bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-infiltrating B lymphocytes as an efficient source of highly specific immunoglobulins recognizing tumor cells
Authors: Pavoni Emiliano , Monteriù Giorgia , Santapaola Daniela , Petronzelli Fiorella , Anastasi Anna Maria , Pelliccia Angela , D'Alessio Valeria , De Santis Rita , Minenkova Olga 
Published: October 2007

Abstract

Background
There is much evidence that tumor cells elicit a humoral immune response in patients. In most cases, the presence of antibodies in peripheral blood is detected only in small proportion of patients with tumors overexpressing the corresponding antigen. In the present study, we analyzed the significance of local humoral response provided by tumor-infiltrating lymphocytes in breast cancer patients.

Methods
The ability of a patient's immune system to produce specific antibodies inside tumor tissue, capable of recognizing tumor cells, was explored through analysis of the oligoclonality of antibodies derived from tumor-infiltrating lymphocytes and construction of a series of recombinant antibody libraries in scFv format, derived from breast tumor-infiltrating B lymphocytes. These libraries and one from peripheral blood lymphocytes of a single breast cancer patient were panned against three purified surface tumor antigens, such as CEA, MUC1 and ED-B domain, and against intact MCF7 breast carcinoma cells.

Results
Application of novel display vector, pKM19, allowed isolation of a large panel of breast cancer-specific antibodies against known tumor antigens, as well as against breast carcinoma cells. Reactivity of novel scFvs was confirmed by ELISA, immunohistochemistry, fluorescence staining and flow cytometry. We demonstrated that seven of ten primary breast tumor specimens, obtained using discarded surgical material, could be exploited as an appropriate source for generation of phage display libraries, giving highly specific antitumor antibodies which recognize heterologous tumor cells.

Conclusion
Local humoral immune response within tumor tissue in breast cancer patients frequently has an oligoclonal character. Efficient selection of specific antitumor antibodies from recombinant antibody libraries, derived from such oligoclonal tumor-infiltrated B lymphocytes, indicates the presence of natural immune response against tumor antigens in these patients. The described method is very promising for development of antitumor antibodies, potentially useful for diagnostic and therapeutic approaches.
Enhancement of cell proliferation in various mammalian cell lines by gene insertion of a cyclin-dependent kinase homolog
Authors: Jaluria Pratik , Betenbaugh Michael , Konstantopoulos Konstantinos , Shiloach Joseph 
Published: October 2007

AbstractBackgroundGenomics tools, particularly DNA microarrays, have found application in a number of areas including gene discovery and disease characterization. Despite the vast utility of these tools, little work has been done to explore the basis of distinct cellular properties, especially those important to biotechnology such as growth. And so, with the intent of engineering cell lines by manipulating the expression of these genes, anchorage-independent and anchorage-dependent HeLa cells, displaying markedly different growth characteristics, were analyzed using DNA microarrays.ResultsTwo genes, cyclin-dependent kinase like 3 (cdkl3) and cytochrome c oxidase subunit (cox15), were up-regulated in the faster growing, anchorage-independent (suspension) HeLa cells relative to the slower growing, anchorage-dependent (attached) HeLa cells. Enhanced expression of either gene in the attached HeLa cells resulted in elevated cell proliferation, though insertion ofcdkl3had a greater impact than that ofcox15. Moreover, flow cytometric analysis indicated that cells with an insert ofcdkl3were able to transition from the G0/G1 phases to the S phase faster than control cells. In turn, expression ofcox15was seen to increase the maximum viable cell numbers achieved relative to the control, and to a greater extent thancdkl3. Quantitatively similar results were obtained with two Human Embryonic Kidney-293 (HEK-293) cell lines and a Chinese Hamster Ovary (CHO) cell line. Additionally, HEK-293 cells secreting adipocyte complement-related protein of 30 kDa (acrp30) exhibited a slight increase in specific protein production and higher total protein production in response to the insertion of eithercdkl3orcox15.ConclusionThese results are consistent with previous studies on the functionalities ofcdkl3andcox15. For instance, the effect ofcdkl3on cell growth is consistent with its homology to thecdk3gene which is involved in G1 to S phase transition. Likewise, the increase in cell viability due tocox15expression is consistent with its role in oxidative phosphorylation as an assembly factor for cytochrome c oxidase and its involvement removing apoptosis-inducing oxygen radicals. Collectively, the present study illustrates the potential of using microarray technology to identify genes influential to specific cellular processes with the possibility of engineering cell lines as desired to meet production needs.
Influence of an e-mail with a drug information attachment on sales of prescribed drugs: a randomized controlled study
Authors: Edward Christina , Himmelmann Anders , Wallerstedt Susanna M 
Published: October 2007

