Radiofrequency ablation (RFA) is considered a curative treatment option for hepatocellular carcinoma (HCC). Growing data have demonstrated that cryoablation represents a safe and effective ...alternative therapy for HCC, but no randomized controlled trial (RCT) has been reported to compare cryoablation with RFA in HCC treatment. The present study was a multicenter RCT aimed to compare the outcomes of percutaneous cryoablation with RFA for the treatment of HCC. In all, 360 patients with Child‐Pugh class A or B cirrhosis and one or two HCC lesions ≤ 4 cm, treatment‐naïve, without metastasis were randomly assigned to cryoablation (n = 180) or RFA (n = 180). The primary endpoints were local tumor progression at 3 years after treatment and safety. Local tumor progression rates at 1, 2, and 3 years were 3%, 7%, and 7% for cryoablation and 9%, 11%, and 11% for RFA, respectively (P = 0.043). For lesions >3 cm in diameter, the local tumor progression rate was significantly lower in the cryoablation group versus the RFA group (7.7% versus 18.2%, P = 0.041). The 1‐, 3‐, and 5‐year overall survival rates were 97%, 67%, and 40% for cryoablation and 97%, 66%, and 38% for RFA, respectively (P = 0.747). The 1‐, 3‐, and 5‐year tumor‐free survival rates were 89%, 54%, and 35% in the cryoablation group and 84%, 50%, and 34% in the RFA group, respectively (P = 0.628). Multivariate analyses demonstrated that Child‐Pugh class B and distant intrahepatic recurrence were significant negative predictors for overall survival. Major complications occurred in seven patients (3.9%) following cryoablation and in six patients (3.3%) following RFA (P = 0.776). Conclusion: Cryoablation resulted in a significantly lower local tumor progression than RFA, although both cryoablation and RFA were equally safe and effective, with similar 5‐year survival rates. (Hepatology 2015;61:1579–1590)
Ecological preferences and life history strategies have enormous impacts on the evolution and phenotypic diversity of salamanders, but the yet established reliable ecological indicators from bony ...skeletons hinder investigations into the paleobiology of early salamanders. Here, we statistically demonstrate by using time-calibrated cladograms and geometric morphometric analysis on 71 specimens in 36 species, that both the shape of the palate and many non-shape covariates particularly associated with vomerine teeth are ecologically informative in early stem- and basal crown-group salamanders. Disparity patterns within the morphospace of the palate in ecological preferences, life history strategies, and taxonomic affiliations were analyzed in detail, and evolutionary rates and ancestral states of the palate were reconstructed. Our results show that the palate is heavily impacted by convergence constrained by feeding mechanisms and also exhibits clear stepwise evolutionary patterns with alternative phenotypic configurations to cope with similar functional demand. Salamanders are diversified ecologically before the Middle Jurassic and achieved all their present ecological preferences in the Early Cretaceous. Our results reveal that the last common ancestor of all salamanders share with other modern amphibians a unified biphasic ecological preference, and metamorphosis is significant in the expansion of ecomorphospace of the palate in early salamanders.
A new salamandroid salamander, Qinglongtriton gangouensis (gen. et sp. nov.), is named and described based on 46 fossil specimens of juveniles and adults collected from the Upper Jurassic (Oxfordian) ...Tiaojishan Formation cropping out in Hebei Province, China. The new salamander displays several ontogenetically and taxonomically significant features, most prominently the presence of a toothed palatine, toothed coronoid, and a unique pattern of the hyobranchium in adults. Comparative study of the new salamander with previously known fossil and extant salamandroids sheds new light on the early evolution of the Salamandroidea, the most species-diverse clade in the Urodela. Cladistic analysis places the new salamander as the sister taxon to Beiyanerpeton, and the two taxa together form the basalmost clade within the Salamandroidea. Along with recently reported Beiyanerpeton from the same geological formation in the neighboring Liaoning Province, the discovery of Qinglongtriton indicates that morphological disparity had been underway for the salamandroid clade by early Late Jurassic (Oxfordian) time.
