piperidines and Mouth-Neoplasms

We investigated the analgesic effect and the neurological recovery time after administration of remifentanil in mechanically ventilated patients in an intensive care unit. Twenty patients, after trauma or major surgery with no intracranial pathology, were randomized to receive either remifentanil/propofol (n=10) or sufentanil/propofol (n=10). A sedation score and a simplified pain score were used to assess adequate sedation and analgesia. Medication was temporarily stopped after 24 h. Immediately before and 10 and 30 min after, the degree of sedation and pain score were evaluated. Adequate analgesia and sedation was achieved with remifentanil 10.6 microg kg(-1) h(-1) and propofol 2.1 mg kg(-1) h(-1), or sufentanil 0.5 microg kg(-1) h(-1) and propofol 1.3 mg kg(-1) h(-1). The difference in propofol dose between groups was significant. Ten minutes after terminating the medication, the degree of sedation decreased significantly after remifentanil and all patients could follow simple commands. During the following 20 min, all patients with remifentanil emerged from sedation and complained of considerable pain. By contrast, in the sufentanil group, only six (7) responded to commands after 10 (30) min and their pain score remained essentially unchanged during the 30-min observation period. We conclude that, in contrast to sufentanil, remifentanil facilitates rapid emergence from analgesia and sedation, allowing a clinical neurological examination within 10-30 min in mechanically ventilated patients with no intracranial pathology.

Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Anesthesia Recovery Period; Anesthetics, Combined; Female; Heart Rate; Humans; Male; Middle Aged; Mouth Neoplasms; Multiple Trauma; Pain, Postoperative; Piperidines; Propofol; Remifentanil; Respiration, Artificial; Sufentanil; Wounds and Injuries

We previously found that marine sponge-derived manoalide induced antiproliferation and apoptosis of oral cancer cells as well as reactive species generations probed by dichloro-dihydrofluorescein diacetate (DCFH-DA) and MitoSOX Red. However, the sources of cellular and mitochondrial redox stresses and the mutual interacting effects between these redox stresses and apoptosis remain unclear. To address this issue, we examined a panel of reactive species and used the inhibitors of cellular reactive species (

Topics: Acetylcysteine; Apoptosis; Cell Line, Tumor; Cell Survival; Ethidium; Fluoresceins; Humans; Mitochondria; Mouth Neoplasms; Oligopeptides; Organophosphorus Compounds; Phenanthridines; Piperidines; Reactive Oxygen Species; Terpenes

Oral squamous cellular carcinoma (OSCC) is considered a life-threatening disease with detection in late stages, which forces us to opt for dangerous treatment with a combination of chemotherapy and radiotherapy. Herbal components such as piperine and quercetin are derived from edible sources, proving their anticancer potential against oral cancer cells in vitro. Encapsulation into lipid matrix-mediated nanostructured lipid carriers (NLCs) can make both drugs bio-accessible. NLCs were synthesised using the high shear homogenisation method and characterised for their physicochemical properties, followed by in vitro cellular evaluation in FaDu oral cancer cells. NLCs showed negatively charged particles smaller than 180 nm with a polydispersity index (PDI) of <0.3. Both drugs were found to encapsulate sufficiently, with >85% entrapment efficiency and an improved drug release profile compared to their pristine counterparts. Differential scanning calorimetry (DSC) thermograms showed conversion into an amorphous matrix in lyophilized NLCs, which was supported by X-ray diffraction (XRD) analysis. The cytotoxicity assay showed the IC

Topics: Alkaloids; Animals; Apoptosis; Benzodioxoles; Drug Liberation; Drug Screening Assays, Antitumor; Fatty Acids; Humans; Membrane Potential, Mitochondrial; Mouth Neoplasms; Nanoparticle Drug Delivery System; Nanostructures; Particle Size; Piperidines; Polyunsaturated Alkamides; Quercetin; Rats; Squamous Cell Carcinoma of Head and Neck; Tissue Distribution

Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck. However, the molecular mechanism underlying its development and progression is yet unclear. Genes that are differentially expressed, that is, differentially expressed genes (DEGs), between normal and diseased tissues are believed to be involved in disease development and progression. To identify the DEGs in OSCC and explore their role in occurrence and progression, we established a Chinese hamster OSCC model, determined the DEG, screened the identified DEGs, and performed Gene Ontology (GO) and KEGG enrichment analyses. A protein-protein interaction (PPI) network was generated to screen potential candidate genes. We then analyzed the expression, tumor stage and prognosis of candidate genes using the Gene Expression Profiling Interactive Analysis (GEPIA) database. Finally, we verified the candidate DEGs by quantitative real-time PCR and Gene Expression Omnibus analysis. The results showed 194 significantly DEGs, 140 enriched GO terms, and 8 KEGG pathways, which suggested that OSCC was closely related to the immune system, cell migration, and extracellular matrix. GEPIA and PPI network analysis revealed that SPP1, TNC, and ACTA1 were significantly related to tumor staging; SPP1, tissue inhibitors of matrix metallopeptidases (MMPs) 1 (TIMP1), and ACTA1 were closely related to prognosis. The scores for the top five highest degree genes were close, and the TIMP1/MMP9 axis appeared to be at the center of the PPI network, indicating that expression changes in the TIMP1/MMP9 axis and related genes may be involved in tumor invasion and metastasis. These findings provide novel insights into the mechanism of oral cancer.

Topics: Animals; Anthracenes; Apoptosis; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Proliferation; Computational Biology; Cricetinae; Cricetulus; Disease Models, Animal; Gene Expression Regulation, Neoplastic; Humans; Male; Matrix Metalloproteinase 9; Mice; Mouth Neoplasms; Piperidines; Prognosis; Tissue Inhibitor of Metalloproteinase-1; Tumor Cells, Cultured

The study focused on identifying the mechanisms or drugs that could sensitize P-glycoprotein (P-gp)-overexpressing resistant KBV20C cancer cells to halaven (HAL) or vincristine (VIC) treatment.. Based on the relatively low dose or IC. DON or SID reduced cell viability, increased G. These results suggest that HAL-FLU or HAL-SID sensitization in KBV20C cells involves both cytotoxic and P-gp inhibitory effects, whereas HAL-DON sensitization may involve only P-gp inhibitory activity of DON.

Topics: Antimitotic Agents; Apoptosis; ATP Binding Cassette Transporter, Subfamily B; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Survival; Donepezil; Down-Regulation; Drug Repositioning; Drug Resistance, Neoplasm; Drug Synergism; Furans; Gene Expression Regulation, Neoplastic; Humans; Indans; Ketones; Mouth Neoplasms; Piperidines; Sildenafil Citrate; Vincristine

Piperine is a nitrogenous pungent substance exhibiting multifunctional pharmacological properties. However, the mechanism underlying its anticancer potential is not well elucidated in human oral squamous carcinoma (KB) cell line. The anticancer potential of piperine was evaluated through potent biomarkers viz. reactive oxygen species (ROS), cellular apoptosis, and loss of mitochondrial membrane potential (MMP). In addition, cell cycle kinetics and caspases-3 activity were also carried out to confirm anticancer activity of piperine. Results showed that various concentrations (25-300 μM) of piperine exposure reduced the cell viability of KB cells significantly (P < 0.01). Piperine induced significant (P < 0.01) dose-related increment in ROS production and nuclear condensation. Moreover, piperine stimulated cell death by inducing loss of MMP, and caspase-3 activation. Cell cycle study revealed that piperine arrested the cells in G2/M phase and decreased the DNA content. Findings of this study suggest the efficacy of piperine in inducing cell death via the decrease in MMP and ROS liberation followed by caspase-3 activation and cell cycle arrest. Further assessment of the anticancer potency of piperine is needed for anticancer drug development.

Topics: Alkaloids; Antineoplastic Agents; Apoptosis; Benzodioxoles; Carcinoma, Squamous Cell; Caspase 3; Cell Cycle Checkpoints; Cell Proliferation; Humans; KB Cells; Membrane Potential, Mitochondrial; Mitochondria; Mouth Neoplasms; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Reactive Oxygen Species

