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Sequence resources at the Candida Genome Database.

The Candida Genome Database (CGD, http://www.candidagenome.org/) contains a curated collection of genomic information and community resources for researchers who are interested in the molecular biology of the opportunistic pathogen Candida albicans. With the recent release of a new assembly of the C.albicans genome, Assembly 20, C.albicans genomics has entered a new era. Although the C.albicans genome assembly continues to undergo refinement, multiple assemblies and gene nomenclatures will remain in widespread use by the research community. CGD has now taken on the responsibility of maintaining the most up-to-date version of the genome sequence by providing the data from this new assembly alongside the data from the previous assemblies, as well as any future corrections and refinements. In this database update, we describe the sequence information available for C.albicans, the sequence information contained in CGD, and the tools for sequence retrieval, analysis and comparison that CGD provides. CGD is freely accessible at http://www.candidagenome.org/ and CGD curators may be contacted by email at candida-curator@genome.stanford.edu.

Candida albicans↗

[Surgical treatment of colonic cancer after 75 years of age. Study of a series of 240 patients].

AIM OF THE STUDY: The aim of this retrospective study was to report the results of the surgical treatment for large bowel cancer in patients over 75 years of age. PATIENTS AND METHOD: From 1985 to 1996, 240 patients. 114 men and 126 women, aged 75 years or over (mean age: 82, range: 75 to 95 years) underwent surgical treatment for large bowel carcinoma. Tumors were located in the right colon (n = 120), left colon (n = 100), transverse colon (n = 5), or were multiple (n = 15). Clinical presentation was failure of general condition (25%), intestinal obstruction (20%), rectal bleeding (20%), abdominal pain (17%). ASA score was I (n = 1), II (n = 69), III (n = 134), or IV (n = 36). Emergency surgery was mandatory in 110 cases (43 urgent and 67 delayed procedures) and 130 patients underwent elective surgery. Surgical resection was performed in 221 cases, including 177 cases with curative intent (67%). Surgical procedures included right colectomy (n = 119), left colectomy (n = 59), transverse colectomy (n = 9) or subtotal colectomy (n = 31). Histopathological staging was Astler--Coller A (n = 8), B (n = 116), C (n = 54) et D (n = 62). RESULTS: The postoperative course was uneventful in 157 cases (65.4%). Medical complications occurred in 46 patients with 34 deaths; and surgical complications in 39 patients with 20 subsequent reoperations and 15 deaths. The overall postoperative mortality rate was 20.4% (n = 49). Postoperative mortality rate was higher after emergency operations (32.7% vs 10%), higher with the level of ASA grading (class II: 8.6%, Class III: 17.1%, Class IV: 38.8%), higher in patients over 90 years (37.4% vs. 19.1%) and in patients without surgical resection (42% vs 18.5%). Disease specific 5-year survival rate was 45% and did not differ when compared to patients younger than 75 years (42%, data not reported). CONCLUSIONS: Patients older than 75 years remain a high risk group, specially if operated on emergency. Nevertheless, age is not a limiting factor in the surgical treatment of colon cancer. Prognosis is mostly depending on ASA grading. Colectomy with curative intent has to be performed when possible.

Age Factors↗

Quality control in the discovery, reporting, and recording of genomic variation.

The usefulness of any database is dependent on the quality of its content. This is so for mutation databases and has been a continuing concern for those interested in such databases. This article discusses the critical points that determine the quality of the data, such as PCR errors, incomplete scanning, examination of the effect of the variation, and reporting and deposition of the mutations in a database. To illustrate the importance of quality control in mutation curation, nine articles reporting 34 novel phenylketonuria mutations were surveyed for the criteria believed to be important in describing mutations. Many articles were deficient in entries in several criteria, but there was still a high degree of certainty that the described mutations caused disease. Finally, strategies to eliminate errors and to enhance or indicate quality are discussed, including expression, the review process, checking deductions, and typing and encouraging compliance. Models for the future are also discussed.

DNA↗

Echogenicity of liver metastases from colorectal carcinoma is an independent prognostic factor in patients treated with regional chemotherapy.

