bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduction in podocyte density as a pathologic feature in early diabetic nephropathy in rodents: Prevention by lipoic acid treatment
Authors: Siu Brian , Saha Jharna , Smoyer William E , Sullivan Kelli A , Brosius Frank C 
Published: April 2006

AbstractBackgroundA reduction in the number of podocytes and podocyte density has been documented in the kidneys of patients with diabetes mellitus. Additional studies have shown that podocyte injury and loss occurs in both diabetic animals and humans. However, most studies in animals have examined relatively long-term changes in podocyte number and density and have not examined effects early after initiation of diabetes. We hypothesized that streptozotocin diabetes in rats and mice would result in an early reduction in podocyte density and that this reduction would be prevented by antioxidants.MethodsThe number of podocytes per glomerular section and the podocyte density in glomeruli from rats and mice with streptozotocin (STZ)-diabetes mellitus was determined at several time points based on detection of the glomerular podocyte specific antigens, WT-1 and GLEPP1. The effect of insulin administration or treatment with the antioxidant, α-lipoic acid, on podocyte number was assessed.ResultsExperimental diabetes resulted in a rapid decline in apparent podocyte number and podocyte density. A significant reduction in podocytes/glomerular cross-section was found in STZ diabetes in rats at 2 weeks (14%), 6 weeks (18%) and 8 weeks (34%) following STZ injection. Similar declines in apparent podocyte number were found in STZ diabetes in C57BL/6 mice at 2 weeks, but not at 3 days after injection. Treatment with α-lipoic acid substantially prevented podocyte loss in diabetic rats but treatment with insulin had only a modest effect.ConclusionSTZ diabetes results in reduction in apparent podocyte number and in podocyte density within 2 weeks after onset of hyperglycemia. Prevention of these effects with antioxidant therapy suggests that this early reduction in podocyte density is due in part to increased levels of reactive oxygen species as well as hyperglycemia.
Effects of high volume saline enemas vs no enema during labour – The N-Ma Randomised Controlled Trial [ISRCTN43153145]
Authors: Cuervo Luis Gabriel , Bernal María del Pilar , Mendoza Natalia 
Published: April 2006

Abstract

Background
Enemas are used during labour in obstetric settings with the belief that they reduce puerperal and neonatal infections, shorten labour duration, and make delivery cleaner for attending personnel. However, a systematic review of the literature found insufficient evidence to support the use of enemas. The objective of this RCT was to address an identified knowledge gap by determining the effect of routine enemas used during the first stage of labour on puerperal and neonatal infection rates.

Methods

Design: RCT (randomised controlled trial; randomized clinical trial).

Outcomes: Clinical diagnosis of maternal or neonatal infections, labour duration, delivery types, episiotomy rates, and prescription of antibiotics

Setting: Tertiary care referral hospital at the Javeriana University (Bogotá, Colombia) that attended 3170 births during study period with a caesarean section rate of 26%.

Participants: 443 women admitted for delivery to the obstetrics service (February 1997 to February 1998) and followed for a month after delivery. Inclusion criteria were women with: low risk pregnancy and expected to remain in Bogotá during follow up; gestational age ≥ 36 weeks; no pelvic or systemic bacterial infection; intact membranes; cervix dilatation ≤7 cm.

Intervention: 1 litre saline enema, versus no enema, allocated following a block random allocation sequence and using sealed opaque envelopes.

Results
Allocation provided balanced groups and 86% of the participants were followed up for one month. The overall infection rate for newborns was 21%, and 18% for women. We found no significant differences in puerperal or neonatal infection rates (Puerperal infection: 41/190 [22%] with enema v 26/182 [14%] without enema; RR 0.66 CI 95%: 0.43 to 1.03; neonatal infection 38/191 [20%] with enema v 40/179 [22%] without enema; RR 1.12, 95% CI 95% 0.76 to 1.66), and median labour time was similar between groups (515 min. with enema v 585 min. without enema; P = 0.24). Enemas didn't significantly change episiorraphy dehiscence rates (21/182 [12%] with enema v 32/190 [17%] without enema; P = 0.30).

