Taxol: Efficacy Against Oral Squamous Cell Carcinoma

Ledwitch, Kaitlyn; Ogburn, Ryenne N.; Cox, J. I.; Graham, Rebekah; Fritzsche, A.; Gosnell, Donna; Manning, Thomas

doi:10.2174/1389557511313040004

Cited by 14 publications

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“…Paclitaxel, a commonly used chemotherapeutic drug, has been used as the first-line therapy for various cancers (42,43). Patients who initially respond to paclitaxel therapy often develop resistance to paclitaxel later (44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

Circadian Clock Gene Bmal1 Inhibits Tumorigenesis and Increases Paclitaxel Sensitivity in Tongue Squamous Cell Carcinoma

et al. 2017

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Circadian clock genes regulate cancer development and chemotherapy susceptibility. Accordingly, chronotherapy based on circadian phenotypes might be applied to improve therapeutic efficacy. In this study, we investigated whether the circadian clock gene Bmal1 inhibited tumor development and increased paclitaxel sensitivity in tongue squamous cell carcinoma (TSCC). Bmal1 expression was downregulated and its rhythmic pattern of expression was affected in TSCC samples and cell lines. Ectopic Bmal1 inhibited cell proliferation, migration and invasion in vitro, and tumor growth in mouse xenograft models of TSCC. After exposure to paclitaxel, Bmal1-overexpressing cells displayed a relative increase in apoptosis and were more susceptible to paclitaxel treatment in vivo Mechanistic investigations suggested a regulatory connection between Bmal1, TERT, and the oncogenic transcriptional repressor EZH2 (enhancer of zeste homolog 2), the recruitment of which to the TERT promoter increased paclitaxel-induced apoptosis and cell growth inhibition. Clinically, paclitaxel efficacy correlated positively with Bmal1 expression levels in TSCC. Overall, our results identified Bmal1 as a novel tumor suppressor gene that elevates the sensitivity of cancer cells to paclitaxel, with potential implications as a chronotherapy timing biomarker in TSCC. Cancer Res; 77(2); 532-44. ©2016 AACR.

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Section: Discussionmentioning

confidence: 99%

Circadian Clock Gene Bmal1 Inhibits Tumorigenesis and Increases Paclitaxel Sensitivity in Tongue Squamous Cell Carcinoma

et al. 2017

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“…O exemplo mais conhecido é o taxol (2), um composto inicialmente isolado da planta Taxus brevifolia (WANI et al, 1971). Este composto tem potente atividade anticancerígena (STIERLE; STROBEL; STIERLE, 1993) e vem sendo utilizado no combate principalmente ao câncer de ovário, de mama e de pulmão; e atualmente está sendo estudado para o tratamento de carcinoma de células escamosas da cavidade oral e língua (LEDWITCH et al, 2013).…”

Section: (1)unclassified

Bioprospecção de fungos endofíticos isolados de guaranazeiros da Amazônia

Elias¹

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Tese apresentada para obtenção do título de Doutora em Ciências. Área de concentração: Microbiologia Agrícola Piracicaba 2015 Aos meus pais José Antônio (Zito) e Lucia Helena, Pelo AMOR, companheirismo e paciência durante todos os dias da minha vida, DEDICO 4 5 AGRADECIMENTOS A Escola Superior de Agricultura "Luiz de Queiroz" (ESALQ-USP) pela infraestrutura disponibilizada para a realização deste trabalho. Ao Programa de Pós-Graduação em Microbiologia Agrícola pela oportunidade e a todos os professores, funcionários e alunos que fazem parte deste programa pelo apoio na realização deste trabalho. Ao CNPq (processo nº 143275/2011-9) e a FAPESP (processo nº 2012/02000-5) pelas bolsas concedidas. Ao Projeto Regular FAPESP (processo nº 2014/15760-3) e ao Projeto Temático FAPESP (processo nº 2013/50228-8) pelo apoio financeiro. A minha orientadora Profa. Dra. Simone Possedente de Lira pela orientação e paciência sempre, por me ensinar a cada dia como me tornar uma cientista e pessoa melhor e principalmente pela amizade, carinho e atenção. Muito obrigada pelas horas e horas dedicadas a minha formação, conselhos e lições de vida. Ao professor Nelson Sidnei Massola Júnior (ESALQ-USP) pelo aprendizado adquirido enquanto monitora das disciplinas de Microbiologia e Fitopatologia, pelas dicas e ajuda. Ao professor André Rodrigues (UNESP, Rio Claro) por disponibilizar seu laboratório para a realização das análises morfológicas e moleculares e aos alunos Lucas e Quimi pela enorme ajuda na interpretação dos dados. Aos meus pais Zito e Lucia pelo amor infinito e por terem investido tanto na minha educação. Aos meus irmãos Rodrigo e Valéria, aos cunhados Waleska e Rodolfo e aos sobrinhos mais lindos do mundo Alícia e Benício por tornarem esta fase da minha vida muito mais agradável e feliz. Amo muito todos! Ao companheiro Matheus pelo amor, paciência, carinho, companheirismo e alegria! Você tornou esta etapa muito mais fácil! A amiga Thaiane pela amizade verdadeira sem fim, pelas conversas, saidinhas e apoio sempre! A prima Maria Clara que mesmo longe sempre esteve presente, dando força, carinho e atenção. Saudades! A todas as pessoas do Marília, Isabelli e Higor. Agradeço a todos pela amizade, convivência e cafézinhos (muitos cafézinhos!). Vou sentir MUITA falta de vocês! Ao amigo Sérgio pelas infinitas risadas, conversas, apoio, amizade e comilanças! Obrigada por me aguentar nos bons e maus momentos e por tornar meus dias mais alegres! Ao amigo Flávio pelo apoio, paciência, ensinamentos, elucidação de moléculas, dicas, conversas. Sem você tudo teria sido muito mais difícil! A amiga Jeane pelas risadas, conversas, confidências, dicas, passeios no shopping, enfim, obrigada pelos muitos momentos de alegria e pela amizade! Ao amigo Marcos (Pipoca) pelas análises estatísticas, dicas e ajuda. Obrigada! As amigas Diana, Gislâine e Joze pelo apoio, dicas, risadas e conversas. Valeu gente! Aos amigos Higor e Marília (processo FAPESP nº 2014/05940-4) pela ajuda e apoio. Desejo muita sorte a vocês dois. Aos técnicos Felipe e Beto pela ajud...

