[Extensive cranioplasty for sagittal synostosis in young children by preserving multiple cranial bone flaps adhered to the dura mater: experience with 63 cases].

[Extensive cranioplasty for sagittal synostosis in young children by preserving multiple cranial bone flaps adhered to the dura mater: experience with 63 cases].

Zhonghua Zheng Xing Wai Ke Za Zhi. 2016 Jan;32(1):9-13

Authors: Bao Nan, Chu Jun, Wang Xue, Yang B, Song Y, Cai J

Abstract
OBJECTIVE: This study aimed to evaluate the effort of applying frontal and occipital bones in extensive cranioplasty and preserving multiple cranial bone flaps adhered to the dura mater in the treatment of sagittal synostosis.
METHODS: From April 2008 to June 2013, sixty-three children with sagittal synostosis, aged 5 months to 3 years, were included in the study. The frontal bone flap was removed using an air drill. The occipital and bilateral temporal bone flaps were cut open but not detached from the dura mater or fixed to produce floating bone flaps. The skull bone was cut into palisade-like structures. Brain compression from both sides and the base of the skull was released and the brain expanded bilaterally through the enlarged space. Only a long strip-shaped bone bridge remained in the central parietal bone. Subsequently, the frontal bone flaps and occipital bone flap were pushed towards the midline and fixed with the parietal bone bridge to shorten the anteroposterior diameter of the cranial cavity and allow the brain to expand bilaterally to correct scaphocephaly. The CT images showed that both sides of the parietal bone of artificial sagittal groove gradually merged postoperative 1 year, and skull almost completely normal healing after operation 2 or 3 years, without deformity recurrence within 5 years. Among them all, 61 children's intelligence is normal and 2 children's lagged behind normal level, no further improvement.
RESULTS: Patients were followed up 1 - 5 years (an average of 43 months). Skull growth was excellent in all patients, the anteroposterior diameter was shortened by 14.6 mm averagely, the transverse diameter was increased by 12.3 mm averagely, the prominent forehead was corrected, and scaphocephaly improved significantly. There were no complications such as death and skull necrosis.
CONCLUSIONS: The application of frontal and occipital bones in extensive cranioplasty and preserving multiple cranial bone flaps adhered to the dura mater can be used in the treatment of sagittal synostosis. Surgery without removing bone flaps is less traumatic and results in no massive bleeding. It can effectively relieve brain compression and promotes transversal expansion of the brain during surgery and subsequent normal brain development.

PMID: 27197472 [PubMed - in process]

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Morphometric study of the medial orbital wall emphasizing the ethmoidal foramina.

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Morphometric study of the medial orbital wall emphasizing the ethmoidal foramina.

Surg Radiol Anat. 2015 Sep;37(7):809-13

Authors: Vadgaonkar R, Rai R, Prabhu LV, Rai AR, Tonse M, Vani PC

Abstract
PURPOSE: Ethmoidal foramina on the medial orbital wall show a higher incidence of variation. Surgeons performing endonasal, anterior cranial fossa and medial orbital wall surgeries must be aware of these variations as they are a source of hemorrhage and also serve as landmark in proximity to the orbital apex.
AIM: The present study aims to describe the morphometric distances of various ethmoidal foramina between anterior lacrimal crest to optic canal in south Indian dry human skulls.
MATERIALS AND METHOD: The study was done on 44 adult dry human skulls. The occurrence of Ethmoidal foramina was noted by direct inspection. The distance of Ethmoidal foramina from anterior lacrimal crest to optic canal was measured with the help of ruler, probe and magnifying glass.
RESULTS: The Posterior ethmoidal foramina were found in all 44 skulls bilaterally. Middle ethmoidal foramen was present in 12 and 13 skulls on right and left, respectively. Anterior ethmoidal foramen was found in 38 and 37 skulls on right and left, respectively. The distance between anterior lacrimal crest (ALC) and posterior lacrimal crest (PLC) was in the range of 3-8 mm and that of ALC to anterior ethmoidal foramen was in the range of 24-30 mm. The range of distance between anterior ethmoidal foramen to posterior ethmoidal foramen was 9-17 mm and that between posterior ethmoidal foramen to optic canal was 5-13 mm.
CONCLUSION: These observations would help to predict the anatomical variations in the position of ethmoidal foramina with respect to anterior and posterior lacrimal crest and ensure the safe and precise performance of medial orbital wall surgeries to avoid injuries to the important neurovascular bundles passing through various foramina and fissures.

PMID: 25563482 [PubMed - indexed for MEDLINE]

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Pigmented villonodular synovitis of the temporomandibular joint with intracranial extension: A case series and systematic review.

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Pigmented villonodular synovitis of the temporomandibular joint with intracranial extension: A case series and systematic review.

Head Neck. 2015 Aug;37(8):1213-24

Authors: Safaee M, Oh T, Sun MZ, Parsa AT, McDermott MW, El-Sayed IH, Bloch O

Abstract
BACKGROUND: Pigmented villonodular synovitis (PVNS) is a rare proliferative disorder of the synovial membrane. PVNS generally affects large joints but occasionally involves the temporomandibular joint (TMJ), with occasional extension into the middle cranial fossa. The purpose of this study was to report our experience with PVNS along with a focused literature review.
METHODS: Patients with PVNS of the TMJ treated at the University of California - San Francisco from 2007 to 2013 were reviewed. A PubMed search was performed to identify additional cases.
RESULTS: Five patients underwent surgical resection, with 1 recurrence at 61 months. A literature review identified 58 patients, 19 of which had intracranial involvement. Interestingly, intracranial extension was more common in men. Intracranial extension was not associated with an increased rate of recurrence.
CONCLUSION: PVNS of the TMJ is a rare entity associated with excellent outcomes, even with intracranial extension. Management should consist of maximal resection, with radiotherapy reserved for extensive or recurrent lesions.

PMID: 24764167 [PubMed - indexed for MEDLINE]

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TAT-IL-24-KDEL -induced apoptosis is inhibited by survivin but restored by the small molecular survivin inhibitor YM155, in cancer cells.

TAT-IL-24-KDEL -induced apoptosis is inhibited by survivin but restored by the small molecular survivin inhibitor YM155, in cancer cells.

Oncotarget. 2016 May 18;

Authors: Zhang J, Xu R, Tao X, Dong Y, Lv X, Sun A, Wei D

Abstract
Interleukin-24 (IL-24) is a cytokine belonging to the IL-10 gene family. This cytokine selectively induces apoptosis in cancer cells, without harming normal cells, through a mechanism involving endoplasmic reticulum (ER) stress response. TAT-IL-24-KDEL is a fusion protein that efficiently enters the tumor cells and locates in the ER. Here we report that TAT-IL-24-KDEL induced apoptosis in human cancer cells, mediated by the ER stress cell death pathway. This process was accompanied by the inhibition of the transcription of an antiapoptotic protein, survivin. The forced expression of survivin partially protected cancer cells from the induction of apoptosis by TAT-IL-24-KDEL, increased their clonogenic survival, and attenuated TAT-IL-24-KDEL-induced activation of caspase-3/7. RNA interference of survivin markedly sensitized the transformed cells to TAT-IL-24-KDEL. Survivin was expressed at higher levels among isolated clones that resistant to TAT-IL-24-KDEL. These observations show the important role of survivin in attenuating cancer-specific apoptosis induced by TAT-IL-24-KDEL. The pharmacological inhibition of survivin expression by a selective small-molecule survivin suppressant YM155 synergistically sensitized cancer cells to TAT-IL-24-KDEL-induced apoptosis in vitro and in vivo. The combined regimen caused significantly higher activation of ER stress and dysfunction of mitochondria than either treatment alone. As survivin is overexpressed in a majority of cancers, the combined TAT-IL-24-KDEL and YM155 treatment provides a promising alternative to the existing therapies.

PMID: 27203744 [PubMed - as supplied by publisher]

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The anti-HER3 (ErbB3) therapeutic antibody 9F7-F11 induces HER3 ubiquitination and degradation in tumors through JNK1/2- dependent ITCH/AIP4 activation.

The anti-HER3 (ErbB3) therapeutic antibody 9F7-F11 induces HER3 ubiquitination and degradation in tumors through JNK1/2- dependent ITCH/AIP4 activation.

Oncotarget. 2016 May 18;

Authors: Le Clorennec C, Lazrek Y, Dubreuil O, Larbouret C, Poul MA, Mondon P, Melino G, Pèlegrin A, Chardès T

Abstract
We characterized the mechanism of action of the neuregulin-non-competitive anti-HER3 therapeutic antibody 9F7-F11 that blocks the PI3K/AKT pathway, leading to cell cycle arrest and apoptosis in vitro and regression of pancreatic and breast cancer in vivo. We found that 9F7-F11 induces rapid HER3 down-regulation. Specifically, 9F7-F11-induced HER3 ubiquitination and degradation in pancreatic, breast and prostate cancer cell lines was driven mainly by the itchy E3 ubiquitin ligase (ITCH/AIP4). Overexpression of the ITCH/AIP4 inhibitor N4BP1 or small-interfering RNA-mediated knockdown of ITCH/AIP4 inhibited HER3 ubiquitination/degradation and PI3K/AKT signaling blockade induced by 9F7-F11. Moreover, 9F7-F11-mediated JNK1/2 phosphorylation led to ITCH/AIP4 activation and recruitment to HER3 for receptor ubiquitination and degradation. ITCH/AIP4 activity was activated by the deubiquitinases USP8 and USP9X, as demonstrated by RNA interference. Taken together, our results suggest that 9F7-F11-induced HER3 ubiquitination and degradation in cancer cells mainly occurs through JNK1/2-dependent ITCH/AIP4 activation.

