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Biomedical subjects

Allan Pickens

Publications and source records attributed to Allan Pickens.

6 recordsLinked to original sources

Diversity of the angiogenic phenotype in non-small cell lung cancer.

Angiogenesis is crucial for tumor biology. There are many mechanisms by which tumors induce angiogenesis. We hypothesize that each individual tumor develops a unique mechanism to induce angiogenesis, and that activation of a particular angiogenic pathway suppresses the evolution of alternative pathways. We characterized 168 human non-small cell lung cancer (NSCLC) specimens for levels of angiogenic factors (angiogenic CXC chemokines, basic fibroblast growth factor, and vascular endothelial growth factor). We also induced lung tumor formation in A/J mice by injecting the tobacco carcinogen NNK. We dissected individual lung tumors and measured expression of angiogenic factors from three distinct families using real-time PCR. Finally, we controlled the angiogenic milieu using in vivo models to determine the resultant phenotype of the angiogenic factors expressed by NSCLC cells. Human tumors displayed marked variation in the expression of angiogenic factors. Individual mouse tumors, even from within the same mouse, displayed variability in their pattern of expression of angiogenic factors. In a sponge model of angiogenesis using murine lung cancer cells, implanting LLC cells with an angiogenic factor suppressed the expression of other angiogenic factors in implanted sponges. This suppressive effect was not seen in vitro. We conclude that lung cancer tumors evolve a unique and dominant angiogenic phenotype. Once an angiogenic pathway is activated, it may allow for tumor growth to proceed in the absence of a selection pressure to activate a second pathway.

Angiogenic Proteins↗

Tension chylothorax.

Thoracic duct injury resulting in chylothorax is a well-known and documented complication of thoracic surgery. However, chylothorax under tension is a rarely reported complication that results in respiratory and hemodynamic collapse. Early recognition and treatment of this entity are essential for optimal patient outcome. Herein we present two cases of postoperative tension chylothorax followed by a review of the diagnostic work-up and therapy for this complication.

Aged↗

Awake tracheobronchial dilation without the use of rigid bronchoscopy.

Benign tracheal strictures have been treated by repeated dilations using rigid bronchoscopy and general anesthesia. An alternative approach using conscious sedation, fluoroscopy, flexible bronchoscopy, and Savary-Gilliard esophageal dilators (Cook Endoscopy, Inc, Winston-Salem, NC) is reported. All patients undergoing dilation while awake had lesions due to inflammatory disease or lesions that were not amenable to resection. This method may be less traumatic than rigid bronchoscopy and can be accomplished on an outpatient basis without the use of general anesthesia.

Adult↗

VATS anatomic pulmonary resection in octogenarians.

Although modern techniques in anesthesia and surgery have reduced morbidity and mortality for pulmonary resection, some physicians still consider advanced age a contraindication to resection of lung cancer. We examined our experience with VATS lobectomy in octogenarians at Cedars-Sinai Medical Center over 12 years (1992-2004). There were 159 patients. Mean age was 83 years (range, 80-94 years) consisting of 61 males (38%) and 96 females (62%). Operations included 153 lobectomies (96%), 3 bilobectomies (2%), and 3 pneumonectomies (2%). Two operations were converted to thoracotomy (1%), one due to bleeding, and one due to poor visualization. Median hospital stay was 4.00 +/- 6.39 days. One hundred thirty-one patients (82%) had no complications. The most common complication was arrhythmias occurring in 8/159 (5%) patients. There were three perioperative deaths (1.8%). Pathology revealed 104 adenocarcinomas (65%), 25 squamous cell carcinomas (16%), 5 adeno-squamous carcinomas (3%), 7 bronchoalveolar carcinomas (4%), 7 large cell carcinomas (4%), 4 carcinoid tumors (3%), 4 non-small cell lung cancer (NSCLC) (3%), 1 mucoepidermoid carcinoma (< 1%), 1 lymphoma (< 1%), and 1 pulmonary metastasis (< 1%). Median follow-up was 29 months. The results of this series show that age alone is not a contraindication to the surgical treatment of lung cancer.

Age Factors↗

Transforming growth factor-alpha: a surrogate endpoint biomarker?

BACKGROUND: Dysplastic oral leukoplakia (DOL) has been the index lesion in prevention trials for upper aerodigestive tract squamous cell carcinoma (SCC). Vitamin A derivatives, including 13-cis retinoic acid (13-CRA), have been used to treat DOL and to reduce the risk of subsequent SCC. Results from a trial of 13-CRA in patients with DOL are presented here. Transforming growth factor-alpha (TGF-alpha) and the epidermal growth factor receptor messenger RNA (mRNA) expression were studied to validate their use as surrogate endpoint biomarkers in prevention trials for SCC. STUDY DESIGN: In a prospective, randomized, double-blind trial of 13-CRA in 28 patients with DOL, TGF-alpha and epidermal growth factor receptor mRNA expression were analyzed in sequential biopsy specimens of DOL and of adjacent normal-appearing mucosa, utilizing a quantitative, competitive, reverse transcriptase polymerase chain reaction and were compared using the Wilcoxon signed-rank test for paired comparisons. RESULTS: In biopsy specimens of DOL, TGF-alpha mRNA expression at baseline, but not baseline expression of epidermal growth factor receptor mRNA, was significantly elevated when compared with its expression in specimens from adjacent normal-appearing mucosa (p = 0.003). In patients randomized to 13-CRA who had > or = 50% clearance of DOL during treatment, significant modulation of TGF-alpha mRNA overexpression was seen after 6 months of treatment (p = 0.016). TGF-alpha mRNA overexpression at baseline predicted a subsequent response to 13-CRA (p 0.066). CONCLUSIONS: The full extent of the association between TGF-alpha overexpression and the development of SCC is unknown. Evidence is presented in this article that TGF-alpha overexpression mediates the relationship between 13-CRA and DOL, but there is no direct evidence that it mediates the relationship between 13-CRA and the prevention of SCC. Determination of the extent to which TGF-alpha overexpression mediates this relationship and complete validation of TGF-alpha's role as a surrogate endpoint biomarker await the results of animal and human trials that utilize reduction in the incidence of SCC as their endpoint.

Aged↗