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PubMed2006

The Common Data Elements for cancer research: remarks on functions and structure.

OBJECTIVES: The National Cancer Institute (NCI) has developed the Common Data Elements (CDE) to serve as a controlled vocabulary of data descriptors for cancer research, to facilitate data interchange and inter-operability between cancer research centers. We evaluated CDE's structure to see whether it could represent the elements necessary to support its intended purpose, and whether it could prevent errors and inconsistencies from being accidentally introduced. We also performed automated checks for certain types of content errors that provided a rough measure of curation quality. METHODS: Evaluation was performed on CDE content downloaded via the NCI's CDE Browser, and transformed into relational database form. Evaluation was performed under three categories: 1) compatibility with the ISO/IEC 11179 metadata model, on which CDE structure is based, 2) features necessary for controlled vocabulary support, and 3) support for a stated NCI goal, set up of data collection forms for cancer research. RESULTS: Various limitations were identified both with respect to content (inconsistency, insufficient definition of elements, redundancy) as well as structure--particularly the need for term and relationship support, as well as the need for metadata supporting the explicit representation of electronic forms that utilize sets of common data elements. CONCLUSIONS: While there are numerous positive aspects to the CDE effort, there is considerable opportunity for improvement. Our recommendations include review of existing content by diverse experts in the cancer community; integration with the NCI thesaurus to take advantage of the latter's links to nationally used controlled vocabularies, and various schema enhancements required for electronic form support.

Biomedical Research↗
PubMed1999

Association of preoperative biliary stenting with increased postoperative infectious complications in proximal cholangiocarcinoma.

BACKGROUND: The indications for preoperative biliary stenting in patients with obstructive jaundice are controversial. We evaluated the effect of preoperative biliary stenting on bacterobilia and infectious complications following surgical treatment of proximal cholangiocarcinoma. DESIGN: A retrospective review was performed of all patients undergoing surgical treatment of proximal cholangiocarcinoma. SETTING: A metropolitan cancer surgery service. PATIENTS AND METHODS: Seventy-one patients underwent palliative biliary bypass or curative resection of proximal cholangiocarcinoma from March 1, 1991, to April 1, 1997, and were entered into a prospective database. Forty-one patients underwent preoperative biliary intubation and stent placement. We analyzed patient, nutritional, laboratory, and operating room factors. Statistical evaluation was performed using Student t test and chi2 analysis. MAIN OUTCOME MEASURE: Data were recorded for a history of cholangitis, operative time, amount of blood loss, incidence of intraoperative bacterobilia, proportion of patients with postoperative infectious and noninfectious complications, and length of hospital stay. RESULTS: All patients (n = 14) with a history of preoperative cholangitis had been subjected to previous endoscopic retrograde cholangiopancreatography and/or percutaneous transhepatic biliary drainage. Groups were equivalent for risk for comorbidity, proportion undergoing curative vs palliative procedures, time spent in the operating room, and amount of blood loss. Patients with stents had a significantly lower bilirubin level (P = .005). Patients with stents had a significantly increased risk for bacterobilia (P = .001) and infectious complications (P = .03). Bacterobilia was present in 11 (100%) of 11 patients undergoing endoscopic stenting and in 15 (65%) of 23 patients undergoing percutaneous stenting. There was no increased risk for noninfectious complications, length of hospital stay, or mortality in patients with stents. In 10 (59%) of 17 patients with postoperative infectious complications and positive findings of intraoperative bile culture, the organism was synonymous. CONCLUSIONS: Preoperative biliary stenting in proximal cholangiocarcinoma increases the incidence of contaminated bile and postoperative infectious complications. Endoscopic stents frequently do not relieve jaundice in high biliary obstruction and are rarely indicated, especially in light of their high contamination rate.

Aged↗
PubMed2005

Data-poor categorization and passage retrieval for gene ontology annotation in Swiss-Prot.