Conclusion
This RCT found no evidence to support routine use of enemas during labour. Although these results cannot rule out a small clinical effect, it seems unlikely that enemas will improve maternal and neonatal outcomes and provide an overall benefit.
Protocol for the immediate delivery versus expectant care of women with preterm prelabour rupture of the membranes close to term (PPROMT) Trial [ISRCTN44485060]
Authors: Morris Jonathan M , Roberts Christine L , Crowther Caroline A , Buchanan Sarah L , Henderson-Smart David J , Salkeld Glenn 
Published: April 2006

Abstract

Background
Preterm prelabour rupture of membranes (PPROM) complicates up to 2% of all pregnancies and is the cause of 40% of all preterm births. The optimal management of women with PPROM prior to 37 weeks, is not known. Furthermore, diversity in current clinical practice suggests uncertainty about the appropriate clinical management.
There are two options for managing PPROM, expectant management (a wait and see approach) or early planned birth. Infection is the main risk for women in which management is expectant. This risk need to be balanced against the risk of iatrogenic prematurity if early delivery is planned. The different treatment options may also have different health care costs. Expectant management results in prolonged antenatal hospitalisation while planned early delivery may necessitate intensive care of the neonate for problems associated with prematurity.

Methods/Design
We aim to evaluate the effectiveness of early planned birth compared with expectant management for women with PPROM between 34 weeks and 366 weeks gestation, in a randomised controlled trial. A secondary aim is a cost analysis to establish the economic impact of the two treatment options and establish the treatment preferences of women with PPROM close to term.
The early planned birth group will be delivered within 24 hours according to local management protocols. In the expectant management group birth will occur after spontaneous labour, at term or when the attending clinician feels that birth is indicated according to usual care. Approximately 1812 women with PPROM at 34–366 weeks gestation will be recruited for the trial.
The primary outcome of the study is neonatal sepsis. Secondary infant outcomes include respiratory distress, perinatal mortality, neonatal intensive care unit admission, assisted ventilation and early infant development. Secondary maternal outcomes include chorioamnionitis, postpartum infection treated with antibiotics, antepartum haemorrhage, induction of labour, mode of delivery, maternal satisfaction with care, duration of hospitalisation, and maternal wellbeing at four months postpartum.

Discussion
This trial will provide evidence on the optimal care for women with PPROM close to term (34–37 weeks gestation). Consideration of both the clinical and economic sequelae of the management of PPROM will enable informed decision making and guideline development.
Zoledronic acid treatment impairs protein geranyl-geranylation for biological effects in prostatic cells
Authors: Goffinet M , Thoulouzan M , Pradines A , Lajoie-Mazenc I , Weinbaum Carolyn , Faye JC , Séronie-Vivien S 
Published: April 2006

AbstractBackgroundNitrogen-containing bisphosphonates (N-BPs) have been designed to inhibit osteoclast-mediated bone resorption. However, it is now accepted that part of their anti-tumor activities is related to interference with the mevalonate pathway.MethodsWe investigated the effects of zoledronic acid (ZOL), on cell proliferation and protein isoprenylation in two tumoral (LnCAP, PC-3,), and one normal established (PNT1-A) prostatic cell line. To assess if inhibition of geranyl-geranylation by ZOL impairs the biological activity of RhoA GTPase, we studied the LPA-induced formation of stress fibers. The inhibitory effect of ZOL on geranyl geranyl transferase I was checked biochemically. Activity of ZOL on cholesterol biosynthesis was determined by measuring the incorporation of14C mevalonate in cholesterol.ResultsZOL induced dose-dependent inhibition of proliferation of all the three cell lines although it appeared more efficient on the untransformed PNT1A. Whatever the cell line, 20 μM ZOL-induced inhibition was reversed by geranyl-geraniol (GGOH) but neither by farnesol nor mevalonate. After 48 hours treatment of cells with 20 μM ZOL, geranyl-geranylation of Rap1A was abolished whereas farnesylation of HDJ-2 was unaffected. Inhibition of Rap1A geranyl-geranylation by ZOL was rescued by GGOH and not by FOH. Indeed, as observed with treatment by a geranyl-geranyl transferase inhibitor, treatment of PNT1-A cells with 20 μM ZOL prevented the LPA-induced formation of stress fibers. We checked that in vitro ZOL did not inhibit geranyl-geranyl-transferase I. ZOL strongly inhibited cholesterol biosynthesis up to 24 hours but at 48 hours 90% of this biosynthesis was rescued.ConclusionAlthough zoledronic acid is currently the most efficient bisphosphonate in metastatic prostate cancer management, its mechanism of action in prostatic cells remains unclear. We suggest in this work that although in first intention ZOL inhibits FPPsynthase its main biological actitivity is directed against protein Geranylgeranylation.
Midline carcinoma with t(15;19) and BRD4-NUTfusion oncogene in a 30-year-old female with response to docetaxel and radiotherapy
Authors: Engleson Jens , Soller Maria , Panagopoulos Ioannis , Dahlén Anna , Dictor Michael , Jerkeman Mats 
Published: April 2006

