Clinical impact of novel treatment strategies

Giaccone, Giuseppe

doi:10.1038/sj.onc.1205565

Cited by 43 publications

(26 citation statements)

References 82 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A larger study will be required to conclusively establish the effect of postoperative radiotherapy, but these data suggest that it may be better to wait for the result of molecular analysis before repairing a defect with a microvascular flap to avoid burying residual carcinoma. Alternative treatment regimens incorporating tumor-targeted agents, such as cetuximab, Iressa, and gefitinib, or antiangiogenic agents (33) are showing benefit when given with radiotherapy or as part of combination treatment regimens, and it is to be hoped that these advances will also provide a step forward in the management of head and neck cancer. …”

Section: Discussionmentioning

confidence: 99%

p53 Mutations in Deep Tissues Are More Strongly Associated with Recurrence than Mutation-Positive Mucosal Margins

Huang¹,

Pateromichelakis²,

Hills³

et al. 2007

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Application of ultrasensitive diagnostics has shown that small numbers of p53 mutation-positive cells may signify the presence of residual tumor in histologically normal tissues after resection of squamous cell carcinomas arising in the head and neck area. To date, most studies in this area have focused on analysis of tissues at the mucosal aspect of the resection and highlighted the importance of molecular changes in the field with respect to the risk of recurrence. Experimental Design: In the present investigation, we analyzed normal tissues from mucosal and deep surgical margins, referred to as ''molecular margins,'' for the presence of the signature p53 mutation identified for each tumor. Results:The p53 mutation status of these carcinomas did not correlate with clinical or histopathologic variables, but these mutations provided an excellent target for ultrasensitive analysis of margin status. We found that 11of 16 (68%) of cases with histologically tumor-free (including 9 without dysplasia), but with p53 mutation-positive molecular margins, developed recurrence.The probability of developing local recurrence was significantly higher for the group with p53 mutation-positive margins when compared with the group with clear margins (P = 0.048) and more strongly associated with p53 mutation-positive deep molecular margins than mutation-positive mucosal molecular margins or positivity at both sites (P = 0.009). Conclusions: This shows that although persistent mucosal fields may contribute to recurrence, clonal p53 mutations in deep tissues are an important cause of treatment failure, and molecular margins from both sites should be analyzed in future prospective series.

show abstract

Section: Discussionmentioning

confidence: 99%

p53 Mutations in Deep Tissues Are More Strongly Associated with Recurrence than Mutation-Positive Mucosal Margins

Huang¹,

Pateromichelakis²,

Hills³

et al. 2007

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…A549 cells (5 Â 10 6 ) were administered in the s.c. tissue of the left dorsal flank of 7-week-old male nude mice. Tumor growth was monitored regularly and volume (V ) was calculated using the formula V = 1/2 Â length Â (width) 2 . When tumor size reached f50 mm 3 (about 10 days post-inoculation), animals were randomized into three groups and vectors were administered by intratumoral injection.…”

Section: Methodsmentioning

confidence: 99%

“…Lung carcinoma is the leading cause of malignancy-related mortality (1) with little change in survival rates over the past two decades (2). Non-small cell lung cancer now accounts for about three-quarters of all cases of lung cancer (3) and most patients continue to die of progressive metastatic disease despite new therapeutic strategies and advances in surgical oncology.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Soluble TRAIL Induces Apoptosis in Human Lung Adenocarcinoma and Inhibits Growth of Tumor Xenografts in Nude Mice

et al. 2005

View full text Add to dashboard Cite

Recombinant adeno-associated virus 2/5 (rAAV2/5), a hybrid rAAV-2 with AAV-5 capsid, seems to be a very efficient delivery vector for the transduction of the lung adenocarcinoma cell line A549. Infection of the A549 cell line with a rAAV2/5 vector encoding the extracellular domain of tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL, amino acids 114-281) resulted in secretion of soluble TRAIL (sTRAIL) and induction of apoptosis in these cells. rAAV2/5-sTRAIL mediated delivery and stable expression of sTRAIL resulted in the presence of the trimeric form of sTRAIL in sera of nude mice that were implanted with s.c. or orthotopic A549 tumors. The rAAV2/5-sTRAIL transduction of the tumors resulted in a statistically significant reduction in tumor growth and prolonged survival of the tumor-bearing animals. Primary cell culture, histologic examination of the tumors, and serum analyses showed the absence of detectable TRAIL-induced toxicity in normal tissues including the liver. The successful inhibition of lung cancer growth and the absence of detectable toxicity suggest a putative role for rAAV2/5-sTRAIL

