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At least 235 records · Page 13Linked to original sources

[External beam radiation therapy and interstitial brachytherapy in the treatment of anal canal carcinomas: a series of 70 patients].

This study is concerning 70 patients (57 female, 13 male) with an epidermoid carcinoma of the anal canal which were treated homogeneously with a combination of an external beam radiation therapy ((45 Gy in 25 fractions of 1.8 Gy for 5 weeks) and a brachytherapy with Iridium wires (15 to 20 Gy delivered to the gross residual disease). The N1 patients and the patients with tumors more than 4 cm in diameter received a chemotherapy also (5 FU and cisplatinum). The overall local control was obtained in 68 cases out of 70 (97.1%). 63 out of 70 patients (90%) are alive and locally controlled. 56 pts out of 70 (80%) did have a preserved anus, and a normal sphincterian function was preserved in 53 pts out of 70 (75.7%). 17 pts had a colostomy (3 without and 14 with an abdominoperineal resection). With the salvage perineal resection, 11 patients out of 12 local recurrences were definitely locally cured (91.7%). The 5-year overall survival is 91.4%. The 5-year disease-free survival is 90%. The 5-year survival with preserved anal sphincter is 80% and with preserved sphincterian function is 75.7%. Five patients died from cancer (3 deaths due to metastases, and only 2 due to a locoregional evolution). These results have been analysed regarding the literature data and demonstrated the curative role of external beam and brachytherapy, in localized tumors, the contribution of chemotherapy in advanced stages and the efficiency of secondary salvage surgery in local recurrences.

Adult↗

Approaches and informatics tools to assist in the integration of similar clinical research questionnaires.

OBJECTIVE: The integration of similar clinical research questionnaires is a complex process that can benefit from informatics approaches and tools that provide a systematic structure for performing mapping and integration. This systematic approach is necessary to address complex issues in integration such as data heterogeneity, differing levels of granularity of questions and responses, and other issues involving semantic differences. Informatics tools and approaches have been successfully applied to various standard clinical vocabulary integration processes but not for questionnaire integration or mapping. METHODS: A systematic approach to questionnaire integration was developed in the context of a collaboration of researchers using Trial/DB, a database designed to support clinical research. This approach was applied to the integration of questionnaires involving breast cancer risk factors from each of three research sites. RESULTS: From 375 questions on the three original questionnaires, we identified 65 concepts that were measured by two or three of the sites. An algorithm was developed and used to formalize the process of mapping questions and answers across the questionnaires. The approach was applied to previously collected data and prospective data in disparate data-base systems to import and merge the data from these three sites into Trial/DB. CONCLUSION: Informatics tools that support a systematic approach to mapping questionnaires can be used throughout the research process from questionnaire integration and creation, legacy data integration to data library maintenance and curation.

Biomedical Research↗

The effects of prostacyclin on early ultrastructural changes in the cytoplasm and nuclei of neuroglial cells following complete cerebral ischemia.

Twelve rabbits were submitted to 20-min global cerebral ischemia. Half of them were treated continuously with prostacyclin (PGI2) for 3 min before and during ischemia, and for 15 min after it. Untreated animals were not given PGI2 medication. The cases treated with PGI2 were found to have recovered bioelectric activity of the brain in half the time that its return took in the untreated cases. In the group that received PGI2, the ischemic ultrastructural changes in the cytoplasm of neuroglial cells were abolished, however, PGI2 did numerous vesicular structures, nuclear inclusions and chromatin clumping and margination. The vesicular structures were enclosed in a single smooth membrane without contact with the nuclear envelope. It is suggested that the vesicular structures may form as the result of disturbances in the water-electrolyte exchange between the cytoplasm and karyoplasm of neuroglial cells. The inclusions consisted of filaments and/or membranes. The amassing in the karyoplasm of vesicular structures and intranuclear inclusions with chromatin clumping and margination probably leads later to the death of the neuroglial cells after total cerebral ischemia. Hence, the described data indicate that the curative effects of PGI2 are directed only to early changes in the neuroglial cells cytoplasm and reflect a transient facilitation of functional recovery and/or metabolism rather then permanent brain protection after complete cerebral ischemia.

