Oral Cancer Pain Includes Thermal Allodynia That May Be Attenuated by Chronic Alcohol Consumption

Background: Oral cancer is one of the most painful cancer types, and is often refractory to existing analgesics. Oral cancer patients frequently develop a tolerance to opioids, the mainstay of current cancer pain therapy, leaving them with limited therapeutic options. Thus, there is a great need to identify molecular mechanisms driving oral cancer pain in an effort to develop new analgesics. Previous reports demonstrate that oral cancer patients experience intense mechanical pain and pain in function. To date, no studies have examined thermal pain in oral cancer patients or the role that alcohol consumption plays in oral cancer pain. This study aims to evaluate patient-reported pain levels and thermal allodynia, potential molecular mechanisms mediating thermal allodynia, and the effects of alcohol consumption on patient-perceived pain. Methods: This study evaluated human oral squamous cell carcinoma (OSCC) cell lines for their ability to activate thermosensitive channels in vitro and validated these findings in a rat model of orofacial pain. Patient-reported pain in a south Texas OSCC cohort (n = 27) was examined using a visual analog scale (VAS). Covariant analysis examined variables such as tobacco and alcohol consumption, ethnicity, gender, and cancer stage. Results: We determined that OSCC secretes factors that stimulate both the Transient Receptor Potential Ankyrin type 1 channel (TRPA1; noxious cold sensor) and the Transient Receptor Potential Vanilloid type 1 channel (TRPV1; noxious heat sensor) in vitro and that OSCC-secreted factors sensitize TRPV1 nociceptors in vivo. These findings were validated in this cohort, in which allodynia to cold and heat were reported. Notably, subjects that reported regular alcohol consumption also reported lower pain scores for every type of pain tested, with significantly reduced cold-induced pain, aching pain, and burning pain. Conclusion: Oral cancer patients experience multiple types of cancer pain, including thermal allodynia. Alcohol consumption correlates with reduced OSCC pain and reduced thermal allodynia, which may be mediated by TRPA1 and TRPV1. Hence, reduced pain in these patients may contribute to a delay in seeking care, and thus a delay in early detection and treatment

Wittig derivatization of sesquiterpenoid polygodial leads to cytostatic agents with activity against drug resistant cancer cells and capable of pyrrolylation of primary amines

Many types of cancer, including glioma, melanoma, non-small cell lung cancer (NSCLC), among others, are resistant to proapoptotic stimuli and thus poorly responsive to current therapies based on the induction of apoptosis in cancer cells. The current investigation describes the synthesis and anticancer evaluation of unique C12-Wittig derivatives of polygodial, a sesquiterpenoid dialdehyde isolated from Persicaria hydropiper (L.) Delabre. These compounds were found to undergo an unprecedented pyrrole formation with primary amines in a chemical model system, a reaction that could be relevant in the biological environment and lead to the pyrrolation of lysine residues in the target proteins. The anticancer evaluation of these compounds revealed their promising activity against cancer cells displaying various forms of drug resistance, including resistance to proapoptotic agents. Mechanistic studies indicated that compared to the parent polygodial, which displays fixative general cytotoxic action against human cells, the C12-Wittig derivatives exerted their antiproliferative action mainly through cytostatic effects explaining their activity against apoptosis-resistant cancer cells. The possibility for an intriguing covalent modification of proteins through a novel pyrrole formation reaction, as well as useful activities against drug resistant cancer cells, make the described polygodial-derived chemical scaffold an interesting new chemotype warranting thorough investigation

