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Experimental chemotherapy of filariasis: comparative evaluation of the efficacy of filaricidal compounds in Mastomys coucha infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi and B. pahangi.

Eleven types/classes of compound with antifilarial activity were comparatively evaluated in Mastomys coucha infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi or B. pahangi. The paper deals with the efficacy of (i) predominantly microfilaricidal compounds [diethylcarbamazine, levamisole, avermectins (ivermectin, milbemycin), nitrofurans (nitrofurantoin, hydroxymethylnitrofurantoin, nifurtimox, furazolidone, furapyrimidone), organophosphorals (metrifonate, haloxon), and aminophenyl-amidines], (ii) predominantly macrofilaricidal compounds [suramin, benzimidazoles (flubendazole, mebendazole, oxfendazole, ciclobendazole, albendazole, cambendazole, fenbendazole), and arsenicals (thiacetarsamide, Mel PH, R7/45)], and (iii) micro- and macrofilaricidal compounds [benzazole derivatives (CGP 20376 and other benzothiazoles) and nitrophenylamines (amoscanate, CGP 6140)]. Minimum effective doses against microfilariae and minimum curative doses against adult filariae as well as detailed data on dose-efficacy relationships are reported for the various drugs. The results obtained in M. coucha are compared with those published for other experimental in vivo filarial systems, thus attempting to describe a general status of in vivo antifilarial activity of the compounds.

Animals↗

Salvage radiotherapy in the treatment of prostate cancer.

For patients undergoing radical prostatectomy for prostate adenocarcinoma, the most common cause of failure is an asymptomatic increase in levels of prostate-specific antigen (PSA). Salvage radiotherapy (RT) to the prostate bed has been used when there is no clinical evidence of metastatic disease. However, this is still not widely accepted because there is currently no consensus on the optimal management of an isolated PSA failure. Salvage RT given in a select group of patients is effective, with a 70% to 80% biochemical response rate and a long-term biochemical control rate as high as 35% to 40%. These data indicate that RT offers a substantial risk of curative salvage of patients who fail radical prostatectomy. Although there is interest in studying investigational modalities (eg, vaccine therapy) among patients with asymptomatic, PSA-detected recurrences after surgery, caution must be applied, and treatment modalities with known curative potential (ie, RT) should be used before noncurative techniques are attempted. This article outlines the rationale, results, and toxicity of salvage RT for an asymptomatic increase in PSA levels, with emphasis on identifying patients with favorable prognostic factors with higher rates of long-term biochemical control with local treatment.

Actuarial Analysis↗

A prognostic score for gastric cancer.

BACKGROUND: Scoring systems are generally used for predicting prognosis in the intensive care unit, but there is no score being used frequently for predicting prognosis in gastric cancer. The aim of this study was to develop a prognostic score for gastric cancer patients. METHODS: Demographic, clinical, laboratory, radiologic, histopathologic data, and operative findings for 128 patients who had curative or palliative resection for gastric cancer were analyzed for their effect on overall and disease-free survival. Ten variables-invasion depth of tumor, node status (American Joint Committed on Cancer, 1992), metastasis, node status (Union Internationale Contre le Cancer, 1997), metastatic lymph node ratio, resectability, tumor location, extent of lymphadenectomy, Borrmann type, Lauren type-that have independent significant effect or borderline significance on both overall and disease-free survival according to multivariate analysis were chosen. Coefficients were calculated for these variables by using Cox regression analysis, and thus the Prognostic Score for Gastric Cancer (PSGC) was designed. All patients were scored using the PSGC and also staged clinically (AJCC 1992) and histopathologically (AJCC 1992 and UICC 1997). RESULTS: Patients were grouped according to their scores: group 1, patients with scores 20 to 50 (probability of 5-year overall survival 50% to 95%); group 2, patients with scores 51 to 80 (probability of 5-year overall survival 10% to 50%); and group 3, patients with scores 81 and higher (probability of 5-year overall survival <10%). Overall survival and disease-free survival decreased significantly with increasing scores. The association of PSGC and staging systems with survival was analyzed by stepwise logistic regression and Cox regression analyses. PSGC was proved to have the most significant association with overall and disease-free survival. CONCLUSIONS: Inclusion of more variables in PSGC seems to make it superior than staging. It is easy to adapt PSGC to different patient populations, which may make it accepted as a practical and useful scoring system in clinical practice.

