Seromic analysis of antibody responses in non-small cell lung cancer patients and healthy donors using conformational protein arrays.

Analysis of antibody responses to self-antigens has driven the development of the field of tumor immunology, with the identification of many protein targets found in cancer but with limited expression in normal tissues. Protein microarray technologies offer an unprecedented platform to assay the serological response of cancer patients to tumor antigens in a comprehensive fashion, against many proteins simultaneously. We developed an array containing 329 full-length proteins, originally identified as antigenic in various cancer patients by serological expression cloning (SEREX), that were immobilized as folded, functional products accessible for antibody binding.

The number of lymph nodes removed predicts survival in esophageal cancer: an international study on the impact of extent of surgical resection.

Objective: Surveillance, Epidemiology and End Results (SEER) data indicate that number of lymph nodes removed impacts survival in gastric cancer. Our aim was to study this relationship in esophageal cancer.

Methods: The study population included 2303 esophageal cancer patients (1381 adenocarcinoma, 922 squamous) from 9 international centers that had R0 esophagectomy prior to 2002 and were followed at regular intervals for 5 years or until death.

Cigarette smoking and risk of lung metastasis from esophageal cancer.

Background: Whereas extensive research has explored the effect of environmental factors on the etiology of specific cancers, the influence of exposures such as smoking on risk of site-specific metastasis is unknown. We investigated the association of cigarette smoking with lung metastasis in esophageal cancer.

Methods: We conducted a case-control study of esophageal cancer patients from two centers, comparing cases with lung metastases to controls without lung metastases.

Total number of resected lymph nodes predicts survival in esophageal cancer.

Objective: Several population-based studies have shown that the total number of surgically removed lymph nodes is independently associated with overall and disease-free survival in a variety of gastrointestinal cancers. In this retrospective study, the impact of total nodal count on overall survival in esophageal cancer was examined using a single institution surgical database.

Methods: We conducted a retrospective review of 264 patients with esophageal cancer treated by esophagectomy without neoadjuvant therapy between January 1988 and December 2006.

ECSA/DPPA2 is an embryo-cancer antigen that is coexpressed with cancer-testis antigens in non-small cell lung cancer.

Purpose: Cancer cells recapitulate many behaviors of pluripotent embryonic cells such as unlimited proliferation, and the capacity to self-renew and to migrate. Embryo-cancer sequence A (ECSA), later named developmental pluripotency associated-2 (DPPA2), is an embryonic gene initially isolated from pluripotent human preimplantation embryos. We hypothesized that ECSA/DPPA2 would be quiescent in most normal tissues but expressed in cancers and may therefore be a useful target for immunotherapy.

Detection of lung cancer using weighted digital analysis of breath biomarkers.

Background: A combination of biomarkers in a multivariate model may predict disease with greater accuracy than a single biomarker employed alone. We developed a non-linear method of multivariate analysis, weighted digital analysis (WDA), and evaluated its ability to predict lung cancer employing volatile biomarkers in the breath.

Methods: WDA generates a discriminant function to predict membership in disease vs no disease groups by determining weight, a cutoff value, and a sign for each predictor variable employed in the model.

Multifocal neoplasia and nodal metastases in T1 esophageal carcinoma: implications for endoscopic treatment.

Objective: There has been an increase in interest in endoscopic therapy (ET) for intramucosal (T1a) or submucosal (T1b) esophageal carcinoma. The objective of the present study was to determine the prevalence of nodal metastases, lymphatic vascular invasion, and multifocal neoplasia in patients with pT1 esophageal carcinoma who underwent esophagectomy without preoperative therapy and assess their potential implication for ET.

Methods: We retrospectively reviewed the records of all patients who underwent esophagectomy without preoperative therapy for pT1 esophageal cancer.

PAX-5 expression in pulmonary neuroendocrine neoplasms: its usefulness in surgical and fine-needle aspiration biopsy specimens.

The World Health Organization classification of lung tumors recognizes 4 histologic subtypes of pulmonary neuroendocrine carcinomas (NECs), which include typical carcinoids (TCs), atypical carcinoids (ACs), small cell carcinomas (SCCs), and large cell NECs (LCNECs). These tumors can be misclassified owing to morphologic parallels, indicating the necessity for adjunctive tests for correct classification. We evaluated immunohistochemical expression of PAX-5 in histologic and fine-needle aspiration (FNA) specimens of pulmonary NECs.

Booster vaccination of cancer patients with MAGE-A3 protein reveals long-term immunological memory or tolerance depending on priming.

We previously reported results of a phase II trial in which recombinant MAGE-A3 protein was administered with or without adjuvant AS02B to 18 non-small-cell lung cancer (NSCLC) patients after tumor resection. We found that the presence of adjuvant was essential for the development of humoral and cellular responses against selected MAGE-A3 epitopes. In our current study, 14 patients that still had no evidence of disease up to 3 years after vaccination with MAGE-A3 protein with or without adjuvant received an additional four doses of MAGE-A3 protein with adjuvant AS02B.

PLAC1, a trophoblast-specific cell surface protein, is expressed in a range of human tumors and elicits spontaneous antibody responses.