Animals↗

Cimetidine-mediated augmentation of lymphocyte responses to phytohemagglutinin in gastric cancer patients.

The effect of cimetidine, a histamine type 2 receptor antagonist, on lymphocyte responses to phytohemagglutinin (PHA) was studied in 58 gastric cancer patients. Cimetidine significantly enhanced lymphocyte responses to PHA in certain gastric cancer patients. The degree of enhancement was associated with tumor load. A significant inverse correlation was observed between the degree of enhancement and that of the original lymphocyte responses to PHA. The degree of enhancement significantly correlated with the proportions of OKT3 and OKT8 positive cells. A determination of the degree of enhancement in selected gastric cancer patients revealed it to fall to a low level after a certain period following curative gastric resection. These data appear to favor the in vivo therapeutic administration of cimetidine to advanced gastric cancer patients.

Adult↗

Cancer "cures" in children, adolescents and young adults versus general cancer cure failure after 50 years of age.

Cancer cure has principally concerned stem cell or embryonic cell tumors in children, adolescents and adults under 50 years of age. Cancers that are termed "curable" are those in which the patient survival curve rapidly becomes parallel to the normal life expectancy curve--a plateau in children--and "almost curable" those in which this phenomenon appears later on and/or which is not completely parallel to the normal life expectancy curve. The failure to cure cancer patients over 50 years of age by chemotherapy suggests that although cytostatics are able to reduce the neoplastic cell number to a level that can be eradicated by the lato sensu immunologic functions of the organism before that age, this is not the case in older patients in which even a low number of neoplastic cells cannot be destroyed in this manner. Experimental and clinical data on preventive and curative effects of immuno-restoration/stimulation after the age of 50 are presented and discussed, as well as both reduced cancer patient survival rate and decreased immunity which follows peri-surgical radiotherapy.

Adolescent↗

Textmining in support of knowledge discovery for vaccine development.

Complete genome data of infectious microorganisms permit systematic computational sequence-based predictions and experimental testing of candidate vaccine epitopes. Both, predictions and the interpretation of experiments rely on existing information in the literature which is mostly manually extracted and curated. The growing amount of data and literature information has created a major bottleneck for the interpretation of results and maintenance of curated databases. The lack of suitable free-text information extraction, processing, and reporting tools prompted us to develop a knowledge discovery support system that enhances the understanding of immune response and vaccine development. The current prototype system, Gene expression/epitpopes/protein interaction (GEpi), focuses on molecular functions of HIV-infected T-cells and HIV epitope information, using textmining, and interrelation of biomolecular data from domain-specific databases with MEDLINE abstract-inferred information. Results showed that extraction and processing of molecular interaction, disease associations, and gene ontology-derived functional information generate intuitive knowledge reports that aid the interpretation of host-pathogen interaction. In contrast, epitope (word and sequence) information in MEDLINE abstracts is surprisingly sparse and often lacks necessary context information, such as HLA-restriction. Since the majority of epitope information is found in tables, figures, and legends of full-text articles, its extraction may not require sophisticated natural language processing techniques. Support of vaccine development through textmining requires therefore the timely development of domain-specific extraction rules for full-text articles, and a knowledge model for epitope-related information.

Animals↗

Management of recurrent colorectal carcinoma.