Adult↗

Influence of nutritional status on the resumption of adequate food intake in patients recovering from colorectal cancer operations.

The influence of nutritional status on the resumption of adequate food intake in 101 patients recovering from colorectal cancer operation was examined. Two thirds of these patients were well-nourished; the others were malnourished. Malnutrition criteria were serum albumin of less than 3.5 gm per dl plus any two of the following four factors: recent weight loss greater than 10 per cent or weight for height, mid-arm circumference, and triceps skinfold thickness lower than the tenth percentile. Over half of the well-nourished patients were eating 60 per cent or greater of their caloric requirements by the tenth postoperative day, whereas only one quarter of the malnourished patients had attained this intake. the morbidity and mortality in 33 malnourished patients was 52 and 12 per cent, respectively, compared with 31 and 6 per cent (p less than 0.01) in 68 nourished patients. The duration of postoperative functional starvation in malnourished patients without complications increased to an average of 22 days following a complication and was further prolonged after a complication. Age or operative procedure (curative or palliative) did not influence complication rate. Our data suggest that postoperative nutritional support as either TPN or enteral feeding using an elemental diet is indicated in malnourished patients and in well-nourished patients immediately following a complication requiring therapeutic intervention.

Adult↗

Topical immunotherapy in alopecia areata. What, how, and why?

At present the induction and elicitation of an ACD with potent contact allergens such as DCP appear to be the most effective, but still not definitively curative, approach in treating extensive forms of AA. Experimental data suggest that cytokines and growth factors such as IL 1 beta are involved in the pathogenesis of AA as well as the therapeutic effect mediated by contact sensitizers. It seems reasonable to assume that factors inherent in the late phase of ACD modulate a T-cell mediated mechanism responsible for AA, thus inducing hair regrowth. Such counteracting activities are most likely mediated by proinflammatory cytokines such as TNF-alpha, IL-10, or TGF-beta 1. This hypothesis may oversimplify the underlying immunologic mechanisms, but the effectiveness of topical immunotherapy in AA would be compatible with this concept. This mode of treatment is, however, a rather rough approach and recurrences are possible. It is hoped that advances in basic science will eventually allow us to find a more specific mode of treatment.

Administration, Topical↗

Whole-body FDG-PET imaging in the management of patients with cancer.

Fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is increasingly used for the management of patients with cancer. The technique is now well accepted by most physicians as an effective complement to the existing imaging modalities. For many malignancies, PET achieves high sensitivity and specificity. The critical role of this powerful technique is realized increasingly in the day-to-day practice of oncology. This is particularly true for the management of patients with non-small-cell lung cancer (NSCLC). The contribution of PET for the selection of patients eligible for curative treatments in this setting is well established. Convincing data also exist to support the use of PET for evaluating patients with recurrent colorectal carcinoma, for staging and restaging lymphomas, and for diagnosing recurrent thyroid carcinoma in the presence of elevated thyroglobulin and negative 131I scans. Other indications include staging of various recurrent malignancies, such as breast cancer, melanoma, and head and neck and gynecologic carcinomas. Existing data are limited for the determination of the impact of PET in certain malignancies, and further studies, which should include outcome information, will allow clarification of the role of this modality for such indications. Despite the small number of studies specifically designed to assess changes in management plans for some malignancies after performing PET the overall favorable results are encouraging enough at this time to include this modality as an essential element of the practice of modern oncology. Finally, the evolving role of PET imaging as a predictor of response after local or systemic treatment may add a major dimension to the application of this novel technique.

Fluorodeoxyglucose F18↗

[Value of positron emission tomography with 18-fluorodeoxyglucose (FDG-PET) in diagnosis of recurrent bronchial carcinoma].

