7618 Background: BV (Avastin) prolongs progression-free (PFS) and overall survival (OS) in advanc... more 7618 Background: BV (Avastin) prolongs progression-free (PFS) and overall survival (OS) in advanced NSCLC. ARIES, a prospective OCS evaluating BV in a real world setting, includes pts underrepresented in randomized controlled trials (RCTs), i.e., pts ≥70y, with poor performance status (PS), or with CNS metastases (mets). Preliminary COs (effectiveness and safety) in ARIES subpopulations are presented. Methods: Pts with locally advanced nonsquamous NSCLC on first-line chemotherapy (CT) and BV enrolled. No prespecified treatments, doses or assessments. Data are collected electronically at baseline (BL) and quarterly (QU), including BV-targeted adverse events (AEs) and serious AEs (SAEs). Descriptive safety analyses were conducted for all pts and for subgroups. Median (med) PFS and OS are Kaplan-Meier estimates. Results: ARIES enrolled 1,970 NSCLC pts. Med follow-up at the 09/2009 data cut was 9.6 mo; 98% have ≥1 QU follow-up. Med PFS is 6.7 mo and OS is 13.6 mo for the entire cohort and were similar across ...
in the execution step of apoptosis, and TUNEL staining, an indicator of DNA fragmentation, increa... more in the execution step of apoptosis, and TUNEL staining, an indicator of DNA fragmentation, increased within six hours of injury. Furthermore they found that p75 NTR , the proapoptotic neurotrophin receptor, also increased by 48 h after injury. Estradiol treatment attenuated these markers of apoptosis, strongly suggesting that it exerts its neuroprotective actions by suppressing factors that mediate apoptotic pathways of cell death. These studies complement others that suggest that estradiol acts on multiple steps of the apoptotic pathway to tip the balance in favor of cell survival and to decrease the chances of cell death. An important aspect of the current study is that it was performed on male gerbils. This confirms the findings of others that estradiol is protective in both sexes [2-4]. The data suggest that if estrogens could be designed so that they did not feminize but exerted protective actions, they would be useful therapies for men as well as women.
Background: Clinician utilization of practice guidelines can reduce inappropriate opioid prescrib... more Background: Clinician utilization of practice guidelines can reduce inappropriate opioid prescribing and harm in chronic non-cancer pain; yet, implementation of “opioid guidelines” is subpar. We hypothesized that a multi-component quality improvement (QI) augmentation of “routine” system-level implementation efforts would increase clinician adherence to the opioid guideline-driven policy recommendations. Methods: Opioid policy was implemented system-wide in 26 primary care clinics. A convenience sample of 9 clinics received the QI augmentation (one-hour academic detailing; 2 online educational modules; 4-6 monthly one-hour practice facilitation sessions) in this non-randomized stepped-wedge QI project. The intervention subjects were volunteer clinic staff. The target patient population was adults with chronic non-cancer pain treated with long-term opioids. The outcomes included the clinic-level percentage of target patients with a current treatment agreement (primary outcome), rates...
The field of steroid hormone action is well established, although it is barely more than four dec... more The field of steroid hormone action is well established, although it is barely more than four decades old. Pivotal experiments in the late 1950s and 1960s showed that hormone-binding components exist within nuclei of target tissues and that steroid hormones act by regulating gene expression, rather than directly influencing enzymatic processes. The understanding that steroid hormone receptors interact with the general transcription machinery and alter chromatin structure came in the 1970s and 1980s, and details of this mechanism continue to be elucidated. In addition, the discovery of rapid cellular responses to steroid hormones has led to the identification of putative membrane-bound steroid receptors that act without affecting gene transcription. As noted in the recent Institute of Medicine report Exploring the Biological Contributions to Human Health: Does Sex Matter?, the effects of steroid hormones and defects in steroid hormone receptor action have a profound impact on human h...
Systematic implementation of guidelines for opioid therapy management in chronic non-cancer pain ... more Systematic implementation of guidelines for opioid therapy management in chronic non-cancer pain can reduce opioid-related harms. However, implementation of guideline-recommended practices in routine care is subpar. The goal of this quality improvement (QI) project is to assess whether a clinic-tailored QI intervention improves the implementation of a health system-wide, guideline-driven policy on opioid prescribing in primary care. This manuscript describes the protocol for this QI project. A health system with 28 primary care clinics caring for approximately 294,000 primary care patients developed and implemented a guideline-driven policy on long-term opioid therapy in adults with opioid-treated chronic non-cancer pain (estimated N = 3980). The policy provided multiple recommendations, including the universal use of treatment agreements, urine drug testing, depression and opioid misuse risk screening, and standardized documentation of the chronic pain diagnosis and treatment plan....
