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Prediction of early and late recurrence in patients with breast carcinoma.

BACKGROUND: The clinical course of patients with recurrent breast carcinoma varies greatly. Better characterization of an individual's clinical course for recurrent patients may aid in their clinical management. However, less attention has been paid to evaluating factors associated with the timing of recurrence in those patients. We investigated the clinicopathological indicators that determined the timing of recurrence by univariate and multivariate analysis. METHODS: We retrospectively examined data on 1428 curatively treated Japanese patients who had been surgically treated for breast cancer between 1983 and 2002. From these, 244(17.1%)who had clearly died of recurrence were entered into this study. RESULTS: By univariate analysis, tumor size, estrogen receptor(ER), and progesterone receptor(PgR)were significantly correlated with time to recurrence. Multivariate analysis indicated that the time between operation and recurrence was independently influenced by ER and PR. CONCLUSIONS: Our research shows that ER and PgR are independent factors influencing the timing of recurrence of breast carcinoma after curative resection. The combined analysis of these independent factors facilitates prediction of the time to recurrence for each patient.

Adult↗

p53 null mutations detected by a p53 yeast functional assay predict a poor outcome in young esophageal carcinoma patients.

Esophageal carcinoma is one of the most common gastrointestinal malignant neoplasms in the world. Recent advances in treatment modalities as well as surgical resection techniques have improved the changes of survival of patients with esophageal carcinoma, although the prognosis is worse than for the other gastrointestinal carcinomas. A more precise stratification beyond clinicopathological classification may help determine optimal treatment. The importance of p53 gene mutations in the pathogenesis of human esophageal carcinoma is well established, but it is still controversial whether the presence of p53 mutations adversely affects individual patient prognosis. In this study, we investigated the p53 mutations of esophageal carcinomas and their correlation with clinicopathologic factors. We employed a p53 yeast functional assay because it is highly sensitive and can detect mutations based on the actual function of the p53 gene, clarifying more precisely the role of this gene in esophageal carcinomas. We also studied young patients (< or =65 years old), because our previous study raised the possibility of differences in the importances in esophageal carcinogenesis in young and old patients. Of 43 young esophageal carcinoma patients (42 squamous cell and 1 undifferentiated carcinoma), 38 (88.4%) harbored p53 mutations. Twenty-seven missense and 11 null mutations were detected, but the presence of p53 mutations did not correlate with any clinicopathologic factor. However, the null mutation was a significant indicator of a poor outcome (P=0.0278). All except one patient who harbored null mutation died within 3 years after a macroscopically curative resection. These data suggest that the type of p53 gene mutation may be predictive of outcome in young esophageal carcinoma patients. Furthermore, null mutations causing loss of function of the gene product may play a more important role than missense mutations in tumor progression.

Aged↗

In silico study of breast cancer associated gene 3 using LION Target Engine and other tools.

Sequence analysis of individual targets is an important step in annotation and validation. As a test case, we investigated human breast cancer associated gene 3 (BCA3) with LION Target Engine and with other bioinformatics tools. LION Target Engine confirmed that the BCA3 gene is located on 11p15.4 and that the two most likely splice variants (lacking exon 3 and exons 3 and 5, respectively) exist. Based on our manual curation of sequence data, it is proposed that an additional variant (missing only exon 5) published in a public sequence repository, is a prediction artifact. A significant number of new orthologs were also identified, and these were the basis for a high-quality protein secondary structure prediction. Moreover, our research confirmed several distinct functional domains as described in earlier reports. Sequence conservation from multiple sequence alignments, splice variant identification, secondary structure predictions, and predicted phosphorylation sites suggest that the removal of interaction sites through alternative splicing might play a modulatory role in BCA3. This in silico approach shows the depth and relevance of an analysis that can be accomplished by including a variety of publicly available tools with an integrated and customizable life science informatics platform.

Adaptor Proteins, Signal Transducing↗

A multifactorial approach for the prognosis of patients with carcinoma of the stomach after curative resection.

