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Heat-responsive ONSEN long terminal repeats integrate heat shock factor motifs, DNA methylation and natural sequence variation in Arabidopsis.

ONSEN is a heat-activated Ty1/copia retrotransposon in Arabidopsis thaliana controlled by heat shock factors (HSFs) and epigenetic silencing. Heat shock element (HSE)-like sequences in ONSEN long terminal repeats (LTRs) contribute to heat responsiveness, but relationships among sequence architecture, basal DNA methylation and natural variation remain unclear. We combined transcription-factor motif prediction, transposable-element comparisons, methylome and RNA sequencing (RNA-seq) data, and Arabidopsis genome assemblies. In silico disruption of five HSE cores eliminated HSF-family motif compatibility in the selected design and all 5119 exact-guanine-cytosine (GC) alternatives. Across 16 curated Columbia-0 terminal windows, ONSEN contained 33-49 non-redundant HSF motif-coordinate placements per 800 bp window and was strongly enriched relative to 1930 non-ONSEN transposable elements across score thresholds and continuous metrics. Direct comparison with 779 non-ONSEN LTR retrotransposons showed selectively elevated basal CHH methylation (where H = A, C or T) at ONSEN termini. Genome-wide RNA-seq analysis revealed broad heat-responsive gene and transposable-element changes, including strong ONSEN induction, whereas candidate-window analysis distinguished ONSEN from most HSF-rich non-ONSEN outliers. ONSEN-like variants across eight accessions generally retained HSF-compatible motifs while altering predicted DNA binding with one finger-family motif composition. Together, these findings define ONSEN terminal regions as HSF-rich regulatory sequences that retain heat-responsive potential within a methylated chromatin context and identify candidates for functional analysis.

DNA Methylation↗

Preoperative examination to detect distant metastasis is not advocated for asymptomatic patients with stages 1 and 2 non-small cell lung cancer. Preoperative examination for lung cancer.

The purpose of the present study was to determine whether all patients with non-small cell lung cancer, clinically defined as stage 1 or 2, should have examinations to determine the presence of distant metastatic (M1) disease. The survival rates of patients who underwent the examinations and those who did not were compared. In all groups, the examinations had in no way positively affected survival. The 33 patients in whom distant recurrence had occurred within 12 months of curative operation, were then evaluated to establish the relationship between the recurrent site and the preoperative examination: negative scans on the examination failed to predict the low incidence of early distant recurrence. Those data suggest that the routine use of radionuclide or CT scans is of no benefit to asymptomatic patients with local, early disease.

Bone Neoplasms↗

Prognostic significance of CyclinD1 and E-Cadherin in patients with esophageal squamous cell carcinoma: multiinstitutional retrospective analysis. Research Committee on Malignancy of Esophageal Cancer, Japanese Society for Esophageal Diseases.

BACKGROUND: Although many molecular biologic molecules have been analyzed for their prognostic influence on patients with esophageal cancer, previous studies have not been able to raise statistically significant prognostic factors. STUDY DESIGN: Immunohistochemical analysis of CyclinD1 expression and E-Cadherin expression was performed retrospectively in 416 esophageal squamous cell cancer patients who underwent curative resection of esophageal cancer at 10 major surgical departments in Japan, where more than 30 esophagectomies are performed in a year. The prognostic impact of these molecules and their relationship to clinicopathologic data of the patients were evaluated. RESULTS: Univariate analysis revealed that pN (pTNM), pT (pTNM), CyclinD1 expression, and E-Cadherin expression were significant prognostic factors, and multivariate analysis revealed that pN (risk ratio (RR) 2.19), pT (RR 3.35), CyclinD1 (RR 1.42), and E-Cadherin (RR 0.71) were significant prognostic factors. Combination analysis of these genes revealed that E-Cadherin-preserved and CyclinD1-negative patients had the best prognosis; E-Cadherin-reduced and CyclinD1-positive patients had the worst prognosis. CONCLUSIONS: Increased CyclinD1 expression and reduced E-Cadherin expression were significant prognostic factors in patients with esophageal squamous cell carcinoma.

Analysis of Variance↗

Prognosis of primary liver carcinoma treated with local resection.

