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At least 145 records · Page 8Linked to original sources

Outcomes for endoscopic resection of sinonasal squamous cell carcinoma.

OBJECTIVES: Preliminary data suggest efficacy for the endoscopic approach for sinonasal malignancy. The purpose of this study is to evaluate the effectiveness of the endoscopic approach for the resection of sinonasal squamous cell carcinoma (SCC). STUDY DESIGN: Retrospective analysis of patients undergoing endoscopic resection of sinonasal SCC from August 1996 to May 2004. METHODS: Eleven patients were treated with curative intent. Demographic data, histopathology, extent of tumor involvement, and need for adjunctive radiation or chemotherapy were determined. Local recurrence (LR), distant metastasis, overall survival (OS), and disease-free survival (DFS) rates were calculated. RESULTS: The mean age for the patient population was 62.5 (52-85) years with a male:female ratio of 8:3. Multimodality therapy including radiation or chemotherapy was used in 8 of 11 (73%) patients. Seven patients were resected using strictly an endoscopic approach, whereas four required combined endoscopic and neurosurgical resection. LR and distant metastatic rates were 20% and 0%, respectively. OS and DFS were both 91%, with mean follow-up of 31.5 (range 6-88) months. CONCLUSIONS: Endoscopic resection in combination with multimodality therapy is an effective method for curative resection of sinonasal SCC. In this preliminary study, it facilitated complete resection with acceptable LR and DFS rates.

Aged↗

Sequence- and structure-based protein function prediction from genomic information.

Existing functional annotation transfer is fraught with inaccuracies that may hinder forward interpretation and mining of genomic data. Hand-curation of the annotation placed into databases is not practical. In lieu of experimental evidence, computational biological approaches offer high-throughput tools to predict function accurately; however, these methods are still notably deficient in defining and describing the complexity of protein function. Enriching genomic sequences obtained from sequencing efforts and expression array methods with protein function information and classification will be an efficient first step for incorporating genomic data into drug discovery programs.

Computational Biology↗

Topical metronidazole. A review of its use in rosacea.

UNLABELLED: Topical application of the antibacterial agent metronidazole is effective in the treatment of moderate to severe rosacea, although its mechanism of action has yet to be clearly established. Metronidazole preparations (0.75 and 1% cream, 0.75% gel and 0.75% lotion) were significantly more effective than placebo in patients with moderate to severe rosacea when administered to the affected area once or twice daily for 7 to 12 weeks. The mean number of papules and pustules decreased by between 48 and 65.1% during the treatment period. Reductions were fairly consistent regardless of formulation, strength or application frequency and were significant compared with placebo (p < 0.05). In 1 study, most of the overall effects of metronidazole were observed within the first 3 weeks. Although data are limited, topical metronidazole appears to improve inflammatory lesions and erythema as effectively as oral tetracyclines. Like tetracyclines, however, metronidazole has no effect on telangiectasia. Metronidazole 0.75% gel seems to be effective in maintaining remission of rosacea symptoms in patients successfully treated with both oral tetracycline and topical metronidazole. In the only study, 77% of patients treated with metronidazole gel compared with 58% of placebo recipients (p < 0.05) remained in remission 6 months after the tetracycline was stopped. The effects of topical metronidazole preparations on rosacea symptoms are palliative, not curative, but preliminary data suggest that relapse rates after cessation of therapy are no worse than those after cessation of oral oxytetracycline. Topical metronidazole formulations are generally well tolerated locally, with stinging, dryness, burning and itching reported in < or = 2% of patients. Because minimal concentrations of metronidazole are absorbed after topical administration, systemic adverse events and drug interactions seen with oral or intravenous metronidazole are unlikely. CONCLUSIONS: Topical metronidazole formulations are significantly more effective than placebo when used in the initial treatment of patients with moderate to severe rosacea. Furthermore, limited evidence suggests that the use of topical metronidazole alone may be as effective as oral tetracyclines against the disorder's inflammatory component. Therefore, for those patients with a preference for topical rather than oral therapy, the use of a topical metronidazole formulation must be a consideration.

Administration, Topical↗

Computerized nuclear morphometry is a useful technique for evaluating the high metastatic potential of colorectal adenocarcinoma.