Canine oral fibrosarcoma (COF) is one of the most common oral tumors in dogs and carries a guarded prognosis due to a lack of effective systemic therapeutic options. Mastinib and imatinib are two commonly used tyrosine kinase inhibitors (TKIs) in veterinary oncology but their potential efficacy against COF is uncharacterized. To begin investigating the rationale for use of these TKIs against COF, the present study tested for the presence TKI targets PDGFR-α, PDGFR-β, Kit, and VEGFR-2 and examined the in vitro effects on cell viability after TKI treatment alone or with doxorubicin. Immunohistochemistry for PDGFR-α, PDGFR-β, Kit, and VEGFR-2 was performed in 6 COF tumor biopsies. Presence of these same receptors within 2 COF cell lines was probed by reverse transcription-polymerase chain reaction and, for those with mRNA detected, confirmed via western blot. Effects on cell viability were assessed using an MTS assay after masitinib or imatinib treatment alone (0-100 μM), or in combination with doxorubicin (0-3000 nM doxorubicin). Anti-PDGFRB siRNA knockdown was performed and the effect on cell viability quantified.. Expression of the TKI targets evaluated was similar between the 2 COF cell lines and the 6 COF tumor biopsies: PDGFR-α and PDGFR-β were detected in neoplastic cells from most COF tumor biopsies (5/6 and 6/6, respectively) and were present in both COF cell lines; KIT and KDR were not detected in any sample. Masitinib and imatinib IC50 values ranged from 7.9-33.4 μM, depending on the specific TKI and cell line tested. The addition of doxorubicin resulted in synergistic cytotoxicity with both TKIs. Anti-PDGFRB siRNA transfection reduced PDGFR-β protein expression by 77% and 67% and reduced cell viability by 24% (p < 0.0001) and 28% (0 = 0.0003) in the two cell lines, respectively.. These results provide rationale for further investigation into the use of TKIs, possibly in combination with doxorubicin, as treatment options for COF.

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Cell Line, Tumor; Cell Proliferation; Dog Diseases; Dogs; Doxorubicin; Fibrosarcoma; Imatinib Mesylate; Mouth Neoplasms; Piperidines; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-kit; Pyridines; Receptor, Platelet-Derived Growth Factor alpha; Receptor, Platelet-Derived Growth Factor beta; Thiazoles; Vascular Endothelial Growth Factor Receptor-2

Development and characterization of animal models for human cancers is important for the improvement of diagnosis and therapy. The oral squamous cell carcinoma (OSCC) of domestic animals resembles human OSCC in many aspects; thus, cell lines derived from OSCC of cats and dogs are a valuable model for human OSCC. We characterized 1 feline OSCC (FeOSCC-Sidney) and 1 canine OSCC (K9OSCC-Abby) cell line and compared their characteristics with human OSCC cell line hSCC-25. We calculated the doubling time of the new OSCC cell lines and evaluated the expression profiles of cancer-related markers and cell-cycle proteins such as c-kit, platelet-derived growth factor receptor, vascular endothelial growth factor receptor, epidermal growth factor receptor, cyclooxygenase (COX)-1, COX-2, and p27 by immunocytochemistry and Western blot analysis. We evaluated the effects of novel receptor tyrosine kinase inhibitor (Masitinib, AB1010) and the nonsteroidal anti-inflammatory drug piroxicam on the previously mentioned OSCC cells. Interestingly, AB1010 increased expression levels of COX-2 in all tested OSCCs. Cotreatment of piroxicam with Masitinib significantly inhibited cell proliferation of OSCC as compared to either drug alone through the c-kit and AKT signaling pathways. Piroxicam inhibited Masitinib-induced COX-2 expression in all tested OSCCs. Therefore, targeting these two signaling pathways simultaneously was more efficient for inhibition of OSCCs across these species.

Topics: Animals; Benzamides; Carcinoma, Squamous Cell; Cats; Cell Line, Tumor; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Dogs; Gene Expression Regulation, Enzymologic; Humans; Mouth Neoplasms; Piperidines; Piroxicam; Protein Kinase Inhibitors; Pyridines; Thiazoles

