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PubMed1996

Gastrointestinal endocrine cancers and nodal metastasis: biologic significance and therapeutic implications.

Gastrointestinal endocrine tumors consist of pancreatic endocrine neoplasms and carcinoid tumors. Except for insulinoma, a majority of gastrointestinal endocrine tumors are malignant. With improved medical treatment of syndromes of hormonal excess, growth of the primary tumor and metastatic spread has increasingly become an important determinant of long-term survival. Although few randomized, prospective data are available given the rare occurrence of malignant gastrointestinal endocrine tumors, surgery appears to be the only potentially curative treatment for malignant endocrine tumors, and complete resection of localized or regional nodal metastases provides the highest probability of cure. Surgery may also be the most effective treatment for hepatic metastases if most or all of the tumor can be resected, and patients with solitary, localized metastatic disease appear to benefit most. Symptoms from extensive metastases may respond to chemotherapy or octreotide. Gastrointestinal endocrine tumors are generally indolent, slow-growing neoplasms, and when symptoms are adequately controlled, patients can live comfortably and productively for many years with metastatic disease.

Carcinoid Tumor↗
PubMed1997

[Non surgical treatment of pancreatic cancers].

Pancreatic cancer is a disease difficult to treat. Diagnosis is late, cancer remaining clinically unapparent even if locally advanced or metastatic. Few patients can be submitted to curative surgery. Even if resection is possible, 5-year survival varies from 0% to 18% according to series. Some data suggest that chemotherapy with or without radiotherapy could influence disease free survival but a benefit on overall survival has not been demonstrated. For locally advanced disease, the results of a trial published in 1968, showed that a combination of radiotherapy and 5-Fluorouracil (5FU) improved median survival as compared to radiotherapy alone (5.5 versus 10 months). Since then, no progress has been achieved. At the present time, survival of patients with metastatic pancreatic cancer cannot be improved. Very recently, a new agent, gemcitabine, has been compared to 5FU. Criteria for activity were based on clinical improvement analgesia consumption, performance status and weight gain. Twenty-four percent of the patients treated with gemcitabine had a clinical benefit as compared to 5% for those treated with 5FU. Other studies comparing chemotherapy to best supportive care show a significant decrease of depression and anxiety as well as an improvement in quality of life for patients being treated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Extended lymphadenectomy in gastric cancer: when, for whom and why.

Although lymph node metastasis is a major prognostic factor in gastric cancer, the optimal extent of lymph node dissection still remains a subject of debate. The influence of extended D2 lymphadenectomy on morbidity and long-term survival is controversial. Reports from many Japanese and some Western institutions show similar morbidity and mortality rates for both limited D1 and extended D2 resections. However, the four available randomised trials show a significant increase in operative morbidity and mortality after a D2 resection. The authors of these trials believe that distal pancreaticosplenectomy is responsible for this increased morbidity and mortality and not the lymphadenectomy itself. Retrospective and prospective non-randomised studies show superior stage (II/IIIA) specific survival rates after D2 resections. However, these studies did not eliminate stage migration and randomised trials failed to show any survival advantage in favour of the D2 resection. Current data suggest that D2 resection is beneficial to the subgroup of patients with N1 or N2 disease undergoing potentially curative resection. However, Western studies that support D2 resection, fail to show any survival advantage for D2 resection in N2 patients, reporting a benefit only to N0 or N1 patients. In contrast, Japanese series report a large number of N2 long-term survivors. The question as to the possible beneficial effect of extended lymphadenectomy in gastric cancer is difficult and complex. D2 resection increases the potentially curative resection rate, at least in N2 patients, achieves a better locoregional tumour control and provides the only chance for cure among N2 patients since adjuvant treatment in gastric carcinoma has not yet been proved effective. However, all randomised comparisons warn of an increased risk after D2 resection. By avoiding pancreaticosplenectomy, however, the morbidity can be within acceptable limits. D2 gastrectomy seems to be the most attractive procedure in the surgical management of gastric cancer.

Humans↗
PubMed1998

Preoperative CA 15-3 concentrations predict outcome of patients with breast carcinoma.

