Cancer statistics and treatment Pilot study - Cimetidine enhances lymphocyte infiltration of human colorectal carcinoma: Results of a small randomized control trial.
Adams WJ Morris DL
Cancer 1997 JUL 1;80(1):15-21
Morris DL, Univ New S Wales, St George Hosp, Dept Surg, Gray St, Sydney, NSW 2217, AUSTRALIA
BACKGROUND, Cimetidine preserves postoperative immune function and inhibits the growth of some cancers. In this study, the effect of cimetidine on the local immune response to colorectal carcinoma was investigated. METHODS, Forty-two patients scheduled for elective resection of colorectal carcinoma were randomized either to receive cimetidine for 1 week perioperatively or to act as controls. A lymphocyte density of 50 cells per high- power field (approximately 50% of the tumor/tissue interface) was considered a positive response. Patient survival was determined by Kaplan-Meier life table analysis. The effects of histamine and cimetidine on normal subject lymphocyte function was determined in a mitogen-stimulated proliferation assay. RESULTS, A positive lymphocyte response was observed in 5 of 24 control carcinoma patients (21%) and 10 of 18 cimetidine-treated carcinoma patients (56%) (P = 0.03). The presence of a lymphocyte response correlated with a better survival (P = 0.02). Histamine had an inhibitory effect on lymphocyte proliferation with a median effective dose of 5 x 10(-7) M. Cimetidine antagonized this effect with a negative logarithm of the cimetidine molar concentration required to reduce the effect of histamine in half of 6.55. CONCLUSIONS, Histamine inhibits normal lymphocyte function, antagonized by cimetidine at a histamine type 2 receptor. Cimetidine increases lymphocyte infiltration of primary colorectal carcinoma, possibly by overcoming the immunosuppressive effects of high local histamine concentrations. The presence of a local lymphocyte response correlates with an improved 3-year survival.
Differentiating and growth inhibitory effects of diallyl disulfide on cancer cells.
Lea MA Ayyala US
Int J Oncol 1997 JUL;11(1):181-185
Lea MA, Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, 185 S Orange Ave, Newark,NJ 07103 USA
Diallyl disulfide caused growth inhibition and differentiation of DS19 mouse erythroleukemic cells as judged by hemoglobin synthesis and induction of acetylcholinesterase activity. There was a 50% inhibition of cell division at about 0.25 mM diall yl disulfide which was much more effective than diallyl sulfide. K562 human erythroleukemia cells and mouse melanoma cells were more resistant to the action of diallyl disulfide. Thymidine incorporation into DNA in 7800NJ and 7288CTC rat hepatoma cells an d in T47D and MCF7 human breast cancer cells was inhibited by 1-2 mM diallyl disulfide. Administration of diallyl disulfide to rats bearing Morris hepatomas caused marked inhibitory effects on precursor incorporation into DNA and protein in both hepatomas and in livers after a dose of 400 mg/kg body weight, but only small differences were seen at a less toxic dose of 200 mg/kg.
Green tea polyphenols inhibit oxidant-induced DNA strand breakage in cultured lung cells.
Leanderson P Faresjo AO Tagesson C
Free Radical Biol Med 1997;23(2):235-242
Leanderson P, Linkoping Univ, Fac Hlth Sci, Dept Occupat & Environm Med, S 58185 Linkoping, SWEDEN
The influence of green tea polyphenols (GTP) on the formation of DNA strand breaks (DNA-SB) and lipid peroxidation products (LPP) in cultured human lung cells (A 549) exposed to different oxidants was investigated. Cells were pretreated with GTP for 2 h and then exposed to cigarette smoke solution, H2O2, or FeCl3 for 30 min. After exposure, the cells were analyzed for DNA-SB, LPP, and viability. In addition, the effects of GTP added directly to the incubation mixtures during exposure were examined, using the same end points. It appeared that pretreatment with GTP inhibited both cigarette smoke- and H2O2-induced DNA breakage; i.e., following exposure to cigarette smoke or H2O2, the fraction of DNA passing through a microfilter increased significantly in cells not subjected to GTP, but this effect was prevented or inhibited in GTP-treated cells. Pretreatment with GTP also reduced the overall toxicity of H2O2 as determined by cell growth after exposure, Moreover, addition of GTP during exposure reduced both cigarette smoke- and H2O2-induced DNA breakage as well as formation of LPP after exposure to Fe3+. These results indicate that GTP inhibit the formation of DNA-SB in cells exposed to oxidants. It is possible that this ability of GTP to inhibit DNA-SB formation might contribute to the antiumorogenic properties of green tea. (C) 1997 Elsevier Science Inc.
Estimating the prevalence of cancer in the United States.