This study was done to define the prognostic role of some clinical and pathologic variables in patients with carcinoma of the stomach who underwent a curative subtotal gastrectomy for cancer located at the lower two-thirds of the stomach. An univariate and multivariate analysis, according to Cox's regression model, was retrospectively performed upon 361 patients operated upon at the Istituto Nazionale Tumori of Milan from 1965 to 1979 by a curative subtotal gastrectomy. Data were stored by an IBM 4331 computer. Several factors were taken into consideration: age, sex, site and size of tumor, gross appearance, histologic type, invasion of the gastric wall, nodal status and symptoms. Of six variables selected by the univariate analysis, only four (sex, age, lymph node status and degree of invasion in the gastric wall) were validated by the multivariate evaluation, whereas tumor size and symptoms lost their prognostic relevance. The most important variables were nodal status and the degree of invasion in the gastric wall. The influence of age had a different impact on survival time, depending upon nodal status. In fact, patients with positive nodes who were less than 60 years old had the worst prognosis; the same age group with negative nodes had the best prognosis. Multifactorial analysis, according to the automatic interaction detection procedure, showed that prognosis worsened progressively beginning with female patients with negative nodes at pT1 or pT2 (91.6 per cent five year survival rate), male patients with negative nodes at pT1 or pT2 (76.3 per cent five year survival rate), female patients with negative nodes at pT3 or pT4 (62.4 per cent), male patients with negative nodes at pT3 or pT4 (40.0 per cent), patients more than 60 years old with negative nodes (36.8 per cent) and patients less than 60 years old with positive nodes (20.8 per cent). In our opinion, these parameters should be taken into consideration when stratification of patients as candidates to undergo adjuvant treatment after surgical treatment is planned.

Adult↗

VIPERdb: a relational database for structural virology.

VIPERdb (http://viperdb.scripps.edu) is a database for icosahedral virus capsid structures. Our aim is to provide a comprehensive resource specific to the needs of the structural virology community, with an emphasis on the description and comparison of derived data from structural and energetic analyses of capsids. A relational database implementation based on a schema for macromolecular structure makes the data highly accessible to the user, allowing detailed queries at the atomic level. Together with curation practices that maintain data uniformity, this will facilitate structural bioinformatics studies of virus capsids. User friendly search, visualization and educational tools on the website allow both structural and derived data to be examined easily and extensively. Links to relevant literature, sequence and taxonomy databases are provided for each entry.

Capsid↗

WormBase: a cross-species database for comparative genomics.

WormBase (http://www.wormbase.org/) is a web-accessible central data repository for information about Caenorhabditis elegans and related nematodes. The past two years have seen a significant expansion in the biological scope of WormBase, including the integration of large-scale, genome-wide data sets, the inclusion of genome sequence and gene predictions from related species and active literature curation. This expansion of data has also driven the development and refinement of user interfaces and operability, including a new Genome Browser, new searches and facilities for data access and the inclusion of extensive documentation. These advances have expanded WormBase beyond the obvious target audience of C. elegans researchers, to include researchers wishing to explore problems in functional and comparative genomics within the context of a powerful genetic system.

Animals↗

[Current status and problem of adjuvant chemotherapy for curatively resected gastric cancer].

Randomized controlled trials (RCT) on adjuvant chemotherapy for gastric cancer published in the West and Japan were reviewed. Although several small trials showed positive data, adjuvant chemotherapy for curatively resected gastric cancer has been thought to be ineffective in western countries. Results of Japanese RCTs also have not become evidence of its benefit. Despite this, suggestive data by non-predefined subset analyses of old RCTs have been misread as definitive evidence of benefit because of less understanding of clinical statistics in Japan. As a result most Japanese patients have received postoperative adjuvant chemoimmunotherapy. Recently understanding of clinical trial has spread gradually and well designed RCTs with sufficient sample size have been reported. First of all we have to determine the efficacy of adjuvant chemotherapy by carefully designed RCT using surgery alone arm as control.

Antineoplastic Combined Chemotherapy Protocols↗

Oncological quality and preliminary long-term results in laparoscopic colorectal surgery.

