bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biliary intraepithelial neoplasia in patients without chronic biliary disease
Authors: Wu Tsung‐Teh , Levy Michael , Correa Arlene M. , Rosen Charles B. , Abraham Susan C. 
Published: August 2009

AbstractBACKGROUND:Biliary intraepithelial neoplasia (BilIN) represents a spectrum of proliferative and/or cytologically atypical lesions of the large intrahepatic bile ducts. BilIN is believed to be a major pathway leading to the development of intrahepatic cholangiocarcinoma (CCA) through a dysplasia‐carcinoma sequence. Recently, a large interobserver agreement study in patients with hepatolithiasis, choledochal cysts, and primary sclerosing cholangitis proposed diagnostic criteria for 3 categories of BilIN based on increasing grades of nuclear atypia and loss of nuclear polarity: BilIN‐1, BilIN‐2, and BilIN‐3. BilIN has not been systematically studied as a potential precursor lesion in patients with nonbiliary liver disease, despite the epidemiologic association between intrahepatic CCA, hepatitis C infection (HCV), and alcohol (EtOH) consumption.METHODS:We submitted 12 paraffin blocks targeted to the large intrahepatic and hilar ducts in each of 244 explanted livers with EtOH cirrhosis (n = 94), HCV cirrhosis (n = 44), EtOH + HCV (n = 26), and noncirrhotic controls (eg, livers removed for metabolic disorders, massive hepatic necrosis) (n = 80), and classified all bile duct profiles as normal/reactive, metaplastic, or BilIN‐1, ‐2, or ‐3 (flat or papillary).RESULTS:Livers transplanted for EtOH and EtOH + HCV cirrhosis had the highest prevalence of BilIN, greater numbers of ducts with BilIN, and a shift toward higher grades of BilIN as compared with HCV alone and with noncirrhotics. In EtOH, the highest grades of BilIN were 0 = 3%, BilIN‐1 = 35%, BilIN‐2 = 57%, BilIN‐3 = 4%; in EtOH + HCV: 4%, 38%, 54%, 4%; in HCV: 18%, 55%, 20%, 7%; and in noncirrhotics: 45%, 39%, 16%, 0%, respectively. In both univariate and multivariate analysis, EtOH (P < .001), EtOH + HCV (P < .001), and HCV cirrhosis (P < .001) were all significant predictors of BilIN grade. Multifocal BilIN (≥10 ducts) was present in 91% of EtOH, 92% of EtOH + HCV, and 61% of HCV cirrhosis, as compared with only 34% of noncirrhotics (P values of <.0001, <.001, and .002, respectively, in both univariate and multivariate analysis). Papillary or micropapillary architecture of BilIN was also more common in EtOH (47%) than in EtOH + HCV (19%), HCV (23%), or noncirrhotics (17%) (P < .001 in both univariate and multivariate analysis). BilIN‐3 occurred only in the setting of cirrhosis (8 of 164 cirrhotic livers, 5%) and was associated with CCA (2 cases) or mixed hepatocellular/CCA (1 case) elsewhere in the liver.CONCLUSIONS:In aggregate, these findings provide morphologic support for the epidemiologic role of alcohol and HCV in the development of CCA. Cancer 2009. © 2009 American Cancer Society.
Why cancer at the primary site and in the lymph nodes contributes to the risk of cancer death
Authors: Michaelson James S. , Chen L. Leon , Silverstein Melvin J. , Cheongsiatmoy Justin A. , Mihm Martin C. , Sober Arthur J. , Tanabe Kenneth K. , Smith Barbara L. , Younger Jerry 
Published: August 2009

