bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytosine arabinoside in addition to VCAA‐based protocols for the treatment of canine lymphoma with bone marrow involvement: does it make the difference?
Authors: Marconato L. , Bonfanti U. , Stefanello D. , Lorenzo M. R. , Romanelli G. , Comazzi S. , Zini E. 
Published: May 2008

AbstractCytosine arabinoside (ara‐C) is a component of many protocols for the treatment of acute leukaemia and non‐Hodgkin lymphomas in humans. The aim of the study was to prospectively evaluate the efficacy of ara‐C in a myeloablative regimen in a cohort of canine lymphomas with bone marrow involvement. Seventeen dogs were enrolled. Eight were treated with a VCAA‐based protocol (Group 1) and nine with the same regimen added with ara‐C (Group 2). Ara‐C was administered on a 5‐day schedule as an i.v. continuous infusion at the dose of 150 mg m−2per day for five consecutive days. During treatment complete remission (CR) was achieved in two dogs in Group 1 and in eight dogs in Group 2. CR rate was significantly higher in Group 2 (P < 0.01). Median survival was 72.5 days (range 6–174) in Group 1 and 243 days (range 73–635) in Group 2. Survival was significantly longer in Group 2 (P < 0.001). Both protocols were well tolerated, with a low incidence of adverse events. Ara‐C added to a VCAA‐based protocol appears to be safe and beneficial in dogs with stage V lymphoma. Incorporation of the nucleoside analogue might be crucial for the development of future therapeutic strategies in dogs.
Adjuvant gemcitabine after surgical removal of aggressive malignant mammary tumours in dogs
Authors: Marconato L. , Lorenzo R. M. , Abramo F. , Ratto A. , Zini E. 
Published: May 2008

AbstractCanine mammary tumours are generally treated with surgery alone, despite the fact that 50% of them are malignant and many will eventually lead to recurrence or metastases. A prospective clinical trial in which dogs with aggressive mammary carcinoma of clinical stages IV and V were treated with surgical excision (n = 9) or with surgery and adjuvant weekly gemcitabine (n = 10) for at least four cycles was conducted. Gemcitabine was given as an intravenous infusion at the dose of 800 mg m−2. Aim of the study was to explore potential beneficial effects of gemcitabine on time to local recurrence (TTR), time to distant metastases (TTM) and overall survival (OS) in canine patients with operated mammary tumours bearing high risk for locoregional failure and distant metastases. Also, factors associated with OS, including neutering status, body weight, age, clinical stage at presentation, tumour size, histological grade and, in dogs receiving chemotherapy, the number of gemcitabine treatments, were investigated. Finally, acute toxicities related to chemotherapy and quality of life were assessed in dogs receiving gemcitabine. Dogs treated with surgery alone or surgery followed by gemcitabine had no difference in TTR, TTM or OS (P > 0.05). In the group of dogs receiving adjuvant chemotherapy, the number of gemcitabine treatments was positively correlated with OS (P = 0.017). Gemcitabine treatment was well tolerated, with no dogs experiencing clinically relevant haematological or gastrointestinal toxicity. Despite being safe at the present dose, gemcitabine chemotherapy as an adjunct treatment to surgical excision may not be recommended in dogs with aggressive mammary carcinoma.
Description of clinical and pathological findings, treatment and outcome of feline large granular lymphocyte lymphoma (1996–2004)*
Authors: Krick E. L. , Little L. , Patel R. , Shofer F. S. , Sorenmo K. , Clifford C. A. , Baez J. L. 
Published: May 2008

