Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
Ετικέτες
Τρίτη 9 Μαΐου 2017
Survival Differences in Women with and without Autologous Breast Reconstruction after Mastectomy for Breast Cancer
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An Innovative Risk-Reducing Approach to Postmastectomy Radiation Delivery after Autologous Breast Reconstruction
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Low-grade Cribriform Cystadenocarcinoma: A Review of the Literature and Case Report
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A Novel Needle Structure that Can Avoid Intravascular Injection of Any Filler
Prediction of Skin Necrosis after Mastectomy for Breast Cancer Using Indocyanine Green Angiography Imaging
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Composite Arteriovenous Radial Conduit Flap for Lower Limb Reconstruction
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A New Local Flap Nipple Reconstruction Technique Using Dermal Bridge and Preoperatively Designed Tattoo
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Difference in Success Treating Proximal Interphalangeal and Metacarpophalangeal Joints with Collagenase: Results of 208 Treatments
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Aging and Sexual Differences of the Human Skull
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Ulnar Head Reconstruction with Microvascular Second Metatarsal
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Absence of Ulnar Artery Inflow Detected by Allen’s Test Prior to Radial Forearm Free Flap
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Inferior Limb Salvage by Combined Free-tissue Transfer and the Crane Principle Revisited
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Establishing Content Validity of the CLEFT-Q: A New Patient-reported Outcome Instrument for Cleft Lip/Palate
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Surgical Factors Associated with Prolonged Hospitalization after Reconstruction for Oncological Spine Surgery
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Distally Based Sural Artery Peroneus Flap (DBSPF) for Foot and Ankle Reconstruction
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Def1 and Dst1 play distinct roles in repair of AP lesions in highly transcribed genomic regions
Source:DNA Repair
Author(s): Norah Owiti, Christopher Lopez, Shivani Singh, Andrei Stephenson, Nayun Kim
Abasic or AP sites generated by spontaneous DNA damage accumulate at a higher rate in actively transcribed regions of the genome in S. cerevisiae and are primarily repaired by base excision repair (BER) pathway. We have demonstrated that transcription-coupled nucleotide excision repair (NER) pathway can functionally replace BER to repair those AP sites located on the transcribed strand much like the strand specific repair of UV-induced pyrimidine dimers. Previous reports indicate that Rad26, a yeast homolog of transcription-repair coupling factor CSB, partly mediates strand-specific repair of UV-dimers as well as AP lesions. Here, we report that Def1, known to promote ubiquitination and degradation of stalled RNA polymerase complex, also directs NER to AP lesions on the transcribed strand of an actively transcribed gene but that its function is dependent on metabolic state of the yeast cells. We additionally show that Dst1, a homolog of mammalian transcription elongation factor TFIIS, interferes with NER-dependent repair of AP lesions while suppressing homologous recombination pathway. Overall, Def1 and Dst1 mediate very different outcomes in response to AP-induced transcription arrest.
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Human somatic cells deficient for RAD52 are impaired for viral integration and compromised for most aspects of homology-directed repair
Source:DNA Repair
Author(s): Yinan Kan, Nizar N. Batada, Eric A. Hendrickson
Homology-directed repair (HDR) maintains genomic integrity by eliminating lesions such as DNA double-strand breaks (DSBs), interstrand crosslinks (ICLs) and stalled replication forks and thus a deficiency in HDR is associated with genomic instability and cancer predisposition. The mechanism of HDR is best understood and most rigorously characterized in yeast. The inactivation of the fungal radiation sensitive 52 (RAD52) gene, which has both recombination mediator and single-strand annealing (SSA) activities in vitro, leads to severe HDR defects in vivo. Confusingly, however, the inactivation of murine and chicken RAD52 genes resulted in mouse and chicken cells, respectively, that were largely aphenotypic. To clarify this issue, we have generated RAD52 knockout human cell lines. Human RAD52-null cells retain a significant level of SSA activity demonstrating perforce that additional SSA-like activities must exist in human cells. Moreover, we confirmed that the SSA activity associated with RAD52 is involved in, but not absolutely required for, most HDR subpathways. Specifically, a deficiency in RAD52 impaired the repair of DNA DSBs and intriguingly decreased the random integration of recombinant adeno-associated virus (rAAV). Finally, an analysis of pan-cancer genome data from The Cancer Genome Atlas (TCGA) revealed an association between aberrant levels of RAD52 expression and poor overall survival in multiple cancers. In toto, our work demonstrates that RAD52 contributes to the maintenance of genome stability and tumor suppression in human cells.
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Heavy mite exposure in the environment can induce allergic systemic reactions.
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Prevention of Dust Mite and Dust Mite Allergen Exposure
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Mite Allergy Research The authors view the following as currently unmet needs in mite allergy research: Since mites constitute the most important allergen source worldwide the information contained in this document needs to be disseminated to all ranks of the medical establishment for educational purposes and to stimulate research Increased knowledge on the cellular basis of the immune responses to mites A better understanding of the link between mite sensitization and allergic diseases Better insights into the genetic influences controlling IgE responses to mite allergens. Effects of epigenetic factors Improved mite allergen standardization Development of purified mite allergens with defined clinically relevant epitopes for molecular diagnosis and evaluation of the response to immunotherapy Development of objective methods to assess allergen exposure and environmental control outcomes Better strategies for immunotherapy and immunoprophylaxis of mite allergy: recombinant allergens, h
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Rick factors for medical and allergic events during air travel An increase of passenger’s age Flight stress and anxiety, including increased security procedures Disruption of routine Changes in the cabin environment (temperature, humidity, air pressure) Decreased seat space Flight delays Alcohol/drug intake Longer flights Altered circadian rhythm Jet lag Pre-existing medical conditions
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
In-flight treatment of allergic emergencies and asthma Treating medical emergencies during flight is a major challenge and air travel is an important concern for subjects with asthma and a history of a SAR. The resources to treat allergic emergencies are somewhat limited. In the United States, the Federal Aviation Administration requires the inclusion of epinephrine in medical kits carried on board [18]. These emergency medical kits typically contain the following medications [19]: Aqueous epinephrine (adrenaline) 1:10000 and 1:1000 dilution. Albuterol (salbutamol) for nebulization. Bronchodilator aerosol inhaler. Cortisol (hydrocortisone). Antihistamines tablets and injectable (commonly diphenhydramine). A recommendation from this World Allergy Organization (WAO) expert group for in-flight treatment of a SAR and AE is: a) For AE, inhaled bronchodilator and oxygen. Consider an oral, intramuscular or intravenous corticosteroid for moderate to severe symptoms and intramuscular epinephr
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Measures that reduce the risk of an in-flight reaction to peanut and tree nuts 1. Passengers requesting any kind of special accommodation (e.g., peanut/tree nut snacks not be distributed, announcement to not eat items with peanut/tree nut, request special peanut/tree nut-free meal, buffer zone, pre-board, request to sit in a certain seat/zone). 2. Peanut/tree nut-free meals. 3. Wiping of tray tables 4. Avoidance of airline pillows or blankets 5. Buffer zones around which peanut or nut products cannot be consumed 6. Request other passengers not to consume peanut/tree nut-containing products 7. Announcement that passengers do not eat peanut/tree nut containing goods 8. Not consuming airline-provided food
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Recommendations to prevent and manage in-flight allergic events • Promote the prevention of allergic diseases via passenger education • Medical consultation for high-risk passengers before traveling • Train and re-train aircrews • Promote general preventive measures during the flight: hydration, food allergen avoidance (especially peanuts, tree nuts, other foods, as necessary) • Provide an appropriate place for furry pets away from subjects with pet allergy • Provide for sufficient quantities of appropriate medications: epinephrine (adrenaline), β2 agonists for inhalation and nebulization, oral and injectable corticosteroids and antihistamines • Oxygen
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
The efficacy of a lip balm containing pseudo-ceramide on the dry lips of sensitive skin-conscious subjects
Summary
Background
Many people use lip care products daily to prevent dry lips. However, some people, especially those with sensitive skin-consciousness, complain of various skin problems on their lips including contact dermatitis caused by lip care products. Dry lips have decreased water holding capacity and cutaneous barrier function as well as reduced stratum corneum ceramide levels. In this study, we investigated the usefulness of a newly formulated lip balm containing pseudo-ceramide for the dry lips of subjects with sensitive skin.