The aim of the present investigation was to evaluate the diagnostic accuracy of positron emission tomography with 18-fluoro-2-deoxyglucose (FDG-PET) in the detection of recurrent lung cancer. PET was performed using an ECAT ART scanner (Siemens CTI) after i.v. injection of 220 +/- 50 MBq 18FDG. PET data were analysed by visual interpretation of coronal, sagittal and transversal slices. PET scans were interpreted independently by two experienced nuclear medicine physicians without prior knowledge of the results of other imaging studies or clinical data. 40 patients (= 41 cases) who had undergone primarily curative tumour treatment, were evaluated. In 29 of 35 cases with recurrent tumour, diagnosis was verified by pathologic means. FDG-PET correctly identified tumour recurrence in 34/35 cases. In 5/6 cases without prevent tumour recurrence PET gave true negative results. The overall accuracy of FDG-PET was 39/41 = 95% (95%-confidence interval 83-99%). FDG-PET shows high diagnostic accuracy in detecting recurrent lung cancer in patients with prior curative tumour treatment, but cannot substitute the need for pathological diagnosis.

Aged↗

Adjuvant and neo-adjuvant chemotherapy in non-small cell carcinoma.

BACKGROUND: There have been many trials investigating the influence of chemotherapy on survival following surgery or radiotherapy in non-small cell lung cancer. Few have been large enough to detect the sort of differences likely to emerge, given the limited efficacy of chemotherapy. The technique of meta-analysis using individual patient data can allow worthwhile conclusions to be derived from the contradictory data generated by multiple small trials. This paper summarizes published data from randomized trials testing: (1) adjuvant chemotherapy following 'curative' surgery; (2) neoadjuvant chemotherapy prior to surgery in cases of borderline operability; (3) chemotherapy in inoperable, but still localized, disease where standard therapy would be radical radiotherapy. CONCLUSION: All the indications are that combinations including cisplatin confer a small, but real, prolongation of survival. However, meta-analysis is not a substitute for individual trials large enough to detect clinically important differences in survival. Other worthwhile endpoints like symptom control, quality of life and cost cannot be addressed in a meta-analysis. Large, well designed and executed randomized trials are still urgently needed if more time and money is not going to be wasted in the search for better treatments in lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗

A new version of the RDP (Ribosomal Database Project).

The Ribosomal Database Project (RDP-II), previously described by Maidak et al. [ Nucleic Acids Res. (1997), 25, 109-111], is now hosted by the Center for Microbial Ecology at Michigan State University. RDP-II is a curated database that offers ribosomal RNA (rRNA) nucleotide sequence data in aligned and unaligned forms, analysis services, and associated computer programs. During the past two years, data alignments have been updated and now include >9700 small subunit rRNA sequences. The recent development of an ObjectStore database will provide more rapid updating of data, better data accuracy and increased user access. RDP-II includes phylogenetically ordered alignments of rRNA sequences, derived phylogenetic trees, rRNA secondary structure diagrams, and various software programs for handling, analyzing and displaying alignments and trees. The data are available via anonymous ftp (ftp.cme.msu. edu) and WWW (http://www.cme.msu.edu/RDP). The WWW server provides ribosomal probe checking, approximate phylogenetic placement of user-submitted sequences, screening for possible chimeric rRNA sequences, automated alignment, and a suggested placement of an unknown sequence on an existing phylogenetic tree. Additional utilities also exist at RDP-II, including distance matrix, T-RFLP, and a Java-based viewer of the phylogenetic trees that can be used to create subtrees.

Base Sequence↗

SilkDB: a knowledgebase for silkworm biology and genomics.