BACKGROUND: In the context of the BioCreative competition, where training data were very sparse, we investigated two complementary tasks: 1) given a Swiss-Prot triplet, containing a protein, a GO (Gene Ontology) term and a relevant article, extraction of a short passage that justifies the GO category assignment; 2) given a Swiss-Prot pair, containing a protein and a relevant article, automatic assignment of a set of categories. METHODS: Sentence is the basic retrieval unit. Our classifier computes a distance between each sentence and the GO category provided with the Swiss-Prot entry. The Text Categorizer computes a distance between each GO term and the text of the article. Evaluations are reported both based on annotator judgements as established by the competition and based on mean average precision measures computed using a curated sample of Swiss-Prot. RESULTS: Our system achieved the best recall and precision combination both for passage retrieval and text categorization as evaluated by official evaluators. However, text categorization results were far below those in other data-poor text categorization experiments The top proposed term is relevant in less that 20% of cases, while categorization with other biomedical controlled vocabulary, such as the Medical Subject Headings, we achieved more than 90% precision. We also observe that the scoring methods used in our experiments, based on the retrieval status value of our engines, exhibits effective confidence estimation capabilities. CONCLUSION: From a comparative perspective, the combination of retrieval and natural language processing methods we designed, achieved very competitive performances. Largely data-independent, our systems were no less effective that data-intensive approaches. These results suggests that the overall strategy could benefit a large class of information extraction tasks, especially when training data are missing. However, from a user perspective, results were disappointing. Further investigations are needed to design applicable end-user text mining tools for biologists.

Computational Biology↗
PubMed2006

Influenza Virus Database (IVDB): an integrated information resource and analysis platform for influenza virus research.

Frequent outbreaks of highly pathogenic avian influenza and the increasing data available for comparative analysis require a central database specialized in influenza viruses (IVs). We have established the Influenza Virus Database (IVDB) to integrate information and create an analysis platform for genetic, genomic, and phylogenetic studies of the virus. IVDB hosts complete genome sequences of influenza A virus generated by Beijing Institute of Genomics (BIG) and curates all other published IV sequences after expert annotation. Our Q-Filter system classifies and ranks all nucleotide sequences into seven categories according to sequence content and integrity. IVDB provides a series of tools and viewers for comparative analysis of the viral genomes, genes, genetic polymorphisms and phylogenetic relationships. A search system has been developed for users to retrieve a combination of different data types by setting search options. To facilitate analysis of global viral transmission and evolution, the IV Sequence Distribution Tool (IVDT) has been developed to display the worldwide geographic distribution of chosen viral genotypes and to couple genomic data with epidemiological data. The BLAST, multiple sequence alignment and phylogenetic analysis tools were integrated for online data analysis. Furthermore, IVDB offers instant access to pre-computed alignments and polymorphisms of IV genes and proteins, and presents the results as SNP distribution plots and minor allele distributions. IVDB is publicly available at http://influenza.genomics.org.cn.

Databases, Genetic↗
PubMed1996

Heterogeneous effects of B7-1 and B7-2 in the induction of both protective and therapeutic anti-tumor immunity against different mouse tumors.

Experimental mouse tumors are classified as intrinsically immunogenic when, after a single injection into syngeneic mice as nonreplicating cell vaccines, they elicit a protective immune response against a subsequent lethal challenge. Tumors that do not retain this residual immunogenicity are defined as poorly immunogenic or nonimmunogenic. The expression of the B7-1 co-stimulatory molecule on immunogenic tumors can further increase their capacity to induce a T cell-dependent anti-tumor immunity, whereas it has limited effects on nonimmunogenic tumors. Recently, B7-2, a second molecule with an apparently similar co-stimulatory activity, has been cloned. In this report, we compare the efficiency of nonreplicating cells from one immunogenic and two nonimmunogenic mouse tumors transfected with B7-1 or B7-2 in the induction of protective and curative anti-tumor immunity. Immunogenic lymphoma cells expressing B7-1 or B7-2 are equally effective in both protecting against a subsequent challenge and curing established tumors. By contrast, nonimmunogenic adenocarcinoma and melanoma cells expressing B7-2 provide superior protective immunity, and only B7-2+ adenocarcinoma cells induce an efficient curative immunity. CD8+ and polymorphonuclear cells, but not CD4+ T cells, are critically involved in the rejection of the adenocarcinoma elicited by both B7-1+ and B7-2+ vaccines. These data indicate that B7-1 and B7-2 are not redundant co-stimulatory molecules and that, in these experimental models, B7-2 is superior to B7-1 in the induction of an efficient immunity when the immunogenicity of a tumor is a limiting factor.