Abstract

Background
Poorly differentiated midline carcinoma with a translocation between chromosomes 15 and 19, i.e. t(15;19), has been recognized as a distinct clinical entity for over a decade. This tumor affects young individuals, shows a rapidly fatal clinical course despite intensive therapy. The t(15;19) results in the fusion oncogene BRD4-NUT. Information concerning treatment of this rare disorder is scarce.

Case presentation
A 30-year-old woman was admitted with a rapidly progressing tumor in the mediastinum, cervical lymph nodes, vertebral column and the epidural space. Pathological, cytogenetic, FISH and PCR analysis revealed a glycogenated carcinoma rarely expressing cytokeratins and showing t(15;19) and BRD4-NUT gene rearrangement. The patient was initially treated with a Ewing sarcoma chemotherapy regimen, but had rapid progression after two cycles. She then received docetaxel and radiotherapy, which resulted in almost complete disappearance of the tumor.

Conclusion
Docetaxel may be considered for initial chemotherapy in young patients presenting with a midline carcinoma with bone marrow involvement and cytogenetic and molecular genetic finding of a t(15;19)/BRD4-NUT-rearrangement. We herein describe, in detail, the laboratory methods by which the BRD4-NUT -rearrangement can be detected.
Relationship between cyclooxygenase 8473T>Cpolymorphism and the risk of lung cancer: a case-control study
Authors: Park Jung Min , Choi Jin Eun , Chae Myung Hwa , Lee Won Kee , Cha Sung Ick , Son Ji-Woong , Kim Chang Ho , Kam Sin , Kang Young Mo , Jung Tae Hoon , Park Jae Yong 
Published: April 2006

AbstractBackgroundCyclooxygenase-2 (COX-2) plays an important role in the development of lung cancer. DNA sequence variations in theCOX-2gene may lead to altered COX-2 production and/or activity, and so they cause inter-individual differences in the susceptibility to lung cancer. To test this hypothesis, we investigated the association between the8473T>Cpolymorphism in the 3'-untranslated region of theCOX-2gene and the risk of lung cancer in a Korean population.MethodsTheCOX-2genotypes were determined using PCR-based primer-introduced restriction analysis in 582 lung cancer patients and in 582 healthy controls that were frequency-matched for age and gender.ResultsThe distribution of theCOX-2 8473T>Cgenotypes was not significantly different between the overall lung cancer cases and the controls. However, when the cases were categorized by the tumor histology, the combined8473 TC+CCgenotype was associated with a significantly decreased risk of adenocarcinoma as compared with the8473 TTgenotype (adjusted OR = 0.64; 95% CI = 0.46–0.90,P= 0.01). On the stratification analysis, the protective effect of the combined8473 TC+CCgenotype against adenocarcinoma was statistically significant in the males, older individuals and ever-smokers (adjusted OR = 0.59; 95% CI = 0.39–0.91,P= 0.02; adjusted OR = 0.55; 95% CI = 0.33–0.93,P= 0.03; and adjusted OR = 0.57; 95% CI = 0.37–0.87,P= 0.01, respectively).ConclusionThese findings suggest that theCOX-2 8473T>Cpolymorphism could be used as a marker for the genetic susceptibility to adenocarcinoma of the lung.
Association between cigarette smoking, APCmutations and the risk of developing sporadic colorectal adenomas and carcinomas
Authors: Sæbø Mona , Skjelbred Camilla F , Breistein Rebecca , Lothe Inger Marie B , Hagen Per Chr , Bock Gunter , Hansteen Inger-Lise , Kure Elin H 
Published: April 2006