OBJECTIVE: To discuss the prognosis of primary liver carcinoma treated with local resection and factors affecting prognosis. METHODS: The data of 130 patients who had been treated from October 1989 to October 1995 were analyzed retrospectively. We analyzed the concrete operating methods, the cause of postoperative complications and factors affecting prognosis. RESULTS: Curative local resection was performed in 130 patients. Operation-related mortality was 0.8% and the incidence of complication was 16.1% (n = 18). The overall 1-, 3- and 5-year survival rates were 82.1%, 60.6% and 48.2%, respectively. Involvement of blood vessels or liver capsules and the elevation of AST before operation were the significant factors affecting prognosis (P < 0.05). CONCLUSION: Local resection is a safe method characterized by little damage, rapid, less blood loss, low complication rate and good prognosis.

Adult↗

Adjuvant therapy in gastric cancer: can we prevent recurrences?

Despite a dramatic decline in the incidence of gastric carcinoma in the United States during the past century, treatment remains a challenging problem for oncologists. Surgery continues to be the primary modality for managing early-stage gastric cancer, but up to 80% of patients who undergo a "curative" resection develop locoregional or distant recurrence. Given these sobering statistics, there has been great interest in developing strategies to prevent recurrences after surgery and improve overall mortality. In this article, we review data on adjuvant treatment modalities for this disease, including radiotherapy, chemotherapy, combination chemotherapy and radiation, intraperitoneal treatment, and immunotherapy. We focus attention on the recent widespread acceptance of adjuvant chemoradiotherapy, based on the results of Intergroup trial 0116. Future strategies incorporating different modalities of treatment will be outlined.

Adenocarcinoma↗

Expression array annotation using the BioMediator biological data integration system and the BioConductor analytic platform.

This paper presents the implementation of a model for expression array annotation (EAA) using the BioMediator biological data integration system along with BioConductor, an analytic tools platform. The model presented addresses the need for annotation sources identified during BioConductor inverted exclamation mark s development. Annotation provides us with well-curated genomic background knowledge for expression array analysis and interpretation. Annotation requests are constructed and posted to the query interface of the EAA package (the EAA model implemented as a component of BioConductor). The software enumerates all possible annotation paths for queries. These are then transformed to PQL queries and processed by BioMediator. Annotation entities returned from the EAA package answer the annotation request.

Computational Biology↗

[Efficiency of combined multiple organs resection in advanced gastric carcinoma].

BACKGROUND & OBJECTIVE: Presently, 26.05% of cases with gastric carcinoma hospitalized in Cancer Center of Sun Yat-sen University were revealed adjacent organs involvement in varying degrees in exploration. There have been many arguments about the issue of surgery therapy on these advanced gastric carcinomas for a long time. This study was designed to demonstrate the feasibility of combined multiple organs resection in such cases. METHODS: Clinical data of 44 advanced gastric cancer patients received combined multiple organs resections from 1985 to 1995 in Cancer Center of Sun Yat-sen University were enrolled retrospectively. Among them, 34 cases received curative resection and 10 cases received palliative resection. The effects of two kinds of operations were analyzed. RESULTS: Median survival time was 588 days (average is 1 676 days) in radical combined multiple organs resection group and 344 days (average is 1 045 days) in palliative resection group respectively (P >0.05). In addition, no serious complication occurred and no patients died of extended resection. CONCLUSION: Combined multiple organs resection is practicable in curative therapy for gastric carcinoma; even palliative resection may have better treatment effect. So, if permission, radical combined multiple organs resection should be top-priority.

Adult↗

Prognostic implications of the localization of carcinoma in the head of the pancreas.