Adenocarcinoma↗
PubMed2004

Non-functioning pituitary carcinoma.

Null-cell carcinomas of the pituitary are extremely rare. We describe a 41-year-old woman with a large adenohypophyseal neoplasm presenting as a primary nonfunctioning tumor without pituitary insufficiency. Signs of mass effect with progressive unilateral ocular motility disorders and anterior pituitary failure developed rapidly. Histopathological examination of the trans-sphenoidally removed tumor showed a primary pituitary null cell tumor with high mitotic index. Pituitary carcinoma was suspected because of rapid relapse of ocular motility disorders and of intra-sellar tumor growth after surgery. Radiotherapy of the sellar and parasellar area with a total dose of 59.4 Gy was performed, achieving marked tumor reduction and a significant improvement of ocular motility disorders. However, 6.5 months after presentation the patient rapidly declined and died of carcinomatous meningitis. Less than 100 pituitary carcinomas have been published so far, most of them as single-case reports, and endocrine, immunohistochemical, and ultrastructural data have not been described in the majority of cases. At presentation, there are no specific symptoms that allow to distinguish benign from malignant tumor. Prognosis is poor, since no curative treatment has been established, but aggressive surgery and radiotherapy has been recommended. Our case highlights the poor prognosis of nonfunctioning pituitary carcinomas.

Adult↗
PubMed2026

An atlas of non-redundant sequences and structures of transcription factor assemblies across domains of life.

Transcription factors (TFs) regulate gene expression by controlling the recruitment of transcriptional machinery to regulatory regions of the genome. Nearly 10% of the human genome encodes TFs, making them one of the largest protein families. Despite their central roles in gene regulation, TFs are historically considered challenging therapeutic targets due to their complex interactions with DNA, RNA and associated proteins. Although recent progress in studying TFs both at molecular and structural level excels our understanding on their function, yet a universal rule decoding their recognition process remains elusive. Here, we present a curated non-redundant dataset of TFs with 3570 sequences and 377 structures. We further characterize "unique interfaces" by quantifying interface identity across interacting chains in TF assemblies. Surprisingly, our data shows that the "unique interfaces" have optimal size ranging from 2000 Å2 to 4000 Å2 irrespective of their quaternary assembly. To understand the functional diversity, we integrate sequence motifs, structural domains, subcellular localization and functional enrichment of TFs. We have also catalogued association of TFs with various human diseases. Our dataset provides a comprehensive platform to perform large scale analysis of TF-assemblies and aid in computational methods for their prediction across domains of life.

Gene regulation↗
PubMed2005

Is it reasonable to add preoperative serum level of CEA and CA19-9 to staging for colorectal cancer?