AbstractBACKGROUND:Cancer at both the primary site and in the lymph nodes is associated with lethality, although the mechanism by which lethality arises from each site has been poorly understood. For breast carcinoma, each positive lymph node contributes an approximately 6% risk of death, and each millimeter of primary tumor greatest dimension contributes approximately 1%; whereas, for melanoma, each positive lymph node contributes an approximately 23% risk, and each millimeter of tumor thickness contributes approximately 8%: This is described by a pair of linked equations, the Size+Nodes method.METHODS:A simple expression, the ProbabilityEstimation equation, which was derived from the authors' binary‐biologic model of cancer metastasis, was used to calculate the probabilities of spread of cancer cells from data on tumor size, lymph node status, and death rate.RESULTS:In this report, the authors demonstrated, that when similar masses of cancer are compared, the chance of lethal spread of a cancer cell to the periphery is approximately the same whether the spread emerges from a lymph node or from the primary site. The greater the number of cells at the primary site (tumor size) or the greater the number of cells in the lymph nodes (number of positive lymph nodes), the greater is the aggregate chance that 1 or more cells has undergone a lethal event of spread, a process captured by the Size+Nodes equations.CONCLUSIONS:The lethal contributions of cancer at the primary site and lymph nodes can be explained by a simple mechanical process of the spread of cancer cells occurring with definable probabilities per cell. The presence of cancer in the lymph nodes does not indicate an intrinsic change in a malignancy but, rather, an increased mass of cancer from which spread can emerge. Cancer 2009. © 2009 American Cancer Society.
The efficacy for unresectable hepatocellular carcinoma may be improved by transcatheter arterial chemoembolization in combination with a traditional Chinese herbal medicine formula
Authors: Yu Yang , Lang Qingbo , Chen Zhe , Li Bai , Yu Chaoqin , Zhu Dezeng , Zhai Xiaofeng , Ling Changquan 
Published: August 2009

AbstractTranscatheter arterial chemoembolization (TACE) is the most widely used primary treatment for unresectable hepatocellular carcinoma (HCC) because of its survival benefit, although its clinical effect is still far from satisfactory. In China, there has been a long history of using traditional Chinese medicine in the treatment of liver cancer and other malignancies. In this study, the authors evaluated the effect of combined therapy with TACE and JDF granule preparation (a traditional Chinese herbal medicine formula) in the treatment of patients with unresectable HCC on survival. Clinical data, including baseline, performance status change, and survival time of 165 patients with unresectable HCC seen between January 2002 and December 2007 were retrospectively analyzed. Among the 165 patients, 80 patients (study group) received combined therapy consisting of TACE and a long‐term maintenance treatment with oral JDF granule preparation, and 85 patients (control group) received TACE alone. The survival rate of both groups was calculated by the Kaplan‐Meier method. Factors possibly affecting survival were assessed by multivariate analysis in the Cox proportional hazard model. The median overall survival was 9.2 months (95% confidence interval [95% CI], 6.94‐1.46) in the study group versus 5.87 months (95% CI, 4.21‐7.52) in the control group. In the study group (TACE + JDF), 1‐year, 2‐year, and 3‐year survival rates were 41.2%, 18.4%, and 9.6%, respectively. The Cox regression analysis revealed the therapy model to be an independent predictor of patient prognosis. Current study data demonstrated that TACE combined with JDF granule preparation could improve the prognosis of patients. TACE combined with JDF granule preparation may prolong survival of patients with unresectable HCC. Cancer 2009. © 2009 American Cancer Society.
Combination therapy with rituximab and intravenous or oral fludarabine in the first‐line, systemic treatment of patients with extranodal marginal zone B‐cell lymphoma of the mucosa‐associated lymphoid tissue type
Authors: Salar Antonio , Domingo‐Domenech Eva , Estany Cristina , Canales Miguel A. , Gallardo Fernando , Servitje Octavio , Fraile Guadalupe , Montalbán Carlos 
Published: August 2009

AbstractBACKGROUND:Currently, there are no consensus guidelines regarding the best therapeutic option for patients with extranodal marginal zone lymphomas of the mucosa‐associated lymphoid tissue (MALT) type.METHODS:Patients with systemically untreated or de novo extranodal MALT lymphoma received rituximab 375 mg/m2 intravenously on Day 1 and fludarabine 25 mg/m2 intravenously on Days 1 through 5 (Days 1‐3 in patients aged >70 years) every 4 weeks, for 4 to 6 cycles. After the first cycle, oral fludarabine could be given orally at 40 mg/m2 on the same schedule. After 3 cycles, a workup was done. Patients who achieved a complete remission (CR) received an additional cycle, and patients who achieved a partial remission (PR) received a total of 6 cycles.RESULTS:Twenty‐two patients were studied, including 12 patients with gastric lymphoma and 10 patients with extragastric MALT lymphoma. Six patients (27%) had stage IV disease. In total, 101 cycles were administered (median, 4 cycles per patients). After the third cycle, 13 patients (62%) achieved a CR, and 8 patients (38%) achieved a PR. Primary extragastric disease was an adverse factor to achieve CR after 3 cycles of chemotherapy (hazard ratio, 23.3; 95% confidence interval, 2.0‐273.3). At the end of treatment, the overall response rate was 100%, and 90% of patients achieved a CR. The progression‐free survival rate at 2 years in patients with gastric and extragastric MALT lymphoma was 100% and 89%, respectively. Toxicities were mild and mainly were hematologic.CONCLUSIONS:Combination therapy with rituximab and fludarabine is a very active treatment with favorable safety profile as first‐line systemic treatment for patients with extranodal MALT lymphoma. Cancer 2009. © 2009 American Cancer Society.
Cuplike nuclei (prominent nuclear invaginations) in acute myeloid leukemia are highly associated with FLT3 internal tandem duplication and NPM1 mutation
Authors: Chen Weina , Konoplev Sergej , Medeiros L. Jeffrey , Koeppen Hartmut , Leventaki Vasiliki , Vadhan‐Raj Saroj , Jones Dan , Kantarjian Hagop M. , Falini Brunangelo , Bueso‐Ramos Carlos E. 
Published: August 2009

