Πέμπτη 3 Μαρτίου 2016
Response to Re: Hepatic resection for malignant liver tumours in the elderly: a systematic review and meta-analysis
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Requesting a magnetic resonance imaging in a patient with a pre-existing implant: a practical surgical guide
Post-oesophagectomy mortality: the centralization debate revisited
Re: Long-term results of the cutting seton for high anal fistula
Re: Hepatic resection for malignant liver tumours in the elderly: a systematic review and meta-analysis
Response to Re: Nausea, vomiting and return of bowel function after colorectal surgery
Medicine in small doses
Upper Airway Endoscopy to Evaluate Pediatric Pulmonary Aspiration.In children with chronic aspiration who warrant further evaluation, flexible laryngoscopy alone is not sufficient. There is a high incidence of aspiration-related airway lesions identified on DLB and not seen on flexible laryngoscopy, with 66.3% (110 of 166) of those lesions eventually requiring surgical intervention. Patients 1 year or older with a history of recurrent pneumonia or intubation are more likely to have an aspiration-
Upper Airway Endoscopy to Evaluate Pediatric Pulmonary Aspiration: This medical record review of children who experienced pulmonary aspiration at a tertiary referral children's hospital assesses the ability of direct laryngoscopy and bronchoscopy under general anesthesia to detect aspiration-related airway lesions and identifies clinical characteristics associated with airway lesions.
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Importance There is no consensus on the evaluation of pediatric patients with aspiration.
Objectives To determine the yield of direct laryngoscopy and bronchoscopy (DLB) using general anesthesia in pediatric patients who aspirate and to identify clinical predictors of aspiration-related airway lesions.
Design, Setting, and Participants Retrospective review at a tertiary referral children's hospital. A medical record review was performed on all patients with a documented diagnosis of pulmonary aspiration who underwent DLB using general anesthesia during a 5-year period (January 2010 to December 2014).
Intervention Direct laryngoscopy and bronchoscopy using general anesthesia.
Main Outcomes and Measures Data were collected and analyzed, including age, sex, history of intubation, flexible laryngoscopy results, DLB findings, recurrent pneumonia, and associated diagnoses.
Results Five hundred thirty-two patients met the inclusion criteria. Their mean (SD) age was 2.2 (3.6) years (age range, 0.1-25.0 years), with more than half younger than 1 year. Sixty-two percent (328 of 532) of the participants were male. Flexible laryngoscopy examination alone identified 93 patients with an airway lesion. Direct laryngoscopy and bronchoscopy identified 173 additional diagnoses and had a greater diagnostic yield for airway lesions (45.1% [240 of 532]) than flexible laryngoscopy examination alone (P < .001). Patients with an aspiration-related airway lesion were older (mean [SD] age, 2.7 [3.8] vs 2.2 [3.8] years; P = .02) and more likely to have another aerodigestive disorder than were patients without an airway lesion (21.7% vs 11.6%; P = .004). Older age (adjusted risk ratio [95% CI], 1.37 [1.08-1.73]; P = .01), recurrent pneumonia (1.40 [1.11-1.76];P = .004), and history of intubation (1.35 [1.07-1.70]; P = .01) were significantly associated with the presence of an aspiration-related airway lesion in the multivariable model. Patients with an aspiration-related airway lesion were less likely to have neurologic disease than were patients without an airway lesion (0.50 [0.34-0.73]; P < .001). In all, 66.3% of patients (110 of 166) eventually underwent surgical repair of an identified aspiration-related airway lesion.
Conclusions and Relevance In children with chronic aspiration who warrant further evaluation, flexible laryngoscopy alone is not sufficient. There is a high incidence of aspiration-related airway lesions identified on DLB and not seen on flexible laryngoscopy, with 66.3% (110 of 166) of those lesions eventually requiring surgical intervention. Patients 1 year or older with a history of recurrent pneumonia or intubation are more likely to have an aspiration-related airway lesion.
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25, 50 & 75 years ago
Localized perianal skin necrosis in neutropenic patients
CLPTM1L antibodies for pancreatic and lung cancer therapy
We and others have recently shown Cisplatin Resistance-Related Protein 9 (CRR9)/Cleft Lip and Palate Transmembrane 1-Like (CLPTM1L) to affect survival and proliferation in lung and pancreatic tumor cells. Our research has indicated that CLPTM1L affects multiple survival signaling pathways in tumor cells under oncogenic, genotoxic, and microenvironmental stress. We have confirmed the association of CLPTM1L with pancreatic cancer by demonstrating overexpression of CLPTM1L in pancreatic tumors and poor survival in patients with high tumor expression of CLPTM1L. Predicting a transmembrane structure, we determined that CLPTM1L could be targeted at the plasma membrane. Herein, we describe the development of monoclonal antibodies targeting CLPTM1L. Lead antibodies inhibited surface accumulation of CLPTM1L, Akt phosphorylation, anchorage-independent growth, and chemotherapeutic resistance in lung and pancreatic tumor cells. Gemcitabine promoted a physical interaction between CLPTM1L and p110α in pancreatic tumor cells, which was inhibited by anti-CLPTM1L. In-vivo treatment with anti-CLPTM1L robustly inhibited the growth of both lung and pancreatic adenocarcinoma xenografts. The efficacy of anti-CLPTM1L correlated with specific epitopes representing important targets in human cancers, particularly those driven by KRas, for which effective targeted therapies have been elusive. This study is the first to report cell-surface exposure of the tumor survival protein CLPTM1L and inhibition of the function of surface CLPTM1L with novel, systematically developed inhibitory monoclonal antibodies establishing proof of concept of clinically practical agents inhibiting this compelling new tumor survival target in cancer.
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Predictive biomarkers of venetoclax efficacy in myeloma
BCL-2 family proteins dictate survival of human multiple myeloma (MM) cells making them attractive drug targets. Indeed, MM cells are sensitive to antagonists that selectively target pro-survival proteins such as BCL-2/BCL-X<sub>L</sub> (ABT-737 and ABT-263/navitoclax) or BCL-2 only (ABT-199/GDC-0199/venetoclax). Resistance to these three drugs is mediated by expression of MCL-1. However, given the selectivity profile of venetoclax it is unclear whether co-expression of BCL-X<sub>L</sub> also affects anti-tumor responses to venetoclax in MM. In MM cell lines (n=21) BCL-2 is expressed but sensitivity to venetoclax correlated with high BCL-2 and low BCL-X<sub>L</sub> or MCL-1 expression. MM cells that co-express BCL-2 and BCL-X<sub>L</sub> were resistant to venetoclax but sensitive to a BCL-X<sub>L</sub> selective inhibitor (A-1155463). MM xenograft models that co-expressed BCL-X<sub>L</sub> or MCL-1 with BCL-2 were also resistant to venetoclax. Resistance to venetoclax was mitigated by co-treatment with bortezomib in xenografts that co-expressed BCL-2 and MCL-1 due to upregulation of NOXA, a pro-apoptotic factor that neutralizes MCL-1. In contrast, xenografts that expressed BCL-X<sub>L</sub>, MCL-1 and BCL-2 were more sensitive to the combination of bortezomib with a BCL-X<sub>L </sub>selective inhibitor (A-1331852) but not with venetoclax co-treatment when compared to monotherapies. Immunohistochemistry of MM patient bone marrow biopsies and aspirates (n=95) revealed high levels of BCL-2 and BCL-X<sub>L</sub> in 62% and 43% of evaluable samples, respectively, while 34% were characterized as BCL-2<sup>High</sup>/BCL-X<sub>L</sub><sup>Low</sup>. In addition to MCL-1, our data suggests that BCL-X<sub>L</sub> may also be a potential resistance factor to venetoclax monotherapy and in combination with bortezomib.
