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Roberts, S. A. et al. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat. Genet. 45, 970–976 (2013). Atiyeh, B. and Chahine, F. (2018) Correction to: Metrics of the Aesthetically Perfect Breast. Aesthetic Plastic Surgery, 42, 1718. Hanzelmann, S., Castelo, R. & Guinney, J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinforma. 14, 7 (2013). Introduce anal play with a Novice Plug, the perfect anal vibrator for newbies with a slim design, smooth silicone, and a remote control from up to 30 feet away." — A.W. The PI3K–AKT–mTOR signaling pathway is one of the most frequently de-regulated pathways in human cancers 41, with repercussions in key cellular processes, such as metabolism, independent cell proliferation, cell invasion, endocrine receptor deregulation and resistance to therapy 45, and consequently supporting cancer cell programs. The pathway can be aberrantly activated through multiple mechanisms, including diverse AKT mutations 46. E17K mutation activates AKT1 by recruiting it to the membrane through a PI3K-independent mechanism, resulting in the activation of PI3K/AKT/mTOR signaling pathway 47. Thus, AKT1 mutations have emerged as an attractive druggable target and there is promising clinical data in ER + ductal BC patients harboring AKT1 E17K mutation treated with the pan-AKT targeted inhibitors AZD5363, MK-220 46, 48 and ipatasertib, another ATP-competitive AKT inhibitor 49.
The mean values for breast volume divided by age group were: 3rd decade of life (R 320.1 cm 3, L 322.9 cm 3), Fourth decade of life (R 347.3 cm 3, L 350.2 cm 3), Fifth decade of life (R 460 cm 3, L 474.5 cm 3), >6 th decade of life (R 467 cm 3, L 477.5 cm 3) ( Figure 4). We found that there is a tendency for the left breast to be larger, regardless of the age group. Nevertheless, this difference is not statistically significant (p < 0.417951) ( Table 4). Comparing the values found in this study to the aesthetically ideal breast described by Malluci, we observe that our measurements fall far from what is considered ideal breast proportion [2] [7] ( Table 6). As mentioned previously this correlates with our findings in everyday practice, where we have detected an important prevalence of tuberous breasts. In recent times, style icon, beauty mogul, and new mom Rihanna is lensed with her curves in focus for the September 2020 cover story. Other famous faces include Goop mogul Gwyneth Paltrow, the always-stunning Jennifer Aniston, as well as burgeoning supermodel, runway fixture, and J6 brand muse Anok Yai—who was featured in a sexy suiting story months earlier. Hailey Bieber, Demi Lovato, and everyone's favorite modeling duo Bella and Gigi Hadid are also on the list.Of note, the Glu17Lys (E17K) mutation within the PHb domain of AKT1, was present in 10 out of the 11 tumors (8%) harboring AKT1 mutations (Fig. 4a, b and Supplementary Data 5) and are predominantly HR + tumors (Fig. 4c). We found no evidence for AKT1 E17K significant mutation (MutSigCV, Q< 0.1 and frequency >5%) in 4464 samples of non-Hispanic ancestry (Supplementary Fig. 7a–c), except for a group of young Korean patients (ICGC, breast cancer - very young women, BRCA-KR) where 8% of cases ( N = 4/50) were mutated. E17K mutation results in a pathogenic activating mutation according to OncoKb, which in turn promotes an active PI3K/AKT/mTOR pathway signaling (Fig. 4d and Supplementary Fig. 7d). As a member of the PI3K/AKT/mTOR axis, only one AKT1 E17k mutant sample (10%) is co-mutated in PIK3CA, thus the altered activation of this oncogenic signaling generally occur by any one of these means in an exclusively manner. Additionally, 40% of AKT1 E17k mutant patients had no additional driver cancer mutations. While 60% had further alterations, other than AKT1 mutation, which likely contribute to cancer development (e.g., truncating mutation in tumor suppressor or gain of oncogenic mutations) (Fig. 4d).