The Silkworm Knowledgebase (SilkDB) is a web-based repository for the curation, integration and study of silkworm genetic and genomic data. With the recent accomplishment of a approximately 6X draft genome sequence of the domestic silkworm (Bombyx mori), SilkDB provides an integrated representation of the large-scale, genome-wide sequence assembly, cDNAs, clusters of expressed sequence tags (ESTs), transposable elements (TEs), mutants, single nucleotide polymorphisms (SNPs) and functional annotations of genes with assignments to InterPro domains and Gene Ontology (GO) terms. SilkDB also hosts a set of ESTs from Bombyx mandarina, a wild progenitor of B.mori, and a collection of genes from other Lepidoptera. Comparative analysis results between the domestic and wild silkworm, between B.mori and other Lepidoptera, and between B.mori and the two sequenced insects, fruitfly and mosquito, are displayed by using B.mori genome sequence as a reference framework. Designed as a basic platform, SilkDB strives to provide a comprehensive knowledgebase about the silkworm and present the silkworm genome and related information in systematic and graphical ways for the convenience of in-depth comparative studies. SilkDB is publicly accessible at http://silkworm.genomics.org.cn.

Animals↗

The SUPERFAMILY database in 2007: families and functions.

The SUPERFAMILY database provides protein domain assignments, at the SCOP 'superfamily' level, for the predicted protein sequences in over 400 completed genomes. A superfamily groups together domains of different families which have a common evolutionary ancestor based on structural, functional and sequence data. SUPERFAMILY domain assignments are generated using an expert curated set of profile hidden Markov models. All models and structural assignments are available for browsing and download from http://supfam.org. The web interface includes services such as domain architectures and alignment details for all protein assignments, searchable domain combinations, domain occurrence network visualization, detection of over- or under-represented superfamilies for a given genome by comparison with other genomes, assignment of manually submitted sequences and keyword searches. In this update we describe the SUPERFAMILY database and outline two major developments: (i) incorporation of family level assignments and (ii) a superfamily-level functional annotation. The SUPERFAMILY database can be used for general protein evolution and superfamily-specific studies, genomic annotation, and structural genomics target suggestion and assessment.

Databases, Protein↗

Perioperative blood transfusion and determinants of survival after liver resection for metastatic colorectal carcinoma.

The authors reviewed their institutional experience with liver resection for metastatic colorectal carcinoma to (1) determine whether perioperative blood transfusion affects survival; (2) identify prognostic determinants; and (3) estimate the patient requirement for a prospective randomized trial designed to demonstrate efficacy of liver resection. Two hundred eighty consecutive patients treated by potentially curative liver resection between 1960 and 1987 were included. Data were obtained for all but 10 patients for at least 5 years after operation or through 1990. Actuarial survival curves related to potential prognostic determinants were analyzed with the log-rank test. Overall, survival was 47 +/- 3% at 3 years and 25 +/- 3% at 5 years, including 4% 60-day operative mortality rate. Eighty-one patients who did not receive blood 7 days before to 14 days after operation had 60 +/- 6% 3-year and 32 +/- 6% 5-year survival compared with 40 +/- 4% and 21 +/- 3% survival rates for 183 patients who received at least one unit (p = 0.03, operative deaths excluded). Extrahepatic disease (p = 0.015), extrahepatic lymph node involvement (p = 0.002), satellite configuration of multiple metastases (p = 0.0052), and initial detection by abnormal liver enzymes (p = 0.0005) were associated with poor survival rates. Synchronous presentation of metastatic and stage B primary disease was associated with a favorable prognosis (p = 0.003). The requirement for a prospective randomized trial estimated by an exponential survival model would be 36, 74, 168, or 428 patients if 5-year survival without resection were 1, 5, 10, or 15%. We conclude that (1) perioperative blood transfusion may be adversely associated with survival; (2) extrahepatic disease, extrahepatic lymph node involvement, satellite configuration, and initial detection by clinical examination or a liver enzyme abnormality portend a poor prognosis; and (3) a prospective randomized trial of liver resection is impractical because of the large patient requirement, at least by a single institution.

Aged↗

Second liver resections are safe and effective treatment for recurrent hepatic metastases from colorectal cancer: a bi-institutional analysis.

