Sphingobacterium spiritivorum is a glucose non-fermenting Gram-negative rod, formerly classified as one of the Flavobacterium species. It is characterized by a large number of cellular...
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Παρασκευή 29 Σεπτεμβρίου 2017
Sphingobacterium spiritivorum bacteremia due to cellulitis in an elderly man with chronic obstructive pulmonary disease and congestive heart failure: a case report
Overt Skeletal Metastases in a Patient of Occult (Microscopic) Follicular Thyroid Carcinoma: a Rare Case
Abstract
Occult follicular thyroid carcinoma (FTC) presenting as distant metastases is a rare occurrence. However, despite being occult in majority of these cases, primary tumor can be detected on thyroid imaging or during surgery. Here, we present an extremely rare case of an occult FTC with overt skeletal metastases in which primary tumor was discernible only on microscopic examination.
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Overt Skeletal Metastases in a Patient of Occult (Microscopic) Follicular Thyroid Carcinoma: a Rare Case
Abstract
Occult follicular thyroid carcinoma (FTC) presenting as distant metastases is a rare occurrence. However, despite being occult in majority of these cases, primary tumor can be detected on thyroid imaging or during surgery. Here, we present an extremely rare case of an occult FTC with overt skeletal metastases in which primary tumor was discernible only on microscopic examination.
http://ift.tt/2fYjxj0
MYC Controls Human Pluripotent Stem Cell Fate Decisions through Regulation of Metabolic Flux
Publication date: Available online 28 September 2017
Source:Cell Stem Cell
Author(s): Timothy S. Cliff, Tianming Wu, Benjamin R. Boward, Amelia Yin, Hang Yin, John N. Glushka, James H. Prestegaard, Stephen Dalton
As human pluripotent stem cells (hPSCs) exit pluripotency, they are thought to switch from a glycolytic mode of energy generation to one more dependent on oxidative phosphorylation. Here we show that, although metabolic switching occurs during early mesoderm and endoderm differentiation, high glycolytic flux is maintained and, in fact, essential during early ectoderm specification. The elevated glycolysis observed in hPSCs requires elevated MYC/MYCN activity. Metabolic switching during endodermal and mesodermal differentiation coincides with a reduction in MYC/MYCN and can be reversed by ectopically restoring MYC activity. During early ectodermal differentiation, sustained MYCN activity maintains the transcription of "switch" genes that are rate-limiting for metabolic activity and lineage commitment. Our work, therefore, shows that metabolic switching is lineage-specific and not a required step for exit of pluripotency in hPSCs and identifies MYC and MYCN as developmental regulators that couple metabolism to pluripotency and cell fate determination.
Graphical abstract
Teaser
Cliff et al. show that, contrary to prior understanding, a metabolic switch away from glycolysis is not a required step for human pluripotent stem cell differentiation, and that, in fact, differentiation to ectoderm requires maintenance of high glycolytic flux via MYC/MYCN activity, indicating its role as a developmental regulator.http://ift.tt/2xOTWmu
Jak1 Integrates Cytokine Sensing to Regulate Hematopoietic Stem Cell Function and Stress Hematopoiesis
Publication date: Available online 28 September 2017
Source:Cell Stem Cell
Author(s): Maria Kleppe, Matthew H. Spitzer, Sheng Li, Corinne E. Hill, Lauren Dong, Efthymia Papalexi, Sofie De Groote, Robert L. Bowman, Matthew Keller, Priya Koppikar, Franck T. Rapaport, Julie Teruya-Feldstein, Jorge Gandara, Christopher E. Mason, Garry P. Nolan, Ross L. Levine
JAK1 is a critical effector of pro-inflammatory cytokine signaling and plays important roles in immune function, while abnormal JAK1 activity has been linked to immunological and neoplastic diseases. Specific functions of JAK1 in the context of hematopoiesis, and specifically within hematopoietic stem cells (HSCs), have not clearly been delineated. Here, we show that conditional Jak1 loss in HSCs reduces their self-renewal and markedly alters lymphoid/myeloid differentiation in vivo. Jak1-deficient HSCs exhibit decreased competitiveness in vivo and are unable to rescue hematopoiesis in the setting of myelosuppression. They exhibit increased quiescence, an inability to enter the cell cycle in response to hematopoietic stress, and a marked reduction in cytokine sensing, including in response to type I interferons and IL-3. Moreover, Jak1 loss is not fully rescued by expression of a constitutively active Jak2 allele. Together, these data highlight an essential role for Jak1 in HSC homeostasis and stress responses.