AbstractFeline large granular lymphocyte (LGL) lymphoma is an uncommon, morphologically distinct variant of feline lymphoma. Limited information exists in the literature regarding pathological and immunohistochemical descriptions, clinical findings, treatment and survival times. The purpose of this study was to describe clinical features, treatment and outcome in feline LGL lymphoma. Medical records of 45 cats with LGL lymphoma were retrospectively evaluated. Decreased appetite/anorexia, weight loss, lethargy and vomiting were the most commonly reported clinical signs. All cats tested for feline leukaemia virus and feline immunodeficiency virus infection were negative. The mesenteric lymph nodes and small intestine were the most commonly affected organs. One complete response and six partial responses were noted in the 23 cats that received chemotherapy as their initial treatment. Median survival time for cats that were treated was 57 days. Based on these results, feline LGL lymphoma appears to be minimally responsive to chemotherapy and is associated with a grave prognosis.
Dose‐escalating vinblastine for the treatment of canine mast cell tumour
Authors: Vickery K. R. , Wilson H. , Vail D. M. , Thamm D. H. 
Published: May 2008

AbstractThe purpose of this study was to evaluate the short‐term adverse events (AEs) in dogs with mast cell tumours (MCT) receiving prednisone and dose‐escalating vinblastine (VBL). Twenty‐four dogs were treated with intravenous VBL starting at 2 mg m−2 and then escalating in weekly increments to 2.33, 2.67 and 3 mg m−2. AEs were graded using a standardized scoring system. No dogs receiving 2 or 2.33 mg m−2 experienced grade 3 or 4 AEs. Among the dogs, 9.5 and 5.9% had grade 3 or 4 AEs at dosages of 2.67 and 3 mg m−2, respectively. Serious AEs included neutropaenia (n = 3) and vomiting (n = 1), only one of which required hospitalization. These data indicate that VBL chemotherapy may be safe to administer at higher than the traditional 2 mg m−2 dosage for dogs with MCT. Randomized prospective trials are necessary to establish whether dose escalation will translate into improved response rates when compared with the standard 2 mg m−2 dosage.
Pulmonary fibrosis after high cumulative dose nitrosourea chemotherapy in a cat
Authors: Skorupski K. A. , Durham A. C. , Duda L. , Sørenmo K. U. 
Published: May 2008

AbstractSmall to intermediate cell alimentary lymphoma was diagnosed in a cat after abdominal exploratory surgery with no prior history of pulmonary disease. Initial response to several chemotherapy regimens was poor, but a long‐term remission was achieved with CCNU (lomustine) and corticosteroid therapy. After receiving a total cumulative CCNU dose of 552 mg m−2 over 12 months, an acute episode of respiratory distress occurred and the cat died. Necropsy identified severe diffuse pulmonary fibrosis and no signs of lymphoma. This is the first report of pulmonary fibrosis following high cumulative dose nitrosourea chemotherapy in a cat.
Serum vascular endothelial growth factor concentrations and postsurgical outcome in dogs with osteosarcoma
Authors: Thamm D. H. , O’Brien M. G. , Vail D. M. 
Published: May 2008

AbstractVascular endothelial growth factor (VEGF) is a key angiogenic growth factor, playing putative roles in both tumour growth and metastasis. The purpose of this study was to correlate pretreatment serum concentrations of VEGF in dogs with osteosarcoma (OSA) with disease‐free interval (DFI) and overall survival (OS). Additionally, the effect of serum from dogs with OSA on ex vivo canine endothelial cell (EC) growth was determined. Pretreatment platelet‐corrected serum VEGF levels correlated significantly with DFI. No other examined variable predicted outcome. The ability of sera from dogs with OSA to stimulate canine EC proliferation did not correlate with VEGF concentration or outcome. These data support a role for VEGF in the development or progression of metastatic disease in dogs with OSA. The VEGF concentration in tested sera was not a major determinant of ex vivo canine EC proliferation in this study.
Investigation of the Immunomodulatory Effects of Lactobacillus casei and Bifidobacterium lactis on Helicobacter pylori Infection
Authors: Zhang Li , Su Ping , Henriksson Anders , O’Rourke Jani , Mitchell Hazel 
Published: May 2008