Identification of genes that are upregulated in tumors, and whose normal expression excludes adult somatic tissues but includes germline and/or embryonic tissues, has resulted in a rich variety of cancer antigens that are attractive targets for cancer vaccine and other therapeutic approaches. In the present study, we extended this approach to include genes strongly and restrictively expressed in the placenta by mining publicly available SAGE and EST databases. We identified a number of genes with high expression in placenta and different cancer types but with relatively restricted expression in normal tissues.

Positron emission tomographic scanning predicts survival after induction chemotherapy for esophageal carcinoma.

Background: The ability to accurately predict clinical and pathological response and survival in patients undergoing preoperative chemotherapy may have a significant impact on treatment strategy for esophageal carcinoma. This study assessed the predictive accuracy of clinical response (CR) and positron emission tomography (PET) scanning in determining pathological downstaging and disease free survival (DFS) after chemotherapy.

Methods: This is a retrospective review of patients who underwent chemotherapy prior to complete surgical resection for esophageal carcinoma between 1999 and 2005.

The role of CT screening for lung cancer.

A person who is at high-risk for lung cancer and asymptomatic, and who is interested in potentially being screened should be fully apprized of the implications of screening and of the treatment that may result. In light of this, it is reasonable for the individual to choose to be screened by a multidisciplinary medical team with experience in performing such screenings, using a well-defined CT regimen of screening, and having appropriate quality assurance procedures in place.

Risk factors for occult mediastinal metastases in clinical stage I non-small cell lung cancer.

Background: In patients deemed to have clinical stage I for non-small cell lung cancer (NSCLC) after computerized tomography (CT) and positron emission tomography (PET) scans, the utility of mediastinoscopy to detect occult mediastinal metastases is unclear. The goal of this study was to analyze the risk factors for occult mediastinal metastases in this subset of patients.

Methods: We conducted a retrospective review during a 7-year period to identify patients with potentially operable clinical stage I NSCLC screened by CT and PET scans.

Prediction of lung cancer using volatile biomarkers in breath.

Background: Normal metabolism generates several volatile organic compounds (VOCs) that are excreted in the breath (e.g. alkanes).

Surgical resection for multifocal (T4) non-small cell lung cancer: is the T4 designation valid?

Background: The current international staging system for lung cancer designates intralobar satellites as T4 disease. In this study, we sought to determine the impact of multifocal, intralobar non-small cell lung cancer (NSCLC) on patient survival and its potential relevance to stage designation.

Methods: We conducted a retrospective review of our thoracic surgical cancer registry from 1990 to 2005.

Long-term survival and recurrence in patients with resected non-small cell lung cancer 1 cm or less in size.

Objective: With the widespread use of computed tomography and the emergence of screening programs, non-small cell lung cancer is increasingly detected in sizes 1 cm or less. We sought to examine the long-term survival and recurrence patterns after resection of these tumors.

Methods: We conducted a retrospective review over a 15-year period to identify patients with surgically resected non-small cell lung cancer measuring 1 cm or less.

Physical interaction of two cancer-testis antigens, MAGE-C1 (CT7) and NY-ESO-1 (CT6).

Cancer/testis (CT) antigens are the protein products of germ line-associated genes that are activated in a wide variety of tumors and can elicit autologous cellular and humoral immune responses. CT antigens can be divided between those that are encoded on the X chromosome (CT-X antigens) and those that are not (non-X CT antigens). Among the CT-X antigens, the melanoma antigen gene (MAGE) family, defined by a shared MAGE homology domain (MHD), is the largest.

Randomized phase II trial of docetaxel/irinotecan and gemcitabine/irinotecan with or without celecoxib in the second-line treatment of non-small-cell lung cancer.

Purpose: Trials combining irinotecan/docetaxel and irinotecan/gemcitabine in second-line treatment of non-small-cell lung cancer (NSCLC) have yielded promising results. Preliminary data suggested that the selective cyclooxygenase -2 inhibitor celecoxib (CBX) might enhance efficacy of chemotherapeutic regimens. This multicenter, phase II, randomized trial investigated efficacy and safety of irinotecan and docetaxel and irinotecan and gemcitabine, with or without CBX, in second-line treatment of NSCLC.

Accuracy of surveillance computed tomography in detecting recurrent or new primary lung cancer in patients with completely resected lung cancer.

Background: To determine the eventual outcome of abnormalities detected on surveillance computed tomography (CT) in patients with previously resected nonsmall-cell lung cancer (NSCLC), and to assess the accuracy of CT when used by the thoracic surgeon, and to determine the characteristics of abnormalities on CT that correlate with the development of recurrent NSCLC.

Methods: A cohort of patients who had abnormal postoperative CT scans of the chest and upper abdomen in 2002 were followed up into 2005. Abnormalities consisted of pulmonary nodules, pleural effusions, or adenopathy.

Downstaging of T or N predicts long-term survival after preoperative chemotherapy and radical resection for esophageal carcinoma.

Background: The purposes of this study were to determine the frequency of downstaging of T or N after neoadjuvant chemotherapy and radical resection in patients with carcinoma of the esophagus, and to evaluate the effect of tumor downstaging on survival.

Methods: A cohort of patients who underwent neoadjuvant chemotherapy followed by radical surgical resection for carcinoma of the esophagus was identified from a large, prospectively maintained, single-institution database of esophageal cancer patients. Patients were included if they had an accurate pretreatment clinical stage determined by the authors.