The association between initiation weekday of radiotherapy and local control in stage 1 glottic carcinoma: a retrospective analysis.

Radiotherapy is one of the definitive treatments for head and neck squamous cell carcinoma, especially early-stage glottic squamous cell carcinoma. Although there are several studies on the initiation weekday of cancer treatment, there are very few studies in the radiotherapy field. Thus, the present study investigated whether the initiation weekday of radiotherapy affects the local control rate for stage 1 glottic squamous cell carcinoma.

Clinical Outcomes of Radiotherapy for Stage 1 Glottic Carcinoma: Comparing Accelerated Hyperfractionation and Once-daily Fractionation.

Background/aim: Accelerated hyperfractionation (AHF) is used in head and neck cancer to improve the local control (LC) rate, but reports of outcomes for early-stage GC are limited. The outcomes of radiotherapy (RT) for stage 1 glottic carcinoma (GC) were retrospectively analyzed, comparing AHF and once-daily fractionation (ODF) using 2.0-2.

Successful Preoperative QUAD SHOT for Bulky Parotid Carcinoma: Potential Preoperative Ultra-Hypofractionated Radiotherapy for Conversion Surgery.

QUAD SHOT is an ultra-hypofractionated radiotherapy (RT) technique that prescribes 14.0-14.8 Gy over 2 days.

Nintedanib-Induced Delayed Mucosal Healing after Adjuvant Radiation in a Case of Oropharyngeal Carcinoma.

Since the launch of imatinib in 2001, tyrosine kinase inhibitors are being used in chemotherapy for a wide range of malignant tumors. Drugs that inactivate multiple molecular mechanisms are called multikinase inhibitors (MKIs). Nintedanib is a type of MKI that inhibits downstream cascades in three systems: vascular endothelial growth factor receptor, fibroblast growth factor receptor, and platelet-derived growth factor receptor inhibitions.

Three cases of organized hematoma of the maxillary sinus: clinical features and immunohistological studies for vascular endothelial growth factor and vascular endothelial growth factor receptor 2 expressions.

Objectives. Organized hematoma (OH) is a rare, nonneoplastic, hemorrhagic lesion causing mucosal swelling and bone thinning, mainly in the maxillary sinus. We aimed to clarify the clinical presentation and treatment of OH.

Galanin receptor 2 utilizes distinct signaling pathways to suppress cell proliferation and induce apoptosis in HNSCC.

Galanin and its receptors, GALR1 and GALR2, are tumor suppressors and represent therapeutic targets in head and neck squamous cell carcinoma (HNSCC). In the present study, it was demonstrated that the re‑expression of GALR1 in GALR1 and GALR2‑negative HNSCC cells suppresses tumor cell proliferation. This is mediated via extracellular‑regulated protein kinase‑1/2 (ERK1/2)‑dependent effects on the cyclin‑dependent kinase inhibitors (CKI) and cyclin D1.

Phonological outcome of laryngeal framework surgery by different anesthesia protocols: a single-surgeon experience.

Conclusion: Similar to combined arytenoid adduction and medialization laryngoplasty (i.e. combined surgery) under local anesthesia, general anesthesia by intubation or by the laryngeal mask airway (LMA) method significantly improves phonological outcome.

Rare case of malignant transformation of recurrent respiratory papillomatosis associated with human papillomavirus type 6 infection and p53 overexpression.

Recurrent respiratory papillomatosis (RRP), a chronic upper respiratory condition characterized by diffuse multiple recurring papillomas, is thought to result from human papillomavirus (HPV) type 6 or 11 infection. Although RRP is an intractable disease, malignant transformation of RRP is rare. The underlying mechanism, however, has not been elucidated.

Mechanism of inverse agonist action of sarpogrelate at the constitutively active mutant of human 5-HT2A receptor revealed by molecular modeling.

We previously reported that sarpogrelate, a selective 5-HT2A antagonist, showed a potent inverse agonist activity to constitutively active mutant (C322K) of human 5-HT2A receptor (5-HT2AR). However, it remains to be unknown about the actual mechanism of this mutant for its constitutive activation as well as inverse agonist activity of sarpogrelate. Our model shows that mutation (C322K) of 5-HT2AR causes electronic repulsion between positively charged Arg173(3.

Practical access to four stereoisomers of naftidrofuryl and their binding affinity towards 5-hydroxytryptamine 2A receptor.

Naftidrofuryl oxalate (Praxilene®, 1) has been used for the treatment of intermittent claudication for more than 30 years. It selectively blocks vascular and platelet 5-hydroxytryptamine 2 (5-HT(2)) receptors. This drug is marketed as a mixture of four stereoisomers, and so far there is no individual biological evaluation on the single isomers.

