Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Peritoneal Neoplasms”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources

Hyperstable U1snRNA complementary to the K-ras transcripts induces cell death in pancreatic cancer cells.

One of the critical steps that governs the inhibitory effect of antisense RNA on target gene expression is the association of the antisense RNA with the target RNA molecules. However, until now, no systematic method has been available to select the suitable parts of a gene as antisense targets. In this study, we utilised U1 small nuclear RNA (snRNA) that binds physiologically to the 5' splice site (5'ss) of pre-mRNA, to develop a novel vector system that permits imposed binding of antisense RNA to its target. The 5' free end of U1snRNA was replaced with the antisense sequence against the K-ras gene to generate a hyperstable U1snRNA, whose binding stability to 5'ss of the K-ras transcript is ten-fold higher than that of wild-type U1snRNA. The efficacy of such hyperstable U1snRNA was examined by transducing the expression plasmids into human pancreatic cancer cell lines. This revealed that two of the hyperstable U1snRNAs induced cell death after gene transduction, and significantly reduced the number of G418-resistant colonies to less than 10% of the controls. Furthermore, hyperstable U1snRNA suppressed intraperitoneal dissemination of pancreatic cancer cells in vivo. Hyperstable U1snRNA might be a novel approach to express effective antisense RNA in target cells.

Animals↗

Effects of platinum/taxane based chemotherapy on acute perfusion in human pelvic tumours measured by dynamic MRI.

Dynamic contrast enhanced MRI (DCE-MRI) is being used increasingly in clinical trials to demonstrate that vascular disruptive and antiangiogenic agents target tumour microcirculation. Significant reductions in DCE-MRI kinetic parameters are seen within 4-24 and 48 h of treatment with vascular disruptive and antiangiogenic agents, respectively. It is important to know whether cytotoxic agents also cause significant acute reductions in these parameters, for reliable interpretation of results. This study investigated changes in transfer constant (K(trans)) and the initial area under the gadolinium curve (IAUGC) following the first dose of chemotherapy in patients with mostly gynaecological tumours. A reproducibility analysis on 20 patients (using two scans performed on consecutive days) was used to determine the significance of DCE-MRI parameter changes 24 h after chemotherapy in 18 patients. In 11 patients who received platinum alone or with a taxane, there were no significant changes in K(trans) or IAUGC in either group or individual patient analyses. When the remaining seven patients (treated with a variety of agents including platinum and taxanes) were included (n=18), there were also no significant changes in K(trans). Therefore, if combination therapy does show changes in DCE-MRI parameters then the effects can be attributed to antivascular therapy rather than chemotherapy.

Adult↗

SCOTROC 2A: carboplatin followed by docetaxel or docetaxel-gemcitabine as first-line chemotherapy for ovarian cancer.

The feasibility of sequential carboplatin followed by docetaxel-based therapy for untreated ovarian cancer was determined. Patients received four q3w cycles of carboplatin AUC 7, then four q3w cycles of either docetaxel 100 mg m(-2) (day 1) (arm A); docetaxel 75 mg m(-2) (day 8) and gemcitabine 1250 mg m(-2) (days 1,8) (arm B) or docetaxel 25 mg m(-2) and gemcitabine 800 mg m(-2) (both given weekly (days 1,8,15)) (arm C). A total of 44 patients were randomised to each treatment arm. None of the arms demonstrated an eight cycle completion rate (70.5/72.7/45.5% in arms A/B/C, respectively), which was statistically greater than 60% (P=0.102, P=0.056, P=0.982) which was our formal feasibility criteria, although only the completion rate in arm C was clearly worse than this level. The overall response rate (ORR) after carboplatin was 65.7% in 70 evaluable patients. In evaluable patients, ORRs after docetaxel-based cycles were: arm A 84.0% (21 out of 25); arm B 77.3% (17 out of 22); arm C 69.6% (16 out of 23). At follow-up (median 30 months), median progression-free survival times were: arm A 15.5 months (95% CI: 10.5-20.6); arm B 18.1 months (95% CI: 15.9-20.3); arm C, 13.7 months (95% CI: 12.8-14.6). Neutropenia was the predominant grade 3-4 haematological toxicity: 77.8/85.7/54.4% in arms A/B/C, respectively. Dyspnoea was markedly increased in both gemcitabine-containing arms (P=0.001) but was worse in arm C. Although just failing to rule out eight cycle completion rates less than 60%, within the statistical limitations of these small cohorts, the overall results for arms A and B are encouraging. Larger phase III studies are required to test these combinations.