BACKGROUND/OBJECTIVE: The records of patients treated for adenocarcinoma of the colon and rectum between 1 January 1988 and 31 December 1995 at Naval Medical Center San Diego were reviewed. Analysis was made of patients who developed recurrences after potentially definitive primary therapy. METHODS: A retrospective review of 410 patients diagnosed with colorectal cancer at our institution was conducted. The focus of this review was to identify patients with recurrent disease after curative initial procedures, and to determine how recurrences were detected and treated. Survival data for 48 patients undergoing various curative and palliative procedures, or no therapy, were generated. RESULTS: The decision to re-operate with curative intent was made after a multidisciplinary review of restaging studies. Laparoscopy was not used in this determination. Curative resection of recurrence confers increased survival over non-curative surgery and no surgery (P < 0.001). This is misleading because of patient selection; several patients undergo potentially curative surgery but are determined intraoperatively to best be palliated, or to have further surgery aborted. Analysis of results in patients undergoing potentially curative surgery vs. those undergoing planned palliation vs. those not operated reveals that these also provide significantly different outcomes (P < 0.003). CONCLUSIONS: Proper delineation of resectable lesions in patients with recurrent colorectal cancer contributes to better outcomes for them. That determination is difficult, and efforts are underway in our institution and elsewhere to better delineate which patients are optimal preoperatively. We consider multidisciplinary Tumor Board evaluation to be central to this process.

Journal Article↗

Gene and protein nomenclature in public databases.

BACKGROUND: Frequently, several alternative names are in use for biological objects such as genes and proteins. Applications like manual literature search, automated text-mining, named entity identification, gene/protein annotation, and linking of knowledge from different information sources require the knowledge of all used names referring to a given gene or protein. Various organism-specific or general public databases aim at organizing knowledge about genes and proteins. These databases can be used for deriving gene and protein name dictionaries. So far, little is known about the differences between databases in terms of size, ambiguities and overlap. RESULTS: We compiled five gene and protein name dictionaries for each of the five model organisms (yeast, fly, mouse, rat, and human) from different organism-specific and general public databases. We analyzed the degree of ambiguity of gene and protein names within and between dictionaries, to a lexicon of common English words and domain-related non-gene terms, and we compared different data sources in terms of size of extracted dictionaries and overlap of synonyms between those. The study shows that the number of genes/proteins and synonyms covered in individual databases varies significantly for a given organism, and that the degree of ambiguity of synonyms varies significantly between different organisms. Furthermore, it shows that, despite considerable efforts of co-curation, the overlap of synonyms in different data sources is rather moderate and that the degree of ambiguity of gene names with common English words and domain-related non-gene terms varies depending on the considered organism. CONCLUSION: In conclusion, these results indicate that the combination of data contained in different databases allows the generation of gene and protein name dictionaries that contain significantly more used names than dictionaries obtained from individual data sources. Furthermore, curation of combined dictionaries considerably increases size and decreases ambiguity. The entries of the curated synonym dictionary are available for manual querying, editing, and PubMed- or Google-search via the ProThesaurus-wiki. For automated querying via custom software, we offer a web service and an exemplary client application.

Abstracting and Indexing↗

Significance of bile-duct changes in schistosomiasis.

Lesions involving the intra-hepatic biliary ducts in schistosomiasis have been reported in the literature, both in mice and man, but there are no data concerning their quantitative, evolutionary or post curative chemotherapeutic aspects on record. In order to obtain such data an investigation on this subject was attempted. Mice infected with 50 Schistosoma mansoni cercariae were submitted to a liver biopsy at the 9th week post-infection, and treated with 400 mg/bw praziquantel immediately afterwards. Infected and non-infected controls were submitted to the same procedures. By 19 weeks from cercarial exposure all surviving animals were sacrificed. The biliary ducts were counted on histological sections and the results were expressed as biliary ducts/portal spaces. This quantitative evaluation was compared with that from normal controls and revealed hyperplasia as the main biliary duct change (p<0.007) in schistosomiasis. Hyperplastic changes underwent only mild partial and not statistically significant regression after specific chemotherapy (p>0.05). Infected and untreated animals presented ductal changes that did not differ from those of the treated group. Measurements of serum bilirubin (total and direct), and gamma-glutamyl-transpeptidase (gamma-GT) did not reveal significant differences when animals from the several groups were compared. Thus, bile ducts exhibit a proliferative response in relation to neighboring S. mansoni injury to portal areas, but although these lesions are histopathologically impressive, they lack a functional or prognostic significance.