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Protein kinase inhibitor H89 enhances immunotoxin activity
HA22 (Moxetumomab pasudotox) is a recombinant immunotoxin (RIT), composed of an anti-CD22 Fv fused to a truncated portion of Pseudomonas exotoxin A. HA22 is in clinical trials to treat patients with hairy cell leukemia and acute lymphoblastic leukemia (ALL). LMB-11 is an improved variant of HA22 with reduced immunogenicity, has a longer half-life in the blood and high activity in vitro and in a Burkitt lymphoma model in vivo. Searching for RIT enhancing combination therapies, we found the protein kinase A inhibitor H89 to enhance LMB-11 and HA22 activity 5- to 10-fold on ALL cell lines and on patient-derived ALL samples. In addition, H89 increased the activity of mesothelin-targeting RITs SS1P (38-fold) and RG7787 (7-fold) against the cervical cancer cell line KB31. Unexpectedly we found that the enhancement by H89 was not due to inhibition of protein kinase A; it was partially recapitulated by inhibition of S6K1, which led to inactivation of its down-stream targets rpS6 and GSK3β, resulting in a fall in MCL1 levels. H89 increased the rate of ADP-ribosylation of eukaryotic elongation factor 2, enhancing the arrest of protein synthesis and the reduction of MCL1 in synergy with the RIT. In summary, H89 increased RIT activity by enhancing the two key events: ADP-ribosylation of eEF2 and reduction of MCL1 levels. Significant enhancement was seen with both CD22- and mesothelin-targeting RITs, indicating that H89 might be a potent addition to RIT treatment of CD22-positive ALL and mesothelin-expressing solid tumors.
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Preclinical Characterization of Entrectinib
Activated ALK and ROS1 tyrosine kinases, resulting from chromosomal rearrangements, occur in a subset of non-small cell lung cancers (NSCLC) as well as other tumor types and their oncogenic relevance as actionable targets has been demonstrated by the efficacy of selective kinase inhibitors such as crizotinib, ceritinib and alectinib. More recently, low frequency rearrangements of TRK kinases have been described in NSCLC, colorectal carcinoma (CRC), glioblastoma and Spitzoid melanoma. Entrectinib, whose discovery and preclinical characterization are reported herein, is a novel, potent inhibitor of ALK, ROS1 and importantly, of TRK family kinases which shows promise for therapy of tumors bearing oncogenic forms of these proteins. Proliferation profiling against over 200 human tumor cell lines revealed that entrectinib is exquisitely potent in vitro against lines that are dependent on the drug's pharmacological targets. Oral administration of entrectinib to tumor-bearing mice induced regression in relevant human xenograft tumors, including the TRKA-dependent colorectal carcinoma KM12, ROS1-driven tumors and several ALK-dependent models of different tissue origins including a model of brain-localized lung cancer metastasis. Entrectinib is currently showing great promise in Phase I/II clinical trials, including the first documented objective responses to a TRK inhibitor in CRC and in NSCLC. The drug is thus potentially suited to the therapy of several molecularly defined cancer settings, especially that of TRK-dependent tumors, for which no approved drugs are currently available.
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BRD4 regulates EZH2 transcription in bladder cancer
People who develop bladder cancer frequently succumb to the intractable disease. Current treatment strategies are limited presumably due to the underlying molecular complexity and insufficient comprehension. Therefore, exploration of new therapeutic targets in bladder cancer remains necessary. Here, we identify that bromodomain-4 protein (BRD4), an important epigenome reader of bromodomain and extraterminal domain (BET) family member, is a key upstream regulator of enhancer of zeste homologue 2 (EZH2), and represents a novel therapeutic target in bladder cancer. We found that BRD4 was significantly overexpressed in bladder cancer cells and tissues. Inhibition of BRD4 decreased bladder cancer cell proliferation concomitantly with the accumulation of cell apoptosis in vitro and suppressed tumor growth in vivo. We further found that suppression of BRD4 decreased the mRNA and protein levels of EZH2, which was reversed by ectopic expression of C-MYC. In particular, individual silencing of BRD4 using shRNA or the BET inhibitor JQ1 strikingly diminished the recruitment of C-MYC to EZH2 promoter in bladder cancer. Briefly, our research reveals that BRD4 positively regulate EZH2 transcription through upregulation of C-MYC, and is a novel promising target for pharmacological treatment in transcriptional program intervention against this intractable disease.
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AR compromises cytotoxicity of NK cells against HCC
Gender disparity has long been considered as a key to fully understand hepatocellular carcinoma development. At the same time, immunotherapy related to interleukin-12 still need more investigation before applied in clinical settings. The aim of this study is to investigate the influence of androgen receptor (AR) on natural killer (NK) cells related innate immune surveillance in liver cancer, and provide a novel therapeutic approach to suppress hepatocellular carcinoma (HCC) via altering IL-12A. By using in vitro cell cytotoxicity test and in vivo liver orthotopic xenograft mice model, we identified the role of AR in modulating NK cells cytotoxicity. Luciferase report assay and chromatin immunoprecipitation assay were applied for mechanism dissection. Immunohistochemistry is performed for sample staining. Our results showed AR could suppress IL-12A expression at the transcriptional level via direct binding to the IL-12A promoter region that resulted in repressing efficacy of NK cell cytotoxicity against HCC, and sorafenib treatment could enhance IL-12A signals via suppressing AR signals. These results not only help to explain the AR roles in the gender disparity of HCC but also provide a potential new therapy to better suppress HCC via combining sorafenib with NK cells related immunotherapy.
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Elevated eIF4E is therapeutic target in Myeloma
eIF4E is the key regulator of protein translation and critical for translation. The oncogenic potential of tumorigenesis which is highly contingent on cap-dependent eIF4E also arises from the critical role in the nuclear export and cytosolic translation of oncogenic transcripts. Inhibition of Exportin1 (XPO1) which is the major nuclear export protein for eIF4E-bound oncoprotein-mRNAs results in decreased tumor cell growth in vitro and vivo suggesting that eIF4E is critical in multiple myeloma (MM). Indeed we found that eIF4E is overexpressed in myeloma cell lines and primary myeloma cells compared to normal plasma cells. While stable overexpression of eIF4E in MM cells significantly increases tumorigenesis, knockdown of eIF4E impairs MM tumor progression in human xenograft mice model. Using a tet-on inducible eIF4E-knockdown system, eIF4E-downregulation, blocks MM tumor growth in vivo correlating with decreased eIF4E expression. Further overexpression and knockdown of eIF4E revealed that eIF4E regulates translation of mRNAs with highly complex 5'-untranslated regions such as c-MYC and C/EBPβ and subsequently proliferation in MM cells, but not in non-malignant bone marrow stromal cells. Since many transcription factors that are critical for MM proliferation exhibit a higher dependency on protein translation, eIF4E is an ideal and selective tool to target MM cell growth.