AbstractBackgroundTo provide doctors with producer-independent information to facilitate choice of treatment is an important task. The objective of the present study was to evaluate if an e-mail with a drug information attachment has effects on sales of prescribed drugs and if the design of the attachment is of importance.MethodsThe Swedish pharmaceutical benefit board found rizatriptan (Maxalt®) 10 mg to be the most cost-effective triptan. All 119 heads of primary care units in western Sweden were randomized to receive information concerning this conclusion via (i) e-mail with attachment I, (ii) e-mail with attachment II or (iii) no information (control). Attachment I was a short one (heading plus three lines text), whereas attachment II was a long one (heading plus one page text and one page with tables). The change in percentage rizatriptan of total triptans sold before and after the intervention (May – July 2004 and May – July 2005, respectively) was compared between the groups.ResultsTotally 48,229 (2004) and 50,674 (2005) defined daily doses of triptans were prescribed and sold during May – July in primary care units in the western part of Sweden. The absolute change in percentage rizatriptan was greater in the intervention groups compared with the control group 2 (25th– 75thpercentile: -3 – 7) vs 0 (-7 - 5), P = 0.031). The absolute change in percentage rizatriptan did not differ between the two attachment groups (P = 0.93).ConclusionAn e-mail with a drug information attachment may influence sales of prescribed drugs. No difference between different designs of the attachment could be detected.
Improved weight management using genetic information to personalize a calorie controlled diet
Authors: Arkadianos Ioannis , Valdes Ana M , Marinos Efstathios , Florou Anna , Gill Rosalynn D , Grimaldi Keith A 
Published: October 2007

Abstract

Background
Gene-environment studies demonstrate variability in nutrient requirements depending upon individual variations in genes affecting nutrient metabolism and transport. This study investigated whether the inclusion of genetic information to personalize a patient's diet (nutrigenetics) could improve long term weight management.

Methods
Patients with a history of failures at weight loss were offered a nutrigenetic test screening 24 variants in 19 genes involved in metabolism. 50 patients were in the nutrigenetic group and 43 patients attending the same clinic were selected for comparison using algorithms to match the characteristics: age, sex, frequency of clinical visits and BMI at initial clinic visit. The second group of 43 patients did not receive a nutrigenetic test. BMI reduction at 100 and > 300 days and blood fasting glucose were measured.

Results
After 300 days of follow-up individuals in the nutrigenetic group were more likely to have maintained some weight loss (73%) than those in the comparison group (32%), resulting in an age and gender adjusted OR of 5.74 (95% CI 1.74–22.52). Average BMI reduction in the nutrigenetic group was 1.93 kg/m2(5.6% loss) vs. an average BMI gain of 0.51 kg/m2(2.2% gain) (p < 0.023). Among patients with a starting blood fasting glucose of > 100 mg/dL, 57% (17/30) of the nutrigenetic group but only 25% (4/16) of the non-tested group had levels reduced to < 100 mg/dL after > 90 days of weight management therapy (OR for lowering glucose to < 100 mg/dL due to diet = 1.98 95%CI 1.01, 3.87, p < 0.046).

Conclusion
Addition of nutrigenetically tailored diets resulted in better compliance, longer-term BMI reduction and improvements in blood glucose levels.
The influence of gender on the effects of aspirin in preventing myocardial infarction
Authors: Yerman Todd , Gan Wen Q , Sin Don D 
Published: October 2007

Abstract

Background
There is considerable variation in the effect of aspirin therapy reducing the risk of myocardial infarction (MI). Gender could be a potential explanatory factor for the variability. We conducted a systematic review and meta-analysis to determine whether gender mix might play a role in explaining the large variation of aspirin efficacy across primary and secondary MI prevention trials.

Methods
Randomized placebo-controlled clinical trials that examined the efficacy of aspirin therapy on MI were identified by using the PUBMED database (1966 to October 2006). Weighted linear regression technique was used to determine the relationship between log-transformed relative risk (RR) of MI and the percentage of male participants in each trial. The reciprocal of the standard error of the RR in each trial (1/SE) was used as the weight.