BACKGROUND: Echogenicity of liver metastases was found to be a predictive biologic factor influencing long-term outcome after curative liver resection. The current analysis focuses on the influence of echogenicity on survival in patients treated with intraarterial chemotherapy for unresectable colorectal carcinoma liver metastases. METHODS: A retrospective analysis of prospectively collected data at the Department of Surgery at the University of New South Wales-affiliated St. George Hospital was performed. Two hundred twelve consecutive patients with unresectable hepatic metastases from colorectal carcinoma treated between May 1992 and September 2000 were analyzed. Echogenicity of metastases was measured intraoperatively using a 5 MHz probe. Overall survival difference was compared between hyper- and hypoechoic metastases on an intention-to-treat basis. RESULTS: At a median followup of 15.1 months, 47 patients (22%) were alive and 165 (78%) had died. A significant survival benefit was observed in patients having hyperechoic lesions (median survival 16.2 months, 95% confidence interval [CI] 13.9-18.5) compared to hypoechoic lesions (median survival 11.6 months, 95% CI 8-15.2), P < 0.01. Other prognostic factors were differentiation of the primary tumor (P < 0.02), percentage hepatic replacement (P < 0.05) and carcinoembryonic antigen decrease (P < 0.03). Echogenicity was identified as an independent prognostic factor in multivariate analysis (P < 0.009). CONCLUSIONS: Echogenicity is an important prognostic survival parameter.

Adult↗

Prognostic factors in the operative treatment of ductal pancreatic carcinoma.

BACKGROUND AND AIMS: The average 5-year survival rate following resection of a ductal adenocarcinoma of the pancreas is 10%, worldwide. Despite increasing resection rates, only about 20% can be operated on with curative intent. A differential histopathological analysis of the resected tumors may help to justify expanding the surgical procedure by extended lymph-node dissection. PATIENTS/METHODS: Between January 1986 and December 1995, a total of 113 patients underwent resection with curative intent for a ductal pancreatic carcinoma with regional lymph-node dissection. All histological findings were reviewed and reclassified in accordance with the 1997 Union Internationale Contra la Cancrum (UICC) classification. Survival data for all of these patients were obtained from family doctors and registration offices. Independent prognostic factors were statistically analyzed. RESULTS: Of the 113 patients, 93 received an R0 resection. The postoperative mortality rate was 2.2% (2 of 93). More than one-half of the tumors had a diameter of between 2.1 cm and 4 cm. Among the 22 tumors measuring up to 2 cm in diameter, 41% already had lymph-node metastasis and 86% invasion of the lymphatic vessels. Carcinomas measuring between 4.1 cm and 6 cm were all associated with lymph-vessel invasion. Perineural invasion was present in 50% of the tumors. A noteworthy finding was the fact that 64% of the 25 tumors with negative lymph nodes had lymph-vessel invasion, and 48% perineural invasion. The cumulative 5-year survival rate of the R0-resected patients was 10. 5%. Patients with lymph-node-negative stages survived significantly longer (26.5%) than patients with lymph-node-positive stages (5%). Furthermore, a significant difference was seen between pN1a and pN1b (16.7% vs 2.2%). Multivariate analysis identified tumor grading, tumor size and lymph vessel invasion as independent prognostic factors. CONCLUSIONS: Apart from the factors tumor size and tumor grading, lymph-vessel invasion appears to be of special significance for the long-term prognosis. Already in the pN0 stage, the latter was present in 64% of the cases and must be considered a precursor of lymphogenic metastasization. Since lymph-vessel invasion was demonstrated in 86% of tumors measuring less than 2 cm, the therapeutic consequence for all ductal pancreatic tumors is an extended lymphatic and soft tissue dissection that goes beyond the regional lymph-node stations.

Aged↗

Data mining for protein-protein interactions in invertebrate model organisms.