BACKGROUND: Our aim here was interpret data on the perioperative course, oncological quality, and preliminary long-term results of laparoscopic colorectal surgery carried out with a curative intent. METHODS: The data were collected within the framework of a prospective multicenter observational study that has been ongoing since 1 Aug 1995 and includes 46 hospitals. Of a total of 3133 patients, 826 (26.4%) underwent a curative resection for colorectal carcinoma. RESULTS: The average age of the patients was 67.9 years; the sex distribution was almost 1:1. UICC staging of tumors (stages I, II, and III) showed the following figures: 301/36.4%, 265/32.1%, and 260/31.5%. In the majority of cases, an oncologically radical resection with high transection of the supplying vessels was performed. Intraoperative seeding of tumor cells was reported in 1.8% of the patients. In eight cases, the seeding was due to spontaneous rupture of the tumor. A mean of 13.5 lymph nodes in the resected specimen were investigated histopathologically (10.9 lymph nodes in stage I, 15 each in stages II and III). Depending on the individual hospital, we found a remarkable variation in the number of lymph nodes investigated. With a mean follow-up period of 2.1 years, Kaplan-Meier survival function showed acceptable results, both for rectal and colonic carcinoma, in comparison with conventional colorectal surgery. A stage-related consideration of the survival data yielded similar results. CONCLUSION: All in all, the results show that a laparoscopic colorectal procedure can meet oncological radicality criteria, even though certain reservations-in particular, in the case of procedures done with a curative intent-have not been completely eliminated.

Aged↗

Patterns of recurrence after curative resection of carcinoma of the colon and rectum.

Data on 818 patients who had undergone curative resection for Dukes' B2 or Dukes' C carcinoma of the colon and rectum were analyzed to determine the timing and patterns of recurrence based on such tumor characteristics as location, Dukes' stage, grade, ploidy and the presence of obstruction, perforation or adherence to adjacent organs or tissues. Three hundred and fifty-three patients (43 per cent) had recurrent disease. There was recurrence in 52 per cent of patients with carcinoma of the rectum and in 40 per cent of patients with carcinoma of the colon. The median time to recurrence for all patients was 16.7 months, with a range from 1 month to 7.5 years. Dukes' C lesions and the presence of adhesion or invasion, or both, or perforation were associated with significantly earlier recurrence. Among patients with recurrence, the most frequent sites were hepatic in 33 per cent, pulmonary in 22 per cent, local or regional, or both, in 21 per cent, intra-abdominal in 18 per cent, retroperitoneal in 10 per cent and peripheral lymph nodes in 4 per cent. Rectal primary sites, when compared with colonic, had proportionally more local or regional, or both, recurrences (p = 0.00003) and fewer involving retroperitoneal nodes (p = 0.022). Both primaries of the rectum and colon at stage C, when compared with stage B, had fewer local or regional recurrences, or both (p = 0.01), but a greater tendency to involve retroperitoneal or peripheral nodes. Primaries of the colon with adhesion to, or invasion of, adjacent organs had a lesser tendency to pulmonary metastasis (p = 0.036). Whereas the grade of anaplasia and ploidy had a strong influence on the rate of recurrence, they did not influence timing or patterns of recurrence. Patterns of recurrence based on the characteristics of the tumor may facilitate selection of the most appropriate adjuvant procedures, particularly those directed toward local or regional recurrence, or both, and also may guide efforts at early recognition of recurrence.

Adenocarcinoma↗

The Mouse Genome Database (MGD): integrating biology with the genome.

The Mouse Genome Database (MGD) is one component of the Mouse Genome Informatics (MGI) system (http://www.informatics.jax.org), a community database resource for the laboratory mouse. MGD strives to provide a comprehensive knowledgebase about the mouse with experiments and data annotated from both literature and online sources. MGD curates and presents consensus and experimental data representations of genetic, genotype (sequence) and phenotype information including highly detailed reports about genes and gene products. Primary foci of integration are through representations of relationships between genes, sequences and phenotypes. MGD collaborates with other bioinformatics groups to curate a definitive set of information about the laboratory mouse and to build and implement the data and semantic standards that are essential for comparative genome analysis. Recent developments in MGD discussed here include an extensive integration of the mouse sequence data and substantial revisions in the presentation, query and visualization of sequence data.

Animals↗

Benchmarking Assembly-Free K-mer Methods for Species Identification in Complex Plant Groups: A Case Study in Populus.