Eukaryotic gene targeting by means of gene replacement vectors is often complicated by unwanted p... more Eukaryotic gene targeting by means of gene replacement vectors is often complicated by unwanted plasmid insertion events involving the ends of transforming DNA molecules. These undesirable and often multiple insertions occur both randomly (i.e. non-homologously) and at the targeted locus. By blocking the 3' ends of transforming DNA with 2'3' dideoxynucleotides, we have reduced the frequency of end-mediated DNA insertion in Dictyostelium amoebae. As a result, only one copy of the selectable gene is introduced at the target locus to achieve a precise gene disruption.
U6 spliceosomal RNA has a complex secondary structure that includes a highly conserved stemloop n... more U6 spliceosomal RNA has a complex secondary structure that includes a highly conserved stemloop near the 3Ј end. The 3Ј stem is unwound when U6 RNA base-pairs with U4 RNA during spliceosome assembly, but likely reforms when U4 RNA leaves the spliceosome prior to the catalysis of splicing. A mutation in yeast U6 RNA that hyperstabilizes the 3Ј stem confers cold sensitivity and inhibits U4/U6 assembly as well as a later step in splicing. Here we show that extragenic suppressors of the 3Ј stem mutation map to the gene coding for splicing factor Prp24. The suppressor mutations are located in the second and third of three RNA-recognition motifs (RRMs) in Prp24 and are predicted to disrupt RNA binding. Mutations in U6 RNA predicted to destabilize a novel helix adjacent to the 3Ј stem also suppress the 3Ј stem mutation and enhance the growth defect of a suppressor mutation in RRM2 of Prp24. Both phenotypes are reverted by a compensatory mutation that restores pairing in the novel helix. These results are best explained by a model in which RRMs 2 and 3 of Prp24 stabilize an extended intramolecular structure in U6 RNA that competes with the U4/U6 RNA interaction, and thus influence both association and dissociation of U4 and U6 RNAs during the splicing cycle.
Journal of the American Board of Family Medicine : JABFM
The success of practice-based research (PBR) depends on the willingness of clinicians and staff t... more The success of practice-based research (PBR) depends on the willingness of clinicians and staff to incorporate meaningful and useful research protocols into already demanding clinic schedules. The impact of participation on those who implement multiple projects and how to address the issues that arise during this complex process remain incompletely described. This article reports a qualitative evaluation of the experiences of primary care clinicians and clinic staff who participated in multiple PBR projects with the Wisconsin Research and Education Network (WREN). Also included are their suggestions to researchers and clinicians for future collaborations. For program evaluation purposes, WREN conducted 4 focus groups at its 2014 annual meeting. The main focus group question was, "How has participation in PBR affected you and your clinic?" A total of 27 project members from 13 clinics participated in 4 groups (physicians, nurses, managers, and other clinical staff). The 2-h...
Journal of applied physiology (Bethesda, Md. : 1985), 2001
The field of steroid hormone action is well established, although it is barely more than four dec... more The field of steroid hormone action is well established, although it is barely more than four decades old. Pivotal experiments in the late 1950s and 1960s showed that hormone-binding components exist within nuclei of target tissues and that steroid hormones act by regulating gene expression, rather than directly influencing enzymatic processes. The understanding that steroid hormone receptors interact with the general transcription machinery and alter chromatin structure came in the 1970s and 1980s, and details of this mechanism continue to be elucidated. In addition, the discovery of rapid cellular responses to steroid hormones has led to the identification of putative membrane-bound steroid receptors that act without affecting gene transcription. As noted in the recent Institute of Medicine report "Exploring the Biological Contributions to Human Health: Does Sex Matter?", the effects of steroid hormones and defects in steroid hormone receptor action have a profound impac...