PMID: 27203743 [PubMed - as supplied by publisher]

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Glutaredoxin 3 promotes nasopharyngeal carcinoma growth and metastasis via EGFR/Akt pathway and independent of ROS.

Glutaredoxin 3 promotes nasopharyngeal carcinoma growth and metastasis via EGFR/Akt pathway and independent of ROS.

Oncotarget. 2016 May 18;

Authors: He F, Wei L, Luo W, Liao Z, Li B, Zhou X, Xiao X, You J, Chen Y, Zheng S, Li P, Murata M, Huang G, Zhang Z

Abstract
Glutaredoxin 3 (GLRX3) is antioxidant enzyme, maintaining a low level of ROS, thus contributing to the survival and metastasis of several types of cancer. However, the expression and functions of GLRX3 have not been addressed in nasopharyngeal carcinoma (NPC). In this study, we found that GLRX3 was overexpressed in NPC. Knockdown of GLRX3 in NPC cell lines inhibited proliferation in vitro, tumorignesis in vivo, and colony formation. In addition, GLRX3 knockdown decreased the migration and invasion capacity of NPC cells by reversing the epithelial-mesenchymal transition (EMT). Furthermore, stabilization of GLRX3 was positively related to with epidermal growth factor receptor (EGFR) expression and negatively with ROS generation. Phosphorylation of Akt, a key downstream effector, was induced by EGFR signaling but did not rely on increasing ROS level in NPC cells. GLRX3 might be an oncoprotein in NPC, playing important roles in increasing redox reaction and activating EGFR/ Akt signals, so it may be a therapeutic target for NPC.

PMID: 27203742 [PubMed - as supplied by publisher]

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Metastatic site-specific polarization of macrophages in intracranial breast cancer metastases.

Metastatic site-specific polarization of macrophages in intracranial breast cancer metastases.

Oncotarget. 2016 May 18;

Authors: Rippaus N, Taggart D, Williams J, Andreou T, Wurdak H, Wronski K, Lorger M

Abstract
In contrast to primary tumors, the understanding of macrophages within metastases is very limited. In order to compare macrophage phenotypes between different metastatic sites, we established a pre-clinical mouse model of intracranial breast cancer metastasis in which cancer lesions develop simultaneously within the brain parenchyma and the dura. This mimics a situation that is commonly occurring in the clinic. Flow cytometry analysis revealed significant differences in the activation state of metastasis-associated macrophages (MAMs) at the two locations. Concurrently, gene expression analysis identified significant differences in molecular profiles of cancer cells that have metastasized to the brain parenchyma as compared to the dura. This included differences in inflammation-related pathways, NF-kB1 activity and cytokine profiles. The most significantly upregulated cytokine in brain parenchyma- versus dura-derived cancer cells was Lymphotoxin β and a gain-of-function approach demonstrated a direct involvement of this factor in the M2 polarization of parenchymal MAMs. This established a link between metastatic site-specific properties of cancer cells and the MAM activation state.

PMID: 27203741 [PubMed - as supplied by publisher]

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MiR-193a-5p/ERBB2 act as concurrent chemoradiation therapy response indicator of esophageal squamous cell carcinoma.

MiR-193a-5p/ERBB2 act as concurrent chemoradiation therapy response indicator of esophageal squamous cell carcinoma.

Oncotarget. 2016 May 18;

Authors: Lin CH, Tsai CH, Yeh CT, Liang JL, Hung WC, Lin FC, Chang WL, Li HY, Yao YC, Hsu TI, Lee YC, Wang YC, Sheu BS, Lai WW, Calkins MJ, Hsiao M, Lu PJ

Abstract
Concurrent chemoradiation therapy (CCRT) is the predominant treatment in esophageal cancer, however resistance to therapy and tumor recurrence are exceedingly common. Elevated ERBB2/Her2 may be at least partially responsible for both the high rates of recurrence and resistance to CCRT. This receptor tyrosine kinase is upregulated in 10-20% of esophageal squamous cell carcinoma (ESCC) tissues, and amplification of ERBB2 has been correlated with poor prognosis in esophageal cancer. Tissues from 131 ESCC patients, along with cell and animal models of the disease were used to probe the underlying mechanisms by which ERBB2 upregulation occurs and causes negative outcomes in ESCC. We found that overexpression of ERBB2 inhibited radiosensitivity in vitro. Furthermore, miR-193a-5p reduced ERBB2 expression by directly targeting the 3'UTR. Increased miR-193a-5p enhanced radiosensitivity and inhibited tumorigenesis in vitro and in vivo. Additionally, low miR-193a-5p expression correlated with poor prognosis in ESCC patients, and ESCC patients with good CCRT response exhibited higher miR-193a-5p expression. Our data suggest that patients with high miR-193a-5p will likely benefit from CCRT treatment alone, however a combination of CCRT with Herceptin may be beneficial for patients with low miR-193a-5p expression.

PMID: 27203740 [PubMed - as supplied by publisher]

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Radiobiological modeling of two stereotactic body radiotherapy schedules in patients with stage I peripheral non-small cell lung cancer.

Radiobiological modeling of two stereotactic body radiotherapy schedules in patients with stage I peripheral non-small cell lung cancer.

Oncotarget. 2016 May 18;

Authors: Huang BT, Lin Z, Lin PX, Lu JY, Chen CZ

Abstract
This study aims to compare the radiobiological response of two stereotactic body radiotherapy (SBRT) schedules for patients with stage I peripheral non-small cell lung cancer (NSCLC) using radiobiological modeling methods. Volumetric modulated arc therapy (VMAT)-based SBRT plans were designed using two dose schedules of 1 × 34 Gy (34 Gy in 1 fraction) and 4 × 12 Gy (48 Gy in 4 fractions) for 19 patients diagnosed with primary stage I NSCLC. Dose to the gross target volume (GTV), planning target volume (PTV), lung and chest wall (CW) were converted to biologically equivalent dose in 2 Gy fraction (EQD2) for comparison. Five different radiobiological models were employed to predict the tumor control probability (TCP) value. Three additional models were utilized to estimate the normal tissue complication probability (NTCP) value for the lung and the modified equivalent uniform dose (mEUD) value to the CW. Our result indicates that the 1 × 34 Gy dose schedule provided a higher EQD2 dose to the tumor, lung and CW. Radiobiological modeling revealed that the TCP value for the tumor, NTCP value for the lung and mEUD value for the CW were 7.4% (in absolute value), 7.2% (in absolute value) and 71.8% (in relative value) higher on average, respectively, using the 1 × 34 Gy dose schedule.

PMID: 27203739 [PubMed - as supplied by publisher]

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Targeted next generation sequencing of endoscopic ultrasound acquired cytology from ampullary and pancreatic adenocarcinoma has the potential to aid patient stratification for optimal therapy selection.

Targeted next generation sequencing of endoscopic ultrasound acquired cytology from ampullary and pancreatic adenocarcinoma has the potential to aid patient stratification for optimal therapy selection.

Oncotarget. 2016 May 18;

Authors: Gleeson FC, Kerr SE, Kipp BR, Voss JS, Minot DM, Tu ZJ, Henry MR, Graham RP, Vasmatzis G, Cheville JC, Lazaridis KN, Levy MJ

Abstract
BACKGROUND & AIMS: Less than 10% of registered drug intervention trials for pancreatic ductal adenocarcinoma (PDAC) include a biomarker stratification strategy. The ability to identify distinct mutation subsets via endoscopic ultrasound fine needle aspiration (EUS FNA) molecular cytology could greatly aid clinical trial patient stratification and offer predictive markers. We identified chemotherapy treatment naïve ampullary adenocarcinoma and PDAC patients who underwent EUS FNA to assess multigene mutational frequency and diversity with a surgical resection concordance assessment, where available.
METHODS: Following strict cytology smear screening criteria, targeted next generation sequencing (NGS) using a 160 cancer gene panel was performed.
RESULTS: Complete sequencing was achieved in 29 patients, whereby 83 pathogenic alterations were identified in 21 genes. Cytology genotyping revealed that the majority of mutations were identified in KRAS (93%), TP53 (72%), SMAD4 (31%), and GNAS (10%). There was 100% concordance for the following pathogenic alterations: KRAS, TP53, SMAD4, KMT2D, NOTCH2, MSH2, RB1, SMARCA4, PPP2R1A, PIK3R1, SCL7A8, ATM, and FANCD2. Absolute multigene mutational concordance was 83%. Incremental cytology smear mutations in GRIN2A, GATA3 and KDM6A were identified despite re-examination of raw sequence reads in the corresponding resection specimens.
CONCLUSIONS: EUS FNA cytology genotyping using a 160 cancer gene NGS panel revealed a broad spectrum of pathogenic alterations. The fidelity of cytology genotyping to that of paired surgical resection specimens suggests that EUS FNA represents a suitable surrogate and may complement the conventional stratification criteria in decision making for therapies and may guide future biomarker driven therapeutic development.

PMID: 27203738 [PubMed - as supplied by publisher]

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The potential role of epigenetic modulations in BPPV maneuver exercises.

The potential role of epigenetic modulations in BPPV maneuver exercises.