BACKGROUND: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the most common tumor markers for colorectal cancer. The aim of this study was to evaluate the possibility of adding them into the current staging system by analyzing their prognostic significance. MATERIALS AND METHODS: The study population was patients (n = 574, 67.1 +/- 11.3 years old, 397 males) who received potentially curative resection of colorectal adenocarcinoma (stage I-III) between January 1994 and August 2002, including preoperative measurements of CEA and CA19-9. Clinicopathological characteristics and associated follow-up data were retrospectively collected by reviewing available medical charts. CEA higher or equal to 5 ng/ml was defined as abnormal (CEA+). The CA19-9 level was set at 37 U/ml (CA19-9+). Patients were further divided into four groups (1, 2, 3, 4) according to the results of these two markers (CEA/CA19-9: -/-, -/+, +/-, and +/+). Survival was analyzed for AJCC staging, CEA (+) versus (-), CA19-9 (+) versus (-), and four groups. RESULTS: CEA and CA19-9 survival curves were not significantly different. However, the combined use of the two markers revealed a significant survival benefit (P = 0.035) of group 1 ("-" for both markers) over 4 ("+" for both) in stage II. CONCLUSIONS: Patients with an elevated level of both CEA and CA19-9 in stage II of colorectal cancer have a significantly poorer prognosis than those with normal levels of these markers. We recommend adding both CEA and CA19-9 to the current staging system.

Adenocarcinoma↗
PubMed2005

Treatment-outcome for synchronous head-and-neck and oesophageal squamous cell carcinoma.

BACKGROUND AND PURPOSE: Although head & neck and oesophageal carcinomas occur synchronously in up to 12%, almost no data on feasibility and outcome after radiotherapy are available. MATERIALS AND METHODS: From 1989 to 2002, 24 patients were treated at Tuebingen University and Fulda hospital with a radiation based, curative approach. These were analyzed retrospectively. RESULTS: The median overall survival was 37 (1-69) months with a few long-term survivors with a median follow-up of 26 months for patients at risk. 7 local recurrences occurred. No major toxicity was seen. DISCUSSION: Even though the prognosis of synchronous head & neck and oesophageal carcinomas is grim, long-term survival is possible. A radiation-based approach is feasible and can be chosen for a curative treatment approach which we recommend.

Aged↗
PubMedDate not supplied

Does neoadjuvant chemoradiation downstage locally advanced pancreatic cancer?

Recent studies suggest that neoadjuvant chemoradiation can downstage locally advanced pancreatic tumors. There is limited evaluable data to support this approach. We review our experience with preoperative chemoradiation for surgically staged, locally advanced pancreatic cancer to determine whether patients are downstaged with multimodal therapy allowing for curative resection. A prospectively collected database from Memorial Sloan-Kettering Cancer Center was reviewed. Patients admitted between January 1993 and March 1999 with locally advanced pancreatic adenocarcinoma were identified (N = 163). Chemoradiation was administered to 87 (53.3%) of 163, and regimens varied from standard 5-fluorouracil/gemcitabine-based therapies to experimental protocols. Only three patients (3/87; 3.4%) had a sufficient clinical response on restaging to warrant reexploration. Of these, two thirds were unresectable on subsequent laparoscopy because of extensive vascular involvement or metastatic disease. Only one patient underwent a potentially curative resection, with a survival of 18 months despite negative margins and no nodal involvement. The overall median survival for all patients with locally advanced disease treated with chemoradiation was 11 months (6.5 months without multimodal therapy; P = 0.004). Although chemoradiation is associated with improved overall survival in locally advanced disease, it rarely leads to surgical "downstaging" allowing for potentially curative pancreatic resections. Novel multimodality approaches are required.

Adenocarcinoma↗
PubMed1998

How robust are district health systems? Coping with crisis and disasters in Rutshuru, Democratic Republic of Congo.

BACKGROUND: Since the eighties, the North Kivu Province socio-economic environment has been deteriorating. This province also faced an influx of Rwandan refugees in July 1994. The objective of the paper is to show how a rural health district has been able to adjust and maintain its medical activities under unfavourable conditions. METHOD: Performances of the local health system were assessed through the analysis of routine medical data collected in the Rutshuru Health District (RHD) between 1985 and 1995. Specific data collected during the Rwandan refugee crisis measured the workload of RHD due to the refugees. RESULTS: For 11 years, health infrastructures have remained accessible and functional in RHD. The curative utilization and preventive coverage rates increased. Obstetrical activities were intensified from a quantitative as well as from a qualitative point of view. Between July and October 1994, the RHD treated 65000 cases of various pathological conditions in Rwandan refugees settled outside the camps. This corresponds to 9.3% of consultations for Rwandan refugees settled on RHD's territory and represents a 400% increase in the curative workload for the RHD health services. Human and financial resources remained at a very low level, especially when compared with those available in the camps through relief agencies. CONCLUSION: The RHD was severely affected by various stresses but its services managed to provide significant and efficient response to these crises. Health district systems may constitute an effective tool to provide health care under adverse conditions.