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GRP78 Increases PDAC Chemoresistance
The prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) is dismal. While gemcitabine (GEM) is the standard chemotherapeutic agent for adjuvant therapy of resectable PDAC, recurrent disease is observed in an alarming number of GEM-treated patients. Regardless of the adjuvant therapy, the vast majority of patients treated with chemotherapy after surgical resection show tumor recurrence. A better understanding of the molecular mechanisms that contribute to chemoresistance woul¬¬¬d aid the development of more effective treatment strategies. GRP78 is an endoplasmic reticulum (ER) chaperone protein that primarily resides in the lumen of the ER and is the master regulator of the unfolded protein response (UPR). Here, we report that expression of GRP78 is significantly higher in GEM-resistant PDAC compared to GEM-sensitive PDAC patient samples. We show that GRP78 induces chemoresistance in PDAC cells. Our results also show that knockdown of GRP78 reduces chemoresistance in PDAC. Finally, we found that IT-139, a ruthenium-based anticancer drug, can overcome GRP78 mediated chemoresistance. In vitro, IT-139 restores sensitivity to cytotoxic drugs in drug resistant PDAC cells and induces twice as much cell death in combination treatment compared with GEM alone. In vivo, a single weekly IT-139 treatment in combination with GEM caused a 35% increase in median survival and a 25% increase in overall survival compared to GEM alone. Collectively, our data show that GRP78 expression promotes chemoresistance in PDAC and therapeutic strategies blocking the activity of GRP78 increase the efficacy of currently available therapies.
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Effects of r-AtHSP70 on breast cancer cells
The chaperone HSP70 protein is widely present in many different tumors and its expression correlates with an increased cell survival, low differentiation and poor therapeutic outcome in human breast cancer. The intracellular protein has prevalently a cytoprotective function, while the extracellular HSP70 mediates immunological responses. Evolutionarily, HSPs are well conserved from prokaryotes to eukaryotes, and human HSP70 shows a strong similarity to that of plant origin. In the present paper, we have tested the potential effect of recombinant HSP70, from Arabidopsis thaliana, on cell survival and metastatic properties of breast cancer cells. Our data show that HSP70 sustains cell viability in MCF-7 and MDA-MB-231 breast tumoral cells and increases Cyclin D1 and Survivin expression. The extracellular HSP70 triggers cell migration and the activation of MMPs particularly in MDA-MB-231 cells. Furthermore, under UV-induced stress condition, the low levels of phospho-AKT were increased by exogenous HSP70, together with the up-regulation of Cyclin D1 particularly in the tumoral cell phenotype. On the other hand, UV increased TP53 expression and the co-incubation of HSP70 lowers the TP53 levels similar to the control. These findings correlate with the cytoprotective and anti-apoptotic role of HSPs, as reported in different cellular contexts. This is the first study on mammary cells that highlights how the heterologous HSP70 from Arabidopsis thaliana sustains cell survival prevalently in breast cancer cell types, thus maintaining their metastatic potential. Therefore, targeting HSP70 would be of clinical importance since HSP70 blocking selectively targets tumor cells, in which it supports cell growth and survival.
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Polymer therapeutics overcome chemotherapy resistance
The success of chemotherapy is limited by poor selectivity of active drugs combined with occurrence of tumor resistance. New star-like structured N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based drug delivery systems containing Doxorubicin (Dox) attached via a pH-sensitive hydrazone bond were designed and investigated for their ability to overcome chemotherapy resistance. These conjugates combine two strategies to achieve a high drug concentration selectively at the tumor site: (I) high accumulation by passive tumor targeting based on enhanced permeability and retention (EPR) - effect and (II) pH-sensitive site-specific drug release due to an acidic tumor microenvironment. Mice bearing Dox resistant xenograft tumors were treated with Dox, PBS, pHPMA precursor or pHPMA-Dox conjugate at different equivalent doses of 5mg/kg bodyweight Dox up to a 7-fold total dose using different treatment schedules. Intratumoral drug accumulation was analyzed by fluorescence imaging utilizing intrinsic fluorescence of Dox. Free Dox induced significant toxicity but hardly any tumor inhibiting effects. Administering of at least 3-fold dose of pHPMA-Dox conjugate was necessary to induce a transient response whereas doses of about 5- to 6-fold induced strong regressions. Tumors completely disappeared in some cases. The onset of response was differential delayed depending on the tumor model which could be ascribed to distinct characteristics of the microenvironment. Further fluorescence imaging based analyses regarding underlying mechanisms of the delayed response revealed a related switch to a more supporting intratumoral microenvironment for effective drug release. In conclusion, the present study demonstrates that the concept of tumor site-restricted high-dose chemotherapy is able to overcome therapy resistance.
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Molecular simulation of cyclohexanyl nucleic acid (CNA) duplexes with CNA, DNA and RNA and CNA triloop and tetraloop hairpin structures
Publication date: Available online 3 March 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Matheus Froeyen, Rania Abu el Asrar, Mikhail Abramov, Piet Herdewijn
As part of a selection strategy for artificial nucleic acids (XNA) (to be considered as potential new information systems in vivo), we have carried out a modelling study on cyclohexanyl nucleic acids (CNA) duplexes and hairpins. CNA may form a duplex as well as hairpin structures, having the carbocyclic nucleosides in the 4C1 conformation (with equatorial basis). The geometry of ds CNA is close to that of a HNA:RNA duplex. We demonstrated that CNA triphosphates function as a substrate for polymerases. Modelling experiments indicate that the monomers are probably presented to the polymerase in the 1C4 conformation.
Graphical abstract
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Quinoxalinone (Part II). Discovery of (Z)-3-(2-(pyridin-4-yl)vinyl)quinoxalinone derivates as potent VEGFR-2 kinase inhibitors
Publication date: Available online 3 March 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Leilei Shi, Jianfeng Zhou, Jifeng Wu, Junya Cao, Yuemao Shen, Hua Zhou, Xun Li
Inhibition of VEGFR-2 kinase has been highlighted as one of the well-defined strategies to suppress tumor growth via blockade of angiogenesis. Guided by the principles of bioisosteric replacement and pharmacophoric fragment migration, a series of novel quinoxalinone derivates were designed, synthesized and evaluated for their VEGFR-2 inhibitory potencies. Among them, compounds 7c, 8b, 8c, 8e and 10b displayed antiangiogenic abilities via the in vitro tube formation assay (cellular level) and ex vivo rat aortic ring assay (tissue level) at a low concentration (0.1 μM). By means of in vivo zebrafish embryo model, two (Z)-3-(2-(pyridin-4-yl)vinyl)quinoxalinone derivates 8c and 8e showed significant antiangiogenesis effects, suggesting they have potentials to be developed into antiangiogenesis agents via further structural optimization. Moreover, these two compounds also demonstrated potent inhibition toward VEGFR-2 and B-raf kinases in a low concentration (1 μM). Apossibleinterpretationofour evaluation resulthas been presented by a molecular docking study by docking representative compound 8c with VEGFR-2.
