Lipofilling after breast conserving surgery: A comprehensive literature review investigating its oncologic safety

Lipofilling has regenerative properties used to improve deformities after breast conserving surgery. Our hypothesis is that there is inadequate data to ensure that lipofilling does not increase locoregional cancer recurrence after breast conserving surgery. A PRISMA comprehensive literature review was conducted of articles published prior to October 2019 investigating recurrence in patients who underwent lipofilling after breast conserving surgery. All forms of breast conserving surgery, fat grafting, and injection intervals were included. Patients undergoing mastectomy were excluded. Requirements to define lipofilling as safe included (I) a defined interval between resection and lipofilling; (II) a minimum follow-up period of 6 years from tumor resection; (III) a minimum follow-up period of 3 years from lipofilling; (IV) presence of a control group; (V) controls matched for ER/PR/Her-2; (VI) a sub-group analysis focusing on ER/PR/Her-2; (VII) adequate powering. Nineteen studies met inclusion criteria. The range in time from breast conserving surgery to fat injection was 0-76 months. The average time to follow-up after lipofilling was 23 days-60 months. Two studies had a sufficient follow-up time from both primary resection and from lipofilling. Seventeen of the nineteen studies specified the interval between resection and lipofilling, but there is currently no consensus regarding how soon lipofilling can be performed following BCS. Eight studies performed a subgroup analysis in cases of recurrence and found recurrence after lipofilling was associated with number of positive axillary nodes, intraepithelial neoplasia, high grade histology, Luminal A subtype, age \u3c50, Ki-67 expression, and lipofilling within 3 months of primary resection. Of the eleven studies that included a comparison group, one matched patient for Her-2 and there was a statistically significant difference in Her-2 positive cancers in the study arms of two articles. Several studies deemed lipofilling safe, two showed association of lipofilling and local recurrence, and most studies concluded that further research was needed. Insufficient and contradictory data exists to demonstrate the safety of lipofilling after breast conserving surgery. A multicentered, well designed study is needed to verify the safety of this practice

Renoprotective effect of tectorigenin glycosides isolated from Iris spuria L. (Zeal) against hyperoxaluria and hyperglycemia in NRK-49Fcells

Oxidative stress has been identified as an underlying factor in the development of insulin resistance, β-cell dysfunction, impaired glucose tolerance and type 2 diabetes mellitus and it also play major role in kidney stone formation. The present study is aimed to elucidate the in vitro nephroprotective activity of two isoflavonoid glycosides, tectorigenin 7-O-β-D-glucosyl-(1→6)-β-D-glucoside (1) and tectorigenin 7-O-β-D-glucosyl-4'-O-β-D-glucoside (2) isolated from the n-BuOH fraction of Iris spuria L. (Zeal) rhizome MeOH extract against oxalate and high glucose-induced oxidative stress in NRK-49F cells. The results revealed that compounds 1 and 2 significantly increased the antioxidant enzyme activities and decreased MDA levels in both oxalate and high glucose stress. Treatment with these phytochemicals effectively down-regulated expression of crystal modulator genes and pro-fibrotic genes in oxalate and high glucose-mediated stress respectively. This study indicates cytoprotective, antioxidant, anti-urolithic and anti-diabetic effects of compounds 1 and 2 against oxalate and high glucose stress

Selaginella bryopteris

The effective long-term cryopreservation of human mesenchymal stem cells (MSCs) is an essential prerequisite step and represents a critical approach for their sustained supply in basic research, regenerative medicine, and tissue engineering applications. Therefore, attempts have been made in the present investigation to formulate a freezing solution consisting of a combination of Selaginella bryopteris water-soluble extract with and without dimethyl sulfoxide (Me2SO) for the efficient long-term storage of human umbilical cord blood- (hUCB-) derived MSCs. The cryopreservation experiment using the formulated freezing solution was further performed with hUCB MSCs in a controlled rate freezer. A significant increase in postthaw cell viability and cell attachment of MSCs was achieved with freezing medium containing Selaginella bryopteris water extract along with 10% Me2SO as compared to the freezing medium containing Me2SO (10% v/v) alone. Furthermore, the decreasing apoptotic events and reactive oxygen species production along with increasing expression of heat shock proteins also confirmed the beneficial effect of Selaginella bryopteris water extract. The beneficial effect of Selaginella bryopteris water extract was validated by its ability to render postpreservation high cell viability. In conclusion, the formulated freezing solution has been demonstrated to be effective for the standardization of cryopreservation protocol for hMSCs

The Atomic-Level Structure of Cementitious Calcium Silicate Hydrate

Efforts to tune the bulk physical properties of concrete are hindered by a lack of knowledge related to the atomic-level structure and growth of calcium silicate hydrate phases, which form about 50-60% by volume of cement paste. Here we describe the first synthesis of compositionally uniform calcium silicate hydrate phases with Ca:Si ratios tunable between 1.0 and 2.0. The calcium silicate hydrate synthesized here does not contain a secondary Ca(OH)(2) phase, even in samples with Ca:Si ratios above 1.6, which is unprecedented for synthetic calcium silicate hydrate systems. We then solve the atomic-level three-dimensional structure of these materials using dynamic nuclear polarization enhanced H-1 and Si-29 nuclear magnetic resonance experiments in combination with atomistic simulations and density functional theory chemical shift calculations. We discover that bridging interlayer calcium ions are the defining structural characteristic of single-phase cementitious calcium silicate hydrate, inducing the strong hydrogen bonding that is responsible for stabilizing the structure at high Ca:Si ratios

Nonparametric Simulation of Signal Transduction Networks with Semi-Synchronized Update

Simulating signal transduction in cellular signaling networks provides predictions of network dynamics by quantifying the changes in concentration and activity-level of the individual proteins. Since numerical values of kinetic parameters might be difficult to obtain, it is imperative to develop non-parametric approaches that combine the connectivity of a network with the response of individual proteins to signals which travel through the network. The activity levels of signaling proteins computed through existing non-parametric modeling tools do not show significant correlations with the observed values in experimental results. In this work we developed a non-parametric computational framework to describe the profile of the evolving process and the time course of the proportion of active form of molecules in the signal transduction networks. The model is also capable of incorporating perturbations. The model was validated on four signaling networks showing that it can effectively uncover the activity levels and trends of response during signal transduction process

Functional genomics reveals serine synthesis is essential in PHGDH-amplified breast cancer

Cancer cells adapt their metabolic processes to drive macromolecular biosynthesis for rapid cell growth and proliferation[superscript 1, 2]. RNA interference (RNAi)-based loss-of-function screening has proven powerful for the identification of new and interesting cancer targets, and recent studies have used this technology in vivo to identify novel tumour suppressor genes[superscript 3]. Here we developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, we screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, phosphoglycerate dehydrogenase (PHGDH) is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of oestrogen receptor (ER)-negative breast cancers. PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, causes a strong decrease in cell proliferation and a reduction in serine synthesis. We find that PHGDH suppression does not affect intracellular serine levels, but causes a drop in the levels of α-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. These results reveal that certain breast cancers are dependent upon increased serine pathway flux caused by PHGDH overexpression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer targets.Susan G. Komen Breast Cancer Foundation (Fellowship)Life Sciences Research Foundation (Fellowship)W. M. Keck FoundationDavid H. Koch Cancer Research FundAlexander and Margaret Stewart TrustNational Institutes of Health (U.S.) (Grant CA103866

Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium

Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87 × 10 -12 for SNP rs634990 in Caucasians, and 9.65 × 10 -4 for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 × 10 -23 for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, P < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, P < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81 × 10 -2 for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide. © The Author(s) 2012