Well-annotated genome databases are available for many invertebrate species, notably the fruitfly, Drosophila melanogaster, and the nematode, Caenorhabditis elegans. An adequate interpretation of this information at the biological level requires the exploration of the interactions between the gene products. Knowledge of protein interactions and the components of cell signalling pathways in the fly and worm are particularly valuable as hypotheses can be rapidly tested using the powerful genetic toolkits available. Invertebrates offer additional experimental advantages when attempting to characterise protein-protein interactions (PPIs). Their relatively small genome size compared to mammals helps to reduce missed interactions due to redundancy, and their function can be addressed using forward (mutants) and reverse (RNA interference) genetics. However, the researcher looking for evidence of PPIs for a protein of interest is faced with the challenge of extracting interaction data from sources that are highly varied, such as the results of microarray experiments in the unstructured text of research papers. This challenge is greatly reduced by a range of public databases of curated information, as well as publicly available, enhanced search engines, which can provide either direct experimental evidence for a PPI, or valuable clues for generating new hypotheses.

Animals↗

The postoperative surveillance of patients with colon cancer and rectal cancer.

BACKGROUND: Colon cancer is relatively common; however, the results of treatment have marginally improved over the last half century. Though about 85% of patients have colorectal tumors resected with curative intent, a significant number of these patients will eventually die from cancer. As a result, many clinicians have advocated intensive follow-up in such patients as an attempt to increase survival. DATA SOURCES: A review of the literature focusing on studies that have specifically addressed postoperative surveillance programs in patients with colorectal cancer was conducted. Only studies with level A evidence were included. Further references were obtained through cross-referencing the bibliography cited in each work. CONCLUSION: One of the six prospective randomized studies demonstrated a statistically significant survival benefit. Undoubtedly, survival benefits can be shown with a well-designed evidence-based follow-up strategy. However, well-designed large prospective multi-institutional randomized studies are needed to establish a consensus for follow-up.

Colonic Neoplasms↗

Feasibility report for retreatment of locally recurrent head-and-neck cancers by combined brachy-chemotherapy using frameless image-guided 3D interstitial brachytherapy.

PURPOSE: Brachytherapy re-irradiation may offer an alternative re-treatment of recurrent head-and-neck cancer even after previous full dose radiation therapy. The purposes of this study were to determine the feasibility and accuracy of frameless image-guided interstitial needle implantation. METHODS AND MATERIALS: Between January 2000 and March 2003, 14 patients with biopsy-proven locally recurrent head-and-neck-cancer were retreated after previous full dose irradiation with combined external beam-brachytherapy with concomitant chemotherapy. Brachytherapy needle implantation was virtually planned taking into account the surrounding risk structures. Needles were implanted using an adapted frameless navigation system. Chemoradiotherapy was followed by 2-4 courses of chemotherapy every fourth week starting 4 weeks after the end of brachytherapy. RESULTS: The 1- and 2-year local control rates were 78% and 57%, respectively. Local control was obtained in 8/14 patients. The actuarial 1- and 2-year survival rates were 83% and 64%, respectively. The median survival was 28 months after a median follow-up of 21 months (range, 8-53). Six weeks after brachytherapy, 1 patient developed localized soft tissue necrosis which did not require surgical intervention. No additional grade III or IV late toxicity was seen after re-irradiation. Mean deviation of image-guided needle implantation was 3.4 mm for each needle (SD, 1.9 mm; range, 0.5-14 mm). The mean deviation of all needles of an implant was 4.3 mm (range, 2.3-8.6 mm). CONCLUSIONS: These data demonstrate that pulsed-dose-rate brachytherapy in combination with sequential chemotherapy is effective and safe in re-irradiation of locally recurrent oropharyngeal carcinomas and can be offered to patients with curative intent. Image guidance allows virtual planning and navigated implantation of brachytherapy needles with regard to optimized needle distribution and risk structures.

Adult↗

Investigating cross-organism prediction of prokaryotic essential proteins using unsupervised language model and ensemble strategy.

Cross-organism prediction of essential proteins is a critical task for drug discovery and microbial engineering, yet the generalizability of existing machine learning models across diverse species remains a significant challenge. In this study, we propose DeepPEP, a large language model-based framework designed to reliably transfer essential protein annotations between distantly related organisms. Utilizing 66 curated prokaryotic datasets, we systematically evaluated DeepPEP's cross-organism performance under various conditions. Initial pairwise predictions revealed a correlation between performance and evolutionary distance; however, further investigation demonstrated that integrating training data from multiple organisms yields superior predictive power. In a benchmark scenario designed to simulate real-world applications, DeepPEP outperformed the state-of-the-art tool Geptop 2.0, showcasing a robust ability to identify species-specific essential proteins. Finally, a case study on novel genomes confirmed the model's practical effectiveness. Our results suggest that DeepPEP is a powerful strategy for prokaryotic essential protein prediction, and the rigorous evaluation framework established in this study provides a new benchmark for the field.

