time PCR and western blot technique, respectively. SV2A, B proteins were identified in non-tumor (MCF-10A) and tumor cell lines (MDA-MB-231 and T47D) while SV2C only was found in the T47D cell line. Furthermore, the genomic expression was consistent with protein expression for a such cell line, but in MDA-MB-231 there was no SV2B genomic expression, and the SV2C mRNA and protein were not found in the non tumoral cell line. These findings suggest a possible cellular transdifferentiation to neural character in breast cancer, of possible relevance to cancer development, and point to possible use of SV2 as molecular marker and a vehicle for cancer treatment with botulinum toxin.

Emerging Drugs for the Treatment of Breast Cancer Brain Metastasis: A Review of Patent Literature

BACKGROUND Despite dramatic advances in cancer treatment that lead to long-term survival, there is an increasing number of patients presenting with clinical manifestations of cerebral metastasis in breast cancer, for whom only palliative treatment options exist. OBJECTIVE The present review based on researches aims to provide identification of recent patens of breast cancer brain metastasis that may have application in improving cancer treatment. METHODS Recent patents regarding the breast cancer brain metastasis were obtained from USPTO patent databases, Esp@cenet, Patentscope and Patent Inspiration®. RESULTS A total of 55 patent documents and 35 drug targets were recovered. Of these, a total of 45 patents and 10 patents were biotech drugs and chemical drugs, respectively. Among the target drugs analyzed were neurotrophin-3, protocadherin 7, CXCR4, PTEN, GABA receptor 3, L1CAM, PI3K-Akt / mTOR, VEGFR2, Claudin-5, Occludin, and NKG2A, among others. CONCLUSION In this study, we found 35 drug targets for metastasis to the brain in breast cancer, with 60% of them including only one patent, which establishes that this area of research is very recent, and that these targets have recently been linked to metastasis to the brain. On the other hand, 19 drug targets, among them VEGF, VEGFR2, CXCL12, and CXCR4, have been addressed for the first time until 6 years ago, confirming that the development of drugs for brain metastasis in breast cancer is an incipient area, but with interesting potential. Interestingly, the stage of inside the brain, was the stage with the lowest amount of drug targets, which places it as a priority for research and drug development.

Neural Transdifferentiation: MAPTau Gene Expression in Breast Cancer Cells.

BACKGROUND In tumor cells, aberrant differentiation programs have been described. Several neuronal proteins have been found associated with morphological neuronal-glial changes in breast cancer (BCa). These neuronal proteins have been related to mechanisms that are involved in carcinogenesis; however, this regulation is not well understood. Microtubule-associated protein-tau (MAP-Tau) has been describing in BCa but not its variants. This finding could partly explain the neuronal-glial morphology of BCa cells. Our aim was to determine mRNA expression of MAP-tau variants 2, 4 and 6 in breast cancer cell lines. MATERIALS AND METHODS Cultured cell lines MCF-10A, MDA-MB-231, SKBR3 and T47D were observed under phase-contrast microscopy for neural morphology and analyzed for gene expression of MAP-Tau transcript variants 2, 4 and 6 by real-time PCR. RESULTS Regarding morphology like neural/glial cells, T47D line shown more cells with these features than MDA-MB-231 and SKBR. In another hand, we found much greater mRNA expression of MAP-Tau transcript variants 2, and to a lesser extent 4 and 6, in T47D cells than the other lines. In conclusion, regulation of MAP- Tau could bring about changes in cytoskeleton, cell morphology and motility; these findings cast further light on neuronal transdifferentiation in BCa.