Animals↗

Curative radiotherapy for a second primary lung cancer arising after pneumonectomy -- techniques and results.

BACKGROUND AND PURPOSE: Only limited data exist on the outcome of curative radiotherapy in patients who develop a second primary lung tumour after pneumonectomy. The treatment of eight such patients is described. MATERIALS AND METHODS: The case records of patients who underwent curative radiotherapy for stage I non-small cell lung cancer after a previous pneumonectomy were reviewed. Treatment was delivered using 3D external radiotherapy to a dose of 50-70 Gy, in once-daily fractions of 2-2.5 Gy. An endobronchial brachytherapy boost was used in three patients. Original treatments were re-planned in an attempt to minimize the volume of irradiated lung. RESULTS: A complete remission was achieved in five (of six) evaluable patients, but two patients subsequently developed a local relapse. All patients survived for a minimum of 1 year after treatment. Only one patient developed significant (grade 2) radiation pneumonitis. When treatments were re-planned to optimize beam arrangements, and when customized blocks were used, the mean lung volume receiving > or = 20 Gy (calculated for 70 Gy) decreased from 24.6+/-4.1 (range, 18-31%) to 17.3+/-5.1% (range, 12-26%). Similarly, the radiation conformity index improved from 0.44+/-0.11 to 0.61+/-0.06. CONCLUSIONS: Involved-field radiotherapy can be curative in patients who develop a new lung tumour after pneumonectomy. Recent advances in defining target volumes, treatment planning and delivery are likely to improve upon these results.

Aged↗

The Rat Genome Database, update 2007--easing the path from disease to data and back again.

The Rat Genome Database (RGD, http://rgd.mcw.edu) is one of the core resources for rat genomics and recent developments have focused on providing support for disease-based research using the rat model. Recognizing the importance of the rat as a disease model we have employed targeted curation strategies to curate genes, QTL and strain data for neurological and cardiovascular disease areas. This work has centered on rat but also includes data for mouse and human to create 'disease portals' that provide a unified view of the genes, QTL and strain models for these diseases across the three species. The disease curation efforts combined with normal curation activities have served to greatly increase the content of the database, particularly for biological information, including gene ontology, disease, pathway and phenotype ontology annotations. In addition to improving the features and database content, community outreach has been expanded to demonstrate how investigators can leverage the resources at RGD to facilitate their research and to elicit suggestions and needs for future developments. We have published a number of papers that provide additional information on the ontology annotations and the tools at RGD for data mining and analysis to better enable researchers to fully utilize the database.

Animals↗

Long-Segment early squamous cell carcinoma of the proximal esophagus: curative treatment and long-term follow-up after 5-aminolevulinic acid (5-ALA)-photodynamic therapy.

Photodynamic therapy (PDT) is an established treatment for the ablation of dysplastic Barrett's epithelium and early esophageal carcinoma, but no data have been published on curative 5-aminolevulinic acid (5-ALA)-PDT for long-segment early esophageal cancer with infiltration of the upper sphincter. We describe successful curative treatment of an unusual early long-segment squamous cell carcinoma (uT1a,N0) of the proximal esophagus (18 - 28 cm aborally), with three sessions of 5-ALA-PDT. Endoscopic and endosonographic follow-up macroscopically showed a complete remission of the tumor, proven by biopsy showing total histological ablation. After a follow-up period of 23 months, there has been no indication of tumor recurrence. Early superficial (< 3 mm) squamous cell carcinomas of the esophagus can be ablated completely by 5-ALA-PDT. However, long-term follow-up is required in order to prove the effectiveness of endoscopic ablation therapy for early esophageal cancer.

Aminolevulinic Acid↗

Enhancing data sharing in collaborative research projects with DASH.