Adult↗

SCOTROC 2B: feasibility of carboplatin followed by docetaxel or docetaxel-irinotecan as first-line therapy for ovarian cancer.

The feasibility of combination irinotecan, carboplatin and docetaxel chemotherapy as first-line treatment for advanced epithelial ovarian carcinoma was assessed. One hundred patients were randomised to receive four 3-weekly cycles of carboplatin (area under the curve (AUC) 7) followed by four 3-weekly cycles of docetaxel 100 mg m(-2) (arm A, n=51) or docetaxel 60 mg m(-2) with irinotecan 200 mg m(-2) (arm B, n=49). Neither arm met the formal feasibility criterion of an eight-cycle treatment completion rate that was statistically greater than 60% (arm A 71% (90% confidence interval (CI) 58-81%; P=0.079; arm B 67% (90% CI 55-78%; P=0.184)). Median-dose intensities were >85% of planned dose for all agents. In arms A and B, 15.6 and 12.2% of patients, respectively, withdrew owing to treatment-related toxicity. Grade 3-4 sensory neurotoxicity was more common in arm A (1.9 vs 0%) and grade 3-4 diarrhoea was more common in arm B (0.6 vs 3.5%). Of patients with radiologically evaluable disease at baseline, 50 and 48% responded to therapy in arms A and B, respectively; at median 17.1 months' follow-up, median progression-free survival was 17.1 and 15.9 months, respectively. Although both arms just failed to meet the formal statistical feasibility criteria, the observed completion rates of around 70% were reasonable. The addition of irinotecan to first-line carboplatin and docetaxel chemotherapy was generally well tolerated although associated with increased gastrointestinal toxicity. Further exploratory studies of topoisomerase-I inhibitors in this setting may be warranted.

Adult↗

Phase II study of capecitabine and irinotecan combination chemotherapy in patients with advanced gastric cancer.

The present study was conducted to evaluate the efficacy and safety of a combination regimen of capecitabine plus irinotecan in patients with advanced gastric cancer. Patients with previously untreated metastatic or recurrent, measurable gastric cancer received oral capecitabine 1000 mg m(-2) twice daily from day 1 to 14 and intravenous irinotecan 100 mg m(-2) on days 1 and 8, based on a 3-week cycle. Forty-one patients were enrolled in the current study, among whom 38 were assessable for efficacy and 40 assessable for toxicity. Three complete responses and 16 partial responses were confirmed, giving an overall response rate of 46.3%. At a median follow-up of 269 days, the median time to progression and overall survival were 5.1 and 8.6 months, respectively. Grade 3/4 neutropenia occurred in four patients and grade 3 febrile neutropenia was observed in two patients. Grade 3 diarrhoea and grade 2 hand-foot syndrome occurred in six patients and eight patients, respectively. The combination of capecitabine and irinotecan was found to be well tolerated and effective in patients with advanced gastric cancer. Accordingly, this regimen can be regarded as one of first-line treatment options for advanced gastric cancer.

Adenocarcinoma↗

Phase II study of docetaxel and irinotecan combination chemotherapy in metastatic gastric carcinoma.

The current treatment for metastatic gastric cancer (MGC) consists of cisplatin and/or fluorouracil (5-FU) based combination chemotherapy, but cisplatin-based regimens are associated with considerable toxicity. We evaluated the efficacy and safety of a noncisplatin-, non-5-FU-containing regimen, docetaxel/irinotecan in MGC. Chemo-naive patients with MGC received docetaxel (30 mg m(-2)) and irinotecan (70 mg m(-2)) on days 1 and 8 every 3 weeks. The 48 eligible patients (median age 56 years) received a median of four cycles of docetaxel/irinotecan (range 1-18). Of the 46 patients in whom efficacy could be evaluated, 21 showed a partial response (response rate=45.7%; 95% confidence interval (CI) 31.3-60.1%). At a median follow-up of 15.0 months, the median time to progression was 4.5 months (95% CI 3.8-5.2 months) and overall survival was 8.2 months (95% CI, 5.8-10.6 months). Grade 3/4 neutropenia developed in 57.4% of patients, and febrile neutropenia/neutropenic infection in 19.1%. Nonhaematological toxicities were moderate; grade 3/4 diarrhoea occurred in 19.1% of patients, however, was manageable by a dose reduction. There was one possible treatment-related death. In conclusion, weekly docetaxel/irinotecan is a promising outpatient regimen in MGC, with appropriate dose modification.