Ferroptosis is a regulated form of necrotic cell death implicated in carcinogenesis and neurodegeneration that is driven by phospholipid peroxidation. Lipid-derived electrophiles (LDEs) generated ...during this process can covalently modify proteins (“carbonylation”) and affect their functions. Here we report the development of a quantitative chemoproteomic method to profile carbonylations in ferroptosis by an aniline-derived probe. Using the method, we established a global portrait of protein carbonylations in ferroptosis with >400 endogenously modified proteins and for the first time, identified >20 residue sites with endogenous LDE modifications in ferroptotic cells. Specifically, we discovered and validated a novel cysteine site of modification on voltage-dependent anion-selective channel protein 2 (VDAC2) that might play an important role in sensitizing LDE signals and mediating ferroptosis. Our results will contribute to the understanding of ferroptotic signaling and pathogenesis and provide potential biomarkers for ferroptosis detection.
Plumage Color Patterns of an Extinct Dinosaur Li, Quanguo; Gao, Ke-Qin; Vinther, Jakob ...
Science (American Association for the Advancement of Science),
03/2010, Volume:
327, Issue:
5971
Journal Article
Peer reviewed
Open access
For as long as dinosaurs have been known to exist, there has been speculation about their appearance. Fossil feathers can preserve the morphology of color-imparting melanosomes, which allow color ...patterns in feathered dinosaurs to be reconstructed. Here, we have mapped feather color patterns in a Late Jurassic basal paravian theropod dinosaur. Quantitative comparisons with melanosome shape and density in extant feathers indicate that the body was gray and dark and the face had rufous speckles. The crown was rufous, and the long limb feathers were white with distal black spangles. The evolution of melanin-based within-feather pigmentation patterns may coincide with that of elongate pennaceous feathers in the common ancestor of Maniraptora, before active powered flight. Feathers may thus have played a role in sexual selection or other communication.
Cervical carcinoma is the fourth most common cause of death in woman, caused by human papillomavirus (HPV) infections and arising from the cervix. Cytoskeleton-associated protein 2 (CKAP2), also ...known as tumor-associated microtubule-associated protein, has been linked to tumorigenic effects. In the present study, we screened CKAP2 as a new candidate gene which promotes development of cervical carcinoma, in two independent datasets (TCGA and GSE27678). Results showed that CKAP2 expression was significantly up-regulated in cervical cancerous tissues compared with normal counterparts. Gene set enrichment analysis (GSEA) showed that metastasis, cell cycle and FAK pathways were related with elevated CKAP2 expression. Knockdown of CKAP2 expression significantly inhibited cell proliferation, migration and invasion both in HeLa and C-33A cells. And depletion of CKAP2 down-regulated the expression of metastasis and cell cycle related proteins as well as the phosphorylation of ERK2 (p-ERK2), except E-cadherin. In vivo experiment revealed that knockdown of CKAP2 inhibited C-33A cells proliferation. However, FAK inhibitor PF-562271 and ERK2 inhibitor VX-11e treatment significantly inhibited CKAP2 overexpression-induced cell proliferation, migration and invasion in SiHa cells. In conclusion, our study suggests that CKAP2 acts as a functional oncogene in cervical carcinoma development and may exert its function by targeting FAK-ERK2 signaling pathway.
A Jurassic salamander, Beiyanerpeton jianpingensis (gen. et sp. nov.), from a recently found site in western Liaoning Province, China is the earliest known record of Salamandroidea. As a Late ...Jurassic record of the group, it extends the range of the clade by approximately 40 Ma. The Late Jurassic taxon is neotenic and represented by exceptionally preserved specimens, including fully articulated cranial and postcranial skeletons and bony gill structures close to the cheek region. The fossil beds, consisting of dark-brown volcanic ash shales of the Upper Jurassic Tiaojishan (Lanqi) Formation (Oxfordian), underlie trachyandesite rocks that have yielded a SHRIMP zircon U-Pb date of 157 ± 3 Ma. The fossiliferous beds are substantially older than the Jehol Group, including the Yixian Formation (40Ar/39Ar dates of 122–129 Ma), but slightly younger than the Middle Jurassic Daohugou horizon (40Ar/39Ar date of 164 ± 4 Ma). The early fossil taxon shares with extant salamandroids derived character states, including: separated nasals lacking a midline contact, angular fused to the prearticular in the lower jaw, and double-headed ribs on the presacral vertebrae. In contrast to extant salamandroids, however, the salamander shows a discrete and tooth-bearing palatine, and unequivocally nonpedicellate and monocuspid marginal teeth in large and presumably mature individuals. The finding provides insights into the evolution of key characters of salamanders, and also provides direct evidence supporting the hypothesis that the split between Cryptobranchoidea and Salamandroidea had taken placed before the Late Jurassic Oxfordian time. In this aspect, both paleontological and molecular data now come to agree.