Assessment of homologous internalization of constitutively active N111G mutant of AT(1) receptor.

Constitutively active mutants (CAMs) of G-protein-coupled receptors mimic the active conformation of the receptor in their ability to activate second messenger systems in the absence of agonist. They have revealed novel properties of drugs that reverse the basal levels of constitutive activity, indicating that the drugs have the inverse agonist activity. Internalization plays an important role in receptor endocytosis and signal transduction.

Engineered mutation of some important amino acids in angiotensin II type 1 (AT1) receptor increases the binding affinity of AT1-receptor antagonists.

The present study was designed to examine the binding affinity and functional potency of selective angiotensin II type 1 (AT(1))-receptor antagonists towards specific mutants of AT(1) receptor using site-directed mutagenesis. We also compared our results with the wild-type AT(1) receptor and investigated the possible reasons behind that. Both wild-type and mutant receptors were expressed in COS-7 cells and the binding affinities of the antagonists were determined by radioligand binding assay.

Internalization of constitutively active N111G MUTANT of AT1 receptor induced by angiotensin II-receptor antagonists candesartan, losartan, and telmisartan: comparison with valsartan.

Based on radioligand binding and signal transduction assays in our previous study, we have determined the binding pattern and functional efficacy of the constitutively active mutant N111G of angiotensin II type 1 (AT(1)) receptor. We have also shown that the N111G mutant induces homologous internalization through mediation of the AT(1)-receptor antagonist valsartan. In this study we demonstrated that other AT(1)-receptor antagonists, candesartan, losartan, and telmi-sartan, also stimulate internalization of N111G mutant receptor to the same extent.

Constitutively active mutant N111G of angiotensin II type 1 (AT(1)) receptor induces homologous internalization through mediation of AT(1)-receptor antagonist.

The present study investigated the internalization behavior of the constitutively active mutant (CAM) N111G of angiotensin II type 1 (AT(1)) receptor and correlated the result with the mechanism of the constitutive activity of the mutant. The inverse agonist activity of valsartan, losartan, candesartan, and telmisartan was also examined by inositol phosphate (IP) accumulation study as well as receptor-internalization assay. Both wild-type (WT) and N111G mutant receptors were transiently expressed in COS-7 cells and the binding affinities towards the agonist and these four AT(1) antagonists were determined.

Assessment of binding affinity to 5-hydroxytryptamine 2A (5-HT2A) receptor and inverse agonist activity of naftidrofuryl: comparison with those of sarpogrelate.

Naftidrofuryl is a peripheral vasodilator that has been clinically used in the treatment of intermittent claudication and dementia. It has 5-hydroxytryptamine 2 (5-HT(2)) antiserotonergic activity and selectively binds with the 5-HT(2) receptor. The purpose of the present study is to assess the binding affinity and functional potency of naftidrofuryl to the 5-HT(2A) receptor, to find out the inverse agonist activity of this compound at a constitutively active mutant of 5-HT(2A) receptor, and finally to compare the findings with those of sarpogrelate.

Mutagenesis of important amino acid reveals unconventional homologous internalization of beta(1)-adrenergic receptor.

Aims: The study was designed to examine the internalization of Asp104Lys mutant of beta(1)-adrenergic receptor (beta(1)-AR) and compared to other mutant (Asp104Ala) and wild type receptors. Moreover, this study needs to perform the role of GRK2 (betaARK1) and beta-arrestin1 on this internalization of Asp104Lys mutant of beta(1)-AR.

Main Methods: Binding affinity, functional potency of agonist and agonist-induced internalization were determined for wild type and both mutants of beta(1)-ARs stably expressed in HEK 293 cells as assessed by [(3)H] CGP12177 radioligand.

Binding sites of valsartan, candesartan and losartan with angiotensin II receptor 1 subtype by molecular modeling.

Aims: This study was designed to examine the importance of interaction in the binding of selective angiotensin II receptor antagonists to angiotensin II type 1 receptor using molecular modeling. The AT(1) antagonists used in this study were valsartan, candesartan and losartan.

Main Methods: AT(1) receptor structural model was constructed by homology modeling using structural models of rhodopsin photointermediates.

Mutation of important amino acid residue of Asp104Lys in human beta(1)-adrenergic receptor triggers functional and constitutive inactivation.