Method
Thirty subjects with dry lips and sensitive skin-consciousness used the test lip balm more than twice a day for 4 weeks. Lip conditions were evaluated before and after 2 and 4 weeks.
Result
Visual evaluation by a dermatologist showed that overall improvements were observed in all subjects as early as week 2. After 4 weeks of usage, 27% of the subjects were objectively judged as "markedly improved" and 60% of the subjects were judged as "improved". No adverse event developed throughout the test period, and all subjects were able to use the lip balm safely for 4 weeks. Usefulness was judged based on all evaluation items, and 27%, 70%, and 3% of the subjects were judged as "very useful," "useful," and "slightly useful," respectively. Ninety percentage of the subjects expressed improvement and acceptance of the lip balm.
Conclusion
Based on these results, the newly formulated lip balm containing pseudo-ceramide is very useful for the lip care of sensitive skin-conscious subjects as well as for daily use by healthy subjects.
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Ca2+ Release Channels Join the ‘Resolution Revolution’
Publication date: Available online 9 May 2017
Source:Trends in Biochemical Sciences
Author(s): Ran Zalk, Andrew R. Marks
Ryanodine receptors (RyRs) are calcium release channels expressed in the sarcoendoplasmic reticula of many cell types including cardiac and skeletal muscle cells. In recent years Ca2+ leak through RyRs has been implicated as a major contributor to the development of diseases including heart failure, muscle myopathies, Alzheimer's disease, and diabetes, making it an important therapeutic target. Recent mammalian RyR1 cryoelectron microscopy (cryo-EM) structures of multiple functional states have clarified longstanding questions including the architecture of the transmembrane (TM) pore and cytoplasmic domains, the location and architecture of the channel gate, ligand-binding sites, and the gating mechanism. As we advance toward complete models of RyRs this new information enables the determination of domain–domain interfaces and the location and structural effects of disease-causing RyR mutations.
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Found in Translation: Applying Lessons from Model Systems to Strigolactone Signaling in Parasitic Plants
Publication date: Available online 9 May 2017
Source:Trends in Biochemical Sciences
Author(s): Shelley Lumba, Asrinus Subha, Peter McCourt
Strigolactones (SLs) are small molecules that act as endogenous hormones to regulate plant development as well as exogenous cues that help parasitic plants to infect their hosts. Given that parasitic plants are experimentally challenging systems, researchers are using two approaches to understand how they respond to host-derived SLs. The first involves extrapolating information on SLs from model genetic systems to dissect their roles in parasitic plants. The second uses chemicals to probe SL signaling directly in the parasite Striga hermonthica. These approaches indicate that parasitic plants have co-opted a family of α/β hydrolases to perceive SLs. The importance of this genetic and chemical information cannot be overstated since parasitic plant infestations are major obstacles to food security in the developing world.
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Mechanisms and Dynamics of T Cell-Mediated Cytotoxicity In Vivo
Publication date: Available online 9 May 2017
Source:Trends in Immunology
Author(s): Stephan Halle, Olga Halle, Reinhold Förster
Cytotoxic T lymphocytes (CTLs) are critical in the elimination of infected or malignant cells and are emerging as a major therapeutic target. How CTLs recognize and kill harmful cells has been characterized in vitro but little is known about these processes in the living organism. Here we review recent insights into CTL-mediated killing with an emphasis on in vivo CTL biology. Specifically, we focus on the possible rate-limiting steps determining the efficiency of CTL-mediated killing. We also highlight the need for cell-based datasets that permit the quantification of CTL dynamics, including CTL location, migration, and killing rates. A better understanding of these factors is required to predict protective CD8 T cell immunity in vivo and to design optimized vaccination protocols.
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Dolichoectatic internal carotid artery presenting as a sellar-suprasellar mass with symptomatic hydrocephalus
Neurology India 2017 65(3):681-682
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1892 and the tribulations of Joseph Babinski
Neurology India 2017 65(3):468-470
In the early 1880s, Joseph Babinski was appointed as Chef de Clinique under Jean-Martin Charcot at Salpétrière, Paris, in France. He appeared for the post of Professeur Agrégé, the pinnacle of academic distinction in France in 1892. Charles Bouchard, the earliest pupil of Charcot, who described the Charcot-Bouchard aneurysm along with his master, was the Chief of the Board of Jury. Charcot and Bouchard did not see eye to eye in the later period, and when German Sée, an external examiner did not join the board of examiners following illness, Bouchard, instead of seeking the assistance of an alternate examiner, employed the special right of Vote of Absence. Babinski and all other pupils of Charcot were unsuccessful, while those of Bouchard, came out with flying colors. An embittered Babinski, along with some of the other unsuccessful candidates, appeared before the Ministry of Public Assistance after a protracted legal battle for nearly 2 years but lost the case. They were even ordered by the court to pay on behalf of the the successful candidates for the legal battle. Babinski never sat for the examination again and this is the story of one of the most ignominious episodes in an examination anywhere.