AbstractBackgroundThe association between colorectal cancer (CRC) and smoking has not been consistent. Incomplete smoking history and association to a specific subset of CRC tumors have been proposed as explanations. The adenomatous polyposis coli (APC) gene has been reported to have a "gatekeeper" function in the colonic mucosa.MethodsTo evaluate the hypothesis that cigarette smoking is associated with adenoma and carcinoma development and further to investigate whether this association is due to mutations in theAPCgene, we used a study population consisting of 133 cases (45 adenomas and 88 carcinomas) and 334 controls. All tumors were sequenced in the mutation cluster region (MCR) of theAPCgene. Cases and controls were drawn from a homogeneous cohort of Norwegian origin.ResultsThe mutational spectra of theAPCgene revealed no difference in frequencies of mutations in cases based on ever and never smoking status. An overall case-control association was detected for adenomas and "ever smoking" OR = 1.73 (95% CI 0.83–3.58). For CRC cases several smoking parameters for dose and duration were used. We detected an association for all smoking parameters and "duration of smoking > 30 years", yielded a statistically significant OR = 2.86 (1.06–7.7). When cases were divided based onAPCtruncation mutation status, an association was detected in adenomas withoutAPCmutation in relation to "ever smoking", with an OR = 3.97 (1.26–12.51). For CRC cases withoutAPCmutation "duration of smoking > 30 years", yielded a statistically significant OR = 4.06 (1.20–13.7). The smoking parameter "starting smoking ≥ 40 years ago" was only associated with CRC cases withAPCmutations, OR = 2.0 (0.34–11.95). A case-case comparison revealed similar findings for this parameter, OR = 2.24 (0.73–6.86).ConclusionOur data suggest an association between smoking and adenoma and CRC development. This association was strongest for cases withoutAPCtruncation mutation. This may implicate other factors in development of these tumors. The association detected between smoking and CRC cases withAPCmutation was in relationship to the smoking parameter "starting smoking ≥ 40 years ago", a time period long enough to proceed CRC initiation.
Alternating current electrical stimulation enhanced chemotherapy: a novel strategy to bypass multidrug resistance in tumor cells
Authors: Janigro Damir , Perju Catalin , Fazio Vincent , Hallene Kerri , Dini Gabriele , Agarwal Mukesh K , Cucullo Luca 
Published: April 2006

Abstract

Background
Tumor burden can be pharmacologically controlled by inhibiting cell division and by direct, specific toxicity to the cancerous tissue. Unfortunately, tumors often develop intrinsic pharmacoresistance mediated by specialized drug extrusion mechanisms such as P-glycoprotein. As a consequence, malignant cells may become insensitive to various anti-cancer drugs. Recent studies have shown that low intensity very low frequency electrical stimulation by alternating current (AC) reduces the proliferation of different tumor cell lines by a mechanism affecting potassium channels while at intermediate frequencies interfere with cytoskeletal mechanisms of cell division. The aim of the present study is to test the hypothesis that permeability of several MDR1 over-expressing tumor cell lines to the chemotherapic agent doxorubicin is enhanced by low frequency, low intensity AC stimulation.

Methods
We grew human and rodent cells (C6, HT-1080, H-1299, SKOV-3 and PC-3) which over-expressed MDR1 in 24-well Petri dishes equipped with an array of stainless steel electrodes connected to a computer via a programmable I/O board. We used a dedicated program to generate and monitor the electrical stimulation protocol. Parallel cultures were exposed for 3 hours to increasing concentrations (1, 2, 4, and 8 μM) of doxorubicin following stimulation to 50 Hz AC (7.5 μA) or MDR1 inhibitor XR9576. Cell viability was assessed by determination of adenylate kinase (AK) release. The relationship between MDR1 expression and the intracellular accumulation of doxorubicin as well as the cellular distribution of MDR1 was investigated by computerized image analysis immunohistochemistry and Western blot techniques.

Results
By the use of a variety of tumor cell lines, we show that low frequency, low intensity AC stimulation enhances chemotherapeutic efficacy. This effect was due to an altered expression of intrinsic cellular drug resistance mechanisms. Immunohistochemical, Western blot and fluorescence analysis revealed that AC not only decreases MDR1 expression but also changes its cellular distribution from the plasma membrane to the cytosol. These effects synergistically contributed to the loss of drug extrusion ability and increased chemo-sensitivity.

