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Fatal Malignancy (fatal + malignancy)
Selected AbstractsPhase II study of irinotecan in combination with capecitabine as a first-line chemotherapy in Asian patients with inoperable hepatocellular carcinomaASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 2 2009Tony MOK Abstract Aim: Hepatocellular carcinoma (HCC) is one of the most commonly fatal malignancies in Asia but treatment options are limited. Methods: This multinational, nonrandomized phase II trial using the combination of irinotecan (Campto or CPT-11) and capecitabine (Xeloda) was conducted to determine efficacy and safety of this combination in Asian patients with advanced inoperable HCC. The starting dose was irinotecan 200 mg/m2 every 3 weeks followed by capecitabine 1000 mg/m2 orally twice daily for 14 days followed by a 7-day rest. The primary endpoint was tumor response rate, based on response evaluation criteria in solid tumors criteria. Secondary objectives included the safety and tolerability of the treatment combination, time to progression, duration of overall response, tumor growth control rate (complete response, partial response plus stable disease) and overall survival. Results: Of the 63 recruited patients, 47 were evaluable. Of these, three (6.4%) achieved a partial response (lasting 2.2, 3.4 and 8.0 months, respectively). The median overall survival was 4.5 months. Grade 4 diarrhea was reported in four patients. Hematologic grade 4 laboratory abnormalities observed in patients while on study treatment included neutropenia (5.2%) and anemia (1.7%). Seven patients (12.1%) had grade 4 elevations in their total bilirubin. Both irinotecan and capecitabine were generally well tolerated, with manageable and reversible toxicities. Conclusion: Combination therapy with irinotecan and capecitabine has limited efficacy in the treatment of advanced-stage HCC. Further investigation of this combination is not warranted. [source] Molecular mechanisms of pancreatic carcinogenesisCANCER SCIENCE, Issue 1 2006Toru Furukawa Pancreatic ductal adenocarcinoma is one of the most fatal malignancies. Intensive investigation of molecular pathogenesis might lead to identifying useful molecules for diagnosis and treatment of the disease. Pancreatic ductal adenocarcinoma harbors complicated aberrations of alleles including losses of 1p, 6q, 9p, 12q, 17p, 18q, and 21q, and gains of 8q and 20q. Pancreatic cancer is usually initiated by mutation of KRAS and aberrant expression of SHH. Overexpression of AURKA mapping on 20q13.2 may significantly enhance overt tumorigenesity. Aberrations of tumor suppressor genes synergistically accelerate progression of the carcinogenic pathway through pancreatic intraepithelial neoplasia (PanIN) to invasive ductal adenocarcinoma. Abrogation of CDKN2A occurs in low-grade/early PanIN, whereas aberrations of TP53 and SMAD4 occur in high-grade/late PanIN. SMAD4 may play suppressive roles in tumorigenesis by inhibition of angiogenesis. Loss of 18q precedes SMAD4 inactivation, and restoration of chromosome 18 in pancreatic cancer cells results in tumor suppressive phenotypes regardless of SMAD4 status, indicating the possible existence of a tumor suppressor gene(s) other than SMAD4 on 18q. DUSP6 at 12q21-q22 is frequently abrogated by loss of expression in invasive ductal adenocarcinomas despite fairly preserved expression in PanIN, which suggests that DUSP6 works as a tumor suppressor in pancreatic carcinogenesis. Restoration of chromosome 12 also suppresses growths of pancreatic cancer cells despite the recovery of expression of DUSP6; the existence of yet another tumor suppressor gene on 12q is strongly suggested. Understanding the molecular mechanisms of pancreatic carcinogenesis will likely provide novel clues for preventing, detecting, and ultimately curing this life-threatening disease. (Cancer Sci 2005) [source] Antiadult T-cell leukemia effects of brown algae fucoxanthin and its deacetylated product, fucoxanthinolINTERNATIONAL JOURNAL OF CANCER, Issue 11 2008Chie Ishikawa Abstract Adult T-cell leukemia (ATL) is a fatal malignancy of T lymphocytes caused by human T-cell leukemia virus type 1 (HTLV-1) infection and remains incurable. Carotenoids are a family of natural pigments and have several biological functions. Among carotenoids, fucoxanthin is known to have antitumorigenic activity, but the precise