Oncotarget. 2016 May 18;

Authors: Tsai KL, Wang CT, Kuo CH, Cheng YY, Ma HI, Hung CH, Tsai YJ, Kao CL

Abstract
Benign paroxysmal positional vertigo (BPPV) is one of the most common complaints encountered in clinics and is strongly correlated with advanced age or, possibly, degeneration. Redistribution exercises are the most effective approaches to treat BPPV, and canalith repositioning procedure (CRP) cure most BPPV cases. However, the mechanisms through which the treatment modulates systemic molecules in BPPV patients remain largely unknown. In this study, we report that the miR-34a and Sirtuin 1 (SIRT1) genes correlated with the treatment effects of CRP in BPPV subjects. We found that miR-34a expression was largely inhibited and SIRT1 expression was significantly reversed after BPPV maneuver treatment. We also confirmed that the PPAR-γ, PGC-1 and FoxO gene expressions were decreased immediately after canalith repositioning procedure (CRP) for BPPV, and were largely increased after a complete cure of BPPV. Moreover, we observed that after a complete recovery of BPPV, the ROS concentrations, pro-inflammatory cytokine concentrations and p53 expression levels were attenuated. We conclude that BPPV treatment might involve some epigenetic regulations through the mediation of miR-34a, SIRT1 functions and repression of redox status.

PMID: 27203679 [PubMed - as supplied by publisher]

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Cabazitaxel operates anti-metastatic and cytotoxic via apoptosis induction and stalls brain tumor angiogenesis.

Cabazitaxel operates anti-metastatic and cytotoxic via apoptosis induction and stalls brain tumor angiogenesis.

Oncotarget. 2016 May 18;

Authors: Ghoochani A, Hatipoglu-Majernik G, Sehm T, Wach S, Buchfelder M, Taubert H, Eyupoglu IY, Savaskan N

Abstract
Taxanes target microtubules and are clinically established chemotherapeutic agents with proven efficacy in human cancers. Cabazitaxel (XRP-6258, Jevtana®) is a second generation semisynthetic taxane with high chemotherapeutic potential in prostate cancer. There, cabazitaxel can overcome docetaxel-resistant prostate cancer. Here, we tested the effects of cabazitaxel on glioma cells, and non-transformed cells such as neurons and astrocytes. Cabazitaxel operates highly toxic in various human glioma cells at nanomolar concentrations. In contrast, primary astrocytes and neurons are not affected by this agent. Cabazitaxel disrupts cytoskeletal F-actin fibers and induces apoptotic cell death in gliomas. Moreover, cabazitaxel displayed highest efficacy in inhibiting glioma cell migration and invasion. Here we demonstrate that cabazitaxel inhibited tumor migration already at 1 nM. We also tested cabazitaxel in the ex vivo VOGiM assay. Cabazitaxel stalled glioma growth and at the same time inhibited tumor-induced angiogenesis. In summary, we found that cabazitaxel operates as an apoptosis-inducing gliomatoxic agent with strongest effects on migration and invasive growth. Thus, our report uncovered cabazitaxel actions on gliomas and on the brain tumor microenvironment. These data reveal novel aspects for adjuvant approaches when applied to brain tumor patients.

PMID: 27203678 [PubMed - as supplied by publisher]

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Sorafenib inhibits macrophage-mediated epithelial-mesenchymal transition in hepatocellular carcinoma.

Sorafenib inhibits macrophage-mediated epithelial-mesenchymal transition in hepatocellular carcinoma.

Oncotarget. 2016 May 18;

Authors: Deng YR, Liu WB, Lian ZX, Li X, Hou X

Abstract
Tumor-associated macrophages, crucial components of the microenvironment in hepatocellular carcinoma, hamper anti-cancer immune responses. The aim of the present study was to investigate the effect of sorafenib on the formation of the tumor microenvironment, especially the relationship between polarized macrophages and hepatocytes. Macrophage infiltration was reduced in patients with hepatocellular carcinoma who were treated with sorafenib. In vitro, sorafenib abolished polarized macrophage-induced epithelial mesenchymal transition (EMT) and migration of hepatocellular carcinoma cells but not normal hepatocytes. Moreover, sorafenib attenuated HGF secretion in polarized macrophages, and decreased plasma HGF in patients with hepatocellular carcinoma. Additionally, sorafenib abolished the polarized macrophage-induced activation of the HGF receptor Met in hepatocellular carcinoma cells. Our findings suggest that sorafenib inhibits polarized macrophage-induced EMT in hepatocellular carcinoma cells via the HGF-Met signaling pathway. These results contribute to our understanding of the immunological mechanisms that underlie the protective effects of sorafenib in hepatocellular carcinoma therapy.

PMID: 27203677 [PubMed - as supplied by publisher]

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Significant change of cytochrome P450s activities in patients with hepatocellular carcinoma.

Significant change of cytochrome P450s activities in patients with hepatocellular carcinoma.

Oncotarget. 2016 May 18;

Authors: Zhou J, Wen Q, Li SF, Zhang YF, Gao N, Tian X, Fang Y, Gao J, Cui MZ, He XP, Jia LJ, Jin H, Qiao HL

Abstract
The lack of information concerning individual variation in drug-metabolizing enzymes is one of the most important obstacles for designing personalized medicine approaches for hepatocellular carcinoma (HCC) patients. To assess cytochrome P450 (CYP) in the metabolism of endogenous and exogenous molecules in an HCC setting, the activity changes of 10 major CYPs in microsomes from 105 normal and 102 HCC liver tissue samples were investigated. We found that CYP activity values expressed as intrinsic clearance (CLint) differed between HCC patients and control subjects. HCC patient samples showed increased CLint for CYP2C9, CYP2D6, and CYP2E1 compared to controls. Meanwhile, CYP1A2, CYP2C8, and CYP2C19 CLint values decreased and CYP2A6, CYP2B6, and CYP3A4/5 activity was unchanged relative to controls. For patients with HCC accompanied by fibrosis or cirrhosis, the same activity changes were seen for the CYP isoforms, except for CYP2D6 which had higher values in HCC patients with cirrhosis. Moreover, CYP2D6*10 (100C>T), CYP2C9*3 (42614 A>C), and CYP3A5*3 (6986A>G) polymorphisms had definite effects on enzyme activities. In the HCC group, the CLint of CYP2D6*10 mutant homozygote was decreased by 95% compared to wild-type samples, and the frequency of this homozygote was 2.8-fold lower than the controls.In conclusion, the activities of CYP isoforms were differentially affected in HCC patients. Genetic polymorphisms of some CYP enzymes, especially CYP2D6*10, could affect enzyme activity. CYP2D6*10 allelic frequency was significantly different between HCC patients and control subjects. These findings may be useful for personalizing the clinical treatment of HCC patients as well as predicting the risk of hepatocarcinogenesis.

PMID: 27203676 [PubMed - as supplied by publisher]

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Co-option of pre-existing vascular beds in adipose tissue controls tumor growth rates and angiogenesis.

Co-option of pre-existing vascular beds in adipose tissue controls tumor growth rates and angiogenesis.

Oncotarget. 2016 May 18;

Authors: Lim S, Hosaka K, Nakamura M, Cao Y

Abstract
Many types of cancer develop in close association with highly vascularized adipose tissues. However, the role of adipose pre-existing vascular beds on tumor growth and angiogenesis is unknown. Here we report that pre-existing microvascular density in tissues where tumors originate is a crucial determinant for tumor growth and neovascularization. In three independent tumor types including breast cancer, melanoma, and fibrosarcoma, inoculation of tumor cells in the subcutaneous tissue, white adipose tissue (WAT), and brown adipose tissue (BAT) resulted in markedly differential tumor growth rates and angiogenesis, which were in concordance with the degree of pre-existing vascularization in these tissues. Relative to subcutaneous tumors, WAT and BAT tumors grew at accelerated rates along with improved neovascularization, blood perfusion, and decreased hypoxia. Tumor cells implanted in adipose tissues contained leaky microvessel with poor perivascular cell coverage. Thus, adipose vasculature predetermines the tumor microenvironment that eventually supports tumor growth.

PMID: 27203675 [PubMed - as supplied by publisher]

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RNF216 contributes to proliferation and migration of colorectal cancer via suppressing BECN1-dependent autophagy.

RNF216 contributes to proliferation and migration of colorectal cancer via suppressing BECN1-dependent autophagy.

Oncotarget. 2016 May 18;

Authors: Wang H, Wang Y, Qian L, Wang X, Gu H, Dong X, Huang S, Jin M, Ge H, Xu C, Zhang Y

Abstract
Originally identified as an E3 ligase regulating toll-like receptor (TLR) signaling, ring finger protein 216 (RNF216) also plays an essential role in autophagy, which is fundamental to cellular homeostasis. Autophagy dysfunction leads to an array of pathological events, including tumor formation. In this study, we found that RNF216 was upregulated in human colorectal cancer (CRC) tissues and cell lines, and was associated with progression of CRC. RNF216 promoted CRC cell proliferation and migration in vitro and in vivo, largely by enhancing proteasomal degradation of BECN1, a key autophagy regulator and tumor suppressor. RNF216 restricted CRC cell autophagy through BECN1 inhibition under nutritional starvation conditions. RNF216 knockdown increased the autophagy, limiting CRC cell proliferation and migration. Moreover, BECN1 knockdown or autophagy inhibition restored proliferation and migration of RNF216-knockdown CRC cells. Collectively, our results suggested that RNF216 promoted CRC cell proliferation and migration by negatively regulating BECN1-dependent autophagy. This makes RNF216 as a potential biomarker and novel therapeutic target for inhibiting CRC development and progression.

PMID: 27203674 [PubMed - as supplied by publisher]

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Effect of nodal status on clinical outcomes of triple-negative breast cancer: a population-based study using the SEER 18 database.

Effect of nodal status on clinical outcomes of triple-negative breast cancer: a population-based study using the SEER 18 database.