BACKGROUND: Nuclear profiles have been reported to be useful prognostic predictors in various cancers. Data from computerized morphometry are objective and are quickly obtained by conventional microscopic analysis. However, this image analysis of nuclear features has been only rarely applied to investigations of colorectal adenocarcinoma. The aim of this study was to evaluate the correlation between the morphologic nuclear features and clinicopathologic parameters in cases of colorectal adenocarcinoma. METHODS: Morphometric nuclear features (nuclear area, perimeter, and shape) were analyzed in 343 patients with colorectal carcinoma and in 57 patients with colorectal adenoma. In each case, 300 nuclei of carcinoma or adenoma cells were analyzed on routine hematoxylin and eosin stained slides by means of a computer-assisted image analysis system that involved tracing the nuclear profiles (magnification x400) on a computer monitor. The morphometric data were compared with patients' survival, clinicopathologic status, and DNA ploidy pattern of tumors. RESULTS: The mean nuclear area (NA) enlarged from normal colorectal mucosa to adenoma and carcinoma (normal mucosa: n = 343, mean NA = 19 micrometer(2); adenoma: n = 57, mean NA = 34 micrometer(2); mucosal carcinoma: n = 15, mean NA = 45 micrometer(2); P < 0.001). In 343 colorectal carcinomas, NAs of cancer cells in tumors with lymphatic invasion, venous invasion, lymph node metastasis, or hepatic metastasis were significantly larger than those of cancer cells in tumors without such factors. The mean NA of DNA aneuploid tumors was larger than that of DNA diploid tumors (P < 0.001). The nuclear area of cancer cells was determined to be one of the independent prognostic factors in multivariate analysis (P < 0.001). Moreover, the large nuclear area of cancer cells was recognized as one of the risk factors of metachronous hematogenic metastasis in patients after curative surgery. CONCLUSIONS: Data from computerized morphometry are objective and can be obtained rapidly by conventional microscopic analysis. The nuclear area of cancer cells appears to predict 1) the ability of cancer cells to invade the microvessels in the colorectal wall and 2) the ability of cancer cells to metastasize to the lymph nodes or liver. Therefore, nuclear morphometry is beneficial in mass screening to select patients who are at risk of hematogenic or lymph node metastatic recurrence after curative surgery for colorectal carcinoma.

Adenocarcinoma↗

Prognostic value of the cyclin-dependent kinase inhibitor p27Kip1 in gastric cancer.

In the present study, the expression and prognostic role of p27 were immunohistochemically investigated in 413 curatively resected gastric carcinomas. Strong p27 expression in more than 50% of the tumour cells could be detected in 57.4% (n = 237) whereas 42.6% of the tumours (n = 176) only showed p27 expression in less than 50% of the tumour cells. No significant correlation could be observed between p27 expression and the prognostic parameters pT category, pN category, blood and lymphatic vessel invasion as well as with tumour histology. Concerning other cell cycle associated proteins, p27 expression was inversely correlated with p21 expression, however, there was no correlation either with cyclin D1 and cyclin E or with expression of p53, bcl-2 and tumour cell proliferation. Univariate survival analysis revealed a poorer prognostic outcome for patients with tumours expressing p27 in more than 50% of the tumour cells (p < 0.049). However, by multivariate analysis, this prognostic influence of p27 could not be verified as independent from the known prognostic parameters of the pTNM-system (p < 0.325). The present data on 413 curatively resected gastric carcinomas suggest, that expression of p27, analyzed alone or in combination with multiple cell cycle regulatory proteins, has no prognostic value in gastric cancer.

Adult↗

Annotation of the Drosophila melanogaster euchromatic genome: a systematic review.

BACKGROUND: The recent completion of the Drosophila melanogaster genomic sequence to high quality and the availability of a greatly expanded set of Drosophila cDNA sequences, aligning to 78% of the predicted euchromatic genes, afforded FlyBase the opportunity to significantly improve genomic annotations. We made the annotation process more rigorous by inspecting each gene visually, utilizing a comprehensive set of curation rules, requiring traceable evidence for each gene model, and comparing each predicted peptide to SWISS-PROT and TrEMBL sequences. RESULTS: Although the number of predicted protein-coding genes in Drosophila remains essentially unchanged, the revised annotation significantly improves gene models, resulting in structural changes to 85% of the transcripts and 45% of the predicted proteins. We annotated transposable elements and non-protein-coding RNAs as new features, and extended the annotation of untranslated (UTR) sequences and alternative transcripts to include more than 70% and 20% of genes, respectively. Finally, cDNA sequence provided evidence for dicistronic transcripts, neighboring genes with overlapping UTRs on the same DNA sequence strand, alternatively spliced genes that encode distinct, non-overlapping peptides, and numerous nested genes. CONCLUSIONS: Identification of so many unusual gene models not only suggests that some mechanisms for gene regulation are more prevalent than previously believed, but also underscores the complex challenges of eukaryotic gene prediction. At present, experimental data and human curation remain essential to generate high-quality genome annotations.