Graphical abstract
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Design, physico-chemical properties and biological evaluation of some new N-[(phenoxy)alkyl]- and N-{[(phenoxy)ethoxy]ethyl}aminoalkanols as anticonvulsant agents
Publication date: Available online 3 March 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): A.M. Waszkielewicz, A. Gunia-Krzyżak, B. Powroźnik, K. Słoczyńska, E. Pękala, M. Walczak, M. Bednarski, E. Żesławska, W. Nitek, H. Marona
A series of thirty N-(phenoxy)alkyl or N-{[2-(phenoxy)ethoxy]ethyl}aminoalkanols has been designed, synthesized and evaluated for anticonvulsant activity in MES, 6 Hz test, and pilocarpine-induced status epilepticus. Among the title compounds, the most promising seems R-(-)-2N-{2-[2-(2,6-dimethylphenoxy)ethoxy]ethyl}aminopropan-1-ol hydrochloride (22a) with proved absolute configuration with X-ray analysis and enantiomeric purity. The compound is effective in MES test with ED50=12.92 mg/kg b.w. and its rotarod TD50=33.26 mg/kg b.w. The activity dose is also effective in a neurogenic pain model – the formalin test. Within high throughput profile assay, among eighty one targets, the strongest affinity of the compound is observed towards σ receptors and 5-HT transporter and the compound does not bind to hERG. It also does not exhibit mutagenic properties in the Vibrio harveyi test. Moreover, murine liver microsomal assay and pharmacokinetics profile (mice, i.v., p.o., i.p.) indicate that the liver is the primary site of biotransformation of the compound, suggesting that both 22a and its metabolite(s) are active, compensating probably low bioavailability of the parent molecule.
Graphical abstract
Highlights
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Investigation of 4-amino-5-alkynylpyrimidine-2(1H)-ones as anti-mycobacterial agents
Publication date: Available online 3 March 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Gaurav Garg, Milind Pande, Ambika Agrawal, Jie Li, Rakesh Kumar
In vitro anti-mycobacterial activities of novel 4-amino-5-alkynylpyrimidine-2(1H)-ones were investigated. 4-Amino-5-heptynylpyrimidine-2(1H)-one (3) and 4-amino-5-(2-phenylethynyl)pyrimidine-2(1H)-one (7) displayed potent in vitro activity against Mycobacterium bovis and Mycobacterium tuberculosis. Compounds 3 and 7 were also assessed for their in vivo activity in BALB/c mice infected with M. tuberculosis (H37Ra). Both compounds showed promising in vivo efficacy at a dose of 25 mg/kg for 2 weeks. Importantly, compounds 3 and 7 interacted synergistically with the front-line anti-tuberculosis drug isoniazid in vitro and in vivo. These results suggest that this class of compounds has strong anti-mycobacterial potential.
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Novel squaramides with in vitro liver stage antiplasmodial activity
Publication date: Available online 3 March 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Carlos J.A. Ribeiro, Margarida Espadinha, Marta Machado, Jiri Gut, Lídia M. Gonçalves, Philip J. Rosenthal, Miguel Prudêncio, Rui Moreira, Maria M. M. Santos
A structure-activity relationship study was performed with ten 8-aminoquinoline-squaramides compounds active against liver stage malaria parasites, using human hepatoma cells (Huh7) infected by Plasmodium berghei parasites. In addition, their blood-schizontocidal activity was assessed against chloroquine-resistant W2 strain Plasmodium falciparum. Compound 3 was 7.3-fold more potent than the positive control primaquine against liver-stage parasites, illustrating the importance of the squarate moiety to activity.
Graphical abstract
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Increased risk of melanoma in patients with chronic lymphocytic leukaemia
An increased risk of melanoma has been variously reported in patients with chronic lymphocytic leukaemia (CLL), analogous with other immunosuppressed populations. To fully assess this association, we performed a systematic review and meta-analysis of available evidence from observational cohort studies. All such longitudinal studies of patients diagnosed with CLL that enabled quantitative assessment of the risk of melanoma compared with the general population were eligible. We identified seven studies from a search of all published literature to July 2014 in Medline, Embase and ISI science citation index databases. Data were pooled using a random-effects model. There was an almost four-fold increase in the risk of melanoma in patients with CLL compared with the general population (pooled standardized incidence ratio 3.88 [95% confidence interval (CI) 2.08–7.22]), although significant heterogeneity was evident among studies (I2=96.0%, Phet
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CLAT1 and ASCT2 in patients with surgically resected esophageal squamous cell carcinoma
Background
Amino acid transporters are highly expressed in various human cancers. L-type amino acid transporter 1 (LAT1) and system alanine-serine-cysteine amino acid transporter-2 (ASCT2) play a crucial role in tumor progression and survival. However, the clinicopathological significance of these transporters in patients with esophageal squamous cell carcinoma (ESCC) remains unclear.
Methods
One hundred and fifty-seven patients with surgically resected ESCC were evaluated. Immunohistochemical analysis was performed for LAT1, ASCT2, CD98, Ki-67, and micro-vessel density (MVD), as determined by CD34 expression.
Results
LAT1 and ASCT2 were positively expressed in 59% (93/157) and 48% (76/157) of tumors respectively. LAT1 and ASCT2 expression significantly correlated with T factor, N factor, lymphatic permeation, vascular invasion, and CD98 expression. The 5-year survival rates of LAT1-high and -low and ASCT2-high and -low expressing patients were 62.0% and 69.6% (P < 0.05) and 59.6% and 70.1% (P = 0.068), respectively. The combined positive expression of LAT1 and ASCT2 was a significant prognostic factor in univariate analysis.
Conclusion
High expression of LAT1 and ASCT2 correlates with metastasis and invasion. Accordingly, these proteins could serve as prognostic biomarkers and therapeutic targets for treating patients with surgically resectable ESCC. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.
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Sex hormones and the risk of keratinocyte cancers among women
Abstract
Men are at a higher risk of developing both squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) than women, but there is emerging evidence that women may be experiencing greater increases in the incidence rates of these malignancies than men. One possible explanation is the expanding use of sex steroids among women, although only a few studies have examined this hypothesis. As part of a population-based, case-control study of women in New Hampshire, USA, we sought to evaluate the risk of SCC, BCC, and early-onset BCC in relation to exogenous and endogenous sex hormones. We found that oral contraceptive (OC) use was associated with an increased risk of SCC (OR = 1.4, 95% CI = 1.1-1.8) and BCC (OR = 1.4, 95% CI = 1.0-1.8), particularly high estrogen dose (>50mg) OC use. Hormone replacement therapy (HRT) use also related to SCC, with an elevated OR largely for progestin use (OR = 1.4, 95% CI = 1.1-1.8). Additionally, both OC use and combination HRT use were associated with more aggressive BCC subtypes. In contrast, menstrual and reproductive history did not appear to influence keratinocyte cancer risk in our data. Our findings provide evidence that use of sex steroids may enhance risk of KC. This article is protected by copyright. All rights reserved.