U6 spliceosomal RNA has a complex secondary structure that includes a highly conserved stemloop n... more U6 spliceosomal RNA has a complex secondary structure that includes a highly conserved stemloop near the 3' end. The 3' stem is unwound when U6 RNA base-pairs with U4 RNA during spliceosome assembly, but likely reforms when U4 RNA leaves the spliceosome prior to the catalysis of splicing. A mutation in yeast U6 RNA that hyperstabilizes the 3' stem confers cold sensitivity and inhibits U4/U6 assembly as well as a later step in splicing. Here we show that extragenic suppressors of the 3' stem mutation map to the gene coding for splicing factor Prp24. The suppressor mutations are located in the second and third of three RNA-recognition motifs (RRMs) in Prp24 and are predicted to disrupt RNA binding. Mutations in U6 RNA predicted to destabilize a novel helix adjacent to the 3' stem also suppress the 3' stem mutation and enhance the growth defect of a suppressor mutation in RRM2 of Prp24. Both phenotypes are reverted by a compensatory mutation that restores pairin...
Large-scale changes in RNA secondary structure, such as those that occur in some of the spliceoso... more Large-scale changes in RNA secondary structure, such as those that occur in some of the spliceosomal RNAs during pre-mRNA splicing, have been proposed to be catalyzed by ATP-dependent RNA helicases. Here we show that deproteinized human U4/U6 spliceosomal RNA complex, which has the potential for extensive intermolecular base pairing, contains a cis-acting element that promotes its dissociation into free U4 and U6 RNAs. The destabilzing element corresponds to the bae of putative intramolecular stem in U6 RNA that includes the 3' three-quarters of the molecule. Oligonucleotides expected to compete for U6 RNA 3' stem formation promote assembly of the human U4/U6 RNA complex under conditions that otherwise result in dissociation of the U4/U6 complex. Truncation of the putative 3' stem-forming sequences in U6 RNA by oligonucleotide-directed RNase H cleavage increases the melting temperature of the U4/U6 RNA complex by almost 20 degree C, to a level commensurate with its inter...
Journal of Women's Health & Gender-Based Medicine, 2000
... and Analysis by Sex REGINA M. VIDAVER, Ph.D.,1 BONNIE LAFLEUR, Ph.D.,2 CYNTHIA TONG, BA,1 ROB... more ... and Analysis by Sex REGINA M. VIDAVER, Ph.D.,1 BONNIE LAFLEUR, Ph.D.,2 CYNTHIA TONG, BA,1 ROBYNNE BRADSHAW, BA, B.Sc.,1 and SHERRY A. MARTS, Ph.D.1 ABSTRACT ... [CrossRef] 10. Winnie WS Mak, Rita W. Law, Jennifer Alvidrez, Eliseo J. Pérez-Stable. ...
Introduction: Bevacizumab, a recombinant humanized monoclonal antibody against vascular endotheli... more Introduction: Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor, was approved by the US Food and Drug Administration for the treatment of advanced non-small-cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel. ARIES (Avastin Regimens: Investigation of Effectiveness and Safety), a prospective observational cohort study, evaluated outcomes in a large, community-based population of patients with first-line NSCLC. Methods: From 2006 to 2009, ARIES enrolled patients with locally advanced or metastatic NSCLC who were eligible for bevacizumab, excluding those with predominantly squamous histology. Patients were required to provide informed consent and to have initiated bevacizumab with chemotherapy within 4 months before enrollment. There were no protocol-defined treatments or assessments. The dosing of bevacizumab and chemotherapy, and the choice of chemotherapy regimen, was at the discretion of the treating physician. Results: ARIES enrolled 1967 patients with first-line NSCLC. At study closure, median follow-up was 12.5 months (range, 0.2-65.5). Median age was 65 years (range, 31-93), and 252 patients (12.8%) identified as never smokers. Median progression-free survival was 6.6 months (95% confidence interval, 6.3-6.9), and median overall survival was 13.0 months (95% confidence interval, 12.2-13.8) with first-line bevacizumab plus chemotherapy. Incidences of bevacizumabassociated adverse events (19.7% overall) were consistent with those in randomized controlled trials of bevacizumab in NSCLC. Conclusion: Results from ARIES demonstrate similar outcomes to randomized controlled trials of bevacizumab when added to standard chemotherapy in a real-world patient population with advanced NSCLC.
Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by... more Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 93, 741-753 17 Gerety, S.S. et al. (1999) Symmetrical mutant phenotypes of the receptor EphB4 and its specific transmembrane ligand ephrin-B2 in cardiovascular development. Mol. Cell 4, 403-414
This report presents highlights from The National Lung Cancer Partnership's Annua... more This report presents highlights from The National Lung Cancer Partnership's Annual Meeting, held in June 2007 in Chicago. It discusses recent refinements in the histologic, genetic, and epigenetic subtyping of lung cancers and suggests reasons why certain therapies benefit only a subset of lung cancer patients. It also describes new molecular data about the subtype-specific differences in drug resistance among bronchioloalveolar-associated non-small cell lung cancers and discusses strategies to avoid or tackle specific drug-resistant tumors. Finally, it describes new findings about epigenetic differences-specifically in DNA hypermethylation-among lung tumors, including some male/female differences, which may prove useful as biomarkers for diagnosis, prognosis, and prediction of response to treatments.
Herein are highlights from National Lung Cancer Partnership's Annual Meeting, hel... more Herein are highlights from National Lung Cancer Partnership's Annual Meeting, held May 30, 2008 in Chicago. Aiming to improve the match between lung cancer patients and their drug treatments, speakers described potential predictive and prognostic biomarkers. Approaches included: (1) in non-small cell lung cancer, testing for predictive links between tumor expression levels of DNA synthesis (RRM1) and repair (ERCC1) enzymes and response to gemcitabine and cisplatin respectively, and looking for a prognostic link with ERCC1 expression; (2) validating a predictive "meta-gene profile" from gene expression microarray studies to distinguish drug-responsive from unresponsive lung cancer tumors; and (3) developing proteomics profiling to distinguish lung cancer patients, including squamous and nonsquamous cell carcinoma patients, who respond to epidermal growth factor receptor tyrosine kinase inhibitors from those who do not. The notion that cancer stem cells are fundamental in the development and progression of solid tumors including lung cancers was also discussed. Potential strategies for using this information to identify useful targets for next-generation therapies were suggested.
Eukaryotic gene targeting by means of gene replacement vectors is often complicated by unwanted p... more Eukaryotic gene targeting by means of gene replacement vectors is often complicated by unwanted plasmid insertion events involving the ends of transforming DNA molecules. These undesirable and often multiple insertions occur both randomly (i.e. non-homologously) and at the targeted locus. By blocking the 3' ends of transforming DNA with 2'3' dideoxynucleotides, we have reduced the frequency of end-mediated DNA insertion in Dictyostelium amoebae. As a result, only one copy of the selectable gene is introduced at the target locus to achieve a precise gene disruption.
7618 Background: BV (Avastin) prolongs progression-free (PFS) and overall survival (OS) in advanc... more 7618 Background: BV (Avastin) prolongs progression-free (PFS) and overall survival (OS) in advanced NSCLC. ARIES, a prospective OCS evaluating BV in a real world setting, includes pts underrepresented in randomized controlled trials (RCTs), i.e., pts ≥70y, with poor performance status (PS), or with CNS metastases (mets). Preliminary COs (effectiveness and safety) in ARIES subpopulations are presented. Methods: Pts with locally advanced nonsquamous NSCLC on first-line chemotherapy (CT) and BV enrolled. No prespecified treatments, doses or assessments. Data are collected electronically at baseline (BL) and quarterly (QU), including BV-targeted adverse events (AEs) and serious AEs (SAEs). Descriptive safety analyses were conducted for all pts and for subgroups. Median (med) PFS and OS are Kaplan-Meier estimates. Results: ARIES enrolled 1,970 NSCLC pts. Med follow-up at the 09/2009 data cut was 9.6 mo; 98% have ≥1 QU follow-up. Med PFS is 6.7 mo and OS is 13.6 mo for the entire cohort and were similar across ...
in the execution step of apoptosis, and TUNEL staining, an indicator of DNA fragmentation, increa... more in the execution step of apoptosis, and TUNEL staining, an indicator of DNA fragmentation, increased within six hours of injury. Furthermore they found that p75 NTR , the proapoptotic neurotrophin receptor, also increased by 48 h after injury. Estradiol treatment attenuated these markers of apoptosis, strongly suggesting that it exerts its neuroprotective actions by suppressing factors that mediate apoptotic pathways of cell death. These studies complement others that suggest that estradiol acts on multiple steps of the apoptotic pathway to tip the balance in favor of cell survival and to decrease the chances of cell death. An important aspect of the current study is that it was performed on male gerbils. This confirms the findings of others that estradiol is protective in both sexes [2-4]. The data suggest that if estrogens could be designed so that they did not feminize but exerted protective actions, they would be useful therapies for men as well as women.
