2014 journal article
Aerosolized MANS and BIO-11006 Peptides Inhibit Lung Cancer Metastasis in SCID Mice
International Journal of Radiation Oncology*Biology*Physics, 90(5), S51.
TL;DR:
Almost 50% of lung adenocarcinoma of all stages harbored an identifiable driver mutation, and amongst the authors' cases, AA patients had a higher frequency of dual mutations than in other patient populations.
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UN Sustainable Development Goal Categories
3. Good Health and Well-being
(OpenAlex)
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Added: February 21, 2020
Purpose/Objective(s)MARCKS, a ubiquitous 332-aa protein with a highly conserved N-terminal sequence, plays a key role in cell migration. MARCKS elevations in cancer are associated with metastasis and worse outcomes; Chen et al found high phospho MARCKS levels in human NSCLC tissues and showed that MANS, a 24-aa N-terminal MARCKS fragment that inhibits MARCKS function, prevents metastasis of PC9 cells orthotopically injected into the left lung of SCID mice by q3d ip injections. In this study we compared anti-metastatic effects of aerosolized inhaled MANS and its much shorter analog, BIO-11006, in NSCLC in vivo.Materials/MethodsForty SCID mice (n=8 per group) were inoculated with 2.5 x 106 A549 cells by tail vein injection, and treated with aerosolized (Aerogen preclinical nebulizer) MANS, BIO-11006 peptide, or PBS qod for 7 weeks. For each treatment, MANS and BIO-11006 peptide (100 μM), dissolved in five mL PBS, were nebulized over 30 min. The treatment, given every other day, was started either at Day -1, or at Day +3. On Day 53, animals were sacrificed and necropsied. Lungs were harvested, weighed, perfused with 15% India ink, washed with Fekete’s solution, photographed, and metastatic tumor nodules counted and recorded. Other organs were also harvested from control and treated groups and examined for metastasis.ResultsBoth aerosolized MANS and BIO-11006 significantly reduced lung metastasis compared to vehicle control. After the seven week treatment period, the vehicle control exhibited 97±21 metastatic nodules while BIO-11006 (-1 day and +3 day) groups had 34±14* and 21±6**, respectively. Similarly, MANS (-1 day and +3 day) groups showed 22±7* and 13±4** metastatic nodules, respectively. [*=P<.05 and **=P<.01 compared to vehicle; 1-way ANOVA/Bonferroni's Multiple Comparison Test]. Reductions in metastasis caused by MANS and BIO-11006 were not different if aerosol treatment was started before versus after A549 cell injections, and were not different from each other. Two animals exhibited metastasis beyond the lungs; both were in vehicle control group.ConclusionsBoth MARCKS inhibitory peptides, MANS and BIO-11006 significantly inhibit metastasis of A549 cells in SCID mice when administered by aerosol whether treatment is initiated before or after tail vein injection of human A549 lung cancer cells. Purpose/Objective(s)MARCKS, a ubiquitous 332-aa protein with a highly conserved N-terminal sequence, plays a key role in cell migration. MARCKS elevations in cancer are associated with metastasis and worse outcomes; Chen et al found high phospho MARCKS levels in human NSCLC tissues and showed that MANS, a 24-aa N-terminal MARCKS fragment that inhibits MARCKS function, prevents metastasis of PC9 cells orthotopically injected into the left lung of SCID mice by q3d ip injections. In this study we compared anti-metastatic effects of aerosolized inhaled MANS and its much shorter analog, BIO-11006, in NSCLC in vivo. MARCKS, a ubiquitous 332-aa protein with a highly conserved N-terminal sequence, plays a key role in cell migration. MARCKS elevations in cancer are associated with metastasis and worse outcomes; Chen et al found high phospho MARCKS levels in human NSCLC tissues and showed that MANS, a 24-aa N-terminal MARCKS fragment that inhibits MARCKS function, prevents metastasis of PC9 cells orthotopically injected into the left lung of SCID mice by q3d ip injections. In this study we compared anti-metastatic effects of aerosolized inhaled MANS and its much shorter analog, BIO-11006, in NSCLC in vivo. Materials/MethodsForty SCID mice (n=8 per group) were inoculated with 2.5 x 106 A549 cells by tail vein injection, and treated with aerosolized (Aerogen preclinical nebulizer) MANS, BIO-11006 peptide, or PBS qod for 7 weeks. For each treatment, MANS and BIO-11006 peptide (100 μM), dissolved in five mL PBS, were nebulized over 30 min. The treatment, given every other day, was started either at Day -1, or at Day +3. On Day 53, animals were sacrificed and necropsied. Lungs were harvested, weighed, perfused with 15% India ink, washed with Fekete’s solution, photographed, and metastatic tumor nodules counted and recorded. Other organs were also harvested from control and treated groups and examined for metastasis. Forty SCID mice (n=8 per group) were inoculated with 2.5 x 106 A549 cells by tail vein injection, and treated with aerosolized (Aerogen preclinical nebulizer) MANS, BIO-11006 peptide, or PBS qod for 7 weeks. For each treatment, MANS and BIO-11006 peptide (100 μM), dissolved in five mL PBS, were nebulized over 30 min. The treatment, given every other day, was started either at Day -1, or at Day +3. On Day 53, animals were sacrificed and necropsied. Lungs were harvested, weighed, perfused with 15% India ink, washed with Fekete’s solution, photographed, and metastatic tumor nodules counted and recorded. Other organs were also harvested from control and treated groups and examined for metastasis. ResultsBoth aerosolized MANS and BIO-11006 significantly reduced lung metastasis compared to vehicle control. After the seven week treatment period, the vehicle control exhibited 97±21 metastatic nodules while BIO-11006 (-1 day and +3 day) groups had 34±14* and 21±6**, respectively. Similarly, MANS (-1 day and +3 day) groups showed 22±7* and 13±4** metastatic nodules, respectively. [*=P<.05 and **=P<.01 compared to vehicle; 1-way ANOVA/Bonferroni's Multiple Comparison Test]. Reductions in metastasis caused by MANS and BIO-11006 were not different if aerosol treatment was started before versus after A549 cell injections, and were not different from each other. Two animals exhibited metastasis beyond the lungs; both were in vehicle control group. Both aerosolized MANS and BIO-11006 significantly reduced lung metastasis compared to vehicle control. After the seven week treatment period, the vehicle control exhibited 97±21 metastatic nodules while BIO-11006 (-1 day and +3 day) groups had 34±14* and 21±6**, respectively. Similarly, MANS (-1 day and +3 day) groups showed 22±7* and 13±4** metastatic nodules, respectively. [*=P<.05 and **=P<.01 compared to vehicle; 1-way ANOVA/Bonferroni's Multiple Comparison Test]. Reductions in metastasis caused by MANS and BIO-11006 were not different if aerosol treatment was started before versus after A549 cell injections, and were not different from each other. Two animals exhibited metastasis beyond the lungs; both were in vehicle control group. ConclusionsBoth MARCKS inhibitory peptides, MANS and BIO-11006 significantly inhibit metastasis of A549 cells in SCID mice when administered by aerosol whether treatment is initiated before or after tail vein injection of human A549 lung cancer cells. Both MARCKS inhibitory peptides, MANS and BIO-11006 significantly inhibit metastasis of A549 cells in SCID mice when administered by aerosol whether treatment is initiated before or after tail vein injection of human A549 lung cancer cells.