AbstractBACKGROUND:A small subset of patients with acute myeloid leukemia (AML) have cuplike nuclei. Other investigators have demonstrated that these neoplasms have distinctive clinicopathologic and molecular features.METHODS:The authors searched for patients who had AML with cuplike nuclei at their institution over a 10‐year interval. A strict definition for cuplike nuclei was used: ≥10% blasts with nuclear invaginations in ≥25% of the nuclear area. The relevant data were reviewed, and the results were compared with a control group of patients who had AML without cuplike nuclei.RESULTS:In total, 22 patients who had AML with cuplike nuclei were identified and were classified as AML without maturation (French‐American‐British classification M1) (AML M1). Compared with the control group (AML M1), patients who had AML with cuplike nuclei were associated significantly with fms‐like tyrosine kinase 3 (FLT3)‐internal tandem duplication (ITD) (86% vs 38%, respectively; P = .002); nucleophosmin 1 (NPM1) mutations (86% vs 19%; P < .0001); both mutations (77% vs 14%; P < .0001); normal karyotype (86% vs 40%; P = .003); bone marrow blast count (90% vs 84%; P = .016); myeloperoxidase positivity (95% vs 30% blasts; P = .001); higher D‐dimer levels (>5000 ng/mL vs 569 ng/mL; P = .001); and the absence of CD7 (91% vs 52%; P = .007), CD34 (82% vs 5%; P < .0001), and human leukocyte antigen, D‐related (59% vs 10%; P = .001). There were no differences in age, sex, or peripheral blood counts. The positive predictive value of recognizing AML with cuplike nuclei for FLT3‐ITD, NPM1, and both mutations was 81%, 86%, and 77%, respectively.CONCLUSIONS:Cuplike nuclei in AML were highly associated with the presence of NPM1 and FLT3‐ITD mutations and with several clinicopathologic and immunophenotypic features. Recognition of the distinctive morphologic features of AML with cuplike nuclei may be helpful in streamlining the workup of these neoplasms. Cancer 2009. © 2009 American Cancer Society.
Estimating breast cancer‐specific and other‐cause mortality in clinical trial and population‐based cancer registry cohorts
Authors: Dignam James J. , Huang Lan , Ries Lynn , Reichman Marsha , Mariotto Angela , Feuer Eric 
Published: August 2009

AbstractBACKGROUND:To compute net cancer‐specific survival rates using population data sources (eg, the National Cancer Institute's Surveillance, Epidemiology, and End Results [SEER] Program), 2 approaches primarily are used: relative survival (observed survival adjusted for life expectancy) and cause‐specific survival based on death certificates. The authors of this report evaluated the performance of these estimates relative to a third approach based on detailed clinical follow‐up history.METHODS:By using data from Cancer Cooperative Group clinical trials in breast cancer, the authors estimated 1) relative survival, 2) breast cancer‐specific survival (BCSS) determined from death certificates, and 3) BCSS obtained by attributing cause according to clinical events after diagnosis, which, for this analysis was considered the benchmark “true” estimate. Noncancer life expectancy also was compared between trial participants, SEER registry patients, and the general population.RESULTS:Among trial patients, relative survival overestimated true BCSS in patients with lymph node‐negative breast cancer; whereas, in patients with lymph node‐positive breast cancer, the 2 estimates were similar. For higher risk patients (younger age, larger tumors), relative survival accurately estimated true BCSS. In lower risk patients, death certificate BCSS was more accurate than relative survival. Noncancer life expectancy was more favorable among trial participants than in the general population and among SEER patients. Tumor size at diagnosis, which is a potential surrogate for screening use, partially accounted for this difference.CONCLUSIONS:In the clinical trials, relative survival accurately estimated BCSS in patients who had higher risk disease despite more favorable other‐cause mortality than the population at large. In patients with lower risk disease, the estimate using death certificate information was more accurate. For SEER data and other data sources where detailed postdiagnosis clinical history was unavailable, death certificate‐based estimates of cause‐specific survival may be a superior choice. Cancer 2009. © 2009 American Cancer Society.
Lymph node status after neoadjuvant radiotherapy for rectal cancer is a biologic predictor of outcome
Authors: Chang George J. , Rodriguez‐Bigas Miguel A. , Eng Cathy , Skibber John M. 
Published: August 2009