Between 1974 and 1989, 411 patients with pathologically and anatomically proven carcinoma of the head of the pancreas underwent endoscopic retrograde cholangiopancreatography (ERCP). According to the localization of the tumor, these patients were divided into those with a cranially, centrally (periductally), caudally, or indeterminately localized tumor. In cranially localized tumors, extrahepatic metastases and vessel invasion were absent or resectable in 53% and 46%, respectively. The tumor was resectable in 41% of cases. If a patient with a cranially localized tumor could not be operated curatively for secondary reasons, the prognosis was better than for tumors with another localization. If there was unresectable vessel invasion and the tumor was not resectable, the 0% survival rate was reached at 33 months. Of the curatively operated patients, 26% were alive at 36 months after the start of complaints. Of the centrally or periductally localized tumors, there were no liver metastases in 73%. Extrahepatic metastases and vessel invasion were absent or resectable in 57% and 53%, respectively. The tumor was resectable in 48% of cases. If there was unresectable vessel invasion or the tumor was unresectable, the 0% survival rate was reached after 18 months. These tumors have maximal chances at curative resection. Of the curatively operated patients, 31% were alive at 36 months after the start of complaints. In caudally localized tumors, there were liver metastases in 59%, unresectable other abdominal metastases in 93%, unresectable vessel invasion in 91%, and the tumor was unresectable in 96%. In patients with an unresectable vessel invasion or an unresectable tumor, the 0% survival rate was reached after 33 months; 3% of these patients were operated curatively. Indeterminately localized tumors had liver metastases in 77%, unresectable extrahepatic metastases in 90%, unresectable vessel invasion in 95%, and the tumor was unresectable in 91%. Only one of the 44 patients (2%) could be operated curatively.

Carcinoma↗

[Hypertension: economic aspects].

The data are provided on the economic losses caused by hypertonic disease (HD) to the national economy of Lithuania in 1980 which are estimated as the sum of money spent by the state on curative and preventive measures and economic losses due to temporary disability, invalidity and premature deaths. Economic losses including damage caused by temporary disability, invalidity and premature deaths accounted for 11.1 million roubles. The major losses were caused by temporary disability. They topped the economic damage due to premature deaths by more than two times. State expenditures on curative and preventive care for hypertonic patients in the structure of economic losses accounted for only 10.6%.

Adult↗

[Surgical treatment and prognosis of stomach carcinoma with special reference to gastrectomy as a standard operation].

Data on 25 early and 227 advanced gastric cancer patients treated surgically in our clinic over an eight-year period from 1979 to 1986 have been analyzed retrospectively. In 45.5% (n = 110) curative resection and in 27.3% (n = 66) palliative resection was performed. In another 27.3% (n = 66) only a non-resecting procedure was possible. The overall hospital mortality was 10.7% (26/242). It was 9.1% (16/176) after resection and 15% (10/66) after non-resecting procedures. Total gastrectomy "de principe" with compartment II lymphadenectomy was performed in 70.5% (124/176). Total hospital mortality was 8.9% (n = 11) and leakage of the proximal anastomosis was observed in 8.1% (n = 10). Hospital mortality of the remaining resected patients was 3.2% (1/31) after distal resection, 20% (3/15) after proximal resection and 16.7% (1/6) after total esophagogastrectomy with colon interposition. All patients were staged according to UICC classification and staging was I 8.5%, II 14%, III 23% and IV 54.5%. Actuarial 5-year survival in all patients surviving resection was depending on stage of disease at operation (stage I 100%, II 53.3%, III 29% and IV 0%). It differed most significantly (p less than 0.001) for curative (49%) and palliative resections (0%). These results indicate that improvement of results requires early diagnosis with immediate surgical intervention.

Adult↗

[Indications for palliative surgery in digestive cancerology].

The data of the literature demonstrate the poor global results of surgical treatment of the principal gastrointestinal cancers: oesophagus, stomach, bile ducts, liver, exocrine pancreas, colon and rectum. Surgery which was thought to be curative all too frequently proves to be simply a palliative procedure. The risk of failure is so high that a strategy should now be systematically adopted, combining surgery, radiotherapy, chemotherapy and symptomatic treatments. The rigor of this multidisciplinary approach is based on comparative studies confirming the prospective series and measuring the quality and duration of survival. Some protocols provide considerable improvement, for example preoperative radiotherapy of cancers of the rectum, or propose an interesting alternative such as the combination of radiotherapy and chemotherapy in cancer of the oesophagus. The participation of surgeons in multicentre prospective studies should validate and improve current oncological practice while also evaluating the contribution of a new method such as laparoscopic surgery. This commitment includes a definition of therapeutic objectives, definition of the reference treatment, selection of the criteria of the quality of the procedures involved in this treatment and objective assessment of the results.

