Single-Arm Resistance Training Study to Determine the Relationship between Training Outcomes and Muscle Growth Factor mRNAs in Older Adults Consuming Numerous Medications and Supplements.

OBJECTIVES: Determine if the muscle mRNA levels of three growth factors (insulin-like growth factor-1 [IGF1], ciliary neurotropic factor [CNTF], and vascular endothelial growth factor-D [VEGFD]) are correlated with muscle size and strength gains from resistance exercise while piloting a training program in older adults taking medications and supplements for age-associated problems. DESIGN: Single-arm prospective study. SETTING: US Veterans Affairs hospital. PARTICIPANTS: Older (70±6 yrs) male Veterans (N=14) of US military service. INTERVENTION: Thirty-five sessions of high-intensity (80% one-rep max) resistance training including leg press, knee curl, and knee extension to target the thigh muscles. MEASUREMENTS: Vastus lateralis biopsies were collected and body composition (DEXA) was determined pre- and post-training. Simple Pearson correlations were used to compare training outcomes to growth factor mRNA levels and other independent variables such as medication and supplement use. RESULTS: Average strength increase for the group was ≥ 25% for each exercise. Subjects averaged taking numerous medications (N=5±3) and supplements (N=2±2). Of the growth factors, a significant correlation (R>0.7, P≤0.003) was only found between pre-training VEGFD and gains in lean thigh mass and extension strength. Mass and strength gains were also correlated with use of α-1 antagonists (R=0.55, P=0.04) and pre-training lean mass (R=0.56, P=0.04), respectively. CONCLUSIONS: Muscle VEGFD, muscle mass, and use of α-1 antagonists may be predisposing factors that influence the response to training in this population of older adults but additional investigation is required to determine if these relationships are due to muscle angiogenesis and blood supply.

Assessment of VEGF-D expression measured by immunohistochemical staining and F-18 FDG uptake on PET as biological prognostic factors for recurrence in patients with surgically resected lung adenocarcinoma.

OBJECTIVE: To assess whether the combined evaluation of vascular endothelial growth factor D (VEGF-D) expression and fluorodeoxyglucose (FDG) uptake correlates with lymph node metastasis and post-operative recurrence in patients with lung adenocarcinoma. METHODS: Forty-six patients with lung adenocarcinomas, who had undergone both preoperative FDG PET imaging and thoracotomy, were enrolled in this study. The surgically resected tumor specimens were used to assess the protein levels of VEGF-D as measured by immunohistochemical assay. RESULTS: The patients were divided into the following four groups: those who were VEGF-D negative and had low FDG uptake (group I, 3 patients), VEGF-D positive and had low FDG uptake (group II, 20 patients), VEGF-D negative and had high FDG uptake (group III, 13 patients), and VEGF-D positive and had high FDG uptake (group IV, 10 patients). Lymph node metastases were seen only in group III. The 5-year disease-free survival rates were 66.7% in group I, 83.9% in group II, 8.3% in group III, and 64.0% in group IV (p < 0.0001). Thus, patients in group III exhibited the most unfavorable prognoses for recurrence. In multivariate analysis, the combined evaluation of VEGF-D expression and FDG uptake was an independent parameter for post-operative recurrence (p = 0.018). CONCLUSION: A combination of low VEGF-D expression and high FDG uptake may be a biological indicator of lymph node metastasis and post-operative recurrence in patients with lung adenocarcinoma.

Expression of VEGF-C and VEGF-D as significant markers for assessment of lymphangiogenesis and lymph node metastasis in non-small cell lung cancer.

Vascular endothelial growth factor (VEGF)-C and VEGF-D induce lymphangiogenesis through activation of VEGF receptor 3 (VEGFR-3) and have been implicated in tumor spread to the lymphatic system. Lymph node dissemination critically determines clinical outcome and therapeutic options of patients with non-small cell lung cancer (NSCLC). However, the relationship of VEGF-C, VEGF-D, and lymph node metastasis in cancers, including NSCLC, is still controversial. To evaluate the relationship between lymphangiogenesis and lymph node metastasis, the expression of VEGF-C and VEGF-D in NSCLC tumors were detected by immunohistochemistry and quantitative real-time polymerase chain reaction (QRT-PCR). QRT-PCR revealed that in marginal region VEGF-C and VEGF-D mRNA was significantly higher than in tumor center, and VEGF-D mRNA was also higher than that in peritumoral lung tissue. Immunohistochemically, we observed the same heterogeneous expression of VEGF-C and VEGF-D proteins. The group with high expression of VEGF-C and VEGF-D in marginal region had a higher incidence of lymph node metastasis compared with the group with low expression. Furthermore, the group with high expression of VEGF-D in marginal region had a higher incidence of lymphatic invasion. The group with high peritumoral lymphatic vessel density (LVD) had higher expression of VEGF-C and VEGF-D mRNA compared with the group with low peritumoral LVD. Our studies suggested that the expression of VEGF-C and VEGF-D at invasive edge was significantly associated with lymph node metastasis or lymphatic invasion in patients with NSCLC and may be involved in regulation of lymphangiogenesis and lymph node metastasis in NSCLC.