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Post-discectomy annular pseudocyst: A rare cause of failed back syndrome
Neurology India 2017 65(3):650-652
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Two founders of Bombay neurosciences: Dr. Ramchandra G. Ginde and Dr. Menino De Souza
Neurology India 2017 65(3):460-467
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Dengue fever triggering hemiconvulsion hemiplegia epilepsy in a child
Neurology India 2017 65(3):636-638
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Dengue encephalitis: “Double doughnut” sign
Neurology India 2017 65(3):670-671
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Pediatric thoracolumbar spinal injuries: A rare and unique clinical scenario
Neurology India 2017 65(3):482-484
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Endoscopic management of intracranial cysts: Need of the hour
Neurology India 2017 65(3):471-472
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Full-field perimetry in pituitary tumors
Neurology India 2017 65(3):690-690
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Role of neuro-endoscopy and fenestration in the management of brain cysts
Neurology India 2017 65(3):473-474
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Cerebral venous thrombosis due to pheochromocytoma in a patient with Von Hippel Lindau mutation
Neurology India 2017 65(3):643-645
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Clinical and health policy-related challenges of pediatric spinal cord injuries
Neurology India 2017 65(3):475-476
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Cost effective, technically simpler, and aesthetically promising cranioplasty in developing countries
Neurology India 2017 65(3):660-663
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Surgical considerations in the management of pediatric thoracolumbar fractures
Neurology India 2017 65(3):477-479
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Central pontine myelinolysis associated with hypokalemia in a diabetic patient with sepsis
Neurology India 2017 65(3):674-675
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Pediatric thoracolumbar fractures: Salient points in management
Neurology India 2017 65(3):480-481
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Clinicopathological conferences: The fading art of playing Sherlock Holmes
Neurology India 2017 65(3):685-688
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Movement disorders in anti-NMDA receptor encephalitis
Neurology India 2017 65(3):632-633
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Epilepsy surgery in children
Neurology India 2017 65(3):485-492
Approximately 60% of all patients with epilepsy suffer from focal epilepsy syndromes. In approximately 15% of these patients, the seizures are not adequately controlled with anticonvulsive drugs, and such patients are potential candidates for surgical treatment and majority are children. Epilepsy surgery in children, who have been carefully chosen, can result in either seizure freedom or a marked (>90%) reduction in seizures in approximately two-third of children with intractable seizures. In the multimodality presurgical evaluation approach, sufficient concordance should be established among various independent investigations, thus identifying the location and extent of the epileptogenic zone with a high degree of confidence. Early surgery improves the quality of life and cognitive and developmental outcome of the child. Surgically remediable epilepsies in children should be identified early and include temporal lobe epilepsy with focal lesions, lesional extratemporal epilepsies, hemispherical epilepsies, and gelastic epilepsy with hypothalamic hamartoma, and can be treated by resective or disconnection surgery. Palliative procedures include corpus callosotomy and vagal nerve stimulation for children with diffuse and multifocal epilepsies, who are not candidates for resective surgery. Deep brain stimulation in patients with epilepsy is still under evaluation. For children with "surgically remedial epilepsy," surgery should be offered as a procedure of choice rather than as a treatment of last resort.
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Radioactive iodine (RAI) therapy for metastatic differentiated thyroid cancer
Publication date: Available online 9 May 2017
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Frederik A. Verburg, Heribert Hänscheid, Markus Luster
Differentiated thyroid cancer (DTC) is the most common endocrine malignancy. It usually has a comparatively benign course. If properly executed, radioiodine therapy can provide an effective treatment of even advanced, metastatic DTC. A major problem in determining the right RAI for a patient with metastatic disease is a comparative lack of evidence. There are no reports on randomized controlled trials in this patient group which can aid us in determining which way to treat which patient. Few non-randomized prospective observational studies have been performed. Most available evidence is based on retrospective analyses which, although often informative, still are hampered by the selection bias inherent to retrospective studies on a small, preselected sample of the total DTC population. The aim of the present review is to provide an overview of the relevant literature on the issues pertinent to the execution of RAI.Radioiodine therapy of metastatic DTC in patients can be an effective treatment modality which will contribute significantly to a patients' life expectancy. However, much is unclear in the management of this malignancy, including which activity to use, how to determine this activity (empiric vs. dosimetric approach) as well as the potential long-term complications. In pediatric patients, special considerations apply with regard to weight-adaptation of activities as well the risk of pulmonary fibrosis in patients with diffuse miliary metastases.
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The molecular basis for RET tyrosine-kinase inhibitors in thyroid cancer
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Valentina De Falco, Francesca Carlomagno, Hong-yu Li, Massimo Santoro
RET receptor tyrosine kinase acts as a mutated oncogenic driver in several human malignancies and it is over-expressed in other cancers. Small molecule compounds with RET tyrosine kinase inhibitory activity are being investigated for the targeted treatment of these malignancies. Multi-targeted compounds with RET inhibitory concentration in the nanomolar range have entered clinical practice. This review summarizes mechanisms of RET oncogenic activity and properties of new compounds that, at the preclinical stage, have demonstrated promising anti-RET activity.
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Stimulus Expectation Prolongs Rather Than Shortens Perceived Duration: Evidence From Self-Generated Expectations.
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Audiovisual Integration in Social Evaluation.
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Synthesis of novel acyl selenoureido benzensulfonamides as carbonic anhydrase I, II, VII and IX inhibitors
Publication date: Available online 9 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Andrea Angeli, Fabrizio Carta, Gianluca Bartolucci, Claudiu T. Supuran
A novel series of acyl selenoureido benzensulfonamides was evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors against the human (h) isoforms hCA I, II, VII and IX, which are involved in a variety of diseases such as glaucoma, retinitis pigmentosa, epilepsy and tumors etc. These compounds showed excellent inhibitory activity for these isoforms, with several low nanomolar derivatives identified against all of them. Furthermore, the selenoureido group may provide an antioxidant activity to these enzyme inhibitors.