Based on our previous molecular modeling and radioligand binding study, we have demonstrated that aspartic acid of 104 in transmembrane helix (TMH) II of beta(1)-adrenergic receptor (beta(1)-AR) is important for functional characteristics of these receptors. We have also showed that mutation of negatively charged aspartic acid to neutral charged alanine exhibited constitutive activity of beta(1)-AR. However, the mutation of negatively charged aspartic acid to positively charged lysine is still remained to be examined, which is very important to know for fully understanding the characteristics of beta(1)-AR.

Mutational analysis of the alpha 1a-adrenergic receptor binding pocket of antagonists by radioligand binding assay.

Computer simulations of the human alpha 1a-adrenergic receptor (alpha 1a-AR) based on the crystal structure of rhodopsin have been combined with experimental site-directed mutagenesis to investigate the role of residues in the transmembrane domains in antagonist binding. Previous molecular dynamics studies from our laboratory indicated that the amino acids Asp106 in the third transmembrane domain (TMD), Gln167 in TMD IV of alpha 1a-AR were directly involved in prazosin, tamsulosin and KMD-3213 binding. The Asp106Ala mutant did not exhibit any affinity for [3H]prazosin.

Amino acids of the human alpha1d-adrenergic receptor involved in antagonist binding.

Computer simulations of the human alpha(1d)-adrenergic receptor (alpha(1d)-AR) based on the crystal structure of rhodopsin have been combined with experimental site-directed mutagenesis to investigate the role of residues in the transmembrane domains in antagonist binding. Our results indicate that the amino acids Asp176 in the third transmembrane domain (TMD), Glu237 in TMD IV, and Ser258 in TMD V of alpha(1d)-AR were directly involved in prazosin and tamsulosin binding. The Asp176Ala mutant did not exhibit any affinity for [(3)H]prazosin and neither did it show agonist-stimulated inositol phosphates (IP) formation.

Asp125 and Thr130 in transmembrane domain 3 are major sites of alpha1b-adrenergic receptor antagonist binding.

Site-directed mutagenesis was used to investigate the molecular interactions involved in prazosin binding to the human alpha(1b)-adrenergic receptor (alpha(1b)-AR) receptor. Based on molecular modeling studies, Thr130 and Asp125 in transmembrane region III of the alpha(1b)-AR receptor were found to interact with prazosin. Thr130 and Asp125 were mutated to alanine (Ala) and expressed in HEK293 cells.

Identification of a key amino acid of the human 5-HT(2B) serotonin receptor important for sarpogrelate binding.

Based on radio-ligand binding and molecular modeling studies, sarpogrelate shows a moderate selectivity for 5-HT(2B) versus 5-HT(2A) receptors. To confirm the modeling data of sarpogrelate to 5-HT(2B) receptors predicting interaction of sarpogrelate towards Asp135 in helix 3 of 5-HT(2B) receptors, we constructed and characterized the mutation of this residue by site-directed mutagenesis. The Asp135Ala mutant did not exhibit any affinity for [(3)H]rauwolscine.

Differential inhibition by oxygen radicals of vasoactive amines-induced contractions in the porcine coronary artery.

Reactive oxygen species (ROS) play an important role in normal metabolic and signaling processes. Excess ROS, however, can cause severe cardiovascular damage. Thus, the present study was designed to examine effects of H(2)O(2) and xanthine plus xanthin oxidase (X/XO) on the serotonin (5HT), histamine (His) and acetylcholine (ACh)-induced contractions of porcine coronary arteries.

Beta-blockers show inverse agonism to a novel constitutively active mutant of beta1-adrenoceptor.

We obtained a new mutant of the beta(1)-adrenergic receptor (beta(1)-AR) by point mutations that can constitutively activate beta(1)-AR. Aspartate104 of the beta(1)-AR in the 2nd transmembrane was replaced with alanine. The beta(1)-AR mutant expressed in human embryonic kidney (HEK)-293 cells displayed high level of constitutive activity with respect to wild-type (P<0.

Inverse agonist activity of sarpogrelate, a selective 5-HT2A-receptor antagonist, at the constitutively active human 5-HT2A receptor.

Mutations producing constitutively active G-protein coupled receptors have been found in the pathophysiology of several diseases, implying that inverse agonists at the constitutively active receptors may have preferred therapeutic applications. Because of the involvement of 5-HT(2A) receptors in mediating many cardiovascular diseases, constitutively active mutants of the 5-HT(2A) receptor may be responsible for the disease states. Thus, the purpose of the present study was to investigate the inverse agonist activity of sarpogrelate, a selective 5-HT(2A)-receptor antagonist, and its active metabolite, M-1; and we compared their activities with those of other 5-HT(2A)-receptor antagonists such as ritanserin, ketanserin, and cyproheptadine.