Large Language Models↗

[Local recurrence in colon and rectal cancer].

Data on the incidence of colorectal cancer are alarming and reveal that it is currently the second cause of death from cancer. Most of these deaths are due to recurrence after surgery with curative intent. The factors associated with locoregional recurrence are mainly related to the tumor's histopathological characteristics and grade of invasion. With adequate training the surgeon should not appear among these factors. In rectal cancer this training involves the technique of mesorectal excision, adequate circumferential margin and selective neoadjuvant chemoradiotherapy. After curative resection, patients should be followed-up to detect asymptomatic recurrence. Isolated local recurrence occurs in 20-30% of patients, but even with liver or lung metastases curative surgery can be attempted and success depends on correct multidisciplinary preoperative evaluation. If the diagnosis is made when the tumor is in an incurable phase, the aim is to improve the patient's quality of life.

Colorectal Neoplasms↗

Radiotherapy for non-small cell lung cancer in patients aged 75 and over: safety, effectiveness and possible impact on survival.

For patients with advanced, inoperable non-small cell lung cancer (NSCLC), increasing age seems to be the primary reason of receiving no treatment. The elderly aged 75 years and over are more likely to be given only supportive care (irrespective of symptoms) or no therapy at all. We evaluated the outcome of 48 patients, aged 75 years and over, treated with radiation therapy for advanced (stage IIIA-B), inoperable, symptomatic NSCLC. A median dose of 50 Gy was delivered to the primary site and mediastinum with standard fractionation. Based on WHO criteria, of 47 assessable patients, 21 had partial remission, 17 stable disease, and nine had progressive disease. Most symptoms were successfully palliated. Toxicity was negligible and mainly consisted of WHO grade I-II esophagitis. Despite the overall median survival being short (5 months), dose-related survival was much better in patients given at least 50 Gy than in those treated with lower doses: 52% versus 35% at 6 months, and 28% versus 4% at 13 months. These results confirm that radiation therapy may be safely delivered to very aged patients with advanced NSCLC at not merely palliative doses, both to achieve better local control and to give likely survival benefits. Adequate pretreatment evaluation should be always performed to exclude any comorbidity unfit to chest radiation and to individualize treatment to the single patient requirements. Because a large amount of literature data now concurs with the feasibility and safety of high-dose radiotherapy in the elderly, specifically designed, age-oriented trials are needed to settle definitively the issue of survival advantage from curative radiotherapy in these patients.

Aged↗

Radiation therapy in tumors of the central nervous system.

OBJECTIVES: To review the role of radiation therapy in the management of primary tumors of the central nervous system (CNS). DATA SOURCES: Book chapters, review articles, and research studies. CONCLUSIONS: Radiation therapy plays an important role in the management of primary and metastatic tumors of the CNS. Radiation and surgery are combined with curative intent for low-grade tumors. Cranial radiation may be used to prevent brain metastases, and palliative radiation may be used to alleviate symptoms. IMPLICATIONS FOR NURSING PRACTICE: Helping patients with tumors of the CNS and their family members understand the anticipated side effects of the disease and the therapeutic goals of radiation therapy may help to alleviate anxiety and maintain an optimal quality of life during therapy.

Adult↗

Repeat liver resection for hepatocellular carcinoma.

