Abstract The seeds of Cleome viscosa are used in traditional systems of medicine for the treatmen... more Abstract The seeds of Cleome viscosa are used in traditional systems of medicine for the treatment of many diseases in Asia. This study evaluated fixed oil from the seeds of Cleome viscosa for analgesic and antiemetic activity by using the acetic acid induced writhing test ...
Cancer is one of the most extreme medical conditions in both developing and developed countries a... more Cancer is one of the most extreme medical conditions in both developing and developed countries around the world, causing millions of deaths each year. Chemotherapy and/or radiotherapy are key for treatment approaches, but both have numerous adverse health effects. Furthermore, the resistance of cancerous cells to anticancer medication leads to treatment failure. The rising burden of cancer overall requires novel efficacious treatment modalities. Natural medications offer feasible alternative options against malignancy in contrast to western medication. Furanocoumarins’ defensive and restorative impacts have been observed in leukemia, glioma, breast, lung, renal, liver, colon, cervical, ovarian, and prostate malignancies. Experimental findings have shown that furanocoumarins activate multiple signaling pathways, leading to apoptosis, autophagy, antioxidant, antimetastatic, and cell cycle arrest in malignant cells. Additionally, furanocoumarins have been shown to have chemo preventiv...
Emesis, also known as nausea and vomiting, are common symptoms associated with ingestion of toxic... more Emesis, also known as nausea and vomiting, are common symptoms associated with ingestion of toxicants, drug side effects, advanced terminal diseases such as cancer and postoperative procedures. Emesis is mediated through the coordinated action of central and peripheral regulatory centres that involve receptors including dopamine Type 2, serotonin, muscarinic cholinergic, histamine, cannabinoids and NK-1 receptors. Many anti-emetic drugs targeting these receptors are currently in use but they also cause undesirable side effects such as excessive sedation, hypote-nsion, dry mouth, dysphoria, hallucinations and extrapyramidal signs. This review highlights the pharmacological mechanism of emesis and current antiemtic drugs together with detailed analysis of in vitro and in vivo anti-emetic bioassay models. The pharmacology of crude natural products extracts and purified anti-emetic compounds (cannabinoids, chalcones, diarylheptanoids, flavonoids, hydroxycinn-amic acids, lignans, phenylp...
Purpose: c-Met is a receptor tyrosine kinase involved in cell growth, invasion, metastases, and a... more Purpose: c-Met is a receptor tyrosine kinase involved in cell growth, invasion, metastases, and angiogenesis. In this study, we investigated the role of c-Met in melanoma biology using a novel small-molecule tyrosine kinase inhibitor SU11274 and small interfering (si) RNA against the receptor. Experimental Design: The effects of SU11274 and c-Met siRNA were studied on proliferation, apoptosis, differentiation, reactive oxygen species, and intracellular signaling. c-Met mutations were examined, and the expression of c-Met and activated c-Met was studied in nevi, primary, and metastatic melanoma. Results: c-Met was expressed in 6:7 melanoma cell lines by immunoblotting. SU11274 inhibited cell growth in all melanoma cell lines by 85% to 98% with an IC50 between 1 and 2.5 ÎĽmol/L and caused apoptosis (12-58%) in five out of six cell lines. siRNA against c-Met inhibited proliferation of melanoma cells by 60%. This is the first study that shows that SU11274 and siRNA induced microphthalmia...
The c-Met receptor tyrosine kinase is emerging as a novel target in many solid tumors, including ... more The c-Met receptor tyrosine kinase is emerging as a novel target in many solid tumors, including lung cancer. PHA-665752 was identified as a small molecule, ATP competitive inhibitor of the catalytic activity of the c-Met kinase. Here, we show that treatment with PHA665752 reduced NCI-H69 (small cell lung cancer) and NCI-H441 (non–small cell lung cancer) tumorigenicity in mouse xenografts by 99% and 75%, respectively. Reduction in tumor size was also observed by magnetic resonance imaging of tumors in mice. PHA665752 inhibited c-Met phosphorylation at the autophosphorylation and c-Cbl binding sites in mouse xenografts derived from non–small cell lung cancer cell lines (NCI-H441 and A549) and small cell lung cancer cell line (NCI-H69). PHA665752 also inhibited angiogenesis by >85% in all the abovementioned cell lines and caused an angiogenic switch which resulted in a decreased production of vascular endothelial growth factor and an increase in the production of the angiogenesis i...