Cancer 1997 JUL 1;80(1):136-141
Polednak AP, Connecticut Dept Publ Hlth & Addict Serv, Connecticut Tumor Registry, 410 Capitol Ave, Hartford,CT 06134 USA
BACKGROUND, Few reports have estimated the prevalence of persons in the U.S. Ever diagnosed with invasive cancer. METHODS, The Connecticut Tumor Registry was used to identify all Connecticut residents ever diagnosed (1935- 1994) with invasive cancer who were known to be alive in 1994. Estimated prevalence rates for Connecticut were compared with those for 1982, and were applied to the total U.S. Population for selected years. RESULTS, Some 95,361 persons ever diagnosed with invasive cancer(s) were confirmed as being alive at the end of 1994. The age-standardized prevalence rate had increased by 40% in males and 13% in females since 1982, due in part to large increases for breast, prostate, and (in females) lung carcinoma. Using the data for Connecticut, an estimated 7.1 million Americans in 1995 had ever been diagnosed with invasive cancer; projected numbers were 7.7 million for 2000 and 13.2 million for 2030. CONCLUSIONS. The prevalence of persons ever diagnosed with invasive cancer could increase considerably in the coming decades, and numbers for elderly males could surpass those for elderly females by 2020. Although projections must be interpreted with caution, these data emphasize the need for primary prevention of cancer and for studies of cancer survivors. (C) 1997 American Cancer Society.
dl-alpha-tocopherol induces apoptosis in erythroleukemia, prostate, and breast cancer cells.
Sigounas G Anagnostou A Steiner M
Nutr Cancer 1997;28(1):30-35
Sigounas G, E Carolina Univ, Sch Med, Div Hematol Oncol, Brody Bldg 3E 127, Greenville,NC 27858 USA
Vitamin E, best known as a potent antioxidant, has been shown to have other functions that are not mediated by this activity. Recent reports have suggested that vitamin E may inhibit smooth muscle cell and also cancer cell growth. We have studied the effect of dl-alpha-tocopherol (vitamin E) on a series of well-established cancer cell lines that included two erythroleukemia cell lines and a hormone-responsive breast and prostate cancer cell line. Cell proliferation was examined in these cell lines, which were maintained at optimal growth conditions. A dose- dependent inhibition of cell growth was found in all cell lines examined, with the MCF-7 breast and CRL-1740 prostate cancer cell lines showing potent suppression of growth at 0.1 mM vitamin E, whereas the erythroleukemia cell lines, HEL and OCIM-1, responded only at 0.25 mM vitamin E with inhibition of proliferation. Studies of [H- 3]thymidine incorporation showed that vitamin E supplementation reduced DNA synthesis in all cell lines. Analysis of high-molecular-weight DNA revealed extensive fragmentation, indicating apoptosis of all cell lines supplemented with vitamin E. Our studies thus give evidence of a general inhibition of cell proliferation by dl-alpha-tocopherol, with breast and prostate cancer cells distinctly more sensitive than erythroleukemia cells.
Effect of megestrol acetate and prepulsid on nutritional improvement in patients with head and neck cancers undergoing radiotherapy.
Chen HC Leung SW Wang CJ Sun LM Fang FM Hsu JH Leung SW, Chang Gung Mem Hosp, Dept Radiat Oncol, 123 Ta Pei Rd, Kaohsiung 813, TAIWAN
Background nod purpose: Anorexia is a common problem in cancer patients who receive radiotherapy. In this current study, we attempt to determine the effect of megestrol acetate and prepulsid on appetite and nutritional improvement in patients with head and neck cancers undergoing radiotherapy. Materials and Methods: One hundred twenty-nine consecutive patients with head and neck cancers treated between July 1993 and June 1993 were prospectively randomized to receive either megestrol acetate, 40 mg qid (megace group), prepulsid, 5 mg lid (cisapride group), or a placebo treatment (control group) during radiotherapy. Before radiotherapy, body weight (kg), appetite score, performance status, biochemical parameters and hematological parameters were evaluated, and the above- noted clinical and biochemical parameters were assessed and recorded every other week. All patients received 6- 10 MV X-rays or Co-60 gamma-ray to head and neck region for a full course of radiotherapy, 61.2-75.6 Gy/7-9 weeks. Results: Forty-eight patients were enrolled in the megace group, 41 patients in the cisapride group, and 40 patients in the control group. At the 2nd, 4th, 6th and 8th week, as the radiation dose escalated, the megace group had significantly less body weight loss than did the cisapride and control groups (P = 0.045, 0.024, 0.006, 0.003, respectively). The appetite scores of the megace group were significantly higher than those of the cisapride and control groups (P = 0.0001). However, there were no statistically significant differences in the change of albumin level among these three groups at the 2nd, 4th, 6th and 8th week (P > 0.05, respectively). Conclusions: Megestrol acetate can significantly decrease the degree of body weight loss, and can prevent the deterioration of appetite in patients with head and neck cancers receiving radiotherapy. However, prepulsid lacks the above-mentioned clinical benefits.