Graphical abstract
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Succinamide derivatives of melampomagnolide B and their anti-cancer activities
Publication date: Available online 8 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Venumadhav Janganati, Jessica Ponder, Shraddha Thakkar, Craig T. Jordan, Peter A. Crooks
A series of succinamide derivatives of melampomagnolide B have been synthesized by coupling MMB monosuccinate (2) with various heterocyclic amines to afford compounds 3a-3l. MMB monosuccinate was also reacted with terminal diaminoalkanes to afford dimeric succinamido analogs of MMB (4a-4h). These succinamide analogs of MMB were evaluated for their anti-cancer activity against a panel of sixty human cancer cell lines. Analogs 3d-3i and dimers 4f-4g exhibited promising anti-cancer activity with GI50 values ranging from 0.28-33.5 µM against most of the cell lines in the panel. The dimeric analogs 4f and 4g were identified as lead compounds with GI50 values in the nanomolar range (GI50 = 280-980 nM) against several cell lines in the panel; i.e. leukemia cell lines CCRF-CEM, HL-60(TB), K-562, MOLT-4, RPMI-8226 and SR; and solid tumor cell lines NCI-H522 (non-small cell lung cancer), SW-620 and HCT-116 (colon cancer), LOX IMVI (melanoma), RXF 393 (renal cancer), and MCF7, BT-549 and MDA-MB-468 (breast cancer). Succinamide analogs 3a, 3c-3l and 4b-4h were also evaluated for their apoptotic activity against M9-ENL1 acute myelogenous leukemia cells; compounds 3h-3j and 4g were equipotent with parthenolide, exhibiting LC50 values in the range 4.1-8.1 μM. Molecular docking studies indicate that these molecules interact covalently with the highly conserved Cys-46 residue of the N-terminal lobe (1-109) of human IKKβ to inhibit the NFκB transcription factor complex, resulting in down-regulation of anti-apoptotic genes under NFκB control.
Graphical abstract
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Design, Synthesis and Evaluation of Indole-2-carboxamides with Pan Anti-mycobacterial Activity
Publication date: Available online 8 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Nicholas D. Franz, Juan Manuel Belardinelli, Michael A. Kaminski, Louis C. Dunn, Vinicius Calado Nogueira de Moura, Michael A. Blaha, Dan D. Truong, Wei Li, Mary Jackson, E. Jeffrey North
Current treatment regimens for non-tuberculous mycobacteria (NTM) and tuberculosis (TB) generally require long duration of therapy with multiple drugs, some of which are broad spectrum antibiotics. Despite some advances in antimicrobial compounds, there remains a need in therapy for antibiotics with specific mycobacterial targets. It has been shown that MmpL3 is an essential transporter required for the translocation of mycolic acids to the mycobacterial cell envelope. Here, we synthesized a series of indole-2-carboxamides that inhibit MmpL3 and have potent pan-activity against mycobacterial species. The compounds were tested against several fast and slow-growing Mycobacterium species, including M. abscessus, M. massiliense, M. bolletii, M. chelonae, M. tuberculosis, M. avium, M. xenopi and M. smegmatis. The target of these indole compounds makes them selective for mycobacteria, while showing no clinically relevant bactericidal activity against S. aureus or P. aeruginosa. These compounds were tested against THP-1, a human-cell line, and showed minimal in vitro cytotoxicity and good selectivity indices. The data shown and discussed suggest that lead indole-2-carboxamides are strong contenders for further preclinical testing as NTM therapeutics.
Graphical abstract
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Metabolic regulation and the anti-obesity perspectives of human brown fat
Publication date: August 2017
Source:Redox Biology, Volume 12
Author(s): Camilla Scheele, Søren Nielsen
Activation of brown adipose tissue (BAT) in adult humans increase glucose and fatty acid clearance as well as resting metabolic rate, whereas a prolonged elevation of BAT activity improves insulin sensitivity. However, substantial reductions in body weight following BAT activation has not yet been shown in humans. This observation raise the possibility for feedback mechanisms in adult humans in terms of a brown fat-brain crosstalk, possibly mediated by batokines, factors produced by and secreted from brown fat. Batokines also seems to be involved in BAT recruitment by stimulating proliferation and differentiation of brown fat progenitors. Increasing human BAT capacity could thus include inducing brown fat biogenesis as well as identifying novel batokines. Another attractive approach would be to induce a brown fat phenotype, the so-called brite or beige fat, within the white fat depots. In adult humans, white fat tissue transformation into beige has been observed in patients with pheochromocytoma, a norepinephrine-producing tumor. Interestingly, human beige fat is predominantly induced in regions that were BAT during early childhood, possibly reflecting that a presence of human beige progenitors is depot specific and originating from BAT. In conclusion, to utilize the anti-obesity potential of human BAT focus should be directed towards identifying novel regulators of brown and beige fat progenitor cells, as well as feedback mechanisms of BAT activation. This would allow for identification of novel anti-obesity targets.
Graphical abstract
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In vivo inhibitory activity of andrographolide derivative ADN-9 against liver cancer and its mechanisms involved in inhibition of tumor angiogenesis
Publication date: 15 July 2017
Source:Toxicology and Applied Pharmacology, Volume 327
Author(s): Wei Yang, Jin Zhao, Yake Wang, Haiwei Xu, Zhenwei Wu, Yangyang Hu, Kunkun Jiang, Pengpeng Shen, Cuiyun Ma, Zhenzhen Guan, Yan Zhang, Jiahui Ma, Ning Shang, Guangming Yan, Zhenji Wang, Guifu Dai
It is well known that liver cancer is a highly aggressive malignancy with poor prognosis. Andrographolide (AD), a major bioactive component of Andrographis paniculata (Burm. F.), is a potential anti-cancer pharmacophore and the synthesis of AD derivatives with better cytotoxicity to cancer cells has attracted considerable attentions. In the present study, we evaluated the in vivo inhibitory effects of ADN-9, a 15-benzylidene substituted derivative of AD, on the growth and metastasis of murine hepatoma H22 using an orthotopic xenograft model and a subcutaneous xenograft model, and we further studied the anti-angiogenic action and the related mechanisms of ADN-9 in vivo and in vitro. Importantly, ADN-9 remarkably suppressed the growth and metastasis of both orthotopic and subcutaneous xenograft tumors, and the serum AFP level in orthotopic hepatoma-bearing mice treated with 100mg/kg ADN-9 (ig.) was decreased to the normal level. We also found that ADN-9 showed stronger abilities than AD in shrinking tumors, suppressing the invasion and metastasis of H22 cells, decreasing the MVD and promoting tumor cell apoptosis in subcutaneous xenograft of mice. Additionally, ADN-9 exhibited stronger inhibitory activity than AD against the migration and VEGF-induced capillary-like tube formation in HUVECs, which was further proved to be associated with attenuating VEGF/VEGFR2/AKT signaling pathway. The present research provides the first evidence that a 15-substituted AD derivative is more promising than the parent compound in therapeutic treatment of liver cancer.
