Login to your account

Username *
Password *
Remember Me

Blog With Right Sidebar

    Vous êtes ici :  
  1. Accueil
  2. Blog With Right Sidebar

Lung cancer stem cells: progress and prospects.

Related Articles

Epithelial stem cells are critical for tissue generation during development and for repair following injury. In both gestational and postnatal stages, the highly branched and compartmentalized organization of the lung is maintained by multiple, resident stem/progenitor cell populations that are responsible for the homeostatic maintenance and injury repair of pulmonary epithelium. Though lung epithelial injury in the absence of oncogenic mutation is more commonly expressed as chronic lung disease, lung cancer is the most common form of death worldwide and poses a highly significant risk to human health.

Cancer is defined by the cell of origin, responsible for initiating the disease. The Cancer Stem Cell Hypothesis proposes that cancer stem cells, identified by stem-like properties of self-renewal and generation of differentiated progeny, are responsible for propagating growth and spread of the disease. In lung cancer, it is hypothesized that cancer stem cells derive from several possible cell sources. The stem cell-like resistance to injury and proliferative potentials of bronchioalveolar stem cells (BASCs) and alveolar epithelial type II cells (AEC2), as well as cells that express the cancer stem cell marker glycoprotein prominin-1 (CD133) or markers for side populations make them potential reservoirs of lung cancer stem cells. The abnormal activation of pathways that normally regulate embryonic lung development, as well as adult tissue maintenance and injury repair, including the Wnt, Hedgehog (Hh) and Notch pathways, has also been identified in lung tumor cells.

It is postulated that therapies for lung cancer that specifically target stem cell signaling pathways utilized by lung cancer stem cells could be beneficial in combating this disease.

A Phase I Clinical Trial of Irinotecan and Carboplatin in Patients with Extensive Stage Small Cell Lung Cancer.

Related Articles

 

Treatment options for small cell lung cancer (SCLC) remain inadequate. Irinotecan has been tested in various combinations with platinum agents but the optimal regimen remains uncertain. We undertook a phase I trial to optimise the dose intensity of a 3-weekly irinotecan/carboplatin combination.

Methods: Twenty patients with extensive stage SCLC received intravenous carboplatin at an area under the curve (AUC) of 5 on day 1, and irinotecan in 40-70 mg/m(2) dose levels on days 1 and 8, every 21 days, for up to 6 cycles.

Results: Dose-limiting toxicity occurred in 1 patient at the 50 mg/m(2) irinotecan level (grade 3 diarrhoea) and in 2 patients at 70 mg/m(2) (grade 5 neutropenic sepsis; combined grade 4 febrile neutropenia, grade 4 diarrhoea and grade 3 thrombosis). Toxicity patterns were consistent with the expected profile for this combination. The objective response rate was 75% and the median survival was 9.3 months (95% confidence interval 7.5-11.2).

Conclusion: Irinotecan 60 mg/m(2) on days 1 and 8 combined with carboplatin AUC 5 every 21 days is recommended for phase II evaluation. This regimen has clinical activity, acceptable toxicity and greater dose intensity over those currently tested in phase III trials.

Transplantation for lung cancer.

Related Articles

 

Recent advances have led to improved outcomes in lung transplantation. The International Society for Heart and Lung Transplantation Registry data have shown a steady increase in the number of cases performed annually. Although somewhat controversial, lung transplantation (LTx) for lung cancer has also slowly increased. The current role of LTx for malignant diseases and the management challenge of incidental lung cancer in the explanted lungs are reviewed herein.

RECENT FINDINGS: For a few particular scenarios (advanced multifocal bronchioloalveolar carcinoma causing chronic respiratory failure, end-stage lung disease concomitant with early stage lung cancer, and metastatic disease restricted to the lungs with the primary site controlled) in which nonsurgical alternatives fail to provide adequate palliation, LTx may be considered. Nevertheless, in order to achieve acceptable results, careful patient selection and staging are paramount. In patients with incidental bronchogenic carcinoma in the explanted lung following transplantation, the prognosis is mainly driven by the malignancy stage.

SUMMARY: LTx can be performed to treat malignant diseases with results approaching those for nonneoplastic indications, given that patients are carefully selected and staged. Although they have not been widely applied in the reported lung transplant literature, modalities such as endobronchial ultrasound and positron emission tomography scan are strongly encouraged and have the potential to further refine staging in this population.

The use of oncolytic viruses to overcome lung cancer drug resistance.

Related Articles

Intrinsic and acquired drug resistance remains a fundamental obstacle to successful applications of anticancer therapies for lung cancer. Combining conventional therapies with immunotherapeutic approaches is a promising strategy to circumvent lung cancer drug resistance. Genetically modified oncolytic viruses (OVs) kill tumor cells via completely unique mechanisms compared to small molecule chemotherapeutics typically used in lung cancer treatment and can also be used to deliver specific toxic, therapeutic or immunomodulatory genes to tumor cells.

Recent pre-clinical and clinical studies with oncolytic vaccine approaches have revealed promising combination strategies that enhance oncolysis of tumor cells and circumvent tumor resistance mechanisms. As clinical trials with oncolytic vaccines progress, and as the knowledge acquired from these studies builds a foundation demonstrating OVs safety and efficacy, novel combination approaches could soon have a major impact on the clinical management of patients diagnosed with lung cancer.

Diagnosis of Lung Adenocarcinoma in Resected Specimens: Implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Lung Classification.

Related Articles

 

A new lung adenocarcinoma classification has been published by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society. This new classification is needed to provide uniform terminology and diagnostic criteria, most especially for bronchioloalveolar carcinoma. It was developed by an international core panel of experts representing all 3 societies with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons.

This summary focuses on the aspects of this classification that address resection specimens. The terms bronchioloalveolar carcinoma and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced, such as adenocarcinoma in situ and minimally invasive adenocarcinoma for small solitary adenocarcinomas with either pure lepidic growth (adenocarcinoma in situ) and predominant lepidic growth with invasion of 5 mm or less (minimally invasive adenocarcinoma), to define the condition of patients who will have 100% or near 100% disease-specific survival, respectively, if they undergo complete lesion resection. Adenocarcinoma in situ and minimally invasive adenocarcinoma are usually nonmucinous, but rarely may be mucinous. Invasive adenocarcinomas are now classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous bronchioloalveolar carcinoma), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous bronchioloalveolar carcinoma), colloid, fetal, and enteric adenocarcinoma.

It is possible that this classification may impact the next revision of the TNM staging classification, with adjustment of the size T factor according to only the invasive component pathologically in adenocarcinomas with lepidic areas.

Search

Search