Animals↗

Neoadjuvant and adjuvant therapy for operable hepatocellular carcinoma.

OBJECTIVES: To determine the efficacy and adverse effects of different neoadjuvant and adjuvant therapies compared to surgery alone or surgery and placebo/supportive therapy when given to improve relapse and survival rates for operable hepatocellular carcinoma. SEARCH STRATEGY: Electronic databases, conference proceedings, bibliographies of identified publications. SELECTION CRITERIA: All truly randomised and quasi-randomised clinical trials that compared hepatocellular carcinoma patients who were given and not given neoadjuvant/adjuvant therapy as a supplement to curative liver resection. DATA COLLECTION AND ANALYSIS: Study data was extracted independently by two reviewers and discrepancies were resolved by consensus. A total of eight randomised controlled clinical trials were identified, totaling 548 randomised patients. Seven of the eight trials reported survival and disease-free survival curves and the results of hypothesis testing (log-rank test). The remaining trial reported only the mean survival times. None reported the hazard ratio and only one did a sample size calculation. The survival and disease-free survival curves were compared using their one, two and three-year survival rates, median survival times and the result of the hypothesis tests. MAIN RESULTS: The size of the randomised clinical trials ranged from 40 to 115 subjects. Both preoperative (neoadjuvant) and postoperative (adjuvant), systemic and locoregional (+/- embolization), chemo- and immunotherapy interventions were tested. None were comparable in terms of both treatment regimen and participants selected, so no pooling was done. Only one regimen using preoperative transcatheter arterial chemoembolization with doxorubicin was approximately duplicated. Seven of the eight trials reported no survival benefit from adjuvant therapy. Only one trial reported a statistically significant difference for survival and disease-free survival for the treatment arm, but the results of both its arms were very poor when compared to other studies. Two of the trials that did not report any absolute survival advantage reported statistically significant differences in disease-free survival. Five of the eight trials did not perform intention-to-treat analysis. The highest toxicity rate was in a trial using oral 1-hexylcarbamoyl 5-fluorouracil which resulted in 12 out of 38 subjects stopping because of adverse events. REVIEWER'S CONCLUSIONS: There is no evidence for efficacy of any of the adjuvant protocols reviewed. In order to detect a realistic treatment advantage, larger trials will have to be conducted.

Antineoplastic Agents↗

Primary bone lymphoma: treatment results and prognostic factors with long-term follow-up of 82 patients.

BACKGROUND: To the authors' knowledge, there is limited information on the preferred treatment and long-term prognosis of primary bone lymphomas (PBLs). All PBL cases treated at the study center between 1963 and 2003 were analyzed to determine patient, disease, and treatment factors that could affect outcome measured by overall survival (OS), cause-specific survival (CSS), and freedom-from-treatment failure (FFTF). METHODS: A total of 101 patients with PBL diagnosed at the study institution were identified. Nineteen patients were excluded because they transferred their treatment or follow-up to another center. Disease control, survival, and prognostic factors were analyzed for all 82 remaining patients. RESULTS: The median age of the patients was 48 years (range, 11-83 years). Approximately 80% presented with diffuse large-cell lymphoma (DLCL), and 81% presented with Ann Arbor Stage I or II disease. Approximately 57% were treated with combined modality therapy, 14% were treated with radiation therapy alone, and 30% were treated with chemotherapy alone. The median follow-up was 67 months (range, 2-280 months). The 5-year OS, CSS, and FFTF were 88%, 96%, and 81%, respectively. The 5-year OS for patients treated with combined modality versus single-modality therapy was 95% versus 78% (P = .013), and the 5-year FFTF for patients treated with combined modality versus single-modality therapy was 90% versus 67% (P = .025). The 5-year CSS for patients treated with combined modality versus single-modality therapy was 95% versus 83% (P = .065). Using a Cox regression for multivariate analysis, age < 40 years and use of combined modality therapy were found to be favorable prognostic factors for OS, CSS, and FFTF. CONCLUSIONS: To the authors' knowledge, the current study is the largest series of patients with PBL treated with modern curative modalities. The data demonstrate that primary lymphoma involving the bone has an excellent prognosis. Patients with PBL treated with combined modality versus single modality therapy were found to have a superior outcome, with a significantly better survival.