BACKGROUND: CA 15-3 is a breast-associated mucin that is elevated in the majority of breast carcinoma patients with distant metastases. Currently, the main application of this marker is in monitoring and detecting recurrences in patients with diagnosed breast carcinoma. METHODS: Preoperative serum concentrations (prior to excision of the primary tumor) of CA 15-3 were measured in 368 patients undergoing potentially curative surgical treatment for early breast carcinoma. These results were compared with prospectively recorded clinicopathologic characteristics and patient outcome data. RESULTS: A weak but significant positive association was found between CA 15-3 concentrations and both tumor stage and the number of involved axillary lymph nodes but not between CA 15-3 concentrations and estrogen receptor status. Patients with high concentrations of CA 15-3 had a significantly worse prognosis than patients with low concentrations. Using an optimum cutoff value of 30.38 U/mL, the probability of disease free survival at 5 years was 44% in patients with high CA 15-3 levels compared with 65% in patients with low CA 15-3 levels (P = 0.002, Mantel-Cox log rank test). The corresponding probabilities for overall survival were 67% and 83%, respectively (P < 0.001). The association of preoperative CA 15-3 levels with outcome was maintained in multivariate survival analysis and was not explained by the association between CA 15-3 and tumor size or lymph node burden. The relation between CA 15-3 and outcome also was found within some patient subgroups identified by traditional prognostic factors (axillary lymph node positive patients, patients with primary tumors >2 cm in greatest dimension, and patients with estrogen receptor positive tumors). CONCLUSIONS: Preoperative serum concentrations of CA 15-3 appear to have a significant relation to outcome in patients with early breast carcinoma and may have a role in the rational selection of patients for appropriate adjuvant treatments. To the authors' knowledge, CA 15-3 thus is one of the first circulating markers shown to be an independent prognostic indicator in patients with breast carcinoma.

Axilla↗
PubMed2005

Dose-volumetric parameters for predicting severe radiation pneumonitis after three-dimensional conformal radiation therapy for lung cancer.

PURPOSE: To retrospectively evaluate dose-volumetric parameters for association with risk of severe (grade >/=3) radiation pneumonitis (RP) in patients after three-dimensional (3D) conformal radiation therapy for lung cancer. MATERIALS AND METHODS: The study was approved by the institutional review board, which did not require informed consent. Data from 76 patients (66 men, 10 women; median age, 60 years; range, 35-79 years) with histologically proved lung cancer treated curatively with 3D conformal radiation therapy between August 2001 and October 2002 were retrospectively analyzed. Twenty patients underwent surgery before radiation therapy; 57 patients received chemotherapy. Median total radiation dose of 60 Gy (range, 54-66 Gy) was delivered in 30 (range, 27-33) fractions over 6 weeks. RP was scored by using Radiation Therapy Oncology Group criteria. Clinical parameters were analyzed. Dose-volumetric parameters analyzed were percentage of lung volume that received a dose of 20 Gy or more (V20), 30 Gy or more (V30), 40 Gy or more (V40), or 50 Gy or more (V50); mean lung dose (MLD); normal tissue complication probability (NTCP); and total dose. Fisher exact test was performed to compare clinical parameters between patients who developed severe RP and those who did not. Univariate and multivariate logistic regression analyses were performed to evaluate data for association between dose-volumetric parameters and severe RP. Pearson chi(2) test was used to assess data for correlations among dose-volumetric parameters. P < or = .05 was considered to indicate statistically significant difference. RESULTS: Of 76 patients, 30 (39%) did not develop RP; 23 (30%) developed RP of grade 1; 11 (14%), grade 2; 11 (14%), grade 3; and 1 (1%), grade 4. None had grade 5 RP. Age (< 60 vs > or =60), sex, Karnofsky performance status (< 70 vs > or =70), forced expiratory volume in 1 second, presence of weight loss, preexisting lung disease, history of thoracic surgery, and history of chemotherapy did not significantly differ between patients who developed severe RP and those who did not. In univariate analyses, MLD, V20, V30, V40, V50, and NTCP were associated with severe RP (P < .05). In multivariate analysis, MLD was the only variable associated with severe RP. CONCLUSION: MLD is a useful indicator of risk for development of severe RP after 3D conformal radiation therapy in patients with lung cancer.

