Publications by authors named "Mohammed J Latif"

3 Publications

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Antitumor activity of paclitaxel is significantly enhanced by a novel proapoptotic agent in non-small cell lung cancer.

J Surg Res 2015 Apr 10;194(2):622-630. Epub 2014 Nov 10.

Division of Thoracic Surgery, Department of Surgery, Mount Sinai St. Luke's Hospital, Mount Sinai Health System, New York, NY, USA; Division of Thoracic Surgery, Department of Surgery, Mount Sinai Roosevelt Hospital, Mount Sinai Health System, New York, NY, USA. Electronic address:

Background: Newer targeted agents are increasingly used in combination chemotherapy regimens with enhanced survival and improved toxicity profile. Taxols, such as paclitaxel, independently potentiate tumor destruction via apoptosis and are used as first line therapy in patients with advanced non-small cell lung cancer (NSCLC). Procaspase-3-activating compound-1 (PAC-1) is a novel proapoptotic agent that directly activates procaspase-3 (PC-3) to caspase-3, leading to apoptosis in human lung adenocarcinoma cells. Hence, we sought to evaluate the antitumor effects of paclitaxel in combination with PAC-1.

Methods: Human NSCLC cell lines (A-549 and H-322m) were incubated in the presence of PAC-1 and paclitaxel. Tumor cell viability was determined by a tetrazolium-based colorimetric assay (MTT assay). Western blot and flow cytometric analysis were performed to evaluate expression of PC-3 and the proportion of apoptotic cells, respectively. A xenograft murine model of NSCLC was used to study the in vivo antitumor effects of PAC-1.

Results: PAC-1 significantly reduced the inhibitory concentration 50% of paclitaxel from 35.3 to 0.33 nM in A-549 and 8.2 to 1.16 nM in H-322m cell lines. Similarly, the apoptotic activity significantly increased to 85.38% and 70.36% in A-549 and H322m, respectively. Significantly enhanced conversion of PC-3 to caspase-3 was observed with PAC-1 paclitaxel combination (P < 0.05). Mice treated with a drug combination demonstrated 60% reduced tumor growth rate compared with those of controls (P < 0.05).

Conclusions: PAC-1 significantly enhances the antitumor activity of paclitaxel against NSCLC. The activation of PC-3 and thus the apoptotic pathway is a potential strategy in the treatment of human lung cancer.
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http://dx.doi.org/10.1016/j.jss.2014.11.004DOI Listing
April 2015

Dietary flaxseed protects against lung ischemia reperfusion injury via inhibition of apoptosis and inflammation in a murine model.

J Surg Res 2011 Nov 7;171(1):e113-21. Epub 2011 Jul 7.

Department of Surgery, St. Luke's-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, New York 10019, USA.

Background: The hallmark of lung ischemia-reperfusion injury (IRI) is the production of reactive oxygen species (ROS), and the resultant oxidant stress has been implicated in apoptotic cell death as well as subsequent development of inflammation. Dietary flaxseed (FS) is a rich source of naturally occurring antioxidants and has been shown to reduce lung IRI in mice. However, the mechanisms underlying the protective effects of FS in IRI remain to be determined.

Methods: We used a mouse model of IRI with 60 min of ischemia followed by 180 min of reperfusion and evaluated the anti-apoptotic and anti-inflammatory effects of 10% FS dietary supplementation.

Results: Mice fed 10% FS undergoing lung IRI had significantly lower levels of caspases and decreased apoptotic activity compared with mice fed 0% FS. Lung homogenates and bronchoalveolar lavage fluid analysis demonstrated significantly reduced inflammatory infiltrate in mice fed with 10% FS diet. Additionally, 10% FS treated mice showed significantly increased expression of antioxidant enzymes and decreased markers of lung injury.

Conclusions: We conclude that dietary FS is protective against lung IRI in a clinically relevant murine model, and this protective effect may in part be mediated by the inhibition of apoptosis and inflammation.
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http://dx.doi.org/10.1016/j.jss.2011.06.017DOI Listing
November 2011

Endoscopic tracheoplasty: segmental tracheal ring resection in a porcine model.

J Bronchology Interv Pulmonol 2010 Jul;17(3):232-5

*Divisions of Thoracic Surgery, Department of Surgery †Department of Otolaryngology, St Luke's-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, NY.

Endoscopic tracheoplasty is used for the relief of airway obstruction because of several benign conditions such as postintubation stenosis, inflammatory disorders such as Wegener granulomatosis, and benign neoplastic processes. Several endoscopic treatment modalities exist for these conditions, all with good initial results. However, recurrence is common and often requires frequent reintervention. Endoscopic segmental tracheal ring resection is a novel therapeutic approach that could potentially provide a durable solution. Endoscopic segmental tracheal ring resection was performed in 3 Yorkshire pigs under general anesthesia. A combination of bipolar cautery and sharp dissection was used to resect 25% to 33% of the circumference of a single tracheal ring. Technical success was achieved in all 3 animals with no intraoperative complications. Full-thickness excision, including the anterior perichondrium, was performed in 1 animal without violation of the pretracheal fascia, with no subcutaneous emphysema or clinically apparent pneumothorax. Average operative time was 31 minutes and estimated blood loss was minimal. Heart rate, oxygen saturation, and peak airway pressures were maintained within normal ranges during the procedure and for the 60-minute postoperative period. Histologic analysis of the resected specimen confirmed complete thickness excision of the segment of tracheal cartilage. Endoscopic tracheoplasty by segmental tracheal ring resection is a safe and feasible technique in a porcine model. Long-term durability could potentially outlast other endoscopic techniques for the treatment of bening tracheal stenosis. Survival studies in a porcine model of tracheal stenosis must be performed to assess the long-term outcomes of this approach.
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http://dx.doi.org/10.1097/LBR.0b013e3181ea9a9bDOI Listing
July 2010
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