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Function of microRNA-143 in different signal pathways in cancer: New insights into cancer therapy
Publication date: July 2017
Source:Biomedicine & Pharmacotherapy, Volume 91
Author(s): Leila Karimi, Behzad Mansoori, Dariush shanebandi, Ali Mohammadi, Mahyar Aghapour, Behzad Baradaran
MicroRNAs (miRNAs) are small non-coding RNAs which participate in the post-transcriptional regulation of gene expression. They play important roles in cellular events such as growth and differentiation. Deregulation of miRNAs is frequently evident in human cancers where their aberrant expression is associated with uncontrolled proliferation, metastasis, impaired cell cycle and DNA damage response. The miRNAs are important in cancer as ∼50% of miRNA genes are located in cancer-associated regions such as fragile sites of genome. MiRNA-143 is defined as an important tumor suppressor in a variety of neoplasms including solid tumors and B-cell malignancies. MiRNA-143 is involved in the pathogenesis of cancers by directly targeting several mRNAs such as Bcl-2, KRAS, HK2, DNMT3A, TP53 and MMP-13. In this study, an overview of the miRNA-143 function in different signaling pathways in cancer will be provided.
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27 Refractory Angina
Publication date: 2018
Source:Chronic Coronary Artery Disease
Author(s): E. Marc Jolicoeur, Timothy D. Henry
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Incorporation of BMP-2 loaded collagen conjugated BCP granules in calcium phosphate cement based injectable bone substitutes for improved bone regeneration
Publication date: 1 August 2017
Source:Materials Science and Engineering: C, Volume 77
Author(s): Gun Hee Lee, Preeti Makkar, Kallyanshis Paul, ByongTaek Lee
The objective of the present study was to incorporate surface modified porous multichannel BCP granule into CPC to enhance its in vivo biodegradation and bone tissue growth. The multichannel BCP granule (15wt%) was first coated with collagen subsequent to BMP-2 loading (ccMCG-B). It was then embedded into CPC to form CPC-ccMCG-B system. The newly developed CPC-ccMCG-B system was then examined for SEM, EDX, XRD, setting time, compressive strength, injectability, pH change, BMP-2 release, in vitro as well as in vivo studies and further compared with CPC. Optimized CPC (0.45mL/g) was found based on setting time and compressive strength studies. In vivo studies exhibited improved new bone formation and better degradation of CPC after 2 and 4weeks of implantation as compared to CPC as resulted from effective BMP-2 signaling. Our results suggest that CPC-ccMCG-B system might be used as a promising injectable bone substitutes in clinical applications.
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Embryonic vascular disruption adverse outcomes: Linking high-throughput signaling signatures with functional consequences
Publication date: August 2017
Source:Reproductive Toxicology, Volume 71
Author(s): Robert G. Ellis-Hutchings, Raja S. Settivari, Alene T. McCoy, Nicole Kleinstreuer, Jill Franzosa, Thomas B. Knudsen, Edward W. Carney
Embryonic vascular disruption is an important adverse outcome pathway (AOP) as chemical disruption of cardiovascular development induces broad prenatal defects. High-throughput screening (HTS) assays aid AOP development although linking in vitro data to in vivo apical endpoints remains challenging. This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay. Both were identified as putative vascular disruptive compounds (pVDCs) in ToxCastDB and disrupted angiogenesis and embryogenesis in the functional assays. Differences were observed in potency and adverse effects: 5HPP-33 was embryolethal (WEC and ZET); TNP-470 produced caudal defects at lower concentrations. This study demonstrates how a tiered approach using HTS signatures and complex functional in vitro assays might be used to prioritize further in vivo developmental toxicity testing.
http://ift.tt/2ptN7Pr
Core-shell hierarchical mesostructured silica nanoparticles for gene/chemo-synergetic stepwise therapy of multidrug-resistant cancer
Publication date: July 2017
Source:Biomaterials, Volume 133
Author(s): Lijun Sun, Dangge Wang, Yu Chen, Liying Wang, Ping Huang, Yaping Li, Ziwei Liu, Heliang Yao, Jianlin Shi
The design and synthesis of hierarchically nanoporous structures for the co-encapsulation and sequential releases of different cargos are still great challenges in biomedical applications. In this work, we report on the elaborate design and controlled synthesis of a unique core-shell hierarchical mesoporous silica/organosilica nanosystem, in which there are large and small mesopores separately present in the shell and core, facilitating the independent encapsulations of large (siRNA) and small (doxorubicin) molecules, respectively. Importantly, the framework of the organosilica shell is molecularly hybridized with disulfide bonds, which enables the unique responsiveness to the reductive tumor microenvironment for the controlled releasing of loaded gene molecules, followed by the subsequent doxorubicin release. The first released large siRNA molecules from the organosilica shell down-regulated the expression of P-gp in the cell membrane and reversed the MDR of cancer cells, thus enhancing the antitumor effect of subsequently released small DOX molecules from the silica core, and in such a synergetic way the MDR tumor growth can be efficiently inhibited. This work shows the significant advantages compared to the traditional small-mesoporous or large-mesoporous nanosystems for drug co-delivery.
Graphical abstract
http://ift.tt/2oyRzg0
39 Hypertension in Pregnancy
Publication date: 2018
Source:Hypertension: A Companion to Braunwald's Heart Disease
Author(s): Line Malha, Tiina Podymow, Phyllis August
http://ift.tt/2qPUllG
20 The Medical Treatment of Stable Angina
Publication date: 2018
Source:Chronic Coronary Artery Disease
Author(s): Lawrence Kwon, Clive Rosendorff
http://ift.tt/2qXSnfr
35 Pulmonary Manifestations of Systemic Diseases
Publication date: 2018
Source:Pulmonary Pathology
Author(s): Haresh Mani, Dani S. Zander
http://ift.tt/2pi8hVG
Angiogenesis in the atherosclerotic plaque
Publication date: August 2017
Source:Redox Biology, Volume 12
Author(s): Caroline Camaré, Mélanie Pucelle, Anne Nègre-Salvayre, Robert Salvayre
Atherosclerosis is a multifocal alteration of the vascular wall of medium and large arteries characterized by a local accumulation of cholesterol and non-resolving inflammation. Atherothrombotic complications are the leading cause of disability and mortality in western countries. Neovascularization in atherosclerotic lesions plays a major role in plaque growth and instability. The angiogenic process is mediated by classical angiogenic factors and by additional factors specific to atherosclerotic angiogenesis. In addition to its role in plaque progression, neovascularization may take part in plaque destabilization and thromboembolic events. Anti-angiogenic agents are effective to reduce atherosclerosis progression in various animal models. However, clinical trials with anti-angiogenic drugs, mainly anti-VEGF/VEGFR, used in anti-cancer therapy show cardiovascular adverse effects, and require additional investigations.
