piperidines and Laryngeal-Neoplasms

In the context of well-known inhibitory effects of Farrerol on the invasion of lung squamous cell carcinoma cells, the unexplored effect and regulatory mechanism of Farrerol on laryngeal squamous cell carcinoma (LSCC) emerged as the target in this study.. After treatment with Farrerol alone, or together with MitoTempo, the viability, apoptosis, cell cycle distribution, migration, and invasion of LSCC cells were measured using MTT, flow cytometry, wound-healing, and transwell assays, respectively. Meanwhile, the levels of cytochrome C (Cyt C), Cleaved caspase-3/9, Cyclin D1, E-cadherin, N-cadherin, and Vimentin in LSCC cells were evaluated by Western blot; the reactive oxygen species (ROS) formation intensity and the disruption of mitochondrial membrane potential (MMP) of LSCC cells were assessed using flow cytometry; and the effect of Farrerol on xenograft tumor formation was evaluated in animal experiment.. Farrerol (10, 20, 50 μM) inhibited the viability, proliferation, cell cycle progression, migration and invasion, but promoted apoptosis, ROS formation intensity and disruption of MMP of LSCC cells. Moreover, Farrerol up-regulated Cyt C (in the cytoplasm), Cleaved caspase-3/9 and E-cadherin levels, but down-regulated Cyclin D1, N-cadherin and Vimentin levels in LSCC cells. Additionally, we uncovered that MitoTempo reversed the promoting effects of Farrerol on ROS formation intensity, apoptosis, and Cyt C and Cleaved caspase-3/9 levels in LSCC cells, while improving the disruption of MMP in Farrerol-treated LSCC cells. Also, Farrerol lessened the volume and weight of mice tumors.. Farrerol suppressed the migration, invasion, and induced the apoptosis of LSCC cells via the mitochondria-mediated pathway.

Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chromones; Gene Expression Regulation, Neoplastic; Humans; Laryngeal Neoplasms; Male; Membrane Potential, Mitochondrial; Mice; Mitochondria; Neoplasm Invasiveness; Organophosphorus Compounds; Piperidines; Reactive Oxygen Species; Squamous Cell Carcinoma of Head and Neck; Up-Regulation; Xenograft Model Antitumor Assays

Although poly (ADP-ribose) polymerase (PARP) inhibitors, as anti-tumor drugs targeting the DNA damage response (DDR), have been used for the therapy of various tumors, few researches reported their effect on laryngeal squamous cell carcinoma (LSCC). Here, we first discovered that the PARP-1/2 inhibitor Niraparib could simultaneously induce cell growth inhibition and autophagy in LSCC TU212 and TU686 cells. Niraparib decelerated cell cycle of LSCC by arresting G1 phase and preventing the cells from entering S phase. DNA lesions were also observed upon Niraparib treatment as evidenced by the accumulation of γH2AX and abatement of pRB expression. In addition, autophagy generation was confirmed by the observation of autophagosomes, LC3-positive autophagy-like vacuoles, and obvious conversion of LC3-I to LC3-II. Moreover, blocking autophagy enhanced Niraparib-induced growth inhibition and DNA lesions. Further studies suggested that autophagy suppression could obstruct the activation of checkpoint kinase 1 (Chk1) through elevating proteasomal activity and then impair the capacity of homologous recombination (HR), thereby improving the anti-LSCC efficiency of Niraparib. Collectively, these findings suggested that simultaneous targeting of Niraparib and autophagy might be a promising therapeutic schedule for LSCC in clinic.

Topics: Autophagic Cell Death; Cell Cycle; Cell Line, Tumor; DNA Damage; Humans; Indazoles; Laryngeal Neoplasms; Piperidines; Poly(ADP-ribose) Polymerase Inhibitors