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Autoimmune hemolytic anemia induced by anti-PD-1 therapy in metastatic melanoma
Autoimmune hemolytic anemia induced by anti-PD-1 therapy in metastatic melanoma:
We report the occurrence of autoimmune hemolytic anemia in a patient receiving the anti-PD-1 monoclonal antibody, nivolumab, for metastatic melanoma in the presence of known red cell alloantibodies, despite having received prior ipilimumab without evidence of hemolysis. The patient had a history of multiple red cell alloantibodies and a positive direct antiglobulin test, identified at the time of a prior transfusion, which occurred before treatment with ipilimumab. The patient developed symptomatic warm autoimmune hemolytic anemia after four cycles of treatment with nivolumab. Clinical improvement was noted following cessation of the drug and treatment with corticosteroids. Given that there was no prior history of hemolysis, even during treatment with ipilimumab, we hypothesize that anti-PD-1 therapy disrupted peripheral tolerance, unmasking an underlying autoimmune predisposition.
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Elasticity Modulation of Fibroblast-Derived Matrix for Endothelial Cell Vascular Morphogenesis and Mesenchymal Stem Cell Differentiation
Tissue Engineering Part A , Vol. 0, No. 0.
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Autoimmune hemolytic anemia induced by anti-PD-1 therapy in metastatic melanoma
Autoimmune hemolytic anemia induced by anti-PD-1 therapy in metastatic melanoma:
We report the occurrence of autoimmune hemolytic anemia in a patient receiving the anti-PD-1 monoclonal antibody, nivolumab, for metastatic melanoma in the presence of known red cell alloantibodies, despite having received prior ipilimumab without evidence of hemolysis. The patient had a history of multiple red cell alloantibodies and a positive direct antiglobulin test, identified at the time of a prior transfusion, which occurred before treatment with ipilimumab. The patient developed symptomatic warm autoimmune hemolytic anemia after four cycles of treatment with nivolumab. Clinical improvement was noted following cessation of the drug and treatment with corticosteroids. Given that there was no prior history of hemolysis, even during treatment with ipilimumab, we hypothesize that anti-PD-1 therapy disrupted peripheral tolerance, unmasking an underlying autoimmune predisposition.
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CLAT1 and ASCT2 in patients with surgically resected esophageal squamous cell carcinoma
Background
Amino acid transporters are highly expressed in various human cancers. L-type amino acid transporter 1 (LAT1) and system alanine-serine-cysteine amino acid transporter-2 (ASCT2) play a crucial role in tumor progression and survival. However, the clinicopathological significance of these transporters in patients with esophageal squamous cell carcinoma (ESCC) remains unclear.
Methods
One hundred and fifty-seven patients with surgically resected ESCC were evaluated. Immunohistochemical analysis was performed for LAT1, ASCT2, CD98, Ki-67, and micro-vessel density (MVD), as determined by CD34 expression.
Results
LAT1 and ASCT2 were positively expressed in 59% (93/157) and 48% (76/157) of tumors respectively. LAT1 and ASCT2 expression significantly correlated with T factor, N factor, lymphatic permeation, vascular invasion, and CD98 expression. The 5-year survival rates of LAT1-high and -low and ASCT2-high and -low expressing patients were 62.0% and 69.6% (P < 0.05) and 59.6% and 70.1% (P = 0.068), respectively. The combined positive expression of LAT1 and ASCT2 was a significant prognostic factor in univariate analysis.
Conclusion
High expression of LAT1 and ASCT2 correlates with metastasis and invasion. Accordingly, these proteins could serve as prognostic biomarkers and therapeutic targets for treating patients with surgically resectable ESCC. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.
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Increased risk of melanoma in patients with chronic lymphocytic leukaemia
An increased risk of melanoma has been variously reported in patients with chronic lymphocytic leukaemia (CLL), analogous with other immunosuppressed populations. To fully assess this association, we performed a systematic review and meta-analysis of available evidence from observational cohort studies. All such longitudinal studies of patients diagnosed with CLL that enabled quantitative assessment of the risk of melanoma compared with the general population were eligible. We identified seven studies from a search of all published literature to July 2014 in Medline, Embase and ISI science citation index databases. Data were pooled using a random-effects model. There was an almost four-fold increase in the risk of melanoma in patients with CLL compared with the general population (pooled standardized incidence ratio 3.88 [95% confidence interval (CI) 2.08–7.22]), although significant heterogeneity was evident among studies (I2=96.0%, Phet
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Sex hormones and the risk of keratinocyte cancers among women
Abstract
Men are at a higher risk of developing both squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) than women, but there is emerging evidence that women may be experiencing greater increases in the incidence rates of these malignancies than men. One possible explanation is the expanding use of sex steroids among women, although only a few studies have examined this hypothesis. As part of a population-based, case-control study of women in New Hampshire, USA, we sought to evaluate the risk of SCC, BCC, and early-onset BCC in relation to exogenous and endogenous sex hormones. We found that oral contraceptive (OC) use was associated with an increased risk of SCC (OR = 1.4, 95% CI = 1.1-1.8) and BCC (OR = 1.4, 95% CI = 1.0-1.8), particularly high estrogen dose (>50mg) OC use. Hormone replacement therapy (HRT) use also related to SCC, with an elevated OR largely for progestin use (OR = 1.4, 95% CI = 1.1-1.8). Additionally, both OC use and combination HRT use were associated with more aggressive BCC subtypes. In contrast, menstrual and reproductive history did not appear to influence keratinocyte cancer risk in our data. Our findings provide evidence that use of sex steroids may enhance risk of KC. This article is protected by copyright. All rights reserved.
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FGFR1 in head and neck squamous cell carcinoma
FGFR1 in head and neck squamous cell carcinoma:
Purpose:FGFR1 (fibroblast growth factor receptor 1) is a promising therapeutic target in multiple tumors, including head and neck squamous cell carcinoma (HNSCC). However, resistance remains a major setback. In this study we have investigated the prognostic value of FGFR1 expression in HNSCC, the therapeutic relevance of targeting FGFR with AZD4547, and potential resistant mechanisms. Experimental Design:Immunohistochemistry and fluorescence in situ hybridization were applied on tissue microarrays to investigate FGFR1 protein expression and FGFR1 gene copy-numbers in 452 HNSCC. The sensitivity of HNSCC cell lines to AZD4547, either as single or combination treatment with the EGFR-inhibitor gefitinib, was assessed using long-term colony formation assays, short-term viability assays, and biochemical analysis. Results:FGFR1 protein overexpression occurred in 82% (36/44) of HPV-positive HNSCC and 75% (294/392) of HPV-negative HNSCC and relates with poor overall survival and disease-free survival in HPV-negative HNSCC (HR: 3.07; 95% CI: 1.74-6.90; P = 0.001, HR: 1.53; 95% CI: 1.04-2.39; P = 0.033). Moreover, the FGFR1 gene was amplified in 3% (3/110) of HPV-negative HNSCC. Treatment of the high FGFR1 expressing cell line CCL30 with AZD4547 reduced cell proliferation and FGFR signaling. Two FGFR-amplified cell lines, SCC147 and BICR16, were resistant to AZD4547 treatment due to EGFR signaling. Combined AZD4547 and gefitinib treatment synergistically inhibited proliferation of resistant cell lines. Conclusions Here we identify high FGFR1 expression as a candidate prognostic biomarker in HPV- negative HNSCC. We provide a rationale for treating FGFR1-expressing HNSCC with the FGFR inhibitor AZD4547 and for combining AZD4547 and gefitinib in FGFR inhibitor resistant HNSCC patients.