OBJECTIVE: To determine the value of repeat liver resection for recurrent colorectal metastases to the liver. SUMMARY BACKGROUND DATA: Liver resection represents the best and a potentially curative treatment for metastatic colorectal cancer to the liver. After resection, however, most patients develop recurrent disease, often isolated to the liver. METHODS: This study reports the combined experience of repeat liver resection for recurrent liver metastases at an American and a European surgical oncology center. Patients were identified from prospective databases and records were retrospectively reviewed. A total of 126 patients (American n = 96, 1986-2001; European n = 30, 1985-1999) underwent repeat liver resection. Patient characteristics were similar in the two institutions. Median follow-up from first liver resection was 88 and 105 months, respectively. RESULTS: Operations performed included 90 minor resections and 36 resections of a lobe or more. The 1-, 3-, and 5-year survival rates were 86%, 51%, and 34%. There were 19 actual 5-year survivors to date. By multivariate regression analysis (proportional hazard model), more than one lesion and tumor size larger than 5 cm were independent prognostic indicators of reduced survival. The interval between the first and second liver resection was not predictive of outcome. CONCLUSIONS: Repeat liver resection for colorectal liver metastases is safe. Patients with a low tumor load are the best candidates for a repeat resection. In well-selected patients, further resection of the liver can provide prolonged survival after recurrence of colorectal liver metastases.

Adult↗

Ependymomas in children.

Ependymomas originate throughout the central nervous system (CNS), representing 10-12% of CNS tumors in children. The majority occur in children less than 5 years of age. Tumors occur most often in the 4th ventricular region. Current controversies regarding ependymomas include histologic categorization or 'differentiation'. It is estimated that approximately 25% of childhood tumors are appropriately categorized as anaplastic or 'high-grade' lesions. Surgical resection is curative for tumors originating in the cauda equina; recent data suggest that surgery alone has achieved disease control in 75% of intramedullary tumors. For intracranial ependymomas, postoperative irradiation has been shown to improve survival in series dating from the 1960-1980 era. Debate regarding the necessary volume for radiation therapy (i.e. local treatment or craniospinal irradiation) centers on the reported rate of neuraxis seeding. An overall incidence of 12% has been documented in the literature, with clinico-histologic correlation suggesting that anaplastic or high-grade infratentorial ependymomas are associated with the highest frequency of subarachnoid spread. Recent reports of chemotherapy show response to several single agents, with no clear documentation that adjuvant chemotherapy has improved survival to date. Current studies utilizing preirradiation chemotherapy address tumor response and ultimate control in a sequence of surgery, chemotherapy, and irradiation primarily in very young children or those with anaplastic or high-grade tumors.

Child↗

[Evaluation of lung cancer treatment in an unselected population].

The modality of lung cancer treatment was retrospectively evaluated in an unselected population. All the lung cancer cases diagnosed among the residents in a Local Sanitary Unit of Lombardy during four years (1974-1979), were identified. The clinical records of the 235 collected patients were reviewed and on this basis the anatomical extent of disease was retrospectively classified in stages according to the TNM of UICC (1978). The relative frequency of clinical stages resulted 29% for stage I, 17% II, 20% III and 32% IV. Only 57% of all the subjects had been treated; 11% by resection, 22% by radiotherapy and 24% by chemotherapy. For the stages I and II the operability rates were 35% and 26% respectively, while the resectability rates were 29% and 17%. An objective reason of exclusion from surgery was found in no more than a quarter of stage I and II lung cancers, while the remaining (40%) had probably been excluded from exploration owing to a subjective prognostic evaluation. If compared with similar reports from other countries, these data show a striking defect in the choice of curative treatment for a high proportion of the examined cases.

Adult↗

wFleaBase: the Daphnia genome database.