To evaluate microviscosity and sorption capacity of erythrocyte membranes (SCEM) from patients with laryngeal cancer (LC).. Samples from 35 patients with LC of stages II and III and 20 healthy volunteers were investigated by electron paramagnetic resonance with Bis(1-oxyl-2,2,6,6-tetramethylpiperidinyl-4)-ester of 5,7-dimethyladamantane-1,3-dicarbonic acid (AdTEMPO) probe. SCEM was evaluated by amount of unabsorbed methylene blue.. Microviscosity of erythrocyte membranes was determined by the effective rotational diffusion correlation times (τeff) and a decrease in radical spectrum signal intensity per hour. The most apparent decrease in mobility of the AdTEMPO in erythrocytes was observed prior to washing of erythrocytes with 0.9% NaCl for 5 min after probe insertion. The deceleration after 60 min was observed only in stage II LC. τeff was at control values after washing of erythrocytes of stage II LC 5 min after probe insertion and was significantly reduced in stage III LC in comparison to control. Radical spectrum signal intensity per hour in samples of stage II and III patients prior to and after washing of erythrocytes was on average 1.5-fold higher than that of control. SCEM in samples of stage II and III LC was found in 40 and 33% cases, respectively and was on average significantly reduced in comparison to control.. The initial interaction of AdTEMPO with erythrocyte membranes of stage II and III LC patients is accompanied by an increase in τeff, indicating deceleration of probe rotation. τeff of the probe in membranes remains unchanged in 60 min, indicating changes in the structural organization of lipid bilayer and its associated proteins in particular. The similarity of SCEM for both studied groups reflects the pathological changes in function of erythrocyte membranes.

Topics: Adamantane; Aged; Carcinoma, Squamous Cell; Electron Spin Resonance Spectroscopy; Erythrocyte Membrane; Humans; Laryngeal Neoplasms; Lipid Bilayers; Male; Membrane Fluidity; Membrane Lipids; Membrane Proteins; Middle Aged; Molecular Probes; Molecular Structure; Neoplasm Staging; Piperidines; Time Factors; Viscosity

We report a case of delayed awakening with characteristic repeated loss of consciousness after remifentanil infusion complicated by leakage from an intravenous catheter. A 30-year-old male underwent microlaryngeal surgery for a vocal cord polyp. During anesthetic induction, infiltration from an intravenous (IV) line in the left forearm was observed 10 min after initiating a continuous infusion of remifentanil 0.5 microg x kg-1 x min -1. A second peripheral IV catheter was placed in the right forearm and general anesthesia was induced with remifentanil infusion at 0.3 microg x kg-1 x min- 1, propofol 120mg, fentanyl 100 microg, and rocuronium 70 mg. Anesthesia was maintained with remifentanil 0.05-0.3 microg x kg-1 x min -1and sevoflurane (1.5% in oxygen) for the 4 min of surgery. A few minutes after tracheal extubation, the patient developed respiratory arrest and loss of consciousness. We immediately ventilated him with a bag-valve-mask and administered naloxone 0.04 mg. Thereafter, he repeatedly awoke and was drowsy three times over the next 5hr. It was followed by an uneventful postoperative period. No remarkable deficit was observed in the patient. Blood gases, electrolytes, glucose values, and body temperature were within normal ranges throughout the perioperative period. Brain computed tomography, mag- netic resonance imaging, and electroencephalography showed no abnormalities. It was considered that the incidental subcutaneous remifentanil accumulation may have caused the respiratory suppression and delayed awakening.

Topics: Adult; Anesthesia Recovery Period; Anesthesia, Intravenous; Anesthetics, Intravenous; Equipment Failure; Humans; Laryngeal Neoplasms; Male; Piperidines; Polyps; Remifentanil; Vascular Access Devices

Topics: Anesthesia, Intravenous; Atracurium; Biopsy; Carcinoma, Squamous Cell; Epilepsies, Partial; Hernia, Hiatal; Humans; Laryngeal Neoplasms; Laryngectomy; Male; Middle Aged; Miller Fisher Syndrome; Monitoring, Intraoperative; Neck Dissection; Neuromuscular Blocking Agents; Piperidines; Propofol; Pulmonary Disease, Chronic Obstructive; Remifentanil; Secondary Prevention; Tracheostomy

A 48-year-old woman was diagnosed with cavernous hemangioma of hypopharynx and larynx, which extended to the trachea and mediastinum. She was scheduled for tracheostomy and open surgical excision of hypopharynx hemangioma under general anesthesia. On induction of anesthesia, we planned awake fiberoptic intubation according to the difficult airway algorithm of the American Society of Anesthesiologists. Under continuous infusion of remifentanil at 0.1-0.2 microg x kg(-1) x min(-1), the patient became sedated while spontaneously breathing, and her pain and laryngeal reflexes were reduced. Although tracheal intubation was successfully accomplished without injuring the hypopharynx hemangioma, tracheostomy was difficult because of bleeding from the surgical site. After 3 hr of surgery with 1880 g of blood loss, the surgeons quitted tracheostomy and the patient was transferred to the intensive care unit. Her airway was managed with endotracheal tube for 7 days, and open surgical excision of hypopharynx hemangioma was performed on day 7. The patient was successfully extubated on day 9 with the support of non-invansive positive pressure ventilation. Awake fiberoptic intubation under remifentanil infusion is safe and useful approach for patients with airway hemangioma.