Adolescent↗

Hellenic National Mutation database: a prototype database for mutations leading to inherited disorders in the Hellenic population.

The exponential discovery rate of new genomic alterations, leading to inherited disorders, as well as the need for comparative studies of different population's mutation frequencies necessitates recording their population-wide spectrum in online mutation databases. We report the construction of the Hellenic National Mutation database (http://www.goldenhelix.org/hellenic), a prototype database derived from a multicenter academic initiative, aiming to provide high quality and up-to-date information on the underlying genetic heterogeneity of inherited disorders found in the Hellenic population. Database records include informative summaries of the various genetic disorders studied in the Hellenic population, focused in particular on their incidence in Greece, a comprehensive reference list, and a well-structured query interface, which provides easy access to the list of the different mutations responsible for the inherited disorders in the Hellenic population. Also, extensive links to the respective Online Mendelian Inheritance in Man (OMIM) entries and, when available, to the locus-specific databases are provided, so that the user can retrieve the maximum amount of information from a single website. Furthermore, the Hellenic National Mutation database design allows easy data entry and curation. Creation of the Hellenic National Mutation database will significantly facilitate molecular diagnosis of inherited disorders in Greece and will motivate further investigation of yet unknown genetic diseases in the Hellenic population.

Computational Biology↗

[Multivisceral resection of advanced colorectal cancer].

From 1 September to 1 January 1990, a total of 1232 patients underwent surgery for colorectal cancer. Resection was performed on 1112 (90.3%) patients. It was curative in 917 cases and palliative in 195. Multivisceral resection was necessary 82 times because of tumour infiltration of adjacent organs (curative: 69 cases; palliative: 13 cases). The complication rate (26.7% vs 27.5%) and mortality rate (3.4% vs 2.9%) were similar to those for curative resections without multivisceral extension. The 5-year survival rate was also similar in the two groups (58% vs 55%). These results show that curative multivisceral resections can lead to the same long-term results as conventional curative resections. These data are encouraging, and tumour infiltration of neighbouring organs should not be taken to demonstrate inoperability.

Abdominal Neoplasms↗

Clinicopathological feature and long-term prognosis of apocrine carcinoma of the breast in Japanese women.

Because of the rarity of apocrine carcinoma and lack of standardized criteria for the diagnosis, the definitive conclusions of clinicopathologic features and the prognosis has not been determined. We retrospectively examined data on 2091 curatively treated Japanese patients with primary breast carcinoma. Among them, 33 (1.6%) who had been diagnosed of apocrine carcinoma were reviewed. Compared with non-apocrine carcinoma, apocrine carcinoma was characterized by less positive rates of ER and PR, and by frequent rates of unilateral multicentric breast carcinoma with significant difference. The clinicopathological factors influencing 12-year survival rate were lymph node metastasis, lymphatic involvement and vascular involvement. There was no difference in survival rates at 10 years after operation between apocrine carcinoma and non-apocrine carcinoma. Our result shows unique hormone response and unilateral multicentricity are only typical clinicopathological features of apocrine carcinoma.

Breast Neoplasms↗

Comparative analysis of BAC and whole genome shotgun sequences from an Anopheles gambiae region related to Plasmodium encapsulation.