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Gamma-interferon-inducible lysosomal thiol reductase is upregulated in human melanoma
Gamma-interferon-inducible lysosomal thiol reductase is upregulated in human melanoma:
T-cell-mediated immunity has the ability to produce durable antimelanoma responses, resulting in improved survival of patients with advanced melanoma. Antigen presentation is a key determinant of T-cell responses. Gamma-interferon-inducible lysosomal thiol reductase (GILT) is critical for MHC class II-restricted presentation of multiple melanoma antigens to CD4+ T cells. However, GILT expression in melanoma has not been defined. We evaluated GILT and MHC class II expression in human primary and metastatic melanomas and nevi using immunohistochemical analysis. GILT staining in melanocytes was observed in 70% of primary and 58% of metastatic melanomas versus 0% of nevi. When present, the GILT staining intensity in melanocytes was typically faint. Both GILT and MHC class II expression were increased in melanocytes of primary and metastatic melanomas compared with nevi. GILT staining in antigen-presenting cells (APCs) was detected in 100% of primary and metastatic melanomas versus 31% of nevi, and it was typically intense. GILT expression was increased in APCs of primary and metastatic melanomas compared with nevi, whereas MHC class II had equivalent high expression in APCs of all melanocytic lesions. GILT staining in keratinocytes was detected in 67% of primary melanomas versus 14% of nevi and 6% of metastatic melanomas. GILT, but not MHC class II, expression was increased in keratinocytes of primary melanomas compared with nevi and metastases. GILT expression is anticipated to result in improved presentation of melanoma antigens and more effective antimelanoma T-cell responses. GILT expression may be a biomarker of immune recognition of melanoma.
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The Troubling Trichotomy 10 Years Later–Where Are We Now?
A decade ago, "Nutrition Support and The Troubling Trichotomy: A Call To Action" was published in this journal, identifying existing conflicts among technological, ethical, and legal aspects of nutrition support therapy, particularly in terminal or end-of-life situations. Over the past 10 years, the American Society for Parenteral and Enteral Nutrition and others have responded to the action call. A "state of the trichotomy" reveals that while much has been achieved, differences in all 3 aspects will continue to exist due to their dynamic and ever-changing states. The technology arena has made it possible to increase the delivery of nutrition support in alternative settings with the use of telemedicine and social media. Critical/crucial conversations and earlier declarations of individual wishes for care and treatment while having decision-making capacity have been enhanced with the focus on patient-centered and family-centered care. The definition of death as brain death has been challenged in at least one instance. Conflicts between the state's interests and the individual's interests have added to recent legal controversies. Notwithstanding the progress made over the past 10 years, several challenges remain. The future challenges presented by the Troubling Trichotomy can be best confronted if we ACT—Accountability, Communication, and Teamwork. The focus of teamwork should move from multidisciplinary and interdisciplinary teams to transdisciplinary teams, reflecting the shift to function rather than form presented by the new healthcare environment. The transdisciplinary team will be able address the opportunities of the Troubling Trichotomy in the next decade by incorporating the 12 Cs, as detailed in the article.
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The Troubling Trichotomy 10 Years Later–Where Are We Now?
A decade ago, "Nutrition Support and The Troubling Trichotomy: A Call To Action" was published in this journal, identifying existing conflicts among technological, ethical, and legal aspects of nutrition support therapy, particularly in terminal or end-of-life situations. Over the past 10 years, the American Society for Parenteral and Enteral Nutrition and others have responded to the action call. A "state of the trichotomy" reveals that while much has been achieved, differences in all 3 aspects will continue to exist due to their dynamic and ever-changing states. The technology arena has made it possible to increase the delivery of nutrition support in alternative settings with the use of telemedicine and social media. Critical/crucial conversations and earlier declarations of individual wishes for care and treatment while having decision-making capacity have been enhanced with the focus on patient-centered and family-centered care. The definition of death as brain death has been challenged in at least one instance. Conflicts between the state's interests and the individual's interests have added to recent legal controversies. Notwithstanding the progress made over the past 10 years, several challenges remain. The future challenges presented by the Troubling Trichotomy can be best confronted if we ACT—Accountability, Communication, and Teamwork. The focus of teamwork should move from multidisciplinary and interdisciplinary teams to transdisciplinary teams, reflecting the shift to function rather than form presented by the new healthcare environment. The transdisciplinary team will be able address the opportunities of the Troubling Trichotomy in the next decade by incorporating the 12 Cs, as detailed in the article.
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Molecular simulation of cyclohexanyl nucleic acid (CNA) duplexes with CNA, DNA and RNA and CNA triloop and tetraloop hairpin structures
Publication date: Available online 3 March 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Matheus Froeyen, Rania Abu el Asrar, Mikhail Abramov, Piet Herdewijn
As part of a selection strategy for artificial nucleic acids (XNA) (to be considered as potential new information systems in vivo), we have carried out a modelling study on cyclohexanyl nucleic acids (CNA) duplexes and hairpins. CNA may form a duplex as well as hairpin structures, having the carbocyclic nucleosides in the 4C1 conformation (with equatorial basis). The geometry of ds CNA is close to that of a HNA:RNA duplex. We demonstrated that CNA triphosphates function as a substrate for polymerases. Modelling experiments indicate that the monomers are probably presented to the polymerase in the 1C4 conformation.
Graphical abstract
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Design, physico-chemical properties and biological evaluation of some new N-[(phenoxy)alkyl]- and N-{[(phenoxy)ethoxy]ethyl}aminoalkanols as anticonvulsant agents
Publication date: Available online 3 March 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): A.M. Waszkielewicz, A. Gunia-Krzyżak, B. Powroźnik, K. Słoczyńska, E. Pękala, M. Walczak, M. Bednarski, E. Żesławska, W. Nitek, H. Marona
A series of thirty N-(phenoxy)alkyl or N-{[2-(phenoxy)ethoxy]ethyl}aminoalkanols has been designed, synthesized and evaluated for anticonvulsant activity in MES, 6 Hz test, and pilocarpine-induced status epilepticus. Among the title compounds, the most promising seems R-(-)-2N-{2-[2-(2,6-dimethylphenoxy)ethoxy]ethyl}aminopropan-1-ol hydrochloride (22a) with proved absolute configuration with X-ray analysis and enantiomeric purity. The compound is effective in MES test with ED50=12.92 mg/kg b.w. and its rotarod TD50=33.26 mg/kg b.w. The activity dose is also effective in a neurogenic pain model – the formalin test. Within high throughput profile assay, among eighty one targets, the strongest affinity of the compound is observed towards σ receptors and 5-HT transporter and the compound does not bind to hERG. It also does not exhibit mutagenic properties in the Vibrio harveyi test. Moreover, murine liver microsomal assay and pharmacokinetics profile (mice, i.v., p.o., i.p.) indicate that the liver is the primary site of biotransformation of the compound, suggesting that both 22a and its metabolite(s) are active, compensating probably low bioavailability of the parent molecule.