Involvement of polyamines in selenomethionine induced apoptosis and mitotic alterations in human tumor cells.
Redman C Xu MJ Peng YM Scott JA Payne C Clark LC Nelson MA
Carcinogenesis 1997 JUN;18(6):1195-1202
Nelson MA, Univ Arizona, Arizona Canc Ctr, Oncol Mol Lab, RM 4921, 1515 N Campbell Ave, Tucson,AZ 85724 USA
The efficacy of dietary selenium supplementation is currently being evaluated in intervention trials. However, the biological mechanisms underlying the cancer chemopreventive effects of selenium supplementation have yet to be elucidated, Selenium metabolism and polyamine biosynthesis are linked in their common requirement for S- adenosylmethionine. Selenomethionine was the predominant form of selenium in the dietary supplement, therefore we evaluated the anti-tumorigenic effects of selenomethionine. We found that selenomethionine inhibited tumor growth (both in A549 lung and HT29 colon cancer cells) in a dose-dependent manner, At 24 and 72 h, polyamine content of A549 and HT29 cancer cell lines was decreased at doses that inhibited 50% of normal growth, Selenomethionine treatment induced apoptosis in both cancer cell lines, Exogenous spermine administration, which replenishes intracellular polyamine levels, prevented selenomethionine induced apoptosis, Selenomethionine administration to the cancer cell lines increased the number of cells in metaphase, This cell cycle effect appeared to be reversed with the co- administration of selenomethionine and spermine, These data suggested that at least part of the anti-carcinogenic effects of selenium supplementation might be due to a depletion in polyamine levels, This depletion of polyamines leads to an induction in apoptosis and perturbations in the cell cycle.
Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: A randomized study in premenopausal breast cancer patients.
Saarto T Blomqvist C Valimaki M Makela P Sarna S Elomaa I
J Clin Oncol 1997 APR;15(4):1341-1347
Elomaa I, Univ Helsinki, Cent Hosp, Dept Oncol, Haartmaninkatu 4, FIN 00290 Helsinki, FINLAND
Purpose: In the majority of premenopausal breast cancer patients, an adjuvant chemotherapy-induced early menopause occurs, which is known to be a strong predictor of osteoporosis. We present data on the effect of adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy on bone mineral density (BMD) and the efficacy of clodronate on the prevention of bone loss in 148 premenopausal breast cancer patients without skeletal metastases. Materials and Methods: Patients were randomized to receive oral clodronate 1,600 mg/d or to a control group. In addition, patients were treated with six cycles of CMF therapy. BMD of the lumber spine and femoral neck was measured by dual-energy x-ray absorptiometry (DEXA) before therapy and at 1 and 2 years. Results: Changes in the BMD of lumbar spine and femoral neck were -5.9% and -2.0% without clodronate and -2.2% and +0.9% with clodronate at 2 years (P = .0005 and .017, respectively). Patients who developed amenorrhea after chemotherapy had a rapid bone loss, which was significantly reduced by clodronote. In controls, bone loss was 9.5% in the lumber spine and 4.6% in the femoral neck, while in the clodronate group, bone loss was 5.9% and 0.4%, respectively, at 2 years. Patients with preserved menstruation had only marginal changes in BMD. Conclusion: Chemotherapy-induced ovarian failure causes rapid bone loss in premenopausal breast cancer patients. Women older than 40 years are at particularly high risk. Clodronate significantly reduces this bone loss.
Can Allium vegetables prevent cancer?.
Phytomedicine 1997 MAR;4(1):79-83
Ernst E, Univ Exeter, Postgrad Med Sch, Dept Complementary Med, 25 Victoria Pk Rd, Exeter EX2 4NT, Devon, ENGLAND
The aim of this paper is to review the evidence for or against an association between regular consumption of Allium vegetables and cancer. A Medline search was conducted to identify all publications on the topic. Twenty epidemiological studies wer e found. The majority investigate the association of onion consumption and cancer, while eight studies assess garlic consumption. With only one exception, these studies suggest that Allium vegetables convey a protective effect, in particular from cancers of the gastrointestinal tract. These results could be due to an artefact but more likely, they are based on plausible biological mechanisms. Anti-bacterial or anti- mutagenic effects of Allium vegetables are prime candidates to explain this relationship. In conclusion, the hypothesis that regular consumption of Allium vegetables reduces the risk of cancer is compelling and would seem to deserve testing in intervention trials.
Current concepts in neuro-oncology: The cell cycle - A review.