Oncotarget. 2016 May 18;

Authors: Wang XX, Jiang YZ, Li JJ, Song CG, Shao ZM

Abstract
Triple-negative breast cancer (TNBC) is an aggressive malignancy with a poor prognosis. Data from the Surveillance, Epidemiology and End Results database (2010-2012) were used to identify 10,771 patients with TNBC, and we assessed the effects of lymph node (LN) status on breast cancer-specific survival (BCSS) and overall survival (OS). In our study, a Kaplan-Meier plot showed that LN-negative patients (N0) had better survival outcomes than LN-positive patients and that patients with ≥10 positive LNs (N3) exhibited the worst survival outcomes regardless of tumor size. A pairwise comparison showed no difference in survival outcomes among each group stratified by tumor size. Further, for LN-positive patients with a tumor size ≤2 cm (T1) or >5 cm (T3), there were similar outcomes between patients with one to three LNs (N1) and those with four to nine LNs (N2), whereas N1 patients experienced significantly better survival outcomes than N3 patients (P<0.001). Therefore, ten metastatic lymph nodes was the cut-off value for poor prognosis. Nevertheless, for patients with a tumor size of 2-5 cm (T2), the extent of LN involvement contributed prognostic value to OS but not BCSS. In summary, we found that nodal status and tumor size exhibited distinct interaction patterns for predicting the outcomes of TNBC. These results provide deeper insight into the prognostic value of nodal status in TNBC.

PMID: 27203673 [PubMed - as supplied by publisher]

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Drug conjugated nanoparticles activated by cancer cell specific mRNA.

Drug conjugated nanoparticles activated by cancer cell specific mRNA.

Oncotarget. 2016 May 18;

Authors: Gossai NP, Naumann JA, Li NS, Zamora EA, Gordon DJ, Piccirilli JA, Gordon PM

Abstract
We describe a customizable approach to cancer therapy in which a gold nanoparticle (Au-NP) delivers a drug that is selectively activated within the cancer cell by the presence of an mRNA unique to the cancer cell. Fundamental to this approach is the observation that the amount of drug released from the Au-NP is proportional to both the presence and abundance of the cancer cell specific mRNA in a cell. As proof-of-principle, we demonstrate both the efficient delivery and selective release of the multi-kinase inhibitor dasatinib from Au-NPs in leukemia cells with resulting efficacy in vitro and in vivo. Furthermore, these Au-NPs reduce toxicity against hematopoietic stem cells and T-cells. This approach has the potential to improve the therapeutic efficacy of a drug and minimize toxicity while being highly customizable with respect to both the cancer cell specific mRNAs targeted and drugs activated.

PMID: 27203672 [PubMed - as supplied by publisher]

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Can immunostimulatory agents enhance the abscopal effect of radiotherapy?

Can immunostimulatory agents enhance the abscopal effect of radiotherapy?

Eur J Cancer. 2016 May 17;62:36-45

Authors: Levy A, Chargari C, Marabelle A, Perfettini JL, Magné N, Deutsch E

Abstract
Ionising radiation (IR) may harm cancer cells through a rare indirect out-of-field phenomenon described as the abscopal effect. Increasing evidence demonstrates that radiotherapy could be capable of generating tumour-specific immune responses. On the other hand, effects of IR also include inhibitory immune signals on the tumour microenvironment. Following these observations, and in the context of newly available immunostimulatory agents in metastatic cancers (anti-cytotoxic T lymphocyte-associated antigen 4 and programmed cell death protein-1 or -ligand 1 [PD1 or PDL-1]), there is a remarkable potential for synergistic combinations of IR with such agents that act through the reactivation of immune surveillance. Here, we present and discuss the pre-clinical and clinical rationale supporting the enhancement of the abscopal effect of IR on the blockade of immune checkpoints and discuss the evolving potential of immunoradiotherapy.

PMID: 27200491 [PubMed - as supplied by publisher]

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Resectable Cholangiocarcinoma: Reviewing the Role of Adjuvant Strategies.

Resectable Cholangiocarcinoma: Reviewing the Role of Adjuvant Strategies.

Clin Med Insights Oncol. 2016;10:43-8

Authors: Cidon EU

Abstract
Cholangiocarcinoma is a very heterogeneous and rare group of neoplasms originating from the perihilar, intra-, or extrahepatic bile duct epithelium. It represents only 3% of gastrointestinal cancers, although their incidence is increasing as its mortality increases. Surgical resection is the only potentially curative option, but unfortunately the resectability rate is low. Overall, these malignancies have got a very poor prognosis with a five-year survival rate of 5-10%. Although the five-year survival rate increases to 25-30% in the cases amenable to surgery, only 10-40% of patients present with resectable disease. Therefore, it is necessary to optimize the benefit of adjuvant strategies after surgery to increase the rate of curability. This study reviewed the role of adjuvant chemotherapy in resectable bile duct cancers.

PMID: 27199577 [PubMed]

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Minireview: Role of Genetic Changes of Faciogenital Dysplasia Protein 1 in Human Disease.

Minireview: Role of Genetic Changes of Faciogenital Dysplasia Protein 1 in Human Disease.

Physiol Genomics. 2016 May 6;:physiolgenomics.00101.2015

Authors: Pedigo NG, Van Delden D, Walters L, Farrell CL

Abstract
The FGD1 gene encodes for a guanine exchange factor (GEF) protein which specifically activates the Rho GTPase Cdc42. For cellular migration, Cdc42 is a key molecular switch that regulates cytoskeleton restructuring, gene transcription, cellular morphology, extension, and cell adhesion. In the past decade, germline mutations in the FGD1 gene have been associated with a rare X-linked disorder known as faciogenital dysplasia (FGDY). Malformations are consistent with a loss of cellular migration during embryonic development. Insertion and deletion mutations in FGD1 result in a frameshift causing inactivation of fgd1 protein. Since Cdc42 is a key molecular switch in cytoskeletal restructuring and cell adhesion, the loss of fgd1 is postulated to attenuate Cdc42 mediated cellular migration in embryonic development. In metastatic tumors, Cdc42 modulates migration and invasiveness. Fgd1 overexpression has been found in infiltrating and poorly differentiated breast and invasive prostate tumors. Amplification at Xp11.21, the FGD1 gene locus, has been reported in several cancers. Sequencing analyses in numerous types of cancer have found missense mutations in the FGD1 gene in metastatic tumors. FGDY and cancer studies suggest that the germline and somatic changes downregulate or upregulate the FGD1 gene playing a key in the development of diseases.

PMID: 27199457 [PubMed - as supplied by publisher]

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Histopathologic assessment of depth of follicular invasion of squamous cell carcinoma (SCC) in situ (SCCis): Implications for treatment approach.

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Histopathologic assessment of depth of follicular invasion of squamous cell carcinoma (SCC) in situ (SCCis): Implications for treatment approach.

J Am Acad Dermatol. 2016 Feb;74(2):356-62

Authors: Christensen SR, McNiff JM, Cool AJ, Aasi SZ, Hanlon AM, Leffell DJ

Abstract
BACKGROUND: Squamous cell carcinoma in situ (SCCis) has been reported to involve the hair follicle epithelium. Deep follicular invasion is often cited as a cause of treatment failure.
OBJECTIVE: We sought to define the frequency and the depth of hair follicle invasion by SCCis.
METHODS: The study included both a retrospective review of intraoperative pathology specimens from 42 SCCis cases treated with Mohs micrographic surgery and a prospective evaluation of serially sectioned SCCis tissue from 12 additional patients. Pathology specimens were analyzed for follicular invasion of SCCis.
RESULTS: SCCis invasion of the superficial hair follicle infundibulum was observed in 61.3% to 87.5% of cases in the 2 cohorts, whereas invasion of the isthmus and lower follicle was observed in only 8.3% to 12.5% of cases. In most tumors the depth of follicular invasion was comparable with the thickness of the surrounding epidermis. The maximum observed depth of follicular invasion was 0.82 mm.
LIMITATIONS: The study was performed on a limited number of cases referred for surgery at a single institution.
CONCLUSIONS: Although SCCis invasion of the upper hair follicle infundibulum is common, deep invasion below the level of the surrounding epidermis is rare. This may have implications for optimal therapy of this condition.

PMID: 26670714 [PubMed - indexed for MEDLINE]

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Reply to the letter to the editor 'Prevalence of rare EGFR mutations in non-small cell lung cancer: a multicenter study on 3856 Polish Caucasian patients' by Krawczyk et al.

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Reply to the letter to the editor 'Prevalence of rare EGFR mutations in non-small cell lung cancer: a multicenter study on 3856 Polish Caucasian patients' by Krawczyk et al.

Ann Oncol. 2016 Feb;27(2):359-60

Authors: Beau-Faller M, Cadranel J

PMID: 26658890 [PubMed - indexed for MEDLINE]

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Ferritin as an early marker of graft rejection after allogeneic hematopoietic stem cell transplantation in pediatric patients.

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Ferritin as an early marker of graft rejection after allogeneic hematopoietic stem cell transplantation in pediatric patients.