Community Health Services↗
PubMed2002

Intrahepatic arterial infusion of chemotherapy: clinical results.

Approximately 60% of patients diagnosed with colorectal cancer (CRC) will go on to develop hepatic metastases. Although surgical resection is the only curative modality, a majority will not be able to undergo surgery. Alternative methods for treating this population have focused on the feasibility of hepatic arterial infusion (HAI) of chemotherapy. Randomized data in this field have been hampered due to small numbers of patients in some trials, or crossover between groups. However, most trials have suggested an improvement in both overall and progression-free survival with HAI therapy. Dose-limiting toxicity associated with HAI is related to hepatobiliary sclerosis, which has been reduced with the use of dexamethasone as part of the treatment. Current research is underway to improve the rate of extrahepatic metastases in patients undergoing HAI.

Antimetabolites, Antineoplastic↗
PubMed2025

Genomic Language Model for Predicting Enhancers and Their Allele-Specific Activity in the Human Genome.

Predicting and deciphering the regulatory logic of enhancers is a challenging problem, due to the intricate sequence features and lack of consistent genetic or epigenetic signatures that can accurately discriminate enhancers from other genomic regions. Recent machine-learning based methods have spotlighted the importance of extracting nucleotide composition of enhancers but failed to learn the sequence context and perform suboptimally. Motivated by advances in genomic language models, we developed DNABERT-Enhancer, a novel enhancer prediction method, by applying DNABERT pre-trained language model on the human genome. We trained two different models, using large collection of enhancers curated from the ENCODE registry of candidate cis-Regulatory Elements. The best fine-tuned model achieved 88.05% accuracy with Matthews correlation coefficient of 76% on independent set aside data. Further, we present the analysis of the predicted enhancers for all chromosomes of the human genome by comparing with the enhancer regions reported in publicly available databases. Finally, we applied DNABERT-Enhancer along with other DNABERT based regulatory genomic region prediction models to predict candidate SNPs with allele-specific enhancer and transcription factor binding activity. The genome-wide enhancer annotations and candidate loss-of-function genetic variants predicted by DNABERT-Enhancer provide valuable resources for genome interpretation in functional and clinical genomics studies.

Journal Article↗
PubMed1990

The myelodysplastic syndromes: current approaches to therapy.

PURPOSE: To review the current therapeutic options for patients with the myelodysplastic syndromes. DATA IDENTIFICATION: Studies reported between 1968 and September 1989 were identified through computer searches using MEDLINE and through extensive searching of bibliographies of identified articles. STUDY SELECTION: All articles, abstracts, and reviews were evaluated, and those that contained therapeutic data were analyzed for response rates, survival, and toxicity. RESULTS OF DATA SYNTHESIS: Therapies for the myelodysplastic syndromes have included hormones, chemotherapy, bone marrow transplantation, and differentiating agents, including hematopoietic growth factors. With the exception of bone marrow transplantation, none is curative or increases survival. Hematopoietic growth factors are of interest for clinical trials, because they increase the number of neutrophils and, occasionally, the number of platelets in patients with the myelodysplastic syndromes. Nonetheless, hematopoietic growth factors are not without toxicity; most notably, they are associated with a risk for acceleration to acute myeloid leukemia, and their effect on survival remains unknown. CONCLUSIONS: Standard therapy for the myelodysplastic syndromes is supportive care. When the disease progresses, patients with aggressive histologic or other poor-risk features should be considered for aggressive chemotherapy, with or without growth factors, or bone marrow transplantation. Patients with good prognostic features are candidates for therapy with growth factors or other potential differentiating agents. Carefully designed and conducted clinical trials that incorporate correlative laboratory science are essential to developing a more rational approach to therapy.

