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1.
Gulf J Oncolog ; 1(45): 35-41, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38774931

RESUMEN

BACKGROUND: Microsatellite instability (MSI) is a pattern of hyper mutation that occurs at microsatellite level in the genome and result due to error in the mismatch repair system. MSI is caused by defective mismatch repair (MMR) genes associated with either hyper methylation of MMR genes or BRAF mutations. Anti-MLH-1, anti-MSH-2, anti-MSH-6 and anti-PMS2 monoclonal antibodies are used for Immunohistochemical analysis. METHODS: The immunohistochemical expression of MSI proteins were assessed in 72 cases of colorectal carcinoma. These were classified based on the expression of MLH1, MSH2, MSH6 and PMS2 proteins. RESULTS: There were 57 percent of cases showing loss of at least one antibodies, and 43 percent cases showing intact expression of all antibodies (MLH1, MSH2, MSH6 and PMS2). CONCLUSION: In conclusion, our study provides valuable insights into the expression of mismatch repair in colorectal adenocarcinoma through immunohistochemistry analysis conducted at our tertiary care centre. These findings hold significant clinical implications, suggesting further testing for BRAF and MLH1 Promoter Hypermethylation to confirm possibility of Lynch syndrome. KEY WORDS: IHC, MMR, CRC.


Asunto(s)
Adenocarcinoma , Neoplasias Colorrectales , Reparación de la Incompatibilidad de ADN , Inmunohistoquímica , Centros de Atención Terciaria , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Masculino , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Inmunohistoquímica/métodos , Femenino , Persona de Mediana Edad , Anciano , Adulto , Homólogo 1 de la Proteína MutL/genética
2.
Int J Cancer ; 104(1): 104-12, 2003 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-12532426

RESUMEN

The nitroreductase (NR)/CB1954 enzyme prodrug system has given promising results in preclinical studies and is currently being assessed in phase I clinical trials. It is well established that there is an immune component to the bystander effect observed with other systems such as thymidine kinase and cytosine deaminase; however, such an effect has not previously been described using NR. We have preliminary data suggesting an immune bystander effect with NR to further examine these effects and their potential enhancement by cytokines, an adenoviral vector containing CMV-NR, an internal ribosome entry site (IRES) and the gene for murine GM-CSF (mGM-CSF) was constructed. The NR-GM-CSF virus was validated in 2 experimental models and demonstrated increased therapeutic efficacy in the MC26 murine colorectal tumour model. These data illustrate that the combination of suicide gene therapy using NR and CB1954 with immune stimulation via GM-CSF gives an improved response compared to either modality alone and suggests that the immune component of this response may be beneficial in combating unresectable, metastatic disease and preventing tumour recurrence.


Asunto(s)
Adenocarcinoma/terapia , Adenovirus Humanos/genética , Adyuvantes Inmunológicos/uso terapéutico , Antineoplásicos Alquilantes/uso terapéutico , Aziridinas/farmacología , Efecto Espectador , Neoplasias Colorrectales/terapia , Virus Defectuosos/genética , Resistencia a Antineoplásicos/genética , Proteínas de Escherichia coli/genética , Terapia Genética , Vectores Genéticos/genética , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Inmunoterapia , Nitrorreductasas/genética , Profármacos/farmacología , Adenocarcinoma/genética , Adenocarcinoma/inmunología , Animales , Antineoplásicos Alquilantes/farmacocinética , Aziridinas/farmacocinética , Aziridinas/uso terapéutico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/inmunología , Terapia Combinada , Citomegalovirus/genética , Proteínas de Escherichia coli/metabolismo , Femenino , Genes , Genes Sintéticos , Vectores Genéticos/uso terapéutico , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Humanos , Mesotelioma/enzimología , Mesotelioma/patología , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Nitrorreductasas/metabolismo , Profármacos/farmacocinética , Profármacos/uso terapéutico , Organismos Libres de Patógenos Específicos , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/trasplante , Células Tumorales Cultivadas/virología
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