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Response of the primary tumor in symptomatic and asymptomatic stage IV colorectal cancer to combined interventional endoscopy and palliative chemotherapy
[Background] The treatment of the primary tumor in advanced metastatic colorectal cancer (CRC) is still a matter of discussion. Little attention has thus far been paid to the endoscopically observable changes of the primary in non-curatively resectable stage IV disease.[Methods] 20 patients [14 men, 6 women, median age 67 (39-82) years] were observed after initial diagnosis of non-curatively resectable metastasized symptomatic (83 %) or asymptomatic (17 %) CRC, from June 2002 to April 2009. If necessary, endoscopic tumor debulking was performed. 5-FU based chemotherapy was given immediately thereafter. In 10 patients, chemotherapy was combined with antibody therapy.[Results] Response of the primary was observed in all patients. Local symptoms were treated endoscopically whenever necessary (obstruction or bleeding), and further improved after chemotherapy was started: Four patients showed initial complete endoscopic disappearance of the primary. In an additional 6 patients, only adenomatous tissue was histologically detected. In both these groups, two patients revealed local tumor relapse after interruption of therapy. Local tumor regression or stable disease was achieved in the remaining 10 patients. 15 patients died during the observation time. In 13 cases, death was related to metastatic disease progression. The mean overall survival time was 19.6 (3-71) months. No complications due to the primary were observed.[Conclusions] This study shows that modern anti-cancer drugs combined with endoscopic therapy are an effective and safe treatment of the symptomatic primary and ameliorate local complaints without the need for surgical intervention in advanced UICC stage IV CRC.
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Prognostic relevance of Wnt-inhibitory factor-1 (WIF1) and Dickkopf-3 (DKK3) promoter methylation in human breast cancer
Background:Secreted Wnt signaling antagonists have recently been described as frequent targets of epigenetic inactivation in human tumor entities. Since gene silencing of certain Wnt antagonists was found to be correlated with adverse patient survival in cancer, we aimed at investigating a potential prognostic impact of the two Wnt antagonizing molecules WIF1 and DKK3 in breast cancer, which are frequently silenced by promoter methylation in this disease.Methods:WIF1 and DKK3 promoter methylation were assessed by methylation-specific PCR with bisulfite-converted DNA from 19 normal breast tissues and 150 primary breast carcinomas. Promoter methylation was interpreted in a qualitative, binary fashion. Statistical evaluations included two-sided Fisher's exact tests, univariate log-rank tests of Kaplan-Meier curves as well as multivariate Cox regression analyses.Results:WIF1 and DKK3 promoter methylation were detected in 63.3% (95/150) and 61.3% (92/150) of breast carcinoma samples, respectively. In normal breast tissues, WIF1 methylation was present in 0% (0/19) and DKK3 methylation in 5.3% (1/19) of samples. In breast carcinomas, WIF1 methylation was significantly associated with methylation of DKK3 (p = 0.009). Methylation of either gene was not associated with clinicopathological parameters, except for DKK3 methylation being associated with patient age (p = 0.007). In univariate analysis, WIF1 methylation was not associated with clinical patient outcome. In contrast, DKK3 methylation was a prognostic factor in patient overall survival (OS) and disease-free survival (DFS). Estimated OS rates after 10 years were 54% for patients with DKK3-methylated tumors, in contrast to patients without DKK3 methylation in the tumor, who had a favorable 97% OS after 10 years (p < 0.001). Likewise, DFS at 10 years for patients harboring DKK3 methylation in the tumor was 58%, compared with 78% for patients with unmethylated DKK3 (p = 0.037). Multivariate analyses revealed that DKK3 methylation was an independent prognostic factor predicting poor OS (hazard ratio (HR): 14.4; 95% confidence interval (CI): 1.9-111.6; p = 0.011), and short DFS (HR: 2.5; 95% CI: 1.0-6.0; p = 0.047) in breast cancer.Conclusions:Although the Wnt antagonist genes WIF1 and DKK3 show a very similar frequency of promoter methylation in human breast cancer, only DKK3 methylation proves as a novel prognostic marker potentially useful in the clinical management of this disease.
