Plasma transforming growth factor-?1 level before radiotherapy correlates with long term outcome of patients with lung carcinoma

Kong, Feng-Ming Spring; Jirtle, Randy L.; Huang, Dale; Clough, Robert; Anscher, Mitchell S.

doi:10.1002/(sici)1097-0142(19991101)86:9<1712::aid-cncr12>3.0.co;2-v

Cited by 124 publications

(36 citation statements)

References 39 publications

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“…In contrast, in patients who experienced disease progression, the fall in postoperative IL-6 and IL-6sR levels after prostate removal was significant (30 and 27%, respectively), whereas postoperative TGF-␤ 1 levels fell only minimally (9%) and were not significantly different from preoperative TGF-␤ 1 levels. These findings are similar to findings reported for other surgically treated malignancies with TGF-␤ 1 decreasing only in patients apparently cured after definitive surgery and remaining elevated in patients found to have lymph node or distant metastases and/or residual disease after surgery (25)(26)(27). In addition, in concordance with our findings, Tsushima et al (27) found that in patients undergoing colon resection for colorectal cancer, both the pre-and postoperative TGF-␤ 1 level were associated with development of liver metastases when controlling for the effects of age, pre-and postoperative carcinoembryonic antigen level, gender, and clinical tumor grade and stage.…”

Section: Discussionsupporting

confidence: 89%

Association of Pre- and Postoperative Plasma Levels of Transforming Growth Factor β1 and Interleukin 6 and Its Soluble Receptor with Prostate Cancer Progression

Shariat

Kattan

Traxel

et al. 2004

Clinical Cancer Research

158

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Purpose:We have shown that preoperative plasma levels of transforming growth factor-␤ 1 (TGF-␤ 1 ), interleukin 6 (IL)-6, and its receptor (IL-6sR) are associated with prostate cancer progression and metastasis. The objectives of this study were to confirm these findings and to examine the association of changes in plasma levels of these markers after surgery with disease progression in a large consecutive cohort of patients.Experimental Design: Plasma levels of TGF-␤ 1 , IL-6, and IL-6sR were measured pre-and postoperatively (6 -8 weeks after surgery) in 302 consecutive patients who underwent radical prostatectomy for clinically localized disease.Results: Pre-and postoperative levels of TGF-␤ 1 were significantly elevated in patients with extraprostatic extension, seminal vesicle involvement, and metastases to lymph nodes. In contrast, preoperative levels of IL-6 and IL-6sR, but not postoperative levels, were significantly associated with tumor volume, prostatectomy Gleason sum, and metastases to lymph nodes. In a postoperative model that included pre-and postoperative TGF-␤ 1 , IL-6, and IL-6sR and standard postoperative parameters, postoperative TGF-␤ 1 and prostatectomy Gleason sum were significant predictors of overall and aggressive disease progression. Although, for all patients, plasma levels of all three markers declined significantly after prostate removal, for patients that experienced disease progression, only IL-6 and IL-6sR levels decreased significantly.Conclusions: For patients undergoing radical prostatectomy, preoperative plasma levels of TGF-␤ 1 and IL-6sR are associated with metastases to regional lymph nodes, presumed occult metastases at the time of primary treatment, and disease progression. After prostate removal, postoperative TGF-␤ 1 level increases in value over preoperative levels for the prediction of disease progression.

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Section: Discussionsupporting

confidence: 89%

Association of Pre- and Postoperative Plasma Levels of Transforming Growth Factor β1 and Interleukin 6 and Its Soluble Receptor with Prostate Cancer Progression

Shariat

Kattan

Traxel

et al. 2004

Clinical Cancer Research

158

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“…Im klinischen Bereich wurde eine Korrelation zwischen zirkulierenden TGF-β-Blutspiegeln und der Inzidenz pulmonaler Komplikationen erstmals bei Patientinnen beobachtet, die aufgrund eines fortgeschrittenen Mammakarzinoms mit Hochdosischemotherapie und nachfolgender autologer Knochenmarktransplantation behandelt wurden [5]. In späteren klinischen Studien konnte dieselbe Arbeitsgruppe zeigen, dass bei Patienten, die sich aufgrund eines Bronchialkarzinoms einer Radiotherapie unterzogen, anhaltend erhöhte TGF-β-Plasmaspiegel während der Radiotherapie mit einer deutlich erhöhten Pneumonitisinzidenz korrelierten [1,2,4,33,68]. In folgenden Studien wurden von dieser Arbeitsgruppe Patienten mit nichtkleinzelligem Bronchialkarzinom aufgrund entsprechend niedriger TGF-β-Plasmaspiegel für eine Dosiseskalation selektioniert, ohne dass bei diesen Patienten pulmonale Komplikationen auftraten [3].…”

Section: Klinische Bedeutung Von Zytokinblutspiegeln Für Die Ermittluunclassified

Die Bedeutung von Zytokinen für die radiogene Lungenreaktion

2004

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The major pro-inflammatory cytokines in the radiation response of the lung include tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6). Transforming growth factor-beta (TGF-beta) appears to be of particular importance in the development of lung fibrosis. First approaches with radioprotective agents and gene therapy to modify radiation-induced cytokine expression have been investigated for prevention of late effects of irradiation lung damage in animal experiments. Preliminary data of clinical studies suggest that elevated plasma TGF-beta-levels during radiotherapy may predict the development of symptomatic radiation pneumonitis. The biological impacts of endogenous radiation-induced cytokine production by tumor cells in respect of tumor behavior, potential damage to normal tissue, and clinical status of the host still need to be determined more precisely.