AbstractBACKGROUND:Lymph node (LN) status after surgery for rectal cancer is affected by preoperative radiotherapy. The purpose of this study was to perform a population‐based evaluation of the impact of pathologic LN status (ypN) after neoadjuvant radiotherapy on survival.METHODS:Patients undergoing radical resection for rectal adenocarcinoma were identified from the Surveillance Epidemiology and End Results registry (1991‐2004). Patient characteristics, overall survival, and cancer‐specific survival (CSS) by ypN stage after surgery and use of preoperative or postoperative radiotherapy were compared.RESULTS:Of the 23,809 patients identified, 12,513 received preoperative (n = 5367) or postoperative (n = 7146) radiotherapy and resection. Preoperative patients were more likely to be younger (P < .001) and histopathologically free of detectable nodal metastasis (ypN0) than postoperative (51.8% vs 31.7%, P < .001). Median total numbers of LNs (6 vs 10) and positive LNs (2 vs 3) were lower among preoperative than postoperative (P < .001 for both). OS and CSS were similar among pN0 patients. However, on proportional hazards regression, ypN+ stage was associated with an increase in relative risk for death by 21% overall (hazard ratio [HR] = 1.21; 95% confidence interval 1.09‐1.35, P < .001) and 23% cancer‐specific (HR = 1.23; P = .001) for preoperative compared with postoperative.CONCLUSIONS:Pathologic LN status after neoadjuvant radiotherapy for rectal cancer is a biologic marker of prognosis. Patients who are ypN+ after preoperative are a subgroup of LN positive patients with adverse outcome. These high‐risk patients should be targeted for studies of novel multidisciplinary approaches, including expanded chemo‐ and biologic therapies. Cancer 2009. © 2009 American Cancer Society.
Local recurrence after surgery for early stage lung cancer
Authors: Kelsey Chris R. , Marks Lawrence B. , Hollis Donna , Hubbs Jessica L. , Ready Neal E. , D'Amico Thomas A. , Boyd Jessamy A. 
Published: August 2009

AbstractBACKGROUND:The objective of the current study was to evaluate the actuarial risk of local failure (LF) after surgery for stage I to II nonsmall cell lung cancer (NSCLC) and assess surgical and pathologic factors affecting this risk.METHODS:The records, including pertinent radiologic studies, of all patients who underwent surgery for T1 to T2, N0 to N1 NSCLC at Duke University between 1995 and 2005 were reviewed. Risks of disease recurrence were estimated using the Kaplan‐Meier method. A multivariate Cox regression analysis assessed factors associated with LF in the entire cohort and a subgroup undergoing optimal surgery for stage IB to II disease.RESULTS:For all 975 consecutive patients, the 5‐year actuarial risk of local and/or distant disease recurrence was 36%. First sites of failure were local only (25%), local and distant (29%), and distant only (46%). The 5‐year actuarial risk of LF was 23%. On multivariate analysis, squamous/large cell histology (hazards ratio [HR], 1.98), stage > IA (HR, 2.02), and sublobar resections (HR, 1.99) were found to be independently associated with a higher risk of LF. For the subset of patients (n = 445) undergoing at least a lobectomy with negative surgical margins and currently considered for adjuvant chemotherapy (stage IB‐II disease), the 5‐year actuarial risk of LF was 27%. Within this subgroup, squamous/large cell histology (HR, 2.5) and lymphovascular space invasion (HR, 1.74) were associated with a higher risk of LF. The 5‐year rate of LF was 13%, 32%, and 47%, respectively, with 0, 1, or 2 risk factors.CONCLUSIONS:Greater than half of disease recurrences after surgery for early stage NSCLC involved local sites. Pathologic factors may help to distinguish those patients at highest risk. Cancer 2009. © 2009 American Cancer Society.
Expression and regulation of vitamin D3 upregulated protein 1 (VDUP1) is conserved in mammalian and insect brain
Authors: Levendusky Mark C. , Basle Jacilyn , Chang Solomon , Mandalaywala Neil V. , Voigt Jeffrey M. , Dearborn Richard E. 
Published: August 2009