Graphical abstract
Teaser
Selective JAK1 inhibition has emerged as a potential strategy for treating autoimmune and hematological diseases. Levine and colleagues show that Jak1 integrates multiple cytokine signals in normal and malignant HSCs to regulate their self-renewal and quiescence, highlighting further potential therapeutic benefits and risks of Jak1 inhibition.http://ift.tt/2xPdas2
Differentiation of Human Pluripotent Stem Cells into Functional Lung Alveolar Epithelial Cells
Publication date: Available online 28 September 2017
Source:Cell Stem Cell
Author(s): Anjali Jacob, Michael Morley, Finn Hawkins, Katherine B. McCauley, J.C. Jean, Hillary Heins, Cheng-Lun Na, Timothy E. Weaver, Marall Vedaie, Killian Hurley, Anne Hinds, Scott J. Russo, Seunghyi Kook, William Zacharias, Matthias Ochs, Katrina Traber, Lee J. Quinton, Ana Crane, Brian R. Davis, Frances V. White, Jennifer Wambach, Jeffrey A. Whitsett, F. Sessions Cole, Edward E. Morrisey, Susan H. Guttentag, Michael F. Beers, Darrell N. Kotton
Lung alveoli, which are unique to air-breathing organisms, have been challenging to generate from pluripotent stem cells (PSCs) in part because there are limited model systems available to provide the necessary developmental roadmaps for in vitro differentiation. Here we report the generation of alveolar epithelial type 2 cells (AEC2s), the facultative progenitors of lung alveoli, from human PSCs. Using multicolored fluorescent reporter lines, we track and purify human SFTPC+ alveolar progenitors as they emerge from endodermal precursors in response to stimulation of Wnt and FGF signaling. Purified PSC-derived SFTPC+ cells form monolayered epithelial "alveolospheres" in 3D cultures without the need for mesenchymal support, exhibit self-renewal capacity, and display additional AEC2 functional capacities. Footprint-free CRISPR-based gene correction of PSCs derived from patients carrying a homozygous surfactant mutation (SFTPB121ins2) restores surfactant processing in AEC2s. Thus, PSC-derived AEC2s provide a platform for disease modeling and future functional regeneration of the distal lung.
Graphical abstract
Teaser
Jacob et al. differentiate human pluripotent stem cells (PSCs) into type II alveolar cells (iAEC2s). They find that iAEC2s display many of the functions, transcriptomic features, and surfactant-processing capacities that characterize primary cells. Finally, they derive AEC2s from gene-edited, patient-specific PSCs to model surfactant protein B deficiency in vitro.http://ift.tt/2xO21YF
The 2017 complete overhaul of adjuvant therapies for high-risk melanoma and its consequences for staging and management of melanoma patients
Source:European Journal of Cancer, Volume 86
Author(s): Alexander M.M. Eggermont, Reinhard Dummer
The spectacular outcomes of the phase III trials regarding nivolumab versus ipilimumab in fully resected stage IIIB/C–IV and of the combination of dabrafenib (D) plus trametinib (T) in BRAF-mutant stage III patients demonstrate that effective treatments in advanced melanoma are also highly effective in the adjuvant setting. In 2016, an overall survival benefit with adjuvant high-dose ipilimumab was demonstrated, and the European Organisation for Research and Treatment of Cancer trial 1325 comparing pembrolizumab versus placebo will complete the picture in the early 2018. Toxicity profiles are in line with the experience in advanced melanoma, i.e. favourable for the anti-PD1 agents and for D + T and problematic for ipilimumab. The 2017 outcomes are practice changing and put an end to the use of interferon (IFN) and ipilimumab. In countries with only access to IFN, its use can be restricted to patients with ulcerated melanoma, based on the individual patient data meta-analysis recently published. Because of the results of the Melanoma Sentinel Lymph node Trial-2 (MSLT-2) trial, completion lymph node dissection (CLND) will decrease sharply, leading to a lack of optimal prognostic information. Prognosis in sentinel node–positive stage IIIA/B patients is extremely heterogeneous with 5-year survival rates varying from 90% to 40% and depends mostly on the number of positive nodes identified by CLND. This information is crucial for clinical decision-making. How to guarantee optimal staging information needs to be discussed urgently. Further improvements of adjuvant therapies will have to address all these questions as well as the exploration of neoadjuvant use of active drugs and combination approaches. Important paradigm shifts in the management of high-risk melanoma patients are upon us.
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Multidisciplinary quality assurance and control in oncological trials: Perspectives from European Organisation for Research and Treatment of Cancer (EORTC)
Source:European Journal of Cancer, Volume 86
Author(s): Members of EORTC QACDenisLacombeCorneelCoensChristinede BalincourtLisaLicitraMarcelden DulkJean-PascalMachielsDamienWeberMartinSpahnRobertoSalgadoBerndKasperPeterHau.Working Groups of Scientific ExpertsFayBetsouKozoKataokaCarmelaCaballeroYanLiuCoenHurkmansSergeEvrard
Quality assurance (QA) programmes are one of the mainstays of clinical research and constitute the pillars on which European Organisation for Research Treatment of Cancer (EORTC) delivers multidisciplinary therapeutic progress. Changing practice treatments require solid evidence-based data, which can only be achieved if integral QA is part of the infrastructure sustaining research projects. Cancer treatment is a multimodality approach, which is often applied either in sequence and/or in combination. Each modality plays a key role in cancer control. The modalities by which QA is applied varies substantially within and across the disciplines. In addition, translational and diagnostic disciplines take an increasing role in the era of precision medicine. Building on the structuring effect of clinical research with fully integrated multidisciplinary QA programmes associated with the solutions addressing the chain of custody for biological material and data integrity as well as compliance ensure at the same time validity of clinical research output but also have a training effect on health care providers, who are more likely to apply such principles as routine. The principles of QA are therefore critical to be embedded in multidisciplinary infrastructure to guarantee therapeutic progress. These principles also provide the basis for the functioning of multidisciplinary tumour board. However, technical, operational and economic challenges which go with the implementation of such programmes require optimal know-how and the coordination of the multiple expertise and such efforts are best achieved through centralised infrastructure.
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ASF1A Facilitates DNA Double-Strand Break Repair by NHEJ [Research Watch]
ASF1A promotes NHEJ over homologous recombination for DNA double-strand break (DSB) repair.
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Tigecycline May Selectively Target Leukemic Stem Cells in CML [Research Watch]
Tigecycline inhibits mitochondrial oxidative phosphorylation to target leukemic stem cells (LSC).
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Durvalumab Promising for NSCLC [News in Brief]
Checkpoint inhibitor increases progression-free survival, response rate in patients with stage III non–small cell lung cancer.