Graphical abstract
http://ift.tt/2qXS2cL
Chapter 5 Diseases of the Immune System
Publication date: 2018
Source:Robbins Basic Pathology
http://ift.tt/2qXG7vv
Role of Nrf2 and protective effects of Metformin against tobacco smoke-induced cerebrovascular toxicity
Publication date: August 2017
Source:Redox Biology, Volume 12
Author(s): Shikha Prasad, Ravi K. Sajja, Mohammad Abul Kaisar, Jee Hyun Park, Heidi Villalba, Taylor Liles, Thomas Abbruscato, Luca Cucullo
Cigarette smoking (CS) is associated with vascular endothelial dysfunction in a causative way primarily related to the TS content of reactive oxygen species (ROS), nicotine, and inflammation. TS promotes glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM) with which it shares other pathogenic traits including the high risk of cerebrovascular and neurological disorders like stroke via ROS generation, inflammation, and blood-brain barrier (BBB) impairment. Herein we provide evidence of the role played by nuclear factor erythroid 2-related factor (Nrf2) in CS-induced cerebrobvascular/BBB impairments and how these cerebrovascular harmful effects can be circumvented by the use of metformin (MF; a widely prescribed, firstline anti-diabetic drug) treatment. Our data in fact revealed that MF activates counteractive mechanisms primarily associated with the Nrf2 pathway which drastically reduce CS toxicity at the cerebrovascular level. These include the suppression of tight junction (TJ) protein downregulation and loss of BBB integrity induced by CS, reduction of inflammation and oxidative stress, renormalization of the expression levels of the major BBB glucose transporter Glut-1 and that of the anticoagulant factor thrombomodulin. Further, we provide additional insights on the controversial interplay between Nrf2 and AMPK.
Graphical abstract
http://ift.tt/2pin4Qf
Myricetin suppresses invasion and promotes cell death in human placental choriocarcinoma cells through induction of oxidative stress
Publication date: 28 July 2017
Source:Cancer Letters, Volume 399
Author(s): Changwon Yang, Whasun Lim, Fuller W. Bazer, Gwonhwa Song
Myricetin is a bioactive compound found in a variety of vegetables and fruits, and its anti-cancer effects are well known. In this study, we confirmed that myricetin reduced proliferation of two choriocarcinoma cell lines (JAR and JEG-3) and also promoted apoptosis and regulated cell cycle progression in a dose-dependent manner in JAR and JEG-3 cells. In addition, we found that invasive and pro-angiogenic properties of malignant JAR and JEG-3 trophoblast cells were attenuated by myricetin treatment via MAPK and PI3K/AKT signaling pathways. In addition, we found that ROS production, lipid peroxidation, glutathione depletion, and loss of mitochondrial membrane potentials were enhanced in JAR and JEG-3 cells treated with myricetin. Moreover, myricetin augmented cytosolic Ca2+ release from the endoplasmic reticulum associated with modulation of ER stress in JAR and JEG-3 cells. Our results also revealed that myricetin had synergistic antiproliferative effects with current chemotherapeutics, etoposide and cisplatin, on choriocarcinoma cells. Collectively, results of the present study provide strong evidence for the potential of myricetin to be an effective therapeutic for the prevention of human placental choriocarcinomas.
http://ift.tt/2p7QcX6
Construction of three-dimensional vascularized functional human liver tissue using a layer-by-layer cell coating technique
Publication date: July 2017
Source:Biomaterials, Volume 133
Author(s): Kazuki Sasaki, Takami Akagi, Tadafumi Asaoka, Hidetoshi Eguchi, Yasunari Fukuda, Yoshifumi Iwagami, Daisaku Yamada, Takehiro Noda, Hiroshi Wada, Kunihito Gotoh, Koichi Kawamoto, Yuichiro Doki, Masaki Mori, Mitsuru Akashi
The creation of artificial liver tissue is an active area of research due to the shortage of donors for liver transplantation. Here we investigated whether a simple and efficient cell coating technique developed in our laboratory could be used to generate functional vascularized liver tissue. This technique creates three-dimensional tissue by loading cells sterically onto other cells that have been coated with layer-by-layer (LbL) nanofilms of fibronectin and gelatin, two extracellular matrix proteins. We used this technique to construct homogenous, dense, well-vascularized liver tissue from cryopreserved human primary hepatocytes, human umbilical vein endothelial cells, and normal human dermal fibroblasts. Using LbL cell coating technique resulted in higher cellular function in terms of human albumin production (P < 0.01) and cytochrome P450 activity (P < 0.01) in vitro. Furthermore, after being transplanted subcutaneously into NOD/SCID mice, the vascularized liver tissue showed greater albumin production in the early stage than non-vascularized tissue or a hepatocyte suspension (P < 0.01). Histological examination demonstrated that compare to non-vascularized tissue, there were many less-morphologically changed and intact hepatocytes in the vascularized tissue. This cell coating technique would be applicable to the generation of vascularized functional liver tissue for regenerative medicine in the future.
http://ift.tt/2q13ULo
Scholar : These new articles for Acta Oncologica are available online
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15 Cancer in Pregnancy
Publication date: 2018
Source:Clinical Gynecologic Oncology
Author(s): Krishnansu S. Tewari
http://ift.tt/2qPVjOF
Baseline carcinoembryonic antigen as a predictive factor of ramucirumab efficacy in RAISE, a second-line metastatic colorectal carcinoma phase III trial
Publication date: June 2017
Source:European Journal of Cancer, Volume 78
Author(s): Takayuki Yoshino, Radka Obermannová, György Bodoky, Rocio Garcia-Carbonero, Tudor Ciuleanu, David C. Portnoy, Tae Won Kim, Yanzhi Hsu, David Ferry, Federico Nasroulah, Josep Tabernero
BackgroundThe RAISE phase III clinical trial demonstrated that ramucirumab + (folinic acid plus 5-fluorouracil plus irinotecan) FOLFIRI significantly improved overall survival (OS) versus placebo + FOLFIRI for second-line metastatic colorectal carcinoma (mCRC) patients failing bevacizumab- and oxaliplatin-based chemotherapy (hazard ratio [HR] = 0.84, 95% CI = 0.73–0.98, P = 0.022). Post hoc analyses of RAISE patient data examined the association of carcinoembryonic antigen (CEA) subgroups with efficacy parameters.MethodsCEA subgroups (≤10 versus >10 ng/ml) were based on 2X upper limit of normal (ULN) (5 ng/ml). The Kaplan–Meier method estimated the median OS and the progression-free survival (PFS). Log-rank test compared the survival distributions within the subgroups. Hazard ratio (HR) (95% confidence interval [CI]) and treatment-by-subgroup interaction p-values were calculated by Cox proportional hazards model.ResultsRamucirumab treatment prolonged survival for the CEA ≤10 subgroup (HR = 0.68; 95% CI = 0.50–0.92; P = 0.013) and CEA >10 subgroup (HR = 0.90; 95% CI = 0.76–1.07; P = 0.233). However, the ramucirumab OS benefit over placebo was greater for the CEA ≤10 subgroup than for the CEA >10 subgroup (median OS: 3.6 versus 0.8 months greater, respectively). The interaction P-value between CEA level and treatment effect on OS was 0.088. This trend was observed across randomisation strata and to a lesser extent for PFS (P = 0.594).ConclusionsAlthough patients in both high- and low-CEA subgroups derive OS and PFS benefits from ramucirumab treatment, the low baseline CEA level may identify a subgroup of patients with mCRC who obtain greater benefit from ramucirumab.