Conclusion
In the present study, we demonstrate that low frequency, low intensity alternating current electrical stimulation drastically enhances chemotherapeutic efficacy in MDR1 drug resistant malignant tumors. This effect is due to an altered expression of intrinsic cellular drug resistance mechanisms. Our data strongly support a potential clinical application of electrical stimulation to enhance the efficacy of currently available chemotherapeutic protocols.
The bone morphogenetic protein antagonist gremlin 1 is overexpressed in human cancers and interacts with YWHAH protein
Authors: Namkoong Hong , Shin Seung Min , Kim Hyun Kee , Ha Seon-Ah , Cho Goang Won , Hur Soo Young , Kim Tae Eung , Kim Jin Woo 
Published: April 2006

Abstract

Background
Basic studies of oncogenesis have demonstrated that either the elevated production of particular oncogene proteins or the occurrence of qualitative abnormalities in oncogenes can contribute to neoplastic cellular transformation. The purpose of our study was to identify an unique gene that shows cancer-associated expression, and characterizes its function related to human carcinogenesis.

Methods
We used the differential display (DD) RT-PCR method using normal cervical, cervical cancer, metastatic cervical tissues, and cervical cancer cell lines to identify genes overexpressed in cervical cancers and identified gremlin 1 which was overexpressed in cervical cancers. We determined expression levels of gremlin 1 using Northern blot analysis and immunohistochemical study in various types of human normal and cancer tissues. To understand the tumorigenesis pathway of identified gremlin 1 protein, we performed a yeast two-hybrid screen, GST pull down assay, and immunoprecipitation to identify gremlin 1 interacting proteins.

Results
DDRT-PCR analysis revealed that gremlin 1 was overexpressed in uterine cervical cancer. We also identified a human gremlin 1 that was overexpressed in various human tumors including carcinomas of the lung, ovary, kidney, breast, colon, pancreas, and sarcoma. PIG-2-transfected HEK 293 cells exhibited growth stimulation and increased telomerase activity. Gremlin 1 interacted with homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide (14-3-3 eta; YWHAH). YWHAH protein binding site for gremlin 1 was located between residues 61–80 and gremlin 1 binding site for YWHAH was found to be located between residues 1 to 67.

Conclusion
Gremlin 1 may play an oncogenic role especially in carcinomas of the uterine cervix, lung, ovary, kidney, breast, colon, pancreas, and sarcoma. Over-expressed gremlin 1 functions by interaction with YWHAH. Therefore, Gremlin 1 and its binding protein YWHAH could be good targets for developing diagnostic and therapeutic strategies against human cancers.
3-Phosphoinositide-dependent Protein Kinase-1 (PDK1) promotes invasion and activation of matrix metalloproteinases
Authors: Xie Zhihui , Yuan Hongyan , Yin Yuzhi , Zeng Xiao , Bai Renkui , Glazer Robert I 
Published: April 2006

Abstract

Background
Metastasis is a major cause of morbidity and mortality in breast cancer with tumor cell invasion playing a crucial role in the metastatic process. PDK1 is a key molecule that couples PI3K to cell proliferation and survival signals in response to growth factor receptor activation, and is oncogenic when expressed in mouse mammary epithelial cells. We now present evidence showing that PDK1-expressing cells exhibit enhanced anchorage-dependent and -independent cell growth and are highly invasive when grown on Matrigel. These properties correlate with induction of MMP-2 activity, increased MT1-MMP expression and a unique gene expression profile.

Methods
Invasion assays in Matrigel, MMP-2 zymogram analysis, gene microarray analysis and mammary isografts were used to characterize the invasive and proliferative function of cells expressing PDK1. Tissue microarray analysis of human breast cancers was used to measure PDK1 expression in invasive tumors by IHC.

Results
Enhanced invasion on Matrigel in PDK1-expressing cells was accompanied by increased MMP-2 activity resulting from stabilization against proteasomal degradation. Increased MMP-2 activity was accompanied by elevated levels of MT1-MMP, which is involved in generating active MMP-2. Gene microarray analysis identified increased expression of the ECM-associated genes decorin and type I procollagen, whose gene products are substrates of MT1-MMP. Mammary fat pad isografts of PDK1-expressing cells produced invasive adenocarcinomas. Tissue microarray analysis of human invasive breast cancer indicated that PDK1pSer241 was strongly expressed in 90% of samples.

Conclusion
These results indicate that PDK1 serves as an important effector of mammary epithelial cell growth and invasion in the transformed phenotype. PDK1 mediates its effect in part by MT1-MMP induction, which in turn activates MMP-2 and modulates the ECM proteins decorin and collagen. The presence of increased PDK1 expression in the majority of invasive breast cancers suggests its importance in the metastatic process.