AbstractOriginally characterized as a cell‐cycle inhibitor induced by vitamin D3, the tumor suppressor vitamin‐D3 upregulated protein 1 (VDUP1) has increasingly been shown to play major physiological roles in cell differentiation and glucose metabolism. Here we show evolutionarily conserved expression patterns of VDUP1 in Drosophila and rat nervous systems, including subcellular localization—cytoplasmic enrichment in neurons and nuclear expression in glia. These anatomical correlates suggested conservation of VDUP1 regulation, which was investigated both functionally and through promoter studies. Characterization of orthologous vdup1 cis‐regulatory regions identified evolutionarily conserved sequence blocks (CSBs) with similarities to neural enhancers, including basic helix‐loop‐helix (bHLH) transcription factor Neurogenin/Math/atonal and Mash/achaete‐scute family members. E‐boxes (CANNTG), the binding sites for bHLH proteins, were associated with these CSBs as well, including E‐boxes known to mediate glucose‐dependent upregulation of VDUP1 in nonneuronal cells. Hyperglycemia‐induced upregulation of VDUP1 was observed in brain tumor cells and in the Drosophila nervous system, which resulted in developmental arrest. Taken together, these data demonstrate evolutionary conservation of VDUP1 regulation and function, and suggest an expanding role for VDUP1 in nervous system development. J. Comp. Neurol. 517:581–600, 2009. © 2009 Wiley‐Liss, Inc.
An alternative procedure for simulating one‐dimensional transport phenomena with shock waves in a gas
Authors: Porto Eliane Maracajá , Martins‐Costa Maria Laura , Saldanha da Gama Rogério M. 
Published: August 2009

AbstractThis article employs an alternative procedure to treat a class of non‐linear hyperbolic systems, using a preliminary model to describe pollutants motion in an atmosphere, accounting for the production or destruction of pollutants, described, as a first approximation, by a source term. The mathematical description consists of a non‐linear hyperbolic system of m+2 partial differential equations representing mass and momentum conservation for the multicomponent mixture of air and gases and mass balance equations for the gases. After simplifying assumptions, the resulting one‐dimensional system of m+2 equations is simulated in such a way that the simultaneous problem is treated sequentially: the operator is splitted into a non‐homogeneous (time‐dependent) ordinary part and a homogeneous associated hyperbolic one. This latter is simulated by a Glimm's scheme for evolution in time, employing an approximate Riemann solver for each two consecutive steps. The employed Riemann solver approximates the solution of the associated Riemann problem by piecewise constant functions always satisfying the jump condition—giving rise to an approximation easier to implement with lower computational cost. Comparison with the standard procedure, employing the complete solution of the associated Riemann problem for implementing Glimm's scheme, has shown good agreement. Copyright © 2009 John Wiley & Sons, Ltd.
Posttranslational regulation of BCL2 levels in cerebellar granule cells: A mechanism of neuronal survival
Authors: Lossi Laura , Gambino Graziana , Ferrini Francesco , Alasia Silvia , Merighi Adalberto 
Published: August 2009

AbstractApoptosis can be modulated by K+ and Ca2+ inside the cell and/or in the extracellular milieu. In murine organotypic cultures, membrane potential‐regulated Ca2+ signaling through calcineurin phosphatase has a pivotal role in development and maturation of cerebellar granule cells (CGCs). P8 cultures were used to analyze the levels of expression of B cell lymphoma 2 (BCL2) protein, and, after particle‐mediated gene transfer in CGCs, to study the posttranslational modifications of BCL2 fused to a fluorescent tag in response to a perturbation of K+/Ca2+ homeostasis. There are no changes in Bcl2 mRNA after real time PCR, whereas the levels of the fusion protein (monitored by calculating the density of transfected CGCs under the fluorescence microscope) and of BCL2 (inWestern blotting) are increased. After using a series of agonists/antagonists for ion channels at the cell membrane or the endoplasmic reticulum (ER), and drugs affecting protein synthesis/degradation, accumulation of BCL2 was related to a reduction in posttranslational cleavage by macroautophagy. The ER functionally links the [K+]e and [Ca2+]i to the BCL2 content in CGCs along two different pathways. The first, triggered by elevated [K+]e under conditions of immaturity, is independent of extracellular Ca2+ and operates via IP3 channels. The second leads to influx of extracellular Ca2+ following activation of ryanodine channels in the presence of physiological [K+]e, when CGCs are maintained in mature status. This study identifies novel mechanisms of neuroprotection in immature and mature CGCs involving the posttranslational regulation of BCL2. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009