Follow-up and Surveillance of the Lung Cancer Patient Following Curative-Intent Therapy*

Colice, Gene; Rubins, Jeffrey B.; Unger, Michael

doi:10.1378/chest.123.1_suppl.272s

Cited by 84 publications

(58 citation statements)

References 80 publications

(96 reference statements)

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“…The paired upregulation of Notch2 and Six1 seemed to be one transcriptional alteration that is responsible for minimally invasive adenocarcinoma-to-lepidic-predominant invasive adenocarcinoma progression, and it defined a clinically aggressive phenotype subset of lepidic-predominant invasive adenocarcinoma. Because Notch2 and Six1 immunohistochemistry seemed to independently discriminate lepidic-predominant invasive adenocarcinomas with high risk of recurrence in a 2-year postoperative period, during which the recurrence of most lung cancers occurs even after curative-intent therapy (42), it could be a clinically useful examination for selecting patients with lepidicpredominant invasive adenocarcinoma needing intensive follow-up.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of Notch2 and Six1 Is Associated with Progression of Early-Stage Lung Adenocarcinoma and a More Aggressive Phenotype at Advanced Stages

Mimae

Okada

Hagiyama

et al. 2012

Clinical Cancer Research

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Purpose: Lung adenocarcinoma often manifests as tumors with mainly lepidic growth. The size of invasive foci determines a diagnosis of in situ, minimally invasive adenocarcinoma, or invasive types and suggests that some adenocarcinomas undergo malignant progression in that order. This study investigates how transcriptional aberrations in adenocarcinoma cells at the early stage define the clinical phenotypes of adenocarcinoma tumors at the advanced stage.Experimental Design: We comprehensively searched for differentially expressed genes between preinvasive and invasive cancer cells in one minimally invasive adenocarcinoma using laser capture microdissection and DNA microarrays. We screened expression of candidate genes in 11 minimally invasive adenocarcinomas by reverse transcriptase PCR and examined their involvement in preinvasive-to-invasive progression by transfection studies. We then immunohistochemically investigated the presence of candidate molecules in 64 samples of advanced adenocarcinoma and statistically analyzed the findings, together with clinicopathologic variables.Results: The transcription factors Notch2 and Six1 were upregulated in invasive cancer cells in all 11 minimally invasive adenocarcinomas. Exogenous Notch2 transactivated Six1 followed by Smad3, Smad4, and vimentin, and enlarged the nuclei of NCI-H441 lung epithelial cells. Immunochemical staining for the transcription factors was double positive in the invasive, but not in the lepidic growth component of a third of advanced Ads, and the disease-free survival rates were lower in such tumors.Conclusions: Paired upregulation of Notch2 and Six1 is a transcriptional aberration that contributes to preinvasive-to-invasive adenocarcinoma progression by inducing epithelial-mesenchymal transition and nuclear atypia. This aberration persisted in a considerable subset of advanced adenocarcinoma and conferred a more malignant phenotype on the subset. Clin Cancer Res; 18(4); 945-55. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 99%

Upregulation of Notch2 and Six1 Is Associated with Progression of Early-Stage Lung Adenocarcinoma and a More Aggressive Phenotype at Advanced Stages

Mimae

Okada

Hagiyama

et al. 2012

Clinical Cancer Research

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“…35 Although respiratory symptoms may signal recurrence or second lung primaries, there is little information about the pattern and extent of the expected symptom burden after curative treatment. To our knowledge, this study is the first to report the respiratory status and pulmonary function of long-term survivors of NSCLC and their relationships to QOL.…”

Section: Discussionmentioning

confidence: 99%

Impact of Respiratory Symptoms and Pulmonary Function on Quality of Life of Long-term Survivors of Non-Small Cell Lung Cancer