BACKGROUND: Although hepatectomy has been accepted as a therapeutic option for the primary tumor of hepatocellular carcinoma (HCC), what role the second liver resection will play in the clinical care of patients with intrahepatic recurrence of HCC after the initial resection has not been well evaluated. STUDY DESIGN: In a retrospective review of the 6-year period between January 1991 and December 1996, records were examined of 94 patients who underwent curative liver resection for HCC. Of these, 57 patients had isolated recurrent disease to the liver; 12 of the 57 patients underwent repeat surgical resection and 45 patients received nonsurgical ablative therapy. Clinical data for these patients were reviewed for operative morbidity and mortality, survival, disease-free survival, and pattern of failure. RESULTS: There were no perioperative deaths during repeat liver resections for recurrent HCC. Operative morbidity in the second resection was comparable to the initial resection. The disease-free survival rate after the second hepatectomy was 31% at 2 years, significantly lower than that after initial hepatectomy (62%) (p = 0.009). The overall survival rate after the second hepatectomy was 90% at 2 years, in contrast to 70% after nonsurgical ablative treatment for recurrent HCC (p = 0.253). CONCLUSIONS: Although the second liver resection for recurrent HCC can be performed safely and may improve survival, the disease-free survival rate after such resection therapy is low. This likelihood of further recurrences encourages studies for the selection of patients who may benefit from repeat liver resection.

Aged↗

Diabetes is associated with increased perioperative mortality but equivalent long-term outcome after hepatic resection for colorectal cancer.

Diabetes is associated with alterations in liver metabolism and immune response that may influence postoperative recovery and long-term survival after hepatectomy for cancer. Patients with type I or type II diabetes mellitus submitted to a potentially curative hepatic resection for metastatic colorectal cancer were identified from the prospective database, and compared with patients with hepatic colorectal metastases submitted to resection during the same time interval, but without diabetes mellitus. Data on operative morbidity and mortality and long-term survival were analyzed. Between December 1990 and July 1999, a total of 727 patients underwent hepatic resection, 61 of whom (8.1%) had type I and type II diabetes mellitus. Operative mortality in the diabetic patients was significantly greater than in nondiabetic patients (8% vs. 2%, P < 0.02). Among patients with diabetes mellitus, four of the five perioperative deaths were due to liver failure after major hepatic resection (lobectomy or greater). All four of these patients had significant parenchymal abnormality (three with steatosis). Long-term survival was identical to that in nondiabetic control subjects. We conclude that the presence of diabetes is associated with a higher incidence of perioperative mortality. In patients with diabetes mellitus and parenchymal steatosis, major hepatic resection should be undertaken with caution.

Adult↗

The p53 knowledgebase: an integrated information resource for p53 research.

The p53 tumor suppressor protein plays a central role in maintaining genomic integrity by occupying a nodal point in the DNA damage control pathway. Here it integrates a wide variety of signals, responding in one of several ways, that is, cell cycle arrest, senescence or programmed cell death (apoptosis). Mutations in the tumor suppressor gene tp53, which affects the key transcriptional regulatory processes in cell growth and death, occur frequently in cancer and helps explain why p53 has been called the guardian of the genome. There is a vast body of published knowledge on all aspects of p53's role in cancer. To facilitate research, it would be helpful if this information could be collected, curated and updated in a format that is easily accessible to the user community. To this end, we initiated the p53 knowledgebase project (http://p53.bii.a-star.edu.sg). The p53 knowledgebase is a user-friendly web portal incorporating visualization and analysis tools that integrates information from the published literature with other manually curated information to facilitate knowledge discovery. This includes curated information on sequence, structural, mutation, polymorphisms, protein-protein interactions, transcription factors, transcriptional targets, antibodies and post-translational modifications that involve p53. The goal is to collect and maintain all relevant data on p53 and present it in an easily accessible format that will be useful to researchers in the field.

Genes, p53↗

Stereotactic radiosurgery XII. Large AVM and the failure of the radiation response modifier gamma linolenic acid to improve the therapeutic ratio.