Species identification in taxonomically complex plant groups is frequently limited by the inadequacy of organellar markers, whose phylogenetic signal is disrupted by cytonuclear discordance and chloroplast capture. Using the taxonomically complex genus Populus as a model, we evaluated an assembly-free k-mer workflow against a curated SNP reference benchmark. Whole-genome resequencing data from 235 Populus individuals were curated to a 202-individual, 34-species reference dataset in which all retained species are strictly monophyletic in a genome-wide SNP analysis. Independent maximum likelihood analyses further confirmed that the 31 non-hybrid backbone species each maintained high-support monophyly, while taxa of documented reticulate origin showed placement patterns consistent with their reticulate histories. ABBA-BABA D-statistics detected widespread residual allele sharing within the backbone, though the strongest signals did not correspond to the species pairs responsible for the few k-mer identification failures. Against this benchmark, complete plastomes showed limited resolution, recovering only 3.0% species monophyly and 71.1% nearest-neighbor assignment. The optimized k-mer workflow, operating directly on raw reads without assembly or alignment, recovered 91.2% species monophyly, 99.0% nearest-neighbor assignment, and 98.0% group-average assignment. K-mer length was the primary accuracy-controlling parameter, with k = 31 falling within a stable accuracy plateau. Distance-based metrics reached near-saturation at 0.2&#xd7; sequencing depth, indicating that low-coverage genome skimming can support scalable nuclear genome-based identification with standard computational resources. K-mer distance heatmaps also flagged unusual genomic affinities in hybrid-origin and outlier samples, providing a rapid screen for subsequent population genomic analyses. These results support assembly-free k-mer distances as an efficient tool for reference-based species identification and sample screening in complex plant groups, with residual limitations concentrated near recently diverged species boundaries. Model-based phylogenomic, coalescent, and network analyses remain necessary for resolving deeper species relationships and detailed introgression histories.

Populus↗

The EMBL Nucleotide Sequence Database. Contributing and accessing data.

The European Molecular Biology Laboratory Nucleotide Sequence Database receives sequence and sequence annotation data from genome projects, sequencing centers, individual scientists, and patent offices. Data may be most efficiently submitted to the database using the Internet based submission tool WEBIN or via previously established genome project accounts. Biologist curators will review the data and provide accession numbers within two working days. Non-confidential data are exchanged daily in an international collaboration between EMBL. DDBJ (the DNA Databank of Japan) and GenBank (USA) and may be accessed and retrieved via the Internet with the Sequence Retrieval System (SRS). Sequence database searching algorithms (e.g., Blitz, Fasta, Blast) are available for comparison of query to database sequences.

Amino Acid Sequence↗

Presentation and prognosis of gastric cancer in patients aged 80 years and older.

The aim of this study was to analyze the characteristics of the presentation and prognosis of patients aged >/= 80 who were diagnosed with gastric adenocarcinoma. We have used a retrospective cohort study of 2334 patients diagnosed between 1975 and 1993 in northwestern Spain, 263 (11.3%)of whom were >/= 80 years of age. No differences were observed with respect to patients of a younger age at diagnosis regarding the site of the tumor, extension of the disease, or Laurén's histologic type. However, fewer resections with curative intent were performed in the older group (49.1% vs. 30.1%; p < 0.0001). Among those operated on with curative or palliative intent, at the end of the first month the survival probability was 0.9 and the 0.95% confidence interval (CI 95%) was 0.93-0.97 for patients < 80 years of age and 0.93 (CI 95% 0.89-0.98) for the older group ( p = 0.19). At the end of 5 years of follow-up these probabilities were 0.29 (CI 95% 0.27-0.31) and 0.18 (CI 95% 0.14-0.23), respectively ( p < 0.0001). If we consider only those patients undergoing curative resection, the survival probability for the two groups ( p = 0.4) was not statistically different. In conclusion, although the two groups showed similar characteristics at presentation, patients >/= 80 years of age underwent surgery with curative intent less frequently and their general prognosis was worse. Our data support the idea that curative surgery should not be ruled out exclusively for reasons of age.

Adenocarcinoma↗

The Zebrafish Information Network: the zebrafish model organism database.

