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Skp2 expression is associated with high risk and Elevated Ki67 expression in gastrointestinal stromal tumours
Background:Gastrointestinal stromal tumors (GIST) exhibit an unpredictable clinical course and can rapidly progress to lethality. Predictions about the biological behavior of GIST are based on a number of canonical clinical and pathologic parameters whose validity in distinguishing between a benign and a malignant tumour is still imperfect. Aim of our study was to investigate the role of morphologic parameters and expression of cells cycle regulators as prognosticators in GIST.Methods:We performed an immunohistochemical analysis for Ki67, p27Kip1, Jab1, and Skp2, on a Tissue Microarray (TMA) containing 94 GIST. Expression of the above proteins was correlated to classically used prognosticators, as well as to risk groups. Clinical significance of histologic and immunohistochemical features were evaluated in 59 patients for whom follow-up information was available.Results:Overexpression of Ki67 and Skp2, and p27Kip1 loss directly correlated with the high risk group (p=0.03, for Ki67 and Skp2, p=0.05, for p27Kip1). Jab1 expression did not exhibit correlation with risk. In 59 cases provided with clinical follow-up, high cellularity, presence of necrosis, and Ki67 overexpression were predictive of a reduced overall survival in a univariate model. The same parameters, as well as mitotic rate, tumour size, and p27Kip1 loss were indicative of a shortened relapse free survival interval. High cellularity, and high mitotic rate retained their prognostic significance by multivariate analysis.Conclusions:Our data suggest that a number of histologic parameters in combination with immunohistochemical expression of cell cycle regulators can facilitate risk categorization and predict biologic behavior in GIST. Importantly this study demonstrates, for the first time, that Skp2 expression correlates with Ki67 expression and high risk in GIST.
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Knockdown of TFIIS by RNA silencing inhibits cancer cell proliferation and induces apoptosis
Background:A common element among cancer cells is the presence of improperly controlled transcription. In cancer cells, the degree of specific activation of some genes is abnormal. Altering the already improper transcription of the cancer cell may therefore directly target cancer. TFIIS is a transcription elongation factor, which directly binds the transcription motor, RNA Polymerase II and allows it to read through various transcription arrest sites. We report on RNA interference of TFIIS, a transcription elongation factor, and its affect on proliferation of cancer cells in culture.Methods:RNA interference was performed by transfecting siRNA to specifically knock down TFIIS expression in MCF7, MCF10A, PL45 and A549 cells. Levels of TFIIS expression were determined by the Quantigene method, and relative protein levels of TFIIS, c-myc and p53 were determined by C-ELISA. Induction of apoptosis was determined by an enzymatic Caspase 3/7 assay, as well as a non-enzymatic assay detecting cytoplasmic mono- and oligonucleosomes. A gene array analysis was conducted for effects of TFIIS siRNA on MCF7 and MCF10A cell lines.Results:Knockdown of TFIIS reduced cancer cell proliferation in breast, lung and pancreatic cancer cell lines. More specifically, TFIIS knockdown in the MCF7 breast cancer cell line induced cancer cell death and increased c-myc and p53 expression whereas TFIIS knockdown in the non-cancerous breast cell line MCF10A was less affected. Differential effects of TFIIS knockdown in MCF7 and MCF10A cells included the estrogenic, c-myc and p53 pathways, as observed by C-ELISA and gene array, and were likely involved in MCF7 cell-death.Conclusions:Although transcription is a fundamental process, targeting select core transcription factors may provide for a new and potent avenue for cancer therapeutics. In the present study, knockdown of TFIIS inhibited cancer cell proliferation, suggesting that TFIIS could be studied as a potential cancer target within the transcription machinery.