show abstract

“…Surgical resection offers the best chance for cure. For patients undergoing surgery, the longterm prognosis remains disappointing, with a 5-year overall survival of 50% only (5). Recent studies showed that survival of surgically resected patients with NSCLC might be improved by systemic platinum-based adjuvant chemotherapy (6,7), but which patients might benefit from this treatment cannot be determined accurately.…”

mentioning

confidence: 99%

Mass Spectrometry-based Proteomic Profiling of Lung Cancer

Ocak¹,

Chaurand²,

Massion³

2009

Proceedings of the American Thoracic Society

View full text Add to dashboard Cite

In an effort to further our understanding of lung cancer biology and to identify new candidate biomarkers to be used in the management of lung cancer, we need to probe these tissues and biological fluids with tools that address the biology of lung cancer directly at the protein level. Proteins are responsible of the function and phenotype of cells. Cancer cells express proteins that distinguish them from normal cells. Proteomics is defined as the study of the proteome, the complete set of proteins produced by a species, using the technologies of large-scale protein separation and identification. As a result, new technologies are being developed to allow the rapid and systematic analysis of thousands of proteins. The analytical advantages of mass spectrometry (MS), including sensitivity and highthroughput, promise to make it a mainstay of novel biomarker discovery to differentiate cancer from normal cells and to predict individuals likely to develop or recur with lung cancer. In this review, we summarize the progress made in clinical proteomics as it applies to the management of lung cancer. We will focus our discussion on how MS approaches may advance the areas of early detection, response to therapy, and prognostic evaluation.Keywords: proteome; translational research; biomarkers Lung cancer is the leading cause of cancer-related death worldwide among both males and females, with more than 1 million deaths annually (1). Non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers. Although advances have been made in diagnosis and treatment strategies in the last decade, the prognosis of NSCLC patients is poor, with a 5-year overall survival of 15 to 20% (2). This is mainly due to a lack of early diagnosis tools, with more than 60% of the patients diagnosed with advanced or metastatic disease (3) and therefore not eligible for a curative surgical resection. Lung cancer is often suspected on the basis of abnormal chest imaging and/or nonspecific symptoms. Bronchoscopy, with cytopathologic examination of bronchoalveolar lavage, endobronchial brushings and biopsies obtained from the suspect area, is in general used as an initial diagnostic tool. However, while this procedure is 100% specific for lung cancer, the sensitivity is low and ranges from 30% for small peripheral lesions to 80% for central endobronchial tumors (4). More invasive and expensive diagnostic tests are often required, delaying the diagnosis and the subsequent treatment initiation. Surgical resection offers the best chance for cure. For patients undergoing surgery, the longterm prognosis remains disappointing, with a 5-year overall survival of 50% only (5). Recent studies showed that survival of surgically resected patients with NSCLC might be improved by systemic platinum-based adjuvant chemotherapy (6, 7), but which patients might benefit from this treatment cannot be determined accurately.To improve lung cancer management and survival, there is a great need to develop screening and early diagnosis strategies that are sensitive,...

show abstract

Clinical impact of novel treatment strategies

Cited by 43 publications

References 82 publications

p53 Mutations in Deep Tissues Are More Strongly Associated with Recurrence than Mutation-Positive Mucosal Margins

p53 Mutations in Deep Tissues Are More Strongly Associated with Recurrence than Mutation-Positive Mucosal Margins

Overexpression of Soluble TRAIL Induces Apoptosis in Human Lung Adenocarcinoma and Inhibits Growth of Tumor Xenografts in Nude Mice

Mass Spectrometry-based Proteomic Profiling of Lung Cancer

Contact Info

Product

Resources

About