Sarna

Evangelista

Tashkin

et al. 2004

Chest

205

153

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Purpose: To describe respiratory symptoms and pulmonary function among long-term survivors of non-small cell lung cancer (NSCLC), and their relationship to quality of life (QOL). Methods: Cross-sectional survey of disease-free, 5-year minimum survivors of NSCLC (n ‫؍‬ 142; 54% women; average age, 71 years); the majority (74%) had received a lobectomy. Analysis included frequency of self-reported respiratory symptoms (cough, phlegm, wheezing, breathlessness) as measured by the American Thoracic Society questionnaire, pulmonary function findings from hand-held spirometry, and QOL (Short Form-36). Results: Two thirds of survivors reported at least one respiratory symptom (mean, 1.3; SD, 1.2): 25% cough, 28% phlegm, 31% wheezing, and 39% dyspnea. Twenty-one percent reported that they spent most of the day in bed in the past 12 months because of respiratory symptoms. Average FEV 1 percentage predicted was 68% (SD, 23); 21% had < 50% predicted FEV 1 . Based on spirometry results, 36% had a moderate/severe obstructive and/or restrictive ventilatory disorder. Survivors exposed to second-hand smoke (28%) were more than three times as likely to report respiratory symptoms. Respiratory symptom burden contributed to diminished QOL in several domains. Conclusions: The majority of these survivors experienced respiratory symptoms, and more than one third reported dyspnea, including one of five patients with seriously diminished pulmonary function. Symptom burden, rather than ventilatory impairment, contributed to diminished QOL. Further study is needed to determine the patterns and effective management of posttreatment respiratory symptoms on survivors of lung cancer. (CHEST 2004; 125:439 -445)Key words: cancer survivors; chronic lung disease; lung neoplasms; pulmonary function; quality of life; respiratory symptoms; tobacco, smoking Abbreviations: ATS ϭ American Thoracic Society; df ϭ degrees of freedom; FEF 25-75% ϭ maximum expiratory flow rate; NSCLC ϭ non-small cell lung cancer; QOL ϭ quality of life; SF-36 ϭ Short Form-36 T he long-term consequences of the curative treatment for non-small cell lung cancer (NSCLC) on pulmonary status, the frequency of respiratory symptoms, and the impact of these pulmonary consequences on the quality of life (QOL) of such survivors have not been previously reported. Respiratory distress, even among the 14% of patients with NSCLC who are disease-free survivors, 1 may negatively affect QOL. Dyspnea and other respiratory symptoms have been reported to negatively impact QOL in those with COPD and other chronic lung conditions, 2-8 but little information is available about the impact on people with cancer. 9 One study 10 suggests that patients with NSCLC may actually have better QOL than those with severe COPD.*From the School of Nursing (Drs. Sarna and Evangelista),

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“…The animals were sacrificed at 10, 14, and 21 days after tumor implantation; the sizes of primary tumors in the lung were measured, and the mediastinal lymph nodes were weighed. The volume of the primary tumor was calculated using the formula 1 ⁄2 ϫ (long diameter) ϫ (short diameter) 2 . Histopathology and Immunohistochemistry.…”

Section: Methodsmentioning

confidence: 99%

A Definitive Role of RhoC in Metastasis of Orthotopic Lung Cancer in Mice

Ikoma

Takahashi

Nagano

et al. 2004

Clinical Cancer Research

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Purpose: Lung cancer is a major cause of cancer death, and its incidence is increasing in the world. Conventional therapies remain less effective for metastases of lung cancer, leading to poor prognosis of this disorder. The present study investigates pathological roles of RhoC in metastasis of lung cancer using a clinically relevant mouse model of lung cancer.Experimental Design: RhoA, RhoC, dominant-negative Rho (dnRho) or green fluorescent protein gene was retrovirally transduced to murine lung cancer cells. For in vivo study, these transduced cells were intrapulmonary inoculated in syngeneic mice, and subsequently, growth and metastasis were analyzed. Migration and invasion activities were further investigated by in vitro chemotaxic chamber assays. Expression levels and activities of certain matrix metalloproteinases (MMPs) were explored by reverse transcription-PCR and gelatin zymography.Results: Metastasis of lung cancer in the animal model, as well as in vitro migration and invasion, were significantly enhanced or inhibited by overexpression of RhoC or dnRho, respectively, without affecting the growth of primary tumors. Expression levels of certain MMPs and the activity of MMP-2 were significantly enhanced or suppressed by overexpression of RhoC or dnRho, respectively. Conclusion:RhoC plays a crucial role in metastasis of lung cancer. RhoC does not affect tumor growth but enhances the metastatic nature of lung cancer by not only stimulating cell motility but also up-regulating certain MMPs. Attenuation of RhoC activity may be a potential target in the development of a novel strategy for treating metastasis of lung cancer.

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Follow-up and Surveillance of the Lung Cancer Patient Following Curative-Intent Therapy*

Cited by 84 publications

References 80 publications

Upregulation of Notch2 and Six1 Is Associated with Progression of Early-Stage Lung Adenocarcinoma and a More Aggressive Phenotype at Advanced Stages

Upregulation of Notch2 and Six1 Is Associated with Progression of Early-Stage Lung Adenocarcinoma and a More Aggressive Phenotype at Advanced Stages

Impact of Respiratory Symptoms and Pulmonary Function on Quality of Life of Long-term Survivors of Non-Small Cell Lung Cancer

A Definitive Role of RhoC in Metastasis of Orthotopic Lung Cancer in Mice

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