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Phase II Trial of Isoflavone in prostate specific antigen recurrent prostate cancer after previous local therapy
Background:Data exist that demonstrate isoflavones have potent antiproliferative effects on prostate cancer cells. We evaluated the efficacy of isoflavone in patients with PSA recurrent prostate cancer after prior therapy. We postulated that isoflavone therapy would slow the rate of rise of serum PSA. Methods:Twenty patients with rising PSA after prior local therapy were enrolled in this open-labeled, Phase II, nonrandomized trial. Patients were treated with 47 mg of isoflavonoid per 8 oz serving three times per day for 12 months. Serum PSA, testosterone, lipids, isoflavone levels (genistein, daidzein, and equol), and quality of life (QOL) were measured at various time points from 0 to 12 months. PSA outcome was evaluated. Results:Within the mixed regression model, it was estimated that PSA had increased 56% per year before study entry and only increased 20% per year for the 12-month study period (p = 0.05). Specifically, the slope of PSA after study entry was significantly lower than that before study entry in 6 patients and the slope of PSA after study entry was significantly higher than before study entry in 2 patients. For the remaining 12 patients, the change in slope was statistically insignificant. Nearly two thirds of the patients were noted to have significant levels of free equol in their serum while on therapy. Conclusion:Dietary intervention with isoflavone supplementation has biologic activity in men with biochemical recurrent prostate cancer as shown by a decline in the slope of PSA. This study provides additional support to the literature that nutritional supplements have biologic activity in prostate cancer and therefore, further, studies with these agents in randomized clinical trials should be encouraged.The study is registered at www.clinicaltrials.gov (registration # NCT00596895).
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Cancercompass: Top Stories News
REYKJAVIK, Iceland -- Scientists in Iceland said they have found a fourth set of genetic variants linked to an increased risk of estrogen receptor-positive breast cancer. The findings, published in the journal Nature genetics, are being used to develop a DNA test to identify women who should be closely screened at an early age for the disease, the biopharmaceutical company deCode Genetics said Sunday in a release. The test is expected to be released later this year, the company's report said. Researchers reported the discovery of two common single-letter variants on chromosome 5 of the human genome that are associated with risk of estrogen receptor-positive breast cancer. They said more than 60 percent of the general...
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New Genes Linked To Breast Cancer
New studies at the University of Adelaide, Australia, will delve into some of the crucial issues surrounding death by brain tumours and stroke. The research, to be conducted in the joint University of Adelaide/IMVS Centre for Neurological Diseases, will aim to find links between chemical signals in the brain and the reasons why brain tumours or strokes become fatal. "There are still many mysteries around how the brain works, and this new research will help to unlock key elements we believe are involved in two separate but equally debilitating conditions," says Professor Robert Vink, Head of the University's School of Medical Sciences and NRF Chair of Neurosurgical Research. Brain tumours account for approximately 2% of all cancer d...
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Unlocking Mysteries Of Brain Cancer, Stroke
BIRMINGHAM, Ala. -- A U.S. university study suggests the drug triphendiol causes tumor cell death in pancreatic and bile duct cancer, as well as slowing tumor growth. The study by University of Alabama at Birmingham researchers led by Assistant Professor Ewan Tytler showed the drug also sensitizes tumors to chemotherapy treatments. Tytler and his colleagues assessed the potential of triphendiol as a treatment for pancreatic adenocarcinoma using three representative cell lines. Triphendiol induced cell death in all three cell lines and pretreating the cell lines with triphendiol increased the effectiveness of chemotherapy. Animal model studies showed triphendiol in combination with chemotherapy inhibited tumor growth...
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Health News
 MRI is better than MDCT for determining if and how far breast cancer has spread into the breast ducts and should be used before patients receive breast conserving treatment, a new study shows. "Patients have a lower survival rate if their surgical margins are positive for tumor cells. A positive surgical margin is commonly the result of inadequate resection of the cancer's intraductal component," said Akiko Shimauchi, MD, at Tohoku University in Sendai, Miyagi, Japan. "Accurate preoperative diagnosis of the intraductal component allows the surgeon to achieve a cancer-free surgical margin," she said........
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MRI Best To Detect Cancer Spread Into Breast Ducts
 Using survey data from April 2003 to March 2005 for Women's Health Clinic patients without breast cancer, scientists observed that while 16% of the participants reported a maternal relative with breast cancer, only 10% reported a paternal relative. Because mothers are much more likely to develop breast cancer than fathers, participants who reported a mother with breast cancer were excluded from the study........
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Family history of breast cancer may be missed
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