Lung Cancer

Choy, Hak; Pass, Harvey I.; Rosell, Rafael; Traynor, Anne M.

doi:10.1007/0-387-31056-8_37

Cited by 2 publications

(4 citation statements)

References 541 publications

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“…We have identified p-benzoquinone (p-BQ) as a risk factor that is tentatively produced from p-benzosemiquinone [ 13 – 15 ] of aqueous extract of CS (AECS). Lung cancer is believed to arise after a series of progressive pathologic changes (preneoplastic lesions) that are initiated by proliferation [ 4 ]. We have shown that low concentration of AECS or equivalent amount of p-BQ derived from AECS causes excessive proliferation of human lung epithelial cells (A549) that is mediated via aberrant phosphorylation of EGFR resulting in persistent activation of EGFR.…”

Section: Discussionmentioning

confidence: 99%

“…The most significant property of cancer cells is that they undergo excessive proliferation. Lung cancer arises after a series of progressive pathologic changes (preneoplastic lesions) that are initiated by proliferation (hyperplasia) [ 4 ]. In almost all instances, unregulated cell proliferation together with suppressed apoptosis constitutes the minimal common platform upon which all neoplastic progression occurs [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Here, we show that CS-induced proliferation of lung cells is completely prevented by antibody to p-BQ and that p-BQ in amounts derived from CS mimics CS-induced lung cell proliferation. Overexpression and/or hyperactivity of the epidermal growth factor receptor (EGFR), accompanied by several downstream cytoplasmic signal transducers, including Ras-MAPK cascade as well as the cell survivor factor Akt (protein kinase B) has been shown to play a causal role in the proliferation and progression of lung tumors [ 4 ]. Lemjabbar et al observed that CS-induced cell proliferation was accompanied by phosphorylation (activation) of the epidermal growth factor receptor (EGFR) [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Molecular Mechanisms of Cigarette Smoke-Induced Proliferation of Lung Cells and Prevention by Vitamin C

Dey

Chattopadhyay²,

Chatterjee³

2011

Journal of Oncology

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Lung cancer is the leading cause of cancer dearth. Cigarette smoking is the strongest risk factor for developing lung cancer, which is conceivably initiated by proliferation. Here, we show that low concentration of aqueous extract of cigarette smoke (AECS) causes excessive proliferation of human lung epithelial cells (A549) without any apoptotic cell death. The causative factor responsible for AECS-induced proliferation has been identified as p-benzoquinone (p-BQ). Coimmunoprecipitation and immunoblot experiments indicate that p-BQ binds with epidermal growth factor receptor (EGFR). However, in contrast to EGF, it causes aberrant phosphorylation of EGFR that lacks c-Cbl-mediated ubiquitination and degradation resulting in persistent activation of EGFR. This is followed by activation of Hras + Kras and the downstream survival and proliferative signaling molecules Akt and ERK1/2, as well as the nuclear transcription factors c-Myc and c-Fos. Vitamin C and/or antibody to p-BQ prevents AECS/p-BQ-induced proliferation of lung cells apparently by inactivating p-BQ and thereby preventing activation of EGFR and the downstream signaling molecules. The results suggest that vitamin C and/or antibody to p-BQ may provide a novel intervention for preventing initiation of lung cancer in smokers.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Molecular Mechanisms of Cigarette Smoke-Induced Proliferation of Lung Cells and Prevention by Vitamin C

Dey

Chattopadhyay²,

Chatterjee³

2011

Journal of Oncology

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“…In addition, with more advanced molecularly targeted therapies, different drugs that form a treatment regimen may be used to deal with cellular heterogeneity within tumours, thus effectively combating tumours before they become resistant to drugs . Combinations of chemotherapeutic drugs may be administered concurrently or non‐concurrently over a treatment cycle, and such a choice is usually dependent on the disease being treated, the treatments being used, and the biological mechanism via which the treatments act . Administering treatments concurrently is often undertaken in order to quickly kill tumour cells and/or prevent remaining tumour cells from developing immunity to particular drugs and thus improve treatment efficacy with respect to disease‐free survival and overall survival .…”

Section: Introductionmentioning

confidence: 99%

Modelling semi‐attributable toxicity in dual‐agent phase I trials with non‐concurrent drug administration

Wheeler

Sweeting

Mander

et al. 2016

Statistics in Medicine

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In oncology, combinations of drugs are often used to improve treatment efficacy and/or reduce harmful side effects. Dual‐agent phase I clinical trials assess drug safety and aim to discover a maximum tolerated dose combination via dose‐escalation; cohorts of patients are given set doses of both drugs and monitored to see if toxic reactions occur. Dose‐escalation decisions for subsequent cohorts are based on the number and severity of observed toxic reactions, and an escalation rule. In a combination trial, drugs may be administered concurrently or non‐concurrently over a treatment cycle. For two drugs given non‐concurrently with overlapping toxicities, toxicities occurring after administration of the first drug yet before administration of the second may be attributed directly to the first drug, whereas toxicities occurring after both drugs have been given some present ambiguity; toxicities may be attributable to the first drug only, the second drug only or the synergistic combination of both. We call this mixture of attributable and non‐attributable toxicity semi‐attributable toxicity. Most published methods assume drugs are given concurrently, which may not be reflective of trials with non‐concurrent drug administration. We incorporate semi‐attributable toxicity into Bayesian modelling for dual‐agent phase I trials with non‐concurrent drug administration and compare the operating characteristics to an approach where this detail is not considered. Simulations based on a trial for non‐concurrent administration of intravesical Cabazitaxel and Cisplatin in early‐stage bladder cancer patients are presented for several scenarios and show that including semi‐attributable toxicity data reduces the number of patients given overly toxic combinations. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

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Lung Cancer

Cited by 2 publications

References 541 publications

Molecular Mechanisms of Cigarette Smoke-Induced Proliferation of Lung Cells and Prevention by Vitamin C

Molecular Mechanisms of Cigarette Smoke-Induced Proliferation of Lung Cells and Prevention by Vitamin C

Modelling semi‐attributable toxicity in dual‐agent phase I trials with non‐concurrent drug administration

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