Ann Hematol. 2016 Jan;95(2):311-23

Authors: Döring M, Cabanillas Stanchi KM, Feucht J, Queudeville M, Teltschik HM, Lang P, Feuchtinger T, Handgretinger R, Müller I

Abstract
Diagnosis of adverse events following hematopoietic stem cell transplantation (HSCT) is mainly assigned to clinical symptoms or biopsies and thus rather unspecific and/or invasive. Studies indicate a distinct role of serum ferritin in HSCT and its correlation with adverse events such as graft-versus-host disease (GvHD), veno-occlusive disease (VOD), or infections. However, published data on the relevance of ferritin as a prognostic marker for post-transplant adverse events is rare, especially in pediatric patients. The present study analyzes ferritin plasma concentrations of 138 pediatric patients after HSCT between 2007 and 2010 including the control group (n = 21). Given the initial results regarding ferritin as a significant predictor for acute graft rejection after allogeneic HSCT in 9 of the 138 pediatric patients, serum ferritin of all pediatric patients (n = 27) who experienced graft rejection between 2007 and 2014 was analyzed. In addition, laboratory parameters including C-reactive protein (CRP), lactate dehydrogenase (LDH), fibrinogen, and D-dimer as possible differentiation markers for graft rejection were determined. In 24 (88.9 %) of the 27 pediatric patients with graft rejection, a significant increase of ferritin levels was observed 1 to 7 days prior to (P < 0.0001) and at the time of graft rejection (P < 0.0001). Moreover, there was an increase of D-dimer, CRP, LDH, and fibrinogen 1-7 days before graft rejection. Ferritin increased significantly at time of VOD (P = 0.0067), at time of intestinal (P < 0.0001) and skin GvHD (P < 0.0001), and at time of sepsis (P = 0.0005) and bacteremia (P = 0.0029). Ferritin might serve as a readily available identification marker for differentiation and identification of adverse events after HSCT in combination with other laboratory markers.

PMID: 26611853 [PubMed - indexed for MEDLINE]

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[Periosteal osteosarcoma - personal experience with five cases].

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[Periosteal osteosarcoma - personal experience with five cases].

Cesk Patol. 2015;51(4):193-8

Authors: Kinkor Z, Šidlová H, Mečiarová I, Švec A, Švajdler Ml M, Vasovčák P, Kodet R, Matějovský Z, Straka Ľ

Abstract
The authors present five cases of periosteal osteosarcoma located in the femur (4) and tibia (1) in children and young adults (1 female and 4 males) with an age range of 9 - 23 years (mean age 15 years). Radiographs in all cases showed a broad-based soft tissue mass attached to the cortex with periosteal reaction and in two of them cortical disruption with extensive medullary involvement. Follow-ups were available in four cases (range 11 - 73 months) and revealed pelvic metastasis after 15 months with ultimately rapid dissemination and death in a 9-year-old girl and metastasis to the humerus after 13 months in a 15-year-old boy. The former tumor widely extended into the medullary cavity and an amputation was carried out, the latter had a pure juxtacortical position and an en block resection was performed; both of them were treated with chemotherapy. All the lesions displayed distinctive structural patterns combining a large island of tumorous cartilage and hypocellular, bland-looking myxoid mesenchymal stroma with abrupt transition between both components. Contrary to conventional osteosarcoma, the delicate flocculent osteoid deposits were produced by innocuous stromal cells lacking apparent atypia. They were strictly situated outside the prevailing chondroid areas and disclosed sometimes only after a meticulous search. Immunohistochemical detection of SATB2, S100protein and D2-40 assisted effectively not only in recognition of the real stromal histogenetic derivation, but also in distinction of true differentiation of a heavily mineralized extracellular matrix. Molecular analysis revealed no IDH1/2 mutation in four examined cases. Regardless of unique low-grade morphology in rare periosteal osteosarcoma, an aggressive therapeutical approach similar to conventional osteosarcoma is justified, particularly in the case of a medullary extension.

PMID: 26585111 [PubMed - indexed for MEDLINE]

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Prevalence of rare EGFR gene mutations in nonsmall-cell lung cancer: a multicenter study on 3856 Polish Caucasian patients.

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Prevalence of rare EGFR gene mutations in nonsmall-cell lung cancer: a multicenter study on 3856 Polish Caucasian patients.

Ann Oncol. 2016 Feb;27(2):358-9

Authors: Krawczyk P, Reszka K, Ramlau R, Powrózek T, Pankowski J, Wojas-Krawczyk K, Kalinka-Warzocha E, Szczęsna A, Nicoś M, Jarosz B, Szyszka-Barth K, Bryl M, Adamowicz K, Szumiło J, Milanowski J

PMID: 26578740 [PubMed - indexed for MEDLINE]

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Rosai-Dorfman Disease of Rare Isolated Spinal Involvement: Report of 4 Cases and Literature Review.

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Rosai-Dorfman Disease of Rare Isolated Spinal Involvement: Report of 4 Cases and Literature Review.

World Neurosurg. 2016 Jan;85:367.e11-6

Authors: Huang BY, Zhang H, Zong WJ, Sun YH

Abstract
BACKGROUND: Rosai-Dorfman disease (RDD) is a rare histioproliferative disorder that only occasionally involves the central nervous system (CNS).
CASE DESCRIPTION: The diagnosis and treatment of 4 patients with isolated spinal RDD are discussed. All 4 patients were treated by total or subtotal surgical resection and none of them experienced recurrence. Histopathologic examination showed a characteristic emperipolesis, and the lymphocytes were engulfed in the S-100-protein-positive histiocytes with no expression of CD1a.
CONCLUSIONS: Preoperative diagnosis of spinal RDD is still challenging because the lesion is usually a dura-based lesion that mimics a meningioma. Surgical resection is an effective treatment, and radiotherapy, steroid therapy, and chemotherapy have not shown reliable therapeutic efficiency.

PMID: 26459700 [PubMed - indexed for MEDLINE]

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Outcome of inferior vena cava and noncaval venous leiomyosarcomas.

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Outcome of inferior vena cava and noncaval venous leiomyosarcomas.

Surgery. 2016 Feb;159(2):613-20

Authors: Illuminati G, Pizzardi G, Calio' F, Pacilè MA, Masci F, Vietri F

Abstract
BACKGROUND: Leiomyosarcoma (LMS) is a rare tumor arising from the smooth muscle cells of arteries and veins. LMS may affect both the inferior vena cava (IVC) and non-IVC veins. Because of its rarity, the experience with the outcome of the disease originating from the IVC compared with that with non-IVC offspring is overall limited. In this study, we compared the clinical features and outcomes after operative resection of IVC and non-IVC LMS to detect possible significant differences that could affect treatment and prognosis.
METHODS: Twenty-seven patients undergoing operative resection of a venous LMS at a single tertiary care center and one secondary care hospital were reviewed retrospectively and divided into 2 groups: IVC-LMS (Group A, n = 18) and non-IVC LMS (Group B, n = 9). As primary end points, postoperative mortality and morbidity, disease-specific survival and, if applicable, patency of venous reconstruction were considered. Bivariate differences were compared with the χ(2) test. Disease-specific survival was expressed by a life-table analysis and compared using the log-rank test.
RESULTS: No postoperative mortality was observed in either group. Postoperative morbidity was 28% in group A and 11% in group B (P = .33). The mean duration of follow-up was 60 months (range, 13-140). Disease-specific survival was 60% in group A and 75% in group B at 3 years (P = .48), and it was 54% in group A and 62% in group B at 5 years (P = .63). Seven grafts were occluded in group A (39%) and 1of 3 were occluded in group B (33%) (P = .85).
CONCLUSION: IVC and non-IVC LMS exhibit similar outcomes in terms of postoperative course and survival. Operative resection associated with vascular reconstruction, if applicable, eventually followed by radiation and chemotherapy may be curative and is associated with good functional results.

PMID: 26435438 [PubMed - indexed for MEDLINE]

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Intradural Spinal Arachnoid Cyst: A Long-Term Postlaminectomy Complication: A Case Report and Review of the Literature.

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Intradural Spinal Arachnoid Cyst: A Long-Term Postlaminectomy Complication: A Case Report and Review of the Literature.

World Neurosurg. 2016 Jan;85:367.e1-4

Authors: Nath PC, Mishra SS, Deo RC, Satapathy MC

Abstract
BACKGROUND: Spinal arachnoid cysts are a rare cause of spinal cord compression. Intradural arachnoid cysts are rarer than extradural arachnoid cysts. Spinal arachnoid cysts are mostly congenital in origin. Arachnoid cysts due to trauma, lumbar puncture, or surgery are rarely reported. Most arachnoid cysts are located posterior to the spinal cord in the thoracic regions. The ideal treatment is laminectomy or laminoplasty with puncture, marsupialization, or excision. But the development of a cervico-thoracic spinal intradural extramedullary arachnoid cyst anteriorly located 28 years after laminectomy is a recognizable complication of laminectomy.
CASE DESCRIPTION: We report here a case of a 45-year-old man who underwent C6-T1 laminectomy at the age of 17 years for cervical intervertebral disc prolapse (C6/7, C7/T1) and compressive myelopathy. Twenty-eight years after laminectomy, he developed spastic quadriparesis and was diagnosed with a spinal intradural extramedullary anterior arachnoid cyst at the laminectomy site with compressive myelopathy.
CONCLUSIONS: So, although laminectomy with excision is usually practiced to treat spinal arachnoid cysts, laminectomy itself is a cause of development of intradural arachnoid cysts.

PMID: 26428320 [PubMed - indexed for MEDLINE]

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Pathogenesis of Delayed Tension Intraventricular Pneumocephalus in Shunted Patient: Possible Role of Nocturnal Positive Pressure Ventilation.

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Pathogenesis of Delayed Tension Intraventricular Pneumocephalus in Shunted Patient: Possible Role of Nocturnal Positive Pressure Ventilation.