Adult↗
PubMed2001

Routine follow-up examinations in breast cancer patients have minimal impact on life expectancy: a simulation study.

BACKGROUND: Little is known about the effects of routine follow-up examinations on life expectancy in cancer patients. Lately, the benefits of follow-up examinations have been debated, which has given rise to less extensive, though still frequent, follow-up strategies. In this study, a simulation model was applied to evaluate the impact of different follow-up strategies on life expectancy in breast cancer patients. MATERIALS AND METHODS: A five-state Markov chain model was developed, with which various follow-up strategies with regard to frequency and elaborateness were simulated. Calculations were based on a hypothetical population of breast cancer patients treated with curative intent. Medical aspects were studied, such as life expectancy and the proportion of patients who died from breast cancer. Social and psychological aspects and quality of life were not taken into account. Data from the literature were used to estimate the parameters needed for the model. RESULTS: The gain in life expectancy with standard follow-up compared to no follow-up examination, was about 2 months in breast cancer patients aged 50 years treated with curative intent. The percentage of patients who died from breast cancer was 45.4% with standard follow-up, versus 45.8% without follow-up. In older women, the gain was even less. Sensitivity analyses showed that the effects on life expectancy were robust. CONCLUSIONS: Our model showed that standard follow-up had minimal impact on the prognosis of breast cancer patients. It may be unnecessary to continue standard follow-up by medical specialists after the end of the surveillance period of the primary therapy, provided that the patients continue to have easy access to health care facilities in the case of symptoms or concern. However, future research is needed to study quality of life aspects of follow-up.

Adult↗
PubMed1996

Long-term follow-up after curative surgery for early gastric lymphoma.

OBJECTIVE: This study was designed to examine the long-term survival of a homogenous group of patients with stage IE or IIE-1 gastric lymphoma after complete surgical resection. SUMMARY BACKGROUND DATA: The management of gastric lymphoma remains controversial. Enthusiasm for multimodality approaches for gastric lymphoma has lead to the current trend of using chemotherapy as primary treatment, thus avoiding gastric resection. Surgery, however, may result in improved long-term survival rates. METHODS: The records of all patients with the diagnosis of gastric lymphoma from 1980 to 1991 were reviewed retrospectively. Of 106 patients examined, 34 underwent curative resection and regional lymphadenectomy for pathologically staged IE or IIE-1 (pN1) gastric lymphoma. Fifteen patients underwent surgery alone, whereas 19 also received postoperative adjuvant therapy. RESULTS: The median follow-up time was 74 months. The 10-year actuarial disease-free survival was 91% for stage IE disease (n = 23) and 82% for stage IIE-1 disease (n = 11). There were no operative deaths and a 26% morbidity rate. No difference in survival was found for those treated with adjuvant therapy. CONCLUSIONS: The results compare favorably to those reported with the use of primary chemotherapy and radiation therapy and suggest that surgery remains the best frontline therapy for early gastric lymphoma.

Female↗
PubMed2002

Metastatic breast cancer with HER2/neu-positive cells tends to have a morbid prognosis.