Biliary Tract Neoplasms↗

[Sialomucins in the follow-up of patients surgically treated for colorectal cancer: preliminary results of a prospective study].

Preliminary results of a prospective study on sialomucin content found either at resection margins of colo-rectal cancer after curative surgery or in endoscopic biopsy specimens of colonic mucosa in thirteen patients selected for the follow up are reported. Though not statistically significant because of the small number of cases enrolled, preliminary data indicate that clinical application of differential mucin staining in colo-rectal neoplasms is potentially useful to predict subgroups of patients at risk for local recurrence as well as metachronous colo-rectal cancers.

Adult↗

Raised carcinoembryonic antigen level as an indicator of recurrent disease in follow up of patients with colorectal cancer.

BACKGROUND: Serum carcinoembryonic antigen level is raised in 80% of patients undergoing colonic resection for cancer. Subsequent elevation in the follow-up period may precede signs and symptoms as an indicator of recurrent disease. there is little evidence that "classical" follow up of patients in the general surgical outpatient clinic improves either survival or quality of life. Regular carcinoembryonic antigen level estimation requested by the general practitioner, allied to day-case colonoscopic surveillance may be a more rational approach. AIM: A study was undertaken to investigate the relationship between raised carcinoembryonic antigen level and the recurrence of colorectal cancer in patients following a curative primary resection. METHOD: Retrospective analysis was carried out on the notes of 125 patients who had attended a dedicated hospital colorectal follow-up clinic between 1988 and 1992. Carcinoembryonic antigen level data were obtained by subsequent examination of the University of Edinburgh Department of Clinical Chemistry (immunoassay section) carcinoembryonic antigen database. RESULTS: A single carcinoembryonic level result of more than 100 ul-1 (normal range less than 60 ul-1) was found to be a highly sensitive (87%), specific (89%), and accurate (88%) indicator of recurrent disease. Raised carcinoembryonic antigen level preceded symptoms in 72% of patients with recurrence of colorectal cancer. CONCLUSION: Sequential laboratory estimation of carcinoembryonic antigen level organized by the general practitioner may represent an accurate method of detecting recurrent colorectal disease. Hospital review could be limited to colonoscopic surveillance and restaging of patients referred with evidence of recurrent disease.

Adult↗

[Malignant tumors of the Vater's ampulla. Presentation of 28 cases and review of the literature].

We present a study of 28 patients, treated for adenocarcinoma of Vater's ampulla. We emphasize the distinct behavior of each one of the peri-ampullar tumors, those which affect Vater's ampulla yielding the best prognosis. We gathered data regarding gender, age, clinical manifestations, and analytical data. The confirmatory diagnosis gives us 100% of CPRE cases. All of the patients were submitted to surgical treatment with anatomic pathological confirmation of the diagnosis, be it pre or postoperative. We practiced curative surgery in 57.2% of the cases and palliative in 42.8% of the cases. We observed postoperative complications in 17.8% of the patients and peroperative mortality in 3.5%. Actual survival of the series of patients for whom exeretic surgery was performed is significantly superior to that of the other patients.

Actuarial Analysis↗

Decreased adenylate energy charge and superoxide anion release in polymorphonuclear leukocytes in septic patients after hepatectomy.

To clarify the process of multiple organ failure after hepatectomy, the adenylate energy charge (EC) and superoxide anion (O2-) release of polymorphonuclear leukocytes (PMN) were measured 19 times on 11 septic patients after curative hepatic resection in relation to arterial ketone body ratio (AKBR), which reflects hepatic mitochondrial redox potential. PMN EC was measured by labeling the adenine nucleotide pool of PMN with radioactive adenine. The data of the septic patients (n = 19) was divided into two groups according to the hepatic energy status: AKBR above 0.7 (septic state A; n = 8) and AKBR below 0.7 for at least 3 successive days (septic state B; n = 11). Thirteen nonseptic patients undergoing hepatic resection were applied to the control group, and all of them showed AKBRs higher than 0.7. The PMN EC of septic patients was significantly lower than that of nonseptic patients [0.80 +/- 0.01 (SEM) vs. 0.88 +/- 0.02, P < 0.01]. In septic patients, moreover, the PMN EC of septic state A was significantly higher than septic state B (0.85 +/- 0.01 vs. 0.77 +/- 0.03, P < 0.05). Superoxide anion release of septic patients was significantly lower than that of nonseptic patients (19.0 +/- 2.1 nmol/5 x 10(5) cells/15 min vs. 29.3 +/- 1.7 nmol/5 x 10(5) cells/15 min, P < 0.01). Superoxide anion release of septic state A was significantly greater than that of septic state B (26.0 +/- 2.8 nmol/5 x 10(5) cells/15 min vs. 15.0 +/- 1.9 nmol/5 x 10(5) cells/15 min, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