In the present work, a new bis heterocyclic compound comprising both the piperidone and thiohydantoin nuclei namely 3-[2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino]-2-thioxoimidazolidin-4-one was synthesised and characterised with the help of mp, elemental analysis, FT-IR, MS and one-dimensional NMR ((1)H and (13)C) spectra. The inhibitory effect of 3-[2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino]-2-thioxoimidazolidin-4-one on 7,12-dimethylbenz[a]anthracene (DMBA) induced buccal pouch carcinogenesis was investigated in Syrian male hamsters. All the hamsters that were painted with DMBA on their buccal pouches for 14 weeks developed squamous cell carcinoma. Administration of 3-[2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino]-2-thioxoimidazolidin-4-one effectively suppressed the oral carcinogenesis initiated with the DMBA as revealed by a reduced incidence of neoplasms. Lipid peroxidation, glutathione (GSH) content and the activities of glutathione peroxidase (GPx), glutathione S-transferase (GST) were used to biomonitor the chemopreventive potential of 3-[2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino]-2-thioxoimidazolidin-4-one. Lipid peroxidation was found to be significantly decreased, whereas GSH, GPx, GST and GGT were elevated in the oral mucosa of tumour bearing animals. Our data suggest that 3-[2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino]-2-thioxoimidazolidin-4-one may exert its chemopreventive effects in the oral mucosa by modulation of lipid peroxidation, antioxidants and detoxification systems.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anthracenes; Anticarcinogenic Agents; Biomarkers; Carcinogens; Carcinoma, Squamous Cell; Cricetinae; Dose-Response Relationship, Drug; Drug Design; gamma-Glutamyltransferase; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Lipid Peroxidation; Male; Mesocricetus; Molecular Structure; Mouth Mucosa; Mouth Neoplasms; Piperidines; Piperidones; Random Allocation; Thiohydantoins; Tumor Burden

Despite recent therapeutic advances, several factors, including field cancerization, have limited improvements in long-term survival for oral squamous cell carcinoma (OSCC). Therefore, comprehensive treatment plans must include improved chemopreventive strategies. Using the 4-nitroquinoline 1-oxide (4-NQO) mouse model, we tested the hypothesis that ZD6474 (Vandetanib, ZACTIMA) is an effective chemopreventive agent. CBA mice were fed 4-NQO (100 μg/mL) in their drinking water for 8 weeks and then randomized to no treatment or oral ZD6474 (25 mg/kg/d) for 24 weeks. The percentage of animals with OSCC was significantly different between the two groups (71% in control and 12% in the ZD6474 group; P ≤ 0.001). The percentage of mice with dysplasia or OSCC was significantly different (96% in the control and 28% in the ZD6474 group; P ≤ 0.001). Proliferation and microvessel density scores were significantly decreased in the ZD6474 group (P ≤ 0.001 for both). Although proliferation and microvessel density increased with histologic progression in control and treatment cohorts, epidermal growth factor receptor and vascular endothelial growth factor receptor-2 phosphorylation was decreased in the treatment group for each histologic diagnosis, including mice harboring tumors. OSCC from ZD6474-treated mice exhibited features of epithelial to mesenchymal transition, as shown by loss E-cadherin and gain of vimentin protein expression. These data suggest that ZD6474 holds promise as an OSCC chemopreventive agent. They further suggest that acquired resistance to ZD6474 may be mediated by the expression of an epithelial to mesenchymal transition phenotype. Finally, the data suggests that this model is a useful preclinical platform to investigate the mechanisms of acquired resistance in the chemopreventive setting.

Topics: 4-Nitroquinoline-1-oxide; Animals; Antineoplastic Agents; Carcinogens; Disease Models, Animal; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; ErbB Receptors; Immunohistochemistry; Mice; Mice, Inbred CBA; Mouth Neoplasms; Neovascularization, Pathologic; Piperidines; Quinazolines; Quinolones; Receptors, Vascular Endothelial Growth Factor