We describe a software framework, called DASH, that enables the facile access, maintenance, curation and sharing of computational biology data among collaborating research scientists. The DASH event-based framework enables members of team-based research projects to describe the multistep computational processing pipelines frequently required to generate data for sharing, monitors multiple distributed data stores for changes, and will then automatically invoke the appropriate processing pipeline(s). These pipelines can be used to communicate the results of data analyses to collaborators using mechanisms such as Web Services. We describe the overall design of the DASH system and the application of a simple DASH prototype to a collaborative pharmacogenomics research project involving several dozen researchers located at several different sites--the UCSF Pharmacogenetics of Membrane Transporters project.

Automation↗

Is surgery-only the adequate treatment approach for T2N0 rectal cancer?

BACKGROUND AND OBJECTIVES: Resection combined with standard lymphadenectomy is generally recommended for T2N0 rectal cancer. In order to evaluate the outcome of this specific tumor category, our own data were reviewed. METHODS: To evaluate the results of patients with curative resected T2N0 rectal carcinoma, we reviewed data of 164 consecutive patients with adenocarcinoma of the rectum between 1981 and 2003 in our department. In addition, patient characteristics were stratified according to the position of the rectal tumor with respect to the anal verge. RESULTS: One hundred ten patients (67.1%) underwent anterior resection and 54 patients (32.9%) received abdominoperineal amputation. The follow-up revealed 6 local recurrences (3.7%); in 10 patients (10.0%), metastases were discovered. Regarding the tumor localization nearly no local recurrence or distant metastases were observed in the middle or the upper rectum. However, in the lower rectum the actuarial 5-year recurrence rate was 16.2%. CONCLUSIONS: Although T2N0 rectal carcinomas are considered as low risk tumors, we found a considerable local recurrence rate of 3.7%. The question arises whether this result can be improved by adjuvant treatment modalities without being compromised by the toxicity of an adjuvant treatment.

Adenocarcinoma↗

Muscle-invasive bladder cancer in elderly-unfit patients with concomitant illness: can a curative radiation therapy be delivered?

AIMS AND BACKGROUND: There is no standard treatment for elderly-unfit patients with muscle-invasive bladder cancer. Pelvic irradiation alone is an usual approach in this instance, and some reports have demonstrated that curative radiotherapy is feasible in elderly patients. To our knowledge, no data exist about the feasibility of a curative treatment in elderly patients with concomitant illness and a Charlson Comorbidity Index (an index of comorbidity that includes age) greater than 2. The main purpose of the present study was to establish the feasibility of irradiation in a cohort of elderly patients in poor general condition. METHODS: The records of 45 elderly-unfit patients (median age, 75 years; range, 70-85), with a comorbid Charlson score >2, treated with curative dose, planned continuous-course, external beam radiotherapy for muscle-invasive bladder cancer were reviewed. The patients were treated to a median total dose of 60 Gy (range, 56-64), with an average fractional dose of 190 +/- 10 cGy using megavoltage (6-15 MV). All patients were treated with radiation fields encompassing the bladder and grossly involved lymph nodes with a radiographic margin of at least 1.5 cm. RESULTS: No treatment-related mortality and clinically insignificant acute morbidity was recorded. No patient was hospitalized during or after the irradiation because of gastrointestinal or urogenital side effects. In one patient a week rest from therapy was necessary due a febrile status. Median survival was 21.5 months; overall 3- and 5-year survival was 36% and 19.5%, respectively. CONCLUSIONS: Elderly-unfit patients with comorbidities and >70 years of age can be submitted to radical pelvic irradiation. The results observed in this retrospective analysis have encouraged us to use non-palliative radiotherapy doses in these patients with muscle-invasive bladder cancer.

Age Factors↗

An individual patient data meta-analysis of long supported adjuvant chemotherapy with oral carmofur in patients with curatively resected colorectal cancer.