AbstractBackground:  Lactobacillus and Bifidobacterium species have shown beneficial effects in the treatment of Helicobacter pylori infection; however, the mechanisms behind such effects are not fully understood. In this study, we have investigated the immunomodulatory effects of probiotics in a mouse model of H. pylori infection.Materials and methods:  H. pylori‐infected C57BL/6 mice were treated with L. casei L26, B. lactis B94, or no probiotics for 5 weeks, respectively. Mice not infected with H. pylori were included as normal controls. Gastric histology, protein levels of interleukin (IL)‐1β, IL‐10, IL‐12/23p40, and H. pylori colonization density in the gastric tissues, as well as H. pylori‐specific antibodies were examined.Results:  In mice receiving L. casei L26 and B. lactis B94, gastric neutrophil infiltration and IL‐1β were significantly decreased and IL‐10 was significantly increased as compared with mice receiving no probiotics. In mice receiving B. lactis B94, IL‐12/23p40 was significantly increased and H. pylori IgG was significantly reduced as compared with mice receiving no probiotics. No significant difference of H. pylori colonization was observed among the three groups of mice.Conclusion:  The reduced level of IL‐1β and neutrophil infiltration observed in mice infected with H. pylori following treatment with L. casei L26 and B. lactis B94 resulted from a modulation of immune response rather than a decrease of H. pylori colonization. Furthermore, B. lactis B94 has the intrinsic ability to promote a Th1 immune response through an increase in IL‐12/IL‐23.
Assessment of Atrophic Gastritis Using the OLGA System
Authors: Satoh Kiichi , Osawa Hiroyuki , Yoshizawa Mitsuyo , Nakano Hidetoshi , Hirasawa Tomosuke , Kihira Ken , Sugano Kentaro 
Published: May 2008

AbstractBackground:  An international group of gastroenterologists and pathologists (Operative Link for Gastritis Assessment (OLGA)) proposed the staging system of atrophy. The aim of this study was to assess the severity of atrophic gastritis using the OLGA system.Materials and Methods:  The subjects comprised 163 H. pylori‐positive patients: 18 with early gastric cancers of the intestinal type (GC), 55 with atrophic gastritis (AG), 49 with gastric ulcers or scars (GU), and 41 with duodenal ulcers or scars (DU). Biopsies were taken from the lesser and greater curvatures of the antrum and middle body. The OLGA gastritis stage (0–IV) (the severity and topography of atrophy) was obtained by combining antral with body atrophy scores. The gastritis grade (the severity and topography of inflammation) was obtained by combining antral and body inflammation scores.Results:  Most (84%) of patients with GC showed stage III or IV. Gastritis stages were significantly higher in patients with GC than in those with AG, GU, and DU. Gastritis stage became higher with age. Gastritis grades were slightly higher in patients with AG than in others.Conclusions:  Our results indicate that higher stages are found in patients with GC using the OLGA staging system and that the high risk of GC can be recognized. It is simple to use and useful for the assessment of the severity of atrophic gastritis.
A Population‐Based Study of Helicobacter pylori Infection in Chinese Children Resident in Hong Kong: Prevalence and Potential Risk Factors
Authors: Tam Yuk Him , Yeung Chung Kwong , Lee Kim Hung , Sihoe Jennifer Dart Yin , Chan Kin Wai , Cheung Sing Tak , Mou Jennifer Wai Cheung 
Published: May 2008