Androgen deprivation therapy (ADT), including enzalutamide, induces resistance in prostate cancer; ADT resistance is associated with neuroendocrine differentiation (NED) and tumor-associated ...macrophages (TAM). This study aimed to investigate the association between enzalutamide-induced NED and TAMs and its mechanism.
The association between enzalutamide-induced NED and TAMs was investigated by IHC using prostate cancer tissues, enzalutamide-resistant mouse xenografts, and a coculture system. The underlying mechanisms were assessed using
cytokine antibody arrays, ELISAs, chromatin immunoprecipitation, and other methods. An orthotopic prostate cancer mouse model was established to evaluate the
effects of combined IL6 receptor (IL6R) and high mobility group box 1 (HMGB1) inhibition on enzalutamide resistance.
High CD163 expression was observed in ADT-treated prostate cancer or castration-resistant prostate cancer (CRPC) tissues with high levels of neuron-specific enolase (NSE) and chromogranin A (CHGA) and in enzalutamide-resistant xenografts, indicating the crucial roles of NED and TAMs in enzalutamide resistance. Specifically, enzalutamide-induced HMGB1 expression facilitated TAM recruitment and polarization and drove NED via β-catenin stabilization. HMGB1-activated TAMs secreted IL6 to augment enzalutamide-induced NED and directly promote HMGB1 transcription via STAT3. Finally, inhibition of the IL6/STAT3 pathway by tocilizumab combined with HMGB1 knockdown inhibited enzalutamide-induced resistance in an orthotopic prostate cancer mouse model.
Enzalutamide elevates HMGB1 levels, which recruits and activates TAMs. Moreover, IL6 secreted by HMGB1-activated TAMs facilitates the enzalutamide-induced NED of prostate cancer, forming a positive feedback loop between NED in prostate cancer and TAMs. The combined inhibition of IL6R and HMGB1 may serve as a new treatment for enzalutamide resistance in patients with advanced or metastatic prostate cancer.
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Indescent feather colors involved in displays of many extant birds are produced by nanoscale arrays of melanin-containing organelles (melanosomes). Data relevant to the evolution of these colors and ...the properties of melanosomes involved in their generation have been limited. A data set sampling variables of extant avian melanosomes reveals that those forming most iridescent arrays are distinctly narrow. Quantitative comparison of these data with melanosome imprints densely sampled from a previously unknown specimen of the Early Cretaceous feathered Microraptor predicts that its plumage was predominantly iridescent. The capacity for simple iridescent arrays is thus minimally inferred in pa ravi a n dinosaurs. This finding and estimation of Microraptor feathering consistent with an ornamental function for the tail suggest a centrality for signaling in early evolution of plumage and feather color.
Accumulating evidences have suggested that percutaneous cryoablation could be a valuable alternative ablation therapy for HCC but there has been no large cohort-based analysis on its long-term ...outcomes.
A series of 866 patients with Child-Pugh class A-B cirrhosis and HCC within Milan criteria who underwent percutaneous cryoablation was long-term followed. The safety, efficacy, 5-year survival, and prognostic factors of percutaneous cryoablation in the treatment of HCC were analyzed.
A total of 1197 HCC lesions were ablated with 1401 cryoablation sessions. Complete response (CR) was achieved in 1163 (97.2%) lesions and 832 (96.1%) patients with 34 (2.8%) major complications, but no treatment-related mortality. After a median of 30.9 months follow-up, 502 (60.3%) patients who achieved CR developed different types of recurrence. The cumulative local tumor recurrence rate was 24.2% at 5-years. Multiple tumor lesions, tumor size > 3 cm, and repeated ablation of same lesion were independent risk factors associated with local recurrence. The 5-year overall survival (OS) rates were 59.5%. Age < 36 years, HCC family history, baseline hepatitis B virus DNA >106 copies/ml, and three HCC lesions were independently and significantly negative predictors to the post-cryoablation OS.
Percutaneous cryoablation is an effective therapy for patients with HCC within Milan criteria, with comparable efficacy, safety and long-term survival to the reported outcomes of radiofrequency ablation.
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