Adenocarcinoma↗

Adenoviral delivery of TIMP1 or TIMP2 can modify the invasive behavior of pancreatic cancer and can have a significant antitumor effect in vivo.

Pancreatic carcinomas overexpress several matrix metalloproteinases (MMPs), in particular MMP2 and MMP9. These enzymes are involved in the degradation of the extracellular matrix to aid tumor cell invasion. The aim of this study was to investigate the effect of TIMP gene therapy on human pancreatic cancer. Human TIMP1 or TIMP2 has been introduced in pancreatic tumor cells under the control of a constitutive promoter using adenoviral vectors, and the effect on tumor invasion observed. It has been demonstrated in vitro that the TIMP-expressing pancreatic tumor cells were significantly less invasive than those cells transfected with a control vector. In vivo, adenoviral delivery of TIMP1 or TIMP2 to nude mice harboring intraperitoneal human pancreatic cancers resulted in prolonged survival compared with control mice if the gene therapy was given early (P<.009 and P<.0293, respectively). The in vivo experiments demonstrated evidence of gene transfer by adenoviral vectors to tumor cells and murine mesenteric cells. There was no evidence of transgene expression in distant organs. These experiments have proved the hypothesis that TIMP overexpression in pancreatic cancer cells can modify the invasive phenotype. Also, TIMP gene transfer to human tumor cells is possible both in vitro and in vivo.

Adenoviridae↗

Genetic imbalance on chromosome 17 in papillary serous carcinoma of the peritoneum.

We extend the evaluation of allelic loss patterns on chromosome 17 to papillary serous carcinoma of the peritoneum (PSCP) which is histologically identical to papillary serous ovarian carcinoma (PSOC). DNA was obtained from 11 archival cases of PSCP, with 1-11 tumor sites per case. Using ten loci spanning chromosome 17, loss of heterozygosity (LOH) was identified in all 11 cases (100%). Furthermore, 75-100% of informative cases exhibited LOH at the loci p53, D17S1322 (intragenic to the tumor suppressor gene BRCA1), D17S1327 and MPO. PSCP cases exhibit a higher rate of LOH at most loci when compared with PSOC. Alternating allelic loss at different tumor sites was identified in three cases supporting a multifocal origin of PSCP. Microsatellite instability (MI) is an uncommon event which was identified in four cases. These data implicate chromosome 17 as a potential location of genetic events important in the pathogenesis of PSCP as well as ovarian cancer.

BRCA1 Protein↗

DCC and SMAD4 alterations in human colorectal and pancreatic tumor dissemination.

Chromosome 18q is lost a high proportion of colorectal and pancreatic cancers. Three candidate tumor suppressor genes, DCC, Smad4 and Smad2 have been identified in this chromosome region. DCC and Smad4 aberrations have been previously identified in pancreatic and colorectal tumors. The aim of this study was to compare the presence of concurrent genetic aberrations in DCC and neighboring Smad4 and Smad2 genes during colorectal and pancreatic distal dissemination. We have used a panel of orthotopically implanted colorectal and pancreatic xenografts and corresponding metastases. We have shown that while LOH at DCC locus occurred at a similar frequency in both tumors, diminished DCC protein expression was exclusively present in colorectal tumors harboring intragenic DCC LOH. In contrast, in pancreatic xenografts loss of DCC protein and mRNA expression was restricted to metastases. Smad4 gene aberrations were detected at a similar frequency in both tumors and were selected for during distal dissemination. Acquisition of alterations in both genes occurred independently. Our results suggest that both DCC and Smad4 contribute to pancreatic and colorectal distal dissemination. However, the role of DCC may differ between both tumor types.