BACKGROUND: Clinically, human epidermal growth factor receptor 2 (HER2) overexpression is associated with a faster rate of tumor growth and an increased rate of metastasis, and a patient who is HER2 strongly positive tends to have a poor prognosis and a decreased disease-free survival and overall survival (OS) time. METHODS: We analyzed data on 526 Japanese adult women with breast cancer with respect to the relationship between the status of HER2/neu receptor expression and the recurrent state and survival from detection of the first recurrence. All these women were treated from 1982 to 2000 in the Department of Surgery, National Beppu Hospital, Kyushu, Japan. In 95 patients with metastatic breast cancer after curative resection, the expression of HER2/neu status was examined by using immunohistochemical staining methods (HercepTest). Scores of 0, 1+, 2+, and 3+ were given according to the HercepTest data. Only scores of 2+ and 3+ were assessed as an overexpression of HER2/neu protein and HER2-positive patients. Between the HER2-positive and HER2-negative patients, the survival after surgical intervention, the disease-free survival time, and the survival time after the initial recurrence were compared. RESULTS: An overexpression of HER2/neu receptor protein occurred at a rate of 23.7% (23/97) in the 97 women with metastatic breast cancer. There was no difference in age, tumor size, TN staging system, and the number of lymph node metastases between HER2-positive and HER2-negative patients. Almost all HER2-positive patients had a negative estrogen receptor status (14/15 [93.3%]). The initial sites of recurrence were classified as (1) soft tissue, bone, and viscera or (2) soft tissue, bone, lung-pleura, liver, and brain. For the HER2-positive patient, viscera, especially the liver and lung, were predominant initial sites of recurrence. Survival rates, OS, disease-free survival time, and time after first recurrence were all analyzed. Although there was no difference in disease-free survival time, there were significant differences between the HER2-positive and HER2-negative groups in OS and the time after initial recurrence. CONCLUSIONS: Metastatic breast cancer with overexpression of HER2/neu tends toward a poor prognosis, especially after the first recurrence. For such patients with metastatic breast cancer, a high-dose anthracycline-containing regimen might be needed.

Adult↗
PubMed2006

TCDB: the Transporter Classification Database for membrane transport protein analyses and information.

The Transporter Classification Database (TCDB) is a web accessible, curated, relational database containing sequence, classification, structural, functional and evolutionary information about transport systems from a variety of living organisms. TCDB is a curated repository for factual information compiled from >10,000 references, encompassing approximately 3000 representative transporters and putative transporters, classified into >400 families. The transporter classification (TC) system is an International Union of Biochemistry and Molecular Biology approved system of nomenclature for transport protein classification. TCDB is freely accessible at http://www.tcdb.org. The web interface provides several different methods for accessing the data, including step-by-step access to hierarchical classification, direct search by sequence or TC number and full-text searching. The functional ontology that underlies the database structure facilitates powerful query searches that yield valuable data in a quick and easy way. The TCDB website also offers several tools specifically designed for analyzing the unique characteristics of transport proteins. TCDB not only provides curated information and a tool for classifying newly identified membrane proteins, but also serves as a genome transporter-annotation tool.

Databases, Protein↗
PubMed2005

Autoimmunity in thrombotic thrombocytopenic purpura.

In the last few years, an autoimmune hypothesis for the pathogenesis of thrombotic thrombocytopenic purpura (TTP) has been proposed often, with variable success because of inconsistent supporting data. We are now aware that at least one subgroup of TTP patients does present with pathogenic autoantibodies (i.e, anti-ADAMTS13); this group consequently is a putative candidate for a curative treatment including plasma exchange (still the cornerstone of TTP treatment), together with corticosteroids or other immunosuppressants. Furthermore, for patients not responding to or relapsing following plasma exchange, the use of stronger immunosuppression (e.g., with the use of the anti-CD20 monoclonal antibody rituximab) should be considered as appropriate. Conversely, few data are actually available regarding the complex relationship between TTP and the antiphospholipid (aPL) syndrome, as well as other autoimmune diseases. Indeed, a correct differential diagnosis should be done on the basis of both different clinical presentations and autoantibody profile. At present, the presence of aPL antibodies should give evidence against a diagnosis of TTP, even though we cannot exclude that aPL antibodies may, in a minority of patients, be associated with a primary endothelial damage ultimately resulting in overt TTP.

ADAM Proteins↗
PubMed1998

Expression of CD44 variants and its association with survival in pancreatic cancer.