[The prevalence of arrhythmias in subjects over 80 years old. The prognostic role of anamnestic symptomatology and the therapeutic directions].

24-hour Holter monitoring was performed in 129 unselected subjects older than 80 years (69 women and 60 men) in order to evaluate arrhythmia incidence and to establish significance of symptoms; 56% patients had lipothymia and/or syncope, chest pain and palpitations, 44% were asymptomatic. All patients showed high incidence of hyperkinetic and hypokinetic arrhythmias; no significant differences between symptomatic and asymptomatic patients in arrhythmia incidence were seen. Moreover, no correlation could be seen of the symptoms reported by the patient to the incidence of any particular type of arrhythmia. In conclusion, these preliminary data suggest a criticism of the opportunity of indiscriminate and long term antiarrhythmic therapy. Nevertheless, Holter monitoring is useful in detecting hypokinetic arrhythmias of asymptomatic patients in whom pacemaker implantation is essential and curative.

Aged↗

Growth factors and bone formation in osteoporosis: roles for IGF-I and TGF-beta.

The cellular mechanisms involved in osteoblast function and bone formation alterations in osteoporosis have been partly elucidated. Recent studies have shown that bone formation abnormalities in various forms of osteopenia result mainly from defective recruitment of osteoblastic cells. These abnormalities in osteoblast function and bone formation are associated with alterations in the expression or production of several growth factors, such as IGFs and TGF-beta, which modulate the proliferation and activity of bone-forming cells. Bone loss related to aging or unloading is characterized by diminished osteoblast proliferation and reduced local concentrations of IGFs and TGF beta. In contrast, estrogen deficiency increases osteoblast proliferation and IGF-I production. These data suggest that alterations in the production of and/or in cell responsiveness to local growth factors may contribute to the bone formation abnormalities seen in these osteopenic disorders. This suggests that preventive or curative treatment with growth factors may be beneficial in osteopenia due predominantly to decreased bone formation. Low doses of IGF-I or TGF-beta have been reported to increase osteoblast recruitment and differentiation, leading to enhanced trabecular bone formation and decreased bone loss in models of osteopenia induced by aging, estrogen deficiency and unloading. A few clinical trials also suggest that low doses of growth factors may stimulate bone formation. Although these findings open up new prospects for the prevention and treatment of osteopenic disorders, progress in this direction awaits the development of factors or analogs that are capable of locally and specifically increasing osteoblast recruitment and differentiation without including side-effects.

Aged↗

Bayesian Modeling of Cancer Outcomes Using Genetic Variables Assisted by Pathological Imaging Data.

With the increasing maturity of genetic profiling, an essential and routine task in cancer research is to model disease outcomes/phenotypes using genetic variables. Many methods have been successfully developed. However, oftentimes, empirical performance is unsatisfactory because of a "lack of information." In cancer research and clinical practice, a source of information that is broadly available and highly cost-effective comes from pathological images, which are routinely collected for definitive diagnosis and staging. In this article, we consider a Bayesian approach for selecting relevant genetic variables and modeling their relationships with a cancer outcome/phenotype. We propose borrowing information from (manually curated, low-dimensional) pathological imaging features via reinforcing the same selection results for the cancer outcome and imaging features. We further develop a weighting strategy to accommodate the scenario where information borrowing may not be equally effective for all subjects. Computation is carefully examined. Simulations demonstrate competitive performance of the proposed approach. We analyze TCGA (The Cancer Genome Atlas) LUAD (lung adenocarcinoma) data, with overall survival and gene expressions being the outcome and genetic variables, respectively. Findings different from the alternatives and with sound properties are made.

Humans↗