Oral carcinoma accounts for 40-50 percent of all cancers in India. Tobacco chewing, smoking and alcohol consumption are the major risk factors associated with the high incidence of oral cancer in India. Our aim was to investigate the chemopreventive potential of curcumin and piperine during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis.. Oral squamous cell carcinoma was developed in the buccal pouch of Syrian golden hamsters, by painting them with 0.5 percent DMBA in liquid paraffin, three times a week for 14 weeks. The tumour incidence, tumour volume and burden were determined in the buccal pouches. The status of phase II detoxification agents, lipid peroxidation and antioxidants were estimated by specific colorimetric methods.. We observed 100 percent tumour formation in DMBA-alone painted hamsters. Disturbances in the status of lipid peroxidation, antioxidants and phase II detoxification agents were noticed in DMBA-alone painted hamsters. Oral administration of curcumin (80 mg/kg body weight) and piperine (50 mg/kg body weight) to DMBA-painted hamsters on alternate days to DMBA painting for 14 weeks completely prevented the formation of oral carcinoma. Also, curcumin and piperine restored the status of lipid peroxidation, antioxidants and detoxifying agents in DMBA-painted hamsters.. The chemopreventive efficacy of curcumin and piperine is probably due to their antilipidperoxidative and antioxidant potential as well as their modulating effect on the carcinogen detoxification process.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Alkaloids; Animals; Anticarcinogenic Agents; Antioxidants; Benzodioxoles; Carcinogens; Carcinoma, Squamous Cell; Cheek; Colorimetry; Cricetinae; Curcumin; Humans; Lipid Peroxidation; Mesocricetus; Mouth Neoplasms; Piperidines; Polyunsaturated Alkamides

Flavopiridol is a synthetic flavone that inhibits tumor growth by suppressing cyclin-dependent kinases (CDKs). We have investigated effects of flavopiridol in oral squamous cell carcinoma (OSCC). Flavopiridol was found to inhibit the growth of OSCC cells in a time- and dose-dependent manner. Induction of apoptosis was observed in all cells showing accumulated cells with sub-G(1) DNA contents, DNA fragmentations, and PARP cleavages. While Bcl-2 and Bax expression did not change, Bcl-x(L) was down regulated and Bcl-xs was up-regulated after being exposed to flavopiridol. Flavopiridol treatments also resulted in remarkable reductions of cyclin A, cyclin B, and cyclin D1 expressions. We also found that expression levels of CDK activation kinase and CDC25C were reduced, and p34 inactive form CDK2 were up-regulated. Our data indicate that flavopiridol has growth inhibition activities against OSCC. Flavopiridol not only inhibits CDKs directly, but it also inhibits the CDKs activation pathway and activates the Bcl-x apoptotic pathway.

Topics: Antineoplastic Agents; Apoptosis; bcl-X Protein; Cell Division; Cyclin-Dependent Kinases; Cyclins; Dose-Response Relationship, Drug; Enzyme Inhibitors; Flavonoids; Growth Inhibitors; Humans; Mouth Neoplasms; Piperidines; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured

A total of 320 Chinese hamsters (Cricetulus griseus) (CH) were subcutaneously (s.c.) treated with 1/5, 1/10, or 1/20 LD50 of N-nitrosomorpholine (NM) or N-nitrosopiperidine (NP). In the CH, NM and NP both produced up to a 100% rate of papillomas of the cheek pouch, tongue, pharynx, esophagus and forestomach. Occasionally squamous cell carcinomas also developed in these organs. A high rate of hepatomas was realized by NP.

Topics: Animals; Carcinogens; Carcinoma, Squamous Cell; Cricetinae; Esophageal Neoplasms; Female; Liver Neoplasms; Male; Morpholines; Mouth Neoplasms; Neoplasms, Experimental; Nitrosamines; Nitroso Compounds; Nose Neoplasms; Papilloma; Pharyngeal Neoplasms; Piperidines; Respiratory Tract Neoplasms; Stomach Neoplasms

Topics: Animals; Carcinogens; Carcinoma, Squamous Cell; Cricetinae; Female; Gastrointestinal Neoplasms; Lung Neoplasms; Male; Morpholines; Mouth Neoplasms; Neoplasms, Experimental; Neoplasms, Multiple Primary; Nitrosamines; Nose Neoplasms; Piperidines; Respiratory Tract Neoplasms

Topics: Antineoplastic Agents; Carcinoma; Cell Line; Cells, Cultured; Humans; In Vitro Techniques; Indolizines; Isoquinolines; Mouth Neoplasms; Neoplasms, Experimental; Phenanthrenes; Piperidines

Topics: Animals; Azepines; Carcinoma, Squamous Cell; Facial Neoplasms; Female; Male; Mice; Mice, Inbred Strains; Mouth Mucosa; Mouth Neoplasms; Nasal Mucosa; Nitroso Compounds; Pharyngeal Neoplasms; Pharynx; Piperidines; Skin Neoplasms; Time Factors