Large arteriovenous malformations (AVM) are less likely to be 'cured' by single fraction stereotactically delivered radiation therapy (radiosurgery) and such treatment is attended by higher complication risks. Out of 200 successive AVM patients accepted for curative radiosurgery at St. Bartholomew's Hospital (and all treated by the same 6MV x-ray technique to 17.5 Gy marginal dose) were 62 patients whose target volume exceeded 10 ml. Laboratory data demonstrating that gamma linolenic [omega-6-] acid (GLA) protected rat spinal cord from the damaging effect of single shot radiation prompted this study which employed GLA in conjunction with radiosurgery for large AVM. Without GLA, 41% of large AVM obliterated, but in the GLA treated cohort the obliteration rate was only 5.3% (p < 0.02). The permanent complication rates in the same patient groups were 20% versus 0%, respectively. There was a small skew to smaller volume 'large AVM' in the GLA treated cohort. This fact strengthens the conclusion concerning a difference for AVM obliteration, but could lead to a false conclusion quae GLA modulation of complications. When four patients were censored to minimize this possible bias, the risk for complications in the GLA treated patients was still significantly (p < 0.05), less than in the control group. We therefore conclude: (1) GLA spares AVM from radiation induced obliteration; (2) GLA modifies the response of normal human brain to radiation damage; (3) GLA does not improve the therapeutic ratio for AVM based radiosurgery; (4) GLA may have other uses (notably after radiation accidents and in radiation neuro-oncology, radiation cranial prophylaxis, chemoradiation protocols, whole brain radiation for metastases etc.).

Adolescent↗

Transplantation strategies for patients with follicular lymphoma.

PURPOSE OF REVIEW: This review summarizes the current status and new developments in autologous and allogeneic transplantation strategies for patients with follicular lymphoma including novel concepts of myeloablative radioimmunotherapy, allogeneic transplantation with dose-reduced conditioning, and in-vivo purging strategies using B-cell-specific antibodies. RECENT FINDINGS: Substantial progress has been made in the clinical management of follicular lymphoma. Besides immunochemotherapeutic approaches combining the B-cell antibody rituximab with conventional chemotherapy regimens, myeloablative chemotherapy or radiochemotherapy supported by autologous peripheral blood stem cell transplantation has been shown to be a highly effective treatment for advanced-stage disease. Dose-reduced conditioning regimens followed by allogeneic transplantation have substantially reduced treatment-related mortality of this approach and ongoing studies are evaluating whether the therapeutic benefit outweighs morbidity and mortality of this potentially curative treatment. Emerging concepts include the use of rituximab for in-vivo purging before reinfusion of autologous stem cells or the application of myeloablative radioimmunotherapy as part of myeloablative consolidation. SUMMARY: The data on myeloablative therapy followed by autologous stem cell transplantation or allogeneic transplantation are encouraging. Allogeneic transplantation with dose-reduced conditioning should be further evaluated within clinical trials, however, in particular for patients with relapsed or refractory lymphoma. Future prospective randomized clinical trials should reevaluate the role of autologous stem cell transplantation in the era of antibody-based therapy and define the role of radioimmunotherapy and of reduced-intensity allogeneic transplantation.

Antibodies, Monoclonal↗

Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch gastric cancer group trial.

PURPOSE: The extent of lymph node dissection appropriate for gastric cancer is still under debate. We have conducted a randomized trial to compare the results of a limited (D1) and extended (D2) lymph node dissection in terms of morbidity, mortality, long-term survival and cumulative risk of relapse. We have reviewed the results of our trial after follow-up of more than 10 years. PATIENTS AND METHODS: Between August 1989 and June 1993, 1,078 patients with gastric adenocarcinoma were randomly assigned to undergo a D1 or D2 lymph node dissection. Data were collected prospectively, and patients were followed for more than 10 years. RESULTS: A total of 711 patients (380 in the D1 group and 331 in the D2 group) were treated with curative intent. Morbidity (25% v 43%; P <.001) and mortality (4% v 10%; P =.004) were significantly higher in the D2 dissection group. After 11 years there is no overall difference in survival (30% v 35%; P =.53). Of all subgroups analyzed, only patients with N2 disease may benefit of a D2 dissection. The relative risk ratio for morbidity and mortality is significantly higher than one for D2 dissections, splenectomy, pancreatectomy, and age older than 70 years. CONCLUSION: Overall, extended lymph node dissection as defined in this study generated no long-term survival benefit. The associated higher postoperative mortality offsets its long-term effect in survival. For patients with N2 disease an extended lymph node dissection may offer cure, but it remains difficult to identify patients who have N2 disease. Morbidity and mortality are greatly influenced by the extent of lymph node dissection, pancreatectomy, splenectomy and age. Extended lymph node dissections may be of benefit if morbidity and mortality can be avoided.

Adenocarcinoma↗