© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 6, 405,
March 20, 2002
© 2002 Oxford University Press
IN THIS ISSUE |
Although the mechanisms responsible for the progression from Barrett’s esophagus to esophageal adenocarcinoma are unclear, it has been postulated that mucosal injury associated with gastric reflux induces the synthesis of prostaglandins and mediators of inflammation. Because cyclooxygenase (COX)-2 is the rate-limiting enzyme involved in prostaglandin synthesis, Buttar et al. (p. 422) examined the effect of inhibiting COX-2 activity in primary cultures of Barrett’s esophageal cells. With the use of the selective COX-2 inhibitor NS-398, the authors studied changes in the proliferation of Barrett’s esophageal epithelial cells. They found that inflammatory cytokines had little effect on COX-2 activity from epithelial cells but increased COX-2 activity from esophageal fibroblasts. Because culture supernatants from fibroblasts increased COX-2 activity from the epithelial cells, the authors conclude that COX-2 activity is a critical component in the proliferation of Barrett’s esophageal epithelial cells and that inhibition of COX-2 may have chemopreventive potential.
In an accompanying editorial, Gupta and DuBois (p. 406) discuss how the recent interest in COX-2 stems from its potential role in tumorigenesis. Moreover, they discuss how the role of COX-2 inhibitors as chemopreventive agents will remain unclear until the results of definitive in vivo studies are known.
Quality of Life After Androgen Deprivation Therapy
Many men diagnosed with clinically localized prostate cancer are treated conservatively for the initial year, receiving neither surgery nor radiotherapy. Treatment patterns and quality of life outcomes in such patients have not been previously reported. Potosky et al. (p. 430) followed for up to 1 year 661 men diagnosed in 1994 and 1995 from a population-based sample from six geographic regions. They assessed disease-specific and generic quality of life outcomes in 245 men receiving androgen deprivation therapy (ADT) and in 416 men receiving no therapy. Among men who were sexually potent before diagnosis, 80% of those on ADT compared with 30% of those receiving no treatment reported being impotent after 1 year. Patients on ADT also experienced a decline in vitality and in physical function, although these differences were reduced after statistical adjustments. The authors conclude that the use of ADT as primary therapy for clinically localized prostate cancer is prevalent despite limited evidence of its efficacy and that this therapy has clinically important effects on sexual function and physical health.
In an editorial, Talcott (p. 407) states that, while the treatment choices in early prostate cancer are less heroic than those faced by critically ill patients, the diagnosis is chilling, the considerations are complex, and the consequences are enduring. He reiterates that patients deserve better information from randomized clinical trials to help them make treatment decisions.
Calcium Intake and Risk of Colon Cancer
Animal studies suggest that calcium may be helpful in reducing the risk of colon cancer. In a recent randomized trial, calcium supplementation was associated with reduction in the risk of recurrent colorectal adenomas. Wu et al. (p. 437) examined the association between calcium intake and colon cancer risk in two prospective cohorts, the Nurses’ Health Study (87,998 women) and the Health Professionals Follow-up Study (47,344 men). Up to 1996, 626 colon cancer cases were identified in women and 399 in men. The authors found that higher total calcium intake (>1250 mg/day versus <500 mg/day) was inversely associated with distal colon cancer but not with proximal colon cancer. They also noted that calcium intake beyond a moderate level may not be associated with a further risk reduction.
p16 and Melanocyte Senescence
Mutations in the INK4A-ARF locus are associated with familial melanoma. The INK4A-ARF locus carries the genetic code for two tumor suppressor proteins, p16 and Arf, that are involved in cell cycle regulation and cellular senescence. Fibroblasts isolated from mice with a homozygous Ink4a-Arf deletion or a homozygous Arf deletion do not senesce normally; Sviderskaya et al. (p. 446) assessed whether p16 and Arf had similar functions in melanocytes. The authors cultured melanocytes isolated from mice with a homozygous deletion (Ink4a-Arf-/-) in Ink4a-Arf. Ink4a-Arf-/- melanocytes did not senesce and contained less melanin pigment than wild-type melanocytes. Restoring p16 expression stopped the growth of Ink4a-Arf-/- melanocytes, which became highly melanized and expressed a marker of senescence. These effects were not seen by restoring Arf expression. The authors conclude that mouse melanocyte senescence requires both copies of Ink4a-Arf and depends more on p16 than on Arf function. Furthermore, mutations in the INK4A-ARF locus may favor melanocyte tumorigenesis by impairing cell senescence and differentiation.
Growth Hormone Genes and Colorectal Cancer
Growth hormone (GH) may be associated with colorectal cancer directly or indirectly by increasing the plasma level of insulin-like growth factor-I (IGF-I) that has been associated with colorectal cancer. A common T-to-A polymorphism at position 1663 in the GH1 gene is putatively associated with lower levels of GH and IGF-I. In this issue, Le Marchand et al. (p. 454) describe the relationship between this polymorphism and the risk of colorectal neoplasia in two case–control studies. They found that a lower risk of cancer was consistently associated with the A allele rather than the T allele. The ratio of plasma IFG-I to IFG-I binding protein-3 reflects the amount of bioavailable IGF-I, and a lower ratio was found to be associated with the A allele rather than with the T allele. They concluded that the T-to-A polymorphism appears to be associated with a decreased risk of colorectal cancer.
Intratumoral Lymphangiogenesis
Metastasis is the major cause of mortality from malignant tumors. Cancer cells can metastasize via the vascular system and/or the lymphatic system. Jain and Fenton (p. 417) provide a commentary regarding the current understanding, or lack thereof, of the lymphatic system as it relates to cancer biology. The authors provide a detailed assessment of the association between clinicopathologic endpoints and the expression of several lymphangiogenic markers and describe how the identification of these molecules is changing the design and focus of lymphatic and vascular biology studies in cancer.
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