METHODS: This is a retrospective observational study of NSCLC patients with sensitising EGFR mutation experiencing disease progression (PD) whilst on first- or second-generation EGFR-TKIs with subsequent investigations to detect acquired T790M mutation at the University of Malaya Medical Centre from 1st January 2015 to 31st December 2017.
RESULTS: A total of 87 patients were included. Upon PD, acquired T790M mutation was found in 55 (63.2%) patients and was significantly more common in patients who achieved partial response (PR) whilst on the EGFR-TKIs (p = 0.008) or had new lung metastasis upon PD (p = 0.048). It was less frequent in patients who developed new symptomatic brain lesions (p = 0.021). Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (p = 0.077). Multivariate analysis revealed PR whilst on EGFR-TKI treatment was an independent predictor of acquiring T790M mutation (p = 0.021), whereas development of new symptomatic brain lesions (p = 0.034) or new lymph node metastases (p = 0.038) upon PD was independently against acquiring T790M mutation. Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (odds ratio: 2.3, 95% confidence interval: 0.84-6.25, p = 0.104).
CONCLUSION: The best tumour response of PR to first- or second-generation EGFR-TKI treatment independently predicts acquired T790M mutation. Patients with exon 19 deletion are likely to acquire T790M mutation. This would prove useful for clinicians to prognosticate and plan subsequent treatments for patients with advanced NSCLC harbouring EGFR mutations.
Methods: Eighty (40 right-sided and 40 left-sided) formalin-fixed, paraffin-embedded primary CRC were immunohistochemically studied for CD133, a putative CRC stem cell marker, and MMR proteins MLH1, MSH2, MSH6 and PMS2. CD133 expression was semi-quantitated for proportion of tumor immunopositivity on a scale of 0-5 and staining intensity on a scale of 0-3 with a final score (units) being the product of proportion and intensity of tumor staining. The tumor was considered immunopositive only when the tumor demonstrated moderate to strong intensity of CD133 staining (a decision made after analysis of CD133 expression in normal colon). Deficient MMR (dMMR) was interpreted as unequivocal loss of tumor nuclear staining for any MMR protein despite immunoreactivity in the internal positive controls.
Results: CD133 was expressed in 36 (90.0%) left-sided and 28 (70.0%) right-sided tumors (p 0.05).
Conclusion: Proficient MMR correlated with high levels of CD133-marked putative cancer stem cells in both right- and left-sided tumors, whereas significantly lower levels of CD133-marked putative cancer stem cells were associated with deficient MMR status in colorectal carcinomas found on the right.
METHODS: We isolated Onchocerca specimens from bearded pigs and examined their morphology. For comparative material, we collected fresh specimens of O. d. dewittei Bain, Ramachandran, Petter & Mak, 1977 from banded pigs (S. scrofa vittatus Boie) in Peninsular Malaysia. Partial sequences of three different genes (two mitochondrial genes, cox1 and 12S rRNA, and one nuclear ITS region) of these filarioids were analysed. By multi-locus sequence analyses based on six genes (16S rDNA, ftsZ, dnaA, coxA, fbpA and gatB) of Wolbachia, we determined the supergroups in the specimens from bearded pigs and those of O. d. dewittei.
RESULTS: Onchocerca borneensis Uni, Mat Udin & Takaoka n. sp. is described on the basis of morphological characteristics and its genetic divergence from congeners. Molecular characteristics of the new species revealed its close evolutionary relationship with O. d. dewittei. Calculated p-distance for the cox1 gene sequences between O. borneensis n. sp. and O. d. dewittei was 5.9%, while that between O. d. dewittei and O. d. japonica was 7.6%. No intraspecific genetic variation was found for the new species. Wolbachia strains identified in the new species and O. d. dewittei belonged to supergroup C and are closely related.
CONCLUSIONS: Our molecular analyses of filarioids from Asian suids indicate that the new species is sister to O. d. dewittei. On the basis of its morphological and molecular characteristics, we propose to elevate O. d. japonica to species level as O. japonica Uni, Bain & Takaoka, 2001. Coevolutionary relationships exist between the Wolbachia strains and their filarial hosts in Borneo and Peninsular Malaysia.