Background: Clinician utilization of practice guidelines can reduce inappropriate opioid prescrib... more Background: Clinician utilization of practice guidelines can reduce inappropriate opioid prescribing and harm in chronic non-cancer pain; yet, implementation of “opioid guidelines” is subpar. We hypothesized that a multi-component quality improvement (QI) augmentation of “routine” system-level implementation efforts would increase clinician adherence to the opioid guideline-driven policy recommendations. Methods: Opioid policy was implemented system-wide in 26 primary care clinics. A convenience sample of 9 clinics received the QI augmentation (one-hour academic detailing; 2 online educational modules; 4-6 monthly one-hour practice facilitation sessions) in this non-randomized stepped-wedge QI project. The intervention subjects were volunteer clinic staff. The target patient population was adults with chronic non-cancer pain treated with long-term opioids. The outcomes included the clinic-level percentage of target patients with a current treatment agreement (primary outcome), rates...
The field of steroid hormone action is well established, although it is barely more than four dec... more The field of steroid hormone action is well established, although it is barely more than four decades old. Pivotal experiments in the late 1950s and 1960s showed that hormone-binding components exist within nuclei of target tissues and that steroid hormones act by regulating gene expression, rather than directly influencing enzymatic processes. The understanding that steroid hormone receptors interact with the general transcription machinery and alter chromatin structure came in the 1970s and 1980s, and details of this mechanism continue to be elucidated. In addition, the discovery of rapid cellular responses to steroid hormones has led to the identification of putative membrane-bound steroid receptors that act without affecting gene transcription. As noted in the recent Institute of Medicine report Exploring the Biological Contributions to Human Health: Does Sex Matter?, the effects of steroid hormones and defects in steroid hormone receptor action have a profound impact on human h...
Systematic implementation of guidelines for opioid therapy management in chronic non-cancer pain ... more Systematic implementation of guidelines for opioid therapy management in chronic non-cancer pain can reduce opioid-related harms. However, implementation of guideline-recommended practices in routine care is subpar. The goal of this quality improvement (QI) project is to assess whether a clinic-tailored QI intervention improves the implementation of a health system-wide, guideline-driven policy on opioid prescribing in primary care. This manuscript describes the protocol for this QI project. A health system with 28 primary care clinics caring for approximately 294,000 primary care patients developed and implemented a guideline-driven policy on long-term opioid therapy in adults with opioid-treated chronic non-cancer pain (estimated N = 3980). The policy provided multiple recommendations, including the universal use of treatment agreements, urine drug testing, depression and opioid misuse risk screening, and standardized documentation of the chronic pain diagnosis and treatment plan....
Eukaryotic gene targeting by means of gene replacement vectors is often complicated by unwanted p... more Eukaryotic gene targeting by means of gene replacement vectors is often complicated by unwanted plasmid insertion events involving the ends of transforming DNA molecules. These undesirable and often multiple insertions occur both randomly (i.e. non-homologously) and at the targeted locus. By blocking the 3' ends of transforming DNA with 2'3' dideoxynucleotides, we have reduced the frequency of end-mediated DNA insertion in Dictyostelium amoebae. As a result, only one copy of the selectable gene is introduced at the target locus to achieve a precise gene disruption.
U6 spliceosomal RNA has a complex secondary structure that includes a highly conserved stemloop n... more U6 spliceosomal RNA has a complex secondary structure that includes a highly conserved stemloop near the 3Ј end. The 3Ј stem is unwound when U6 RNA base-pairs with U4 RNA during spliceosome assembly, but likely reforms when U4 RNA leaves the spliceosome prior to the catalysis of splicing. A mutation in yeast U6 RNA that hyperstabilizes the 3Ј stem confers cold sensitivity and inhibits U4/U6 assembly as well as a later step in splicing. Here we show that extragenic suppressors of the 3Ј stem mutation map to the gene coding for splicing factor Prp24. The suppressor mutations are located in the second and third of three RNA-recognition motifs (RRMs) in Prp24 and are predicted to disrupt RNA binding. Mutations in U6 RNA predicted to destabilize a novel helix adjacent to the 3Ј stem also suppress the 3Ј stem mutation and enhance the growth defect of a suppressor mutation in RRM2 of Prp24. Both phenotypes are reverted by a compensatory mutation that restores pairing in the novel helix. These results are best explained by a model in which RRMs 2 and 3 of Prp24 stabilize an extended intramolecular structure in U6 RNA that competes with the U4/U6 RNA interaction, and thus influence both association and dissociation of U4 and U6 RNAs during the splicing cycle.