Results
A total of 23 trials (n = 113 494 participants) were identified. Overall, compared with placebo, aspirin reduced the risk of non-fatal MI (RR = 0.72, 95% confidence interval (CI) 0.64–0.81, p < 0.001) but not of fatal MI (RR = 0.88, 95% CI 0.75–1.03, p = 0.120). A total of 27% of the variation in the non-fatal MI results could be accounted for by considering the gender mix of the trials (p = 0.017). Trials that recruited predominantly men demonstrated the largest risk reduction in non-fatal MI (RR = 0.62, 95% CI 0.54–0.71), while trials that contained predominately women failed to demonstrate a significant risk reduction in non-fatal MI (RR = 0.87, 95% CI 0.71–1.06).

Conclusion
Gender accounts for a substantial proportion of the variability in the efficacy of aspirin in reducing MI rates across these trials, and supports the notion that women might be less responsive to aspirin than men.
Dietary intake and breast density in high-risk women: a cross-sectional study
Authors: Tseng Marilyn , Byrne Celia , Evers Kathryn A , Daly Mary B 
Published: October 2007

Abstract
Background
Women with a family history of breast cancer may be at higher risk for breast cancer, but few previous studies evaluating diet and breast cancer have focused on such women. The objective of the present study was to determine whether diet, a modifiable risk factor, is related to breast density among women at high genetic risk for breast cancer.

Methods
Women with at least one first-degree or second-degree relative with breast cancer or ovarian cancer participating in the Fox Chase Cancer Center Family Risk Assessment Program completed health history and food frequency questionnaires and received standard screening mammograms. Cranial–caudal mammographic images were classified into the four Breast Imaging Reporting and Data System categories ranging from 'entirely fatty' to 'extremely dense'. Logistic regression analysis using proportional odds models for polychotomous outcomes provided estimates of odds ratios for having a higher category versus a lower category of breast density.

Results
Among 157 high-risk women, breast density was inversely associated with vitamin D intake (odds ratio for third tertile versus first tertile, 0.5; 95% confidence interval, 0.2–1.0). In contrast, intakes above the median level for protein (odds ratio, 3.0; 95% confidence interval, 1.3–6.9) and above the median level for animal protein (odds ratio, 4.3; 95% confidence interval, 1.8–10.3) were associated with higher breast density, but only among women whose family history did not reflect a known familial cancer syndrome or a breast cancer predisposition gene.

Conclusion
For women with a strong family history that was not associated with known cancer syndromes, dietary factors may be associated with breast density, a strong predictor of breast cancer risk. Since women with strong family history are often very motivated to change their lifestyle habits, further studies are needed to confirm whether changes in diet will change the breast density and the subsequent onset of breast cancer in these women.
Improved survival of children with sepsis and purpura: effects of age, gender, and era
Authors: Maat Martine , Buysse Corinne MP , Emonts Marieke , Spanjaard Lodewijk , Joosten Koen FM , de Groot Ronald , Hazelzet Jan A 
Published: October 2007

Abstract
Background
To gain insight into factors that might affect results of future case-control studies, we performed an analysis of children with sepsis and purpura admitted to the paediatric intensive care unit (PICU) of Erasmus MC-Sophia Children's Hospital (Rotterdam, The Netherlands).

Methods
Between 1988 and 2006, all 287 children consecutively admitted with sepsis and purpura were included in various sepsis studies. Data regarding age, gender, ethnicity, serogroup of Neisseria meningitidis, severity, therapy, and survival were collected prospectively. These data were pooled into one database and analyzed retrospectively.

Results
The case fatality rate (CFR) from sepsis and purpura was 15.7%. During the study period, survival improved significantly. Younger age was significantly associated with more severe disease and a higher CFR. Children under the median age of 3.0 years had an increased risk of case fatality (odds ratio 4.3, 95% confidence interval 2.1 to 9.2; p < 0.001). Gender was not associated with CFR. However, males did have higher Paediatric Risk of Mortality scores, fewer PICU-free days, and more presence of shock. The course of sepsis and purpura was not related to ethnic origin. A causative organism was isolated in 84.3% of cases. N. meningitidis was the major organism (97.5%). Although N. meningitidis serogroup B was observed more often in younger children, serogroups were not associated with severity or survival. During the study period, the use of inotropic agents and corticosteroids changed substantially (less dopamine and more dobutamine, norepinephrine, and corticosteroids).

