Feng-Ming Kong

Plasma transforming growth factor-β1 level before radiotherapy correlates with long term outcome of patients with lung carcinoma

Plasma transforming growth factor‐β1 (TGFβ1) levels are increased in many malignancies at the time of diagnosis, including all forms of lung carcinoma. Therefore, the potential use of TGFβ1 as a plasma marker to predict the long term outcome of lung carcinoma patients treated with radiotherapy (RT) was evaluated.

M6P/IGF2R is mutated in squamous cell carcinoma of the lung

In addition to the intracellular sorting of lysosomal enzymes, the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) plays a critical role in regulating the bioavailability of extracellular proteolytic enzymes and growth factors. It has also been shown to be mutated in a number of human cancers, and to suppress cancer cell growth. The purpose of this study was to determine if the M6P/IGF2R is mutated in lung cancer, a leading cause of cancer death worldwide. Archival pathology specimens were obtained on 22 patients with newly diagnosed, untreated squamous cell carcinoma of the lung. Two polymorphisms in the 3′-untranslated region of the M6P/IGF2R were used to screen lung tumors for loss of heterozygosity (LOH) by PCR amplification of DNA. Nineteen of 22 (86%) patients were informative (heterozygous), and 11/19 (58%) squamous cell carcinomas of the lung had LOH at the M6P/IGF2R locus. The remaining allele in 6/11 (55%) LOH patients contained mutations in either the mannose 6-phosphate or the IGF2 binding domain of the M6P/IGF2R. Thus, the M6P/IGF2R is mutated frequently in squamous cell carcinoma of the lung, providing further support for its function as a tumor suppressor.

Transforming growth factor-beta receptors and mannose 6-phosphate/insulin-like growth factor-II receptor expression in human hepatocellular carcinoma.

ObjectiveThe authors examined the expression of transforming growth factor-beta receptor (TGF-βr) types I and II and the mannose 6-phosphate/insulin-like growth factor-II receptor (M6-P/IGF-IIr) in human hepatocellular carcinoma (HCC). Summary Background DataTransforming growth factor-beta (TGF-β) is part of a superfamily of peptide-signaling molecules that play an important role in modulating cell growth. It is secreted as a latent complex and therefore, must be activated to elicit a biological response. Bioactivaton of the TGF-β complex is facilitated by binding to the M6-P/IGF-IIr. Once activated, TGF-β exerts its effects by binding to specific cell membrane TGF-β receptors. The loss of responsiveness of hepatocytes to TGF-β has been implicated in hepatocarcinogenesis and could result from a loss in the expression of either the TGF-β receptors or the M6-P/IGF-IIr. MethodsHuman hepatocellular carcinomas and surrounding normal tissue were collected from operating room samples and snap-frozen in liquid nitrogen (n = 13). Tissues from two tumors were fixed in Omni-fix for sectioning and immunohistochemistry staining for the M6-P/IGF-IIr and TGF-β1. RNA was extracted from both normal and malignant liver tissue and analyzed using an RNase protection assay. SDS-PAGE of purified membrane hybridized with 125I-IGF-β1 and 125I-IGF-II was used to determine the TGF-β type I (TGF-βrl) and type II (TGF-βrll) receptors and M6-P/IGF-IIr protein levels, respectively. Gels were quantitated by phosphorimager, and a paired t test was used for statistical analysis. ResultsIn HCC, a 60% (p < 0.01) and 49% (p < 0.02) reduction in the mRNA levels for Tβrl and Tβrll, respectively, relative to the receptor levels in surrounding normal liver, was shown. A similar decrease in the receptor protein levels also was observed. The M6-P/IGF-IIr mRNA and protein

Plasma transforming growth factor-β1 reflects disease status in patients with lung cancer after radiotherapy: a possible tumor marker

PURPOSE To determine the frequency with which elevated plasma transforming growth factor-beta 1 (TGF beta 1) concentrations occur in lung cancer patients, to determine the kinetics of TGF beta 1 expression during and after radiotherapy and to correlate plasma TGF beta 1 levels with disease status after treatment. MATERIALS AND METHODS Plasma samples were obtained before, during and after radiotherapy in 54 patients with lung cancer and 20 normal controls. Plasma TGF beta 1 levels were measured using an enzyme-linked immunosorbent assay. RESULTS Baseline TGF beta 1 levels in lung cancer patients and normal controls were 13.0 +/- 2.5 and 4.4 +/- 0.3 ng/ml, respectively. Elevated TGF beta 1 were found in 50% (27/54) of lung cancer patients. During radiation therapy plasma TGF beta 1 levels declined, however, by the completion of treatment the mean TGF beta 1 level had not normalized in patients with lung cancer. The TGF beta 1 level at last follow-up correlated with disease status in those patients with an increased pretreatment plasma level. Three of four patients with no evidence of cancer had normal follow-up TGF beta 1 levels, compared to 2/16 patients with residual or recurrent tumor (P = 0.02). CONCLUSIONS Elevated plasma TGF beta 1 levels occur frequently in patients with lung cancer. In those patients with an elevated plasma TGF beta 1 level at diagnosis, monitoring this level may be useful in detecting both disease persistence and recurrence after therapy.

The relevance of transforming growth factor β1 in pulmonary injury after radiation therapy

The maximum dose of radiation which can be delivered to a tumor is limited by the tolerance of the surrounding normal tissues. The ability to identify patients at high or low risk of injury from radiation therapy might enable the clinician to tailor radiation doses in order to maximize efficacy and minimize risk. The cytokine transforming growth factor beta 1 (TGF beta 1) has been implicated in the development of normal tissue injury after irradiation in several organs, including the lung. Herein, the evidence supporting the role of TGF beta 1 in radiation-induced lung injury is reviewed. Using the treatment of non-small cell lung cancer as a model, we also discuss how it may be possible to identify patients at risk for this complication using measurements of plasma TGF beta 1, and how this information may be used in the future to adjust doses of radiation in the treatment of lung cancer.

2155 Plasma transforming growth factor beta1 (TGFβ1): A monitor for persistence or recurrence of disease in patients with lung cancer

These data demonstrate that plasma TGFBl is a independent marker which could be used to monitor the persistence and/or recurrence of disease in lung cancer patients. The end RT TGFDl levels might be used to choose patients who need further adjuvent treatment.