Journal of the American Board of Family Medicine : JABFM
The success of practice-based research (PBR) depends on the willingness of clinicians and staff t... more The success of practice-based research (PBR) depends on the willingness of clinicians and staff to incorporate meaningful and useful research protocols into already demanding clinic schedules. The impact of participation on those who implement multiple projects and how to address the issues that arise during this complex process remain incompletely described. This article reports a qualitative evaluation of the experiences of primary care clinicians and clinic staff who participated in multiple PBR projects with the Wisconsin Research and Education Network (WREN). Also included are their suggestions to researchers and clinicians for future collaborations. For program evaluation purposes, WREN conducted 4 focus groups at its 2014 annual meeting. The main focus group question was, "How has participation in PBR affected you and your clinic?" A total of 27 project members from 13 clinics participated in 4 groups (physicians, nurses, managers, and other clinical staff). The 2-h...
Journal of applied physiology (Bethesda, Md. : 1985), 2001
The field of steroid hormone action is well established, although it is barely more than four dec... more The field of steroid hormone action is well established, although it is barely more than four decades old. Pivotal experiments in the late 1950s and 1960s showed that hormone-binding components exist within nuclei of target tissues and that steroid hormones act by regulating gene expression, rather than directly influencing enzymatic processes. The understanding that steroid hormone receptors interact with the general transcription machinery and alter chromatin structure came in the 1970s and 1980s, and details of this mechanism continue to be elucidated. In addition, the discovery of rapid cellular responses to steroid hormones has led to the identification of putative membrane-bound steroid receptors that act without affecting gene transcription. As noted in the recent Institute of Medicine report "Exploring the Biological Contributions to Human Health: Does Sex Matter?", the effects of steroid hormones and defects in steroid hormone receptor action have a profound impac...
U6 spliceosomal RNA has a complex secondary structure that includes a highly conserved stemloop n... more U6 spliceosomal RNA has a complex secondary structure that includes a highly conserved stemloop near the 3' end. The 3' stem is unwound when U6 RNA base-pairs with U4 RNA during spliceosome assembly, but likely reforms when U4 RNA leaves the spliceosome prior to the catalysis of splicing. A mutation in yeast U6 RNA that hyperstabilizes the 3' stem confers cold sensitivity and inhibits U4/U6 assembly as well as a later step in splicing. Here we show that extragenic suppressors of the 3' stem mutation map to the gene coding for splicing factor Prp24. The suppressor mutations are located in the second and third of three RNA-recognition motifs (RRMs) in Prp24 and are predicted to disrupt RNA binding. Mutations in U6 RNA predicted to destabilize a novel helix adjacent to the 3' stem also suppress the 3' stem mutation and enhance the growth defect of a suppressor mutation in RRM2 of Prp24. Both phenotypes are reverted by a compensatory mutation that restores pairin...
Large-scale changes in RNA secondary structure, such as those that occur in some of the spliceoso... more Large-scale changes in RNA secondary structure, such as those that occur in some of the spliceosomal RNAs during pre-mRNA splicing, have been proposed to be catalyzed by ATP-dependent RNA helicases. Here we show that deproteinized human U4/U6 spliceosomal RNA complex, which has the potential for extensive intermolecular base pairing, contains a cis-acting element that promotes its dissociation into free U4 and U6 RNAs. The destabilzing element corresponds to the bae of putative intramolecular stem in U6 RNA that includes the 3' three-quarters of the molecule. Oligonucleotides expected to compete for U6 RNA 3' stem formation promote assembly of the human U4/U6 RNA complex under conditions that otherwise result in dissociation of the U4/U6 complex. Truncation of the putative 3' stem-forming sequences in U6 RNA by oligonucleotide-directed RNase H cleavage increases the melting temperature of the U4/U6 RNA complex by almost 20 degree C, to a level commensurate with its inter...
Journal of Women's Health & Gender-Based Medicine, 2000
... and Analysis by Sex REGINA M. VIDAVER, Ph.D.,1 BONNIE LAFLEUR, Ph.D.,2 CYNTHIA TONG, BA,1 ROB... more ... and Analysis by Sex REGINA M. VIDAVER, Ph.D.,1 BONNIE LAFLEUR, Ph.D.,2 CYNTHIA TONG, BA,1 ROBYNNE BRADSHAW, BA, B.Sc.,1 and SHERRY A. MARTS, Ph.D.1 ABSTRACT ... [CrossRef] 10. Winnie WS Mak, Rita W. Law, Jennifer Alvidrez, Eliseo J. Pérez-Stable. ...