Conclusion
Age and gender are determinants of severity of paediatric sepsis and purpura. Survival rates have improved during the last two decades.
ITIM-dependent endocytosis of CD33-related Siglecs: role of intracellular domain, tyrosine phosphorylation, and the tyrosine phosphatases, Shp1 and Shp2
Authors: Walter Roland B , Raden Brian W , Zeng Rong , Häusermann Peter , Bernstein Irwin D , Cooper Jonathan A 
Published: October 2007

AbstractThe leukocyte CD33-related sialic acid-binding Ig-like lectins (Siglecs) are implicated in glycan recognition and host defense against and pathogenicity of sialylated pathogens. Recent studies have shown endocytosis by CD33-related Siglecs, which is implicated in clearance of sialylated antigens and antigen presentation and makes targeted immunotherapy possible. Using CD33 as a paradigm, we have now investigated the reasons underlying the comparatively slow rate of endocytosis of these receptors. We show that endocytosis is largely limited and determined by the intracellular domain while the extracellular and transmembrane domains play a minor role. Tyrosine phosphorylation, most likely through Src family kinases, increases uptake of CD33 depending on the integrity of the two cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Simultaneous depletion of the protein tyrosine phosphatases, Src homology-2-containing tyrosine phosphatase 1 (Shp1) and Shp2, which bind to phosphorylated CD33, increases internalization of CD33 slightly in some cell lines, whereas depletion of spleen tyrosine kinase (Syk) has no effect, implying that Shp1 and Shp2 can dephosphorylate the ITIMs or mask binding of the phosphorylated ITIMs to an endocytic adaptor. Our studies show that restraint of CD33 internalization through the intracellular domain is relieved partly when the ITIMs are phosphorylated and show that Shp1 and Shp2 can modulate this process.
In Vivo Sampling of Extracellular β‐Thymosin by Ultrafiltration Probes
Authors: LIU YU‐TSUENG , HUANG CHUN‐MING 
Published: October 2007

Abstract:
In vivo detection and monitoring of extracellular β‐thymosin will facilitate the understanding of their biological function and association with disease progression.  A novel technique using capillary ultrafiltration (CUF) probes linked to mass spectrometry is capable of sensing extracellular thymosin β‐4 and/or thymosin β‐10 in vivo in wounded skin and other tissue microenvironments. In this review, we highlight the association of extracellular β‐thymosin with skin wound healing and the potential adjuvant effects on vaccination. The fabrication and biological application of CUF probes are also described. Data from CUF probe‐captured β‐thymosin may guide future exploration of extracellular β‐thymosin.
Rational Selection of Patients for Antibacterial Prophylaxis After Chemotherapy
Authors: Cullen Michael H. , Billingham Lucinda J. , Gaunt Claire H. , Steven Neil M. 
Published: October 2007

Purpose The SIGNIFICANT (Simple Investigation in Neutropenic Individuals of the Frequency of Infection after Chemotherapy ± Antibiotic in a Number of Tumours) trial reported a reduction in febrile episodes (FEs) among 1,565 patients with solid cancers and lymphomas receiving cyclical, myelosuppressive chemotherapy (causing grade 4 neutropenia) in a randomized, placebo-controlled, double-blind trial of levofloxacin (P = .01). In response to concerns that increased antibacterial prescribing selects for microbial resistance, we examined our data to explore the rationale for more limited prophylaxis. Patients and Methods The risk of FE was calculated for control patients on first versus nonfirst cycles, with or without first-cycle FE, and within subgroups defined by cancer type, performance status (PS), age, and treatment context (adjuvant v nonadjuvant). Using the randomized trial data, the prophylactic efficacy of levofloxacin was examined for the same subgroups. Results The per-cycle FE incidence was much lower on nonfirst (3.3%) versus first cycles (8.0%). Prophylaxis was less effective for nonfirst (odds ratio [OR] = 0.78; P = .16) compared with first cycles (OR = 0.42; P < .001). However, FE on cycle 1 predicted a much higher risk of FE and a trend to continued prophylactic efficacy on subsequent cycles. FE rate was greatest for testicular cancer (27.9%), then small-cell lung cancer (17.3%), and lowest for breast cancer (11.5%). Prophylactic efficacy was consistent across age, sex, PS, treatment context, and disease type (except possibly non-Hodgkin's lymphoma). Conclusion Under pressure to limit antibacterial use, these exploratory data support offering prophylactic levofloxacin on cycle 1 only of myelosuppressive cancer chemotherapy and on subsequent cycles after a cycle-1 fever. Prophylactic levofloxacin is effective regardless of age, PS, or tumor type.
Hidden Morbidity in Cancer: Spouse Caregivers
Authors: Braun Michal , Mikulincer Mario , Rydall Anne , Walsh Andrew , Rodin Gary 
Published: October 2007