Graphical abstract
Highlights
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Investigation of 4-amino-5-alkynylpyrimidine-2(1H)-ones as anti-mycobacterial agents
Publication date: Available online 3 March 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Gaurav Garg, Milind Pande, Ambika Agrawal, Jie Li, Rakesh Kumar
In vitro anti-mycobacterial activities of novel 4-amino-5-alkynylpyrimidine-2(1H)-ones were investigated. 4-Amino-5-heptynylpyrimidine-2(1H)-one (3) and 4-amino-5-(2-phenylethynyl)pyrimidine-2(1H)-one (7) displayed potent in vitro activity against Mycobacterium bovis and Mycobacterium tuberculosis. Compounds 3 and 7 were also assessed for their in vivo activity in BALB/c mice infected with M. tuberculosis (H37Ra). Both compounds showed promising in vivo efficacy at a dose of 25 mg/kg for 2 weeks. Importantly, compounds 3 and 7 interacted synergistically with the front-line anti-tuberculosis drug isoniazid in vitro and in vivo. These results suggest that this class of compounds has strong anti-mycobacterial potential.
Graphical abstract
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Quinoxalinone (Part II). Discovery of (Z)-3-(2-(pyridin-4-yl)vinyl)quinoxalinone derivates as potent VEGFR-2 kinase inhibitors
Publication date: Available online 3 March 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Leilei Shi, Jianfeng Zhou, Jifeng Wu, Junya Cao, Yuemao Shen, Hua Zhou, Xun Li
Inhibition of VEGFR-2 kinase has been highlighted as one of the well-defined strategies to suppress tumor growth via blockade of angiogenesis. Guided by the principles of bioisosteric replacement and pharmacophoric fragment migration, a series of novel quinoxalinone derivates were designed, synthesized and evaluated for their VEGFR-2 inhibitory potencies. Among them, compounds 7c, 8b, 8c, 8e and 10b displayed antiangiogenic abilities via the in vitro tube formation assay (cellular level) and ex vivo rat aortic ring assay (tissue level) at a low concentration (0.1 μM). By means of in vivo zebrafish embryo model, two (Z)-3-(2-(pyridin-4-yl)vinyl)quinoxalinone derivates 8c and 8e showed significant antiangiogenesis effects, suggesting they have potentials to be developed into antiangiogenesis agents via further structural optimization. Moreover, these two compounds also demonstrated potent inhibition toward VEGFR-2 and B-raf kinases in a low concentration (1 μM). Apossibleinterpretationofour evaluation resulthas been presented by a molecular docking study by docking representative compound 8c with VEGFR-2.
Graphical abstract
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Novel squaramides with in vitro liver stage antiplasmodial activity
Publication date: Available online 3 March 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Carlos J.A. Ribeiro, Margarida Espadinha, Marta Machado, Jiri Gut, Lídia M. Gonçalves, Philip J. Rosenthal, Miguel Prudêncio, Rui Moreira, Maria M. M. Santos
A structure-activity relationship study was performed with ten 8-aminoquinoline-squaramides compounds active against liver stage malaria parasites, using human hepatoma cells (Huh7) infected by Plasmodium berghei parasites. In addition, their blood-schizontocidal activity was assessed against chloroquine-resistant W2 strain Plasmodium falciparum. Compound 3 was 7.3-fold more potent than the positive control primaquine against liver-stage parasites, illustrating the importance of the squarate moiety to activity.
Graphical abstract
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Elasticity Modulation of Fibroblast-Derived Matrix for Endothelial Cell Vascular Morphogenesis and Mesenchymal Stem Cell Differentiation
SPECTRUM OF LESIONS IN URINARY BLADDER -A HISTOPATHOLOGICAL STUDY
2016-03-03T22-53-24Z
Source: International Journal of Current Research and Review
Pooja Y. Shah, Monika Nanavati, Ravi G. Patel, Hansa M. Goswami.
Background: Diseases of the bladder, particularly inflammation (cystitis), constitute an important source of clinical signs and symptoms. Tumors of the bladder are an important source of both morbidity and mortality. Objectives: 1) To study the histopathological features of various lesions in bladder. 2) To study the frequency of different pathological lesions, particularly Papillary Urothelial Neoplasms in urinary bladder. Results: 35 cases of urinary bladder were received. Out of 35 patients, 27 were males and 8 were females with male to female ratio being 3.38:1.The spectrum of pathological lesions included inflammations, metaplastic lesions, cystic lesions and tumors. Out of 35 cases 12(34.28%) were Non neoplastic lesions and 23(65.71%) were Neoplastic lesions. Among the non neoplastic lesions cystitis (41.67%) was the most common finding. Others were non-specific inflammation due to various etiology, hydatid cyst, benign epithelial inclusion cyst and abscess. Most common age groups affected by the neoplastic lesions were 41-50 years and 61-70 years with male to female ratio being 2.29:1. Among the neoplastic lesions 19(82.60%) cases were of urothelial neoplasms, others being Squamous Cell Carcinoma, Poorly Differentiated Carcinoma with Neuroendocrine differentiation and Paraganglioma. Most common Urothelial neoplasm was Non invasive Papillary Urothelial Carcinoma, Low Grade (9 cases). Among all the bladder biopsies received there was no muscle layer in 3 cases (8.3%). Conclusions: Our study has revealed that the bladder tumors are the commonest lesions in the urinary bladder tissues received and Papillary Urothelial Neoplasms were the predominant tumor type.
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Advaxis Study in Head and Neck Cancer Selected for Late-Breaking Poster at the American Association for Cancer … – Nasdaq
 Proactive Investors USA & Canada | Advaxis Study in Head and Neck Cancer Selected for Late-Breaking Poster at the American Association for Cancer … Nasdaq More than 90 percent of head and neck squamous cell oropharyngeal cancers originate from the mucosal linings of the oral cavity, pharynx, or larynx. Currently, 60 to 80 percent of these cancers are caused by HPV. Head and neck cancers are treated by … Advaxis to present 'remarkable progress' at cancer conferenceProactive Investors USA & Canada all 11 news articles » |
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HISTOMORPHOLOGICAL SPECTRUM OF SKIN ADNEXAL TUMORS AT A TERTIARY CARE HOSPITAL – A RETROSPECTIVE STUDY
2016-03-03T22-53-24Z
Source: International Journal of Current Research and Review
Nirali Amin, Smita Shah, Shreedhan Prajapati, Hansa Goswami.