The only natural mechanism of malaria transmission in sub-Saharan Africa is the mosquito, generally Anopheles gambiae. Blocking malaria parasite transmission by stopping the development of Plasmodium in the insect vector would provide a useful alternative to the current methods of malaria control. Toward this end, it is important to understand the molecular basis of the malaria parasite refractory phenotype in An. gambiae mosquito strains. We have selected and sequenced six bacterial artificial chromosome (BAC) clones from the Pen-1 region that is the major quantitative trait locus involved in Plasmodium encapsulation. The sequence and the annotation of five overlapping BAC clones plus one adjacent, but not contiguous clone, totaling 585kb of genomic sequence from the centromeric end of the Pen-1 region of the PEST strain were compared to that of the genome sequence of the same strain produced by the whole genome shotgun technique. This project identified 23 putative mosquito genes plus putative copies of the retrotransposable elements BEL12 and TRANSIBN1_AG in the six BAC clones. Nineteen of the predicted genes are most similar to their Drosophila melanogaster homologs while one is more closely related to vertebrate genes. Comparison of these new BAC sequences plus previously published BAC sequences to the cognate region of the assembled genome sequence identified three retrotransposons present in one sequence version but not the other. One of these elements, Indy, has not been previously described. These observations provide evidence for the recent active transposition of these elements and demonstrate the plasticity of the Anopheles genome. The BAC sequences strongly support the public whole genome shotgun assembly and automatic annotation while also demonstrating the benefit of complementary genome sequences and of human curation. Importantly, the data demonstrate the differences in the genome sequence of an individual mosquito compared to that of a hypothetical, average genome sequence generated by whole genome shotgun assembly.

Amino Acid Sequence↗

IRIS: a database surveying known human immune system genes.

We have compiled an online database of known human defense genes: the Immunogenetic Related Information Source (IRIS). As of October 1, 2004, there are 1562 immune genes recorded in IRIS, representing 7% of the human genome. This resource contains searchable information including chromosomal location, sequence data, and a curated functional annotation for each entry. We used IRIS as a basis for analyzing the composition and characteristics of the immune genome, such as gene clustering, polymorphism, and relationship to disease. High protein sequence similarity correlated inversely with distance between immune genes, consistent with clustering of duplicated loci. We also found that, even though some immune genes exhibit high levels of polymorphism, such as MHC class I, the range of levels of polymorphism in immune genes is similar to that of nonimmune genes. Approximately 20% of immune genes have a known disease association. IRIS is available online at .

Databases, Genetic↗

Partial cystectomy for muscle invasive urothelial carcinoma of the bladder: a contemporary review of the M. D. Anderson Cancer Center experience.

PURPOSE: Partial cystectomy is a surgical option for select patients diagnosed with urothelial carcinoma. We review our experience with partial cystectomy for muscle invasive urothelial carcinoma to assess local control and survival rates. MATERIAL AND METHODS: From 1982 to 2003 a total of 37 patients with muscle invasive urothelial carcinoma underwent partial cystectomy with curative intent. Reviewed data included history of superficial tumors, presence of variant histology, tumor location, clinical stage, pathological stage, presence of carcinoma in situ, adjuvant therapy and disease status. RESULTS: The 5-year overall, disease specific and recurrence-free survival rates were 67%, 87% and 39%, respectively. Mean followup was 72.6 months (range 6 to 217). Of the 37 patients 19 (51%) did not have tumor recurrence, 9 (24%) had superficial recurrence in the bladder that was treated successfully and 9 (24%) had recurrence with advanced disease. A total of 24 patients (65%) had an intact bladder with no evidence of disease after a median of 53 months. There were 6 patients (16%) who died of bladder cancer, 3 of whom died of late recurrence of muscle invasive cancer (41, 44 and 138 months after partial cystectomy). On multivariate analysis higher pathological stage (HR 3.4, p = 0.04) was associated with shorter recurrence-free survival. A history of superficial tumors (p <0.01) and clinical stage (p = 0.01) was associated with advanced recurrence-free survival. The use of adjuvant chemotherapy (HR 0.18, p = 0.03) was associated with prolonged advanced recurrence-free survival, however adjuvant chemotherapy did not impact overall survival. CONCLUSIONS: Partial cystectomy provides adequate local control of muscle invasive bladder cancer in select patients. Because late recurrence is not uncommon and is potentially life threatening, lifelong followup with cystoscopy is recommended.

Adult↗

The role SWISS-PROT and TrEMBL play in the genome research environment.