Since the CD44 variant 6(v6) molecule has been noted as a marker for tumor metastasis and prognosis in several tumors, we examined whether or not v6 is a useful marker for evaluating the prognosis of pancreatic cancer patients. In addition, we attempted to assess the clinicopathological implications for pancreatic cancer of the variant 2 (v2) isoform using a recently developed monoclonal antibody against a v2 epitope. The expression of CD44 variants was evaluated immunohistochemically in paraffin-embedded pancreatic cancer tissues from 42 patients who were confirmed surgically and histologically to have received curative resection. An indirect immunoperoxidase method was used with monoclonal antibodies against epitopes of the standard (CD44s) portion, v6 and v2. Protein expression data were evaluated statistically for any correlations with the length of survival or with histological parameters. The expression of CD44v6 and v2 was observed only in tumor cells, if at all. On the other hand, expression of total CD44 (including CD44v, as well as CD44s) was observed in both tumors and adjacent normal sites. Tumor tissue from 21 (50%) and 16 (38%) patients showed positive immunoreactivity with mAb 2F10 (anti-CD44v6) and mAb M23.6.1 (anti-CD44v2), respectively. The expression of CD44v6 and v2 was correlated with decreased overall survival (P = 0.0160 and P = 0.0125, respectively). A significant correlation was obtained between CD44v2 peptide expression and vessel invasion (P = 0.026). These results suggest that CD44v2 and CD44v6 may be useful markers for poor prognosis in curatively resected primary pancreatic cancer.

Antigens, CD↗
PubMed2005

Plant protein annotation in the UniProt Knowledgebase.

The Swiss-Prot, TrEMBL, Protein Information Resource (PIR), and DNA Data Bank of Japan (DDBJ) protein database activities have united to form the Universal Protein Resource (UniProt) Consortium. UniProt presents three database layers: the UniProt Archive, the UniProt Knowledgebase (UniProtKB), and the UniProt Reference Clusters. The UniProtKB consists of two sections: UniProtKB/Swiss-Prot (fully manually curated entries) and UniProtKB/TrEMBL (automated annotation, classification and extensive cross-references). New releases are published fortnightly. A specific Plant Proteome Annotation Program (http://www.expasy.org/sprot/ppap/) was initiated to cope with the increasing amount of data produced by the complete sequencing of plant genomes. Through UniProt, our aim is to provide the scientific community with a single, centralized, authoritative resource for protein sequences and functional information that will allow the plant community to fully explore and utilize the wealth of information available for both plant and non-plant model organisms.

Amino Acid Sequence↗
PubMed2001

Autofluorescence bronchoscopy improves staging of radiographically occult lung cancer and has an impact on therapeutic strategy.

BACKGROUND: The ability of conventional CT scans and fiberoptic bronchoscopy to localize and properly stage radiographically occult lung cancer (ROLC) in the major airways is limited. High-resolution CT (HRCT) scanning and autofluorescence bronchoscopy (AFB) may improve the assessment of ROLC before the most appropriate therapy can be considered. PATIENTS AND METHODS: We prospectively studied 23 patients with ROLC, who were referred for intraluminal bronchoscopic treatment (IBT) with curative intent. Additional staging with HRCT and AFB was performed prior to treatment. Twenty patients were men, 9 patients had first primary cancers, and 14 patients had second primary cancers or synchronous cancers. RESULTS: HRCT scanning showed that 19 patients (83%) had no visible tumor or enlarged lymph nodes. With AFB, only 6 of the 19 patients (32%) proved to have tumors < or = 1 cm(2) with visible distal margins. They were treated with IBT. In the remaining 13 patients, abnormal fluorescence indicated more extensive tumor infiltration than could be seen with conventional bronchoscopy alone. Six patients underwent radical surgery for stage T1-2N0 (n = 5) and stage T2N1 (n = 1) tumors. Specimens showed that tumors were indeed more invasive than initially expected. The remaining seven patients technically did not have operable conditions, so they were treated with external irradiation (n = 4) and IBT (n = 3). The range for the time of follow-up for all patients has been 4 to 58 months (median, 40 months). The follow-up data underscore the correlation between accurate tumor staging and survival. CONCLUSIONS: Our data showed that 70% of patients presenting with ROLC had a more advanced cancer than that initially diagnosed, which precludes IBT with curative intent. Additional staging with HRCT and AFB enabled better classification of true occult cancers. Our approach enabled the choice of the most appropriate therapy for each individual patient with ROLC.