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“…In various groups of normal subjects these vary from 0.1 ng/ml to over 25 ng/ml, [7] but where steps have been taken to minimise platelet degranulation in healthy subjects the published range is 2.0 Á12.0 ng/ml. Previous studies in patients with lung cancer have shown mean pre-treatment levels of 11.7 ng/ml, [5] while breast cancer patients show mean pre-treatment levels of approximately 20 ng/ml [4]. Our lower levels, found in previously untreated patients (range 0.81 to 10.97 ng/ml; median 2.83 ng/ ml), are likely to reflect the careful precautions taken to minimise platelet degradation.…”

Section: To the Editormentioning

confidence: 48%

Plasma TGFβ₁during pelvic radiotherapy for gynaecological malignancy

et al. 2006

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The pro-fibrotic cytokine transforming growth factor b 1 (TGFb 1 ) is implicated in the pathogenesis of radiation fibrosis [1 Á6], which contributes to late morbidity following radiotherapy. Relatively few laboratories have conducted studies during radiotherapy and none to our knowledge during pelvic radiotherapy. Neither have strict precautions been observed to minimise platelet degradation and supra-physiological TGFb 1 release. Excessive platelet degranulation during standard venepuncture causes immediate release of TGFb 1 and further increments can occur during long-term storage of blood/serum unless samples are frozen at (/208C. These factors hinder reliable inter-comparisons of results from different laboratories.Here we report a detailed study involving eight patients: five had cervix cancers and received radical radiotherapy (at 1.8 Gy per fraction) and weekly cisplatinum chemotherapy (numbers 2, 4, 5, 7 and 8), while three received pelvic radiotherapy after hysterectomy for endometrial malignancy (numbered 1, 3 and 6). Following informed consent procedures, venous blood was collected without a tourniquet, through a wide-gauge butterfly needle into a prechilled CTAD tube. Vacutainers and syringes were not used because of the turbulence (and platelet degradation) they induce. Samples were gently mixed by inversion and placed immediately on ice. Within one hour samples were centrifuged for 30 min at 1200 )/g at 4 o C. One millilitre aliquots of supernatant were stored at (/70 o C. All plasma samples were assayed for TGFb 1 within six months of collection in order to minimise the increases during long-term storage which have been reported in previous studies and which are thought to result from release of covalently bound TGFb 1 from a-macroglobulin [7]. In order to avoid inclusion of latent TGFb 1 complexes in human plasma, we used the R&D Quantikine ELISA System for human TGFb 1 , with pre-treatment of samples with 2.5N acetic acid/10M urea to disrupt a range of TGFb 1 complexes. Each sample was assayed in duplicate at three serial dilutions and the mean and standard error calculated from the resulting six readings.The baseline plasma TGFb 1 results (see Figure 1) were generally lower than the published data relating to lung and breast cancer, which is consistent with our sample collection technique. The standard error values are small. Most remained below 5 ng/ml during treatment, but two patients had levels /10 ng/ml. Close inspection of Figure 1 reveals that there are possible cyclical fluctuations in plasma TGFb 1 . Such fluctuations could be due to random variation (or are associated with the assay technique), rather than being a result of ordered homeostatic cyclical activity. Another possibility is that results were heavily influenced by the weekly sampling times: for example, if twice weekly sampling had been used, then further fluctuations and a shorter cyclical period might have been found. One patient (number 5) with recurrent cancer and who had undergone previous radiotherapy and extensive pelv...

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Plasma transforming growth factor-?1 level before radiotherapy correlates with long term outcome of patients with lung carcinoma

Cited by 124 publications

References 39 publications

Association of Pre- and Postoperative Plasma Levels of Transforming Growth Factor β1 and Interleukin 6 and Its Soluble Receptor with Prostate Cancer Progression

Association of Pre- and Postoperative Plasma Levels of Transforming Growth Factor β1 and Interleukin 6 and Its Soluble Receptor with Prostate Cancer Progression

Die Bedeutung von Zytokinen für die radiogene Lungenreaktion

Plasma TGFβ₁during pelvic radiotherapy for gynaecological malignancy

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Plasma transforming growth factor-?1 level before radiotherapy correlates with long term outcome of patients with lung carcinoma

Cited by 124 publications

References 39 publications

Association of Pre- and Postoperative Plasma Levels of Transforming Growth Factor β1 and Interleukin 6 and Its Soluble Receptor with Prostate Cancer Progression

Association of Pre- and Postoperative Plasma Levels of Transforming Growth Factor β1 and Interleukin 6 and Its Soluble Receptor with Prostate Cancer Progression

Die Bedeutung von Zytokinen für die radiogene Lungenreaktion

Plasma TGFβ1during pelvic radiotherapy for gynaecological malignancy

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Product

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Plasma TGFβ₁during pelvic radiotherapy for gynaecological malignancy