BACKGROUND: wFleaBase is a database with the necessary infrastructure to curate, archive and share genetic, molecular and functional genomic data and protocols for an emerging model organism, the microcrustacean Daphnia. Commonly known as the water-flea, Daphnia's ecological merit is unequaled among metazoans, largely because of its sentinel role within freshwater ecosystems and over 200 years of biological investigations. By consequence, the Daphnia Genomics Consortium (DGC) has launched an interdisciplinary research program to create the resources needed to study genes that affect ecological and evolutionary success in natural environments. DISCUSSION: These tools include the genome database wFleaBase, which currently contains functions to search and extract information from expressed sequenced tags, genome survey sequences and full genome sequencing projects. This new database is built primarily from core components of the Generic Model Organism Database project, and related bioinformatics tools. SUMMARY: Over the coming year, preliminary genetic maps and the nearly complete genomic sequence of Daphnia pulex will be integrated into wFleaBase, including gene predictions and ortholog assignments based on sequence similarities with eukaryote genes of known function. wFleaBase aims to serve a large ecological and evolutionary research community. Our challenge is to rapidly expand its content and to ultimately integrate genetic and functional genomic information with population-level responses to environmental challenges. URL: http://wfleabase.org/.

Animals↗

Evaluation of the extent of lymphadenectomy in a randomized trial of Western- versus Japanese-type surgery in gastric cancer.

PURPOSE: In the context of a prospective, randomized trial of gastric cancer treatment, comparing Western surgical resection with limited lymphadenectomy (R1) versus Japanese surgical resection with extended lymphadenectomy (R2), we analyzed adherence to the specified surgical-pathologic guidelines. PATIENTS AND METHODS: Following evaluation of 389 patients, we quantified noncompliance (ie, performance of less dissection than specified) and contamination (ie, performance of more extensive dissection than specified). Of 389 patients, pathologic data permitted identification of 237 eligible patients treated with curative intent. RESULTS: Noncompliance occurred in 84% of R1 and R2 cases, with magnitude significantly (P < .001) higher in R2 cases versus R1 cases. Contamination occurred in 48% of R1 cases and 52% of R2 cases, with the magnitude of contamination moderate and equally distributed between the two groups. The contamination in R1 resections and the noncompliance in R2 resections lead to a partial homogenization of the groups, undermining the likelihood of detecting any potential therapeutic advantage to R2 dissection. CONCLUSION: The observed tendency to perform R1 resections combined with insufficient retrieval of lymph nodes underlines the need for increased surgical-pathologic standardization in this trial. Potential remedies are discussed. Proper conduct of clinical trials requires reliable means of standardizing performance of the surgical-pathologic team, an elusive but important goal.

Adenocarcinoma↗

Undetectable preoperative levels of serum CA 19-9 correlate with improved survival for patients with resectable pancreatic adenocarcinoma.

BACKGROUND: Serum levels of CA19-9 have been shown to correlate with both recurrence and survival in patients with pancreatic cancer. However, little is known about the prognosis for patients with undetectable levels of serum CA19-9. METHODS: One hundred twenty-nine patients with pancreatic cancer who underwent preoperative assessment of serum CA19-9 followed by resection with curative intent between 1990 and 2002 were retrospectively analyzed. Data collected included preoperative serum CA19-9 level (U/mL), age, pathologic staging, and survival. Data were analyzed with the SAS system according to four distinct preoperative serum CA19-9 levels: undetectable, normal (<37), 38-200, and >200 U/mL. RESULTS: Serum CA19-9 levels ranged from undetectable to 16,300 U/mL. Stage III/IV disease accounted for 86%, 67%, 59%, and 53% of patients in the four CA19-9 groups. The overall median and 5-year survivals were 19 months and 11%, respectively. Survival was similar between nonsecretors and those with normal CA 19-9 levels. However, both groups had statistically significant prolonged survival compared with the two groups with elevated CA 19-9 levels (P =.003). The only factors that were significant on univariate and multivariate analysis for overall survival were lymph node positivity (P =.015 and.002) and CA 19-9 grouping (P =.003 and P <.0001). Although this group of patients presented with predominately advanced-stage disease, their overall survival was superior. CONCLUSIONS: These findings suggest that patients who present with undetectable preoperative CA19-9 levels and potentially resectable pancreatic cancer, regardless of advanced stage, should be considered candidates for aggressive therapy.

Adenocarcinoma↗