http://ift.tt/2oIoodp
Targeting tumor associated macrophages (TAMs) via nanocarriers
Publication date: 28 May 2017
Source:Journal of Controlled Release, Volume 254
Author(s): Yuvraj Singh, Vivek Kumar Pawar, Jaya Gopal Meher, Kavit Raval, Animesh Kumar, Richa Shrivastava, Smrati Bhadauria, Manish K. Chourasia
Recruitment of inflammatory cells to tumor has been well documented, with the most frequent inhabitants being macrophages termed as tumor associated macrophages, (TAMs). Their presence was thought to be an evidence of immune system initiating a fight response towards the tumor, i.e. immune surveillance. This is the case too initially, when TAMs majorly exhibit an M1 phenotype, but their continued presence in tumor microenvironment brings about their polarization to M2 phenotype, which not only participate in continued sustenance of existing tumor but also open up deleterious avenues for further progression and metastasis of cancer. Current perspective is built around this very premise and focuses specifically on TAMs and how they are being targeted by researchers working in annals of nanomedicine. To do so, we dwell into tumor microenvironment and focus on nanotechnology based drug delivery aspects which have either been already or can be potentially employed in the future to target tumor associated macrophages for improved immunoadjuvant therapy of cancer.
Graphical abstract
http://ift.tt/2nYP1L5
11 Epithelial Ovarian Cancer
Publication date: 2018
Source:Clinical Gynecologic Oncology
Author(s): Eric L. Eisenhauer, Ritu Salani, Larry J. Copeland
http://ift.tt/2qPHmjQ
Phase I clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell
Publication date: June 2017
Source:Regenerative Therapy, Volume 6
Author(s): Yoshio Sakai, Masayuki Takamura, Akihiro Seki, Hajime Sunagozaka, Takeshi Terashima, Takuya Komura, Masatoshi Yamato, Masaki Miyazawa, Kazunori Kawaguchi, Alessandro Nasti, Hatsune Mochida, Soichiro Usui, Nobuhisa Otani, Takahiro Ochiya, Takashi Wada, Masao Honda, Shuichi Kaneko
IntroductionAdipose tissue stromal cells contain a substantial number of mesenchymal stem cells. As such, their application to regeneration of miscellaneous impaired organs has attracted much attention.MethodsWe designed a clinical study to investigate freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell (ADRC) therapy for liver cirrhosis and conducted treatment in four cirrhotic patients. ADRCs were isolated from autologous subcutaneous adipose tissue obtained by the liposuction method, followed with use of the Celution system adipose tissue dissociation device. The primary endpoint is assessment of safety one month after treatment. We also characterized the obtained ADRCs.ResultsTwo patients had type C cirrhosis, one had nonalcoholic steatohepatitis-cirrhosis, and one had type B cirrhosis. No serious adverse events were observed during the 1-month study period after freshly isolated ADRC infusion. Serum albumin concentrations were maintained or improved during this period as well as during the succeeding follow-up of approximately 1 year in two patients and 6 months in another patient. Liver regeneration-related factors, namely hepatocyte growth factor and interleukin-6, were elevated 1 day after ADRC treatment in all patients. The obtained freshly isolated ADRCs were expanded in culture and found to express mesenchymal stem cell markers. Gene expression profile analysis of ADRCs was shown to involve inflammatory features, suggesting that characteristics of the obtained ADRCs were related to immunomodulatory biological effects.ConclusionThis clinical study treatment for liver cirrhosis using ADRCs was proven to be safely conductible, and can be further investigated in future for regeneration/repair of liver cirrhosis.
http://ift.tt/2lH9Ni3
Mechanisms of sphingosine 1-phosphate receptor signalling in cancer
Publication date: June 2017
Source:Cellular Signalling, Volume 34
Author(s): Sathya Narayanan Patmanathan, Wei Wang, Lee Fah Yap, Deron R. Herr, Ian C. Paterson
S1P is a small bioactive lipid which exerts its effects following binding to a family of five G protein-coupled receptors, known as S1P1–5. Following receptor activation, multiple signalling cascades are activated, allowing S1P to regulate a range of cellular processes, such as proliferation, apoptosis, migration and angiogenesis. There is strong evidence implicating the involvement of S1P receptors (S1PRs) in cancer progression and the oncogenic effects of S1P can result from alterations in the expression of one or more of the S1PRs and/or the enzymes that regulate the levels of S1P. However, cooperativity between the individual S1PRs, functional interactions with receptor tyrosine kinases and the sub-cellular localisation of the S1PRs within tumour cells also appear to play a role in mediating the effects of S1PR signalling during carcinogenesis. Here we review what is known regarding the role of individual S1PRs in cancer and discuss the recent evidence to suggest cross-talk between the S1PRs and other cellular signalling pathways in cancer. We will also discuss the therapeutic potential of targeting the S1PRs and their downstream signalling pathways for the treatment of cancer.
http://ift.tt/2mVKbh8
17 Basic Principles of Chemotherapy
Publication date: 2018
Source:Clinical Gynecologic Oncology
Author(s): Christina S. Chu, Stephen C. Rubin
http://ift.tt/2m80cMJ
Osteonecrosis of jaw after antiangiogenic agent administration in a renal cell carcinoma patient
Publication date: June 2017
Source:Oral and Maxillofacial Surgery Cases, Volume 3, Issue 2
Author(s): Tae-Young Jung
A 62-year-old patient had characteristics corresponding to the diagnostic criteria of medication-related osteonecrosis of the jaw (MRONJ). She had been treated for renal cell carcinoma with radical nephrectomy and chemotherapy with pazopanib (Votrient®) and everolimus (Afinitor®) antiangiogenic agents. There was no history of radiation therapy, obvious metastatic disease or surgical treatment. Bone exposure was observed in both mandibular posterior regions. Bone necrosis had developed surrounding the #35=37 and 46, 47 implants installed 6 years prior. The lesions were diagnosed as MRONJ and the patient was treated by sequestrectomy, saucerization and reconstruction with a reconstruction plate. The clinical results were good.