Purpose This study assesses psychological distress among advanced cancer patients and their spouse caregivers, while examining the relative contribution of caregiving burden and relational variables (attachment orientation and marital satisfaction) to depressive symptoms in the spouse caregivers. Methods A total of 101 patients with advanced GI or lung cancer and their spouse caregivers were recruited for the study. Measures included Beck Depression Inventory–II (BDI-II), Caregiving Burden scale, Experiences in Close Relationships scale, and ENRICH Marital Satisfaction scale. Results A total of 38.9% of the caregivers reported significant symptoms of depression (BDI-II ≥ 15) compared with 23.0% of their ill spouses (P < .0001). In a hierarchical regression predicting caregiver's depression, spouse caregiver's age and patient's cancer site were entered in the first step, objective caregiving burden was entered in the second step, subjective caregiving burden was entered in the third step, caregiver's attachment scores were entered in the fourth step, and caregiver's marital satisfaction score was entered in the fifth step. The final model accounted for 37% of the variance of caregiver depression, with subjective caregiving burden (β = .38; P < .01), caregiver's anxious attachment (β = .21; P < .05), caregiver's avoidant attachment (β = .20; P < .05), and caregiver's marital satisfaction (β = −.18; P < .05) making significant contributions to the model. Conclusion Spouse caregivers of patients with advanced cancer are a high-risk population for depression. Subjective caregiving burden and relational variables, such as caregivers' attachment orientations and marital dissatisfaction, are important predictors of caregiver depression.
Randomized, Controlled Trial of Irinotecan Plus Infusional, Bolus, or Oral Fluoropyrimidines in First-Line Treatment of Metastatic Colorectal Cancer: Results From the BICC-C Study
Authors: Fuchs Charles S. , Marshall John , Mitchell Edith , Wierzbicki Rafal , Ganju Vinod , Jeffery Mark , Schulz Joseph , Richards Donald , Soufi-Mahjoubi Raoudha , Wang Benjamin , Barrueco José 
Published: October 2007

Purpose This phase III study compared the safety and efficacy of the following three different irinotecan-containing regimens in the first-line treatment of metastatic colorectal cancer: irinotecan plus infusional fluorouracil (FU)/leucovorin (LV) (FOLFIRI), irinotecan plus bolus FU/LV (mIFL), and irinotecan plus oral capecitabine (CapeIRI). Patients and Methods A total of 430 previously untreated metastatic colorectal cancer patients were randomly assigned to receive FOLFIRI (n = 144), mIFL (n = 141), or CapeIRI (n = 145). Patients were concurrently randomly assigned to a double-blind treatment with celecoxib or placebo. After a protocol amendment, an additional 117 patients were randomly assigned to either FOLFIRI plus bevacizumab (FOLFIRI+Bev; n = 57) or mILF plus bevacizumab (mIFL+Bev; n = 60), whereas the CapeIRI arm was discontinued. The primary study end point was progression-free survival (PFS), with secondary end points of overall survival (OS), response rate, and toxicity. Results Median PFS was 7.6 months for FOLFIRI, 5.9 months for mIFL (P = .004 for the comparison with FOLFIRI), and 5.8 months for CapeIRI (P = .015). Median OS was 23.1 months for FOLFIRI, 17.6 months for mIFL (P = .09), and 18.9 months for CapeIRI (P = .27). CapeIRI was associated with higher rates of severe vomiting, diarrhea, and dehydration. After the amendment to add bevacizumab, the median survival time has not yet been reached for FOLFIRI+Bev and was 19.2 months for mIFL+Bev (P = .007). FOLFIRI+Bev was associated with a higher rate of ≥ grade 3 hypertension than mIFL+Bev. Conclusion FOLFIRI and FOLFIRI+Bev offered superior activity to their comparators and were comparably safe. An infusional schedule of FU should be the preferred irinotecan-based regimen in first-line metastatic colorectal cancer.