World Neurosurg. 2016 Jan;85:365.e17-20

Authors: Salem-Memou S, Vallee B, Jacquesson T, Jouanneau E, Berhouma M

Abstract
BACKGROUND: Delayed intraventricular pneumocephalus is a very rare and potentially serious complication of ventriculoperitoneal shunt. It can occur several months or years after shunting. Its pathogenesis is unclear. We herein discuss the underlying mechanisms and particularly the possible role of positive pressure ventilation.
CASE DESCRIPTION: A 60 year-old man presented with a lateral ventricle neurocytoma microsurgically resected complicated by a late-onset (15 months) postoperative hydrocephalus requiring an adjustable ventriculoperitoneal (VP) shunt. One month later, the patient was diagnosed with a sleep apnea and required a continuous positive airway pressure (CPAP) device. A few weeks afterward the patient presented with headaches and alteration of consciousness. CT-Scan revealed a massive intraventricular pneumocephalus associated with a millimetric left petrous bone defect. A transient breakout of the positive ventilation and a subtemporal surgical repair of the defect led to the rapid resolution of the pneumocephalus.
DISCUSSION: Delayed intraventricular pneumocephalus requires two conditions: a VP shunt and an osteodural defect. The CPAP may play an important trigger role in the pathogenesis of this complication through a ball valve mechanism. The management relies on transient suspension of the positive ventilation and the surgical repair of the identified defect with or without pressure adjustments of the valve.
CONCLUSION: Intraventricular pneumocephalus is a potentially serious complication of patients with a VP shunt and receiving positive pressure ventilation. The introduction of a CPAP device must be discussed with the neurosurgeon beforehand in shunted patients.

PMID: 26363220 [PubMed - indexed for MEDLINE]

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Endoscopic Endonasal Approach in Skull Base Chondrosarcoma Associated with Maffucci Syndrome: Case Series and Literature Review.

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Endoscopic Endonasal Approach in Skull Base Chondrosarcoma Associated with Maffucci Syndrome: Case Series and Literature Review.

World Neurosurg. 2016 Jan;85:365.e7-15

Authors: Beer-Furlan A, Balsalobre L, Vellutini EA, Stamm AC

Abstract
BACKGROUND: Maffucci syndrome is a nonhereditary disorder in which patients develop multiple enchondromas and cutaneous, visceral, or soft tissue hemangiomas. The potential malignant progression of enchondroma into a secondary chondrosarcoma is a well-known fact. Nevertheless, chondrosarcoma located at the skull base in patients with Maffuci syndrome is a very rare condition, with only 18 cases reported in the literature.
CASE DESCRIPTION: We report 2 other cases successfully treated through an expanded endoscopic endonasal approach and discuss the condition based on the literature review.
CONCLUSIONS: Skull base chondrosarcoma associated with Maffucci syndrome is a rare condition. The disease cannot be cured, therefore surgical treatment should be performed in symptomatic patients aiming for maximal tumor resection with function preservation. The endoscopic endonasal approach is a safe and reliable alternative for the management of these tumors.

PMID: 26348567 [PubMed - indexed for MEDLINE]

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Gradually Progressive Symptoms of Normal Pressure Hydrocephalus Caused by an Arachnoid Cyst in the Fourth Ventricle: a Case Report.

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Gradually Progressive Symptoms of Normal Pressure Hydrocephalus Caused by an Arachnoid Cyst in the Fourth Ventricle: a Case Report.

World Neurosurg. 2016 Jan;85:364.e19-22

Authors: Sugimoto T, Uranishi R, Yamada T

Abstract
BACKGROUND: Arachnoid cysts in the fourth ventricle are extremely rare, with only 13 cases having been described in the literature. Especially, only 1 case of a patient older than 70 years has been reported. Arachnoid cysts in the fourth ventricle may cause obstructive hydrocephalus. Here, we report the case of a 72-year-old man who presented with an arachnoid cyst in the fourth ventricle that caused gradually progressive symptoms of normal pressure hydrocephalus.
METHODS: A 72-year-old man complaining of persistent dizziness and gait difficulty was admitted to our hospital due to a gradual worsening of his symptoms and apparent cognitive impairment. Computed tomography scan of the head showed symmetrically dilated third, fourth, and lateral ventricles.
RESULT: Though we performed a ventriculoperitoneal shunt operation, his trunk ataxia persisted. We finally diagnosed an arachnoid cyst in the fourth ventricle by direct ventricular infusion of enhanced material. We performed direct surgical fenestration of the cyst and achieved a good outcome.
CONCLUSION: Arachnoid cysts of the fourth ventricle are exceedingly rare, but it is important to recognize them because they cause normal pressure hydrocephalus symptoms and cerebellar or brainstem deficit. We propose detailed neurologic and radiologic examinations of patients with normal pressure hydrocephalus symptoms to avoid unnecessary shunt.

PMID: 26342780 [PubMed - indexed for MEDLINE]

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The Appropriate Surgical Approach to a Greater Petrosal Nerve Schwannoma in the Setting of Temporal Lobe Edema.

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The Appropriate Surgical Approach to a Greater Petrosal Nerve Schwannoma in the Setting of Temporal Lobe Edema.

World Neurosurg. 2016 Jan;85:364.e5-10

Authors: Kusumi M, Oka H, Aliabadi H, Sato S, Kumabe T

Abstract
BACKGROUND: Facial nerve schwannomas are rare lesions that constitute only 0.8% of all intrapetrous mass lesions. The least frequent lesions are tumors originating in the greater petrosal nerve (GPN). We present a case of a GPN schwannoma with temporal lobe edema in which the patient was operated on using an extradural and intradural approach to prevent complications.
CASE DESCRIPTION: A 66-year-old woman with vertigo and abnormal magnetic resonance imaging findings was referred to our department. Computed tomography scan revealed an isodense subtemporal mass with partial rim calcification and petrosal bone apex erosion. Magnetic resonance imaging confirmed a 22-mm left middle fossa lesion with heterogeneous enhancement and edema of the temporal lobe. A left temporal craniotomy to the middle fossa was performed. The initial extradural exploration revealed the tumor to be in the Glasscock triangle, mainly involving the location of the GPN. The tumor was removed through an intradural approach in piecemeal fashion. Finally, using an extradural and intradural middle fossa approach, the tumor was totally removed, leaving the capsule on the middle fossa floor with continuous facial nerve monitoring. The postoperative course was uneventful without complications of xerophthalmia and facial palsy.
CONCLUSIONS: GPN schwannomas are very rare lesions. The extradural and intradural middle fossa approach was used to preserve the tumor capsule around the GPN. Using this technique, one can safely protect the geniculate ganglion and the GPN.

PMID: 26341443 [PubMed - indexed for MEDLINE]

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Calcifying Pseudoneoplasm of the Cervicomedullary Junction: Case Report and a Literature Review.

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Calcifying Pseudoneoplasm of the Cervicomedullary Junction: Case Report and a Literature Review.

World Neurosurg. 2016 Jan;85:364.e11-8

Authors: Alshareef M, Vargas J, Welsh CT, Kalhorn SP

Abstract
BACKGROUND: Calcifying pseudoneoplasm of the neuroaxis (CAPNON) is a rare, slow-growing tumor of a fibro-osseous origin that may present anywhere in the neuroaxis. Although typically benign, symptoms of CAPNONs typically present secondary to compression and surrounding mass effect. Histologically, the tumor has the characteristics of a foreign body reaction with giant cells, ossification, and the formation of psammoma bodies. On imaging, they can easily be confused with malginant lesions such as chondrosarcoma or chondroblastoma or even more benign pathologies like meningioma.
CASE DESCRIPTION: We present a case of a patient with an incidentally found calcifying pseudoneoplasm involving the cervicomedullary junction with further involvement of the vertebral artery and the hypoglossal nerve. We also review the literature on these tumors to date.
CONCLUSION: Calcifying pseudoneoplasm of the neuroaxis is a slow-growing, benign, noninfiltrative lesion whose pathogensis and natural history remains unclear. It can appear anywhere in the neuroaxis and does not have a prevelant location. Because of the indolent course and relative rarity of this tumor, there are no current guidelines on the immediate and long-term management of CAPNONs. This entity, although quite rare, should be considered in the differential for calcified lesions at the cervicomedullary junction. The consensus for treatment of CAPNONs when symptomatic is surgical resection.

PMID: 26341436 [PubMed - indexed for MEDLINE]

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[Pleural epithelioid hemangioendothelioma: a case report and review of the literature].

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[Pleural epithelioid hemangioendothelioma: a case report and review of the literature].

Zhonghua Jie He He Hu Xi Za Zhi. 2015 Mar;38(3):174-8

Authors: Sanxi A, Yalan B, Qinfeng Z, Xinchao L, Jing Z, Wei Z, Longyun L, Yi X, Wenbing X, Mengzhao W

Abstract
OBJECTIVE: To explore the etiology, clinical manifestation, diagnosis, differential diagnosis, management and prognosis of pleural epithelioid hemangioendothelioma.
METHODS: The clinical data of a patient with pleural epithelioid hemangioend othelioma admitted to Peking Union Medical College Hospital were retrospectively analyzed and the related literature was reviewed. We searched databases PubMed, Embase, Ovid, Cochrane, Wanfang and Chinese National Knowledge infrastructure (CNKI) using the keyword "pleural epithelioid hemangioendothelioma" by December 2013.
RESULTS: The patient was a 40-year-old male presented with chest pain, and his chest CT scan revealed thickening of the left pleura and left pleural effusion. Biopsy of the pleura showed epithelioid tumor cells, and immunohistochemistry was positive for CD31, CD34 and vimentin. From January 1975 to December 2013, 18 related articles were retrieved and 29 cases of pleural epithelioid hemangioendothelioma were reported. Among all 30 cases, there were 20 males and 10 females, ranging from 31 to 82 years old, and the average age was 50. 3 years old. The etiology of the disease remained unknown. Chest pain, cough, and dyspnea were the common symptoms. Computed tomography usually revealed pleural effusion and pleural thickening or mass. Histological examinations revealed mainly epithelioid cells. Immunohistochemical stains were positive for vascular endothelial markers. The mean survival time was 8.2 months.
CONCLUSIONS: Pleural epithelioid hemangioendothelioma is rare and the etiology is unknown. Clinical and imaging manifestations are not specific, and diagnosis is relied on histological findings. It should be differentiated from adenocarcinoma, hemangiosarcoma, mesothelioma and pulmonary epithelioid hemangioendothelioma. There is no effective treatment and its prognosis is poorer than its pulmonary counterpart.