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PPARG-Activated Bladder Cancer Cells Exhibit a PPARG Dependency [Research Watch]
PPARG-selective inverse agonists can suppress proliferation in PPARG-activated bladder cancer cells.
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The EGFR-AS1 Long Noncoding RNA Modulates EGFR TKI Sensitivity [Research Watch]
A synonymous EGFR mutation promotes TKI response by reducing EGFR-AS1 levels in squamous-cell cancer.
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Fatty-Acid Catabolism Promotes T-cell Revitalization in Melanoma [Research Watch]
A hypoxic and hypoglycemic tumor microenvironment induces the metabolic reprogramming of CD8+ TILs.
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Somatic super-enhancer duplications and hotspot mutations lead to oncogenicactivation of the KLF5 transcription factor [Research Articles]
The Krüppel-like family of transcription factors (KLF) plays critical roles in human development and is associated with cancer pathogenesis. KLF5 has been shown to promote cancer cell proliferation and tumorigenesis, and to be genomically amplified in cancer cells. We recently reported that the KLF5 gene is also subject to other types of somatic coding and noncoding genomic alterations in diverse cancer types. Here we show that these alterations activate KLF5 by three distinct mechanisms. 1) Focal amplification of super-enhancers activates KLF5 expression in squamous cell carcinomas. 2) Missense mutations disrupt KLF5-FBXW7 interactions to increase KLF5 protein stability in colorectal cancer. 3) Cancer type-specific hotspot mutations within a zinc-finger DNA binding domain of KLF5 change its DNA binding specificity and reshape cellular transcription. Utilizing data from CRISPR/Cas9 gene knockout screening, we reveal that cancer cells with KLF5 overexpression are dependent on KLF5 for their proliferation, suggesting KLF5 as a putative therapeutic target.
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mTOR and HDAC inhibitors converge on the TXNIP/thioredoxin pathway to cause catastrophic oxidative stress and regression of RAS-driven tumors [Research Articles]
While agents that inhibit specific oncogenic kinases have been successful in a subset of cancers, there are currently few treatment options for malignancies that lack a targetable oncogenic driver. Nevertheless, during tumor evolution cancers engage a variety of protective pathways, which may provide alternative actionable dependencies. Here we identify a promising combination therapy that kills NF1-mutant tumors by triggering catastrophic oxidative stress. Specifically, we show that mTOR and HDAC inhibitors kill aggressive nervous system malignancies and shrink tumors in vivo by converging on the TXNIP/thioredoxin anti-oxidant pathway, through cooperative effects on chromatin and transcription. Accordingly, TXNIP triggers cell death by inhibiting thioredoxin and activating Apoptosis Signal-regulating Kinase 1 (ASK1). Moreover, this drug combination also kills NF1-mutant and KRAS-mutant non-small cell lung cancers. Together these studies identify a promising therapeutic combination for several currently untreatable malignancies, and reveal a protective nodal point of convergence between these important epigenetic and oncogenic enzymes.
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Intraoperative 5-aminolevulinic acid-induced photodynamic diagnosis of metastatic brain tumors with histopathological analysis
Abstract
Background
Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is a promising real-time navigation method in the surgical resection of malignant gliomas. In order to determine whether this method is applicable to metastatic brain tumors, we evaluated the usefulness of intraoperative fluorescence patterns and histopathological features in patients with metastatic brain tumors.
Methods
We retrospectively reviewed the cases of 16 patients with metastatic brain tumors who underwent intraoperative 5-ALA fluorescence-guided resection. Patients were given 20 mg/kg of 5-ALA orally 2 h prior to the surgery. High-powered excitation illumination and a low-pass filter (420, 450, or 500 nm) were used to visualize the fluorescence of protoporphyrin IX (PpIX), the 5-ALA metabolite. We evaluated the relationships between the fluorescence and histopathological findings in both tumoral and peritumoral brain tissue.
Results
Tumoral PpIX fluorescence was seen in only 5 patients (31%); in the remaining 11 patients (69%), there was no fluorescence in the tumor bulk itself. In 14 patients (86%), vague fluorescence was seen in peritumoral brain tissue, at a thickness of 2–6 mm. The histopathological examination found cancer cell invasion of adjacent brain tissue in 75% of patients (12/16), at a mean ± SD depth of 1.4 ± 1.0 mm (range 0.2–3.4 mm) from the microscopic border of the tumor. There was a moderate correlation between vague fluorescence in adjacent brain tissue and the depth of cancer cell invasion (P = 0.004).
Conclusion
Peritumoral fluorescence may be a good intraoperative indicator of tumor extent, preceding more complete microscopic gross total resection.
Trial registration
Institutional Review Board of Osaka Medical College No. 42, registered February 17, 1998, and No. 300, registered April 1, 2008. They were retrospectively registered.
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Targeting RNA helicases in cancer: The translation trap
Publication date: Available online 28 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Marise R. Heerma van Voss, Paul J. van Diest, Venu Raman
Cancer cells are reliant on the cellular translational machinery for both global elevation of protein synthesis and the translation of specific mRNAs that promote tumor cell survival. Targeting translational control in cancer is therefore increasingly recognized as a promising therapeutic strategy. In this regard, DEAD/H box RNA helicases are a very interesting group of proteins, with several family members regulating mRNA translation in cancer cells. In this review, we delineate the mechanisms by which DEAD/H box proteins modulate oncogenic translation and how inhibition of these RNA helicases can be exploited for anti-cancer therapeutics.
http://ift.tt/2fF2ZQv
Intraoperative 5-aminolevulinic acid-induced photodynamic diagnosis of metastatic brain tumors with histopathological analysis
Abstract
Background
Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is a promising real-time navigation method in the surgical resection of malignant gliomas. In order to determine whether this method is applicable to metastatic brain tumors, we evaluated the usefulness of intraoperative fluorescence patterns and histopathological features in patients with metastatic brain tumors.
