Carbon nanomaterials sensitize prostate cancer cells to docetaxel and mitomycin C via induction of apoptosis and inhibition of proliferation

We have previously shown that carbon nanofibers (CNFs) and carbon nanotubes (CNTs) can sensitize prostate cancer (PCa) cells to platinum-based chemotherapeutics. In order to further verify this concept and to avoid a bias, the present study investigates the chemosensitizing potential of CNFs and CNTs to the conventional chemotherapeutics docetaxel (DTX) and mitomycin C (MMC), which have different molecular structures and mechanisms of action than platinum-based chemotherapeutics. DU-145 PCa cells were treated with DTX and MMC alone or in combination with the carbon nanomaterials. The impact of the monotreatments and the combinatory treatments on cellular function was then systematically analyzed by using different experimental approaches (viability, short-term and long-term proliferation, cell death rate). DTX and MMC alone reduced the viability of PCa cells to 94% and 68%, respectively, whereas a combined treatment with CNFs led to less than 30% remaining viable cells. Up to 17- and 7-fold higher DTX and MMC concentrations were needed in order to evoke a similar inhibition of viability as mediated by the combinatory treatments. In contrast, the dose of platinum-based chemotherapeutics could only be reduced by up to 3-fold by combination with carbon nanomaterials. Furthermore, combinatory treatments with CNFs led mostly to an additive inhibition of short- and long-term proliferation compared to the individual treatments. Also, higher cell death rates were observed in combinatory treatments than in monotreatments, e.g., a combination of MMC and CNFs more than doubled the cell death rate mediated by apoptosis. Combinations with CNTs showed a similar, but less pronounced impact on cellular functions. In summary, carbon nanomaterials in combination with DTX and MMC evoked additive to partly synergistic anti-tumor effects. CNFs and CNTs possess the ability to sensitize cancer cells to a wide range of structurally diverse chemotherapeutics and thus represent an interesting option for the development of multimodal cancer therapies. Co-administration of chemotherapeutics with carbon nanomaterials could result in a reduction of the chemotherapeutic dosage and thus limit systemic side effects

Carbon nanomaterials sensitize prostate cancer cells to docetaxel and mitomycin C via induction of apoptosis and inhibition of proliferation

We have previously shown that carbon nanofibers (CNFs) and carbon nanotubes (CNTs) can sensitize prostate cancer (PCa) cells to platinum-based chemotherapeutics. In order to further verify this concept and to avoid a bias, the present study investigates the chemosensitizing potential of CNFs and CNTs to the conventional chemotherapeutics docetaxel (DTX) and mitomycin C (MMC), which have different molecular structures and mechanisms of action than platinum-based chemotherapeutics. DU-145 PCa cells were treated with DTX and MMC alone or in combination with the carbon nanomaterials. The impact of the monotreatments and the combinatory treatments on cellular function was then systematically analyzed by using different experimental approaches (viability, short-term and long-term proliferation, cell death rate). DTX and MMC alone reduced the viability of PCa cells to 94% and 68%, respectively, whereas a combined treatment with CNFs led to less than 30% remaining viable cells. Up to 17- and 7-fold higher DTX and MMC concentrations were needed in order to evoke a similar inhibition of viability as mediated by the combinatory treatments. In contrast, the dose of platinum-based chemotherapeutics could only be reduced by up to 3-fold by combination with carbon nanomaterials. Furthermore, combinatory treatments with CNFs led mostly to an additive inhibition of short- and long-term proliferation compared to the individual treatments. Also, higher cell death rates were observed in combinatory treatments than in monotreatments, e.g., a combination of MMC and CNFs more than doubled the cell death rate mediated by apoptosis. Combinations with CNTs showed a similar, but less pronounced impact on cellular functions. In summary, carbon nanomaterials in combination with DTX and MMC evoked additive to partly synergistic anti-tumor effects. CNFs and CNTs possess the ability to sensitize cancer cells to a wide range of structurally diverse chemotherapeutics and thus represent an interesting option for the development of multimodal cancer therapies. Co-administration of chemotherapeutics with carbon nanomaterials could result in a reduction of the chemotherapeutic dosage and thus limit systemic side effects