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“…The first‐line treatment of both very large and unresectable OSCC and ESCC involves the use of drugs, such as cisplatin (Cis, 1 ; Figure ), carboplatin ( 2 ), 5‐fluorouracil (5‐FU, 3 ), methotrexate (MTX, 4 ), and taxanes (paclitaxel, 5 and docetaxel, 6 ) . Such therapies, however, did not show any significant increase in the level of overall survival (OS) over the past two decades.…”

Section: Introductionmentioning

confidence: 99%

Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas

Khan

Relitti

Brindisi

et al. 2019

Medicinal Research Reviews

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Oral squamous cell carcinomas (OSCC) and esophageal squamous cell carcinomas (ESCC) exhibit a survival rate of less than 60% and 40%, respectively. Late-stage diagnosis and lack of effective treatment strategies make both OSCC and ESCC a significant health burden. Autophagy, a lysosome-dependent catabolic process, involves the degradation of intracellular components to maintain cell homeostasis. Targeting autophagy has been highlighted as a feasible therapeutic strategy with clinical utility in cancer treatment, although its associated regulatory mechanisms remain elusive. The detection of relevant biomarkers in biological fluids has been anticipated to facilitate early diagnosis and/or prognosis for these tumors. In this context, recent studies have indicated the presence of specific proteins and small RNAs, detectable in circulating plasma and serum, as biomarkers. Interestingly, the interplay between biomarkers (eg, exosomal microRNAs) and autophagic processes could be exploited in the quest for targeted and more effective therapies for OSCC and ESCC. In this review, we give an overview of the available biomarkers and innovative targeted therapeutic strategies, including the application of autophagy modulators in OSCC and ESCC.Additionally, we provide a viewpoint on the state of the art Tuhina Khan and Nicola Relitti contributed equally to this work. and on future therapeutic perspectives combining the early detection of relevant biomarkers with drug discovery for the treatment of OSCC and ESCC. K E Y W O R D S autophagy, autophagy modulators, biomarkers, esophageal squamous cell carcinoma, exosomes, oral squamous cell carcinoma, targeted therapy 1 | INTRODUCTION Oral squamous cell carcinoma (OSCC) is the predominant malignant neoplasm of the oral cavity followed by verrucous carcinoma, undifferentiated carcinoma, and small salivary adenocarcinoma. 1 Esophageal squamous cell carcinoma (ESCC) is the first histological type and accounts for 80% of cases of esophageal cancer. 2 OSCC and ESCC are indicated as one of the most common cancers by the International Union Against Cancer with an annual incidence of 275 000 and 456 000 cases worldwide, respectively. 3,4 The primary etiology in both OSCC and ESCC is attributed to the environmental factors (tobacco abuse, alcohol consumption), genetic factors (eg, mutations in enzymes), viral factors (human papilloma virus [HPV] infection), and/or the coexistence of these factors. Alcohol intake and tobacco use are responsible for at least 75% of these carcinomas. The underlying initiation and progression mechanisms of OSCC and ESCC are generally characterized by the accumulation of serial epigenetic and genetic alterations, which eventually lead to uncontrolled proliferation of the mutated cells, followed by vigorous cell division. 5,7 Early-stage OSCC detection displays an 80% survival rate at 5 years, while detection at advanced stage leads to survival rates ranging from 20% to 40%. 6 In ESCC, the 5-year survival rate for early-stage detection may reach 85%, whereas a dr...

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Taxol: Efficacy Against Oral Squamous Cell Carcinoma

Cited by 14 publications

References 0 publications

Circadian Clock Gene Bmal1 Inhibits Tumorigenesis and Increases Paclitaxel Sensitivity in Tongue Squamous Cell Carcinoma

Circadian Clock Gene Bmal1 Inhibits Tumorigenesis and Increases Paclitaxel Sensitivity in Tongue Squamous Cell Carcinoma

Bioprospecção de fungos endofíticos isolados de guaranazeiros da Amazônia

Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas

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