To reappraise the benefits of the long supported chemotherapy with carmofur, a meta-analysis based on individual patient data from the three clinical trials was performed by pooling 614 patients from three trials, there is a statistically significant survival benefit (2p=0.032) and disease-free survival (DFS) benefit (2p=0.021) for carmofur; and a highly significant advantage for carmofur in DFS (2p=0.0004) and in survival (2p=0.004) in Dukes' C patients. This IPD meta-analysis strongly suggested an effect of oral carmofur in a long supported chemotherapy for curatively resected colorectal carcinoma.

Administration, Oral↗

Multi-omics Mendelian Randomization Prioritizes Neutrophil Extracellular Trap-related Genes Associated with Atrial Fibrillation Risk.

BACKGROUND: Neutrophil extracellular traps (NETs) participate in thrombosis, inflammation, and cardiovascular remodeling, yet whether NET-related genes (NRGs) are associated with atrial fibrillation (AF) risk across multiple molecular layers remains unclear. This study used a multiomics Mendelian randomization framework to prioritize NRGs supported by methylation, expression, and protein quantitative trait loci (QTL) data. METHODS: Genome-wide significant cis instruments (P < 5 &#xd7; 10-8) were obtained for 90 methylation QTLs (mQTLs), 100 expression QTLs (eQTLs), and 38 protein QTLs (pQTLs) mapped to 137 literature- curated NRG entries. Summary-data-based Mendelian randomization (SMR) coupled with the heterogeneity in dependent instruments (HEIDI) test was applied using whole-blood mQTL data (n = 1,980), eQTLGen blood eQTL data (n = 31,684), and deCODE plasma pQTL data (n = 35,559). AF outcome data were obtained from a meta-analysis including 60,620 cases and 970,216 controls of European ancestry. RESULTS: At the methylation level, 21 CpG-feature associations across 13 genes remained significant after HEIDI filtering and false discovery rate (FDR) correction. Expression-level analysis identified eight significant gene-AF associations, whereas protein-level analysis identified seven significant features representing five unique proteins. Cross-omics integration prioritized C3, MAPK3, and STAT3 as Tier 1 genes, CTSC, LPAR3, and THBD as Tier 2 genes, and fourteen additional genes as Tier 3 candidates. C3 showed risk-increasing protein-level associations together with multiple significant CpG signals, whereas MAPK3 and STAT3 showed directionally protective expression/protein or methylation/protein patterns. DISCUSSION: The cross-omics convergence on C3, MAPK3, and STAT3 is consistent with complement activation, immune-fibrotic signaling, and cytokine-regulatory pathways implicated in AF biology, but the findings should be interpreted as genetic prioritization rather than definitive intervention-ready causality. CpG-level heterogeneity at the C3 locus and the blood/plasma origin of the QTL resources further support a cautious interpretation. Modest colocalization support and the unresolved possibility of pQTL sample overlap further support this cautious, hypothesis-generating interpretation. CONCLUSION: Multi-omics SMR prioritizes C3, MAPK3, and STAT3 as the most consistently supported NET-related genes associated with AF risk. These findings provide a framework for atrialtissue replication and mechanistic validation of NET-related pathways in AF.

Atrial fibrillation↗

Genew: the human gene nomenclature database.

Genew, the Human Gene Nomenclature Database, is the only resource that provides data for all human genes which have approved symbols. It is managed by the HUGO Gene Nomenclature Committee (HGNC) as a confidential database, containing over 16 000 records, 80% of which are represented on the Web by searchable text files. The data in Genew are highly curated by HGNC editors and gene records can be searched on the Web by symbol or name to directly retrieve information on gene symbol, gene name, cytogenetic location, OMIM number and PubMed ID. Data are integrated with other human gene databases, e.g. GDB, LocusLink and SWISS-PROT, and approved gene symbols are carefully co-ordinated with the Mouse Genome Database (MGD). Approved gene symbols are available for querying and browsing at http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/searchgenes.pl.

Confidentiality↗