Aged↗
PubMed2001

Quality of life in patients receiving radiation therapy for non-small cell lung cancer.

PURPOSE/OBJECTIVES: To determine whether perceptions of quality of life (QOL) change over time in patients with non-small cell lung cancer (NSCLC) who receive curative radiation therapy (XRT). DESIGN: Descriptive, longitudinal. SETTING: Radiotherapy clinic of a comprehensive cancer center. SAMPLE: 23 patients with NSCLC, selected by nonprobability, consecutive sampling, receiving curative XRT. METHODS: Subjects completed the Functional Assessment of Cancer Therapy-Lung (FACT-L) before, during, and twice after completion of the XRT treatment course. Data were analyzed using descriptive statistics and a multivariate approach to analysis of variance for repeated measures. MAIN RESEARCH VARIABLE: QOL. FINDINGS: FACT-L scores were significantly lower during XRT than before XRT, were significantly higher one month after XRT than before or during XRT, and were not significantly different from the pretreatment level four months after XRT. CONCLUSION: Perceptions of QOL change over time in patients with NSCLC receiving curative XRT. If the study findings are validated in a larger sample, nurses may be able to counsel patients with NSCLC receiving XRT. Nurses can inform patients that although QOL declines during XRT, the change is temporary because QOL will return to a level at least as high as the pretreatment level. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to assess patients perceptions of QOL throughout the course of XRT and assess for sequelae of treatment that affect QOL. Nursing interventions need to be developed and implemented to more effectively manage treatment sequelae and maintain QOL in patients with NSCLC while they receive curative XRT.

Activities of Daily Living↗
PubMed1999

Liver resection for metastatic colorectal cancer: assessing the risk of occult irresectable disease.

BACKGROUND: Liver resection is standard therapy for selected patients with metastatic colorectal cancer. Extrahepatic metastases and inability to remove all hepatic disease usually preclude curative resection and are the most common contraindications. This study analyzes irresectability in patients considered to have resectable disease taken to operation for potentially curative hepatic resection. We describe preoperative factors associated with irresectability and propose a preoperative scoring system that identifies patients at particularly high risk for occult irresectable disease. STUDY DESIGN: Patients considered to have resectable hepatic colorectal metastases were identified from a prospective database. Intraoperative findings that precluded liver resection were recorded. Demographic data, characteristics of the primary tumor, and characteristics of the hepatic metastases were recorded and analyzed. RESULTS: From April 1992 through July 1997, 416 patients were explored with the intention of performing a potentially curative liver resection; 329 (79%) were resected. Eighty-seven patients (21%) had apparently resectable tumors on preoperative imaging but irresectable disease at laparotomy. Forty-four patients (51%) had irresectable disease limited to the liver; 32 had extensive bilobar disease not appreciated before surgery, and 12 were not resected for technical or other reasons unrelated to disease extent. Forty-three patients (49%) had extrahepatic disease, 31 of whom had resectable hepatic tumors. Of the several preoperative factors analyzed, only the estimated number of hepatic tumors was an independent predictor of irresectable findings at operation. This held true for patients with extrahepatic metastases and those with extensive hepatic disease. From these data, we devised a preoperative scoring system that estimates the probability of finding occult irresectable disease. Resectability ranged from 95% in patients with a score of 0 (solitary, unilobar) to 62% in those with a score of 3 (multiple, bilobar; p = 0.0001). The predictive value of this scoring system was then validated by applying it prospectively to an additional group of 118 patients taken to surgery for resection; the results were similar. CONCLUSIONS: Standard preoperative investigations predicted resectability in 79% of patients with hepatic colorectal metastases. Unresectable disease limited to the liver and extrahepatic disease were seen with nearly equal frequency. The majority of patients with extrahepatic metastases had resectable hepatic disease (31 of 43, 72%). A preoperative scoring system is proposed that identifies patients at high risk for unrecognized irresectable disease and may help focus the use of additional diagnostic modalities such as laparoscopy and positron emission tomography (PET).

Colorectal Neoplasms↗
PubMed2006

Clinical implications of combined portal vein resection as a palliative procedure in patients undergoing pancreaticoduodenectomy for pancreatic head carcinoma.