Dirks PB Rutka JR
Neurosurgery 1997 MAY;40(5):1000-1013
Dirks PB, Univ Toronto, Hosp Sick Children, Div Neurosurg, Brain Tumor Res Lab, Suite 1504, 555 Univ Ave, Toronto, ON M5G 1X8, CANADA
UNCONTROLLED CELLULAR PROLIFERATION is the hallmark of human malignant brain tumors. Their growth proceeds inexorably, in part because their cellular constituents have an altered genetic code that enables them to evade the checks and balances of the normal cell cycle. Recently, a number of major advances in molecular biology have led to the identification of several critical genetic and enzymatic pathways that are disturbed in cancer cells resulting in uncontrolled cell cycling. We now know that the progression of a cell through the cell cycle is controlled in part by a series of protein kinases, the activity of which is regulated by a group of proteins called cyclins. Cyclins act in concert with the cyclin- dependent kinases (CDKs) to phosphorylate key substrates that facilitate the passage of the cell through each phase of the cell cycle. A critical target of cyclin-CDK enzymes is the retinoblastoma tumor suppressor protein, and phosphorylation of this protein inhibits its ability to restrain activity of a family of transcription factors (E2F family), which induce expression of genes important for cell proliferation, In addition to the cyclins and CDKs, there is an emerging family of CDK inhibitors, which modulate the activity of cyclins and CDKs. CDK inhibitors inhibit cyclin CDK complexes and transduce internal or external growth-suppressive signals, which act on the cell cycle machinery. Accordingly, all CDK inhibitors are candidate tumor suppressor genes. It is becoming clear that a common feature of cancer cells is the abrogation of cell cycle checkpoints, either by aberrant expression of positive regulators (for example, cyclins and CDKs) or the loss of negative regulators, including p21(Cip 1) through loss of function of its transcriptional activator p53, or deletion or mutation of p16(INK4A) (multiple tumor suppressor 1/CDKN2) and the retinoblastoma tumor suppressor protein. In this review, we describe in detail our current knowledge of the normal cell cycle and how it is disturbed in cancer cells. Because there have now been a number of recent studies showing alterations in cell cycle gene expression in human brain tumors, we wilt review the derangements in both the positive and negative cell cycle regulators that have been reported for these neoplasms. A thorough understanding of the molecular events of the cell cycle may lead to new opportunities by which astrocytoma cell proliferation can be controlled either pharmacologically or by gene transfer techniques.
Curcumin and genistein, plant natural products, show synergistic inhibitory effects on the growth of human breast cancer MCF-7 cells induced by estrogenic pesticides.
Verma SP Salamone E Goldin B
Biochem Biophys Res Commun 1997 APR 28;233(3):692-696
Verma SP, Tufts Univ, Sch Med, Dept Community Hlth, 136 Harrison Ave, Boston,MA 02111 USA
Curcumin and genistein are two natural products of plants obtained from Curcuma longa Linn (turmeric) and soybeans, respectively. Both compounds when present at micromolar concentrations are able to inhibit the growth of estrogen- positive human breast MCF-7 cells induced individually or by a mixture of the pesticides endosulfane, DDT and chlordane or 17-beta estradiol. When curcumin and genistein were added together to MCF-7 cells, a synergistic effect resulting in a total inhibition of the induction of MCF-7 cells by the highly estrogenic activity of endosulfane/chlordane/DDT mixtures was noted. These data suggest that the combination of curcumin and genistein in the diet have tile potential to reduce the proliferation of estrogen-positive cells by mixtures of pesticides or la-beta estradiol. Since it is difficult to remove pesticides completely from the environment or the diet and since both turmeric and soybeans are not toxic to humans, their inclusion in the diet in order to prevent hormone related cancers deserves consideration.
Differential induction of growth arrest inducible genes by selenium compounds.
Kaeck M Lu JX Strange R Ip C Ganther HE Thompson HJ
Biochem Pharmacol 1997 APR 4;53(7):921-926
Lu JX, Amc, Ctr Canc Res, Div Lab Res, Denver,CO 80214 USA
The effects of two types of selenium compounds on the expression levels of growth arrest and DNA damage- inducible (gadd) genes and on selected cell death genes were examined in mouse mammary MOD cells to test the hypothesis that the diversity of selenium-induced cellular responses to these compounds could be distinguished by unique gene expression patterns. Whereas the expression patterns of known cell death-related genes (bcl-2 and bax) were not informative with respect to the cellular response patterns upon exposure to selenium compounds, time- dependent and selenium species-specific induction patterns were observed for gadd34, gadd45 and gadd153 genes. It was also observed that the MOD cells expressed a truncated p53 transcript but no detectable immunoreactive P53 protein, indicating a null p53 phenotype. The fact that selenium compounds induced growth arrest and death of these cells and that these compounds induced specific patterns of expression of gadd genes indicates that these genes may mediate some selenium-induced cellular responses. The findings further imply that selenium compounds may be effective chemopreventive agents for human breast carcinogenesis, in which p53 mutations are frequent.