Introduction: Bevacizumab, a recombinant humanized monoclonal antibody against vascular endotheli... more Introduction: Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor, was approved by the US Food and Drug Administration for the treatment of advanced non-small-cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel. ARIES (Avastin Regimens: Investigation of Effectiveness and Safety), a prospective observational cohort study, evaluated outcomes in a large, community-based population of patients with first-line NSCLC. Methods: From 2006 to 2009, ARIES enrolled patients with locally advanced or metastatic NSCLC who were eligible for bevacizumab, excluding those with predominantly squamous histology. Patients were required to provide informed consent and to have initiated bevacizumab with chemotherapy within 4 months before enrollment. There were no protocol-defined treatments or assessments. The dosing of bevacizumab and chemotherapy, and the choice of chemotherapy regimen, was at the discretion of the treating physician. Results: ARIES enrolled 1967 patients with first-line NSCLC. At study closure, median follow-up was 12.5 months (range, 0.2-65.5). Median age was 65 years (range, 31-93), and 252 patients (12.8%) identified as never smokers. Median progression-free survival was 6.6 months (95% confidence interval, 6.3-6.9), and median overall survival was 13.0 months (95% confidence interval, 12.2-13.8) with first-line bevacizumab plus chemotherapy. Incidences of bevacizumabassociated adverse events (19.7% overall) were consistent with those in randomized controlled trials of bevacizumab in NSCLC. Conclusion: Results from ARIES demonstrate similar outcomes to randomized controlled trials of bevacizumab when added to standard chemotherapy in a real-world patient population with advanced NSCLC.
Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by... more Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 93, 741-753 17 Gerety, S.S. et al. (1999) Symmetrical mutant phenotypes of the receptor EphB4 and its specific transmembrane ligand ephrin-B2 in cardiovascular development. Mol. Cell 4, 403-414
This report presents highlights from The National Lung Cancer Partnership's Annua... more This report presents highlights from The National Lung Cancer Partnership's Annual Meeting, held in June 2007 in Chicago. It discusses recent refinements in the histologic, genetic, and epigenetic subtyping of lung cancers and suggests reasons why certain therapies benefit only a subset of lung cancer patients. It also describes new molecular data about the subtype-specific differences in drug resistance among bronchioloalveolar-associated non-small cell lung cancers and discusses strategies to avoid or tackle specific drug-resistant tumors. Finally, it describes new findings about epigenetic differences-specifically in DNA hypermethylation-among lung tumors, including some male/female differences, which may prove useful as biomarkers for diagnosis, prognosis, and prediction of response to treatments.
Herein are highlights from National Lung Cancer Partnership's Annual Meeting, hel... more Herein are highlights from National Lung Cancer Partnership's Annual Meeting, held May 30, 2008 in Chicago. Aiming to improve the match between lung cancer patients and their drug treatments, speakers described potential predictive and prognostic biomarkers. Approaches included: (1) in non-small cell lung cancer, testing for predictive links between tumor expression levels of DNA synthesis (RRM1) and repair (ERCC1) enzymes and response to gemcitabine and cisplatin respectively, and looking for a prognostic link with ERCC1 expression; (2) validating a predictive "meta-gene profile" from gene expression microarray studies to distinguish drug-responsive from unresponsive lung cancer tumors; and (3) developing proteomics profiling to distinguish lung cancer patients, including squamous and nonsquamous cell carcinoma patients, who respond to epidermal growth factor receptor tyrosine kinase inhibitors from those who do not. The notion that cancer stem cells are fundamental in the development and progression of solid tumors including lung cancers was also discussed. Potential strategies for using this information to identify useful targets for next-generation therapies were suggested.
Eukaryotic gene targeting by means of gene replacement vectors is often complicated by unwanted p... more Eukaryotic gene targeting by means of gene replacement vectors is often complicated by unwanted plasmid insertion events involving the ends of transforming DNA molecules. These undesirable and often multiple insertions occur both randomly (i.e. non-homologously) and at the targeted locus. By blocking the 3' ends of transforming DNA with 2'3' dideoxynucleotides, we have reduced the frequency of end-mediated DNA insertion in Dictyostelium amoebae. As a result, only one copy of the selectable gene is introduced at the target locus to achieve a precise gene disruption.
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Papers by Regina Vidaver