Methods
We retrospectively reviewed the cases of 16 patients with metastatic brain tumors who underwent intraoperative 5-ALA fluorescence-guided resection. Patients were given 20 mg/kg of 5-ALA orally 2 h prior to the surgery. High-powered excitation illumination and a low-pass filter (420, 450, or 500 nm) were used to visualize the fluorescence of protoporphyrin IX (PpIX), the 5-ALA metabolite. We evaluated the relationships between the fluorescence and histopathological findings in both tumoral and peritumoral brain tissue.
Results
Tumoral PpIX fluorescence was seen in only 5 patients (31%); in the remaining 11 patients (69%), there was no fluorescence in the tumor bulk itself. In 14 patients (86%), vague fluorescence was seen in peritumoral brain tissue, at a thickness of 2–6 mm. The histopathological examination found cancer cell invasion of adjacent brain tissue in 75% of patients (12/16), at a mean ± SD depth of 1.4 ± 1.0 mm (range 0.2–3.4 mm) from the microscopic border of the tumor. There was a moderate correlation between vague fluorescence in adjacent brain tissue and the depth of cancer cell invasion (P = 0.004).
Conclusion
Peritumoral fluorescence may be a good intraoperative indicator of tumor extent, preceding more complete microscopic gross total resection.
Trial registration
Institutional Review Board of Osaka Medical College No. 42, registered February 17, 1998, and No. 300, registered April 1, 2008. They were retrospectively registered.
http://ift.tt/2fyiuWJ
Kids First Pediatric Research Program Moves Forward
Progress continues to be made with the Gabriella Miller Kids First Research Program, which is creating opportunities for investigators from different research communities to share resources and collaborate on research into childhood cancers and certain birth defects.
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Kids First Pediatric Research Program Moves Forward
Progress continues to be made with the Gabriella Miller Kids First Research Program, which is creating opportunities for investigators from different research communities to share resources and collaborate on research into childhood cancers and certain birth defects.
http://ift.tt/2xRH1At
NLRC and NLRX gene family mRNA expression and prognostic value in hepatocellular carcinoma
Abstract
Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR)C and NLRX family proteins play a key role in the innate immune response. The relationship between these proteins and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic significance of NLRC and NLRX family protein levels in HCC patients. Data from 360 HCC patients in The Cancer Genome Atlas database and 231 patients in the Gene Expression Omnibus database were analyzed. Kaplan–Meier analysis and a Cox regression model were used to determine median survival time (MST) and overall and recurrence-free survival by calculating the hazard ratio (HR) and 95% confidence interval (CI). High NOD2 and low NLRX1 expression in tumor tissue was associated with short MST (P = 0.012 and 0.014, respectively). A joint-effects analysis of NOD2 and NLRX1 combined revealed that groups III and IV had reduced risk of death from HCC as compared to group I (adjusted P = 0.001, adjusted HR = 0.31, 95% CI = 0.16–0.61 and adjusted P = 0.043, adjusted HR = 0.63, 95%CI = 0.41–0.99, respectively). NOD2 and NLRX1 expression levels are potential prognostic markers in HCC following hepatectomy.
Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR)C and NLRX family proteins play a key role in the innate immune response. The relationship between these proteins and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic significance of NLRC and NLRX family protein levels in HCC patients.
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NLRC and NLRX gene family mRNA expression and prognostic value in hepatocellular carcinoma
Abstract
Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR)C and NLRX family proteins play a key role in the innate immune response. The relationship between these proteins and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic significance of NLRC and NLRX family protein levels in HCC patients. Data from 360 HCC patients in The Cancer Genome Atlas database and 231 patients in the Gene Expression Omnibus database were analyzed. Kaplan–Meier analysis and a Cox regression model were used to determine median survival time (MST) and overall and recurrence-free survival by calculating the hazard ratio (HR) and 95% confidence interval (CI). High NOD2 and low NLRX1 expression in tumor tissue was associated with short MST (P = 0.012 and 0.014, respectively). A joint-effects analysis of NOD2 and NLRX1 combined revealed that groups III and IV had reduced risk of death from HCC as compared to group I (adjusted P = 0.001, adjusted HR = 0.31, 95% CI = 0.16–0.61 and adjusted P = 0.043, adjusted HR = 0.63, 95%CI = 0.41–0.99, respectively). NOD2 and NLRX1 expression levels are potential prognostic markers in HCC following hepatectomy.
Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR)C and NLRX family proteins play a key role in the innate immune response. The relationship between these proteins and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic significance of NLRC and NLRX family protein levels in HCC patients.
http://ift.tt/2wnU09j
Genetic heterogeneity of uncharacterized childhood autoimmune diseases with lymphoproliferation
Abstract
Autoimmune diseases in children are rare and can be difficult to diagnose. Single causative genes have been identified for some pediatric autoimmune diseases. Such orphan diseases may not be diagnosed properly due to the variability of patients' phenotypes. Guidelines for the diagnostic process need to be developed. Fifteen patients with uncharacterized childhood autoimmune diseases with lymphoproliferation that had negative testing for autoimmune lymphoproliferative syndrome were subjected to whole-exome sequencing to identify genes associated with these conditions. Five causative genes, CTLA4, STAT3, TNFAIP3, IKZF1, and PSTPIP1, were identified. These genes should be considered as candidates for uncharacterized childhood autoimmune diseases with lymphoproliferation.
http://ift.tt/2fvXPT7
Genetic heterogeneity of uncharacterized childhood autoimmune diseases with lymphoproliferation
Abstract
Autoimmune diseases in children are rare and can be difficult to diagnose. Single causative genes have been identified for some pediatric autoimmune diseases. Such orphan diseases may not be diagnosed properly due to the variability of patients' phenotypes. Guidelines for the diagnostic process need to be developed. Fifteen patients with uncharacterized childhood autoimmune diseases with lymphoproliferation that had negative testing for autoimmune lymphoproliferative syndrome were subjected to whole-exome sequencing to identify genes associated with these conditions. Five causative genes, CTLA4, STAT3, TNFAIP3, IKZF1, and PSTPIP1, were identified. These genes should be considered as candidates for uncharacterized childhood autoimmune diseases with lymphoproliferation.
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Grainyhead-like 2 (GRHL2) regulates epithelial plasticity in pancreatic cancer progression
Abstract
The epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) contribute to cancer metastasis of pancreatic ductal adenocarcinoma (PDAC). We explored the role of grainyhead-like 2 (GRHL2), a suppressor of EMT, in the progression of PDAC. Expressions of GRHL2 were assessed using surgically resected PDAC tissues by immunohistochemistry analysis, and in vitro using human and mouse PDAC cells. Effects on epithelial plasticity and stemness of GRHL2 were examined in vitro using liver metastatic PDAC cells (CFPAC-1) with GRHL2 knockdown by specific siRNAs. GRHL2 has a significantly positive correlation with E-cadherin and CD133 in 155 resected human primary PDAC tissues. GRHL2 is highly expressed in liver metastatic cells than in primary invasive cells of both human and mouse PDAC, accompanied by a positive correlation with E-cadherin expression. GRHL2 knockdown CFPAC-1 cells demonstrated morphological changes into mesenchymal appearances and reduced proliferation through EMT. Notably, knockdown studies followed by flow cytometry analysis for a subpopulation of CD133+ showed that GRHL2 facilitates CFPAC-1 cells to maintain stem-like characters including self-renewal capacity and anoikis resistance. GRHL2 regulates epithelial plasticity along with stemness in PDAC, both of which are crucial for metastasis, implicating the possibility of GRHL2 as a therapeutic target for PDAC liver metastasis.
GRHL2 has a significantly positive correlation with E-cadherin and CD133 in 155 resected human primary PDAC tissues. GRHL2 is highly expressed in liver metastatic cells than in primary invasive cells of both human and mouse PDAC, accompanied by a positive correlation with E-cadherin expression. Knockdown studies followed by flow cytometry analysis for a subpopulation of CD133+ showed that GRHL2 facilitates CFPAC-1 cells to maintain stem-like characters including self-renewal capacity and anoikis resistance.
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Expression profiling of long noncoding RNA identifies lnc-MMP3-1 as a prognostic biomarker in external auditory canal squamous cell carcinoma
Abstract
Our previous studies suggested external auditory canal squamous cell carcinoma (EACSCC) is a rare malignancy with heterogeneous outcomes. This study aimed to identify lncRNA profile of EACSCC and determine the clinical application. Differential expression genes (DEGs) were investigated in EACSCC by whole transcriptome lncRNA arrays (GPL23178). RT-PCR was used to quantify the microarray data. Bioinformatics analyses were performed to evaluate DEGs regulations in gene ontology and cellular pathways. Fluorescence in situ hybridization (FISH) was utilized to validate lncRNA expression. The overall survival was determined by Kaplan–Meier and log-rank analyses. Our microarrays data had been submitted to Gene Expression Omnibus (GSE98912). We identified 5621 DEGs (3185 mRNAs, 2436 lncRNAs) in EACSCC. Lnc-MMP3-1 was the top one upregulated lncRNA in EACSCC with fold change of 237.2 (P < 0.001). RT-PCR results showed similar expression levels as microarrays data. Bioinformatics analyses indicated development of EACSCC was involved in aberrant alternations of multiple biological processes and cellular pathways. FSIH assays also found lnc-MMP3-1 was significantly differentially overexpressed in EACSCC (P < 0.001). Tumor lnc-MMP3-1 levels were closely associated with differentiation degree (P = 0.016), tumor invasion (P = 0.015) and TNM stage (P = 0.015). Moreover, lnc-MMP3-1 expression was a significant prognostic factor in EACSCC (χ2 = 4.276, P = 0.039). The study is the first screening and analysis of lncRNAs profile in EACSCC and provides new insights into pathogenesis of this rare disease. Our findings offered convincing evidences that lnc-MMP3-1 is a novel survival predictor of EACSCC patients.
The study is the first analysis of lncRNAs profile in external auditory canal squamous cell carcinoma and provides new insights into molecular pathogenesis. We also demonstrated that lnc-MMP3-1 is a novel prognostic predictor for this rare disease.
