O PAPEL DO BCG NO CONTROLE DA EXPRESSAO DOS GENES PD1 E PDL1 EM ESTUDO IN VITRO DE CARCINOMA UROTELIAL DE BEXIGA

Denis Reis Morais, Vanessa Guimarães , Nayara Viana, Sabrina Thalita Reis , Iran Amourin Silva, Ruan Pimenta, Gabriel A G D dos Santos , Cristina Massoco, Katia Ramos Moreira Leite

Universidade Anhembi Morumbi – Faculdade de medicina - Sao Paulo - Brasil, Faculdade de Medicina da Universidade de São Paulo - Sao Paulo - Brasil

Introdução e objetivo:

A imunoterapia com o uso do Bacilo de Calmet Guerin (BCG) é o tratamento mais eficaz para o carcinoma urotelial (CUB) superficial de bexiga, diminuindo principalmente o número de recidivas, característica da neoplasia. Novas drogas foram desenvolvidas recentemente com alta atividade na estimulação do sistema imunológico, bloqueando os mecanismos de escape adquiridos pelas neoplasias que são a expressão de PD1 e PDL1. O mecanismo de ação do BCG ainda não foi totalmente elucidado e nossa hipótese é que possa atuar no controle de expressão dessas proteínas. Assim, nosso objetivo á a avaliação da expressão de PD1 e PDL1 em estudo in vitro do carcinoma urotelial de bexiga tratado com BCG.

Método:
Cultura de células de carcinoma urotelial de bexiga de baixo grau, recidivante, RT4 foi tratada com 3 concentrações de BCG, 5, 10 e 20 bacilos/célula tumoral. Após 4 e 24 horas, o RNA foi extraído e os níveis de expressão de PD1 e PDL1 foram avaliados pela reação em cadeia da polimerase quantitativa em tempo real (qRT-PCR).

Resultados:
Após 4 horas de exposição ao BCG observamos um aumento da expressão dos genes PD1 e PDL-1 proporcional ao número de bacilos/célula tumoral quando comparado ao grupo controle. O aumento da expressão de PD1 nas células tratadas na concentração de 20:1 foi significativamente maior comparado ao grupo tratado com 5:1 (p= 0,0203).
No experimento de 24 horas de tratamento houve uma pequena redução na expressão de PD1 e PDL1 em relação ao controle, sendo ainda observado uma redução significativa entre o grupo de células tratada com 5:1 e o grupo 20:1 (p= 0,0232).

Conclusão:
Nossos resultados apontam um papel do BCG na regulação da expressão dos genes PD1 e PDL1 na qual a concentração de bacilos e o tempo de exposição parecem influenciar nesse mecanismo. Esses dados são inéditos e nos proporcionam uma melhor compreensão sobre o mecanismo de ação do BCG no tratamento do CUB.

Palavras Chave

PD1, PDL1, câncer de bexiga

Disponível em: www.congressourooncologia.com.br

THALIDOMIDE ADMINISTRATION THROUGH A NASOGASTRIC TUBE

Asif Yusuf*, Aujla Harjinder, Correa West Joanna. Birmingham Children’s Hospital

Introduction LA, 15 year old female diagnosed with tuberculosis meningitis (TBM). General paediatric team recommended, in combination with existing adjunctive therapy, initiation of Thalidomide, a non-formulary drug.Challenge Administration of medication, for LA, was via a nasogastric tube. The cytotoxic nature of Thalidomide compounded with the lack of information from Celgene, the manufacturer of the only licensed Thalidomide in the United Kingdom (UK) that supplied oral capsules, provided numerous issues for administration. In addition, TBM was an unlicensed indication for Thalidomide. 

Outcome Approval through the Drug and Therapeutics Committee (DTC) was gained. Upon investigating into previous use at the trust, another patient had received Thalidomide for TBM in 2014, this was requested from the same consultant, however on that occurrence there was ease of administration through the oral route so the licensed oral capsules were used. Combined with this previous case and a thorough literature search, a dose was calculated of 200 mg (3 mg/kg once a day), which was agreed by the general paediatrics team. 

An unlicensed oral tablet formulation was sourced from another manufacturer in the UK. Crushing syringes were sourced to ensure the ‘crushing and dispersing process’ would occur in a closed system. The relevant forms for Thalidomide initiation were completed by the requesting consultant, with the patient and family advised on the appropriate pregnancy prevention measures. An administration guide via feeding tubes was developed for the nursing team. 

Steps included: wearing gloves and apron, using a crushing syringe to crush the Thalidomide tablet in a closed system, drawing 20 ml of water from a medicine pot into the crushing syringe, agitating the syringe to disperse the tablet, using the appropriate ENFIT adaptor to administer the dispersed medication into the feeding tube and disposing of appropriate waste into cytotoxic and clinical waste. 

Incorporated into this, a safety information leaflet for staff was developed, also for the nursing team, detailing the appropriate ward storage (controlled drugs cupboard) and handling measures, stressing the importance of the teratogenic nature of Thalidomide. The nursing team on the relevant ward, caring for LA, were counselled on and supplied with the guidance that was produced for them. A brief pharmacy guide was developed, detailing to the pharmacy team, the teratogenic nature of Thalidomide along with the special storage conditions (controlled drugs cupboard) and handling measures. 

The pharmacy team were informed of the case and guidance was sent out, to ensure that the correct safety measures were in place. Prior to dispensing, dispensing staff and screening pharmacists were asked to complete a consent form, in order to dispense/screen prescriptions for Thalidomide. Dispensing took place as per cytotoxic medications, with Thalidomide delivered in the relevant yellow sealed bags. Moving on A Thalidomide policy was drafted and will be submitted to the DTC for approval. Once approved, this will be available for the medical, nursing and pharmacy team, in the future. A pharmacy Thalidomide folder was created, that would house the policy and all the relevant forms required for audit.

Archives of Disease in Childhood 2018:103(2).