O onome što predvidljivo ne obuhvaća. Zamišljanje budućnosti u Srbiji

In order to be able to contextualize and understand social worlds, anthropologists pay close attention. We observe how individuals and communities relate to each other and to their ideas. We study the intimate and subjective, as well as the large-scale cosmologies by which people make themselves and the world. Our participatory methods and reflective analysis document the complex, intricate, patterned, and also random aspects of people’s reasoning and actions. These activities, on anthropology’s part, supposedly offer not only critical descriptions of the present (on its historical trajectories), but possible intimations of a society’s future. Anthropological analysis, in other words, not only describes but also anticipates. This position paper focuses on the notions of anticipation, predictability, and possibility in anthropology. It asks what methodological and theoretical assumptions are built into our ways of making predictions about our field sites. It invites the reader to consider the effects certain anticipatory practices have for the people and phenomena we study as well as for the discipline. Centrally, the paper proposes different ways of attending to visions that anticipate the future. By reflecting on my ethnographic and analytical journeys in Serbia, I attempt to explain why I currently make so much of questions of predictability and possibility in both the field and the discipline. My desire is to open up a discussion on the value of cultivating attention to what seems to emerge on the side of predictable.Da bi mogli kontekstualizirati i razumjeti društvene svjetove, antropolozi pomno promatraju. Promatramo kako se pojedinci i zajednice odnose jedni prema drugima i prema svojim idejama. Proučavamo intimno i subjektivno, kao i kozmologije velikih razmjera pomoću kojih ljudi ostvaruju sebe i svijet. Naše participativne metode i reflektivne analize dokumentiraju kompleksne, zamršene, uobličene, ali i nasumične aspekte ljudskog razmišljanja i djelovanja. U antropologiji takve aktivnosti nude ne samo kritičke opise sadašnjosti (na njihovim povijesnim putanjama) već i moguće nagovještaje budućnosti nekog društva. Drugim riječima, antropološka analiza ne samo da opisuje nego i predviđa. Ovaj rad razmatra ideje predviđanja, procjenjivanja i mogućnosti u antropologiji. Propituje koje su metodološke i teorijske pretpostavke ugrađene u antropološke načine predviđanja, odnosno opisa i posljedične analize naših terena. Istražuje kakve učinke imaju prakse anticipacije, kako na ljude i fenomene koje proučavamo tako i na disciplinu. U središtu rada su prijedlozi različitih načina pristupanja vizijama koje predviđaju budućnost. Reflektirajući o svojim etnografskim i analitičkim putovanjima po Srbiji, nastojim pojasniti zašto sam trenutačno posvećena pitanjima predvidljivosti i mogućnosti i na terenu i u disciplini. Želja mi je potaknuti raspravu o vrijednosti pažnje usmjerene na ono što predvidljivošću ne možemo obuhvatiti

Germline SDHx variants modify breast and thyroid cancer risks in Cowden and Cowden-like syndrome via FAD/NAD-dependant destabilization of p53

Cowden syndrome (CS), a Mendelian autosomal-dominant disorder, predisposes to breast, thyroid and other cancers. Germline mutations in phosphatase and tensin homolog (PTEN) have been recently reported in 23% of a large series of classic CS. Here, we validated our small (n = 10) pilot study in a large patient series that germline variations in succinate dehydrogenase genes (SDHx) occur in 8% (49/608) of PTEN mutation-negative CS and CS-like (CSL) individuals (SDHvar+). None of these SDHx variants was found in 700 population controls (P < 0.0001). We then found that SDHx variants also occur in 6% (26/444) of PTEN mutation-positive (PTENmut+) CS/CSL individuals (PTENmut+/SDHvar+). Of 22 PTENmut+/SDHvar+ females, 17 had breast cancers compared with 34/105 PTENmut+ (P < 0.001) or 27/47 SDHvar+ patients (P = 0.06). Notably, individuals with SDHvar+ alone had the highest thyroid cancer prevalence (24/47) compared with PTENmut+ patients (27/105, P = 0.002) or PTENmut+/SDHvar+ carriers (6/22, P = 0.038). Patient-derived SDHvar+ lymphoblastoid cells had elevated cellular reactive oxygen species, highest in PTENmut+/SDHvar+ cells, correlating with apoptosis resistance. SDHvar+ cells showed stabilized and hyperactivated hypoxia inducible factor (HIF)1α signaling. Most interestingly, we also observed the loss of steady-state p53 in the majority of SDHvar+ cells. This loss of p53 was regulated by MDM2-independent NADH quinone oxidoreductase 1-mediated protein degradation, likely due to the imbalance of flavin adenine dinucleotide/nicotinamide adenine dinucleotide in SDHvar+ cells. Our data suggest the potential regulation of HIF1α, p53 and PTEN signaling by mitochondrial metabolism in CS/CSL tumorigenesis. Together, our findings suggest the importance of considering SDHx as candidate predisposing and modifier genes for CS/CSL-related malignancy risks, and a mechanism which suggests ways of therapeutic reversal or prevention