Lung cancer is characterized by abnormal cell growth and invasion, and the actin cytoskeleton pla... more Lung cancer is characterized by abnormal cell growth and invasion, and the actin cytoskeleton plays a major role in these processes. The focal adhesion protein paxillin is a target of a number of oncogenes involved in key signal transduction and important in cell motility and migration. In lung cancer tissues, we have found that paxillin was highly expressed (compared with normal lung), amplified (12.1%, 8 of 66) and correlated with increased MET and epidermal growth factor receptor (EGFR) gene copy numbers, or mutated (somatic mutation rate of 9.4%, 18 of 191). Paxillin mutations (19 of 21) were clustered between LD motifs 1 and 2 and the LIM domains. The most frequent point mutation (A127T) enhanced lung cancer cell growth, colony formation, focal adhesion formation, and colocalized with Bcl-2 in vitro. Gene silencing from RNA interference of mutant paxillin led to reduction of cell viability. A murine in vivo xenograft model of A127T paxillin showed an increase in tumor growth, c...
Vasoactive intestinal peptide (VIP) is an anti-inflammatory immunomodulatory neuropeptide with th... more Vasoactive intestinal peptide (VIP) is an anti-inflammatory immunomodulatory neuropeptide with therapeutic potential demonstrated for collagen-induced arthritis. The aim of this study was to characterise its potential anti-arthritic effect on human monocytes, macrophages, T cells, and rheumatoid arthritis synovial membrane cells. Monocytes, macrophages, and T cells derived from human peripheral blood were treated with VIP and compared with other cAMP-elevating drugs for a range of activating stimuli. Cytokine production was assessed for cell cultures and, in addition, the ability of VIPs to activate cAMP response element binding protein. VIP partially suppressed monocyte- and macrophage-derived tumour necrosis factor alpha (TNF-alpha) with no effect on IL-10, whereas VIP fails to regulate IL-10 and TNF-alpha production by T lymphocytes. No such modulation of cytokine profile was observed for rheumatoid arthritis synovial membrane cells. Elevation of intracellular cAMP, on the other ...
Abstract The seeds of Cleome viscosa are used in traditional systems of medicine for the treatmen... more Abstract The seeds of Cleome viscosa are used in traditional systems of medicine for the treatment of many diseases in Asia. This study evaluated fixed oil from the seeds of Cleome viscosa for analgesic and antiemetic activity by using the acetic acid induced writhing test ...
Cancer is one of the most extreme medical conditions in both developing and developed countries a... more Cancer is one of the most extreme medical conditions in both developing and developed countries around the world, causing millions of deaths each year. Chemotherapy and/or radiotherapy are key for treatment approaches, but both have numerous adverse health effects. Furthermore, the resistance of cancerous cells to anticancer medication leads to treatment failure. The rising burden of cancer overall requires novel efficacious treatment modalities. Natural medications offer feasible alternative options against malignancy in contrast to western medication. Furanocoumarins’ defensive and restorative impacts have been observed in leukemia, glioma, breast, lung, renal, liver, colon, cervical, ovarian, and prostate malignancies. Experimental findings have shown that furanocoumarins activate multiple signaling pathways, leading to apoptosis, autophagy, antioxidant, antimetastatic, and cell cycle arrest in malignant cells. Additionally, furanocoumarins have been shown to have chemo preventiv...
Emesis, also known as nausea and vomiting, are common symptoms associated with ingestion of toxic... more Emesis, also known as nausea and vomiting, are common symptoms associated with ingestion of toxicants, drug side effects, advanced terminal diseases such as cancer and postoperative procedures. Emesis is mediated through the coordinated action of central and peripheral regulatory centres that involve receptors including dopamine Type 2, serotonin, muscarinic cholinergic, histamine, cannabinoids and NK-1 receptors. Many anti-emetic drugs targeting these receptors are currently in use but they also cause undesirable side effects such as excessive sedation, hypote-nsion, dry mouth, dysphoria, hallucinations and extrapyramidal signs. This review highlights the pharmacological mechanism of emesis and current antiemtic drugs together with detailed analysis of in vitro and in vivo anti-emetic bioassay models. The pharmacology of crude natural products extracts and purified anti-emetic compounds (cannabinoids, chalcones, diarylheptanoids, flavonoids, hydroxycinn-amic acids, lignans, phenylp...
