Small Molecule-directed Immunotherapy against Recurrent Infection by Mycobacterium tuberculosis

Bhattacharya, Debapriya; Dwivedi, Ved Prakash; Maiga, Mamoudou; Maiga, Mariama C.; Kaer, Luc Van; Bishai, William R.; Das, Gobardhan

doi:10.1074/jbc.m114.558098

Cited by 42 publications

(47 citation statements)

References 38 publications

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“…Bhattacharya et al suggested that small molecule therapeutic inhibitors of TGF-β, including Alk5 inhibitors, are less expensive when compared with conventional recombinant therapeutic agent such as antibodies and could avoid complications associated with recombinant therapeutic agents (37). The TGF-β1 pathway, via its receptor Alk5, is known to increase collagen synthesis in tumors, and blocking this pathway increases vessel perfusion and decreases resistance of the interstitial matrix (18).…”

Section: Discussionmentioning

confidence: 99%

Alk5 inhibition increases delivery of macromolecular and protein-bound contrast agents to tumors

et al. 2016

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Limited transendothelial permeability across tumor microvessels represents a significant bottleneck in the development of tumor-specific diagnostic agents and theranostic drugs. Here, we show an approach to increase transendothelial permeability of macromolecular and nanoparticle-based contrast agents via inhibition of the type I TGF-β receptor, activin-like kinase 5 (Alk5), in tumors. Alk5 inhibition significantly increased tumor contrast agent delivery and enhancement on imaging studies, while healthy organs remained relatively unaffected. Imaging data correlated with significantly decreased tumor interstitial fluid pressure, while tumor vascular density remained unchanged. This immediately clinically translatable concept involving Alk5 inhibitor pretreatment prior to an imaging study could be leveraged for improved tumor delivery of macromolecular and nanoparticle-based imaging probes and, thereby, facilitate development of more sensitive imaging tests for cancer diagnosis, enhanced tumor characterization, and personalized, image-guided therapies.

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Section: Discussionmentioning

confidence: 99%

Alk5 inhibition increases delivery of macromolecular and protein-bound contrast agents to tumors

et al. 2016

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“…Therapeutic small molecules that could inhibit Th2 cells and Tregs, Suplatast tosylate, have been shown to disrupt production of IL-4 and other Th2-type cytokines without impeding IFN-c production. During progression of TB, Mtb elicits Th2 and Treg cell responses in susceptible hosts, which facilitates disease progression by antagonizing host protective immune responses [82]. Another study established proof of concept for host-directed treatment strategies that manipulate the host eicosanoid network.…”

Section: Alternative Treatmentsmentioning

confidence: 98%

Childhood Tuberculosis

Faddoul

2015

Advances in Pediatrics

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“…11,12 The clinical manifestations of both the diseases do not occur simultaneously because the levels of these subgroups of lymphocytes are not increased at the same time in an individual.…”

Section: Discussionmentioning

confidence: 99%

Association between tuberculosis and bronchial asthma

Garg

Karahyla

2017

Int J Res Med Sci

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Background: Everything that wheezes is not asthma. In patients of tuberculosis (TB), wheezing can be because of bronchial asthma, or many other causes. Asthma and other causes of wheezing need to be differentiated, as the treatment should be planned accordingly.Methods: Patients of active/quiescent tuberculosis who presented to Department of Tuberculosis and Chest Diseases, Government Medical College, Patiala, Punjab, India, with complaints of breathlessness and had rhonchi on examination were subjected to bronchodilator reversibility testing to prove if they were suffering from concomitant asthma. Patients thus found to have tuberculosis along with asthma were analyzed with respect to age, sex, rural urban differences and timing of diagnosis of either disease. Patients who developed asthma after tuberculosis were further analyzed for duration between completion of anti-tubercular treatment (ATT) and onset of asthma, family history of asthma and correlation of radiological manifestations and lung function measurements. Aim was to find association, if any, between tuberculosis and asthma.Results: Over 6 months, 69 patients of tuberculosis along with asthma were found. Only 21/69 (30.4%) patients developed tuberculosis after asthma. 48/69 (69.6%) patients developed asthma after tuberculosis. Majority (25/48=52.1%) of them developed asthma within 5 years of completion of ATT (p=0.020). Only 2/48 (2.9%) patients had a positive family history for asthma. Lung function abnormalities correlated with the extent of radiological involvement in these patients who developed asthma after tuberculosis (p ≤0.0001).Conclusions: Patients of active/quiescent tuberculosis who present with breathlessness and have rhonchi on examination should be treated for asthma only after confirmation of the diagnosis, as there can be other reasons for the same.

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Small Molecule-directed Immunotherapy against Recurrent Infection by Mycobacterium tuberculosis

Cited by 42 publications

References 38 publications

Alk5 inhibition increases delivery of macromolecular and protein-bound contrast agents to tumors

Alk5 inhibition increases delivery of macromolecular and protein-bound contrast agents to tumors

Childhood Tuberculosis

Association between tuberculosis and bronchial asthma

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