Neuroanatomy of fragile X syndrome is associated with aberrant behavior and the fragile X mental retardation protein (FMRP)

To determine how neuroanatomic variation in children and adolescents with fragile X syndrome is linked to reduced levels of the fragile X mental retardation-1 protein and to aberrant cognition and behavior

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Carbon nanomaterials sensitize prostate cancer cells to docetaxel and mitomycin C via induction of apoptosis and inhibition of proliferation

We have previously shown that carbon nanofibers (CNFs) and carbon nanotubes (CNTs) can sensitize prostate cancer (PCa) cells to platinum-based chemotherapeutics. In order to further verify this concept and to avoid a bias, the present study investigates the chemosensitizing potential of CNFs and CNTs to the conventional chemotherapeutics docetaxel (DTX) and mitomycin C (MMC), which have different molecular structures and mechanisms of action than platinum-based chemotherapeutics. DU-145 PCa cells were treated with DTX and MMC alone or in combination with the carbon nanomaterials. The impact of the monotreatments and the combinatory treatments on cellular function was then systematically analyzed by using different experimental approaches (viability, short-term and long-term proliferation, cell death rate). DTX and MMC alone reduced the viability of PCa cells to 94% and 68%, respectively, whereas a combined treatment with CNFs led to less than 30% remaining viable cells. Up to 17- and 7-fold higher DTX and MMC concentrations were needed in order to evoke a similar inhibition of viability as mediated by the combinatory treatments. In contrast, the dose of platinum-based chemotherapeutics could only be reduced by up to 3-fold by combination with carbon nanomaterials. Furthermore, combinatory treatments with CNFs led mostly to an additive inhibition of short- and long-term proliferation compared to the individual treatments. Also, higher cell death rates were observed in combinatory treatments than in monotreatments, e.g., a combination of MMC and CNFs more than doubled the cell death rate mediated by apoptosis. Combinations with CNTs showed a similar, but less pronounced impact on cellular functions. In summary, carbon nanomaterials in combination with DTX and MMC evoked additive to partly synergistic anti-tumor effects. CNFs and CNTs possess the ability to sensitize cancer cells to a wide range of structurally diverse chemotherapeutics and thus represent an interesting option for the development of multimodal cancer therapies. Co-administration of chemotherapeutics with carbon nanomaterials could result in a reduction of the chemotherapeutic dosage and thus limit systemic side effects

Preoperative MRI and LDH in women undergoing intra-abdominal surgery for fibroids: Effect on surgical route.

IntroductionOur institution implemented a preoperative protocol to identify high-risk cases for which power morcellation should be avoided.Material and methodsIn this retrospective cohort study, an institutional protocol requiring preoperative Magnetic Resonance Imaging with diffusion-weighted imaging and serum Lactate Dehydrogenase levels was implemented. Chart review was performed including all women who underwent intra-abdominal surgery for symptomatic fibroids from 4/23/2013 to 4/23/2015.ResultsA total of 1,085 women were included, 479 before and 606 after implementation of the Magnetic Resonance Imaging / Lactate Dehydrogenase protocol. The pre-protocol group had more post-menopausal women (4% vs. 2%, p = 0.022) and women using tamoxifen (2% vs. 0%, p = 0.022) than those in the post-protocol group, but baseline patient characteristics were otherwise similar between groups. Incidence of malignant pathological diagnoses did not change significantly over the time period in relation to protocol implementation. The rate of open surgery for both hysterectomy and myomectomy remained the same in the year preceding and the year following initiation of the protocol (open hysterectomy rate was 19% vs. 16% in pre- and post-protocol groups, respectively, P = 0.463, and open myomectomy rate was 10% vs. 9% rates in pre- and post-protocol groups, respectively, P = 0.776). There was a significant decrease in the use of power morcellation (66% in pre- and 50% in post-protocol cohorts, pConclusionsRates of MIS procedures were decreased for women with abnormal preoperative Magnetic Resonance Imaging results. False positive results appear to be one of the main drivers for the use of an open surgical route