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The application of crowdsourcing approaches to cancer research: a systematic review
Abstract
Crowdsourcing is "the practice of obtaining participants, services, ideas, or content by soliciting contributions from a large group of people, especially via the Internet." (Ranard et al. J. Gen. Intern. Med. 29:187, 2014) Although crowdsourcing has been adopted in healthcare research and its potential for analyzing large datasets and obtaining rapid feedback has recently been recognized, no systematic reviews of crowdsourcing in cancer research have been conducted. Therefore, we sought to identify applications of and explore potential uses for crowdsourcing in cancer research. We conducted a systematic review of articles published between January 2005 and June 2016 on crowdsourcing in cancer research, using PubMed, CINAHL, Scopus, PsychINFO, and Embase. Data from the 12 identified articles were summarized but not combined statistically. The studies addressed a range of cancers (e.g., breast, skin, gynecologic, colorectal, prostate). Eleven studies collected data on the Internet using web-based platforms; one recruited participants in a shopping mall using paper-and-pen data collection. Four studies used Amazon Mechanical Turk for recruiting and/or data collection. Study objectives comprised categorizing biopsy images (n = 6), assessing cancer knowledge (n = 3), refining a decision support system (n = 1), standardizing survivorship care-planning (n = 1), and designing a clinical trial (n = 1). Although one study demonstrated that "the wisdom of the crowd" (NCI Budget Fact Book, 2017) could not replace trained experts, five studies suggest that distributed human intelligence could approximate or support the work of trained experts. Despite limitations, crowdsourcing has the potential to improve the quality and speed of research while reducing costs. Longitudinal studies should confirm and refine these findings.
Crowdsourcing has the potential to improve the quality and speed of cancer research while reducing costs. Thus, it is critical to increase the visibility and accessibility of crowdsourcing methods, perhaps by providing online educational offerings to cancer researchers.
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Grainyhead-like 2 (GRHL2) regulates epithelial plasticity in pancreatic cancer progression
Abstract
The epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) contribute to cancer metastasis of pancreatic ductal adenocarcinoma (PDAC). We explored the role of grainyhead-like 2 (GRHL2), a suppressor of EMT, in the progression of PDAC. Expressions of GRHL2 were assessed using surgically resected PDAC tissues by immunohistochemistry analysis, and in vitro using human and mouse PDAC cells. Effects on epithelial plasticity and stemness of GRHL2 were examined in vitro using liver metastatic PDAC cells (CFPAC-1) with GRHL2 knockdown by specific siRNAs. GRHL2 has a significantly positive correlation with E-cadherin and CD133 in 155 resected human primary PDAC tissues. GRHL2 is highly expressed in liver metastatic cells than in primary invasive cells of both human and mouse PDAC, accompanied by a positive correlation with E-cadherin expression. GRHL2 knockdown CFPAC-1 cells demonstrated morphological changes into mesenchymal appearances and reduced proliferation through EMT. Notably, knockdown studies followed by flow cytometry analysis for a subpopulation of CD133+ showed that GRHL2 facilitates CFPAC-1 cells to maintain stem-like characters including self-renewal capacity and anoikis resistance. GRHL2 regulates epithelial plasticity along with stemness in PDAC, both of which are crucial for metastasis, implicating the possibility of GRHL2 as a therapeutic target for PDAC liver metastasis.
GRHL2 has a significantly positive correlation with E-cadherin and CD133 in 155 resected human primary PDAC tissues. GRHL2 is highly expressed in liver metastatic cells than in primary invasive cells of both human and mouse PDAC, accompanied by a positive correlation with E-cadherin expression. Knockdown studies followed by flow cytometry analysis for a subpopulation of CD133+ showed that GRHL2 facilitates CFPAC-1 cells to maintain stem-like characters including self-renewal capacity and anoikis resistance.
http://ift.tt/2xHtUzz
Expression profiling of long noncoding RNA identifies lnc-MMP3-1 as a prognostic biomarker in external auditory canal squamous cell carcinoma
Abstract
Our previous studies suggested external auditory canal squamous cell carcinoma (EACSCC) is a rare malignancy with heterogeneous outcomes. This study aimed to identify lncRNA profile of EACSCC and determine the clinical application. Differential expression genes (DEGs) were investigated in EACSCC by whole transcriptome lncRNA arrays (GPL23178). RT-PCR was used to quantify the microarray data. Bioinformatics analyses were performed to evaluate DEGs regulations in gene ontology and cellular pathways. Fluorescence in situ hybridization (FISH) was utilized to validate lncRNA expression. The overall survival was determined by Kaplan–Meier and log-rank analyses. Our microarrays data had been submitted to Gene Expression Omnibus (GSE98912). We identified 5621 DEGs (3185 mRNAs, 2436 lncRNAs) in EACSCC. Lnc-MMP3-1 was the top one upregulated lncRNA in EACSCC with fold change of 237.2 (P < 0.001). RT-PCR results showed similar expression levels as microarrays data. Bioinformatics analyses indicated development of EACSCC was involved in aberrant alternations of multiple biological processes and cellular pathways. FSIH assays also found lnc-MMP3-1 was significantly differentially overexpressed in EACSCC (P < 0.001). Tumor lnc-MMP3-1 levels were closely associated with differentiation degree (P = 0.016), tumor invasion (P = 0.015) and TNM stage (P = 0.015). Moreover, lnc-MMP3-1 expression was a significant prognostic factor in EACSCC (χ2 = 4.276, P = 0.039). The study is the first screening and analysis of lncRNAs profile in EACSCC and provides new insights into pathogenesis of this rare disease. Our findings offered convincing evidences that lnc-MMP3-1 is a novel survival predictor of EACSCC patients.
The study is the first analysis of lncRNAs profile in external auditory canal squamous cell carcinoma and provides new insights into molecular pathogenesis. We also demonstrated that lnc-MMP3-1 is a novel prognostic predictor for this rare disease.