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Fatty fish and fish omega-3 fatty acid intakes decrease the breast cancer risk: a case-control study
Background:Although it is believed that fish omega-3 fatty acids may decrease breast cancer risk, epidemiological evidence has been inconclusive. This study examined the association between fish and fish omega-3 fatty acids intake with the risk of breast cancer in a case-control study of Korean women.Methods:We recruited 358 incident breast cancer patients and 360 controls with no history of malignant neoplasm from the National Cancer Center Hospital between July 2007 and April 2008. The study participants were given a 103-item food intake frequency questionnaire to determine their dietary consumption of fish (fatty and lean fish) and omega-3 fatty acids derived from fish (eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)).Results:Using a multivariate logistic regression model, high intake of fatty fish was associated with a reduced risk for breast cancer in both pre- and postmenopausal women (OR [95% CI] for highest vs. lowest intake quartiles, p for trend: 0.19 [0.08 to 0.45], p < 0.001 for premenopausal women, 0.27 [0.11 to 0.66], p = 0.005 for postmenopausal women). Similarly, reductions in breast cancer risk were observed among postmenopausal subjects who consumed more than 0.101 g of EPA (OR [95% CI]: 0.38 [0.15 to 0.96]) and 0.213 g of DHA (OR [95% CI]: 0.32 [0.13 to 0.82]) from fish per day compared to the reference group who consumed less than 0.014 g of EPA and 0.037 g of DHA per day. Among premenopausal women, there was a significant reduction in breast cancer risk for the highest intake quartiles of omega-3 fatty acids (ORs [95% CI]: 0.46 [0.22 to 0.96]), compared to the reference group who consumed the lowest quartile of intake.Conclusions:These results suggest that high consumption of fatty fish is associated with a reduced risk for breast cancer, and that the intake of omega-3 fatty acids from fish is inversely associated with postmenopausal breast cancer risk.
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Cancercompass: top stories News
The status of the axillary lymph nodes, the most common sites of breast cancer metastases, is the most important factor in determining the prognosis of patients with invasive breast cancer.1,2 The goals of axillary lymph node dissection are to provide accurate staging information and local control of the disease.3,4 However, the procedure has many potential complications, including lymphedema, persistent seroma, shoulder dysfunction, and paresthesias. Fewer breast cancer patients have presented with axillary lymph node involvement during the past 2 decades because of the increased use of breast cancer screening programs and detection of the disease at an earlier stage. Lymphatic mapping with sentinel lymph node (SLN) biopsy for breast...
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Identification And Biologic Significance Of Micrometastases In Axillary Lymph Nodes In Patients With Invasive Breast Cancer
Access Pharmaceuticals, Inc., provided an update today on the progress in the Company's clinical development plan for ProLindac, a novel DACH platinum drug that has shown to be active in many solid tumor types in human clinical studies. Access recently announced positive safety and efficacy results from its Phase 2 monotherapy clinical study of ProLindac(TM) in late-stage, heavily pretreated ovarian cancer patients. In this study, 66% of patients who received the highest dose achieved clinically meaningful disease stabilization according to RECIST criteria. No patient in any dose group exhibited any signs of acute neurotoxicity, which is a major adverse side-effect of the approved DACH platinum, Eloxatin, and ProLindac was well tolerated ov...
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Access Pharmaceuticals Provides Update On Prolindac Phase 2 Ovarian Cancer Trial And Clinical Development Plan
New data presented today at the 2009 American Society of Clinical Oncologist (ASCO) Annual Meeting support the use of a laboratory test, ChemoFX(R), to help physicians predetermine the effectiveness of chemotherapy in treating a woman's endometrial cancer. Investigators found a significant correlation between the test results from 405 patient specimens analyzed using ChemoFx and published patient response rates for each chemotherapeutic regimen, suggesting less effective therapies could be eliminated prior to patient administration. Endometrial cancer is the most common gynecologic cancer among women in the United States. "Limiting a patient's exposure to chemotherapy is important, however determining the appropriate treatment the first...
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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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