mechanism of action is not elucidated. We evaluated the anti-ATL effects of fucoxanthin and its metabolite, fucoxanthinol. Both carotenoids inhibited cell viability of HTLV-1-infected T-cell lines and ATL cells, and fucoxanthinol was approximately twice more potent than fucoxanthin. In contrast, other carotenoids, ,-carotene and astaxanthin, had mild inhibitory effects on HTLV-1-infected T-cell lines. Importantly, uninfected cell lines and normal peripheral blood mononuclear cells were resistant to fucoxanthin and fucoxanthinol. Both carotenoids induced cell cycle arrest during G1 phase by reducing the expression of cyclin D1, cyclin D2, CDK4 and CDK6, and inducing the expression of GADD45,, and induced apoptosis by reducing the expression of Bcl-2, XIAP, cIAP2 and survivin. The induced apoptosis was associated with activation of caspase-3, -8 and -9. Fucoxanthin and fucoxanthinol also suppressed I,B, phosphorylation and JunD expression, resulting in inactivation of nuclear factor-,B and activator protein-1. Mice with severe combined immunodeficiency harboring tumors induced by inoculation of HTLV-1-infected T cells responded to treatment with fucoxanthinol with suppression of tumor growth, showed extensive tissue distribution of fucoxanthinol, and the presence of therapeutically effective serum concentrations of fucoxanthinol. Our preclinical data suggest that fucoxanthin and fucoxanthinol could be potentially useful therapeutic agents for patients with ATL. © 2008 Wiley-Liss, Inc. [source] Treatment of Helicobacter pylori and prevention of gastric cancerJOURNAL OF DIGESTIVE DISEASES, Issue 1 2008Ting Kin CHEUNG Gastric cancer is the second commonest fatal malignancy in the world with a high incidence in China. Helicobacter pylori infection is an important factor in the pathogenesis of gastric cancer. Epidemiological studies have shown a strong causal relationship between H. pylori infection and gastric cancer. Animal studies also show that eradication of H. pylori infection, especially at the early stage, is effective in preventing H. pylori -related gastric carcinogenesis. H. pylori eradication leads to regression and prevents the progression of gastric precancerous lesions, but only in a minority of cases. H. pylori eradication appears to be the most promising approach in gastric cancer prevention. The current available data in human studies showed that H. pylori eradication can reduce the risk of developing gastric cancer and this strategy is more useful in patients without atrophic gastritis or intestinal metaplasia. A longer follow-up and additional studies are needed for better understanding this issue. [source] CHARACTERISTIC OF GASTRIC CANCER IN INDONESIA: THE ROLE OF HELICOBACTER PYLORI INFECTIONJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2000Murdani Abdullah Background Gastric cancer is the second most common fatal malignancy in the world. In 1996, approximately one million new cases of gastric cancer were found. It is generally agreed that the pathogenesis is multifactorial which may include, dietary factors, environmental factors, bacterial and viral infections. Aim to evaluate the frequent of gastric cancer in Indonesia and itís relating factors. Methods A sample size of 7902 subjects were determined based on hospital data of dyspeptic patients following gastroduodenoscopy procedure from January 1997 to September 1999. Patients were recruited from 9 endoscopic centers located in 5 cities in Indonesia. Endoscopic biopsy specimens were taken 2 specimens from the antrum (2 cm from pylorus) and 2 specimens from the corpus. Helicobacter pylori infections were determined by serology (ELISA), rapid urea test (CLO test), or histopathology examination using Haematoxyline Eosin and Giemsa staining. The criteria used to diagnose Helicobacter pylori infection were a positive result either from one of these tests and/or in combination. Results The frequent of proximal gastric cancer and distal gastric cancer finding were 0.63 % and 0.54 %, consecutively. In the proximal and distal gastric cancer groups the present of Helicobacter pylori were 55.77 % and 85.36 %, consecutively (p>0.05). The finding of gastric cancer among ethnic groups were 0.65 % for Chinese ethnicity and 0.81 % for Non-Chinese ethnicity, statistically has no significant different (p=0,9514). The distal-to-proximal gastric cancer ratio was 0.85. The proximal gastric