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The application of crowdsourcing approaches to cancer research: a systematic review
Abstract
Crowdsourcing is "the practice of obtaining participants, services, ideas, or content by soliciting contributions from a large group of people, especially via the Internet." (Ranard et al. J. Gen. Intern. Med. 29:187, 2014) Although crowdsourcing has been adopted in healthcare research and its potential for analyzing large datasets and obtaining rapid feedback has recently been recognized, no systematic reviews of crowdsourcing in cancer research have been conducted. Therefore, we sought to identify applications of and explore potential uses for crowdsourcing in cancer research. We conducted a systematic review of articles published between January 2005 and June 2016 on crowdsourcing in cancer research, using PubMed, CINAHL, Scopus, PsychINFO, and Embase. Data from the 12 identified articles were summarized but not combined statistically. The studies addressed a range of cancers (e.g., breast, skin, gynecologic, colorectal, prostate). Eleven studies collected data on the Internet using web-based platforms; one recruited participants in a shopping mall using paper-and-pen data collection. Four studies used Amazon Mechanical Turk for recruiting and/or data collection. Study objectives comprised categorizing biopsy images (n = 6), assessing cancer knowledge (n = 3), refining a decision support system (n = 1), standardizing survivorship care-planning (n = 1), and designing a clinical trial (n = 1). Although one study demonstrated that "the wisdom of the crowd" (NCI Budget Fact Book, 2017) could not replace trained experts, five studies suggest that distributed human intelligence could approximate or support the work of trained experts. Despite limitations, crowdsourcing has the potential to improve the quality and speed of research while reducing costs. Longitudinal studies should confirm and refine these findings.
Crowdsourcing has the potential to improve the quality and speed of cancer research while reducing costs. Thus, it is critical to increase the visibility and accessibility of crowdsourcing methods, perhaps by providing online educational offerings to cancer researchers.
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Risk-reducing salpingo-oophorectomy in BRCA1 and BRCA2 mutated patients: an evidence-based approach on what women should know
Source:Cancer Treatment Reviews
Author(s): F. De Felice, C. Marchetti, S. Boccia, A. Romito, C. Sassu, MG. Porpora, L. Muzii, V. Tombolini, P. Benedetti Panici
This review is focused on the ovarian cancer risk reduction management in BRCA mutation carriers and is intended to assist with clinical decision-making. Obviously, treatment decisions must be based on the available evidence. Despite risk-reducing salpingo-oophorectomy is firmly recommended, several separate questions can be raised to address the variety of intense controversy of this approach. A special emphasis lies in the effective preventive surgical measure against ovarian cancer risk, in an attempt to detect the optimal timing and mitigate the impact on patients. The long term implications of risk-reducing salpingo-oophorectomy as well as hormone replacement therapy are also actively debated. This is expected to represent an opportunity for improved management modelling of BRCA mutated patients.
http://ift.tt/2xDcjLv
Trends in prescribing systemic treatment and overall survival for non-small cell lung cancer stage IIIB/IV in the Netherlands: 2008–2012
Publication date: December 2017
Source:Cancer Epidemiology, Volume 51
Author(s): Bas J.M. Peters, Christine M. Cramer-vd Welle, Arthur A.J. Smit, Franz M.N.H. Schramel, Ewoudt M.W. van de Garde
BackgroundThe present study aims to give a detailed overview of day-to-day practice in the systemic treatment of NSCLC stage IIIB/IV and its clinical outcomes in six large teaching hospitals in the Netherlands in the period 2008–2012.MethodsA retrospective observational cohort study was conducted in the Care for Outcome registry. Patients diagnosed with stage IIIB/IV NSCLC were included and drug data were collected. Outcomes included percentage of patients treated with systemic treatment, percentage of different first line treatment options, survival, and number and percentage of switches, dose reductions (<80% of the initial dose), and early discontinuation (<4 cycles). Descriptive analyses were conducted per hospital, year of diagnosis and several patient characteristics. Predictors for early discontinuation were explored in a logistic regression model.ResultsOverall, 47,9% of 2158 patients that were included received systemic treatment and 33,7% of those received second line treatment. Treatment frequencies were different between age categories, disease stage, PS and hospital (p<0.001). Half of the patients received <4 cycles and dose reductions were found for 20% of all patients. Interhospital differences were observed for early discontinuation and the number of switches. PS2-3 was associated with early discontinuation (OR 1.97 (p=0,007). Median survival was not different between hospitals and years of diagnosis.DiscussionWe provided detailed overview of day-to-day systemic treatment of NSCLC for six hospitals that (a) can fuel interhospital discussion to streamline treatment towards best practice and (b) can serve as reference data for follow-up of the adoption of novel systemic treatment options for advanced lung cancer.
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Trends in prescribing systemic treatment and overall survival for non-small cell lung cancer stage IIIB/IV in the Netherlands: 2008–2012
Publication date: December 2017
Source:Cancer Epidemiology, Volume 51
Author(s): Bas J.M. Peters, Christine M. Cramer-vd Welle, Arthur A.J. Smit, Franz M.N.H. Schramel, Ewoudt M.W. van de Garde
BackgroundThe present study aims to give a detailed overview of day-to-day practice in the systemic treatment of NSCLC stage IIIB/IV and its clinical outcomes in six large teaching hospitals in the Netherlands in the period 2008–2012.MethodsA retrospective observational cohort study was conducted in the Care for Outcome registry. Patients diagnosed with stage IIIB/IV NSCLC were included and drug data were collected. Outcomes included percentage of patients treated with systemic treatment, percentage of different first line treatment options, survival, and number and percentage of switches, dose reductions (<80% of the initial dose), and early discontinuation (<4 cycles). Descriptive analyses were conducted per hospital, year of diagnosis and several patient characteristics. Predictors for early discontinuation were explored in a logistic regression model.ResultsOverall, 47,9% of 2158 patients that were included received systemic treatment and 33,7% of those received second line treatment. Treatment frequencies were different between age categories, disease stage, PS and hospital (p<0.001). Half of the patients received <4 cycles and dose reductions were found for 20% of all patients. Interhospital differences were observed for early discontinuation and the number of switches. PS2-3 was associated with early discontinuation (OR 1.97 (p=0,007). Median survival was not different between hospitals and years of diagnosis.DiscussionWe provided detailed overview of day-to-day systemic treatment of NSCLC for six hospitals that (a) can fuel interhospital discussion to streamline treatment towards best practice and (b) can serve as reference data for follow-up of the adoption of novel systemic treatment options for advanced lung cancer.