PMID: 26269304 [PubMed - indexed for MEDLINE]

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Primary renal extra-osseous osteosarcoma.

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Primary renal extra-osseous osteosarcoma.

Can J Urol. 2015 Aug;22(4):7929-31

Authors: Flynn KJ, Kaimakliotis HZ, Cheng L, Sundaram CP

Abstract
Primary renal extra-osseous osteosarcoma is an exceedingly rare and deadly kidney neoplasm with only 27 reported cases to date. Extra-osseous osteosarcoma is a mesenchymal sarcoma that produces osteoid, but has no skeletal or periosteal involvement and most commonly arises in the lower extremities. Yet, it can arise in other locations such as the kidney. Extra-osseous osteosarcoma behaves as a separate entity from osseous osteosarcoma and should be treated as such. The treatment is surgical resection. Five year overall survival is 46% for local and 10% for metastatic disease. Additionally, 45%-50% of patients experience disease recurrence. We present a 77-year-old woman who underwent work up for recurrent gross hematuria and subsequently underwent radical nephroureterectomy for presumed upper tract urothelial cell carcinoma. However, pathologic analysis revealed a diagnosis of primary renal extra-osseous osteosarcoma. She is alive with no evidence of disease 30 months after surgery.

PMID: 26267034 [PubMed - indexed for MEDLINE]

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Nodular pulmonary amyloidosis and obvious ossification due to primary pulmonary MALT lymphoma with extensive plasmacytic differentiation: Report of a rare case and review of the literature.

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Nodular pulmonary amyloidosis and obvious ossification due to primary pulmonary MALT lymphoma with extensive plasmacytic differentiation: Report of a rare case and review of the literature.

Int J Clin Exp Pathol. 2015;8(6):7482-7

Authors: Xiang H, Wu Z, Wang Z, Yao H

Abstract
Localized (primary) pulmonary amyloidosis associated with pulmonary low-grade B cell lymphoma is rarely occurred. Here we report an unusual case of nodular pulmonary amyloidosis and obvious ossification due to primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma with extensive plasmacytic differentiation in a 59-year-old man; moreover, two bronchial lymph nodes were involved histologically. The patient underwent a left lower lobectomy along with mediastinal lymphadenectomy. He received no adjuvant therapy and the postoperative course was uneventful within the 14 months follow-up period after his initial diagnosis.

PMID: 26261657 [PubMed - indexed for MEDLINE]

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Carcinosarcoma of the gallbladder: a case report and review of the literature.

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Carcinosarcoma of the gallbladder: a case report and review of the literature.

Int J Clin Exp Pathol. 2015;8(6):7464-9

Authors: Gao S, Huang L, Dai S, Chen D, Dai R, Shan Y

Abstract
Carcinosarcoma of the gallbladder is a rare malignancy characterized by malignant epithelial and mesenchymal components. The disease usually presents at an advanced stage, and as a result, curative resection is uncommon. This report describes a case that underwent curative resection. We herein declare the case of a patient in a 62-year-old male, with carcinosarcoma of the gallbladder with chondroid differentiation. The patient is treated by a simple cholecystectomy, a wedge resection of the underlying liver tissue and the pericholedochal lymph nodes for a tumor which occupied the entire gallbladder. Histologically, the epithelial component of the tumor was composed of adenocarcinoma and the mesenchymal component was composed of fibrosarcoma. The tumor was identified as extend to the serosa tissue and to have metastasized to no lymph node. The prognosis of carcinosarcoma of the gallbladder remains poor despite curative resection, and thus, the authors recommend that effort should be made to improve surgical outcomes. The patient survived 13 months and is still alive today.

PMID: 26261654 [PubMed - indexed for MEDLINE]

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Serum levels of hepatocyte growth factor as a potential tumor marker in patients with malignant melanoma.

Serum markers can be important tools for prognostic classification and treatment monitoring in cancer patients. The MAP-kinase pathway, which is upregulated in the majority of melanoma patients, can be activated by hepatocyte-growth factor (HGF) through the proto-oncogene c-MET. The aim of this study was to evaluate the predictive and prognostic value of circulating HGF in terms of treatment outcome and survival compared with a widely established serum marker, protein S-100B, in patients with advanced metastatic melanoma. HGF and S-100B were measured in serum samples of 101 patients with metastatic melanoma (American Joint Committee on Cancer stage IV) before and after treatment and 50 patients with stage I/II melanoma. HGF and S-100B correlated significantly with the stage of disease (P=0.032 and P

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When DNA Repair Goes Wrong: BER-Generated DNA-protein Crosslinks to Oxidative Lesions

Publication date: Available online 20 May 2016
Source:DNA Repair
Author(s): Jason Luis Quiñones, Bruce Demple
Free radicals generate an array of DNA lesions affecting all parts of the molecule. The damage to deoxyribose receives less attention than base damage, even though the former accounts for ∼20% of the total. Oxidative deoxyribose fragments (e.g., 3′-phosphoglycolate esters) are removed by the Ape1 AP endonuclease and other enzymes in mammalian cells to enable DNA repair synthesis. Oxidized abasic sites are initially incised by Ape1, thus recruiting these lesions into base excision repair (BER) pathways. Lesions such as 2-deoxypentos-4-ulose can be removed by conventional (single-nucleotide) BER, which proceeds through a covalent Schiff base intermediate with DNA polymerase β (Polβ) that is resolved by hydrolysis. In contrast, the lesion 2-deoxyribonolactone (dL) must be processed by multinucleotide ("long-patch") BER: attempted repair via the single-nucleotide pathway leads to a dead-end, covalent complex with Polβ crosslinked to the DNA by an amide bond. We recently detected these stable DNA-protein crosslinks (DPC) between Polβ and dL in intact cells. The features of the DPC formation in vivo are exactly in keeping with the mechanistic properties seen in vitro: Polβ-DPC are formed by oxidative agents in line with their ability to form the dL lesion; they are not formed by non-oxidative agents; DPC formation absolutely requires the active-site lysine-72 that attacks the 5′-deoxyribose; and DPC formation depends on Ape1 to incise the dL lesion first. The Polβ-DPC are rapidly processed in vivo, the signal disappearing with a half-life of 15–30min in both mouse and human cells. This removal is blocked by inhibiting the proteasome, which leads to the accumulation of ubiquitin associated with the Polβ-DPC. While other proteins (e.g., topoisomerases) also form DPC under these conditions, 60-70% of the trapped ubiquitin depends on Polβ. The mechanism of ubiquitin targeting to Polβ-DPC, the subsequent processing of the expected 5′-peptidyl-dL, and the biological consequences of unrepaired DPC are important to assess. Many other lyase enzymes that attack dL can also be trapped in DPC, so the processing mechanisms may apply quite broadly.



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Molecular mechanisms of DNA damage recognition for mammalian nucleotide excision repair

Publication date: Available online 20 May 2016
Source:DNA Repair
Author(s): Kaoru Sugasawa
For faithful DNA repair, it is crucial for cells to locate lesions precisely within the vast genome. In the mammalian global genomic nucleotide excision repair (NER) pathway, this difficult task is accomplished through multiple steps, in which the xeroderma pigmentosum group C (XPC) protein complex plays a central role. XPC senses the presence of oscillating 'normal' bases in the DNA duplex, and its binding properties contribute to the extremely broad substrate specificity of NER. Unlike XPC, which acts as a versatile sensor of DNA helical distortion, the UV-damaged DNA-binding protein (UV-DDB) is more specialized, recognizing UV-induced photolesions and facilitating recruitment of XPC. Recent single-molecule analyses and structural studies have advanced our understanding of how UV-DDB finds its targets, particularly in the context of chromatin. After XPC binds DNA, it is necessary to verify the presence of damage in order to avoid potentially deleterious incisions at damage-free sites. Accumulating evidence suggests that XPA and the helicase activity of transcription factor IIH (TFIIH) cooperate to verify abnormalities in DNA chemistry. This chapter reviews recent findings about the mechanisms underlying the efficiency, versatility, and accuracy of NER.



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Protein oxidation, UVA and human DNA repair

Publication date: Available online 20 May 2016
Source:DNA Repair
Author(s): Peter Karran, Reto Brem
Solar UVB is carcinogenic. Nucleotide excision repair (NER) counteracts the carcinogenicity of UVB by excising potentially mutagenic UVB-induced DNA lesions. Despite this capacity for DNA repair, non-melanoma skin cancers and apparently normal sun-exposed skin contain huge numbers of mutations that are mostly attributable to unrepaired UVB-induced DNA lesions. UVA is about 20-times more abundant than UVB in incident sunlight. It does cause some DNA damage but this does not fully account for its biological impact. The effects of solar UVA are mediated by its interactions with cellular photosensitizers that generate reactive oxygen species (ROS) and induce oxidative stress. The proteome is a significant target for damage by UVA-induced ROS. In cultured human cells, UVA-induced oxidation of DNA repair proteins inhibits DNA repair. This article addresses the possible role of oxidative stress and protein oxidation in determining DNA repair efficiency − with particular reference to NER and skin cancer risk.