SWISS-PROT, a curated protein sequence data bank, contains not only sequence data but also annotation relevant to a particular sequence. The annotation added to each entry is done by a team of biologists and comes, primarily, from articles in journals reporting the actual sequencing and sometimes characterisation. Review articles and collaboration with external experts also play a role along with the use of secondary databases like PROSITE and Pfam in addition to a variety of feature prediction methods. Annotation added by these methods is checked for relevance and likelihood to a particular sequence. The onset of genome sequencing has led to a dramatic increase in sequence data to be included in SWISS-PROT. This has led to the production of TrEMBL (Translation of the EMBL database). TrEMBL consists of entries in a SWISS-PROT format that are derived from the translation of all coding sequences in the EMBL nucleotide sequence database, that are not in SWISS-PROT. Unlike SWISS-PROT entries those in TrEMBL are awaiting manual annotation. However, rather than just representing basic sequence and source information, steps have been taken to add features and annotation automatically. In taking these steps it is hoped that TrEMBL entries are enhanced with some indication as to what a protein is, could or may be.

Amino Acid Sequence↗

Predictive design of tissue-specific mammalian enhancers that function in the mouse embryo.

Enhancers control tissue-specific gene expression across animals1. Although deep learning2,3 has enabled enhancer prediction and design in mammalian cell lines and non-mammalian model organisms4-10 (reviewed in a previous publication11), it remains unclear whether such approaches can operate within the regulatory complexity of mammalian genomes and tissues in vivo. Here we present a general strategy for designing tissue-specific enhancers that function reliably in mice. We use deep learning to train compact convolutional neural networks on curated chromatin accessibility data and fine-tune them by transfer learning on validated human and mouse enhancers. Guided by these models, we design 15 synthetic enhancers for the heart, limb and central nervous system in mouse embryos, all of which are active in their intended target tissue. These results demonstrate that mammalian enhancer function can be reliably inferred from DNA sequence alone, enabling the predictive de novo design of tissue-specific synthetic enhancers from modest training sets. This work establishes a generalizable framework for programmable control of mammalian gene expression in vivo, opening new avenues in functional genomics, synthetic biology and gene therapy.

Animals↗

The validity of quick intraoperative parathyroid hormone assay: an evaluation in seventy-two patients based on gross morphologic criteria.

BACKGROUND: Parathyroidectomy for primary hyperparathyroidism has conventionally required identification of all parathyroid glands with excision of grossly abnormal glands. Using this approach, cure rates exceed 95%. Directed cervical exploration has been advocated using quick intraoperative parathyroid hormone (QPTH) assay with preoperative localization. Adoption of this approach requires validation of the accuracy of QPTH assay. METHODS: Patients with primary hyperparathyroidism undergoing bilateral neck exploration during a 31-month period were reviewed. Uniglandular (UGD) or multiglandular (MGD) disease was determined by gross morphologic criteria. QPTH assays were performed before skin incision and at 5, 10, and 20 minutes after excision of each abnormal gland. A 10-minute QPTH decrease of 50% from baseline levels indicated curative excision. These data were not used to guide extent of exploration or tissue resection. RESULTS: Of 72 patients, 55 (76%) had UGD and 17 (24%) had MGD. QPTH assay accurately predicted the disease state in 89%. Four (7%) UGD patients did not have an appropriate QPTH decline at 10 minutes. Four (24%) MGD patients had an inappropriate QPTH decline at 10 minutes. CONCLUSIONS: Using QPTH guided exploration, 6% (4 of 72) of patients would undergo unnecessary extended exploration and 6% (4 of 72) (95% CI, 1% to 13%) may require reoperation for unidentified MGD. These results validate the accuracy of QPTH assay.

Calcium↗

Large-scale analysis of the human and mouse transcriptomes.

High-throughput gene expression profiling has become an important tool for investigating transcriptional activity in a variety of biological samples. To date, the vast majority of these experiments have focused on specific biological processes and perturbations. Here, we have generated and analyzed gene expression from a set of samples spanning a broad range of biological conditions. Specifically, we profiled gene expression from 91 human and mouse samples across a diverse array of tissues, organs, and cell lines. Because these samples predominantly come from the normal physiological state in the human and mouse, this dataset represents a preliminary, but substantial, description of the normal mammalian transcriptome. We have used this dataset to illustrate methods of mining these data, and to reveal insights into molecular and physiological gene function, mechanisms of transcriptional regulation, disease etiology, and comparative genomics. Finally, to allow the scientific community to use this resource, we have built a free and publicly accessible website (http://expression.gnf.org) that integrates data visualization and curation of current gene annotations.

Animals↗