AbstractBackground:  Data of Helicobacter pylori prevalence in children and its risk factors provide clues to the health authority to estimate burden of H. pylori‐associated diseases usually encountered in adulthood and facilitate healthcare planning.Materials and Methods:  A cross‐sectional population‐based study was conducted in Chinese children in elementary and high schools. Schools were selected from all three major areas of Hong Kong. H. pylori infection was defined by a positive 13C‐urea breath test. Study subjects were stratified into six age groups for estimation of prevalence. Potential risk factors were analyzed from data of self‐administered questionnaires.Results:  A total of 2480 children (aged 6–19, male: 47.3%) participated in the study. Overall, 324 (13.1%) were positive for H. pylori. There was no difference in prevalence between sexes, and no statistical trend in the prevalence across the six age groups. Multivariate logistic regression identified lack of formal education of mother (OR = 2.43, 95%CI 1.36–4.34), family history of gastric cancer (OR = 2.19, 95%CI 1.09–4.41), and household member > 5 (OR = 1.57, 95%CI 1.12–2.19) to be positively associated with H. pylori infection in our children.Conclusions:  The H. pylori prevalence of Hong Kong children is comparable to the data of developed countries. The association with family history of gastric cancer justifies further study to investigate the cost‐benefit of community screening program for such children to decrease the incidence of gastric cancer in adulthood.
Helicobacter pylori‐Pulsed Dendritic Cells Induce H. pylori‐Specific Immunity in Mice
Authors: Zhang Min , Berndt Bradford E. , Eaton Kathryn A. , Rathinavelu Sivaprakash , Pierzchala Anna , Kao John Y. 
Published: May 2008

AbstractBackground:  The growing concern over the emergence of antibiotic‐resistant Helicobacter pylori infection is propelling the development of an efficacious vaccine to control this highly adaptive organism.Aim:  We studied the use of a dendritic cell (DC)‐based vaccine against H. pylori infection in mice.Methods:  The cellular immune responses to murine bone marrow‐derived DCs pulsed with phosphate‐buffered saline (PBS‐DC) or live H. pylori SS1 (HP‐DC) were assessed in vitro and in vivo. The protective immunity against H. pylori SS1 oral challenge was compared between HP‐DC or PBS‐DC immunized mice. The effect of regulatory T‐cell (Treg) depletion by anti‐CD25 antibody on HP‐DC vaccine efficacy was also evaluated.Results:  HP‐DC induced a Th1‐dominant response in vitro. In vivo, HP‐DC immunized mice were characterized by a mixed Th1/Th2 peripheral immune response. However, in the stomach, HP‐DC immunized mice expressed a higher level of IFN‐γ compared to PBS‐DC immunized mice; no difference was found for interleukin‐5 expressions in the stomach. A lower bacterial colonization post‐H. pylori challenge was observed in HP‐DC immunized mice compared to PBS‐DC immunized mice with no significant difference in gastritis severity. H. pylori‐specific Th1 response and protective immunity were further enhanced in vivo by depletion of Treg with anti‐CD25 antibody.Conclusion:  DC‐based anti‐H. pylori vaccine induced H. pylori‐specific helper T‐cell responses capable of limiting bacterial colonization. Our data support the critical role of effector cellular immune response in the development of H. pylori vaccine.
Protection Against Helicobacter pylori Infection in Mongolian Gerbil by Intragastric or Intramuscular Administration of H. pylori Multicomponent Vaccine
Authors: Wu Chao , Shi Yun , Guo Hong , Zou Wei‐Ying , Guo Gang , Xie Qing‐Hua , Mao Xu‐Hu , Tong Wen‐De , Zou Quan‐Ming 
Published: May 2008