Antineoplastic Agents↗
PubMed1976

Occlusive mesenteric infarction. A retrospective study of 83 cases.

Acute mesenteric infarction was diagnosed clinically or post mortem in 83 patients over a 10 years period in 4 surgical departments. The present study is concerned with 56 of these patients who suffered occlusive disease of the mesenteric vessels and on whom sufficient data were available. Of these 17, patients had presented at least one symptom of chronic intestinal ischemia before the fatal exacerbation. Of 42 patients treated surgically 14 had operations with curative intend and 3 patients, all with venous thrombosis, survived after small bowel resection. Only 19 percent of the patients who underwent surgery were treated within 24 hours after onset of symptoms. Early diagnosis promptly followed by surgery might save some patients. A radical improvement of survival rate can however no be expected for the acute cases. More attention should be paid to the syndrome of abdominal angina, as elective arterial reconstruction in patients with chronic intestinal ischemia carries a low mortality and renders satisfactory results.

Acute Disease↗
PubMed2001

[Intratracheal lymphotropic ozone therapy in erosive-ulcerous tracheitis].

Under observation there were 452 patients with chronic stenosis of hollow organs of the neck having cannulas during the period from 3 months to several years. During the tracheobronchoscopic examination it was found that 35 patients had trachea ulcers, 46 patients had erosive tracheobronchitis. The ulcers were localized on the anterior wall of the thoracic part of the trachea. Their diameter was from 1 to 2.5 cm. The ulcers were accompanied by diffuse bilateral bronchitis of the II-III degree of the inflammation intensity. 2-3 ml of ozonated sodium chloride solution with the concentration of ozone in it 5 mg/l were introduced into the ulcer edges, i.e. lymphotropically, into the submucous membrane. The same solution (40-60 ml) was used for daily sanitation of the tracheobronchial tree. Complete epithelization of the ulcers and cleansing of the bronchial tree took 3-4 curative bronchoscopies.

Animals↗
PubMedDate not supplied

Modulation of liver injury by interleukin-10.

Inflammation is commonly observed in liver diseases and is frequently complicated by fibrosis and cirrhosis in end-stage disease. The only curative treatment for cirrhotic patients is liver transplantation. However, organ shortage as well as an increasing organ demand call for early treatment of liver disease and prevention of fibrosis. Experimental data have shown the critical role of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in the development of liver injury. Here, we review our work on the role of endogenously produced interleukin-10 (IL-10), a potent anti-inflammatory cytokine, in several experimental models of acute and chronic liver injury. First, in acute macrophage-mediated hepatitis induced by galactosamine/lipopolysaccharide administration, IL-10 neutralisation led to a more severe liver damage, whereas IL-10 injection, even delayed, was able to limit liver necrosis. A similar protective effect of IL-10 was observed in acute T cell-mediated hepatitis induced by concanavalin A (Con A) injection. The immunoregulatory role of IL-10 was then established after repeated exposition to Con A. In carbon tetrachloride liver injury, two other properties of IL-10 have been suggested: modulation of hepatocyte proliferation and modulation of liver fibrosis. Finally, the potential therapeutic applications in human liver disease as well as the potential side effects are discussed.

Animals↗
PubMed1955

Detection of cancer of the lung; results of a chest x-ray survey in Los Angeles.

In a mass survey by x-ray minifilm in Los Angeles County, apparently suspicion of cancer of the lung was reported in more than 90 per cent of cases in which the condition existed. Of the patients who were appropriate for resection with intent to cure, 35.8 per cent had "three-year cures." This high cure rate indicates that if the condition is detected early by the survey method and "curative" operation is done, cure rate for lung cancer may be much higher than is usually thought.

Data Collection↗