http://ift.tt/2fDWCNg
Periprosthetic total knee fracture after remote reconstruction of the anterior cruciate ligament: a case report
Distal femoral fracture is a rare, but significant, postoperative complication of anterior cruciate ligament reconstruction. However, there has not been a reported case of periprosthetic total knee arthroplast...
http://ift.tt/2hAczoh
Five-field IMRT Class solutions and dosimetric planning guidelines for implementing accelerated partial breast irradiation
Source:Practical Radiation Oncology
Author(s): Sarah Quirk, Petra Grendarova, Michael Roumeliotis
PurposeA comprehensive set of planning guidelines was developed to aid in reproducible dosimetric results for external beam accelerated partial breast irradiation (APBI). Methodology for development of class solutions for dosimetric planning of the APBI technique, including dose constraint recommendations, is presented for target coverage and conformity as well as normal tissues.Methods and MaterialsA conservative patient setup was simulated on a TrueBeam™ linear accelerator and a comprehensive arrangement of gantry and couch angles were measured for clearance. This provided the foundation for available beam arrangements to develop reproducible and conformal five-field IMRT partial breast plans. Forty patients were planned. Patient plans were assessed according to anatomy specific features, such as laterality and seroma location within the breast.Results and DiscussionClearance tables are presented to give permissible gantry and couch orientations according to measurements facilitated by patient simulation. Beam arrangement class solutions are presented for left and right-sided APBI patients. Dosimetric recommendations are made based on the results of 40 patient plans. The median and range, describing target coverage and target conformity are reported, as well as normal tissue constraints for ipsilateral lung, ipsilateral breast, heart, liver, and contralateral breast. In all cases, the dose recommendations were at least as strict as multi-institutional accelerated partial breast irradiation trials. In the case of ipsilateral lung and ipsilateral breast, the planning recommendations are more stringent.ConclusionsAccelerated partial breast irradiation using a five-field IMRT technique was comprehensively developed and evaluated to provide recommendations yielding highly conformal and reproducible treatment plans. This provides a clear method to implement external beam APBI planning and delivery.
from Cancer via ola Kala on Inoreader http://ift.tt/2fwliDO
via IFTTT
Five-field IMRT Class solutions and dosimetric planning guidelines for implementing accelerated partial breast irradiation
Source:Practical Radiation Oncology
Author(s): Sarah Quirk, Petra Grendarova, Michael Roumeliotis
PurposeA comprehensive set of planning guidelines was developed to aid in reproducible dosimetric results for external beam accelerated partial breast irradiation (APBI). Methodology for development of class solutions for dosimetric planning of the APBI technique, including dose constraint recommendations, is presented for target coverage and conformity as well as normal tissues.Methods and MaterialsA conservative patient setup was simulated on a TrueBeam™ linear accelerator and a comprehensive arrangement of gantry and couch angles were measured for clearance. This provided the foundation for available beam arrangements to develop reproducible and conformal five-field IMRT partial breast plans. Forty patients were planned. Patient plans were assessed according to anatomy specific features, such as laterality and seroma location within the breast.Results and DiscussionClearance tables are presented to give permissible gantry and couch orientations according to measurements facilitated by patient simulation. Beam arrangement class solutions are presented for left and right-sided APBI patients. Dosimetric recommendations are made based on the results of 40 patient plans. The median and range, describing target coverage and target conformity are reported, as well as normal tissue constraints for ipsilateral lung, ipsilateral breast, heart, liver, and contralateral breast. In all cases, the dose recommendations were at least as strict as multi-institutional accelerated partial breast irradiation trials. In the case of ipsilateral lung and ipsilateral breast, the planning recommendations are more stringent.ConclusionsAccelerated partial breast irradiation using a five-field IMRT technique was comprehensively developed and evaluated to provide recommendations yielding highly conformal and reproducible treatment plans. This provides a clear method to implement external beam APBI planning and delivery.
http://ift.tt/2fwliDO
Embolization of a cavernous carotid fistula through the vein of Labbe: a new alternative transvenous access route
Endovascular treatment of carotid cavernous fistulas (CCFs) via a transvenous approach is standard, but in rare cases this approach is challenging due to absence or thrombosis of the commonly used venous routes. A 61-year-old woman presented with a symptomatic CCF with all but one of the venous access routes to the CCF thrombosed, leaving an engorged superficial middle cerebral vein (SMCV) as the only venous outflow from the cavernous sinus. Access to the CCF was made possible after careful navigation of the sigmoid sinus, the vein of Labbé and the SMCV, bypassing the need for surgical access to the SMCV or for a direct transorbital puncture. The CCF was completely occluded by coiling and Onyx embolization. The patient made an uneventful recovery, with resolution of her symptoms. To the best of our knowledge, this access route has not been previously reported in the treatment of CCFs.
http://ift.tt/2x1xfYg
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