The Zebrafish Information Network (ZFIN; http://zfin.org) is a web based community resource that implements the curation of zebrafish genetic, genomic and developmental data. ZFIN provides an integrated representation of mutants, genes, genetic markers, mapping panels, publications and community resources such as meeting announcements and contact information. Recent enhancements to ZFIN include (i) comprehensive curation of gene expression data from the literature and from directly submitted data, (ii) increased support and annotation of the genome sequence, (iii) expanded use of ontologies to support curation and query forms, (iv) curation of morpholino data from the literature, and (v) increased versatility of gene pages, with new data types, links and analysis tools.

Animals↗

Prognostic power of Doppler perfusion index in colorectal cancer. Correlation with survival.

OBJECTIVE: The authors assessed the relative value of Dukes' staging and Doppler perfusion index (DPI) as prognostic indices of early death in patients with colorectal cancer who have had apparently curative surgery. SUMMARY BACKGROUND DATA: Dukes' classification is recognized as the gold standard against which other prognostic factors should be compared; however, its discriminatory power is limited. No established method exists for accurately identifying patients who, despite having undergone an apparently curative resection for colorectal carcinoma, are at high risk. METHODS: Eighty consecutive patients undergoing apparently curative surgery for colorectal cancer were staged using Dukes' classification. In addition, DPI (ratio of hepatic arterial to total liver blood flow) was measured before surgery by means of a duplex/color Doppler sonography. RESULTS: On the basis of 2-year follow-up data, Dukes' classification failed to define clearly those patients who died or who developed recurrent disease. In contrast, DPI clearly identified two groups of patients: 78% of patients with an abnormally elevated DPI value developed recurrent disease or died, whereas 97% of patients with a normal DPI value survived. CONCLUSION: This technique can identify patients at high risk for colorectal cancer, after having undergone apparently curative resection, who would be suitable for adjuvant therapy.

Colorectal Neoplasms↗

The Lipid Interactome: an interactive and open access platform for exploring cellular lipid-protein interactions.

SUMMARY: Lipid-protein interactions play essential roles in cellular signaling and membrane dynamics, yet their systematic characterization has long been hindered by the inherent biochemical properties of lipids. Recent advances in functionalized lipid probes-equipped with photoactivatable crosslinkers, affinity handles, and photocleavable protecting groups-have enabled proteomics-based identification of lipid interacting proteins with unprecedented specificity and resolution. Despite the growing number of published lipid interactomes, there remains no centralized effort to harmonize, compare, or integrate these datasets. The Lipid Interactome addresses this gap by providing a structured, interactive web portal that adheres to FAIR data principles-ensuring that lipid interactome studies are Findable, Accessible, Interoperable, and Reusable. Through standardized data formatting, interactive visualizations, and direct cross-study comparisons, this resource enables researchers to systematically explore the protein-binding partners of diverse bioactive lipids. By consolidating and curating lipid interactome proteomics data from multiple studies, the Lipid Interactome database serves as a critical tool for deciphering the biological functions of lipids in cellularsystems. AVAILABILITY AND IMPLEMENTATION: This site can be viewed at LipidInteractome.org. All data are available for download. No user information is collected or necessary for data navigation, interaction, or download.

Proteins↗

Follow-up strategies for patients treated for non-metastatic colorectal cancer.