cancer more frequent to be found in the age group of 41-60 years old (47.83%), while the distal gastric cancer in the age group of 51-70 years old (61.54%). Conclusion The distal-to-proximal gastric cancer ratio was 0.85. The present of Helicobacter pylori were lower in proximal gastric cancer rather than distal gastric cancer, but statistically has of no significant. [source] Traditional Chinese herbal medicines for treatment of liver fibrosis and cancer: from laboratory discovery to clinical evaluationLIVER INTERNATIONAL, Issue 7 2007John M. Luk Abstract Liver disease afflicts over 10% of the world population. This includes chronic hepatitis, alcoholic steatosis, fibrosis, cirrhosis and hepatocellular carcinoma (HCC), which are the most health-threatening conditions drawing considerable attention from medical professionals and scientists. Patients with alcoholism or viral hepatitis are much more likely to have liver cell damage and cirrhosis, and some may eventually develop HCC, which is unfortunately, and very often, a fatal malignancy without cure. While liver surgery is not suitable in many of the HCC cases, patients are mostly given palliative support cares or transarterial chemoembolization or systemic chemotherapies. However, HCC is well known to be a highly chemoresistant tumour, and the response rate is <10,20%. To this end, alternative medicines are being actively sought from other sources with hopes to halt the disease's progression or even eliminate the tumours. Traditional Chinese herbal medicine has begun to gain popularity worldwide for promoting healthcare as well as disease prevention, and been used as conventional or complementary medicines for both treatable and incurable diseases in Asia and the West. In this article, we discuss the laboratory findings and clinical trial studies of Chinese herbal medicines (particularly small molecule compounds) for the treatment of liver disease ranging from fibrosis to liver cancer. [source] Mechanisms of lymphatic metastasis in human colorectal adenocarcinoma,THE JOURNAL OF PATHOLOGY, Issue 5 2009Daniel Royston Abstract The invasion of lymphatic vessels by colorectal cancer (CRC) and its subsequent spread to draining lymph nodes is a key determinant of prognosis in this common and frequently fatal malignancy. Although tumoural lymphangiogenesis is assumed to contribute to this process, review of the current literature fails to support any notion of a simple correlation between lymphatic vessel density and CRC metastasis. Furthermore, attempts to correlate the expression of various lymphangiogenic growth factors, most notably VEGF-C and VEGF-D, with the lymphatic metastasis of CRC have provided contradictory results. Recent evidence from animal and human models of tumour metastasis suggests that complex functional and biochemical interactions between the microvasculature of tumours and other cell types within the tumour microenvironment may play a pivotal role in the behaviour of commonly metastasizing tumours. Indeed, previous insights into tumoural blood vessels have provided candidate markers of tumoural angiogenesis that are currently the subject of intense investigation as future therapeutic targets. In this review article we survey the current evidence relating lymphangiogenesis and lymphangiogenic growth factor production to metastasis by CRC, and attempt to provide some insight into the apparent discrepancies within the literature. In particular, we also discuss some new and provocative insights into the properties of tumoural lymphatics suggesting that they have specific expression profiles distinct from those of normal lymphatic vessels and that appear to promote metastasis. These findings raise the exciting prospect of future biomarkers of lymphatic metastasis and identify potential targets for new generation anti-tumour therapies. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Race/ethnic variations in ovarian cancer mortality in the United States, 1992,1997,CANCER, Issue S10 2003Holly L. Howe Ph.D. Ovarian cancer is reported to be the most fatal malignancy of the female genital tract and the fifth leading cause of cancer deaths among women. In the current study, the authors describe ovarian cancer mortality by race and ethnicity in the U.S. during the years 1992,1997, a period comparable to the ovarian cancer incidence data presented in this supplement. [source] | ||||||||||