BACKGROUND: The clinical implications of combined portal vein resections are controversial. METHODS: One-hundred and forty-nine consecutive patients underwent macroscopically curative pancreatectomies for pancreatic head carcinoma between January 1, 1996 and December 31, 2004. Portal vein resection was performed in 86 patients (58%). Data on surgical mortality, morbidity, perioperative outcome, pathological factors, initial recurrence site, and survival were retrospectively compared between the patients with and without portal vein resection. RESULTS: The incidence of postoperative pancreatic fistula was lower among patients who underwent portal vein resection. The median survival period was 14 months for the portal vein resection group and 35 months for the non-portal vein resection group, respectively. Combined portal vein resection was a significant predictor of poor survival using a multivariate analysis. Portal vein resection was strongly associated with larger tumor size, the degree of retropancreatic tissue invasion, the presence of extrapancreatic nerve plexus invasion, lymph node metastases, and positive cancer infiltration at the surgical margins. CONCLUSIONS: Portal vein resection at the time of pancreaticoduodenectomy can be safely performed. However, most of patients requiring portal vein resection do not achieve a potentially curative resection or a favorable survival term. As a result, the aggressive application and the strict selection of portal vein resection might reduce the incidence of positive surgical margins, enabling long-term survival in patients who do not require portal vein resection.

Adult↗
PubMed2005

GPS: a comprehensive www server for phosphorylation sites prediction.

Protein phosphorylation plays a fundamental role in most of the cellular regulatory pathways. Experimental identification of protein kinases' (PKs) substrates with their phosphorylation sites is labor-intensive and often limited by the availability and optimization of enzymatic reactions. Recently, large-scale analysis of the phosphoproteome by the mass spectrometry (MS) has become a popular approach. But experimentally, it is still difficult to distinguish the kinase-specific sites on the substrates. In this regard, the in silico prediction of phosphorylation sites with their specific kinases using protein's primary sequences may provide guidelines for further experimental consideration and interpretation of MS phosphoproteomic data. A variety of such tools exists over the Internet and provides the predictions for at most 30 PK subfamilies. We downloaded the verified phosphorylation sites from the public databases and curated the literature extensively for recently found phosphorylation sites. With the hypothesis that PKs in the same subfamily share similar consensus sequences/motifs/functional patterns on substrates, we clustered the 216 unique PKs in 71 PK groups, according to the BLAST results and protein annotations. Then, we applied the group-based phosphorylation scoring (GPS) method on the data set; here, we present a comprehensive PK-specific prediction server GPS, which could predict kinase-specific phosphorylation sites from protein primary sequences for 71 different PK groups. GPS has been implemented in PHP and is available on a www server at http://973-proteinweb.ustc.edu.cn/gps/gps_web/.

Animals↗
PubMed1998

A Bayesian hierarchical survival model for the institutional effects in a multi-centre cancer clinical trial.

In randomized clinical trials comparing treatment effects on diseases such as cancer, a multi-centre trial is usually conducted to accrue the required number of patients in a reasonable period of time. While we interpret the average treatment effect, it is necessary to examine the homogeneity of the observed treatment effects across institutions, that is, treatment-by-institution interaction. If the homogeneity is confirmed, the conclusions concerning treatment effects can be generalized to a broader patient population. In this paper, a Bayesian hierarchical survival model is used to investigate the institutional effects on the efficacy of treatment as well as on the baseline risk. The marginal posterior distributions are estimated by a Markov chain Monte Carlo method, that is, Gibbs sampling, to overcome current computational limitations. The robustness of the inferences to the distributional assumption for the random effects is also examined. We illustrate the methods with analyses of data from a multi-centre cancer clinical trial, which investigated the efficacy of immunochemotherapy as an adjuvant treatment after curative resection of gastric cancer. In this trial there is little difference in the treatment effects across institutions and the treatment is shown to be effective, while there appears to be substantial variation in the baseline risk across institutions. This result indicates that the observed treatment effects might be generalized to a broader patient population.

Adjuvants, Immunologic↗