AbstractBackground:  Development of Helicobacter pylori vaccine would be a new effective strategy for prevention and treatment of H. pylori infection. Recombinant H. pylori vaccine comprising a single subunit antigen can only induce immune response with limited protection efficiency. In this study, the protective effect of H. pylori multicomponent vaccines consisting of three recombinant subunit antigens was investigated using the Mongolian gerbil model.Materials and methods:  Mongolian gerbils were immunized with different formulations of three recombinant H. pylori antigens (UreB, HspA, and HpaA) with two different adjuvants (Al(OH)3, LTR72DITH) by intragastric (i.g.) or intramuscular (i.m.) routes. The protective effects of multicomponent vaccines were assessed after H. pylori challenge in different studies. The specific IgG antibodies in serum were monitored by ELISA, and the mRNA expressions of IL‐4 and IFN‐γ in spleen tissue were detected by reverse transcribed polymerase chain reaction (RT‐PCR).Results:  The protective effect against H. pylori challenge in gerbils immunized with three recombinant antigens and LTR72DITH or Al(OH)3 was significantly higher than that in single‐ or double‐antigen vaccine‐immunized and control gerbils. Furthermore, the protective effect of the triple‐antigen vaccine combined with the LTR72DITH adjuvant (average 86.3%) was significantly greater than that of vaccine combined with the Al(OH)3 adjuvant (average 53.4%). After the first immunization, the anti‐UreB/HspA/HpaA serum IgG level in gerbils immunized with triple‐antigen vaccine combined with Al(OH)3 was higher than that in gerbils immunized with the vaccine combined with LTR72DITH. Splenic interferon (IFN)‐γ and interleukin (IL)‐4 transcript levels were significantly increased in LTR72DITH vaccine‐immunized gerbils as compared to the Al(OH)3 vaccine group. Moreover, splenic IL‐4 mRNA levels were higher than IFN‐γ in gerbils immunized with triple‐antigen vaccine with either LTR72DITH or Al(OH)3.Conclusions:  This study indicated that the recombinant multicomponent vaccine provided effective protection against H. pylori infection as compared to the single‐antigen vaccine. This protective immunity would be closely associated with a predominant Th2‐type response.
CONDITIONAL PRODUCTION OF A FUNCTIONAL FISH GROWTH HORMONE IN THE TRANSGENIC LINE OF NANNOCHLOROPSIS OCULATA (EUSTIGMATOPHYCEAE)1
Authors: Chen Hsin Liang , Li Si Shen , Huang Rang , Tsai Huai‐Jen 
Published: May 2008

Plasmid phr‐YPGHc, containing the fish growth hormone (GH) cDNA driven by a heat shock protein 70A promoter and a RUBISCO SSU 2 promoter, was transferred into the protoplast of marine microalga Nannochloropsis oculata (Droop) D. J. Hibberd by electroporation. Four transgenic clones were obtained in which the transferred phr‐YPGHc was integrated into the genome and existed stably at least until the 50th generation. When we treated these transgenic microalgae by heat shock, the heterologous fish GH was produced in the amount of 0.42 to 0.27 μg · mL−1 from the 50 mL of medium. We incubated artemia with the wildtype and transgenic N. oculata for 6 h and then fed these microalgae‐treated artemia to red‐tilapia larvae. After feeding, the growth of larvae that were fed artemia incubated with transgenic microalgae was greater (i.e., statistically significant: P < 0.05) than that of larvae that were fed artemia incubated with nontransgenic microalgae: 316% versus 104% in weight gain, and 217% versus 146% in body length increase, respectively. Therefore, the N. oculata enables production of functional GH, and we propose that it might be an excellent bioreactor material.
Estimating the pathogen safety of manufactured human plasma products: application to fibrin sealants and to thrombin
Authors: Horowitz Bernard , Busch Michael 
Published: May 2008