Goldhirsch, A. et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann. Oncol. 24, 2206–2223 (2013).This study was reviewed and approved by the HCSAE’s Research and Ethics committee. All the measurements were taken from volunteering women from July to October 2021. The sample size was based on previous similar studies in another population, using simple random sampling. Breast Anthropometric measurements were performed in a total of 100 patients. 22 patients were excluded because they did not fulfill previously mentioned criteria. A total of 78 female Mexican volunteers aged between 20 to 60 years old were considered for this study. Another clip shows how her bosom makes it difficult for Billie — who goes by @billiebopbillie online — to comfortably fit into a dress. c protein visualization for AKT mutation was performed with RCSB PDB (rcsb.org) 77 for AKT E17K mutation (2UZS) with the NGL Viewer, and RCSB PDB 78. Mutational signatures To standardize measurements, first from a front view a horizontal line at the level of the nipples is drawn (Horizontal nipple plane), then a vertical line is drawn from the nipple to the inframammary fold (Lower breast pole length). From a lateral view a horizontal line is drawn at the breaking point where the breast starts from the chest wall (superior breast limit). The upper breast pole is described as the area between the superior breast limit and the horizontal nipple plane. The lower breast pole is described as the area between the nipple and the Inframammary Fold (IMF). The proportion of each breast pole was established by diving the length of each pole by the sum of the vertical distance, over the breast, between the superior limit and the inframammary fold at the level of the nipple, and then multiplied by 100 (LBPL/(LBPL + UBPL) * 100).
Moreno-Estrada, A. et al. Human genetics. The genetics of Mexico recapitulates Native American substructure and affects biomedical traits. Science 344, 1280–1285 (2014). Pereira, B. et al. The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Nat. Commun. 7, 11479 (2016).Lefebvre C, et al. Mutational Profile of Metastatic Breast Cancers: A Retrospective Analysis. PLoS Med 13, e1002201 (2016). Hannah also pointed out she gets “serious underboob sweat” but said she would be rolling on deodorant under her breasts each day. Whole-exome was captured through Agilent SureSelect ExomePlus bait system (Agilent Technologies, USA) and biotinylated RNA baits 67 process. ~155 Mb baits were target including the standard exome, plus intronic and promoter sequences for known cancer genes, relevant targets identified by cancer genomic studies, TCGA and the Cancer Cell Line Encyclopedia. Exome libraries were sequenced on Illumina GAII or HiSeq 2000 (Illumina, USA) sequencers with 76 base-paired-end reads achieving a mean of 141x. Alignment was performed with the Burrows–Wheeler Alignment tool 68 and standard Picard pipeline to the human genome assembly hg19/GRCh37. Somatic mutation analysis
Prat, A. et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 12, R68 (2010). Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754–1760 (2009). Kim, S. B. et al. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 18, 1360–1372 (2017). Genomics Laboratory, Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México-Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, MéxicoMeasurements were taken in healthy patients with absence of any deformity, during the follicular phase of the menstrual cycle. The inclusion criteria are being Mexican, good health and normal physical development. Excluding criteria are previously diagnosed benign or malignant breast pathology, previous breast surgery, taking any type of hormone treatment, suffering any endocrine illness, pregnancy, lactation or presenting any thorax deformity. I.S-G., R.R-V., and S.L.R.-C. contributed equally to this work. S.L.R.-C. and A.H.-M. conceived and designed the study. R.R.-V., S.L.R.-C., and L.A.-R. collected tumoral specimens (Fresh-frozen and formalin-fixed paraffin-embedded tumor tissue). I.S.-G., R.R.-V., S.L.R.-C., and A.H.-M. designed the pipeline-analysis. R.R.-V., L.A.-R., and L.U.F. performed nucleic acid extraction and sample preparation for microarray analysis. I.S.-G. and S.L.R.-C. performed all the genomic analysis. I.S.-G. and S.L.R.-C. wrote the paper. R.R.-V., A.H.-M. and L.U.F. drafted, edit, discuss, and finalized the paper. I.S.-G., S.L.R.-C. and J.C.F.-L. provided bioinformatics support. V.B.-P., F.V.C., A.T.-T., C.D.-R. procured patient tumoral specimens, assisted the pathological assessment, and immunochemistry evaluation, and provided clinical features of analyzed samples. R.R.-V. performed immunohistochemical evaluation for triple-negative tumors (extended markers). R.R.-V. and L.A.-R. managed the clinical data bases. J.C.F.-L. performed ancestry analysis of HM tumors. All authors reviewed and approved the final manuscript. Corresponding authors For the statistical analysis the latest version of SPSS software was used. We performed a Student-T test for data comparison and for data correlation, the Pearson correlation coefficient was obtained. All the results are represented in mean ± SD. Detected mutations were annotated and classified as driver and passenger somatic mutations using the method implemented in OncodriveMUT algorithm 76 and the Cancer Genome Interpreter ( https://www.cancergenomeinterpreter.org/home) framework, which allows to identify the most likely driver mutations of a tumor. The oncogenic classification: known and predicted mutation (in any neoplasia), were considered as driver alteration and taken into account for analysis. Structural 3D view of AKT1 mutations
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