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Mutational Signature of Aristolochic Acid: clue to the recognition of a global disease

Publication date: Available online 20 May 2016
Source:DNA Repair
Author(s): Thomas A. Rosenquist, Arthur P. Grollman
Mutational signatures associated with specific forms of DNA damage have been identified in several forms of human cancer. Such signatures provide information regarding mechanisms of tumor induction which, in turn, can reduce exposure to carcinogens by shaping public health policy. Using a molecular epidemiologic approach that takes advantage of recent advances in genome sequencing while applying sensitive and specific analytical methods to characterize DNA damage, it has become increasingly possible to establish causative linkages between certain environmental mutagens and disease risk, In this perspective, we use aristolochic acid, a human carcinogen and nephrotoxin found in Aristolochia herbs, to illustrate the power and effectiveness of this multidisciplinary approach. The genome-wide mutational signature for this toxin, detected initially in cancers of the upper urinary tract, has subsequently been associated with cancers of the liver and kidney. These findings have significant implications for global public health, especially in China, where millions of individuals have used Aristolochia herbal remedies as part of traditional Chinese medicine and, thus, are at risk of developing aristolochic acid nephropathy and/or upper urinary tract carcinomas. The studies reported here set the stage for research into prevention and early detection, both of which will be required to manage a potentially devastating global disease.



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Protein damage, radiation sensitivity and aging

Publication date: Available online 20 May 2016
Source:DNA Repair
Author(s): Miroslav Radman
This paper promotes a concept that protein damage determines radiation resistance and underlies aging and age-related diseases. The first bottleneck in cell recovery from radiation damage is functional (proteome) rather than informational (DNA), since prokaryotic and eukaryotic cell death correlates with incurred protein, but not DNA, damage. Proteome protection against oxidative damage determines survival after ionizing or UV irradiation, since sufficient residual proteome activity is required to turn on the DNA damage response, activating DNA repair and protein renewal processes.Extreme radiation and desiccation resistance of rare bacterial and animal species is accounted for by exceptional constitutive proteome protection against oxidative damage. After excessive radiation their well-protected proteome faithfully reconstitutes a transcription-competent genome from hundreds of DNA fragments. The observation that oxidative damage targeted selectively to cellular proteins results in aging-like phenotypes suggests that aging and age-related diseases could be phenotypic consequences of proteome damage patterns progressing with age. (149 words)



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XPA: A key scaffold for human nucleotide excision repair

Publication date: Available online 20 May 2016
Source:DNA Repair
Author(s): Norie Sugitani, Robert M. Sivley, Kelly E. Perry, John A. Capra, Walter J. Chazin
Nucleotide excision repair (NER) is essential for removing many types of DNA lesions from the genome, yet the mechanisms of NER in humans remain poorly understood. This review summarizes our current understanding of the structure, biochemistry, interaction partners, mechanisms, and disease-associated mutations of one of the critical NER proteins, XPA.



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Metronidazole Containing Pyrazole Derivatives Potently Inhibit Tyrosyl-tRNA Synthetase: Design, Synthesis and Biological Evaluation

Abstract

As an important enzyme in bacterial protein biosynthesis, tyrosyl-tRNA synthetase (TyrRS) has been an absorbing therapeutic target for exploring novel antibacterial agents. A series of metronidazole-based antibacterial agents has been synthesized and identified as TyrRS inhibitors with low cytotoxicity and significant antibacterial activity, especially against Gram-negative organisms. Out of the compounds obtained, 4f is the most potent agent which inhibited the growth of Pseudomonas aeruginosa ATCC 13525 (MIC = 0.98 μg/mL), and exhibited TryRS inhibitory activity (IC₅₀ = 0.92 μM). Docking simulation was performed to further understand its potency. Membrane-mediated apoptosis in P. aeruginosa was verified by flow cytometry.

This article is protected by copyright. All rights reserved.

A series of metronidazole-pyrazole derivatives were designed and synthesized as anti-bacterial agent to target the tyrosyl-tRNA synthetase (TyrRS). All of the synthesized compounds were examined by bioactivity assays, and the structure-activity relationship was also discussed. Membrane-mediated apoptosis in P. aeruginosa induced by compound 4f was verified by flow cytometry.

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Carbon nanotube modification of microbial fuel cell electrodes

Publication date: 15 November 2016
Source:Biosensors and Bioelectronics, Volume 85
Author(s): Alireza Ahmadian Yazdi, Lorenzo D'Angelo, Nada Omer, Gracia Windiasti, Xiaonan Lu, Jie Xu
The use of carbon nanotubes (CNTs) for energy harvesting devices is preferable due to their unique mechanical, thermal, and electrical properties. On the other hand, microbial fuel cells (MFCs) are promising devices to recover carbon–neutral energy from the organic matters, and have been hindered with major setbacks towards commercialization. Nanoengineered CNT–based materials show remarkable electrochemical properties, and therefore have provided routes towards highly effective modification of MFC compartments to ultimately reach the theoretical limits of biomass energy recovery, low–cost power production, and thus the commercialization of MFCs. Moreover, these CNT–based composites offer significant flexibility in the design of MFCs that enable their use for a broad spectrum of applications ranging from scaled–up power generation to medically related devices. This article reviews the recent advances in the modification of MFCs using CNTs and CNT–based composites, and the extent to which each modification route impacts MFC power and current generation.



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Assessment of Surgery Residents’ Interpersonal Communication Skills: Validation Evidence for the Communication Assessment Tool in a Simulation Environment

Publication date: Available online 20 May 2016
Source:Journal of Surgical Education
Author(s): Amber W. Trickey, Anna B. Newcomb, Melissa Porrey, Jeffrey Wright, Jordan Bayless, Franco Piscitani, Paula Graling, Jonathan Dort
ObjectivesAlthough development of trainees' competency in interpersonal communication is essential to high-quality patient-centered surgical care, nontechnical skills present assessment challenges for residency program directors. The Communication Assessment Tool (CAT) demonstrated internal reliability and content validity for general surgery residents, though the tool has not yet been applied in simulation. The study provides validation evidence for using the CAT to assess surgical residents' interpersonal communication skills in simulation scenarios.DesignSimulations of delivering bad news were completed by 21 general surgery residents during a mandatory communication curriculum. Upon completion of the 10-minute scenario, standardized participants (SPs) assessed performance using the 14-item CAT rating scale and individually provided feedback to residents. Discrete communication behaviors were recorded on video review by a trained blinded observer. The traits emotional intelligence questionnaire short form (TEIQue-SF) was completed by the residents 6 months later. SP-CAT ratings are evaluated with respect to learner characteristics, observed behaviors, and TEIQue results.SettingSurgical simulation center in a 900-bed tertiary care hospital.ParticipantsGeneral surgery residents were targeted learners. Trauma survivors network volunteers served as SPs, acting as a family member of a patient who developed an intracerebral hemorrhage following a small bowel procedure.ResultsDiscrete communication behaviors were reliably assessed by the observer (interrater reliability with trainer: 89% agreement, κ = 0.77). SP-CAT ratings ranged from 34 to 61. Higher SP-CAT ratings were correlated with positive communication behaviors (Spearman ρ = 0.42, p = 0.056). Total TEIQue was positively related to SP-CAT ratings (ρ = 0.42, p = 0.061). The TEIQue emotionality factor was strongly correlated with SP-CAT ratings (ρ = 0.52, p = 0.016).ConclusionsThe CAT demonstrates content validity in a simulation environment with former patients acting as SPs. This study provides validation evidence relating the SP-CAT to discrete observations of communication behaviors by a trained, reliable observer as well as residents' self-reported emotional intelligence traits.



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National Orthopedic Residency Attrition: Who Is At Risk?

Publication date: Available online 20 May 2016
Source:Journal of Surgical Education
Author(s): Jennifer M. Bauer, Ginger E. Holt
BackgroundNational U.S. orthopedic resident attrition rates have been historically low, but no literature exists as to the characteristics of those who leave nor the circumstance of the departure. We aimed to determine factors that may place a resident at higher risk for attrition. Additionally, we planned to determine whether the 2003-work hour restriction affected attrition rate.Materials and MethodsAll orthopedic surgery residency program directors in the United States were surveyed on demographic data for their current resident class, the number of residents who left the program, as well as demographic description for each of the residents who left their program from 1998 to 2013. Exclusion criteria included military programs and those younger than 3 years. All data were deidentified and compared to the Accreditation Council for Graduate Medical Education Data Resource book to protect against sample error in respondents.ResultsOf 146 programs included, the overall response rate was 54% of residency directors, representing 51% of orthopedic residents. The respondent demographic make-up of 13.7% female, and average program size of 22.3 residents, compared similarly to the Accreditation Council for Graduate Medical Education national average of 13% female and 23-resident program size. Compared to all respondents, residents who left their program were more likely to be female (27%, p = 0.0018), single (51%, p = 0.0028), and without children (80%, p = 0.0018). There was no statistical difference based on minority status or 2003-instituted work hour restriction. Of those who left, 45% transferred to another specialty, 34% were dismissed, 14% voluntarily withdrew or cited personal reasons, and 6% transferred to another orthopedic program. The most common specialties to transfer into were radiology (30%), emergency medicine (25%), and anesthesia (18%).ConclusionsOrthopedic residents who are female, single, or without children are statistically more likely to undergo attrition. Consideration could be given to targeted mentoring of these resident groups.



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Vitamin D: The Need of the Hour

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