Adenocarcinoma↗

Abdominal lymphangioma in adults and children.

BACKGROUND: Abdominal lymphangioma is a rare tumour usually classified with mesenteric and retroperitoneal cysts. This experience of abdominal lymphangiomas contrasts the differences between tumours in children and adults. METHODS: Between 1970 and 1996, six patients had surgical resection of an abdominal lymphangioma. RESULTS: There were three children aged 4 years or less and three adults aged 36-76 years. Two children presented with an acute abdomen and one with a rapidly enlarging abdominal girth. Lymphangiomas were located in the mesentery and gastrointestinal tract. In adults, symptoms lasted from months to years and lymphangiomas were found in the pancreas, spleen and retroperitoneum. CONCLUSION: In this series, abdominal lymphangioma presented more acutely in children and usually involved the mesentery, whereas in adults the history was longer and the tumour was found in the retroperitoneum.

Abdominal Neoplasms↗

Gastrointestinal autonomic nerve tumours: a report of nine cases.

We describe the clinicopathological features of gastrointestinal autonomic nerve tumours in nine patients where the diagnosis was confirmed by electronmicroscopy. Most patients presented with abdominal pain. At laparotomy, large intra-abdominal tumour masses were found which tended to be cystic and haemorrhagic. The predominant histological patterns were nests, sheets and fascicles of spindle and epithelioid cells. Immunohistochemistry showed positive staining for neuron specific enolase (9/9), PGP 9.5 (9/9), NKI/C3 (7/9), vimentin (7/9), alpha-smooth muscle actin (5/9), vasoactive intestinal peptide (3/9) and CD34/QBend10 (2/9). Grimelius staining was positive in two of nine cases. All tumours were negative for CAM 5.2, chromogranin, synaptophysin, Leu 7, neurofilament protein, muscle-specific actin (HHF-35) and desmin (D33). Ultrastructural examination showed cellular processes and dense-core granules in all cases. Three tumours had microtubules and/or intermediate filaments, particularly in cell processes. Skeinoid fibres were seen in three cases. No convincing synapses or small (synaptic-type) vesicles were identified. There was no evidence of epithelial, smooth muscle or nerve sheath differentiation. Two patients died due to tumour, two died of unknown causes and the remainder are alive 2-44 months after presentation. Four of the five survivors have recurrent/residual intra-abdominal tumour. So-called gastrointestinal autonomic nerve tumours are apparently slow-growing malignant tumours showing neuronal differentiation. Four cases arose in the mesentery/retroperitoneum or omentum rather than bowel wall and therefore a more appropriate nomenclature might be intra-abdominal stromal tumour with neuronal differentiation.

Actins↗

Pseudomyxoma peritonei as a cause of culture-negative peritonitis for a patient undergoing peritoneal dialysis.

Culture-negative peritonitis accounts for up to 20% of all peritoneal dialysis-related peritonitis, the causes of which include culture-associated technical errors, prior use of antibiotics, infection caused by certain unusual or fastidious microorganisms, the development of abdominal or retroperitoneal organ inflammation, and the presence of malignancies. Here, we report a patient with end-stage renal disease receiving peritoneal dialysis who presented with culture-negative peritonitis and ultrafiltration failure caused by the rare pseudomyxoma peritonei. For cases of culture-negative peritonitis such as this, early imaging studies may help recognize intraperitoneal/retroperitoneal visceral inflammation and malignant conditions.

Adult↗

Clinical implications of expression of vascular endothelial growth factor in metastatic lesions of ovarian cancers.

Vascular endothelial growth factor (VEGF) has been identified as an important factor for tumour angiogenesis, which is essential for the growth, invasion and metastasis of solid tumours. Significantly increased VEGF level from the primary tumour to the metastatic lesion of ovarian cancers was found in 8 of 30 cases. The 24-month survival rate of the patients with significantly increased VEGF level was extremely poor (0/8 = 0%) in comparison with that of patients with no change in the level (15/22 = 68%) from the primary tumour to the metastatic lesion. This indicates that VEGF may contribute to the advancement of metastatic lesions, and that VEGF level in metastatic lesions may be a prognostic indicator.

Adult↗