The role of bioreductive activation of antitumour anthracycline drugs in cytotoxic activity against sensitive and multidrug resistant leukaemia HL60 cells

Background: Thyroid carcinoma (TC) is the most common endocrine system malignancy, and papillary thyroid carcinoma (PTC) accounts for >80% of all TC cases. Nevertheless, PTC pathogenesis is still not fully understood. The aim of the study was to elucidate the role of the FRMD5 protein in the regulation of biological pathways associated with the development of PTC. We imply that the presence of certain genetic aberrations (e.g., BRAF V600E mutation) is associated with the activity of FRMD5. Methods: The studies were conducted on TPC1 and BCPAP (BRAF V600E) model PTC-derived cells. Transfection with siRNA was used to deplete the expression of FRMD5. The mRNA expression and protein yield were evaluated using RT-qPCR and Western blot techniques. Proliferation, migration, invasiveness, adhesion, spheroid formation, and survival tests were performed. RNA sequencing and phospho-kinase proteome profiling were used to assess signaling pathways associated with the FRMD5 expressional status. Results: The obtained data indicate that the expression of FRMD5 is significantly enhanced in BRAF V600E tumor specimens and cells. It was observed that a drop in intracellular yield of FRMD5 results in significant alternations in the migration, invasiveness, adhesion, and spheroid formation potential of PTC-derived cells. Importantly, significant divergences in the effect of FRMD5 depletion in both BRAF-wt and BRAF-mutated PTC cells were observed. It was also found that knockdown of FRMD5 significantly alters the expression of multidrug resistant genes. Conclusions: This is the first report highlighting the importance of the FRMD5 protein in the biology of PTCs. The results suggest that the FRMD5 protein can play an important role in controlling the metastatic potential and multidrug resistance of thyroid tumor cells.

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Lung Resection for Multidrug-Resistant Tuberculosis

Asian Cardiovascular and Thoracic Annals ◽

10.1177/021849230501300216 ◽

2005 ◽

Vol 13 (2) ◽

pp. 172-174 ◽

Cited By ~ 17

Author(s):

Rishen Naidoo ◽

Anu Reddi

Keyword(s):

Lung Resection ◽

Postoperative Mortality ◽

Multidrug Resistant ◽

Cure Rate ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Traditional Drug ◽

Localized Disease ◽

Cure Rates

The emergence of multidrug-resistant tuberculosis poses a serious challenge to traditional drug therapy. In view of the relapse rate of up to 50% following medical management, there has been renewed interest in the role of surgery for this problem. We report our experience with lung resection for this condition. Over a 5-year period, resection was performed in 23 patients who were diagnosed with multidrug resistance after completing a course of standard chemotherapy and at least 3 months of second-line therapy. Pneumonectomy was performed in 17 patients and lobectomy in 6. There was no operative or postoperative mortality. Major complications developed in 4 patients (17.4%): 2 had post-pneumonectomy empyema and 2 underwent rethoracotomy for bleeding. Ten patients were sputum positive preoperatively, and only 1 remained positive after surgery. The patients were put on appropriate chemotherapy and followed up for 18 months. The cure rate was 95.6%. Pulmonary resection can be considered as an important adjunct to medical therapy in carefully selected patients: those who have localized disease with adequate pulmonary reserve, or who have multiple previous relapses, or whose sputum remains positive after 4 to 6 months of appropriate medical treatment. Surgery offers high cure rates with acceptable morbidity and mortality.

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Molecular survey of mcr1 and mcr2 plasmid mediated colistin resistance genes in Escherichia coli isolates of animal origin in Iran

BMC Research Notes ◽

10.1186/s13104-021-05519-6 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Kayhan Ilbeigi ◽

Mahdi Askari Badouei ◽

Hossein Vaezi ◽

Hassan Zaheri ◽

Sina Aghasharif ◽

...

Keyword(s):

Escherichia Coli ◽

Resistance Genes ◽

Companion Animals ◽

Multidrug Resistant ◽

Animal Origin ◽

Colistin Resistance ◽

E Coli ◽

High Level ◽

Farming Industry

Abstract Objectives The emergence of colistin-resistant Enterobacteriaceae from human and animal sources is one of the major public health concerns as colistin is the last-resort antibiotic for treating infections caused by multidrug-resistant Gram-negative bacteria. We aimed to determine the prevalence of the prototype widespread colistin resistance genes (mcr-1 and mcr-2) among commensal and pathogenic Escherichia coli strains isolated from food-producing and companion animals in Iran. Results A total of 607 E. coli isolates which were previously collected from different animal sources between 2008 and 2016 used to uncover the possible presence of plasmid-mediated colistin resistance genes (mcr-1 and mcr-2) by PCR. Overall, our results could not confirm the presence of any mcr-1 or mcr-2 positive E. coli among the studied isolates. It is concluded that despite the important role of food-producing animals in transferring the antibiotic resistance, they were not the main source for carriage of mcr-1 and mcr-2 in Iran until 2016. This study suggests that the other mcr variants (mcr-3 to mcr-9) might be responsible for conferring colistin resistance in animal isolates in Iran. The possible linkage between pig farming industry and high level of mcr carriage in some countries needs to be clarified in future prospective studies.

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