BACKGROUND: Plasma fractionators have implemented many improvements over the past decade directed toward reducing the likelihood of pathogen transmission by purified blood products, yet little has been published attempting to assess the overall impact of these improvements on the probability of safety of the final product.STUDY DESIGN AND METHODS: Safety margins for human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), hepatitis A virus (HAV), parvovirus B19, and variant form of Creutzfeldt‐Jakob disease (vCJD) were calculated for the two fibrin sealants licensed in the United States and for thrombin. These products were selected because their use in a clinical setting is, in most cases, optional, and both were relatively recently approved for marketing by the US Food and Drug Administration (FDA). Moreover, thrombin and fibrinogen both undergo two dedicated virus inactivation steps and/or removal steps in accord with the recommendations of regulatory agencies worldwide. Safety margins were determined by comparing the potential maximum viral loads in contaminated units to viral clearance factors, ultimately leading to the calculation of the residual risk per vial.RESULTS: The residual risk of pathogen transmission per vial was calculated to be less than 1 in 10−15 for HIV, HCV, HBV, and HAV for both fibrinogen and thrombin. Owing to the greater quantities that can be present and its greater thermal stability, the calculated risk for parvovirus transmission was 1 in 500,000 vials for fibrinogen and less than 1 in 107 per vial for thrombin. Assuming that vCJD is found to be present in plasma donations, its risk of transmission by these purified and processed plasma derivatives would appear to be very low.CONCLUSIONS: The pathogen safety initiatives implemented by plasma fractionators over the past 10 to 20 years have resulted in products with excellent pathogen safety profiles. Of the agents examined, parvovirus continues to have the lowest calculated margin of safety. Despite this, parvovirus transmissions should be rare. Manufacturers are encouraged to continue exploring processes to further enlarge parvovirus safety margins and to continue exploring ways of eliminating prions.
U2OS cells lacking Chk1 undergo aberrant mitosis and fail to activate the spindle checkpoint
Authors: Carrassa Laura , Sanchez Yolanda , Erba Eugenio , Damia Giovanna 
Published: May 2008

AbstractChk1 is a conserved protein kinase originally identified in fission yeast, required to delay entry of cells with damaged or unreplicated DNA into mitosis. The requirement of Chk1 for both S and G2/M checkpoints has been elucidated while only few studies have connected Chk1 to the mitotic spindle checkpoint. We used a small interference RNA strategy to investigate the role of Chk1 in unstressed conditions. Chk1 depletion in U2OS human osteosarcoma cells inhibited cell proliferation and raised the percentage of cells with a 4N DNA content, which correlated with accumulation of giant polynucleated cells morphologically distinct from apoptotic cells, while no increased number of cells in G2 or mitosis could be detected. Down‐regulation of Chk1 also caused accumulation of cells in the last step of cytokinesis, and of tetraploid cells in G1 phase, which coincided with activation of p53 and increased levels of p21. In addition, Chk1‐depleted U2OS cells failed to arrest in mitosis after spindle disruption by nocodazole and showed decreased protein levels of Mad2 and BubR1. These studies show that U2OS cells lacking Chk1 undergo abnormal mitosis and fail to activate the spindle checkpoint, suggesting a role of Chk1 in this checkpoint.
RAD001 (everolimus) inhibits tumour growth in xenograft models of human hepatocellular carcinoma
Authors: Huynh Hung , Pierce Chow K.H. , Soo Khee Chee , Toh Han Chong , Choo Su Pin , Foo Kian Fong , Poon Donald , Ngo Van Chanh , Tran Evelyn 
Published: May 2008

AbstractHepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and highly resistant to available chemotherapies. Mammalian target of rapamycin (mTOR) functions to regulate protein translation, angiogenesis and cell cycle progression in many cancers including HCC. In the present study, subcutaneous patient‐derived HCC xenografts were used to study the effects of an mTOR inhibitor, RAD001 (everolimus), on tumour growth, apoptosis and angiogenesis. We report that oral administration of RAD001 to mice bearing patient‐derived HCC xenografts resulted in a dose‐dependent inhibition of tumour growth. RAD001‐induced growth suppression was associated with inactivation of downstream targets of mTOR, reduction in VEGF expression and microvessel density, inhibition of cell proliferation, up‐regulation of p27Kip1 and down‐regulation of p21Cip1/Waf1, Cdk‐6, Cdk‐2, Cdk‐4, cdc‐25C, cyclin B1 and c‐Myc. Our data indicate that the mTOR pathway plays an important role in angiogenesis, cell cycle progression and proliferation of liver cancer cells. Our study provides a strong rationale for clinical investigation of mTOR inhibitor RAD001 in patients with HCC.