Purpose: c-Met is a receptor tyrosine kinase involved in cell growth, invasion, metastases, and a... more Purpose: c-Met is a receptor tyrosine kinase involved in cell growth, invasion, metastases, and angiogenesis. In this study, we investigated the role of c-Met in melanoma biology using a novel small-molecule tyrosine kinase inhibitor SU11274 and small interfering (si) RNA against the receptor. Experimental Design: The effects of SU11274 and c-Met siRNA were studied on proliferation, apoptosis, differentiation, reactive oxygen species, and intracellular signaling. c-Met mutations were examined, and the expression of c-Met and activated c-Met was studied in nevi, primary, and metastatic melanoma. Results: c-Met was expressed in 6:7 melanoma cell lines by immunoblotting. SU11274 inhibited cell growth in all melanoma cell lines by 85% to 98% with an IC50 between 1 and 2.5 ÎĽmol/L and caused apoptosis (12-58%) in five out of six cell lines. siRNA against c-Met inhibited proliferation of melanoma cells by 60%. This is the first study that shows that SU11274 and siRNA induced microphthalmia...
The c-Met receptor tyrosine kinase is emerging as a novel target in many solid tumors, including ... more The c-Met receptor tyrosine kinase is emerging as a novel target in many solid tumors, including lung cancer. PHA-665752 was identified as a small molecule, ATP competitive inhibitor of the catalytic activity of the c-Met kinase. Here, we show that treatment with PHA665752 reduced NCI-H69 (small cell lung cancer) and NCI-H441 (non–small cell lung cancer) tumorigenicity in mouse xenografts by 99% and 75%, respectively. Reduction in tumor size was also observed by magnetic resonance imaging of tumors in mice. PHA665752 inhibited c-Met phosphorylation at the autophosphorylation and c-Cbl binding sites in mouse xenografts derived from non–small cell lung cancer cell lines (NCI-H441 and A549) and small cell lung cancer cell line (NCI-H69). PHA665752 also inhibited angiogenesis by >85% in all the abovementioned cell lines and caused an angiogenic switch which resulted in a decreased production of vascular endothelial growth factor and an increase in the production of the angiogenesis i...
Lung cancer is characterized by abnormal cell growth and invasion, and the actin cytoskeleton pla... more Lung cancer is characterized by abnormal cell growth and invasion, and the actin cytoskeleton plays a major role in these processes. The focal adhesion protein paxillin is a target of a number of oncogenes involved in key signal transduction and important in cell motility and migration. In lung cancer tissues, we have found that paxillin was highly expressed (compared with normal lung), amplified (12.1%, 8 of 66) and correlated with increased MET and epidermal growth factor receptor (EGFR) gene copy numbers, or mutated (somatic mutation rate of 9.4%, 18 of 191). Paxillin mutations (19 of 21) were clustered between LD motifs 1 and 2 and the LIM domains. The most frequent point mutation (A127T) enhanced lung cancer cell growth, colony formation, focal adhesion formation, and colocalized with Bcl-2 in vitro. Gene silencing from RNA interference of mutant paxillin led to reduction of cell viability. A murine in vivo xenograft model of A127T paxillin showed an increase in tumor growth, c...
Vasoactive intestinal peptide (VIP) is an anti-inflammatory immunomodulatory neuropeptide with th... more Vasoactive intestinal peptide (VIP) is an anti-inflammatory immunomodulatory neuropeptide with therapeutic potential demonstrated for collagen-induced arthritis. The aim of this study was to characterise its potential anti-arthritic effect on human monocytes, macrophages, T cells, and rheumatoid arthritis synovial membrane cells. Monocytes, macrophages, and T cells derived from human peripheral blood were treated with VIP and compared with other cAMP-elevating drugs for a range of activating stimuli. Cytokine production was assessed for cell cultures and, in addition, the ability of VIPs to activate cAMP response element binding protein. VIP partially suppressed monocyte- and macrophage-derived tumour necrosis factor alpha (TNF-alpha) with no effect on IL-10, whereas VIP fails to regulate IL-10 and TNF-alpha production by T lymphocytes. No such modulation of cytokine profile was observed for rheumatoid arthritis synovial membrane cells. Elevation of intracellular cAMP, on the other ...
Uploads
Papers by Salman Ahmed