http://ift.tt/2ptk92i
18 Targeted Therapy and Molecular Genetics
Publication date: 2018
Source:Clinical Gynecologic Oncology
Author(s): Shannon N. Westin, Anil K. Sood, Robert L. Coleman
http://ift.tt/2qPVkSJ
PDGFs and their receptors
Publication date: 30 May 2017
Source:Gene, Volume 614
Author(s): Andrius Kazlauskas
The platelet-derived growth factor (PDGF)/PDGFR receptor (PDGFR) family is essential for a vast array of physiological processes such as migration and proliferation of percityes that contribute to the formation and proper function of blood vessels. While ligand-dependent de-repression of the PDGFR's kinase activity is the major mode by which the PDGFR is activated, there are additional mechanisms to activate PDGFRs. Deregulated PDGFR activity contributes to various pathological conditions, and hence the PDGF/PDGFR family members are viable therapeutic targets. An increased appreciation of which PDGFR contributes to pathology, biomarkers that indicate the amplitude and mode of activation, and receptor-specific antagonists are necessary for the development of next-generation therapies that target the PDGF/PDGFR family.
http://ift.tt/2moMybw
Chapter 1 The Cell as a Unit of Health and Disease
Publication date: 2018
Source:Robbins Basic Pathology
http://ift.tt/2qZKuqw
3 Invasive Cervical Cancer
Publication date: 2018
Source:Clinical Gynecologic Oncology
Author(s): Krishnansu S. Tewari, Bradley J. Monk
http://ift.tt/2mtLyRC
18 Cardiopulmonary Complications of Cirrhosis
Publication date: 2018
Source:Zakim and Boyer's Hepatology
Author(s): Moises I. Nevah, Asha C. Kuruvilla, Michael B. Fallon
http://ift.tt/2lHwkqf
Targeting ligand–receptor interactions for development of cancer therapeutics
Publication date: June 2017
Source:Current Opinion in Chemical Biology, Volume 38
Author(s): Jun Woo Kim, Jennifer R Cochran
The biological importance and druggable properties of receptors and their cognate ligands have designated them as especially useful clinical targets. This significance continues to expand as new molecular insights underlying disease pathophysiology are uncovered. While both ligands and receptors have been exploited as drug targets, their differing biochemical properties require nuanced considerations for drug development, including where in the body they are located and how they are regulated on a cellular and molecular level. In this review we will discuss ligands and receptors as therapeutics targets, including their biodistribution and biological function. We provide examples of monoclonal antibodies (mAbs) used to modulate the activity of these targets, and discuss approaches for using engineered versions of ligands and receptors themselves for therapeutic intervention in cancer.
Graphical abstract
http://ift.tt/2qp7z9g
64 Fibrocystic Diseases of the Liver
Publication date: 2018
Source:Zakim and Boyer's Hepatology
Author(s): Joost P.H. Drenth, Jesus M. Banales, Kalpana M. Devaraj, Steve M. Helmke, Gregory Thomas Everson
http://ift.tt/2qp0jdA
Efficacy of bevacizumab therapy in recurrent malignant gliomas in relation to the prior recurrence pattern or tumor location
Publication date: June 2017
Source:Journal of Clinical Neuroscience, Volume 40
Author(s): Masahide Matsuda, Eiichi Ishikawa, Tetsuya Yamamoto, Hiroyoshi Akutsu, Shingo Takano, Akira Matsumura
Although promising preliminary results have been widely observed with bevacizumab for recurrent malignant gliomas, many unanswered questions remain to be resolved to achieve an optimal outcome. No predictive biomarkers of a survival benefit from bevacizumab have been established, and no consensus exists about the response or survival benefit regarding the prior recurrence pattern or tumor location. Here we retrospectively analyzed the clinical benefit from bevacizumab for recurrent malignant gliomas in relation to the prior recurrence pattern or tumor location. Thirty-one consecutive patients with recurrent malignant gliomas who were treated with bevacizumab were investigated. The treatment response and survival benefit from bevacizumab were analyzed in association with age, sex, Karnofsky performance status, prior pathological diagnosis, prior recurrence pattern, primary location of tumor, recurrence status, and expression of angiogenic and hypoxic markers. The group with leptomeningeal dissemination had a significantly shorter median overall survival with bevacizumab (OSBev) (6.0months, 95% confidence interval (CI) 1.4–10.7) compared to those in the local/distant group (11.8months, 95% CI 6.1–17.4). The median OSBev of the infratentorial tumor group and supratentorial tumor group were 9.2months (95% CI 5.0–13.4) and 10.4months (95% CI 6.6–14.3), respectively. With multivariate analysis, the prior recurrence pattern was the only independent prognostic factor of OSBev. Patients with leptomeningeal dissemination of recurrent malignant glioma experienced minimal benefit from bevacizumab. Therefore, in the context of cost effectiveness, bevacizumab is not recommended for patients with leptomeningeal dissemination.
http://ift.tt/2qZKsPq
Recent advances in the development of novel protein scaffolds based therapeutics
Publication date: September 2017
Source:International Journal of Biological Macromolecules, Volume 102
Author(s): Asim Azhar, Ejaj Ahmad, Qamar Zia, Mohd. Ahmar Rauf, Mohammad Owais, Ghulam Md Ashraf
Antibodies occupy a central position when it comes to binding proteins with desired antigenic specificities. During the past decade, a plethora of recombinant or humanized versions of antibodies have entered clinical settings with outstanding accomplishments. Yet, they suffer from several drawbacks such as high molecular weight, limited tissue penetration, instability, high production cost, requirement for large doses and potential cytotoxicity. As a result, new generation of receptor proteins has been developed, that are derived from small and robust immunoglobulin (Ig) or non-immunoglobulin based "scaffolds". Combinatorial protein engineering has tremendous scope in the development of these protein scaffolds with immunoglobulin like specificity and/or prescribed binding functions. The advancement made in this regard can boast of developing various validated Ig based and non-Ig protein scaffolds with desirable therapeutic potential. The newly emerging technology has profound scope in translational biology and offer matching replacement for existing immunotherapeutic agents. Only few data from early clinical studies are available yet, but many more are likely to come in the near future. Here, we provide a glimpse of recent clinical advances in the field of existing protein scaffolds.
http://ift.tt/2qpl4Wr
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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