Otro título: Elementos folklóricos y creación estética del Lazarillo de Tormes

Gregorio Marañón Moya, Dir. ICH. Dámaso Alonso, escritor. Elsa Mercado, Embajadora de Panamá en España.Cinta 1: Presentación por parte de Marañón -- Min. 0.24: El secretario general entrega las condecoraciones: Miembros de honor: Yolanda de Arzate Avendeyo. José Solís Ruiz, Mº Scret. Gral. del Movimiento. Antonio Garrigues, Embajador de España en Washington. José Antonio Giménez-Arnau, Embajador de España en Guatemala. James A. Farley, Ex-presidente del partido demócrata de EE.UU. Edmundo Correa, Ex-rector de la Universidad de Cuya. Francisco Javier Sánchez Cantón, Miembro de la Real Academia de la Historia. Federico García Sanchís, Miembro de la RAE. Juán José López Ibor, Catedrático Facultad de Medicina Madrid. Hermenegildo Arruga, Conde de Arruga. José de la Peña, Dir. Archivo de Indias. José Antonio Elola-Olaso, Delegado Nal. de Educación Física y Deportes. Alfonso de la Peña, Catedrático Facultad de Medicina de Madrid. Miembros titulares del ICH: Elvira Pérez Peña, Inst. Cuyano de Cultura Hispánica. Alberico Praga, Rector de la Unv. de Bahía. Francisco Monterde, de la Academia Mexicana de la Lengua. José Barroso, Presidente del Inst. Hispano-Mexicano. Jorge Montoya, Dir. Inst. Antioqueño de Cultura Hispánica. Paul Bouchard, Prof. Hª Precolombina Unv. Laval Canadá. George Age Ornstein, Dir. United Airlines. Luis Alfonso D'Escargnolle, Arquitecto Brasileño de la Casa de Brasil. Juán José Espinosa, Dir. Gral. PSOE. Marcos Peña Royo, Gobernador Civil de Asturias. Plácido Careaga, Pdte. Diputación Vizcaya. José Burgos y Rosado, Marqués de la Liseda. Gabriel Cañadas, Scre. Gral. Mº Infomación y Turismo. Jose María Mor, Dir. Personal Mº Asuntos Exteriores. Fernando Luis Ybarra y López de Dóriga, Marqués de de Agridulce y Pte. Del Ins. Cultura Vascongadas. Antonio Fondán, Dir. Escuela Periodismo Vascongadas. Jose Ignacio Ramos, Delegado de Prensa Embajada de España en Buenos Aires. Salvador Bermúdez, Delegado de Prensa Embajada de España en Lima. Jaime de Abrisqueta, Scre. Embajada de España en Quito. Tomás Lozano, Embajador de España en Honduras. Francisco Javier Chapa, Embajador de España en México. Amaro González de Mesa, Embajador de España en la Santa Sede. Jose Luís Aparicio, Cónsul España en Nueva Orleans. Joaquín Tomás, Cónsul de España en Mendoza. Enrique de la Hoz Díaz, Scret. Gral. Mº de Información -- MIn. 11.35: Conferencia de Dámaso Alonso "Elementos folklóricos y creación estética del Lazarillo de Tormes" -- Cinta 2: Continuación de la conferencia de Dámaso Alonso -- Min. 27.56: Discurso de Elsa Mercado, Embajadora de Panamá en España -- Min. 33.14: Palabras de clausura de Gregorion Marañó

Wittig derivatization of sesquiterpenoid polygodial leads to cytostatic agents with activity against drug resistant cancer cells and capable of pyrrolylation of primary amines

Many types of cancer, including glioma, melanoma, non-small cell lung cancer (NSCLC), among others, are resistant to proapoptotic stimuli and thus poorly responsive to current therapies based on the induction of apoptosis in cancer cells. The current investigation describes the synthesis and anticancer evaluation of unique C12-Wittig derivatives of polygodial, a sesquiterpenoid dialdehyde isolated from Persicaria hydropiper (L.) Delabre. These compounds were found to undergo an unprecedented pyrrole formation with primary amines in a chemical model system, a reaction that could be relevant in the biological environment and lead to the pyrrolation of lysine residues in the target proteins. The anticancer evaluation of these compounds revealed their promising activity against cancer cells displaying various forms of drug resistance, including resistance to proapoptotic agents. Mechanistic studies indicated that compared to the parent polygodial, which displays fixative general cytotoxic action against human cells, the C12-Wittig derivatives exerted their antiproliferative action mainly through cytostatic effects explaining their activity against apoptosis-resistant cancer cells. The possibility for an intriguing covalent modification of proteins through a novel pyrrole formation reaction, as well as useful activities against drug resistant cancer cells, make the described polygodial-derived chemical scaffold an interesting new chemotype warranting thorough investigation.SCOPUS: ar.jinfo:eu-repo/semantics/publishe