Topics: Anesthesia, General; Anesthetics, Intravenous; Female; Fiber Optic Technology; Hemangioma, Cavernous; Humans; Hypopharyngeal Neoplasms; Intubation, Intratracheal; Laryngeal Neoplasms; Middle Aged; Neoplasms, Multiple Primary; Piperidines; Remifentanil; Tracheostomy

It has been demonstrated that substance P (SP) induces cell proliferation and neurokinin-1 (NK-1) receptor antagonists inhibit growth in several human cancer cell lines, but it is currently unknown whether such actions are exerted on human laryngeal carcinoma cell line HEp-2. In addition, the presence of NK-1 receptor has not been demonstrated in this cell line. We carried out an in vitro study of the growth inhibitory capacity of the NK-1 receptor antagonists L-733,060 and L-732,138 against human laryngeal carcinoma cell line HEp-2. Coulter counter was used to determine viable cell numbers followed by application of the tetrazolium compound MTS. Furthermore, an immunoblot analysis was used to determine the NK-1 receptor, and the 4',6-diamidino-2-phenylindole (DAPI) method was applied to demonstrate apoptosis of the laryngeal carcinoma cells. We observed the presence of several NK-1 receptors isoforms (34, 46, 58 and 75 kDa). Nanomolar concentrations of SP increased the growth rate of the cell line and micromolar concentrations of L-733,060 and L-732,138 inhibited the growth of the HEp-2 cells in a dose-dependent manner, with and without previous administration of SP. The 50% inhibition concentration values were 21.34 microM and 37.97 (48 h) respectively for HEp-2. NK-1 receptor presence on HEp-2 cells was confirmed by western blotting. DAPI staining revealed the presence of apoptosis following NK-1 receptor antagonists treatment. We demonstrated that NK-1 receptors were present in this laryngeal cancer cell line; these findings demonstrate that SP acts as a mitogen on the human laryngeal carcinoma cell line HEp-2 through the NK-1 receptor, and also indicate that both NK-1 receptors antagonists induced apoptosis of the tumour cells. This new action, reported here for the first time, suggests that the NK-1 receptor is a new and promising target in the treatment of human laryngeal carcinoma.

Topics: Antineoplastic Agents; Apoptosis; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Delivery Systems; Drug Evaluation, Preclinical; Drug Screening Assays, Antitumor; Humans; Laryngeal Neoplasms; Mitosis; Neurokinin-1 Receptor Antagonists; Piperidines; Receptors, Neurokinin-1; Substance P; Tryptophan

Topics: Anesthetics, Intravenous; Heart-Lung Transplantation; Humans; Laryngeal Neoplasms; Male; Middle Aged; Piperidines; Remifentanil

We report the safe use of remifentanil as part of the anaesthetic technique in a patient undergoing major head and neck surgery who was being treated for depressive illness with the non-specific monoamine oxidase inhibitor (MAOI) phenelzine.

Topics: Analgesics, Opioid; Antidepressive Agents; Carcinoma, Squamous Cell; Drug Interactions; Humans; Laryngeal Neoplasms; Male; Middle Aged; Monoamine Oxidase Inhibitors; Phenelzine; Piperidines; Remifentanil

Topics: Animals; Bronchial Neoplasms; Cricetinae; Epithelial Cells; Epithelium; Female; Laryngeal Neoplasms; Lethal Dose 50; Male; Microscopy, Electron, Scanning; Morpholines; Neoplasms, Experimental; Nitroso Compounds; Nose Neoplasms; Piperidines; Polyps; Respiratory Tract Neoplasms; Trachea; Tracheal Neoplasms

Topics: Animals; Carcinoma; Culture Techniques; Fibroblasts; Galantamine; Humans; Isoquinolines; Laryngeal Neoplasms; Mice; Nitrofurans; Piperidines