BACKGROUND: It is common clinical practise to follow patients with colorectal cancer (CRC) for several years following their definitive surgery and/or adjuvant therapy. Despite this widespread practice there is considerable controversy about how often patients should be seen, what tests should be performed and whether these varying strategies have any significant impact on patient outcomes. OBJECTIVES: To review the available evidence concerning the benefits of intensive follow-up of colorectal cancer patients with respect to survival. Secondary endpoints include time to diagnosis of recurrence, quality of life and the harms and costs of surveillance and investigations. SEARCH STRATEGY: Relevant trials were identified by electronic searches of MEDLINE, EMBASE, CINAHL, CANCERLIT, Cochrane Controlled Trials Register, Science Citation Index, conference proceedings, trial registers, reference lists and contact with experts in the field. SELECTION CRITERIA: Only randomised controlled trials comparing different follow-up strategies for patients with non-metastatic CRC treated with curative intent were included. DATA COLLECTION AND ANALYSIS: Trial eligibility and methodological quality were assessed independently by the three reviewers. MAIN RESULTS: Five trials were included. There was evidence that an overall survival benefit at 5 years exists for patients undergoing more intensive follow-up (OR = 0.67, 95% confidence interval 0.53 - 0.84; RD = -0.07, CI -0.12 - -0.02). The absolute number of recurrences was similar (OR = 0.91; 95% confidence interval 0.72 - 1.14; RD = 0.00, CI -0.07 - 0.07) and although the weighted mean difference for the time to recurrence was significantly reduced by 6.75 (95% confidence interval -11.06 - -2.44) there was significant heterogeneity between the studies. Analyses demonstrated a mortality benefit for performing more tests versus fewer tests (OR = 0.66; 95% confidence interval 0.46 - 0.95) and liver imaging versus no liver imaging (OR = 0.66; 95% confidence interval 0.46 - 0.95). However when both these results are expressed as a risk difference this significance is lost (RD = -0.06; CI -0.25 - 0.13). No useful data on quality of life, harms or cost-effectiveness were available for further analysis. REVIEWER'S CONCLUSIONS: The results of our review suggest that there is an overall survival benefit for intensifying the follow-up of patients after curative surgery for colorectal cancer. Because of the wide variation in the follow-up programmes used in the included studies it is not possible to infer from the data the best combination and frequency of clinic (or family practice) visits, blood tests, endoscopic procedures and radiological investigations to maximise the outcomes for these patients. Nor is it possible to estimate the potential harms or costs of intensifying follow-up for these patients in order to adopt a cost-effective approach in this clinical area. Large clinical trials underway or about to commence are likely to contribute valuable further information to clarify these areas of clinical uncertainty.

Clinical Protocols↗

Role of splenectomy in gastric cancer surgery: adverse effect of elective splenectomy on longterm survival.

BACKGROUND: Splenectomy, and in some cases pancreatico splenectomy, has been advocated by surgeons in an effort to improve clearance of metastatic nodes to splenic hilum (node 10) and splenic artery (node 11). Although splenectomy has known effects on increasing morbidity and even mortality after a variety of surgical maneuvers including gastrectomy, the longterm effect on survival is controversial. The purpose of this study is to review and analyze the effect of splenectomy on survival in patients having curative gastrectomy for stomach cancer. METHODS: We reviewed the role of splenectomy in patients having curative gastrectomy in a data base of stomach cancer patients that had been collected in 1987 as part of an American College of Surgeons Patterns of Care Study. This analysis had involved 18,344 patients, of whom 11,252 were first diagnosed in 1982 as part of a longterm study, and 7,092 were first diagnosed in 1987 as part of a shortterm study. From the two data collection periods information was available on 12,439 patients who received cancer directed abdominal surgery; 21.2% of these patients received a splenectomy. Among the 3,477 patients reported as having a curative gastrectomy (pathologically clear margins), 26.2% received a splenectomy. RESULTS: The operative mortality was 9.8% with splenectomy and 8.6% without splenectomy. In patients having a curative gastrectomy, the 5-year observed survival rate was 20.9% in patients having splenectomy versus 31% in patients who did not receive splenectomy (p < 0.0001). Examination of differences in survival by stage of diagnosis showed significantly reduced survival outcomes among patients with stage II and III, but not for those diagnosed with stage I or IV disease. The pattern of recurrence was moderately different with a larger proportion of patients having distant metastases among the group of patients who had undergone splenectomy compared with the patients who had not, 29% and 15.5%, respectively. Whether these differences are inherent in the splenectomy or in the associated cofactors was not determined in this study. CONCLUSIONS: The data suggest elective splenectomy should generally be avoided in patients with stage II and III gastric cancer. In patients with resectable proximal advanced (stage IV) cancer or who have extension to spleen and pancreas or macroscopic nodal metastases to splenic hilum, splenectomy might be necessary to facilitate complete removal of the tumor in an effort to achieve longterm tumor control. The importance of surgical judgment is emphasized as the major deciding factor in determining the need for splenectomy in the individual cancer patient.

Elective Surgical Procedures↗