Background: Skin adnexal tumors (SAT) are a large and diverse group of benign and malignant tumors which exhibit morphological differentiation towards one of the different types of adnexal epithelium present in normal skin: pilosebaeceous unit, eccrine and apocrine. The aim of this study was to recognize various histomorphology of skin adnexal tumors, their frequency, age and site distribution. Methods: It was a retrospective study of 50 cases of skin adnexal turmors, diagnosed on histopathological examination over a period of 3 years (January 2012 to December 2014) in the Department of Pathology, B.J. Medical college, Ahmedabad. Histopathological examination was done on Formalin fixed, Paraffin embedded tissue sections stained with Haematoxylin and Eosin. Special histochemical stains like PAS stain and Reticulin stain were also used, wherever required. Results: Skin adnexal tumors were most common in the age group of 31 to 40 years (38%, 19/50). Male to female ratio was 1:1.27. The head and neck region was the most common site affected (60%) with 32% cases located on the face. 98% cases were benign and only a single case (2%) was malignant. The sweat gland tumors formed the largest group involving 70% of cases followed by hair follicle tumors followed by sebaceous gland tumors. Nodular hidradenoma was the most common benign tumor. Sebaceous carcinoma was the only malignant adnexal tumor reported in our study. Conclusion: Skin adnexal tumors are relatively rare. Benign adnexal tumors are far more common than their malignant counterparts. There is slight Female preponderance. Face is the commonest site for occurrence of SATs. Nodular hidradenoma is the most frequently encountered tumor among all SATs. Histopathological examination is mandatory in their diagnosis as they have very wide spectrum and frequency of differentiation along different lines in the same lesion.
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Patents and Information in Genes: Australia, Policy and the Distinction between DNA and cDNA
The post Patents and Information in Genes: Australia, Policy and the Distinction between DNA and cDNA appeared first on Welcome to Avens.
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Rugae Profiling: A Pilot Study in Udaipur, Rajasthan
The post Rugae Profiling: A Pilot Study in Udaipur, Rajasthan appeared first on Welcome to Avens.
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Bloodless surgery to the scalp
New technique for bloodless surgery to the scalp: Skin cancers such as malignant melanoma, squamous cell carcinoma, and basal cell carcinoma are common on the scalp,1 and the usual treatment is wide local excision with disease- free margins. Margins vary depending on the type of cancer, the size and depth of invasion, and the cytological findings, as described in the British Association of Dermatology guidelines.2
Carbon dioxide laser in scalp tumor surgery
V Sacchini, GF Lovo, N Arioli, M Nava… – Lasers in surgery …, 1984 – Wiley Online Library
… The versatility of the last instrument helps surgeons satisfy many surgical requirements in plastic
and reconstructive fields. … Cot Laser in Scalp Tumor Surgery 267 … be weighed against the benefits
of the greater intraoperative precision in the relatively bloodless surgical fields, and …
Γίνεται αναφορά σε 24 Σχετικά άρθρα Όλες οι 4 εκδοχές Παράθεση Αποθήκευση
[HTML] από mayoclinicproceedings.org
Trichloroacetic acid chemexfoliation (chemical peel) for extensive premalignant actinic damage of the face and scalp
DG BRODLAND, RK ROENIGK – Mayo Clinic Proceedings, 1988 – Elsevier
… An appropriate medical and surgical history should be elicited. … cell carcinoma of morpheaform
histologic subtype was removed by Mohs' micrographic surgery in our … The physician may choose
this bloodless procedure in patients with communicable infections such as human …
Γίνεται αναφορά σε 46 Σχετικά άρθρα Όλες οι 7 εκδοχές Παράθεση Αποθήκευση
Surgical anatomy of the scalp
GE Seery – Dermatologic surgery, 2002 – Wiley Online Library
… and their spatial or depth location are of critical importance to the surgeon. … Pericranial dissection
from bone is bloodless other than the occasional, easily controlled, minimal … serviceable tissue
and probably is underutilized in reconstructive and cosmetic craniofacial surgery. …
Γίνεται αναφορά σε 27 Σχετικά άρθρα Όλες οι 5 εκδοχές Παράθεση Αποθήκευση
Laser hair transplantation
RE Fitzpatrick – Dermatologic surgery, 1995 – Wiley Online Library
… has led to the investigation of their use in hair transplantation, as bloodless surgery with tissue …
An important consideration for both the patient and the surgeon is the time required for … using freshly
excised scalp tissue obtained as a result of scalp reduction surgery performed for …
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[ΒΙΒΛΙΟ] CO2 laser surgery
I Kaplan, S Giler – 2012 – books.google.com
… blood vessels smaller than 1 mm are sealed resulting in a dry, almost bloodless procedure. …
Moreover, the hemostatic effect enables the surgeon to distinguish accurately between pathologic
and normal … that the hypothesis upon which the use of lasers in cancer surgery is based …
Γίνεται αναφορά σε 51 Σχετικά άρθρα Παράθεση Αποθήκευση
Scalp reduction surgery with the carbon dioxide laser
RG Wheeland, PL Bailin – The Journal of dermatologic surgery …, 1984 – Wiley Online Library
… already own this equipment, so existing facilities can, and should, be utilized without modification
to permit the dermatologic surgeon to perform … In conclusion, we believe the use of the CO 2 laser
for scalp reduction surgery provides a safe, rapid, relatively bloodless and less …
Γίνεται αναφορά σε 8 Σχετικά άρθρα Όλες οι 6 εκδοχές Παράθεση Αποθήκευση
Current CO2 laser surgery
I Kaplan – Optoelectronics in Medicine, 1982 – Springer
… blood vessels smaller than mm are sealed resulting in a dry almost bloodless procedure. … whereas
the haemostatic effect enables the surgeon to distin- guish accurately between pathological and …
indicate that the hypothesis upon which its introduction in cancer surgery is based …
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Mini‐Slit Graft Hair Transplantation Using the Ultrapulse Carbon Dioxide Laser Handpiece
C Ho, Q Nguyen, G Lask, N Lowe – Dermatologic surgery, 1995 – Wiley Online Library
… Address correspondence and reprint requests to: Gary Lask, MD, UCLA Dermatologic Laser
Surgery Center, 200 … minimal bleeding so the hair transplant surgeon is left with a near bloodless
surgical field. … that requires greater skill and a great deal of expe- rience by the surgeon. …
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The Sharplan carbon dioxide laser in clinical surgery: 7 years' experience
I Kaplan, J Raif – The biomedical laser, 1981 – Springer
… in which blood vessels smaller than 0.5 mm are cauterized, resulting in a dry, almost bloodless,
procedure. … Moreover, the hemostatic effect enables the surgeon to distinguish accurately between
pathologic and normal … Hence the laser's application in cancer surgery is obvious. …
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Carbon dioxide laser surgery
I Kaplan, S Giler – CO2 laser surgery, 1984 – Springer
… blood vessels smaller than 1 mm are sealed resulting in a dry, almost bloodless procedure. …
Moreover, the hemostatic effect enables the surgeon to distinguish accurately between pathologic
and normal … that the hypothesis upon which the use of lasers in cancer surgery is based …
Γίνεται αναφορά σε 12 Σχετικά άρθρα Παράθεση Αποθήκευση
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