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Metastatic Progression (metastatic + progression)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

Selective dose escalation of chemoradiotherapy for locally advanced esophageal cancer

DISEASES OF THE ESOPHAGUS, Issue 7 2008
S. K. Seung
SUMMARY., This phase II study assessed the use of concurrent continuous infusion of 5-fluorouracil and weekly carboplatin plus paclitaxel with selective radiation dose escalation for patients with localized esophageal cancer. Patients with esophageal carcinoma were staged by thoracic and abdominal computed tomography, endoscopic ultrasound, and positron emission tomography scans. Patients received a continuous infusion of 5-fluorouracil 225 mg/m2 on days 1 to 38 and intravenous paclitaxel 45 mg/m2 and carboplatin AUC 2 on days 1, 8, 15, 22, 29, and 36. Radiotherapy was delivered in 1.8-Gy fractions, 5 d/wk for 5.5 weeks. Six to 8 weeks after initial therapy, patients without metastatic progression but with a positive biopsy, or less than partial response received a 9-Gy boost with the same concurrent chemotherapy. Twenty-four patients were enrolled: 18 patients were enrolled initially; 6 additional patients were enrolled following a protocol amendment designed to reduce the esophagitis by adding the radioprotectant amifostine. Median follow-up was 30 months. Twenty (83%) patients had adenocarcinomas of the lower esophagus/gastroesophageal junction. Seventeen patients (81%) attained at least a partial response. Six patients received boost treatment. At 4 years, overall survival was 28%, cause-specific survival was 38%, locoregional control was 61%, and distant metastasis-free survival was 52%. Radiation delays ranged from 0 to 62 days (median, 8 d), primarily owing to esophagitis. In total, 28% of patients developed esophageal strictures requiring dilatations. There were no differences in esophageal strictures, local control, or survival with the addition of amifostine. [source]

The tale of transforming growth factor-beta (TGF,) signaling: A soigné enigma

IUBMB LIFE, Issue 10 2009
Arindam Chaudhury
Abstract Transforming growth factor-beta (TGF,) is a secreted cytokine, which intricately controls a plethora of physiological and pathological processes during development and carcinogenesis. TGF, exerts antiproliferative effects and functions as a tumor suppressor during early stages of tumorigenesis, whereas at later stages it functions as a tumor promoter aiding in metastatic progression through an autocrine TGF, loop. Intricate knowledge of TGF, signaling and its regulation are still evolving. In this review, we make an attempt to showcase the associated enigma of TGF, signaling in its dual functional role as tumor suppressor and metastatic promoter during early and late stages of carcinogenesis, respectively. © 2009 IUBMB IUBMB Life, 61(10): 929,939, 2009 [source]

The role of the disintegrin metalloproteinase ADAM15 in prostate cancer progression

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2009
Neali Lucas
Abstract The metalloproteinase ADAM15 is a multi-domain disintegrin protease that is upregulated in a variety of human cancers. ADAM15 mRNA and protein levels are increased in prostate cancer and its expression is significantly increased during metastatic progression. It is likely that ADAM15 supports disease progression differentially through the action of its various functional domains. ADAM15 may downregulate adhesion of tumor cells to the extracellular matrix, reduce cell,cell adhesion, and promote metastasis through the activity of its disintegrin and metalloproteinase domains. Additionally, ADAM15 can influence cell signaling by shedding membrane-bound growth factors and other proteins that interact with receptor tyrosine kinases, leading to receptor activation. There is also evidence supporting a role for ADAM15 in angiogenesis and angioinvasion of tumor cells, which are critical for unrestrained tumor growth and metastatic spread. Given its diverse functions, ADAM15 may represent a pivotal regulatory component of tumor progression, an important target for therapeutic intervention, or emerge as a biomarker of disease progression. J. Cell. Biochem. 106: 967,974, 2009. © 2009 Wiley-Liss, Inc. [source]

After radical retropubic prostatectomy ,insignificant' prostate cancer has a risk of progression similar to low-risk ,significant' cancer

BJU INTERNATIONAL, Issue 2 2008
Shomik Sengupta
OBJECTIVE To assess progression and survival among patients with small-volume, well-differentiated, organ-confined prostate cancer found at radical retropubic prostatectomy (RRP), often defined as being ,insignificant', thus testing whether they are indeed ,insignificant'. PATIENTS AND METHODS We identified 6496 men treated for prostate cancer by RRP between 1990 and 1999, and defined ,insignificant' tumours as those in men having a prostate-specific antigen (PSA) level of <10 ng/mL before RRP, a cancer volume of ,0.5 mL, a specimen Gleason of score ,6 and stage ,pT2. Survival was assessed using the Kaplan-Meier method and compared using the two-sided log-rank test. RESULTS ,Insignificant' tumours were found in 354 (5.5%) men, of whom only one had metastatic progression and none died from prostate cancer, with a median (range) follow-up of 9.2 (0.8,15.6) years. Biochemical progression-free survival (87% vs 85%, respectively, at 10 years, P = 0.5), systemic progression-free survival (100% vs 99%, P = 0.3), overall survival (91% vs 88%, P = 0.16) and cancer-specific survival (100% in each group, P = 0.32) were each similar among men with ,insignificant' prostate cancer and men with low-risk (defined by Gleason score, preoperative PSA level, seminal vesicle and surgical margin status) ,significant' cancer. Clinical stage, biopsy Gleason score and preoperative PSA doubling time were multivariably predictive of ,insignificant' tumours at RRP. CONCLUSIONS ,Insignificant' prostate cancer at RRP is associated with a comparable risk of biochemical progression as low-risk ,significant' cancer. Although clinical predictors for ,insignificant' pathology can be identified, it remains to be established whether such patients can be safely managed conservatively. [source]